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1.
  • Abu Seman, N, et al. (författare)
  • Genetic and biological effects of sodium-chloride cotransporter (SLC12A3) in diabetic nephropathy
  • 2014
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 40:5, s. 408-416
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background/Aims:</i></b> Solute carrier family 12 member 3 (<i>SLC12A3</i>) encodes a sodium/chloride transporter in kidneys. Previous reports suggest that Arg913Gln polymorphism in this gene is associated with diabetic nephropathy (DN), but the data appear to be inconsistent. Up to now, there is no biological evidence concerning the effects of <i>SLC12A3</i> in DN. In this study, we aim to evaluate the genetic effects of the <i>SLC12A3 </i>gene and its Arg913Gln polymorphism with genetic and functional analyses. <b><i>Methods:</i></b> We genotyped <i>SLC12A3</i> genetic polymorphisms including Arg913Gln in 784 non-diabetes controls and 633 type 2 diabetes (T2D) subjects with or without DN in a Malaysian population and performed a meta-analysis of the present and previous studies. We further analyzed the role of <i>slc12a3</i> in kidney development and progress of DN in zebrafish and db/db mice. <b><i>Results:</i></b> We found that <i>SLC12A3</i> Arg913Gln polymorphism was associated with T2D (p = 0.028, OR = 0.772, 95% CI = 0.612-0.973) and DN (p = 0.038, OR = 0.547, 95% CI = 0.308-0.973) in the Malaysian cohort. The meta-analysis confirmed the protective effects of <i>SLC12A3</i> 913Gln allele in DN (Z-value = -1.992, p = 0.046, OR = 0.792). Furthermore, with knockdown of zebrafish ortholog, <i>slc12a3 </i>led to structural abnormality of kidney pronephric distal duct at 1-cell stage. <i>Slc12a3</i> mRNA and protein expression levels were upregulated in kidneys of db/db mice from 6, 12, and 26 weeks at the age. <b><i>Conclusion:</i></b> The present study provided the first biological and further genetic evidence that <i>SLC12A3</i> has genetic susceptibility in the development of DN, while the minor 913Gln allele in this gene confers a protective effect in the disease. i 2014 S. Karger AG, Basel
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2.
  • Axelsson, J, et al. (författare)
  • Is fetuin-A/alpha2-Heremans-Schmid glycoprotein associated with the metabolic syndrome in patients with chronic kidney disease?
  • 2008
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 28:4, s. 669-676
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Introduction:</i> Components of the metabolic syndrome are highly prevalent in chronic kidney disease (CKD) patients – some of which paradoxically appear to predict an improved outcome in this population. We hypothesized that the circulating calcification inhibitor fetuin-A/AHSG, which is also a natural inhibitor of the tyrosine kinase insulin receptor, could be one factor explaining the association between increased fat mass and a survival advantage in CKD and thus conducted an explorational study to provide preliminary data to support further research into this hypothesis. <i>Patients and Methods:</i> In a cross-sectional study, we evaluated 198 CKD stage 5 patients (GFR 6.8 ± 0.2 ml/min; 62% males, mean age 52 ± 1 years) close to the start of renal replacement therapy. We studied circulating AHSG (ELISA) and two common functional <i>AHSG</i> gene polymorphisms (at amino acids Thr248Met (C-T) and Thr256Ser (C-G) using Pyrosequencing®) and related these to multiple components of the metabolic syndrome. <i>Results:</i> Median circulating AHSG was lower (p < 0.01) in type-2 (0.22 g/l) and type-1 (0.16 g/l) diabetics as compared to non-diabetic CKD-5 patients (0.24 g/l). AHSG correlated with both total and truncal fat mass in type-2 diabetics (rho 0.37 and 0.39; p < 0.001, respectively), but not in type-1 diabetics or non-diabetics. Both SNPs significantly influenced circulating levels of AHSG, and were also associated with significant differences in serum triglycerides and HDL cholesterol. Furthermore, there were significant differences in the prevalence of metabolic syndrome criteria between the <i>AHSG</i> Thr256Ser (C-G) genotype groups, with a more atherogenic lipid profile in AHSG high producers (Thr/Thr homozygotes). In multivariate analysis, the association between circulating AHSG and fat mass remained significant also after adjustment for age, gender, inflammation (CRP >10 mg/l), and <i>AHSG</i> genotype. <i>Conclusions:</i> The present, explorational, study supports further, mechanistic, studies into a physiological link between AHSG and body fat mass in patients with CKD. As we observed an association between higher fat mass and elevated AHSG levels, these preliminary results may form the basis of further study to establish if the observed associations may be one reason why obesity has been reported to constitute a survival advantage in CKD.
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3.
  • Axelsson, J, et al. (författare)
  • Serum retinol-binding protein concentration and its association with components of the uremic metabolic syndrome in nondiabetic patients with chronic kidney disease stage 5
  • 2009
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 29:5, s. 447-53
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Introduction:</i> Chronic kidney disease (CKD) is associated with insulin resistance also in the absence of overt diabetes mellitus. The liver-derived transport protein retinol-binding protein (RBP) has recently been proposed as a novel adipokine involved in the metabolism of glucose. Although RBP is elevated in type 2 diabetics with mild CKD, its role in advanced CKD is not well studied. We hypothesized that altered RBP levels in CKD could be one factor contributing to the uremic insulin resistance. <i>Patients and Methods:</i> In a cross-sectional study, we evaluated 141 nondiabetic stage 5 CKD patients (GFR 6.8 ± 2.0 ml/min; 62% males, mean age 52 ± 11 years) close to the start of renal replacement therapy. We studied circulating RBP (RIA), retinol and metabolic markers. Body composition was also assessed using DEXA and patients were divided according to truncal fat mass above (obese) or below (lean) the sex-specific median. A fasting plasma glucose ≥6.1 m<i>M</i> was defined as impaired glucose tolerance (IGT). <i>Results:</i> Serum RBP levels were significantly elevated in CKD as compared to previous reports in non-renal patients. Whereas levels of RBP did not differ between lean and obese patients without IGT, they were lower in lean CKD patients with IGT (5.9 ± 2.9 μ<i>M</i>) than in obese CKD patients with IGT (7.0 ± 2.9 μ<i>M</i>; p < 0.05). While RBP did not correlate with truncal or total fat mass or biomarkers of inflammation, in univariate analysis, we found weak correlations with HbA1c% (rho = 0.17; p < 0.05), fasting serum triglycerides (rho = 0.20; p < 0.001) and fasting apolipoprotein (Apo) A1 (rho = 0.29; p < 0.001). RBP also correlated negatively with ApoB (rho = –0.29; p < 0.001). In multivariate analysis, RBP was a significant and independent predictor of both HbA1c% and ApoA1 levels. Finally, RBP was strongly correlated with serum retinol, and calculating a retinol/RBP index further strengthened the observed correlations with HOMA-IR and HbA1c%. <i>Conclusions:</i> RBP is elevated in nondiabetic stage 5 CKD and correlates weakly with HbA1c and ApoA1. As RBP is thought to induce insulin resistance and directly affect lipoprotein metabolism in other disease states, these findings may support a role for RBP in contributing to the uremic metabolic syndrome, putatively by altering ApoA1 metabolism, but further studies are needed to test this hypothesis.
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4.
  • Bakris, George L, et al. (författare)
  • Design and Baseline Characteristics of the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease Trial.
  • 2019
  • Ingår i: American Journal of Nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 50:5, s. 333-344
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Among diabetics, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality, and progression of their underlying disease. Finerenone is a novel, non-steroidal, selective mineralocorticoid-receptor antagonist which has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD), while revealing only a low risk of hyperkalemia. However, the effect of finerenone on renal and CV outcomes has not been investigated in long-term trials yet.METHODS: The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease -(FIDELIO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important renal and CV outcomes in T2D patients with CKD. FIDELIO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 5.5 years. FIDELIO-DKD randomized 5,734 patients with an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30-≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of kidney failure, a sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death.CONCLUSION: FIDELIO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of renal and CV events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen.
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5.
  • Banerjee, T, et al. (författare)
  • Dietary Factors and Prevention: Risk of End-Stage Kidney Disease by Fruit and Vegetable Consumption
  • 2021
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 52:5, s. 356-367
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> The association between fruit and vegetable (FV) intake and the risk of end-stage kidney disease (ESKD) has not been examined in the general population and fully explored in chronic kidney disease (CKD). We prospectively evaluated this relationship in US representative sample of adults and evaluated consistency by the presence or absence, and severity, of CKD. <b><i>Methods:</i></b> We used data from the Third National Health and Nutrition Examination Survey (1988–1994) linked with the US Renal Data System, including 14,725 adults aged ≥20 years and with follow-up for ESKD through 2008. Daily FV intake was ascertained using a food frequency questionnaire. We examined the association between selected categories of FV intake and ESKD using a Fine Gray competing risk model adjusting for sociodemographics, lifestyle, clinical and nutritional factors, estimated glomerular filtration rate, and albuminuria. We evaluated whether risk varied in individuals with severe versus any CKD. <b><i>Results:</i></b> 230 participants (1.5%) developed ESKD during follow-up. In the adjusted model, compared to highest intake, those in lowest categories of FV intake had a higher risk of ESKD, for &#x3c;2 times/day (1.45 [1.24–1.68], 2 to &#x3c;3 times/day (1.40 [1.18–1.61]), 3 to &#x3c;4 times/day (1.25 [1.04–1.46]), and 4 to &#x3c;6 times/day (1.14 [0.97–1.31]). There was suggestion of heterogeneity (<i>p</i> for interaction = 0.03) with possible stronger inverse association in patients with CKD than those without CKD. After stratification, we obtained similar strong inverse association when we examined ESKD incidence across intake of FVs in participants with CKD stages 1–4 (<i>n</i> = 5,346) and specifically in those with CKD stages 3–4 (<i>n</i> = 1,084). <b><i>Conclusions:</i></b> Low intake of FVs was associated with higher risk of ESKD in US adults with and without CKD, supporting an emerging body of literature on the potential benefits of plant-rich diets for prevention of ESKD.
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6.
  • Chen, M, et al. (författare)
  • Prenatal exposure to high level of glucocorticoids increases the susceptibility of renal proximal tubular cells to apoptosis induced by uropathogenic Escherichia coli toxins
  • 2004
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 24:5, s. 497-502
  • Tidskriftsartikel (refereegranskat)abstract
    • Prenatal exposure to excessive glucocorticoids may alter the developing fetus inducing metabolic and endocrine imbalance in various organs, including the kidney. This study aimed at evaluating whether prenatal exposure to high levels of glucocorticoids adversely affects renal cell survival and predisposes to renal cell death. Pregnant rats were injected with 0.1 mg/kg dexamethasone (DEX) i.p. from day 1 of gestation. Renal proximal tubular cells (PTCs) were prepared from 20-day-old offspring in the DEX (DEX cells) and control groups (CON cells). After 4 days’ culture, cells were exposed to uropathogenic <i>Escherichia coli</i> ARD6 toxins at concentrations known to induce apoptotic cell death. We found that cell death rate was significantly higher in DEX than in CON cells. Cells exhibited morphological and biochemical features of apoptosis. Conversely, the activity of the antioxidant enzyme catalase was significantly increased in renal cortex homogenate from 20-day-old DEX rats. The antioxidant vitamin E did not prevent apoptosis. These results indicate that prenatal exposure to high levels of glucocorticoids induces alterations in renal PTCs rendering them more sensitive to <i>E. coli</i> toxins via nonoxidative stress. With the increasing use of multiple doses of glucocorticoids in preterm infants, the possibility that antenatal glucocorticoids may lead to renal adverse consequences is of clinical relevance.
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7.
  • Chen, M, et al. (författare)
  • Uropathogenic Escherichia coli toxins induce caspase-independent apoptosis in renal proximal tubular cells via ERK signaling
  • 2003
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 23:3, s. 140-151
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> Pyelonephritis is a risk factor for renal tubular epithelial cell damage. Recent studies have shown that <i>Escherichia coli</i> and/or its toxins may stimulate apoptotic cell death in renal tubular cells, but the underlying molecular mechanisms remain to be elucidated. <i>Methods:</i> Confluent LLC-PK<sub>1</sub> cells were exposed to <i>E. coli</i> toxins from overnight cultures of the uropathogenic O6K13H1 (O6) and the nonpathogenic W3110. The cell death was studied with morphological and biological assay. <i>Results:</i><i>E. coli</i> soluble toxins from uropathogenic O6:K13:H1(O6) strain were found to induce apoptosis in a dose- and time-dependent manner in LLC-PK1 cells. The expression of FasR and the phosphorylation of ERK1/2 were significantly upregulated by O6 soluble toxins in a time-dependent manner. Cell death was completely inhibited by two specific ERK1/2 inhibitors, but not by a broad caspase inhibitor, zVAD-fmk, implicating a caspase-independent pathway via ERK. Moreover, we found that lysophosphatidic acid could trigger a survival signal through G-proteins and PI3K. <i>Conclusion:</i> We demonstrate that apoptosis induced by uropathogenic <i>E. coli</i> toxins is dependent on ERK1/2. Caspases, although being activated, are not necessary for cell death, and they act after the ERK signaling at which point cells become committed to cell death or can be rescued.
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8.
  • Cheng, LT, et al. (författare)
  • Sex difference in the prevalence of left ventricular hypertrophy in dialysis patients
  • 2009
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 29:5, s. 398-405
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> Left ventricular hypertrophy (LVH) is an important, independent negative predictor of cardiovascular morbidity and mortality in the general population and in dialysis patients. Previous studies suggest a sex dimorphism in the prevalence of LVH; however, this issue has never been approached in dialysis patients. <i>Methods:</i> This study enrolled 237 prevalent dialysis patients: 49 on hemodialysis (HD) and 188 on peritoneal dialysis (PD) from a single center. LVH was defined by echocardiography measurements, which were normalized to body surface area (BSA) and height<sup>2.7</sup>, respectively. <i>Results:</i> The mean ages in HD and PD patients were 60 ± 14 and 60 ± 13 years, with a median dialysis vintage of 43 and 20 months, respectively. Although there was no significant difference in age, diabetes, proportion of uncontrolled hypertension, antihypertensive medication and blood pressure between male and female patients within each dialysis modality, the prevalence of LVH (whether indexed to BSA or height<sup>2.7</sup>) was consistently higher in females than in males. When these patients were divided into LVH or non-LVH groups, a significant difference in sex distribution was observed between the two groups (62.0% vs. 41.0% when the BSA-indexed standard was used, p < 0.01; 62.8% vs. 37.1% when the height<sup>2.7</sup>-indexed standard was used, p < 0.001). In logistic regression analysis, female sex was identified as a risk factor of LVH (odds ratio, OR = 2.48, 95% confidence interval, CI = 1.33–4.59; when BSA-indexed LVH was treated as dependent variable, and OR = 4.05, 95% CI = 1.96–8.38, when height<sup>2.7</sup>-indexed LVH was treated as dependent variable) even after adjustment for age, diabetes, blood pressure and antihypertensive medication. <i>Conclusion:</i> This study showed that the prevalence of LVH determined by echocardiography was significantly higher in female dialysis patients than in male dialysis patients. Compared with males, female patients had a 2.5- to 4-fold higher risk to develop LVH even after adjustment for other potential confounding factors, which may indicate that elderly females in the uremic scenario are more prone to develop LVH than elderly males.
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9.
  • Cherney, DZI, et al. (författare)
  • Initial eGFR Changes with Ertugliflozin and Associations with Clinical Parameters: Analyses from the VERTIS CV Trial
  • 2022
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 53:7, s. 516-525
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Introduction:</i></b> Using data from the ertugliflozin cardiovascular outcomes trial in patients with type 2 diabetes mellitus (VERTIS CV; NCT01986881), associations between the initial estimated glomerular filtration rate (eGFR) “dip” with eGFR slope, glucosuria/natriuresis-related measures, and safety were investigated. <b><i>Methods:</i></b> Patients were categorized into tertiles based on change in eGFR at week 6: &#x3e;+1.00 mL/min/1.73 m<sup>2</sup> (tertile 1), &#x3e;−5.99 and ≤+1.00 (tertile 2), and ≤−6.00 (tertile 3). eGFR slope after week 6 and week 18 was assessed by tertile. Glucosuria/natriuresis-related measures were also determined. Adverse events (AEs) were analyzed in the acute (baseline–week 6) and chronic periods (week 6–30 days after last dose of trial medication). <b><i>Results:</i></b> In the ertugliflozin group, chronic eGFR slopes (95% CI, mL/min/1.73 m<sup>2</sup>/year; weeks 6–156) were −0.76 (−1.03, −0.50), −0.29 (−0.51, −0.07), and −0.05 (−0.26, 0.17) in tertiles 1, 2, and 3, respectively (<i>p</i> value &#x3c;0.001), and approximately −1.5 mL/min/1.73 m<sup>2</sup>/year across tertiles in the placebo group (<i>p</i> value = 0.79). At week 18, least squares mean (LSM) changes from baseline in glycated hemoglobin (%) were −0.77, −0.71, and −0.67 in tertiles 1, 2, and 3, respectively, in the ertugliflozin group; a similar tertile-associated trend was observed for uric acid. At week 18, LSM changes from baseline in hematocrit (%) were 2.07, 2.33, and 2.55 in tertiles 1, 2, and 3, respectively, in the ertugliflozin group; similar tertile-associated trends were observed for blood pressure. All <i>p</i><sub>interaction</sub> values were &#x3c;0.0001 for glucosuria- and natriuresis-related measures. Kidney-related AEs were reported more frequently in tertiles 3 and 2 in the chronic period for both placebo- and ertugliflozin-treated groups. In both periods and in all tertiles, incidences of AEs did not differ between placebo- and ertugliflozin-treated groups. <b><i>Conclusion:</i></b> With ertugliflozin, the tertile with the largest initial dip in eGFR had a slower rate of chronic eGFR decline. Initial eGFR changes were associated with changes in both glucosuria- and natriuresis-related measures.
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10.
  • Chertow, GM, et al. (författare)
  • Study Design and Baseline Characteristics of the CARDINAL Trial: A Phase 3 Study of Bardoxolone Methyl in Patients with Alport Syndrome
  • 2021
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 52:3, s. 180-189
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Introduction:</i></b> Alport syndrome is a rare genetic disorder that affects as many as 60,000 persons in the USA and a total of 103,000 persons (&#x3c;5 per 10,000) in the European Union [1, 2]. It is the second most common inherited cause of kidney failure and is characterized by progressive loss of kidney function that often leads to end-stage kidney disease. Currently, there are no approved disease-specific agents for therapeutic use. We designed a phase 3 study (CARDINAL; NCT03019185) to evaluate the safety, tolerability, and efficacy of bardoxolone methyl in patients with Alport syndrome. <b><i>Methods:</i></b> The CARDINAL phase 3 study is an international, multicenter, double-blind, placebo-controlled, randomized registrational trial. Eligible patients were of ages 12–70 years with confirmed genetic or histologic diagnosis of Alport syndrome, eGFR 30–90 mL/min/1.73 m<sup>2</sup>, and urinary albumin to creatinine ratio (UACR) ≤3,500 mg/g. Patients with B-type natriuretic peptide values &#x3e;200 pg/mL at baseline or with significant cardiovascular histories were excluded. Patients were randomized 1:1 to bardoxolone methyl or placebo, with stratification by baseline UACR. <b><i>Results:</i></b> A total of 371 patients were screened, and 157 patients were randomly assigned to receive bardoxolone methyl (<i>n</i> = 77) or placebo (<i>n</i> = 80). The average age at screening was 39.2 years, and 23 (15%) were &#x3c;18 years of age. Of the randomized population, 146 (93%) had confirmed genetic diagnosis of Alport syndrome, and 62% of patients had X-linked mode of inheritance. Mean baseline eGFR was 62.7 mL/min/1.73 m<sup>2</sup>, and the geometric mean UACR was 141.0 mg/g. The average annual rate of eGFR decline prior to enrollment in the study was −4.9 mL/min/1.73 m<sup>2</sup> despite 78% of the patient population receiving ACE inhibitor (ACEi) or ARB therapy. <b><i>Discussion/Conclusion:</i></b> CARDINAL is one of the largest interventional, randomized controlled trials in Alport syndrome conducted to date. Despite the use of ACEi or ARB, patients were experiencing significant loss of kidney function prior to study entry.
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11.
  • Christensson, Anders, et al. (författare)
  • Family History of Myocardial Infarction Increases Risk of Renal Dysfunction in Middle Age.
  • 2014
  • Ingår i: American Journal of Nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 39:2, s. 85-91
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aims: Chronic kidney disease (CKD) is common in the general population, may lead to end-stage renal disease, and is most frequently found among males. Familial clustering of kidney diseases has been observed. We aimed to study a potential association between the family history of myocardial infarction (MI) and renal dysfunction. Methods: 22,297 males and 10,828 females, aged 33-60 years, from a population-based cohort study were studied. Estimated glomerular filtration rate (eGFR) was assessed by the CKD-EPI creatinine equation. Every participant filled in a self-administered questionnaire including family history. Heredity for MI was defined as mother or father having had MI and/or died from MI, and/or brother or sister having had MI. Binary logistic regression and multiple linear regression were used in the analyses. Results: Multiple linear regression revealed a significantly increased risk of renal dysfunction in those with a positive heredity for MI (the whole cohort p = 0.01, males p = 0.000, females p = 0.169). Binary logistic regression showed that males with heredity for MI with a mean age of 43 years have a 2 times higher risk (p = 0.02) of belonging to the group with GFR <45 ml/min/1.73 m(2) compared to those without heredity. For the whole cohort the increased risk was 1.6 times (p = 0.07). There was no significant association for females (p = 0.88). Conclusion: These findings demonstrate that a familial burden of MI is associated with renal dysfunction, in men, already in middle age. Genetic variants may underlie predisposition to CKD in those with heredity for MI. © 2014 S. Karger AG, Basel.
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12.
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13.
  • Cordeiro, AC, et al. (författare)
  • Influence of erythropoiesis-stimulating agents on glycated hemoglobin in nondiabetic kidney diseases at the start of dialysis
  • 2011
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 33:1, s. 17-24
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> Although glycated hemoglobin (HbA<sub>1C</sub>) is a practical tool to assess long-term glucose control in the general population, it may underestimate glycemic control in chronic kidney disease (CKD) patients – especially those undergoing treatment with erythropoiesis-stimulating agents (ESA). We evaluated the association of HbA<sub>1C</sub> with other parameters of glucose homeostasis and tested its association with ESA use and mortality in nondiabetic incident dialysis patients. <i>Methods:</i> We studied 270 nondiabetic CKD stage 5 patients referred to initiate dialysis therapy [median age: 54 years (43–63), 154 males]. Patients were followed for up to 5 years for survival analysis. <i>Results: </i>HbA<sub>1C</sub> was positively correlated with age (Rho = 0.13; p = 0.031), C-reactive protein (Rho = 0.14; p = 0.024), total cholesterol (Rho = 0.19; p = 0.001), triglycerides (Rho = 0.21; p < 0.001) and glucose (Rho = 0.21; p = 0.001), but it was negatively correlated with HDL-cholesterol (Rho = –0.22; p < 0.001) and ESA dose (Rho = –0.27; p < 0.001). Across increasing HbA<sub>1C</sub> tertiles, increased glucose levels and reduced use of ESA and dose of ESA were observed (p < 0.001), but there were no differences in insulin and HOMA index. In a stepwise multivariate linear regression analysis, ESA dose was negatively associated with logHbA<sub>1C</sub>. HbA<sub>1C</sub> did not predict mortality. <i>Conclusion:</i> In nondiabetic CKD stage 5 patients, HbA<sub>1C</sub> levels were associated with ESA dose. HbA<sub>1C</sub> was not independently associated with surrogate markers of insulin resistance or mortality.
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14.
  • Dadfar, E, et al. (författare)
  • Granulocyte extravasation and recruitment to sites of interstitial inflammation in patients with renal failure
  • 2004
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 24:3, s. 330-339
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> We have shown that leukocytes collected from sites of interstitial inflammation in patients on hemodialysis have a disturbed expression of CD11b compared to cells from healthy subjects. The aim of the present study was to study adhesion molecule expression on granulocytes in the peripheral circulation and at sites of interstitial inflammation in patients with renal failure. <i>Methods:</i> Two skin blisters were raised in 10 patients and 19 healthy subjects and interstitial exudates collected (0 h). Skin chambers were applied and exposed to buffer or serum for 10 h in order to induce an intermediate and an intense interstitial inflammation. Cells and blister fluid were collected for determination of leukocyte count, CD11b/CD62L expression, interleukin-8 (IL-8) concentration in the interstitium and blister activity in terms of CD11b up-regulation. <i>Results:</i> At the sites of intermediate and intense inflammation, granulocytes from patients with renal failure showed significantly higher expression of CD62L (p < 0.01 and p < 0.001, respectively) and significantly lower expression of CD11b (p < 0.0001 and p < 0.0001, respectively) compared to corresponding cells from healthy subjects. The interstitial concentration of IL-8 was significantly lower at the sites of intermediate (p < 0.005) and intense inflammation (p < 0.05) in patients with renal failure compared to in healthy subjects. In order to explore whether the decreased CD11b expression observed in patients is due to the interstitial milieu, blister exudates from patients and healthy subjects were incubated with leukocytes from healthy blood donors. Blister exudates from patients had a similar capacity to mobilize CD11b on granulocytes in vitro compared with blister exudates from healthy subjects. There was no consistent correlation between the expression of adhesion molecules on granulocytes in the interstitium and the concentration of IL-8 or the total interstitial concentration of chemotactic mediators. <i>Conclusion:</i> Constitutive cellular determinants are probably involved in the disturbed expression of adhesion molecules on granulocytes at sites of interstitial inflammation in patients with renal failure.
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16.
  • Demirel, Isak, 1987-, et al. (författare)
  • Nitric oxide activates IL-6 production and expression in human renal epithelial cells
  • 2012
  • Ingår i: American Journal of Nephrology. - Basel, Switzerland : S. Karger. - 0250-8095 .- 1421-9670. ; 36:6, s. 524-530
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aims: Increased nitric oxide (NO) production or inducible form of NO synthase activity have been documented in patients suffering from urinary tract infection (UTI), but the role of NO in this infection is unclear. We investigated whether NO can affect the host response in human renal epithelial cells by modulating IL-6 production and mRNA expression. Methods: The human renal epithelial cell line A498 was infected with a uropathogenic Escherichia coli (UPEC) strain and/or the NO donor DETA/NO. The IL-6 production and mRNA expression were evaluated by ELISA and real-time RT-PCR. IL-6 mRNA stability was evaluated by analyzing mRNA degradation by real-time RT-PCR.Results: DETA/NO caused a significant (p < 0.05) increase in IL-6 production. Inhibitors of p38 MAPK and ERK1/2 signaling, but not JNK, were shown to significantly suppress DETA/NO-induced IL-6 production. UPEC-induced IL-6 production was further increased (by 73 ± 23%, p < 0.05) in the presence of DETA/NO. The IL-6 mRNA expression increased 2.1 ± 0.17-fold in response to DETA/NO, while the UPEC-evoked increase was pronounced (20 ± 4.5-fold). A synergistic effect of DETA/NO on UPEC-induced IL-6 expression was found (33 ± 7.2-fold increase). The IL-6 mRNA stability studies showed that DETA/NO partially attenuated UPEC-induced degradation of IL-6 mRNA.Conclusions: NO was found to stimulate IL-6 in renal epithelial cells through p38 MAPK and ERK1/2 signaling pathways and also to increase IL-6 mRNA stability in UPEC-infected cells. This study proposes a new role for NO in the host response during UTI by modulating the transcription and production of the cytokine IL-6.
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17.
  • Gong, XZ, et al. (författare)
  • N-acetylcysteine amide protects renal proximal tubular epithelial cells against iohexol-induced apoptosis by blocking p38 MAPK and iNOS signaling
  • 2010
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 31:2, s. 178-188
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> The pathogenesis of contrast-induced nephropathy (CIN) is still poorly understood and apoptosis via oxidative stress has been proposed as one possible mechanism. We therefore studied the apoptotic signaling mechanism in CIN and also tested whether the new antioxidant N-acetylcysteine amide (NACA) could prevent CIN. <i>Methods:</i> LLC-PK1 cells were exposed to a widely used contrast agent, iohexol (IH). Cytotoxicity was assessed with morphology and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell death was analyzed by the DNA content analysis and PARP cleavage. Protein expression was assessed with Western blotting. <i>Results:</i> We observed cell death with apoptotic features in a dose- and time-dependent manner. Initiation of IH-induced apoptosis was mediated by upregulation of Bax and downregulation of Bcl-2 and Mcl-1, which was preceded by p38 MAPK activation and iNOS induction. Inhibitors of p38 MAPK and iNOS partially abolished IH-induced apoptosis. Furthermore, we found pretreatment with NACA partially protected cells from IH-induced death by reverting the expression of Bcl-2, Mc1-1 and Bax expression through inhibition of p38 MAPK and iNOS pathway. <i>Conclusions:</i> This study demonstrates that apoptosis occurs during CIN. Apoptosis is associated with activations of p38 MAPK and iNOS. Pretreatment with the antioxidant NACA could prevent IH-induced cell death by blocking the p38 MAPK/iNOS signaling pathway.
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18.
  • Gong, XZ, et al. (författare)
  • Tetramethylpyrazine prevents contrast-induced nephropathy by inhibiting p38 MAPK and FoxO1 signaling pathways
  • 2013
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 37:3, s. 199-207
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> Apoptosis is recognized as an important mechanism in contrast-induced nephropathy (CIN). As tetramethylpyrazine (TMP) has been recently found to be renoprotective and anti-apoptotic in multiple kidney injuries, we hypothesized that TMP would prevent CIN. <b><i>Methods:</i></b> An experimental model of CIN was established in rats. Serum creatinine, blood urea nitrogen, plasma cystatin C, urinary N-acetyl-β-glucosaminidase, and urinary &#947;-glutamyl transpeptidase were measured to evaluate kidney function. Apoptosis was assessed by transmission electron microscopy, transferase-mediated deoxyuridine triphosphate nick end-labeling staining, and poly-ADP-ribose polymerase cleavage. Fork-head box O1 transcriptional factor (FoxO1) mRNA expression was evaluated by quantitative real-time PCR. Phospho-p38 mitogen-activated protein kinase (MAPK) protein expression was assessed by immunohistochemistry and Western blotting. <b><i>Results:</i></b> TMP significantly attenuated the resulting renal dysfunction and renal tubular cell apo-ptosis. Mechanistically, TMP decreased the expression of phospho-p38 MAPK protein and attenuated the increased FoxO1 mRNA and nuclear protein expression. In addition, TMP inhibited inducible nitric oxide synthase and Bax protein expression while it upregulated Bcl-2. <b><i>Conclusion:</i></b> In summary, this study demonstrated the protective role of TMP against CIN and indicated the effects of TMP may be mediated by the inhibition of p38 MAPK and FoxO1 pathways. Thus, TMP may be a new potential therapeutic agent to prevent CIN.
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19.
  • Guo, Q, et al. (författare)
  • N-terminal pro-brain natriuretic peptide independently predicts protein energy wasting and is associated with all-cause mortality in prevalent HD patients
  • 2009
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 29:6, s. 516-523
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> N-terminal pro-brain natriuretic peptide (NT-proBNP) has been demonstrated to be associated with cardiovascular disease (CVD) and mortality in end-stage renal disease patients. We hypothesized that common confounders, such as protein-energy wasting (PEW) and inflammation could modulate this relationship. <i>Methods:</i> NT-proBNP was measured in 222 prevalent hemodialysis (HD) patients (55.4% male, mean age 66 years, range 51–74) using commercial ELISA. Levels were related to clinical characteristics, biochemical markers and survival. <i>Results:</i> NT-proBNP levels were positively associated with IL-6 (ρ = 0.37, p <0.001) and C-reactive protein (ρ = 0.25, p <0.001), but negatively associated with serum IGF-1 (ρ = –0.34, p < 0.001), handgrip strength (ρ = –0.30, p <0.001) and body weight (ρ = –0.20, p < 0.001). In multivariate analysis, an NT-proBNP level above the cutoff of the receiver-operating curve (9,761 pg/ml) was associated with PEW (odds ratio = 2.30, p = 0.008) even following adjustment for age, dialysis vintage, inflammation and the Davies score. As expected, NT-proBNP predicted clinical CVD (odds ratio = 1.90, p = 0.05) and all-cause mortality (Cox regression hazard ratio = 1.57, p = 0.03) also after adjustment for confounders. Patients with an NT-proBNP above the cutoff also exhibited a higher mortality (Kaplan-Meier χ<sup>2</sup> = 13.95, p < 0.001). <i>Conclusion:</i> We demonstrate a novel association between NT-proBNP and PEW, which may be part of the explanation for the strong links between NT-proBNP and mortality in HD patients.
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20.
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21.
  • Jacobson, SH, et al. (författare)
  • Monocyte-related determinants of inflammation in patients on peritoneal dialysis
  • 2001
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 21:1, s. 40-46
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Aims:</i> We studied markers of monocyte activation, i.e., the cell surface expression of CD11b and CD62L, and the serum concentrations of monocyte chemotactic protein 1 (MCP-1; a monocyte-specific chemoattractant) and soluble vascular cell adhesion molecule 1 (sVCAM-1; an adhesion molecule involved in monocyte recruitment) in 20 patients on peritoneal dialysis (PD), in 25 patients with chronic renal insufficiency, and in 27 healthy subjects. <i>Results:</i> Monocytes obtained from the peripheral blood of PD patients had a significantly higher expression of CD62L (p = 0.02) as compared with monocytes from healthy subjects and a lower CD11b/CD18 expression as compared with monocytes collected from healthy subjects (p < 0.001) and from patients with renal insufficiency (p < 0.001). Monocytes from PD patients had, however, the capacity to increase the expression of CD11b following stimulation with a potent chemotactic factor. The serum concentrations of MCP-1 and sVCAM-1 were higher in PD patients (575 ± 51 and 1,517 ± 89 ng/ml) than in healthy subjects (225 ± 17 and 668 ± 64 ng/ml, respectively; p < 0.001 for both comparisons). There was a correlation between the levels of sVCAM-1 and MCP-1 (r = 0.48, p < 0.05) in patients on PD, but neither correlated with the monocyte expression of CD11b/CD18 or CD62L. The concentration of C-reactive protein was higher in patients on PD as compared with healthy subjects and correlated significantly with the concentration of sVCAM-1 (r = 0.63, p < 0.01). <i>Conclusions:</i> Monocytes in the peripheral circulation of patients on PD have a CD62L<sup>high</sup>/CD11b<sup>low</sup> phenotype, indicating that they have not undergone complete differentiation. Patients also have an increase in the systemic chemotactic activity for monocytes in combination with increased levels of sVCAM-1 and C-reactive protein. These inflammatory aberrations may play a pathophysiological role in the response to inflammatory and infectious diseases in patients on PD.
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22.
  • Jaconbson, SH, et al. (författare)
  • Correlation between soluble markers of endothelial dysfunction in patients with renal failure
  • 2002
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 22:1, s. 42-47
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Aim:</i> Damage to the endothelium is an important component of atherosclerosis. It has been suggested to be quantified by measuring plasma markers, such as von Willebrand factor and thrombomodulin and soluble adhesion molecules. We hypothesized there may exist a correlation between the plasma levels of von Willebrand factor and thrombomodulin as markers of endothelial cell dysfunction and the serum concentrations of soluble adhesion molecules and monocyte chemoattractant protein-1 (MCP-1) in patients with renal insufficiency, and in patients on peritoneal dialysis or hemodialysis since these three groups of kidney patients are highly prone to develop cardiovascular diseases. <i>Results:</i> The concentrations of von Willebrand factor and thrombomodulin in plasma were significantly higher in patients with kidney diseases as compared to healthy subjects (p = 0.017 and p < 0.001, respectively). The patients also had significantly higher concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and MCP-1 compared to healthy controls (p < 0.001 for both comparisons). There were strong correlations between the concentration of soluble intercellular adhesion molecule-1 (sICAM-1) and von Willebrand factor in patients with kidney failure (r = 0.63, p < 0.001) and between the concentration of thrombomodulin and sVCAM-1 (r = 0.61, p < 0.001). Furthermore, a negative correlation was observed between the concentration of thrombomodulin and the cell surface expression of CD11b on monocytes and granulocytes in the peripheral circulation (p < 0.01 in both cases). <i>Conclusion:</i> The strong correlation between markers of endothelial dysfunction and soluble adhesion molecules in patients with renal insufficiency and on dialysis strengthen the view that an ongoing stress on endothelial cells is present in this group of patients. This may play a pathophysiological role in the development of cardiovascular disease.
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23.
  • Jia, Ting, et al. (författare)
  • Determinants of Fibroblast Growth Factor-23 and Parathyroid Hormone Variability in Dialysis Patients
  • 2013
  • Ingår i: American Journal of Nephrology. - : Karger. - 0250-8095 .- 1421-9670. ; 37:5, s. 462-471
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aims: Treatment strategies for abnormal mineral metabolism in chronic kidney disease are largely based on achieving target ranges of biomarkers that vary considerably over time, yet determinants of their variability are poorly defined. Methods: Observational study including 162 patients of three dialysis cohorts (peritoneal dialysis, n = 78; hemodialysis, n = 49; hemodiafiltration, n = 35). Clinical and biochemical determinants of parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) variability were analyzed in the peritoneal dialysis cohort. All cohorts were used for comparison of PTH and FGF23 intra-subject variability (intra-class correlation), and their intra-subject variability in different modes of dialysis was explored. Results: High PTH variability was independently associated with lower 25-hydroxyvitamin D concentration and factors of lipid and glucose metabolism, whereas high FGF23 variability was mainly associated with lower baseline serum phosphorous. These results were consistent in multivariate and sensitivity analyses. The intra-subject variability of FGF23 was lower than for PTH irrespective of dialysis mode. Conclusions: Baseline vitamin D status and serum phosphorous are independent determinants of the longitudinal variation in PTH and FGF23, respectively. The clinical utility of FGF23 measurement remains unknown, yet it appears favorable based on its greater temporal stability than PTH in dialysis patients.
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24.
  • Kocyigit, I, et al. (författare)
  • Early arterial stiffness and inflammatory bio-markers in normotensive polycystic kidney disease patients
  • 2012
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 36:1, s. 11-18
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background/Aims:</i></b> Cardiovascular disease is the main cause of morbidity and mortality in autosomal-dominant polycystic kidney disease (ADPKD) patients. To clarify temporal relationship between ADPKD, hypertension and the loss of renal function, we examined these factors in patients with early-stage ADPKD who did not yet have hypertension. <b><i>Methods:</i></b> Fifty patients with ADPKD (42% males, 36.6 ± 9.9 years, no blood pressure medication) and 50 healthy controls (44% males, 35.4 ± 6.4 years) were studied cross-sectionally. Pulse wave velocity (PWV), cardiac morphology and function, aortic elastic indexes, estimated glomerular filtration rate (eGFR), 24-hour ambulatory blood pressure, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and highly sensitive C-reactive protein (hs-CRP) were measured in all participants, using conventional methods. <b><i>Results:</i></b> Despite a normal blood pressure, aortic stiffness index and pulse wave velocity values were increased in patients compared to controls (6.8 ± 4.7 vs. 5.1 ± 3.3, p = 0.043 and 9.6 ± 1.3 vs. 5.8 ± 1.1 m/s, p < 0.001). In univariate analysis, IL-6, TNF-α, hs-CRP and eGFR were all significantly correlated with PWV. The independence of these correlations were analyzed in a regression model, and showed PWV to be significantly predicted by IL-6, TNF-α and hs-CRP. <b><i>Conclusion:</i></b> Increased arterial stiffness and pulse wave velocity are early manifestations of ADPKD appearing before hypertension or reduced eGFR. However, these vascular abnormalities are related to signs of systemic low grade inflammation, suggesting a common pathophysiological mechanism apparently present also in other vascular diseases but yet to be elucidated.
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25.
  • Kronbichler, A, et al. (författare)
  • Rituximab treatment for relapsing minimal change disease and focal segmental glomerulosclerosis: a systematic review
  • 2014
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 39:4, s. 322-330
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) remain a therapeutic challenge, since steroids and other immunosuppressive agents exhibit an unfavorable adverse event spectrum. The aim of this review was to systematically summarize and analyze data from preexisting studies reporting the outcome of rituximab (RTX) treatment in these patients. <b><i>Methods:</i></b> Study data on adult patients with either steroid-dependent or frequently relapsing MCD/FSGS were identified by a PubMed and Embase search. The number of relapses was calculated and the use of immunosuppressive co-medication prior to and after RTX treatment was quantified. <b><i>Results:</i></b> We identified<b> </b>14 studies<b> </b>including 86 patients with frequently relapsing and steroid-dependent MCD or FSGS. Treatment with RTX reduced the number of relapses per year from 1.3 (0-9) relapses prior to treatment compared to 0 (0-2) after therapy (p < 0.001). Proteinuria decreased from 2.43 (0-15) g/day to 0 (0-4.89) g/day (p < 0.001), while serum albumin increased from 2.9 (1.2-4.6) at baseline to 4.0 (1.8-5.09) g/l after RTX (p = 0.001). The use of immunosuppression used at the time of RTX administration was also reduced after RTX therapy (p < 0.001). Baseline serum albumin was lower (p = 0.018), whereas the number of immunosuppressants prior to RTX was higher (p = 0.018) in patients with relapse after RTX. <b><i>Conclusions:</i></b> The published data suggest that RTX is effective in reducing the number of relapses and sparing immunosuppression in frequently relapsing and steroid-dependent nephrotic syndrome due to MCD and FSGS. These promising findings have to be confirmed in controlled and prospective studies.
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26.
  • Lee, SMK, et al. (författare)
  • Low serum uric acid level is a risk factor for death in incident hemodialysis patients
  • 2009
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 29:2, s. 79-85
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> A reverse epidemiology of classic cardiovascular risk factors was observed in hemodialysis patients with a high comorbidity burden. We hypothesized that uric acid, a novel cardiovascular risk factor, also has an altered association with survival in these patients. <i>Methods:</i> A retrospective study was conducted on 168 consecutive outpatient hemodialysis patients over a 6-year period. Serum uric acid, albumin levels and relevant laboratory information were recorded monthly. The disease severity was assessed using Comorbidity Index (CoI) scores. Patients were stratified into 3 groups according to their serum uric acid concentrations: group I was the lowest quintile, group II was the middle 3 quintiles and group III was the highest quintile. The risks of death were calculated utilizing a Cox regression model. <i>Results:</i> Using group II as a reference group, the hazard ratio of group I was 2.23 [95% confidence interval (CI) 1.21–4.11, p = 0.01] and group III was 0.89 (95% CI 0.47–1.71, p = 0.74). The serum uric acid levels correlated inversely with CoI scores (r = –0.31, 95% CI –0.44 to –0.17, p < 0.0001) and positively with serum albumin levels (r = 0.35, 95% CI 0.21–0.48, p < 0.0001). <i>Conclusion:</i> Low serum uric acid is a mortality risk factor in incident hemodialysis patients with a high comorbidity burden and hypoalbuminemia.
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27.
  • Li, XJ, et al. (författare)
  • Cardiovascular Risk Prediction in Chronic Kidney Disease
  • 2023
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 53:10, s. 730-739
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> As one of the main complications of chronic kidney disease (CKD), the incidence of cardiovascular disease (CVD) in CKD patients is high. CVD risk is markedly increased even at early stages of CKD, and CVD deaths account for half of all known causes of mortality in end-stage renal disease patients. The alarming rate of CVD in CKD patients demands accurate risk prediction to identify individuals at greater risk and therefore needing intensive surveillance and treatment in order to improve their prognosis. <b><i>Summary:</i></b> Since the CVD risk prediction models used in general population did not perform well in CKD patients, novel CVD risk biomarkers and improved risk predictive models adapted to CKD are receiving increasing attention in recent years. In this article, we review the applicability and performance of some of the available cardiovascular risk prediction tools in CKD. <b><i>Key Messages:</i></b> Cardiovascular risk prediction in CKD needs and deserves continued attention and in-depth research that helps clinicians set out timely and effective interventions.
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28.
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29.
  • Lindgren, BF, et al. (författare)
  • Insulin-like growth factor I correlates with protein intake estimated from the normalized protein catabolic rate in hemodialysis patients
  • 2000
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 20:4, s. 255-262
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background/Aim:</i> Malnutrition and catabolism are predominant problems in patients undergoing hemodialysis. The aim of this study was to clarify the relationship between insulin-like growth factor I (IGF-I), the serum levels of which are influenced by nutrition and which by itself promotes amino acid uptake, and insulin-like growth factor binding protein 1 (IGFBP-1), known to regulate serum (s) IGF-I and protein intake, in end-stage renal disease patients. <i>Methods:</i> Thirty hemodialysis patients were studied, and s-IGF-I and s-IGFBP-1 levels were measured by radioimmunoassay. The s-IGF-I method used was validated according to a reference method. The s-IGF-I standard deviation (SD) score was calculated, giving the individual deviation from the mean of a reference population. The protein intake was estimated both directly by 3-day food recall by a dietician and indirectly by normalized protein catabolic rate (PCRn). <i>Results:</i> The mean serum IGF-I level was 166 ± 10 μg/l, corresponding to a normal s-IGF-I SD score (0.5 ± 0.3). S-IGFBP-1 was elevated threefold to 101 ± 11 μg/l as compared with normal subjects. The s-albumin was 39.9 ± 0.5 g/l and the s-bicarbonate 24 ± 0.4 mmol/l. There were significant correlations between s-IGF-I SD score or s-IGF-I (log-transformed) and PCRn (r = 0.37, p < 0.004, and r = 0.41, p < 0.001, respectively). The s-IGF-I/s-IGFBP-1 ratio was also positively correlated with PCRn (r<sub>s</sub> = 0.36, p < 0.007, by Spearman’s rank correlation). The s-albumin was inversely correlated with log s-IGFBP-1 (r = –0.38, p < 0.01) and positively with the s-IGF-I/s-IGFBP-1 ratio (r = 0.36, p < 0.007) but not with s-IGF-I (p < 0.13). Serum total cholesterol, triglycerides, and total body fat as percentage of body weight correlated with s-IGF-I (r = 0.47, p < 0.004, r = 0.45, p < 0.01, and r = 0.42, p < 0.004, respectively) as well as with the s-IGF-I SD score. No correlations were seen between s-IGF-I and protein or caloric intake by direct estimates from dietary food recalls. <i>Conclusions:</i> The s-IGF-I and the s-IGF-I/s-IGFBP-1 ratio were correlated with estimates of protein intake of the patients calculated from urea kinetics (PCRn) but not with direct estimates by the dietitian. The s-IGF-I SD score and the ratio s-IGF-I/s-IGFBP-1 might be a tool to monitor anabolic status and to select hemodialysis patients for therapeutic intervention with recombinant human IGF-I and/or recombinant human growth hormone to counteract catabolism.
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30.
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31.
  • Long, Thorir E., et al. (författare)
  • Postoperative Acute Kidney Injury : Focus on Renal Recovery Definitions, Kidney Disease Progression and Survival
  • 2019
  • Ingår i: American Journal of Nephrology. - : KARGER. - 0250-8095 .- 1421-9670. ; 49:3, s. 175-185
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of this study was to examine different definitions of renal recovery following postoperative acute kidney injury (AKI) and how these definitions associate with survival and the development and progression of chronic kidney disease (CKD).Methods: This was a retrospective study of all patients who underwent abdominal, cardiothoracic, vascular, or orthopedic surgery at a single university hospital between 1998 and 2015. Recovery of renal function following postoperative AKI was assessed comparing 4 different definitions: serum creatinine (SCr) (i) < 1.1 x baseline, (ii) 1.1-1.25 x baseline, (iii) 1.25-1.5 x baseline, and (iv) > 1.5 x baseline. One-year survival and the development or progression of CKD within 5 years was compared with a propensity score-matched control groups.Results: In total, 2,520 AKI patients were evaluated for renal recovery. Risk of incident and progressive CKD within 5 years was significantly increased if patients did not achieve a reduction in SCr to < 1.5 x baseline (hazard ratio [HR] 1.50; 95% CI 1.29-1.75) and if renal recovery was limited to a fall in SCr to 1.25-1.5 x baseline (HR 1.32; 95% CI 1.12-1.57) within 30 days. The definition of renal recovery that best predicted survival was a reduction in SCr to < 1.5 x baseline within 30 days. One-year survival of patients whose SCr decreased to < 1.5 x baseline within 30 days was significantly better than that of a propensity score-matched control group that did not achieve renal recovery (85 vs. 71%, p < 0.001).Conclusions: These findings should be considered when a consensus definition of renal recovery after AKI is established.
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32.
  • Lundwall, K, et al. (författare)
  • Paricalcitol, Microvascular and Endothelial Function in Non-Diabetic Chronic Kidney Disease: A Randomized Trial
  • 2015
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 42:4, s. 265-273
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> Vitamin D deficiency, sympathetic activation and endothelial dysfunction are associated with increased cardiovascular risk in patients with chronic kidney disease (CKD). Studies have so far failed to establish the role of vitamin D and vitamin D receptor activator (VDRA) treatment in moderate CKD. This trial was designed to assess whether VDRA treatment can ameliorate sympathetic activation and macro- and microvascular dysfunction in non-diabetic patients with moderate CKD. <b><i>Methods:</i></b> We conducted a randomized controlled double-blind trial using placebo, 1 or 2 μg of paricalcitol, a VDRA, for 3 months. We assessed muscle sympathetic nerve activity (MSNA) by microneurography, pulse wave velocity (PWV) by tonometry, flow mediated vasodilatation (FMD) by brachial ultrasound, skin microcirculation assessed by iontophoresis and capillary blood velocity (CBV) by videophotometric capillaroscopy. <b><i>Results:</i></b> Thirty-six patients with a mean age of 65 years and mean estimated glomerular filtration rate of 40 ml/min/1.73 m<sup>2</sup> were included. We found a significant decline in endothelial function after 3 months, except in the group receiving 2 μg of paricalcitol. The higher dose (2 μg) seemed to attenuate the decline in microvascular endothelial function, assessed by iontophoresis of acetylcholine (p = 0.06 for all groups, p = 0.65 for the 2 μg group) and for FMD (p = 0.006 for all groups, p = 0.54 for the 2 μg group). We found a borderline significance (p = 0.05) for improved CBV in the treated groups. We found no significant changes between treatments in MSNA, PWV or albuminuria. <b><i>Conclusions:</i></b> Endothelial function declined significantly over 3 months in patients with moderate CKD, and this decline could be ameliorated by VDRA treatment (NCT01204528).
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33.
  • Ozen, KP, et al. (författare)
  • Nutritional state alters the association between free triiodothyronine levels and mortality in hemodialysis patients
  • 2011
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 33:4, s. 305-312
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background:</i> Serum free triiodothyronine (fT3) level is suggested to be a risk factor for mortality in unselected dialysis patients. We investigated the prognostic value of serum fT3 levels and also low-T3 syndrome on overall survival in a large cohort of hemodialysis (HD) patients with normal thyroid-stimulating hormone levels. <i>Methods:</i> A total of 669 prevalent HD patients were enrolled in the study. Serum fT3 level was measured by enzyme immune assay in frozen sera samples at the time of enrollment. Overall mortality was assessed during 48 months of follow-up. <i>Results:</i> Baseline fT3 was 1.47 ± 0.43 (0.01–2.98) pg/ml, and low-T3 syndrome was present in 71.7% of the cases. During a mean follow-up of 34 ± 16 months, 165 (24.7%) patients died. fT3 level was a strong predictor for mortality in crude and adjusted Cox models including albumin or high-sensitivity C-reactive protein (hs-CRP). Further adjustment for both albumin and hs-CRP made the impact of fT3 on mortality disappear. The presence of low-T3 syndrome was associated with mortality in only the unadjusted model. <i>Conclusions:</i> Low-T3 syndrome is a frequent finding among HD patients, but it does not predict outcome. However, serum fT3 level is a strong and inverse mortality predictor, in part explained by its underlying association with nutritional state and inflammation.
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34.
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35.
  • Ruge, Toralph, et al. (författare)
  • Endostatin Level is Associated with Kidney Injury in the Elderly : Findings from Two Community-Based Cohorts
  • 2014
  • Ingår i: American Journal of Nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 40:5, s. 417-424
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to investigate the associations between circulating endostatin and the different aspects of renal dysfunction, namely, estimated (cystatin C) glomerular filtration rate (GFR) and urine albumin-creatinine ratio (ACR). Methods: Two independent longitudinal community-based cohorts of elderly. ULSAM, n = 786 men; age 78 years; median GFR 74 ml/min/1.73 m(2); median ACR 0.80 mg/mmol); and PIVUS, n = 815; age 75 years; 51% women; median GFR; 67 ml/min/1.73 m(2); median ACR 1.39 mg/mmol. Cross-sectional associations between the endostatin levels and GFR as well as ACR, and longitudinal association between endostatin at baseline and incident CKD (defined as GFR <60 ml/min/1.73 m(2)) were assessed. Results: In cross-sectional regression analyses adjusting for age, gender, inflammation, and cardiovascular risk factors, serum endostatin was negatively associated with GFR (ULSAM: B-coefficient per SD increase -0.51, 95% CI (-0.57, -0.45), p < 0.001; PIVUS -0.47, 95% CI (-0.54, -0.41), p < 0.001) and positively associated with ACR (ULSAM: B-coefficient per SD increase 0.24, 95% CI (0.15, 0.32), p < 0.001; PIVUS 0.13, 95% CI (0.06-0.20), p < 0.001) in both cohorts. Moreover, in longitudinal multivariable analyses, higher endostatin levels were associated with increased risk for incident CKD defined as GFR < 60 ml/min/1.73 m(2) at re-investigations in both ULSAM (odds ratio per SD increase of endostatin 1.39 (95% CI 1.01-1.90) and PIVUS 1.68 (95% CI 1.36-2.07)). Conclusions: Higher circulating endostatin is associated with lower GFR and higher albuminuria and independently predicts incident CKD in elderly subjects. Further studies are warranted to investigate the underlying mechanisms linking endostatin to kidney pathology, and to evaluate the clinical relevance of our findings. (C) 2014 S. Karger AG, Basel
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36.
  • Ruilope, LM, et al. (författare)
  • Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
  • 2019
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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37.
  • Schneider, Andreas, et al. (författare)
  • Determinants of Cardiovascular Risk in Haemodialysis Patients : Post hoc Analyses of the AURORA Study
  • 2013
  • Ingår i: American Journal of Nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 37:2, s. 144-151
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Haemodialysis patients are at high risk for cardiovascular (CV) events. The aim of the current study was to characterise the role of traditional and uraemia-specific CV risk factors in this patient population. Methods: A post hoc analysis of the AURORA trial which enrolled 2,776 haemodialysis patients from 280 centres and had a mean follow-up period of 3.2 years. Determinants of CV endpoints (time to major cardiovascular event (MACE), cardiac event, CV death) were identified by univariate Cox regression analysis. Subsequently, independent determinants were identified by multivariate regression analysis. Results: For the primary endpoint MACE (myocardial infarction, stroke and cardiac death), multivariate analysis revealed that independent determinants were: age (hazard ratio (HR) 1.03 per year), serum phosphate level (HR 1.50 per mmol/l), albumin level (HR 0.94 per gip, years on haemodialysis (HR 1.03 per year), diabetes mellitus (HR 1.38), preexisting coronary heart disease (HR 1.54) and C-reactive protein (CRP) level (HR 1.14 per mg/l). However, conventional risk factors such as smoking, dyslipidaemia, systolic and diastolic blood pressure and pulse pressure had no significant effect. Conclusions: Although we identify CRP, low albumin, and high phosphorus as risk factors for MACE, lowering CRP did not influence MACE outcomes in our trial. Caution is therefore warranted in implying risk factors being causal in end-stage renal disease.
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38.
  • Shah, Shivani, et al. (författare)
  • Treatment of Severe Renal Disease in ANCA Positive and Negative Small Vessel Vasculitis with Rituximab.
  • 2015
  • Ingår i: American Journal of Nephrology. - : S. Karger. - 0250-8095 .- 1421-9670. ; 41:4-5, s. 296-301
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND/AIMS: Rituximab and glucocorticoids are a non-inferior alternative to cyclophosphamide and glucocorticoid therapy for induction of remission in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) patients with moderate renal disease. The efficacy and safety of this approach in patients with severe renal impairment are unknown. We report the outcomes and safety profile of rituximab and glucocorticoid therapy for induction of remission in patients with AAV and ANCA-negative vasculitis presenting with severe renal disease.METHODS: A multicenter, retrospective, cohort study was conducted between 2005 and 2014. Patients with new or relapsing disease with an estimated glomerular filtration rate (eGFR) of ≤20 ml/min/1.73 m(2) treated with rituximab and glucocorticoid induction with or without plasmapheresis were included. Fourteen patients met the inclusion criteria. The primary outcomes were rate of remission and dialysis independence at 6 months. The secondary outcomes were eGFR at 6 months, end-stage renal disease (ESRD), survival rates and adverse events.RESULTS: All patients were Caucasian, and 57% were male. The mean eGFR was 12 ml/min/1.73 m(2) at diagnosis. All patients achieved remission with a median time to remission of 55 days. Seven patients required dialysis at presentation of which 5 patients recovered renal function and discontinued dialysis by 6-month follow-up. The mean eGFR for the 11 patients without ESRD who completed 6-month follow-up was 33 ml/min/1.73 m(2). Four patients ultimately developed ESRD, and one died during the follow-up period.CONCLUSION: Patients with AAV and severe renal disease achieve high rates of remission and dialysis independence when treated with rituximab and glucocorticoids without cyclophosphamide. © 2015 S. Karger AG, Basel.
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39.
  • Sun, Ying, et al. (författare)
  • Glomerular Transcriptome Changes Associated with Lipopolysaccharide-Induced Proteinuria
  • 2009
  • Ingår i: American Journal of Nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 29:6, s. 558-570
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Global gene expression patterns have recently been characterized in normal glomeruli, but gene expression changes that accompany glomerular disease remain poorly characterized. Method: Here, we mapped global glomerular gene expression profile changes occurring in conjunction with lipopolysaccharide (LPS)-induced proteinuria in mice. Results: We observed dramatic transcriptional reprogramming in glomeruli in response to LPS, representing some 20% of all genes and about 45% of the genes that are normally highly expressed in glomeruli. Bioinformatic analysis revealed significant changes in transcripts encoding proteins involved in the regulation of adherence junctions, actin cytoskeleton and survival in podocytes. In the LPS-treated mice, we observed dysregulation of genes expressed in glomerular endothelial and mesangial cells and in podocytes, there was also a significant decrease in podocyte number. Moreover, collagen alpha 1, alpha 2 (IV) and laminin 10 (laminin alpha 5 beta 1 gamma 1), which are expressed in immature glomeruli, were upregulated in the glomeruli of LPS-treated mice, suggesting remodeling of the glomerular basement membrane and activation of mesangial cells. By superimposing the LPS-induced changes onto GlomNet, a protein-protein interaction network was predicted for podocyte proteins affected by LPS. Conclusions: The detected changes in glomerular gene expression and their involvement in protein interaction networks provide putative markers for early and transient glomerular injury and proteinuria. Copyright (c) 2009 S. Karger AG, Basel
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40.
  • Tasevska, Irina, et al. (författare)
  • Increased Levels of Copeptin, a Surrogate Marker of Arginine Vasopressin, Are Associated with an Increased Risk of Chronic Kidney Disease in a General Population
  • 2016
  • Ingår i: American Journal of Nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 44:1, s. 22-28
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Our aim was to test if plasma copeptin, a stable surrogate marker of arginine vasopressin, predicts decline of glomerular filtration rate (GFR) and risk of chronic kidney disease (CKD). Methods: We measured copeptin and renal function at the Malmö Diet and Cancer Cardiovascular Cohort baseline exam and reassessed renal function after a follow-up time of 16.6 ± 1.5 years (n = 3,186). Furthermore, we defined CKD based on an estimated GFR (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) MDRD), MDRD) and MDRD) ml/min/1.73 m2. Results: After multivariate adjustment (gender, age, baseline eGFR, smoking status, systolic blood pressure, antihypertensive treatment and follow-up time), copeptin (beta-coefficient per 1 SD increment of copeptin) was independently associated with significantly greater annual decline of eGFR (ml/min/1.73 m2) according to the MDRD formula (OR 0.057, 95% CI 0.022-0.093; p = 0.001) as well as according to the CKD Epidemiology Collaboration (CKD-EPI) formula (OR 0.050, 95% CI 0.022-0.077; p <0.001). Each SD increment of copeptin independently predicted incident CKD_60MDRD (OR 1.19, 95% CI 1.04-1.36; p = 0.010), CKD_45MDRD (OR 1.33, 95% CI 1.04-1.71; p = 0.026) and CKD_30MDRD (OR 3.69, 95% CI 1.41-9.66; p = 0.008). The relationship between copeptin and CKD defined by CKD-EPI gave similar results. Conclusion: Our data suggest that increased levels of copeptin independently predict decline in eGFR and greater risk of new-onset CKD.
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41.
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42.
  • Tong, ML, et al. (författare)
  • Genistein attenuates advanced glycation end product-induced expression of fibronectin and connective tissue growth factor
  • 2012
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 36:1, s. 34-40
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Objective:</i></b> To investigate the effect of advanced glycation end products (AGEs) on the expression of connective tissue growth factor (CTGF) and fibronectin (FN) in human peritoneal mesothelial cells (HPMC). To observe the effect of genistein (Gen) on the expression of CTGF and FN in HPMC induced by AGEs. <b><i>Methods:</i></b> First, HPMC were stimulated with different concentrations of AGEs (0, 200, 600 and 1,000 mg/l) for 48 h; the expression of FN was detected by reverse transcription-polymerase chain reaction (RT-PCR). Second, HPMC were divided into the following groups: (1) control group, (2) AGE-treated group (600 mg/l AGEs) and (3) Gen-treated groups with 600 mg/l AGEs and 25, 50 and 100 µ<i>M</i>Gen, respectively. The expression of messenger RNA (mRNA) for FN and CTGF was measured by RT-PCR; the expression of FN and CTGF protein was detected by enzyme-linked immunosorbent assay (ELISA) after 48 h. <b><i>Results:</i></b> The expression of FN mRNA in HPMC increased in a dose-dependent manner after induction with AGEs. Compared with controls, 600 mg/l AGEs markedly promoted the expression of mRNA and protein for FN and CTGF. Compared with the AGE-treated group (600 mg/l), 25, 50, and 100 µ<i>M</i> Gen significantly inhibited the expression of mRNA and protein for FN and CTGF. <b><i>Conclusion:</i></b> AGEs can markedly increase the expression of mRNA and protein for FN and CTGF; however, Gen can inhibit the expression of FN and CTGF mRNA and protein stimulated by AGEs, which implies that Gen probably decreases the accumulation of extracellular matrix through inhibiting the expression of CTGF, and it may play a role in anti-peritoneal fibrosis.
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43.
  • Wallquist, C, et al. (författare)
  • Early Changes in Monocyte Adhesion Molecule Expression and Tumor Necrosis Factor-α Levels in Chronic Kidney Disease - A 5-Year Prospective Study
  • 2016
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 44:4, s. 268-275
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> Despite the absence of clinical symptoms, patients with chronic kidney disease (CKD) exhibit elevated levels of pro-inflammatory markers. To investigate whether it is possible to detect inflammatory activity and altered monocyte function at an early stage of renal disease, we studied patients with CKD stages 2-3 over 5 years. <b><i>Methods:</i></b> The expression of adhesion molecules on monocytes at resting state and after stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP), as well as oxidative metabolism capacity was measured with flow cytometry in 108 CKD patients and healthy controls. Soluble markers of inflammation, such as cytokines, were analyzed using the Milliplex technique. <b><i>Results:</i></b> Patients showed significantly lower CD11b expression after stimulation during the 3rd (p = 0.002) and the 5th year (p < 0.001), together with a lower oxidative burst in response to fMLP over time (p = 0.02). The expression of CD62L on resting monocytes was lower during the 3rd (p = 0.001) and the 5th (p = 0.001) year in patients. Levels of tumor necrosis factor-α and RANTES were significantly increased (p = 0.001, p = 0.006) and interleukin-12 levels were also higher in CKD patients during the 5th year (p = 0.007). <b><i>Conclusion:</i></b> Monocytes in CKD stages 2-3 show emerging functional abrasions, with altered adhesion molecule expression and impaired fMLP response. These findings suggest that a transformation of monocyte function occurs at an early phase of renal impairment and may together with increased plasma levels of pro-inflammatory cytokines contribute to the higher vulnerability of CKD patients to comorbidities, such as infections and cardiovascular disease.
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44.
  • Westman, K W, et al. (författare)
  • Persistent high prevalence of thyroid antibodies after immunosuppressive therapy in subjects with glomerulonephritis. A prospective three-year follow-up study
  • 1998
  • Ingår i: American Journal of Nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 18:4, s. 9-274
  • Tidskriftsartikel (refereegranskat)abstract
    • The prevalence of thyroid antibodies, indicating an autoimmune thyroiditis, has been shown to be significantly increased in patients with autoimmune diseases. A 3-year prospective follow-up study of 42 patients with biopsy-confirmed glomerulonephritis is presented. Although the majority of patients had been treated with immunosuppressants, the prevalence of thyroid peroxidase antibodies was unchanged in both females and males, 47 and 15% respectively, at follow-up. Likewise, the prevalence of thyroglobulin antibodies was unaffected as was that of antinuclear antibodies (ANA) when analysing males and females together. However, for males there was a trend to higher prevalence for ANA at follow-up. On the other hand, the prevalence of antineutrophil cytoplasmic antibodies declined. Furthermore, thyroid antibodies were not restricted to membranous nephropathy, and notably found in 4 out of the 8 patients with vasculitis.
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45.
  • Wändell, Per, et al. (författare)
  • End-stage kidney diseases in immigrant groups : a nationwide cohort study in Sweden
  • 2019
  • Ingår i: American Journal of Nephrology. - : S. Karger AG. - 0250-8095 .- 1421-9670. ; 49:3, s. 186-192
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Our aim was to study the association between the country of birth and incident end-stage kidney disease (ESKD) in several immigrant groups in Sweden, using individuals born in Sweden or with Swedish-born parents as referents.METHODS: A cohort study of first- and second-generation immigrants residing in Sweden between January 1, 1998 and December 31, 2012 was performed. Outcomes were defined as having at least one registered diagnosis of ESKD in the National Patient Register. The incidence of ESKD in different immigrant groups was used in the Cox regression models to estimate hazard ratios (HRs) and 95% CIs. All models were stratified by sex and adjusted for age, geographical residence, educational level, marital status, and neighbourhood socioeconomic status.RESULTS: Compared to their referents, higher incidence rates and HRs of ESKD (HR; 95% CI) were observed in general among foreign-born men (1.10; 1.04-1.16) and women (1.12; 1.04-1.21) but not among second-generation immigrants (persons born in Sweden with foreign-born parents). A particularly high -incidence was noted among men and women from -East-European countries, as well as from non-European regions. A lower incidence of ESKD was noted among men from Finland.CONCLUSIONS: We observed substantial differences in incidence of ESKD between immigrant groups and the Swedish-born population, which may be clinically relevant when monitoring preventive measures in patient subgroups with a higher risk of deteriorating kidney disease, and suggest higher attention to hypertension and diabetes control in immigrants. Mechanisms attributable to the migration process or ethnic differences may lead to an increased risk of ESKD.
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46.
  • Yilmaz, MI, et al. (författare)
  • Predictors of carotid artery intima-media thickness in chronic kidney disease and kidney transplant patients without overt cardiovascular disease
  • 2010
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 31:3, s. 214-221
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background/Aims:</i> Carotid intima-media thickness (IMT) assessed using ultrasonography is a widely used marker of atherosclerosis. In the largest study to date of IMT and chronic kidney disease (CKD), we assessed correlates of IMT in CKD patients with a wide range of renal dysfunction, and also investigated what happens to IMT following renal transplantation. <i>Methods:</i> We studied 406 patients with different stages of nondiabetic CKD (50% males, 46 ± 12 years), and 58 kidney transplant recipients (27 ± 6 years), testing relationships between IMT, assessed by ultrasonography, and selected biomarkers. <i>Results:</i> Despite a lack of overt CVD, patients had significantly higher IMT as compared to controls (0.9 [0.7–1.0] vs. 0.6 [0.4–0.7] mm; p > 0.001). Furthermore, in multivariate analysis IMT was independently associated with CKD stage, mean arterial pressure (MAP) and calcium-phosphate product, but not with Framingham risk factors. Following kidney transplantation, IMT decreased rapidly, reaching levels comparable to those in the controls within 90 days. In a time-dependent multivariate analysis, this decrease was predicted by changes in GFR, MAP, and uric acid levels. <i>Conclusion:</i> Our data does not exclude IMT as a predictor of mortality in CKD, but suggests that other etiologies than atherosclerosis may be more important in determining IMT levels in the population with CKD.
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47.
  • Zhang, D, et al. (författare)
  • Evaluation of genetic association and expression reduction of TRPC1 in the development of diabetic nephropathy
  • 2009
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 29:3, s. 244-251
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background/Aims:</i> The TRPC1 gene on chromosome 3q22–24 resides within the linkage region for diabetic nephropathy (DN) in type 1 (T1D) and type 2 diabetes mellitus (T2D). A recent study has demonstrated that TRPC1 expression is reduced in the kidney of diabetic ZDF- and STZ-treated rats. The present study aimed to evaluate the genetic and functional role of TRPC1 in the development of DN. <i>Methods:</i> Genetic association study was performed with two independent cohorts, including 1,177 T1D European Americans with or without DN from GoKinD population and 850 African-American subjects with T2D-associated end-stage renal disease (ESRD), or with hypertensive (non-diabetic) ESRD, and nondiabetic controls. Seven tag SNP markers derived from HapMap data (phase II) were genotyped. TRPC1 gene expression was examined using real time RT-PCR. <i>Results:</i> No significant association of TRPC1 DNA polymorphisms with DN or ERSD was found in GoKinD and African-American populations. TRPC1 gene mRNA expression in kidney was found to be trendily reduced in 12-week and significantly in 26-week-old db/db mice. <i>Conclusions:</i> TRPC1 genetic polymorphism may not fundamentally contribute to the development of DN, while reduction of the gene expression in kidney may be a late phenomenon of DN as seen in diabetic animal models.
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48.
  • Zhang, DY, et al. (författare)
  • Genetic and functional effects of membrane metalloendopeptidase on diabetic nephropathy development
  • 2011
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 34:5, s. 483-490
  • Tidskriftsartikel (refereegranskat)abstract
    • <i>Background/Aims:</i> Vasopeptidase as an agent inhibits membrane metalloendopeptidase (MME, also known as neutral endopeptidase). MME is widely distributed in the body and particularly abundant in the kidney. The <i>MME </i>gene is located on chromosome 3q25.1 within a linkage region for diabetic nephropathy (DN). The present study aims to evaluate the genetic and functional effects of MME in the development of DN. <i>Methods:</i> A case-control genetic study of the<i> MME</i> gene in type 1 diabetes (T1D) patients with and without DN (n = 578/599) was performed. All subjects were selected from the Genetics of Kidneys in Diabetes study. Genotyping was performed with TagMan allelic discrimination. <i>Mme </i>mRNA and protein expression levels in kidney tissues of db/db mice at the ages of 5, 12 and 26 weeks were analyzed with TaqMan real-time RT-PCR and Western blot. <i>Results:</i> The haplotype A-C constructed with single nucleotide polymorphisms (SNPs) rs3796268A/G and rs3773885C/T in the <i>MME</i> gene was found to be associated with DN (p = 0.015, OR = 1.33, 95% CI 1.05–1.68) in female T1D patients. Further analyses of renal traits in T1D patients with DN and end-stage renal disease according to the genotypes of SNP rs3773885 indicated that the C allele carriers had higher serum creatinine levels compared to the subjects carrying T allele in both females and males. <i>Mme </i>expression at mRNA and protein levels was upregulated in kidneys of db/db mice at the ages of 12 and 26 weeks (p = 0.017 and <0.001) but not at the age of 5 weeks compared to the controls. <i>Conclusions:</i> The present study provides the first evidence that <i>MME </i>has genetic and biological effects on the development of DN, and suggests that the inhibition of <i>MME </i>expression in the kidney with the agent of vasopeptidase may be a useful therapeutic approach for this disease.
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49.
  • Zhang, XQ, et al. (författare)
  • Serum Lysyl Oxidase Is a Potential Diagnostic Biomarker for Kidney Fibrosis
  • 2020
  • Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 51:11, s. 907-918
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> Kidney fibrosis is the ultimate consequence of advanced stages of chronic kidney disease (CKD); however, there are currently no reliable biomarkers or noninvasive diagnostic tests available for the detection of kidney fibrosis. Lysyl oxidase (LOX) promotes collagen cross-linking, and serum LOX levels have been shown to be elevated in patients with fibrosis of the heart, lungs, and liver. However, serum LOX levels have not been reported in patients with kidney fibrosis. We explored whether serum LOX levels are associated with kidney fibrosis. <b><i>Method:</i></b> Overall, 202 patients with kidney disease underwent renal biopsy, scoring of kidney fibrosis, and determination of the area of kidney fibrosis. LOX levels were measured in serum and in kidney tissues. We analyzed the association of circulating LOX and tissue LOX levels with the scores and areas of kidney fibrosis. LOX expression was also investigated with in vitro and in vivo kidney fibrosis models. <b><i>Results:</i></b> Serum LOX levels were higher in patients with kidney fibrosis than in those without kidney fibrosis (<i>p</i> &#x3c; 0.001) and higher in patients with moderate-severe kidney fibrosis than in patients with mild kidney fibrosis (<i>p</i> &#x3c; 0.001). Both serum LOX and renal tissue LOX levels correlated with the area of kidney fibrosis (<i>r</i> = 0.748, <i>p</i> &#x3c; 0.001; <i>r</i> = 0.899, <i>p</i> &#x3c; 0.001, respectively). Receiver operating characteristic curve analysis of serum LOX levels showed an area under the curve of 0.80 (95% CI: 0.74–0.86). The optimal serum LOX level cutoff point was 253.34 pg/mL for the prediction of kidney fibrosis and 306.56 pg/mL for the prediction of moderate-severe kidney fibrosis. LOX expression levels were significantly upregulated (2.3–2.6 and 6-fold, respectively) in in vitro and in vivo interstitial fibrosis models. <b><i>Conclusions:</i></b> Both serum LOX and tissue LOX levels correlated with the presence and degree of kidney fibrosis in patients with CKD. These results suggest that serum LOX levels could potentially serve as a noninvasive diagnostic biomarker for kidney fibrosis and may further potentially serve as a stratified biomarker for the identification of mild and moderate-severe kidney fibrosis.
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50.
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