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| 2. |
- Akrawi, Delshad Saleh, et al.
(författare)
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Heritability of End-Stage Renal Disease : A Swedish Adoption Study
- 2018
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Ingår i: Nephron. - : S. Karger AG. - 1660-8151 .- 2235-3186. ; 138:2, s. 157-165
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: The heritability of end-stage renal disease (ESRD) among adoptees has not been examined so far. By studying adoptees and their biological and adoptive parents, it is possible to differentiate between the genetic causes and environmental causes of familial aggregation. This nationwide study aimed to disentangle the genetic and shared environmental contribution to the familial transmission of ESRD. Methods: We performed a family study for Swedish-born adoptees (born between 1945 until 1995) and their biological and adoptive parents. The Swedish Multi-Generation Register was linked to the National Patient Registry for the period 1964–2012. ESRD was defined as patients in active uremic care, that is, chronic dialysis or kidney transplantation. OR for ESRD was determined for adoptees with an affected biological parent with ESRD compared with adoptees without a biological parent with ESRD. The OR for ESRD was also calculated in adoptees with an adoptive parent with ESRD compared with adoptees with an adoptive parent without ESRD. Moreover, heritability for ESRD was estimated with Falconer’s regression. Results: A total of 111 adoptees, 463 adoptive parents, and 397 biological parents were affected by ESRD. The OR for ESRD was 6.41 in adoptees (95% CI 2.96–13.89) of biological parents diagnosed with ESRD. The OR for ESRD was 2.40 in adoptees (95% CI 0.76–7.60) of adoptive parents diagnosed with ESRD. The heritability of ESRD was 59.5 ± 18.2%. Conclusion: The family history of ESRD in a biological parent is an important risk factor for ESRD. The high heritability indicates that genetic factors play an important role in understanding the etiology of ESRD.
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| 3. |
- Eckersten, Dag, et al.
(författare)
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Impact of Kidney Transplantation on Reproductive Hormone Levels in Males : A Longitudinal Study
- 2018
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Ingår i: Nephron. - : S. Karger AG. - 1660-8151 .- 2235-3186. ; 138, s. 192-201
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Male patients with end-stage renal disease suffer from sexual disturbances and infertility. Disturbances in the hypothalamic-pituitary-gonadal axis are one of the causes of this. Decreased testosterone synthesis in Leydig cells of the testes and hyperprolactinemia are common. Kidney transplantation, unlike hemodialysis, normalizes these changes. However, how kidney transplantation affects Sertoli cell function is poorly understood. This study is aimed at investigating the changes in fertility-related hormones in men before, during, and after renal transplantation. Methods: This longitudinal and prospective single center study enrolled 12 men undergoing living donor kidney transplantation. Plasma levels of creatinine, cystatin C, and serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, testosterone, sex hormone-binding globulin, inhibin B, and anti-Müllerian hormone (AMH) were assayed at 10 different time points before, during, and after kidney transplantation. Results: A rapid decrease in creatinine and cystatin C levels indicated successful renal transplantation. High pre-transplantation plasma levels of prolactin (mean 516 ± 306 mIE/L) and LH (9.4 ± 4.7 IU/L) were normalized after 7 days (248 ± 161 mIE/L and 6.1 ± 3.1 IU/L, respectively). Testosterone decreased rapidly during transplantation and increased again one week post-transplantation. Sertoli cell-derived hormone inhibin B decreased after transplantation, and there was a small non-significant trend of increased AMH after 12 months. Conclusion: Sertoli cell function, based on AMH and inhibin B levels, does not improve to the same extent or as fast as Leydig cell function after kidney transplantation, as determined by testosterone and LH levels.
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| 4. |
- Feehally, J, et al.
(författare)
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Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy
- 2016
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Ingår i: Nephron. - : S. Karger AG. - 2235-3186 .- 1660-8151. ; 132:1, s. 15-24
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits. <b><i>Methods:</i></b> The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy. <b><i>Results:</i></b> Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR. <b><i>Conclusion:</i></b> In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline.
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| 5. |
- Grincenkov, FRD, et al.
(författare)
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Impact of baseline health-related quality of life scores on survival of incident patients on peritoneal dialysis: a cohort study
- 2015
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Ingår i: Nephron. - : S. Karger AG. - 2235-3186 .- 1660-8151. ; 129:2, s. 97-103
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> In an attempt to decrease mortality in patients with end-stage renal disease, an increase in the lifetime of these patients without much focus on health-related quality of life (HRQOL) was pursued for a long period of time. However, lately, an improvement in the quality of this extended lifetime has focused on both the physical as well as the social and emotional aspects, as these parameters may be associated with clinical outcomes in end-stage renal disease patients. <b><i>Aim:</i></b> To evaluate the impact of self-determined HRQOL at admission on survival of incident peritoneal dialysis (PD) patients. <b><i>Patients and Methods:</i></b> A total of 1,624 incident Brazilian PD patients participating in a multicenter prospective cohort study (BRAZPD) were evaluated. HRQOL was assessed using the SF-36, divided into mental and physical components. Cox proportional regression analysis was used to determine the influence of<b> </b>HRQOL (mental and physical components) on mortality. Multivariate Cox proportional hazards analyses were used to adjust gradually for more potential explanatory variables: first for demographic variables, followed by additional adjustment for socioeconomic, clinical and laboratory variables. The significance level in all analyses was set at p < 0.05. All analyses were carried out with SPSS 17.0. <b><i>Results:</i></b> Incident PD patients presented with low HRQOL scores on admission to therapy. Even after correction for sociodemographic variables, comorbidities, PD modality and laboratory parameters, HRQOL (both the mental and the physical components) remained a predictor [HR: 0.97 (CI: 0.95-0.98); HR: 0.97 (CI: 0.96-0.99), respectively] of survival. <b><i>Conclusion:</i></b> On admission to therapy, patients presenting with low HRQOL scores for both the mental and the physical components were associated with a higher mortality. These results suggest that early and timely intervention measures to improve the QOL of these patients are important.
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| 6. |
- Levin, A, et al.
(författare)
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Serum Glutaredoxin Activity as a Marker of Oxidative Stress in Chronic Kidney Disease: A Pilot Study
- 2018
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Ingår i: Nephron. - : S. Karger AG. - 2235-3186 .- 1660-8151. ; 140:4, s. 249-256
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Inflammation and oxidative stress play important roles in the pathogenesis and progression of chronic kidney disease (CKD) and in its complications, in particular cardiovascular disease, a major cause of death among patients undergoing dialysis treatment. We recently described that Glutaredoxin1 (Grx), an intracellular antioxidant, catalyzes oxidoreductase reactions also extracellularly, and that serum Grx levels correlate to disease severity in type 2 diabetes. <b><i>Aim:</i></b> In the current study we assess Grx as a potential clinical marker of oxidative stress in CKD. <b><i>Methods:</i></b> We examined Grx activity in 25 patients with different stages of chronic kidney failure, 19 control subjects, and 36 patients at initiation of dialysis and after 2 years of dialysis. <b><i>Results:</i></b> We found that Grx activity was significantly higher in CKD patients compared to control subjects, indicating an oxidized extracellular environment in CKD. Grx levels correlated to interleukin-6 and pentosidine, but not to age or GFR. In dialysis patients with Grx sampling before dialysis start and after 2 years of dialysis, Grx levels increased more in hemodialysis (HD) patients than in peritoneal dialysis patients, indicating an increased oxidative stress imbalance in HD patients. Patients who experienced a stroke or myocardial infarction at any time had a significantly higher increase in Grx during the 2 years of dialysis, compared to patients without stroke or myocardial infarction, indicating a possible association between high Grx levels and a cardiovascular event. <b><i>Conclusion:</i></b> Our pilot study indicates that Grx may be a useful marker for assessing the degree of oxidative stress in CKD, however this needs further investigation in a larger prospective patient cohort.
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| 7. |
- Mansouri, L, et al.
(författare)
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Hemodialysis Patients Display a Declined Proportion of Th2 and Regulatory T Cells in Parallel with a High Interferon-γ Profile
- 2017
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Ingår i: Nephron. - : S. Karger AG. - 2235-3186 .- 1660-8151. ; 136:3, s. 254-260
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> A high prevalence of cardiovascular diseases (CVDs) and infections in patients with chronic kidney disease (CKD) arises partly due to a high inflammatory state and aberrations in immune cells function. Following in vitro stimulation of leukocytes with different T-cell mitogens, we observed a lower level of interleukin (IL)-2 and IL-10 production in CKD patients. To gain more knowledge as to whether this is the result of an alteration in T-cell function, we investigated the T-cell subsets profile and cytokine production in hemodialysis patients. <b><i>Methods:</i></b> CD4+ cells were isolated from whole blood of 10 hemodialysis patients and 10 age- and gender-matched healthy controls. Following in vitro stimulation with an antigen-independent T-cell mitogen, Th1, Th2, and regulatory T (Treg) cell subsets were analyzed by flow cytometry through the expression of specific transcription factors. The levels of cytokines, interferon (IFN)-γ, IL-4, and IL-10 were analyzed by enzyme-linked immunosorbent assay in the supernatants. <b><i>Results:</i></b> The proportion of CD4+CD25+FOXP3+ (Treg) and CD4+GATA3+ (Th2) cells was significantly lower in patients compared to healthy controls, while the proportion of CD4+T-bet+ (Th1) cells was similar. Moreover, levels of IL-4 were significantly lower in supernatants from patients, while IFN-γ levels were higher. IL-10 levels did not differ compared to those of the healthy controls. <b><i>Conclusions:</i></b> Our findings indicate a diminished anti-inflammatory Treg, and Th2 cell profile in hemodialysis patients, accompanied by a high pro-inflammatory IFN-γ profile. Since this profile is characterized in CVDs, we propose that an imbalance between the inflammatory and anti-inflammatory responses may contribute to the pathogenesis of CVD in advanced CKD.
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| 8. |
- Wallquist, C, et al.
(författare)
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Associations of Fibroblast Growth Factor 23 with Markers of Inflammation and Leukocyte Transmigration in Chronic Kidney Disease
- 2018
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Ingår i: Nephron. - : S. Karger AG. - 2235-3186 .- 1660-8151. ; 138:4, s. 287-295
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Patients with chronic kidney disease (CKD) show elevated levels of inflammatory markers and have an increased risk of infections as well as cardiovascular morbidity. Recent studies have implied effects of fibroblast growth factor 23 (FGF23) on inflammation in CKD. We analyzed potential correlations between levels of FGF23 with pro-inflammatory chemokines and markers of leukocyte transmigration in CKD patients. <b><i>Methods:</i></b> One hundred three patients with CKD 2–5ND and 54 healthy controls, had biochemical markers in blood and urine analyzed according to routine protocol. Pro-inflammatory cytokines were analyzed by Milliplex technique and leukocyte CD11b adhesion molecule expression was measured by flow cytometry. FGF23 levels were measured with ELISA technique. Treatment of leukocytes from healthy blood donors with FGF23 was performed in vitro and effects analyzed by flow cytometry. <b><i>Results:</i></b> Tumor necrosis factor-alpha, RANTES and interleukin (IL)-12 levels were significantly higher (<i>p</i> = 0.001, <i>p</i> < 0.001, and <i>p</i> < 0.001) in patients with CKD. Elevated FGF23 levels in the CKD group correlated to glomerular filtration rate, parathyroid hormone, urinary albumin excretion and phosphate as well as to IL-12 and RANTES. CD11b expression on resting granulocytes and monocytes, and on activated monocytes, was associated with FGF23<i>.</i> In vitro treatment of leukocytes with FGF23 reduced CD11b expression in resting as well as in formyl-methyinoyl-leucyl-phenylalanine-stimulated granulocytes (<i>p</i> = 0.03). <b><i>Conclusion:</i></b><i></i> FGF23 levels are associated with various inflammatory markers such as pro-inflammatory cytokines and adhesion molecules on innate immune cells. However, further studies are warranted to define the direct role of FGF23 in modulation of the innate immune system in CKD.
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| 9. |
- Werner, Karin, et al.
(författare)
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Combining Cystatin C and Creatinine Yields a Reliable Glomerular Filtration Rate Estimation in Older Adults in Contrast to β-Trace Protein and β2-Microglobulin
- 2017
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Ingår i: Nephron. - : S. Karger AG. - 1660-8151 .- 2235-3186. ; 137, s. 29-37
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Tidskriftsartikel (refereegranskat)abstract
- Background: The glomerular filtration rate (GFR) is the most important measure of kidney function and chronic kidney disease (CKD). This study aims to validate commonly used equations for estimated GFR (eGFR) based on creatinine (cr), cystatin C (cys), β-trace protein (BTP), and β2-microglobulin (B2M) in older adults. Method: We conducted a validation study with 126 participants aged between 72 and 98 with a mean measured GFR (mGFR) by iohexol clearance of 54 mL/min/1.73 m2. The eGFR equations (CKD-Epidemiology collaboration [CKD-EPI], Berlin Initiative Study [BIS], Full Age Spectrum [FAS], Modification of Diet in Renal Disease [MDRD]cr, Caucasian-Asian-Pediatric-Adult [CAPA]cys, Lund-Malmö Revised [LM-REV]cr, and MEAN-LM-CAPAcr-cys), were assessed in terms of bias (median difference: eGFR-mGFR), precision (interquartile range of the differences), and accuracy (P30: percentage of estimates ±30% of mGFR). The equations were compared to a benchmark equation: CKD-EPIcr-cys. Results: All cystatin C-based equations underestimated the GFR compared to mGFR, whereas bias was mixed for the equations based only on creatinine. Accuracy was the highest for CKD-EPIcr-cys (98%) and lowest for MDRD (82%). Below mGFR 45 mL/min/1.73 m2 only equations incorporating cystatin C reached P30 accuracy >90%. CKD-EPIcr-cys was not significantly more accurate than the other cystatin C-based equations. In contrast, CKD-EPIcr-cys was significantly more accurate than all creatinine-based equations except LM-REVcr. Conclusion: This study confirms that it is reasonable to use equations incorporating cystatin C and creatinine in older patients across a wide spectrum of GFR. However, the results call into question the use of creatinine alone below mGFR 45 mL/min/1.73 m2. B2M and BTP do not demonstrate additional value in eGFR determination in older adults.
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