| 1. |
- Abeling, T., et al.
(author)
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Risk factors for death in kidney transplant patients: analysis from a large protocol biopsy registry
- 2019
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In: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 34:7, s. 1171-1181
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Journal article (peer-reviewed)abstract
- BACKGROUND: Identification and quantification of the relevant factors for death can improve patients' individual risk assessment and decision-making. We used a well-documented patient cohort (n = 892) in a renal transplant programme with protocol biopsies to establish multivariable Cox models for risk assessment at 3 and 12 months post-transplantation. METHODS: Patients transplanted between 2000 and 2007 were observed up to 11 years (total observation 5227 patient-years; median 5.9 years). Loss to follow-up was negligible (n = 15). A total of 2251 protocol biopsies and 1214 biopsies for cause were performed. All rejections and clinical borderline rejections in protocol biopsies were treated. RESULTS: Overall 10-year patient survival was 78%, with inferior survival of patients with graft loss and superior survival of patients with living-donor transplantation. Eight factors were common in the models at 3 and 12 months, including age, pre-transplant heart failure and a score of cardiovascular disease and type 2 diabetes, post-transplant urinary tract infection, treatment of rejection, new-onset heart failure, coronary events and malignancies. Additional variables of the model at 3 months included deceased donor transplantation, transplant lymphocele, BK virus nephropathy and severe infections. Graft function and graft loss were significant factors of the model at 12 months. Internal validation and validation with a separate cohort of patients (n = 349) demonstrated good discrimination of the models. CONCLUSIONS: The identified factors indicate the important areas that need special attention in the pre- and post-transplant care of renal transplant patients. On the basis of these models, we provide nomograms as a tool to weigh individual risks that may contribute to decreased survival. © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
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| 2. |
- Afghahi, Henri, 1966, et al.
(author)
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Risk factors for the development of albuminuria and renal impairment in type 2 diabetes—the Swedish National Diabetes Register (NDR)
- 2010
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In: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 26:4, s. 1236-1243
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Journal article (peer-reviewed)abstract
- Background. The aim of this study was to identify clinical risk factors associated with the development of albuminuria and renal impairment in patients with type 2 diabetes (T2D). In addition, we evaluated if different equations to estimate renal function had an impact on interpretation of data. This was done in a nationwide population-based study using data from the Swedish National Diabetes Register. Methods. Three thousand and six hundred sixty-seven patients with T2D aged 30-74 years with no signs of renal dysfunction at baseline (no albuminuria and eGFR >60 mL/min/1.73 m(2) according to MDRD) were followed up for 5 years (2002-2007). Renal outcomes, development of albuminuria and/or renal impairment [eGFR < 60 mL/min/1.73 m(2) by MDRD or eCrCl > 60 mL/min by Cockgroft-Gault (C-G)] were assessed at follow-up. Univariate regression analyses and stepwise regression models were used to identify significant clinical risk factors for renal outcomes. Results. Twenty percent of patients developed albuminuria, and 11% renal impairment; thus, ~6-7% of all patients developed non-albuminuric renal impairment. Development of albuminuria or renal impairment was independently associated with high age (all P < 0.001), high systolic BP (all P < 0.02) and elevated triglycerides (all P < 0.02). Additional independent risk factors for albuminuria were high BMI (P < 0.01), high HbA1c (P < 0.001), smoking (P < 0.001), HDL (P < 0.05) and male sex (P < 0.001), and for renal impairment elevated plasma creatinine at baseline and female sex (both P < 0.001). High BMI was an independent risk factor for renal impairment when defined by MDRD (P < 0.01), but low BMI was when defined by C-G (P < 0.001). Adverse effects of BMI on HbA1c, blood pressure and lipids accounted for ~50% of the increase risk for albuminuria, and for 41% of the increased risk for renal impairment (MDRD). Conclusions. Distinct sets of risk factors were associated with the development of albuminuria and renal impairment consistent with the concept that they are not entirely linked in patients with type 2 diabetes. Obesity and serum triglycerides are semi-novel risk factors for development of renal dysfunction and BMI accounted for a substantial proportion of the increased risk. The equations used to estimate renal function (MDRD vs. C-G) had an impact on interpretation of data, especially with regard to body composition and gender.
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| 3. |
- Andersson, Lena, 1980, et al.
(author)
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Methodological issues on the use of urinary alpha-1-microglobuline in epidemiological studies.
- 2008
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In: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 23:4, s. 1252-1256
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Journal article (peer-reviewed)abstract
- Background. Alpha-1-microglobulin (A1M) is a low molecular weight protein that can be measured in urine and used as a marker for tubular function, assuming that the normal variability within and between individuals is known. The aims of this study were to investigate this variability, to find the optimal way of sampling and quantifying A1M in spot urine samples to reflect the 24 h excretion and to examine storage stability. Method. Timed urine specimens were collected from 29 healthy volunteers at fixed time points over 24 h on two separate days. Volumes, creatinine and specific gravity were determined. All samples were analysed with a commercial ELISA for A1M. Results. We found a clear diurnal variation in A1M excretion rate and a gender effect (higher in males). The excretion rate was higher in the daytime, with high urinary flow, compared to overnight values. A1M excretion in spot urine samples was highly correlated with the 24 h excretion at all times except 22:00 in male subjects. Urinary A1M adjusted for creatinine concentration correlated well with the 24 h excretion. Variability within individuals was only 20% of the total variability in 24 h A1M excretion, but 43% in first morning urine. Expressed as CV, the intra-individual variability (between days) was 29% in 24 h excretion. Conclusion. We conclude that diurnal variation and gender should be taken into account when comparing groups. Moreover, in spot samples (e.g. first morning samples) adjustment of A1M for creatinine or specific gravity is a reliable alternative to 24 h urine.
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| 4. |
- Braide, Magnus, 1955, et al.
(author)
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Citrate supplementation of PD fluid: effects on net ultrafiltration and clearance of small solutes in single dwells
- 2009
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In: Nephrol Dial Transplant. - 1460-2385. ; 24:1, s. 286-92
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Journal article (peer-reviewed)abstract
- BACKGROUND: Inflammatory reactions affect the general performance as well as the technique survival of peritoneal dialysis (PD). Anti-inflammatory additives like heparin and sodium citrate have shown favourable results in these respects. The present study is the first to evaluate citrate-supplemented PD fluids (PDFs) in humans. METHODS: Crossover design was used to evaluate sodium citrate and heparin-supplemented Gambrosol Trio (2.5% glucose) in 28 stable outpatients from the PD unit. Comparisons were made between single dwells of each fluid. Citrate supplementation at 5 mM/L was compared with standard PDF, and citrate supplementation at 10 mM/L was compared with low-molecular-weight heparin (4500 units of tinzaparin) supplementation and standard PDF. The initial osmolarity of the fluids was equalized by adding sodium chloride. RESULTS: Citrate supplementation at 5 mM/L significantly increased net ultrafiltration, measured as drained volume gain, by 126 mL. Creatinine and phosphate clearance, but not glucose clearance, was significantly improved by supplementation with citrate or heparin. Heparin supplementation created an insignificant trend towards an increased ultrafiltration (P = 0.08). No negative side effects were reported for any of the treatments; however, citrate supplementation led to a small calcium loss by the drained PD fluid (0.4 mmol) and a transient fall in the plasma concentration (0.04 mM/L) of free calcium ions at 5 mM/L citrate. Effects on plasma bicarbonate concentration were insignificant. CONCLUSIONS: Citrate supplementation of PD fluid improved ultrafiltration and clearance of small solutes with only minor effects on calcium turnover. The mechanism is unknown and, according to the results, not related to complement inhibition.
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| 5. |
- Bruun, Laila, et al.
(author)
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Increase in percent free prostate-specific antigen in men with chronic kidney disease.
- 2009
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In: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 24:4, s. 1238-41
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Journal article (peer-reviewed)abstract
- BACKGROUND: Prostate-specific antigen (PSA) occurs in different molecular forms in serum: free PSA (fPSA) and complexed PSA (cPSA), the sum of which corresponds to total PSA (tPSA). In addition to tPSA, percent fPSA is widely used in the detection of prostate cancer. Free PSA, approximately 28 kDa, is eliminated by glomerular filtration. Previous data showed that men with end-stage renal dysfunction requiring chronic dialysis have increased percent fPSA. In this study, we evaluated whether moderate-to-severe chronic renal dysfunction, but with no need for dialysis, also importantly affects percent fPSA. METHODS: The study group consisted of 101 men (median age 57 years, interquartile range 46-68) with chronic kidney disease and no diagnosis of prostate cancer. Their median glomerular filtration rate (GFR) was 23 mL/min/1.73 m(2) (interquartile range 16-33; range 8-83), determined by iohexol clearance. Controls included 5264 men (median age 57 years, interquartile range 54-62) attending a prostate cancer screening program with no diagnosis of prostate cancer during 8 years of follow-up. RESULTS: With adjustment for age, median fPSA levels and percent fPSA were significantly higher (P < 0.001) in patients with renal dysfunction, 0.45 microg/L and 47.2%, respectively, compared to controls, 0.29 microg/L and 29.9%, respectively. Regression analysis in the study group showed a significant association between GFR and percent fPSA (P = 0.036). CONCLUSIONS: The percent fPSA is importantly influenced by moderately impaired renal function in men with chronic kidney disease. For such men, use of the current clinical decision limits for percent fPSA could cause some men with prostate cancer to be misdiagnosed as having benign disease, and therefore fPSA should not be used to diagnose prostate cancer in these patients.
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| 6. |
- Fehrman-Ekholm, Ingela, 1947, et al.
(author)
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Post-nephrectomy development of renal function in living kidney donors: a cross-sectional retrospective study
- 2011
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In: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 26:7, s. 2377-2381
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Journal article (peer-reviewed)abstract
- BACKGROUND: Increasing numbers of living donor kidney transplantations calls for better knowledge about long-term donor outcomes and risks. METHODS: To explore long-term kidney donor outcomes and risks, we conducted a cross sectional retrospective study. To this end, we analysed renal function using measured glomerular filtration rate (mGFR) and estimated glomerular filtration rate (eGFR) as well as microalbuminuria, blood pressure (BP), body mass index, haemoglobin, albumin and parathyroid hormone in kidney donors nephrectomized between 1965 and 2005. RESULTS: A total number of 573 kidney donors agreed to undergo medical follow-up examinations. The mean age (standard deviation) at donation was 47 (11) years and the mean time since donation was 14 (9) years. Both mean mGFR [68 (15) mL/min/1.73m(2) body surface; P = 0.028] and mean eGFR [71 (16) mL/min/1.73m(2) body surface; P < 0.001], based on modified diet renal dysfunction and iohexol or Cr-EDTA clearance, respectively, were found to decrease with age and to increase with time since donation. Special multivariable regression analyses reveal that for 30-year old donors, the median eGFR typically increases during the first 17 years, then remains constant for ∼8 years and slowly declines thereafter. For 50-year-old donors, the median eGFR is expected to increase during the first 15 years or so and then to enter a phase of slight progressive decline. In total, 23% (126/546) of the donors were on antihypertensive medication. An additional 22% (117/543) of the donors were found to suffer from hitherto undiagnosed hypertension (BP >140/90 mm Hg). CONCLUSION: Renal function of the remaining kidney in living donors is expected to improve for many years but will show signs of slight deterioration in the longer run.
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| 7. |
- Fischbach, M., et al.
(author)
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Effect of peritoneal dialysis fluid composition on peritoneal area available for exchange in children
- 2004
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In: Nephrol Dial Transplant. - : Oxford University Press (OUP). - 0931-0509. ; 19:4, s. 925-32
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Journal article (peer-reviewed)abstract
- BACKGROUND: Although conventional peritoneal dialysis fluids (PDFs), such as Dianeal, are non-physiological in composition, new PDFs including Physioneal have a more neutral pH, are at least partially buffered with bicarbonate and, most importantly, contain low concentrations of glucose degradation products (GDPs). METHODS: To evaluate the impact of new PDFs in childcare, we performed a comparative crossover study with Dianeal and Physioneal. We examined both intraperitoneal pressure (IPP), which partly reflects pain induction, and the total pore area available for exchange, which indicates the number of capillaries perfused in the peritoneal membrane at any given moment and therefore partly reflects peritoneal dialysis capacity. The IPP was determined after inflow of 1000 ml/m(2) body surface area (BSA) of dialysate (intraperitoneal volume; IPV). The steady-state unrestricted area over diffusion distance (A(0)/ triangle up x, in cm(2)/cm per 1.73 m(2) BSA) was calculated from the three-pore theory. Six children were enrolled in the study. On the first day, two consecutive peritoneal equilibration tests of 90 min each were performed using first Dianeal and then Physioneal. On the second study day, the procedure was repeated with the fluids given in the opposite order. RESULTS: The mean IPP normalized to IPV (ml/m(2)) was significantly higher for Dianeal (9.5 +/- 0.9 cm/1000 ml/m(2)) than for Physioneal (7.9 +/- 1.2 cm/1000 ml/m(2), P < 0.01). The mean A(0)/ triangle up x was 17 +/- 4% larger with Dianeal (36 095 +/- 2009 cm(2)/cm per 1.73 m(2)) than with Physioneal (31 780 +/- 2185 cm(2)/cm per 1.73 m(2), P < 0.001; based on 24 data pairs). CONCLUSIONS: These pilot study results suggest a higher biocompatibility for Physioneal than for Dianeal. Less inflow pain associated with Physioneal induced a lower IPP reflecting enhanced fill volume tolerance, and the lower A(0)/ triangle up x reflected less capillary recruitment. Taken together, these results suggest that the new more biocompatible PDFs will improve peritoneal dialysis therapy, although this conclusion will require verification in extended clinical trials.
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| 8. |
- Galle, Jan-Christoph, et al.
(author)
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An observational cohort study of extended dosing (once every 2 weeks or once monthly) regimens with darbepoetin alfa in patients with chronic kidney disease not on dialysis: the EXTEND study.
- 2012
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In: Nephrology, dialysis, transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 27:6, s. 2303-2311
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Journal article (peer-reviewed)abstract
- BACKGROUND: Darbepoetin alfa (DA) has been shown to be an effective treatment of anaemia in patients with chronic kidney disease (CKD) not on dialysis (NoD). EXTEND is an observational study assessing the effectiveness of DA administered once biweekly (Q2W) or monthly (QM) in a general CKD-NoD population.METHODS: Adult CKD-NoD patients starting DA Q2W/QM treatment in June 2006 or later were eligible. Retrospective and/or prospective data including haemoglobin levels and erythropoiesis-stimulating agent (ESA) dosing were collected for 6 months before and 12 months after DA initiation. Mean Hb levels were calculated every 3 months, and ESA dose was converted to a geometric mean weekly DA equivalent dose and summarized monthly.RESULTS: Data from 4278 patients showed that patients receiving ESA treatment before DA Q2W/QM initiation had a mean (95% confidence interval) Hb level of 11.9 g/dL (11.8-12.0 g/dL) at initiation and 11.6 g/dL (11.6-11.7 g/dL) at Months 10-12, with mean ESA dose of 22 μg/week (21-23 μg/week) prior to initiation, 16 μg/week (15-16 μg/week) at initiation and 16 μg/week (15-16 μg/week) at Month 12. In ESA-naive patients, Hb levels increased from 10.3 g/dL (10.2-10.3 g/dL) at initiation to 11.7 g/dL at Months 4-6 and were maintained at a mean level of 11.7 g/dL (11.7-11.8 g/dL) at Months 10-12, with mean ESA dose of 16 μg/week (16-17 μg/week) at initiation and 16 μg/week (16-17 μg/week) at Month 12. In the 85% of patients receiving DA at extended intervals (Q2W or less frequently) at Month 12, 12 patients (0.3%) experienced DA-related adverse reactions.CONCLUSION: DA Q2W/QM was an effective treatment of anaemia in the general CKD-NoD patient population and a dose increase was not required in patients switching from a previous ESA regimen.
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| 9. |
- Galle, J. C., et al.
(author)
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Outcomes in patients with chronic kidney disease not on dialysis receiving extended dosing regimens of darbepoetin alfa: long-term results of the EXTEND observational cohort study
- 2016
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In: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 31:12, s. 2073-2085
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Journal article (peer-reviewed)abstract
- Background. Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA. Methods. Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012. Outcomes included haemoglobin (Hb) concentration, ESA dosing, mortality rates and receipt of dialysis and renal transplantation. Subgroup analyses were conducted for selected outcomes. Results. Of 6035 enrolled subjects, 5723 (94.8%) met analysis criteria; 1795 (29.7%) received dialysis and 238 (3.9%) underwent renal transplantation. Mean (standard deviation) Hb concentration at commencement of extended dosing was 11.0 (1.5) g/dL. Mean [95% confidence interval (CI)] Hb 12 months after commencement of extended dosing (primary outcome) was 11.6 g/dL (11.5, 11.6) overall and was similar across countries, with no differences between subjects previously treated with an ESA versus ESA-naive subjects, subjects with versus without prior renal transplant or diabetics versus non-diabetics. Weekly ESA dose gradually decreased following commencement of extended DA dosing and was similar across subgroups. The decrease in weekly DA dose was accompanied by an increase in the proportion of patients receiving iron therapy. Hb concentrations declined following changes in ESA labels and treatment guidelines. The mortality rate (95% CI) was 7.06 (6.68, 7.46) deaths per 100 years of follow-up. Subjects alive at study end had stable Hb concentrations in the preceding year, while those who died had lower and declining Hb concentrations in their last year. Conclusions. Long-term, extended dosing of DA maintained Hb concentrations in patients already treated with an ESA and corrected and maintained Hb in ESA-naive patients.
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| 10. |
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