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Background: Mortality in hemodialysis patients still remains unacceptably high. Enhanced arterial stiffness is a known cardiovascular risk factor, and pulse wave velocity (PWV) has proven to be a valid parameter to quantify risk. Recent studies showed controversial results regarding the prognostic significance of PWV for mortality in hemodialysis patients, which may be due to methodological issues, such as assessment of PWV in the office setting (Office-PWV)., Method: This study cohort contains patients from the "Risk stratification in end-stage renal disease - the ISAR study," a multicenter prospective longitudinal observatory cohort study. We examined and compared the predictive value of ambulatory 24-hour PWV (24 h-PWV) and Office-PWV on mortality in a total of 344 hemodialysis patients. The endpoints of the study were all-cause and cardiovascular mortality. Survival analysis included Kaplan-Meier estimates and Cox regression analysis., Results: During a follow-up of 36 months, a total of 89 patients died, 35 patients due to cardiovascular cause. Kaplan-Meier estimates for tertiles of 24 h-PWV and Office-PWV were similarly associated with mortality. In univariate Cox regression analysis, 24 h-PWV and Office-PWV were equivalent predictors for all-cause and cardiovascular mortality. After adjustment for common risk factors, only 24 h-PWV remained solely predictive for all-cause mortality (hazard ratio 2.51 [95% CI 1.31-4.81]; p = 0.004)., Conclusions: Comparing both measurements, 24 h-PWV is an independent predictor for all-cause-mortality in hemodialysis patients beyond Office-PWV., (© 2019 S. Karger AG, Basel.)

Background/aims: This study compares the peritoneal elimination of the low-molecular-weight-protein (LMWP) C-terminal agrin fragment (tCAF, size 22 kDa), a promising biomarker for kidney function, in continuous cycling peritoneal dialysis (CCPD) and continuous ambulatory peritoneal dialysis (CAPD)., Methods: 103 sets of serum, 24h-urine and dialysate samples were obtained in 15 CCPD (63 sets) and 11 CAPD (40 sets) patients. Total, renal and peritoneal substrate removals/clearances were measured/calculated for tCAF, creatinine, blood-urea-nitrogen (BUN), cystatin C and albumin and correlated with the peritoneal transport type., Results: Serum und urine concentrations of all biomarkers did not differ between both groups, urinary substrate removal was higher in CAPD patients for all biomarkers due to better residual renal function. Peritoneal substrate removal of tCAF and albumin were significantly higher in CAPD (tCAF: 35.3 vs. 19.3 µg/d, p<0.001; albumin: 4.3 vs. 3.7 g/d, p=0.001), whereas cystatin C and creatinine did not differ between CAPD and CCPD (cystatin: 7.7 vs. 6.1 mg/d, p=0.08, creatinine: 423.9 vs. 456.7 mg/d, p=0.241). BUN was better removed by CCPD (4846.6 vs. 3393.4 mg/d, p<0.001). CAPD patients with high-transporter characteristics had a higher peritoneal tCAF removal compared to high-average-transporters (49.8 vs. 28.4 µg/d, p<0.001), no differences could be detected in CCPD patients between these groups. CAPD patients using icodextrin twice/day had higher peritoneal clearance of tCAF compared to once daily (4.4 vs. 2.8 l/wk/1.73 m2 body-surface-area, p<0.001)., Conclusions: CAPD was superior to CCPD concerning peritoneal tCAF removal. This finding was pronounced in high-transporters and CAPD patients using icodextrin twice daily., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Background: The C-terminal agrin fragment (CAF) is a cleavage product of agrin, the major proteoglycan of the glomerular basement membrane. This article studies if CAF could serve as a biomarker for renal function in renal transplant recipients., Material and Methods: We measured serum CAF and creatinine concentrations and calculated estimated glomerular filtration rate (eGFR) (MDRD) in 96 healthy individuals and in 110 end-stage renal disease patients undergoing kidney transplantation before and after transplantation. Correlation between CAF and creatinine concentrations/eGFR was calculated as within-patient (cWP) and between-patient correlations (cBP). Moreover, we evaluated the association of CAF with delayed graft function (DGF). The diagnostic value of CAF for early detection of DGF compared to creatinine was evaluated by receiver operating characteristics (ROC) analysis., Results: CAF concentrations strongly correlated with creatinine (r = 0.86 (cWP), r = 0.74 (cBP)) and eGFR (MDRD) (r = 0.86 (cWP), r = 0.77 (cBP)). Pre-transplant (pre-Tx) CAF concentrations were 19-fold higher than in healthy individuals (1,115.0 (258.4-3,990.0) vs. 56.6 (20.0-109.5) pM). After transplantation, CAF decreased significantly faster than creatinine (postoperative days 1-3 (POD 1-3): 562.8 (101.6-2,113.0) pM; creatinine: pre-Tx 6.9 (3.1-15.7), POD 1-3: 6.4 (1.7-12.7) mg/dl, p < 0.001). Stable concentrations were reached 1-3 months after transplantation for CAF and creatinine (CAF 145.1 (6.7-851.0) pM; creatinine 1.6 (0.7-8.0) mg/dl). CAF concentrations at POD 1-3 were significantly associated with DGF and outperformed creatinine in early detection of DGF (area under the curve (AUC) CAF 80.7% (95% CI 72.3-89.1%) vs. AUC creatinine 71.3% (95% CI 61.8-81.1%), p = 0.061)., Conclusion: CAF is a promising new and fast biomarker for kidney function and may serve as a new tool for the early detection of DGF., (© 2013 S. Karger AG, Basel.)

Background/aims: Single cases of lithium carbonate dosing in hemodialysis patients have been published. We investigate the dose-serum level relationship after single and multiple lithium acetate dosing in a hemodialysis patient and review the literature., Methods: Lithium acetate was administered orally over a period of 11 months in a patient with major depressive episodes after being placed on hemodialysis three times a week. The serum trough levels of lithium before and after hemodialysis were analyzed. The data were compared with those reported in the literature, and potential drug interactions and the importance of the residual renal function are discussed., Results: No adverse events due to the lithium therapy were documented. Steady state levels of between 0.6 and 0.8 mmol/l of lithium acetate were achieved 17 days after initiating the therapy, using 24 mmol/l of lithium three times a week, in a patient with a residual diuresis of about 400 ml/day. In contrast, data reported in the literature implicate that only 9.6-14.4 mmol/l of lithium (450-600 mg of lithium carbonate) is sufficient to achieve adequate serum levels., Conclusions: The residual renal function can be important for lithium clearance. The creatinine clearance does not reflect this point., (Copyright 2004 S. Karger AG, Basel)

Aims: Chronic allograft nephropathy and/or calcineurin inhibitor toxicity are common problems after organ transplantation. The aim of this study was to examine the safety and efficacy of switching from a calcineurin inhibitor-based to a calcineurin inhibitor-free immunosuppressive regimen consisting of sirolimus and mycophenolate mofetil (MMF) late after renal transplantation., Methods: Kidney biopsies were performed in renal-transplanted patients with increasing serum creatinine levels at least 6 months after transplantation (mean time +/- SD after renal transplantation: 76.4 +/- 50.4 months). Patients with no signs of acute rejection were switched to MMF (500-2,000 mg/day) in combination with a low dose of sirolimus (1 mg/day). Renal function, serum chemistry, blood trough levels of sirolimus and MMF, and blood pressure were monitored., Results: 13 patients were investigated. During our observation period (mean observation time +/- SD: 11.2 +/- 5.9 months), an improvement in renal function was observed in 10/13 patients. In 3/13 patients, renal function deteriorated further and hemodialysis was initiated in 2 patients within the next 6 months. However, a serum creatinine concentration above 3.5 mg/dl was measured in 2 of those 3 patients prior to the switch of the immunosuppressive protocol. Administration of a low dosis of sirolimus (1 mg/day) led to relevant sirolimus (4.16 +/- 1.85 ng/ml) and MMF blood trough levels (month 1: 6.8 +/- 3.46; month 3: 4.67 +/- 1.78 mg/l). The following adverse events were observed: borderline acute rejection (1/11 patients), anemia responding to higher dosage of erythropoietin (3/11), hyperlipidemia (1/11), and urinary tract infections (4/11)., Conclusions: Low-dose sirolimus therapy in combination with concentration-adjusted MMF therapy leads to improvement of organ function late after renal transplantation. The follow-up of those patients should include assessments of blood cell counts, serum lipids and urinalysis to recognize the possible side effects., (Copyright 2004 S. Karger AG, Basel)