Residual Renal Function In Peritoneal Dialysis Research Articles

Soluble CD59 in peritoneal dialysis: a potential biomarker for peritoneal membrane function

IntroductionVarious studies have reported the importance of complement regulators in preventing mesothelial damage during peritoneal dialysis (PD). Its assessment, however, is limited in clinical practice due to the lack of easy access to the peritoneal membrane. Recently, a soluble form of the complement regulatory protein CD59 (sCD59) has been described. We therefore aimed to investigate the role of sCD59 in PD.MethodsPlasma sCD59 was measured in 48 PD patients, 41 hemodialysis patients, 15 non-dialysis patients with chronic kidney disease and 14 healthy controls by ELISA (Hycult; HK374-02). Additionally, sCD59 and sC5b-9 were assessed in the peritoneal dialysate.ResultssCD59 and sC5b-9 were detectable in the peritoneal dialysate of all patients, and marginally correlated (r = 0.27, P = 0.06). Plasma sCD59 levels were significantly higher in PD patients than in patients with chronic kidney disease and healthy controls, but did not differ from hemodialysis patients. During follow-up, 19% of PD patients developed peritoneal membrane failure and 27% of PD patients developed loss of residual renal function. In adjusted models, increased sCD59 levels in the dialysate (HR 3.44, 95% CI 1.04–11.40, P = 0.04) and in plasma (HR 1.08, 95% CI 1.01–1.17, P = 0.04) were independently associated with the occurrence of peritoneal membrane failure. Higher plasma levels of sCD59 were also associated with loss of residual renal function (HR 1.10, 95% CI 1.04–1.17, P < 0.001).ConclusionsOur study suggests that sCD59 has potential as a biomarker to predict peritoneal membrane function and loss of residual renal function in PD, thereby offering a tool to improve patient management.Graphic abstract

Estimation of residual renal function using beta-trace protein: Impact of dialysis procedures.

Beta-trace protein (BTP), a low molecular weight protein of 23-29kDa, has been proposed as a promising biomarker to estimate residual renal function (RRF) in patients on maintenance hemodialysis (HD). Indeed, BTP is cleared by native kidney but not during conventional HD session. By contrast, the removal rate of BTP using convective processes (mainly hemodiafiltration [HDF]) and peritoneal dialysis (PD) has been little or not investigated. Therefore, an aim of this study was to evaluate the impact of dialysis procedures (high-flux HD, on-line post-dilution HDF and PD) on BTP removal in comparison with beta-2 microglobulin (B2M) and cystatin C (CYSC) removals after a single session. In addition, the ability of BTP to predict RRF in PD was assessed. This observational cross-sectional study included a total of 82 stable chronic kidney disease patients, 53 patients were on maintenance dialysis (with n=26 in HD and n=27 in HDF) and 29 were on PD. Serum concentrations of BTP, B2M, and CYSC were measured (a) before and after a single dialysis session in HD and HDF anuric patients to calculate reduction percentages, (b) in serum, 24-hour-dialysate and 24-hour-urine in PD patients to compute total, peritoneal, and urinary clearance. RRF was estimated using four equations developed for dialysis patients without urine collection and compared to the mean of the urea and creatinine clearances in PD. The concentrations of the three studied molecules were significantly reduced (P<.001) after dialysis session with significantly higher reduction ratio using HDF compared to HD modality (P<.001): BTP 49.3% vs 17.5%; B2M 82.3% vs 69.7%; CYSC 77.4% vs 66% in HDF and HD, respectively. In non-anuric PD patients, B2M and CYSC were partly removed by peritoneal clearance (72.3% and 57.6% for B2M and CYSC, respectively). By contrast, BTP removal by the peritoneum was negligible and a low bias for the BTP-based equation to estimate RRF (-1.4mL/min/1.73m2 ) was calculated. BTP is significantly removed by high-flux HD or HDF, thereby compromising its use to estimate RRF. By contrast, BTP appears as a promising biomarker to estimate RRF in PD patients since it is not affected by peritoneal clearance, unlike B2M and CYSC, and it is well correlated to RRF.

Dialysis monitoring: peritoneal equilibrium test, regional citrate anticoagulation and residual renal function

The SFBC working group aimed to deal with biological tests outside the French nomenclature that may be useful for the follow-up of dialysis patients. Our discussion was divided into 3 parts: 1) evaluation of peritoneal membrane characteristics; 2) monitoring of renal replacement therapy using regional citrate anticoagulation; 3) estimation of residual renal function (RRF). International recommendations underline the importance of assessing peritoneal membrane characteristics for peritoneal dialysis prescription. This peritoneal equilibrium test requires the measurement in dialysate of the following parameters: glucose, urea, creatinine and sodium. As part of the monitoring of continuous renal replacement therapy using regional citrate anticoagulation, the determination of ionized calcium assay is essential according to national and international guidelines to ensure a balance between effective anticoagulation and appropriate calcium levels. Finally, the RRF plays a key role in the dialysis adequacy and patient survival. European and international recommendations highlight the potential interest of RRF in peritoneal dialysis and hemodialysis. The RRF corresponds to the mean of urinary urea and creatinine clearance, assessed from a urine collection with measurement of urinary urea.

E impact of visit-to-visit systolic blood pressure variability on residual renal function and le ventricular hypertrophy in peritoneal dialysis patients

Background/aim: Blood pressure (BP) variability is more closely associated with adverse outcomes than ‘usual’ BP in the general population. Residual renal function (RRF) and left ventricular hypertrophy (LVH) are thought to be predictors of poor outcome in dialysis patients. However, only a few studies have focused on BP variation and its link to RRF, LVH, and outcome in peritoneal dialysis (PD) patients. Therefore, we aimed to explore the effect of visit-to-visit BP variability on RRF and LVH in continuous ambulatory PD (CAPD) patients. Materials and methods: We performed an observational study that included all prevalent PD patients between 1 February 2006 and 31 January 2007. All patients underwent BP measurements, pulse wave velocity (PWV), cardiac ultrasound, and biochemical examination during the 1-year observation. Patients were divided into the HBPV group (higher BP variability) and LBPV group (lower BP variability) based on the standard deviation of systolic BP (SBP). Results: There were 70 patients recruited for the final analysis. Patients with HBPV had a higher SBP as compared to patients with LBPV at baseline. Renal Kt/V decreased significantly from 0.50 ± 0.49 to 0.32 ± 0.35 (P < 0.01) in HBPV group (but not in the LBPV group) during follow-up. Patients with HBPV also showed a higher left ventricular mass index (LVMI) and PWV than those with LBPV at the end of follow-up. Conclusion: Our study suggests that BP variability may affect RRF in PD patients. PD patients with HBPV had a faster decline in RRF and higher PWV and LVH.

Low Serum Bicarbonate Predicts Residual Renal Function Loss in Peritoneal Dialysis Patients.

Low residual renal function (RRF) and serum bicarbonate are associated with adverse outcomes in peritoneal dialysis (PD) patients. However, a relationship between the 2 has not yet been determined in these patients. Therefore, this study aimed to investigate whether low serum bicarbonate has a deteriorating effect on RRF in PD patients.This prospective observational study included a total of 405 incident patients who started PD between January 2000 and December 2005. We determined risk factors for complete loss of RRF using competing risk methods and evaluated the effects of time-averaged serum bicarbonate (TA-Bic) on the decline of RRF over the first 3 years of dialysis treatment using generalized linear mixed models.During the first 3 years of dialysis, 95 (23.5%) patients became anuric. The mean time until patients became anuric was 20.8 ± 9.0 months. After adjusting for multiple potentially confounding covariates, an increase in TA-Bic level was associated with a significantly decreased risk of loss of RRF (hazard ratio per 1 mEq/L increase, 0.84; 0.75–0.93; P = 0.002), and in comparison to TA-Bic ≥ 24 mEq/L, TA-Bic < 24 mEq/L conferred a 2.62-fold higher risk of becoming anuric. Furthermore, the rate of RRF decline estimated by generalized linear mixed models was significantly greater in patients with TA-Bic < 24 mEq/L compared with those with TA-Bic ≥ 24 mEq/L (−0.16 vs −0.11 mL/min/mo/1.73 m2, P < 0.001).In this study, a clear association was found between low serum bicarbonate and loss of RRF in PD patients. Nevertheless, whether correction of metabolic acidosis for this indication provides additional protection for preserving RRF in these patients is unknown. Future interventional studies should more appropriately address this question.

Fluid overload and residual renal function in peritoneal dialysis: the proof of the pudding is in the eating

McCafferty and colleagues report on a retrospective analysis in peritoneal dialysis patients in whom fluid status was assessed by multifrequency bioimpedance. During 12 months of follow-up, overhydration, as identified by an increased ratio of extracellular over total body water, was not associated with better preservation of residual renal function (RRF). These findings suggest that running patients 'wet' might not contribute to better preservation of RRF in peritoneal dialysis.

BENEFICIAL EFFECT OF KETO AMINO ACIDS FOR DIALYSIS PATIENTS

Nutritional status is an important predictor of clinical outcome in dialysed patients. Beside decreased serum protein/albumin,lower BMI with decreased muscle mass is the most significant predictor of morbidity and mortality. Keto amino acids (KA) represent an additional source for protein anabolism influencing indirectly also carbohydrate and lipid metabolism,Ca-P and acid base balance.Additionaly,by concominant metabolic and hemodynamic effect on residual nefrons, KA can help to slow progression of residual renal function (RRF) mainly in peritoneal dialysis patients. We conducted a long-term prospective randomized placebo controlled trial to test whether a modified low-protein diet (LPD) with or without keto acids (KA) would be safe ,well tolerated and associated with an increase of metabolic status and preservation of RRF in peritoneal dialysis (PD). We evaluated a total of 62 PD patients (32M/30F) aged 26-72 yrs with creatinine clearance (Ccr) 7.9-5.7 mL/min/1.73m2 for a period of 12 months. All patients were on modified LPD containing 0.8 protein/kg/IBW/day and 135/kJ/kg/IBW/day. LPD was randomly supplemented with KA at dosage of 100 mg/kg/IBW/day (30 patients, Group I) while 30 patients (Group II) received placebo. We analysed also muscle and fat metabolism by MR spectroscopy (MRS, m.tibialis anterior)) and imagining (MRI,visceral fat).Patients from Group I were before enrolment on conservative management using LPD + KA (0.6g P + 0.1g KA/kg/IBW/day) for longer time (18-48 months, median 28) with good compliance (SGA). Patients from group II were never treated with LPD and KA.All patients were monitored at the beginning of PD and at every 3 months for 12 months.;A neutral or positive long- term nitrogen balance (nPCR in g/kg IBW/day) was achieved in Group I (p

Human RAGE antibody protects against AGE-mediated podocyte dysfunction

Residual renal function (RRF) contributes to better patient survival in peritoneal dialysis (PD). It is known that glucose degradation products (GDP) and advanced glycation end-products (AGE) resorbed from the peritoneal cavity do not only cause local peritoneal toxicity but also systemic damage resulting in a loss of RRF. We hypothesize that GDP and AGE affect the structure and function of podocytes and investigate whether these effects can be rescued by human RAGE antibody (hRAGEab) to prevent AGE/RAGE interaction and podocyte damage. Differentiated human podocytes were pre-incubated with ±hRAGEab to block the AGE/RAGE interaction and incubated afterwards either with control solution (control), PD fluid (PDF) or a GDP mixture (GDP) for 48 h. We analysed podocyte damage and rescue by hRAGEab using immunofluorescence, western blot, enzyme-linked immunosorbent assay and a functional migration assay. For quantitation, a semiquantitative score was used. When pre-incubating podocytes with hRAGEab, damage mediated by PDF and GDP was reduced. We observed lower expression of AGE in PDF and GDP as well as decreased levels of inflammation as shown by activation of nuclear factor kappa B and interleukin-6 release. The reorganization of the podocyte actin cytoskeleton was reduced in the presence of hRAGEab as well as ameliorated synaptopodin expression could be observed, both functionally associated with normal podocyte motility. Finally, podocytes underwent less apoptosis. It has been investigated that GDP-containing PDF causes a loss of RRF in PD. Our findings suggest that hRAGEab confers protection against PDF- and GDP-induced podocyte dysfunction. Blocking the AGE/RAGE interaction provides specific protective effects against PDF- and GDP-induced cytoskeletal reorganization, dynamics and stabilizes podocyte survival; this might be an implication for the preservation of RRF in PD.

Rationale and design of the balANZ trial: A randomised controlled trial of low GDP, neutral pH versus standard peritoneal dialysis solution for the preservation of residual renal function

BackgroundThe main hypothesis of this study is that neutral pH, low glucose degradation product (GDP) peritoneal dialysis (PD) fluid better preserves residual renal function in PD patients over time compared with conventional dialysate.Methods/DesignInclusion criteria are adult PD patients (CAPD or APD) aged 18-81 years whose first dialysis was within 90 days prior to or following enrolment and who have a residual GFR ≥ 5 ml/min/1.73 m2, a urine output ≥ 400 ml/day and an ability to understand the nature and requirements of this trial. Pregnant or lactating patients or individuals with an active infection at the time of enrolment, a contra-indication to PD or participation in any other clinical trial where an intervention is designed to moderate rate of change of residual renal function are excluded. Patients will be randomized 1:1 to receive either neutral pH, low GDP dialysis solution (Balance®) or conventional dialysis solution (Stay.safe®) for a period of 2 years. During this 2 year study period, urinary urea and clearance measurements will be performed at 0, 3, 6, 9, 12, 18 and 24 months. The primary outcome measure will be the slope of residual renal function decline, adjusted for centre and presence of diabetic nephropathy. Secondary outcome measures will include time from initiation of peritoneal dialysis to anuria, peritoneal small solute clearance, peritoneal transport status, peritoneal ultrafiltration, technique survival, patient survival, peritonitis rates and adverse events. A total of 185 patients has been recruited into the trial.DiscussionThis investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysis solution for preserving residual renal function in PD patients.Trial RegistrationAustralian New Zealand Clinical Trials Registry Number: ACTRN12606000044527

Preserved residual renal function is associated with lower oxidative stress in peritoneal dialysis patients

Residual renal function (RRF) correlates with survival in peritoneal dialysis (PD). We investigated the association between oxidative stress and RRF in PD. Adequacy of dialysis, total and free malondialdehydes (MDA), and lipid hydroperoxides (LHP) were obtained from 23 stable PD patients. Free MDA level decreased with total weekly Kt/V urea (r = -0.51, P = 0.013) and urinary Kt/V (KRU) (r = -0.53, P = 0.009), but not with peritoneal Kt/V. Similar results were found with LHP level. In multivariate analysis, total weekly Kt/V urea and KRU remained associated with free MDA and LHP, independently of gender, nutritional or inflammatory status, and peritoneal permeability. A preserved RRF is associated with lower serum levels of lipid peroxidation products among PD patients.

Renal toxicity mediated by glucose degradation products in a rat model of advanced renal failure

In peritoneal dialysis (PD) residual renal function contributes to improved patient survival and quality of life. Glucose degradation products (GDP) generated by heat sterilization of PD fluids do not only impair the peritoneal membrane, but also appear in the systemic circulation with the potential for organ toxicity. Here we show that in a rat model of advanced renal failure, GDP affect the structure and function of the remnant kidney. Sprague-Dawley rats were randomly assigned to a two stage subtotal nephrectomy (SNX) or sham operation and were left untreated for 3 weeks. The SNX + GDP group continuously received chemically defined GDP intravenously for 4 weeks; the SNX and the sham-operated rats remained without GDP. The complete follow-up for all groups was 7 weeks postoperatively. We analysed renal damage using urinary albumin excretion as well as a semiquantitative score for glomerulosclerosis and tubulointerstitial damage, as well as for immunohistochemical analyses. The SNX + GDP rats developed significantly more albuminuria and showed a significantly higher score of glomerulosclerosis index (GSI) and tubulointerstitial damage index (TII) as compared to SNX or control rats. In the SNX + GDP group the expression of carboxymethyllysine and methylglyoxal was significantly higher in the tubulointerstitium and the glomeruli compared to the SNX rats. Caspase 3 staining and TUNEL assay were more pronounced in the tubulointerstitium and the glomeruli of the SNX + GDP group. In SNX + GDP animals, the expression of the slit diaphragm protein nephrin, was significantly lower compared to SNX or control animals. In summary, our data suggests that GDP can significantly advance chronic kidney disease and argues that PD solutions containing high GDP might deteriorate residual renal function in PD.

Effect of aminoglycoside use on residual renal function in peritoneal dialysis patients.

Residual renal function (RRF) is a major contributor to total solute clearance in peritoneal dialysis (PD) patients, and maintenance of RRF has been linked to decreased morbidity and mortality in PD. There have been few clinical studies examining the impact of factors that potentially affect RRF in PD. This is a prospective observational study that examines the effects of parenteral aminoglycosides, a common nephrotoxin in the general population, on RRF in a cohort of PD patients. Seventy-two patients from two Rhode Island PD units were observed over 4 years. Twenty-four-hour renal creatinine clearances and urine volumes were measured every 4 to 6 months. The patients were divided into three groups, depending on exposure to peritonitis and aminoglycoside use. Group I included patients without peritonitis who received no intravenous (IV) or intraperitoneal (IP) antibiotics. Group II included patients with peritonitis who received IV or IP penicillins, cephalosporins, vancomycin, or quinolones, but no aminoglycosides. Group III included patients with peritonitis who received IV or IP aminoglycosides for at least 3 days. Patients in group III had a more rapid decline in renal creatinine clearance (-0.66 +/- 0.58 mL/min/mon) than groups I and II (P < 0.005) and had a more rapid decline in daily urine volume (-74 +/- 62 mL/d/mon) than groups I and II (P < 0.01). We conclude that IV or IP aminoglycosides seem to increase the rapidity of decline in RRF in PD patients. In patients with solute clearance dependent on RRF, it seems reasonable to withhold aminoglycosides, especially if other antibiotics are available and appropriate.