Renal replacement therapy in Ukraine: epidemiology and international comparisons.

BACKGROUND: Little is known about the status of renal replacement therapy (RRT) in the post-Soviet countries. We therefore investigated the epidemiology and treatment outcomes of RRT in Ukrainian patients and put the results into an international perspective. METHODS: Data from the Ukrainian National Renal Registry for patients on RRT between 1 January 2010 and 31 December 2012 were selected. We calculated the incidence and prevalence of RRT per million population (pmp) and the 3-, 12- and 24-month patient survival using the Kaplan-Meier method and Cox regression. RESULTS: There were 5985 prevalent patients on RRT on 31 December 2012 (131.2 pmp). Mean age was 46.5 ± 13.8 years, 56% men and 74% received haemodialysis (HD), while peritoneal dialysis and kidney transplantation both represented 13%. The most common cause of end-stage renal disease was glomerulonephritis (51%), while only 12% had diabetes. In 2012, 1129 patients started dialysis (incidence 24.8 pmp), with 80% on HD. Mean age was 48 ± 14 years, 58% men and 20% had diabetes. Three, 12- and 24-month patient survival on dialysis was 95.1%, 86.0% and 76.4%, respectively. The transplant rate in 2012 was 2.1 pmp. CONCLUSIONS: The incidence and prevalence of RRT and the transplantation rate in Ukraine are among the lowest in Europe, suggesting that the need for RRT is not being met. Strategies to reduce the RRT deficit include the development and improvement of transplantation and home-based dialysis programmes. Further evaluation of the quality of Ukrainian RRT care is needed.

Treatment with angiotensin II inhibitors and residual renal function in peritoneal dialysis patients.

BACKGROUND: Many studies have shown the renoprotective effect of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) in patients with chronic kidney disease stages I-IV. Two randomized controlled trials (RCTs) showed a positive effect of AII inhibitors on residual glomerular filtration rate (rGFR) in peritoneal dialysis (PD) patients. However, these studies were small and were performed in a highly selected group of PD patients. Our aim was to confirm the above findings in a larger number of prospectively followed PD patients. METHODS: First we analyzed the time course of decline of rGFR in 452 incident PD patients that were not anuric at the start of dialysis and that had structured follow-up data, with measurements at 3, 6, 12, 18, 24, 30, and 36 months after the start of dialysis. Changes in rGFR over time were analyzed with a linear mixed model for repeated measures. In addition, Cox regression models were used to estimate the risk of developing anuria. In a second approach, we aimed to repeat the above analyses in a selected group of patients that theoretically could have been randomized and therefore resembled the population studied in the 2 mentioned RCTs. In this group the follow-up was restricted to 1 year. RESULTS: 201 patients were treated with ACEi/ARBs and 251 did not take these drugs at the start of PD. More patients from the treated group had diabetes and used more antihypertensive medications. The time course of decline of rGFR was not different between the 2 groups over the 3 years of PD treatment (p = 0.52). Less than 25% of patients from each group became anuric and there was no difference in time to development of complete anuria between the treated and untreated groups. In the second approach, 130 patients were included: 37 were treated with ACEi/ARBs and 93 were not. Again, no difference was found between the 2 groups with respect to the rate of decline of rGFR and time of anuria development. CONCLUSION: Our findings are not in line with the results of previous RCTs. The biggest limitation of observational studies is the inability to avoid confounding by indication. However, a RCT in such a setting also does not give a reliable answer. Given all the benefits of ACEi/ARBs, the medications should not be withheld from PD patients. However, their renoprotective effects may often be overruled by other factors influencing the time course of rGFR.

Time-dependent reasons for peritoneal dialysis technique failure and mortality.

BACKGROUND: Peritoneal dialysis (PD) technique failure is high compared to hemodialysis (HD). There is a lack of data on the impact of duration of PD treatment on technique survival and on whether there is a difference in risk factors with respect to early and late failure. The aim of this study was to clarify these issues by performing a time-dependent analysis of PD technique and patient survival in a large cohort of incident PD patients. METHODS: We analyzed 709 incident PD patients participating in the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), who started their treatment between 1997 and 2007. We compared technique and patient survival on PD in 4 periods of follow-up: within the first 3 months, and after 3 - 12 months, 12 - 24 months, and 24 - 36 months of treatment. Cox proportional hazards model was used to analyze survival on PD and technique failure. Risk factors were also identified by comparing patients that were transferred to HD with those that remained on PD. Incidence rates for every cause of dropout for each period of follow-up were calculated to establish their trends with respect to PD treatment duration. RESULTS: There was a significant increase in transplantation rate after the first year of treatment. The rate of switching to HD was highest during the first 3 months and decreased afterward. One-, 2- and 3-year technique survival was 87%, 76%, and 66%, respectively. Age, diabetes, and cardiovascular disease appeared to be risk factors for death on PD or switch to HD: a 1-year increase in age was associated with a relative risk (RR) of PD failure of 1.04 [95% confidence interval (CI) 1.003 - 1.06]; for diabetes, RR of stopping PD after 3 months of treatment increased from 1.8 (95% CI 1.1 - 3) during the first year to 2.2 (95% CI 1.3 - 4) after the second year; cardiovascular disease had a major impact in the earliest period (RR 2.5, 95% CI 1.2 - 5) and had a stable influence further on (RR 2, 95% CI 1.1 - 3.5). Loss of 1 mL/minute residual glomerular filtration rate (rGFR) appeared to be a significant predictor of PD failure after 3 months of treatment, but within the first 2 years, RR was 1.1 (95% CI 1.04 - 1.25). CONCLUSIONS: In The Netherlands, transplantation is a main reason to stop PD treatment. The incidence of PD technique failure is at its highest during the earliest months after treatment initiation and decreases later due to fewer catheter and abdominal complications as well as less influence of psychosocial factors. Risk factors for PD discontinuation are those responsible for patient survival: age, cardiovascular disease, diabetes, and rGFR.

Karl d. Nolph state of the art lecture: feasible and future options for salvation of the peritoneal membrane.

A review is given of the various available strategies that can be used to protect the peritoneal membrane. A discussion of experimental studies on approaches that are still experimental, but that might be applied in patients in the future, follows. The currently available approaches include dietary sodium restriction, use of high-dose loop diuretics and of inhibitors of the renin-angiotensin system. All should preferably be combined with a dialysis prescription aimed at reducing the patient's exposure to glucose and its degradation products. The experimental studies indicate favorable effects of combining osmotic agents, together with drugs that interfere with the polyol pathway and the formation of advanced glycosylation end-products.

A positive effect of AII inhibitors on peritoneal membrane function in long-term PD patients.

BACKGROUND: Experimental studies showed that inhibition of AII effects attenuates the development of peritoneal membrane fibrosis and neoangiogenesis. The latter leads to an increase of peritoneal solute transport and ultrafiltration failure. The results of a single-centre study showed that use of ACEI/ARB can prevent the increase of small solute transport in long-term PD patients. Our aim was to investigate whether these results would also be present in a larger population and influence patient and technique survival in long-term PD. METHODS: We analysed data from 217 long-term CAPD patients, participating in the Netherlands Cooperative Study on Adequacy of Dialysis (NECOSAD). Included patients underwent CAPD therapy for at least 2 years; 120 of them were treated with the ACE/AII inhibitors-ACEI/ARB group. The control group consisted of 87 patients who received none of the above drugs and 10 patients who had them for <25% of their time on PD. RESULTS: A significant difference in the time course of peritoneal transport was found between the two groups. The value of 24-h D/P creatinine was associated with the PD duration (P = 0.01) and its time course was influenced by use of ACEI/ARB (P = 0.05). We found no effect of ACEI/ARB on patient survival, but some benefit was found for the technique survival: in a multivariate model the hazard ratio for the group with the longest use of ACEI/ARB was 0.5 (CI 0.22-1.4), P = 0.19. CONCLUSIONS: We conclude that AII inhibition prevents the increase in small solute transport in long-term PD. These drugs may also have some positive influence on PD technique survival.

Impact of ACE inhibitors and AII receptor blockers on peritoneal membrane transport characteristics in long-term peritoneal dialysis patients.

BACKGROUND: Long-term peritoneal dialysis (PD) may lead to peritoneal fibrosis and ultrafiltration failure. The latter occurs due to high solute transport rates and diabetiform peritoneal sclerosis. Angiotensin-II (AII) is known to be a growth factor in the development of fibrosis and a number of animal studies have shown it likely that inhibiting the effects of AII by angiotensin-converting enzyme (ACE) or angiotensin receptor blocker (ARB) will attenuate these complications. OBJECTIVE: To investigate the effects of ACE/AII inhibitors in long-term PD patients. PATIENTS AND SETTING: We analyzed data from 66 patients treated with PD therapy at our center for at least 2 years, during which time at least 2 standard peritoneal permeability analyses (SPAs) were performed. 36 patients were treated with ACE/AII inhibitors (ACE/ARB group); the other 30 received none of the above drugs during the entire follow-up (control group). The two groups were compared with respect to changes in peritoneal transport over the follow-up time. RESULTS: A significant difference in time course of peritoneal transport was found between the 2 groups: in the ACE/ARB group, small solute transport had decreased, while it had increased in the control group. This finding was confirmed by analysis using mixed model for repeated measures. The value of mass transfer area coefficient of creatinine was influenced by the duration of PD therapy (p = 0.017) and this interaction was different with respect to use of ACE/AII inhibitors (p = 0.037). The trend was not found in protein clearances or fluid kinetics. CONCLUSION: Our findings suggest that ACE/AII inhibition is likely to prevent the increase in mass transfer area coefficients that occurs in long-term PD, which is in line with results of experimental animal studies.