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Oct 27, 2013 - Liliana Gârneata˘ • Irina Mititiuc • Dimitrie Siriopol •. Adrian Covic. Received: 11 September 2013 / Accepted: 17 September 2013 / Published ...

Int Urol Nephrol (2014) 46:443–451 DOI 10.1007/s11255-013-0571-3

NEPHROLOGY - ORIGINAL PAPER

Outcomes of dialytic modalities in a large incident registry cohort from Eastern Europe: the Romanian Renal Registry Gabriel Mircescu • Gabriel S¸tefan • Liliana Gaˆrneat¸ a˘ • Irina Mititiuc • Dimitrie Siriopol Adrian Covic



Received: 11 September 2013 / Accepted: 17 September 2013 / Published online: 27 October 2013 Ó Springer Science+Business Media Dordrecht 2013

Abstract Background Studies comparing survival in hemodialysis (HD) or peritoneal dialysis (PD) patients reported controversial results, mainly during the first 2 years of treatment. Moreover, there is a significant geographic variation in the use of these modalities. We aimed to compare the survival of HD and PD patients using data from the Romanian Renal Registry. Methods In an intention-to-treat analysis using Kaplan– Meier and Cox proportional hazard (CPH) models, survival was compared between 8,252 incident HD patients and 1,000 incident PD patients treated between 2008 and 2011. The patients were followed from the dialysis initiation and stratified by modality on day 90. The time on dialysis was separated into four periods (3–12, 12–24, 24–36 and [36 months), and outcome comparisons were made. Results Mean survival time was 46.3 (44.9–47.6) months in PD group and 45.8 (45.3–46.3) months in HD group G. Mircescu  G. S¸ tefan  L. Gaˆrneat¸ a˘ ‘‘Dr Carol Davila’’ Teaching Hospital of Nephrology, Bucharest, Romania G. Mircescu  G. S¸ tefan  L. Gaˆrneat¸ a˘ Nephrology Department, ‘‘Carol Davila’’ University of Medicine and Pharmacy, Bucharest, Romania G. Mircescu  G. S¸ tefan  L. Gaˆrneat¸ a˘ Romanian Renal Registry, Bucharest, Romania I. Mititiuc  A. Covic (&) ‘‘C.I. Parhon’’ University Hospital, Iasi, Romania e-mail: [email protected]; [email protected]; [email protected] I. Mititiuc  D. Siriopol  A. Covic Nephrology Department, ‘‘Gr. T. Popa’’ University of Medicine and Pharmacy, Iasi, Romania

(p = 0.9, log-rank test). In the multivariate CPH models, age, diabetes-associated kidney disease (DM), primary renal disease and center size significantly influenced survival. In the first year of therapy, the mortality was higher in HD than in PD patients (HR = 1.34 (1.12–1.60), p = 0.001), while in the second and third year, HD patients survived better (HR = 0.69 (0.53–0.89), p = 0.005); HR = 0.56 (0.41–0.78), p = 0.001) and after 36 months, the survival difference was not statistically significant (HR = 0.63 (0.34–1.13), p = 0.1), respectively. Conclusions Despite the survival advantage for PD patients during the first year and that of HD in the next 2 years of dialysis, the overall survival in HD and PD patients was similar and was influenced by age, DM and center size. Keywords Cox proportional hazard model  Hemodialysis  Incident data  Peritoneal dialysis  Romanian Renal Registry  Survival

Introduction With the rising incidence and prevalence of treated endstage renal disease (ESRD), expenditures on dialysis are putting a tremendous pressure on dialysis capacity and national health budgets. Several investigations have concluded that the decision to start the renal replacement therapy (RRT) with either hemodialysis (HD) or peritoneal dialysis (PD) is influenced by patient and physician preference and by macroeconomic factors [1]. There are notable differences between countries in dialysis mix and RRT survival [2]. Solid outcome data are thus needed for all involved stakeholders, in order to select the best initial dialysis modality, when transplantation cannot be performed at ease.

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In the context of a growing ESRD population, the survival difference between PD and HD is still a subject of debate, as it could greatly influence patient allocation to one of the RRT methods. Some, but not all observational studies comparing the outcomes of the two RRT modalities suggested a survival advantage for PD patients in the first 1–2 years [3–9]. A randomized controlled trial would be the best way to compare outcomes, but a previous attempt was complicated by poor recruitment and lack of statistical power [10]. Therefore, important information is still required and may be best offered by comprehensive registry data. In Romania, where reporting to the Romanian Renal Registry (RRR) is compulsory, the Registry monitors the outcome in over 95 % of ESDR patients in the country, which allowed us to conduct an epidemiologic study in order to investigate the effect of dialysis modality on prognosis.

Subjects and methods Patients We examined the outcome on December 31, 2012 of the incident patients who started RRT between January 1, 2008 and December 31, 2011. The patients entered the study on day 1 of the therapy and were stratified by modality on day 90. We excluded patients who were younger than 18 years, patients who received a preemptive transplantation, or kidney transplantation during the first 90 days of RRT and patients who had recovery of renal function or who were lost to follow-up during the first 90 days of RRT. Data collection As reporting to registry is compulsory, RRR collects data regarding over 95 % of patient receiving RRT in Romania, a country with a population of 20,121,6411 and 14,879 ESRD patients (739 per million population) on 31 of December 2012.2 The register contains data on patient age, gender, primary renal disease, date of first RRT and history of RRT and date and cause of death. The RRT modality was classified as HD (home hemodialysis, center hemodialysis and hemodiafiltration) and PD (continuous ambulatory peritoneal dialysis and automated peritoneal dialysis). The primary renal diagnosis was summarized in six categories: glomerulonephritis (GN), renovascular disease (RVD), tubulointerstitial disease (TID), diabetic nephropathy

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www.recensamantromania.ro (REZULTATE DEFINITIVE RPL 2011). 2 Romanian Renal Registry Report 2012.

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Fig. 1 Number of incident patients receiving renal replacement therapy in each year from 2008 to 2011, by age group

(DN), familial or hereditary nephropathies (HN) and other or unknown renal diagnosis. Dialysis centers performing PD were classified as small (fewer than 20 PD patients) or as large centers (more than 20 PD patients). The time since the initiation of dialysis was separated into four periods: 3–12, 12–24, 24–36 and [36 months. Statistical analysis Categorical variables are presented as percentages, and comparisons were performed with the v2 test. Continuous variables are displayed as mean or median with 95 % confidence interval (95 % CI), according to their distribution. Comparisons were done with Student T test or Kruskal–Wallis test, as appropriate. The statistical analysis was conducted using an intention-to-treat approach; multiple switches between dialysis procedures were ignored, as were patients who received kidney transplants. The deaths registered during the follow-up period were allocated to the treatment modality on day 90. Survival analyses were conducted with the Kaplan–Meier method, and the log-rank test was used for comparison. The intent-to-treat analysis used the Cox proportional hazard (CPH) model to estimate hazard ratio (HR) and 95 % CI for the two dialysis modalities. The analysis of the variables related to survival was carried out using the multivariate CPH model. Subgroup analyses were performed by stratifying the patients according to age, diabetic status (diabetesassociated kidney disease (DM)) and time on dialysis. A p B 0.05 was considered statistically significant.

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Table 1 Patient characteristics p*

All

HD

PD

Number of patients (%)

9,252

8,252 (89.2)

1,000 (10.8)

Age (years)

60.7 (60.4–61.1)

60.7 (60.4–61.1)

60.7 (59.5–61.5)

Male gender (%)

57.2

58

50.7

\0.0001

Diabetes (%)

15.5

15.1

19.4

0.001

\0.0001

0.25

Primary renal disease (%) GN

15.9

16

15.4

DN

15.5

15.1

19.4

TID

12.6

12.5

12.8

RVD

7.3

6.7

11.9

HN

6

6.1

5.6

Other/ unknown

42.8

43.6

34.9

Year of first RRT (%) 2008 2009

21.8 24.3

20.2 24.4

35.5 23.7

2010 2011

26.9

27.3

23.4

27

28.1

17.4

\0.0001

Status (%) Death

24.7

24.5

26.3

HD ? PD

0.6





PD ? HD

0.9





HD only

86.1





PD only

9.4





Transplant

2.5

2.1

0.4

Lost to followup

0.48

0.42

0.06

0.2

DN diabetic nephropathy, GN glomerulonephritis, HD hemodialysis, HN hereditary nephropathies, PD peritoneal dialysis, RRT renal replacement therapy, RVD renovascular disease, TID tubulointerstitial disease * HD versus PD

Statistical analyses were performed with SPSS (SPSS Inc., Chicago, IL) and Analyse-it (Analyse-it Software, Ltd., Leeds, UK) packages.

Fig. 2 Nonadjusted Kaplan–Meier survival curves for PD and HD patients. The log-rank test showed no statistical significant difference (p = 0.9) between the two groups

observation period (Fig. 1); 57.2 % were male. GN, DN and TID were the main primary renal diseases (15.9, 15.5 and 12.6 %, respectively). However, the primary diagnosis was unknown in a large proportion of patients (36.9 %). Of the patients included in the study, 8,252 (89.2 %) were incident on HD and 1,000 (10.8 %) on PD. HD and PD subjects had similar median age; more men and fewer DM patients received HD (Table 1). The number of patients starting HD increased during the four-year enrollment period, while the number of PD patients decreased (Table 1). After day 90, 59 (0.6 %) patients on HD switched to PD at a median time of 11 (95 % CI 9–16) months. Among PD patients, 87 (0.9 %) changed to HD at a median time of 13 (95 % CI 9–18) months (Table 1). Two hundred thirty-three (2.5 %) patients received a kidney graft during follow-up; 202 (2.1 %) HD subjects at a median time of 11 (95 % CI, 10–13) months and 31 (0.4 %) PD subjects at a median time of 9.5 (95 % CI, 6–16) months. Univariate survival analysis

Results Patients characteristics A total of 9,252 patients started RRT on PD or HD and fulfilled the study criteria. Median age was 60.7 years, and the number of older patients had a rising trend in the

The mean survival time for the entire cohort was 45.8 (95 % CI, 45.4–46.3) months. Survivals at 12, 24, 36 and 48 months were 83.1, 77.6, 73.6 and 71.7 %, respectively. In univariate analysis, the difference in survival between PD and HD groups was not statistically significant, p = 0.9 (log-rank test) (Fig. 2). Mean survival time was 46.3 (95 % CI, 44.9–47.6) months for the PD group and 45.8 (95 % CI,

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Table 2 Cause of death in the investigated cohort All

HD

Number

2,288

Cardiovascular (%)

48.3

Gastrointestinal (%)

*

PD

p

2,024

264

0.2

48.5

47.3

0.7

1.8

2.02

0.7

0.1

Infectious (%)

3.0

3.1

2.2

0.4

Neoplasia (%)

3.0

3.2

1.8

0.2

Other cause (%)

4.8

5.1

3.0

0.1

Unknown (%)

38.7

37.9

44.6

0.03

HD hemodialysis, PD peritoneal dialysis * HD versus PD—v2-test for each cause of death; overall: p = 0.1

Table 3 Multivariate adjusted model in incident ESRD patients (multivariate CPH model) HR

p

Age at first RRT

1.033 (1.030–1.037)

\0.001

Male versus female gender

1.061 (0.976–1.153)

0.165 \0.001

Primary renal disease versus GN DN

1.733 (1.476–2.035)

\0.001

TID

1.292 (1.085–1.538)

0.004

RVD

1.356 (1.117–1.647)

0.002

HN

0.810 (0.626–1.049)

0.1

Other

1.521 ((1.318–1.756)

\0.001

PD versus HD

1.012 ((0.889–1.151)

0.860

DN diabetic nephropathy, GN glomerulonephritis, HD hemodialysis, HN hereditary nephropathies, HR hazard ratio, PD peritoneal dialysis, RRT renal replacement therapy

45.3–46.3) months for the HD group. Crude hazard ratio for death in HD versus PD patients was 1.00 (95 % CI 0.88–1.14). Cause of death A total of 2,288 patients died during the period of the study. Cardiovascular disease was the leading cause of death. There was no significant difference in causes of death between HD and PD, but the rate of unknown cause of death was higher in the PD group (Table 2). Multivariate survival analysis In the multivariate CPH model, higher age at RRT initiation, DM and primary renal disease, but not dialysis modality, were significantly associated with a poorer survival (Table 3). Subgroup analysis To further investigate the factors that were statistically significant in the CPH model, we stratified the cohort by

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age group (B60 years of age and [60 years) and by DM. With the exception of the DM patients younger than 60 years—in whom survival was better on HD—no differences in survival were observed in the other groups (Fig. 3). In the survival analysis by dialysis modality and primary diagnosis—adjusted for age and gender— patients with HN and GN had a better outcome than patients with DN in both modalities (Figs. 4, 5). A survival analysis between HD and PD patients was performed in the subgroups defined by the time since the initiation of dialysis. During the period of 3–12 months, the survival was significantly better in PD than in HD patients. During the periods of 12–24 and 24–36 months, HD patients had a survival advantage, while after 36 months, the difference in survival between the HD and PD groups was no more significant (Table 4). In a multivariate CPH model restricted to centers practicing both HD and PD, patients who received RRT in a small center (\20 patients on PD) had a significantly higher mortality risk than patients treated in large dialysis center (C20 patients on PD) (Table 5).

Discussion There are few registry reports from Western Europe and none from Central and Eastern Europe that compare survival in RRT patients according to the initial dialysis modality. Analysis of our registry data, taking advantage of the compulsory reporting, showed that HD and PD patients experience similar overall survival, even though adjustments were made for demographic and clinical differences in patients’ characteristics. The subgroup analysis confirmed that PD patients had a survival advantage during the first year of dialysis, while during the second and third year, HD patients had a better prognosis, and after the third year, no difference in survival was observed. Moreover, patients who received RRT in a small dialysis center had a significantly higher mortality risk. Considerable geographic variation exists in the use of PD and HD [11]. Eleven percent of the global dialysis population is currently on PD. Despite a continuous decline in the proportion of PD patients in developed countries, the number of patients per million population treated by PD increased over the last decade [11]. According to the RRR 2012 report, in Romania, a country with 20,121,641 inhabitants and 14,879 RRT patients (point prevalence of 739 per million population) on 31 of December 2012, the proportion of PD patients was 11 % in 2012, declining from 20 % in 2007 [12]. We noted the same declining trend in the number of incident PD patients during the currently reported observation period, in this countrywide

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Fig. 3 a–d Survival analysis for hemodialysis (HD) and peritoneal dialysis (PD) patients, adjusted for age and diabetes associated kidney disease (DM)

Fig. 4 Adjusted survival for incident HD patients from day 91, by primary diagnosis, adjusted for age and gender. DN diabetic nephropathy, GN glomerulonephritis, HN hereditary nephropathies, RVD renovascular disease, TID tubulointerstitial disease

Fig. 5 Adjusted survival for incident PD patients from day 91, by primary diagnosis, adjusted for age and gender. DN diabetic nephropathy, GN glomerulonephritis, HN hereditary nephropathies, RVD renovascular disease, TID tubulointerstitial disease

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Table 4 Subgroups comparison defined by modality and time since the initiation of dialysis (univariate CPH model for each subgroup) Time period (months) 3–12 12–24 24–36 [36

RRT modality

No. of patients

No. of deaths (%)

HR*

p

1.34 (1.12–1.60)

0.001

0.69 (0.53–0.89)

0.005

0.56 (0.41–0.78)

0.001

0.63 (0.34–1.13)

0.1

HD

8,252

1,432 (17.3)

PD

1,000

134 (13.4)

HD

6,673

367 (5.4)

PD

850

70 (8.2)

HD

4,445

173 (3.8)

PD

636

45 (7.0)

HD

2,629

51 (1.9)

PD

419

14 (3.3)

HR hazard ratio, No number, RRT renal replacement therapy * HR \ 1 indicates a lower mortality rate for HD patients, compared with PD patients; HR [ 1 indicates a higher mortality rate for HD patients, compared with PD patients Table 5 Multivariable adjusted model for incident ESRD patients from centers which performed peritoneal dialysis (multivariate CPH model) HR

p

Age at first RRT

1.035 (1.032–1.039)

\0.001

Male versus female gender Large center versus small center

1.038 (0.952–1.132) 0.884 (0.805–0.970)

0.394 0.009

DM

1.253 (1.116–1.407)

\0.001

HD versus PD

0.961 (0.833–1.108)

0.580

DM diabetes-associated kidney disease, HD hemodialysis, HR hazard ratio, PD peritoneal dialysis, RRT renal replacement therapy

and comprehensive investigated cohort. Based on the RRR report, the percent of patients treated in private centers increased during the study period, reaching 88 % of the total point prevalent patients on 31 of December 2012. Thus, the expansion of the private sector could be a factor: Similar to countries with dominant private dialysis providers, where PD is less frequently used than in countries with a dominant public provider [13, 14]. Median age at dialysis initiation was close to the overall median age in the countries reporting individual patient data to the ERA–EDTA Registry (60.7 vs. 61.6 years) [2]. Among the causes leading to ESRD, GN and DN had comparable percentages. This finding is similar to that registered in Norway (16.6 % GN and 16.8 % DN) [2]. However, the 15.5 % prevalence of DN in our incident RRT patients remains lower than the 20–30 % reported by West European countries and the 40–45 % reported by USA [2, 15]. A larger proportion of DM patients were on PD compared with HD, which is consistent with previous reports [5, 16, 17]. However, these figures are confounded by the important percentage of cases with unknown primary renal disease, which also points to the need for a better pre-ESRD care in Romania. Despite the improvement in ESRD patient’s life expectancy since the introduction of dialysis, the rate of

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all-cause mortality is still 6.3–8.2 times greater in the dialysis population as compared to the general population [15]. The cumulative chances of survival at 12 and 24 months were similar in our cohort to those reported by the ERA–EDTA Registry for the 2004–2008 cohort (83.1 vs. 83.7 % and 77.6 vs. 71.1 %, respectively) [2]. Moreover, in the EVEREST study (Explaining the Variation in Epidemiology of RRT through Expert Opinion, Secondary Data Sources, and Trends over Time), which was based on a 2003–2005 cohort, Romanian patients had the best twoyear survival on dialysis (89.8 %) [18]. However, this survival advantage could be confounded by a series of factors: From all the countries compared in the EVEREST study, Romania had the lowest rate of incident dialysis patients; the incident patients had the lowest mean age and prevalence of diabetes. Nevertheless, the mortality risks of the dialysis in Romanian population were one of the lowest [18, 19]. As compared to the 1995–2001 Romanian cohort, in the actual cohort, the median age and the proportion of DM patients were notably higher (49.5 and 60.7 years, 6.5 and 13.2 %, respectively), which could explain the decrease in chances of survival for 1 year (91 vs. 83 %). The increase in dialysis therapy addressability—as reflected by the increase in Romanian ESRD patients point prevalence from 240 in 2003 to 740 patients per million population in 2012—is a factor to be taken in consideration when analyzing survival. The unadjusted overall survival analysis showed no significant difference between the two dialysis methods. This is in accordance with a previous study from our country (1995–2003 cohort), which showed that the initial treatment modality did not influence patient survival [20]. In an intention-to-treat analysis using a CPH model, we observed that the overall adjusted survival for the Romanian RRT patients who started dialysis between 2008 and 2011 was similar in PD and HD. This is in line with previous registry-based studies performed in other countries

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[4, 5, 17, 21–23]. However, our study showed a survival advantage for PD patients during the first year of dialysis, an advantage which decreased in the second and third year when HD patients had a better outcome. These findings are similar with van der Wal et al. [24] who used a marginal structural model analysis to investigate dialysis modality differentials in Netherlands. Also, using the same model, Lukowsky et al. found that PD is associated with 48 % lower mortality than HD over the first 2 years of dialysis therapy in USA [25]. This initial survival advantage of PD patients was explained by a combination of the higher comorbidity burden in HD patients at therapy initiation [26] and the better preservation of the residual renal function in patients on PD [27]. However, as data on the patient comorbidities and residual renal function are unavailable in our registry, a more detailed analysis was not possible in this study. The observational studies that compared the survival of PD and HD patients in the 1990s yielded mixed results, e.g., better outcome for HD patients [28] or comparable survival [7]. Interestingly, the studies of 2000s from different parts of the world consistently noticed the absence of survival differences between HD and PD for up to 4–5-year periods of follow-up [5, 9, 16, 23, 29–31]. However, conflicting results still persists between the initial survival advantage of PD over HD [24, 25]. These differences in findings may partly reflect international discrepancy in dialysis practices, besides variation in study design. The initial variability in the survival of patients on HD and PD across countries should provide insight into new ways to manage the growing demand for dialysis service, rather than predispose to further controversy. With knowledge of survival patterns for each dialysis modality in population with similar socioeconomic structures, health policy makers could promote a better complementary approach between HD and PD. In patients younger than 60 years and with DM, survival is better on HD than on PD. The rest of the subgroups showed equivalent survival. These results are partially in line with Sanabria et al. [16] who found survival difference in favor of PD only in patients younger than 65 years and nondiabetic. The outcome of patients treated with different forms of dialysis is highly dependent on age, diabetic status and baseline comorbidities [17]. According to our data, DM, age and the primary renal disease were risk factors for a poorer survival. Patients suffering from GN had a better survival than patients with DN, which is in line with the survival reports from the ERA–EDTA Registry [2]. Death from cardiovascular causes reached 48.3 % and was not associated with the initial dialysis modality, percentage that is in accordance with the reports from de Jager et al. in Europe (44 %) and US Renal Data System (45 %) [15, 32].

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In a model restricted only to centers that performed both PD and HD, patients from centers with more than 20 subjects on PD had a better survival. According to Spiegel et al. [33], characteristics such as patient engagement, physician communication, and staff coordination could explain the difference in survival among centers. These features may be more frequent in large centers. Also, the higher level of experience in these centers could be related to the better survival. Our study has several limitations. First, the study design was nonrandomized, which predisposes to selection bias. Second, the data from RRR, while providing specific clinical and demographic data for a large sample size, do not include information on comorbidity and laboratory tests. Third, our study design used an intention-to-treat censoring strategy, rather than an as-treated one. There are also several strengths: compulsory reporting similar to United Kingdom, incident data and large cohort of dialysis patients. In summary, the present study identified age, DM and the size of dialysis center as significant factors affecting survival in the Romanian dialysis population. Patients on HD and on PD experienced similar long-term survival. Subgroup analysis showed that patients on PD had a survival advantage during the first year of dialysis, the advantage switched to HD during the second and third year, and after the third year, no survival difference was observed between HD and PD. Acknowledgments Participating centers Turkes Ablachim, MD, CMDTA Dialysis Center, Bucures¸ ti; Constanta Andone, MD, IHS Buza˘u Dialysis Center; Carina Daniela Andrei, MD, ‘‘Mavromati’’ Botos¸ ani County Hospital Dialysis Center; Mihaela Anghel, MD, Diaverum Romania Roman Dialysis Center; Daniela Anghel, MD, FMC Alba Iulia Dialysis Center; Carmen Elena Anton, MD, AVITUM Suceava Dialysis Center; Luminita Ardelean, MD, Nefrocare Bucures¸ ti Dialysis Center; Mihai Ardeleanu, MD, ‘‘Sf. Ioan cel Nou’’ Suceava County Hospital Dialysis Center; Gabriel Bako, MD, FMC Nephrocare Oradea Dialysis Center; Mihaela Ba˘lgra˘dean, MD, PHD, ‘‘Marie Curie’’ Children Hospital Dialysis Center, Bucures¸ ti; Anca Barbu, MD, IHS‘‘Fundeni’’ Dialysis Center, Bucures¸ ti; Cezarina Bejan, MD, Nefromed Baˆrlad Dialysis Center; Marilena Bidea, MD, ‘‘Sf. Ap. Andrei’’ Galat¸ i County Teaching Hospital Dialysis Center; Aurel Bizo, MD, PhD, Nefrocare Dej Dialysis Center; Anca Blaga, MD, Renamed Nefrodial Oradea Dialysis Center; Ioan Boca, MD, Diaverum Romania Sibiu Dialysis Center; Eniko Bodurian, MD, Diaverum Romania Odorheiu Secuiesc Dialysis Center; Gheorghe Botan, MD, IHS Ca˘la˘ras¸ i Dialysis Center; Lavinia Bratescu, MD, IHS Petros¸ ani Dialysis Center; Constantin Bulancea, MD, Fa˘ga˘ras¸ City Hospital Dialysis Center; Mirinela Buruiana, MD, IHS Focs¸ ani Dialysis Center; Viorica Butnaru, MD, Ploies¸ ti County Hospital Dialysis Center; Maia Caraman, MD, Moines¸ ti Dialysis Station; Nicoleta Carastoian, MD, Gral Medical Bucures¸ ti Dialysis Center; Carmen Volova˘¸t , MD, PhD, MEDISS CENTER Taˆrgu Neamt¸ Dialysis Center; Cecilia Jitea, MD, Renal Care Group Tulcea Dialysis Center; Adela Chindris, MD, Satu Mare County Hospital Dialysis Center; Bogdan Cimpineanu, MD, Nefrocare Medgidia Dialysis Center; Iuliana Ciocanea, MD, Nefrocare Caˆmpulung Dialysis Center; Daniela Ciortea, MD, IHS ‘‘Sf. Ioan’’ Bucures¸ ti Dialysis Center;

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450 Cezar Lucian Cocerjin, MD, Nefromed Zala˘u Dialysis Center; Elisaveta Codospan, MD, VAMAGO Res¸ it¸ a Dialysis Center; Maria Covic, MD, PhD, Dialnefromed Botos¸ ani Dialysis Center; Olimpia Cretu, MD, NEFROLMED Alexandria Dialysis Center; Constantin Cruceru, MD, Drobeta Turnu-Severin CFR Hospital Dialysis Center; Luminita Damian, MD, Bucures¸ ti City Teaching Hospital Dialysis Center; Dionisie Dubinciuc, MD, Renamed Raˆmnicu Vaˆlcea Nefrodiamed Dialysis Center; Sergiu Dumitrache, MD, Dia Medical Port Bucures¸ ti Dialysis Center; Hortensia Viorica Epure, MD, ‘‘ERIKA’’ Bras¸ ov Dialysis Center; Lidia Florescu, MD, Diaverum Romania Taˆrgu Jiu Dialysis Center; Gabriela Maria Fociuc, MD, Specimed Bra˘ila Dialysis Center; Nicoleta Irina Fofica, MD, Renamed Dialcare Craiova Dialysis Center; Valentina Georgescu, MD, FMC Nephrocare Pites¸ ti Dialysis Center; Ivona Georgescu, MD, Raˆmnicu Vaˆlcea County Hospital Dialysis Center; Adrian Ghenu, MD, Taˆrgovis¸ te County Hospital Dialysis Center; Mirela Gherman Caprioara, MD, Cluj Teaching County Hospital Dialysis Center; Mirela Liana Gliga, MD, Hiparion Med Taˆrgu Mures¸ Dialysis Center; Ovidiu Golea, MD, Timis¸ oara County Hospital Dialysis Center; Sabina Grigorescu, MD, NefroClinic Ploies¸ ti Dialysis Center; Monica Simona Heteganu, MD, Avitum Taˆrgu Jiu Dialysis Center; Mariana Iacob, MD, ‘‘Sf. Ioan’’ Galat¸ i Children Teaching Hospital Dialysis Center; Ioana Iacob, MD, ‘‘Sf. Pantelimon’’ Focs¸ ani County Hospital Dialysis Center; Ion Iancu, MD, FMC Nefrocare Constant¸ a Dialysis Center; Rodica Ilies, MD, S. C. Diaverum Romania Bistrit¸ a Dialysis Center; Ligia Iosub, MD, S. C. Nefromed Botos¸ ani Dialysis Center; Zsofia Rozalia Ivacson, MD, ‘‘Dr. Fogolyan Kristof’’ Sfaˆntu Gheorghe Hospital Dialysis Center; Christian Klein, MD, PhD, FMC Nephrocare ‘‘Dr. Carol Davila’’ Dialysis Center, Bucures¸ ti; Raluca Ungureanu Lie, MD, Medical Arnaldo Bras¸ ov Dialysis Center; Doriana Lucaciu, MD, Cluj Napoca Teaching City Hospital Dialysis Center; Radu Macavei, MD, FMC Nefrocare Bras¸ ov Dialysis Center; Florin Margineanu, MD, SC Renamed Medical Service II Drobeta Turnu Severin Dialysis Center; Simona Marian, MD, SC Med Center Vaslui Dialysis Center; Adriana Marinescu, MD, S. C. Nefromed Alexandria Dialysis Center; Ioana Diana Maris, MD, ‘‘ Louis Turcanu’’ Timis¸ oara Children Teaching Hospital Dialysis Center; Beatrice Marusceac, MD, SC Nefrocare Sighetu Marmat¸ iei Dialysis Center; Sorina Masek, MD, Lugoj City Hospital Dialysis Center; Marilena Micu, MD, SC Nefromed Satu Mare Dialysis Center; Ileana Mihailescu, MD, Slatina County Hospital Dialysis Center; Eugen Mota, MD, PhD, Craiova County Teaching Hospital Dialysis Center; Dan Munteanu, MD, IHS ‘‘Sf. Pantelimon’’ Dialysis Center, Bucures¸ ti; Mihaela Munteanu, MD, ‘‘Sf. Maria’’ Ias¸ i Children Teaching Hospital Dialysis Center; Ioana Nicoleta Nicolae, MD, S.C. Diasys Medical Taˆrgovis¸ te Dialysis Center; Marcel Palamar, MD, Deva County Hospital Dialysis Center; Radu Viorel Patea, MD, Arad County Teaching Hospital Dialysis Center; Ioan Mihai Patiu, MD, S. C. Nefromed Cluj Dialysis Center; Marilena Piper, MD, Bra˘ila County Hospital Dialysis Center; Mariana Pop, MD, S. C. Nefromed Baia Mare Dialysis Center; Luminita Popa, MD, Baca˘u County Hospital Dialysis Center; Marcela Pravat, MD, Renal Care Group Slobozia Dialysis Center; Daniela Pricop, MD, Ph D, Baia Mare County Hospital Dialysis Center; Monica Radu, MD, Caˆmpia Turzii City Hospital Dialysis Center; Dana Radulescu, MD, PhD, ‘‘Sf. Ioan’’ Bucures¸ ti Teaching Hospital Dialysis Center; Mihai Raicu, MD, S. C. Hemo Vest Zala˘u Dialysis Center; Eugenia Railean, MD, Diaverum Romania Medias¸ Dialysis Center; Violeta Roman, MD, Avitum Sighis¸ oara Dialysis Center; Leonard Rosu, MD, S. C. Renal Med Ones¸ ti Dialysis Center; Mihaela Rosu, MD, Tulcea County Hospital Dialysis Center; Cornel Rusan, MD, FMC Nefrocare Deva Dialysis Center; Oana Schiller, MD, Avitum Timis¸ oara Dialysis Center; Liviu Segall, MD, SC Nefromed Ra˘da˘ut¸ i Dialysis Center; Cristian Serafinceanu, MD, PhD ‘‘N. Paulescu’’ Bucures¸ ti Institute Dialysis Center; Aurelian Simionescu, MD, S. C. Nefrolab Slatina Dialysis Center; Petronela Sodolescu, MD, ‘‘Wolfgan Steger’’ Petros¸ ani County Hospital Dialysis Center; Costel Spanu, MD, PhD, S.

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Int Urol Nephrol (2014) 46:443–451 C. Rena Clinic Cluj Dialysis Center; Roxana Dorina Stavar, MD, IHS Galat¸ i Dialysis Center; Ioana Suciu, MD, Bistrit¸ a Na˘sa˘ud County Hospital Dialysis Center; Dorina Tacu, MD, PhD, Bucures¸ ti ‘‘Fundeni’’ Institute—Transplant and Dialysis Dept; Catalin Tacu, MD, S.C. Diaverum Romania Industriilor Dialysis Center, Bucures¸ ti; Mircea Tandrau, MD, S. C. Hemo Vest Arad Dialysis Center; Cristina Teodoru, MD, S. C. Diaverum Romania Sibiu Dialysis Center; Delia Timofte, MD, S.C. Diaverum Romania—Sema Parc Dialysis Center, Bucures¸ ti; Daniela Elena Tir, MD, Tg. Ca˘rbunes¸ ti City Hospital Dialysis Center; Camelia Totolici, PhD, MD, SC Nefromed Timis¸ oara Dialysis Center; Carmen Turcea, MD, SC Nefromed Piatra Neamt¸ Dialysis Center; Liliana Tuta, PhD, MD, S.C. Eurodializa Mangalia Dialysis Center; Coriolan Ulmeanu, MD, PhD, Bucures¸ ti ‘‘Grigore Alexandrescu’’ Children Hospital Dialysis Center; Cristina Vaduva, MD, IHS Craiova Dialysis Center; Peter Varga, MD, Miercurea Ciuc County Hospital Dialysis Center; Mariana Vasilescu, MD, Bucures¸ ti‘‘Fundeni’’ Institute—Children Dept Dialysis Center; Adina Monica Veres, MD, Zala˘u County Hospital Dialysis Center; Gabriela Voicu, MD, IHS Bra˘ila Dialysis Center; Mihai Voiculescu, MD, PhD, Bucures¸ ti ‘‘Fundeni’’ Institute Dialysis Center; Carmen Volovat, MD, PhD, SC MEDISS Tg. Neamt Dialysis Center; Diana Zilisteanu, MD, IHS Bus¸ teni Dialysis Center; Adrian Zugravu, MD, ‘‘Dr. Carol Davila’’ Bucures¸ ti Teaching Hospital of Nephrology, Dialysis Center. Romanian Registry staff Isar.

Eugen Podgoreanu, Viorica Ion, Daniela

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