Should CAPD be the first choice for dialysis in Romania? Audit of the Iasi ‘C. I. Parhon’ Dialysis Center: 1995–2000

Adrian C. Covic, David J. Goldsmith, Laura Florea, Paul Gusbeth, Carmen Volovat, Traian Taranu, Nicolae Suditu, Costica Novac and Maria Covic

‘C. I. Parhon’ University Hospital Dialysis and Transplantation Center, Iasi, Romania

Abstract

Peritoneal dialysis was first introduced in Romania in 1995. We are reporting data on patient and technique outcomes, based on the 5-year experience of one of the first two Romanian continuous ambulatory peritoneal dialysis (CAPD) centres. During this period, Romania had the highest rate of increase in renal replacement therapy (RRT) and CAPD (28 times over baseline) in Europe: CAPD increase in Romania vs Eastern Europe was 6.7 compared to a similarly defined ratio of 5.6 for haemodialysis (HD).

Between 1995 and 2000, at the ‘C. I. Parhon’ Hospital in Iasi, 259 patients were started on HD and 102 on CAPD. The 90 CAPD patients we followed were treated for a total of 1896 months. 86.7% of the patients were alive on 31 July 2000—67.8% continuing on CAPD, 15.6% on HD and 3.3% transplanted. The 61 patients still on PD on that date, represented 11.1% of the actual Romanian CAPD population and 31% of our RRT population (compared to 13.7% nationwide).

The gross mortality rate was comparable to the mean calculated for the HD population nationwide. Mean survival of the CAPD patients was 45.4±2.6 months (95% CI=40.4–50.4 months). One-year and 5-year patient survival rates were 97.5% and 52.7% respectively, superior and similar to mean figures nationwide. Mean technique survival was 36.6±0.6 months (95% CI=31.5–41.6 months). One- and 5-year technique survival rates were 83.1% and 34.3% respectively. Technique failure was mainly due to dialysis inefficiency: 50% of cases. Mean weekly Kt/V for the 5-year period was 1.92±0.21 while mean weekly creatinine clearance was 61.2±12.4 ml/1.73 m2/week.

Eighty-four episodes of peritonitis were recorded in 46 patients (0.25 episodes/patient/year); mean duration to peritonitis was 23 months (95% CI=18.2–27.5). Malnutrition was noted (SGA score) in 25.5% of the cases. Blood pressure (assessed by 24-h ABPM) was adequately controlled in 83.3% of the patients. Left ventricular hypertrophy was ubiquitous (77.7%), but left ventricular dilatation and systolic dysfunction (fractioning shortening index <25%) were rare—4.4% and 3.3% respectively (similar in prevalence to the Iasi HD population). No statistically significant changes in echocardiographic parameters were recorded between the first and subsequent years on CAPD treatment.

Peritoneal dialysis had a rapid increase in the last 5 years in Romania and particularly in the region of Moldova. Outcomes and complication rates are equal or superior to nationwide HD data and comparable to distinguished centres of CAPD in economically developed countries. We conclude that, provided that optimal medical practice is available, CAPD should be the RRT of choice in Romania, and that it represents the only solution to the country's limited dialysis resources.

Keywords: continuous ambulatory peritoneal dialysis; haemodialysis; treatment modalities; complications; survival

Introduction

An increase in the incidence of end-stage renal disease (ESRD) has been observed worldwide: the expansion rate of the renal replacement therapy (RRT) pool being estimated to be 8.0% in 1995 for the European Union countries [1,2]. This formidable challenge needs to be addressed, keeping in mind the striking inequalities between different regions of the world in the availability of renal replacement resources. The different distribution of ESRD patients across the world, and the rate of increase in uraemia therapy are strongly influenced by the level of gross domestic product [2]. A special situation is seen in Central and Eastern Europe (CEE) where, since the fall of communist regimes in the 1990s, a strong economic recovery associated with profound changes in the national health legislature have taken place. A detailed study of the increase in RRT after political and economical liberalization has been recently published [3], indicating as a major contributor the rapid development of peritoneal dialysis programmes, but, at the same time, pointing to overall lower acceptance rates. In this respect, Romania probably provides the best case for study, as continuous ambulatory peritoneal dialysis (CAPD) was introduced in three centres (one in Iasi and two in Bucharest) only in 1995, at a time where the prevalence of treated ESRD patients was the lowest in CEE countries: 57 p.m.p vs 157–305 p.m.p for all others (Poland, Hungary, Bulgaria and Czechoslovakia) and 315 for ERA-EDTA [4].

Romania has a population of 22.8 million inhabitants. In 1995, when the decision to initiate CAPD was made, the nephrological community was faced with 65–75 p.m.p. new cases of ESRD per year—1700 new subjects requiring dialysis—for only 29 available haemodialysis (HD) centres [4]. Renal transplantation in Romania is only now emerging. Geographically, the mean travel distance from patients' homes to dialysis centres exceeds 125 km. The situation is worst in the province of Moldova, which had only one major centre (Iasi) serving six counties (travel distances up to 300 km) and nearly 6 million inhabitants (26 RRT patients p.m.p. compared to 57 nationwide and 86 in the developed Banat-Timisoara region). Thus, the ‘C. I. Parhon’ IASI Dialysis Center adopted a policy of intensively developing CAPD as the only means to cover as much as possible of the huge demands for RRT, in an economically disadvantaged region. Moreover, the inclusion policy was similar to that applied to HD, whereas, in other comparable Romanian peritoneal dialysis (PD) centres, diabetic patients were either in a minority or were completely excluded. We are reporting the 5-year (1995–2000) experience of the largest Romanian CAPD unit—‘C. I. Parhon’ University Hospital, Iasi—one of the three units where PD was initiated. The results are also discussed in light of a previous report reviewing the state of nephrology and RRT in Romania in 1995 [4].

Subjects and methods

Between January 1995 and January 2000, 102 Tenckhoff catheters were inserted (patients initiated in 2000 were not included). Catheters were inserted only by surgeons. The surgical procedure was classical in 90 out of the 102 cases and laparoscopical in the other 12. All Tenckhoff cannulae were straight T. Three patients (all diabetics) died of sepsis less than 1 month after initiation of dialysis. Nine patients were transferred to other CAPD centres. The remaining 90 subjects were included in the analysis (Figure 1Go). The cut off time in this analysis was 31 July 2000—all living patients had at least 6 months of therapy.



View larger version (15K):
[in this window]
[in a new window]
 
Fig. 1. Demographic data for the CAPD population, ‘C. I. Parhon’ Hospital, Iasi 1995–2000. *Significant difference compared with other categories: P=0.001; **significant difference compared with other categories: P=0.025.

 
The system used for dialysis was Fresenius Stay-Safe in all cases with four exchanges per day. The dialysis programme was modelled on that of the renal unit of Withington Hospital, Manchester, with logistic advice from Dr D. J. Goldsmith (Guy's Hospital, London, UK). Obese patients (>100 kg) without residual renal function and patients with large anterior abdominal wall herniae or with significant abdominal surgery, were not chosen for peritoneal dialysis de novo. Two blind patients and one with crippling rheumatoid arthritis received CAPD and their family carers were trained to do the dialysis. Nurses had been trained for PD training and supervision by a Fresenius-sponsored PD training nursing sister.

Dialysis efficiency (weekly Kt/V and creatinine clearance) were measured monthly. Failure to deliver a total (renal+method) weekly Kt/V >2.0 and a creatinine clearance >60 ml/min, for two consecutive months, prompted us, after 1997, to increase the number of exchanges to five per day or to switch to haemodialysis. Peritoneal equilibration tests were performed twice a year. Erythropoietin was used on a routine basis from 1997 in all patients with a haemoglobin level <10.0 g/dl (the target level was 10.0 g/dl between 1997 and 1999 and 11.0–12.0 g/dl from the beginning of the year 2000). Calcium carbonate and 0.25–0.75 µg/day 1-alfa calcidol were used to bring plasma phosphate to <1.8 mmol/l and PTH levels to <200 pg/ml. Antihypertensive medication was titrated to bring BP levels <140/90 mmHg.

An individual database was created for each patient when dialysis was commenced. This included all biochemical parameters, blood pressure data, weight and nutrition parameters, dialysis efficiency, renal and peritoneal ultrafiltration data, complications and patient outcome. Each patient was seen on a monthly basis. Blood pressure was assessed from monthly visits and twice-yearly 24-h ambulatory blood pressure measurements (ABPM). All patients underwent echocardiography once a year. Nutrition was evaluated using the Subjective Global Assessment Score.

Statistical analysis
Survival of patients was analysed using the Kaplan-Meier method and differences compared using the log-rank test. Modality changes (transfer to haemodialysis or transplantation) were treated according to the history method. Since the risk with this method is to artificially improve the results of PD, those deaths which occurred during the first 2 months after shifting, and which were related to illnesses or problems present during or continuing from the period of treatment by the first modality, were ascribed to CAPD. Data were analysed retrospectively using an SPSS package. In order to be more relevant for the situation in Romania, the results were compared, when possible, with data recently reported from the second largest CAPD unit: the ‘Fundeni’ Hospital, Bucharest, 3 years experience and 75 patients [5].

Results

Between 1995 and 2000 at the ‘C. I. Parhon’ Hospital in Iasi, 259 patients were started on HD and 102 on CAPD. The 90 CAPD patients studied (see Methods) were treated for a total of 1896 months (21.1 months per patient vs 19.4 for the ‘Fundeni’ CAPD Center [5]). A total of 86.7% of the patients were alive on 31 July 2000 (compared with 89.3% for the ‘Fundeni’ Hospital [5]): 67.8% continuing on CAPD, 15.6% on HD and 3.3% transplanted. The 61 patients in Iasi still being treated by CAPD at that date, represent 11.1% of the actual Romanian CAPD population. CAPD represents 31% of our RRT population compared with 13.7% nationwide. The prevalence of dialysis (HD and CAPD) in Iasi, Romania, and Central and Eastern Europe is shown in Table 1Go.


View this table:
[in this window]
[in a new window]
 
Table 1. Trends of CAPD and HD development in IASI, ‘C. I. Parhon’ Dialysis Center, Romania and Central and Eastern Europe

 
The demographics of the reported CAPD population are presented in Figure 1Go and Table 2Go.


View this table:
[in this window]
[in a new window]
 
Table 2. Demograpghics of the CAPD population ‘C. I. Parhon’ IASI Dialysis Center 1995–2000

 
Patient survival*
The gross mortality rate was comparable to the mean calculated for the HD population nationwide. Mean survival of the CAPD patients was 45.4±2.6 months (95% CI=40.4–50.4 months). There was no significant difference in mean survival between males (44.7±3.1 months) and females (45.2±4.2 months). One-year and 5-year patient survival rates were 97.5% and 52.7% respectively (Figure 2Go). First-year survival rate is significantly higher than that of HD nationwide, while 5-year survival rate is similar to that of HD for Romania. Comparison with HD survival data from our centre is shown in Figure 3Go. These data are also higher than those calculated in a recent meta-analysis [6] (Table 3Go) for ESRD treatment outcomes in databases from single centres and registries. Cardiovascular mortality represented 75% of all causes of death (strokes, acute myocardial infarction and sudden cardiac death being equally distributed).



View larger version (21K):
[in this window]
[in a new window]
 
Fig. 2. CAPD survival rates ‘C. I. Parhon’ Hospital, Iasi Dialysis Center, 1995–2000.

 


View larger version (20K):
[in this window]
[in a new window]
 
Fig. 3. Comparison between CAPD and HD outcomes for the ‘C. I. Parhon’ Hospital, Iasi Dialysis Center.

 

View this table:
[in this window]
[in a new window]
 
Table 3. Comparison of 1- and 5-year survival rates for the IASI CAPD population with data from Romanian HD population and PD outcome studies

 

Technique survival*
Mean technique survival was 36.6±2.6 months (95% CI=31.5–41.6 months). One-year and 5-year technique survival rates were 83.1% and 34.3% respectively. However, although mean technique survival was similar between male (35.6±3.3 months) and female patients (36.9±3.9 months), there was a significant impact of gender on the technique outcomes. During the second year on CAPD, female subjects had a clear advantage—by at least 10% compared to males. This, however, was reversed by the third year of dialysis. At 5 years, the difference between sexes was not significant: males (44.7±3.1 months) vs females (45.2±4.2 months). Technique failure (50% of cases) was mainly due to dialysis inefficiency (inadequate clearance—defined by DOQI Guidelines [12] or fluid control—due to lack of peritoneal ultrafiltration). Other causes determining transfer to HD were: peritonitis+exit site infection—28.6%; patient refusal to continue on CAPD—7.1%; other—14.2%.

Infectious complications
Eighty-four episodes of peritonitis were recorded in 46 of our patients (49% of patients without any peritonitis vs 72% for ‘Fundeni’ Hospital Dialysis Center, Bucharest [5]) (Figure 4Go). Mean duration from peritonitis was 23 months (95% CI=18.2–27.5). The probability of being completely free of peritonitis was less than 25% at 5 years. Overall there were 0.25 peritonitis episodes/patient/year (vs 0.27 for Fundeni). Patients with two or more episodes had a significant longer course of CAPD, more exit site infections and a higher prevalence of diabetes (Table 4Go and Figure 5Go). Fifty per cent of these patients with repeated episodes of peritonitis were transferred to HD or died (almost double the rate for subjects without or with only one episode of peritonitis).



View larger version (21K):
[in this window]
[in a new window]
 
Fig. 4. Probability of remaining peritonitis-free in the ‘C. I. Parhon’ Hospital CAPD programme.

 

View this table:
[in this window]
[in a new window]
 
Table 4. Comparison of patients with and without peritonitis

 


View larger version (17K):
[in this window]
[in a new window]
 
Fig. 5. Infectious complications in the CAPD population treated between 1995–2000 in the ‘C. I. Parhon’ Iasi Dialysis Center.

 
There were no cases of sclerosing peritonitis in the study period.

Dialysis efficiency
Mean weekly Kt/V for the 5-year period was 1.92±0.21. Mean weekly creatinine clearance was 61.2±12.4 ml/1.73 m2/week.

Residual renal function declined relentlessly. The diuresis at first adequacy testing was 1056±423 ml/day, then 789±604 ml/day 12 months later, 550±492 ml/day at 24 months, 220±190 ml/day at 36 months, 104±107 ml/day at 48 months, and <50 ml/day at 60 months.

Nutritional status
Malnutrition was noted in 25.5% of the cases (3.33% were severely malnourished and 21.66% were mildly malnourished). A total of 16.6% of the subjects had albumin levels <3.0 g/l with no patient below 2.5 g/l.

Cardiovascular status
Blood pressure (assessed by 24-h ABPM) was adequately controlled in 83.3% of the patients (65–75% for the ‘Fundeni’ Hospital Dialysis Center, Bucharest [5]), but 80% of all patients were on anihypertensive medication. Non-dipping was present in 77.7% of the patients. The first echocardiographic evaluation of a patient was performed after 6 months on CAPD. Left ventricular hypertrophy was ubiquitous (77.7%) but left ventricular dilatation (cavity volume >90 ml/m2) and systolic dysfunction (fractioning shortening index <25%) were rare (4.4% and 3.3% respectively). The same data for the Iasi HD population were: 75% LVH, 4.2% dilatation and systolic dysfunction (P=ns vs CAPD).

Economics
CAPD cost per patient (including treatment of peritonitis episodes and follow-up visits) for the ‘C. I. Parhon’ Iasi Dialysis Center was 7220.00 USD/patient/year, 20% less than the HD cost (9000.00 USD/patient/year). These figures only included supplies and medication. Furthermore, personnel requirements were, as expected, significantly less for the CAPD programme compared to the HD unit. Excluding peritonitis-related admissions, the hospitalization rate was similar for HD and CAPD patients.

Discussion

Recently, detailed reports [3,4] outlined the status and evolution of renal replacement therapies in Central and Eastern Europe during the first part of the 1990s, subsequent to the dramatic political and socio-economic changes caused by the fall of the communist regimes. Romania probably represents the quintessence of this phenomenon: initial insufficient resources and a dramatic increase in dialysis facilities and number of patients treated in recent years [4]. We are presenting the 5-year experience of one of the first centres where peritoneal dialysis was introduced in 1995.

Romania had, during the 1995–2000 period, the greatest rate of increase in CAPD-treated patients—almost 10 times more rapid than the country's corresponding rate for HD and seven times higher than that recorded in the Central and Eastern European region. Iasi, the historical capital of the Moldova region (with a quarter of the country's population but its lowest per capita income and infrastructure), developed the largest CAPD programme. This intensive development has been matched by equally favourable outcomes: CAPD patient survival data are superior compared to haemodialysis data nationwide or, for the first 3 years of the RRT period, to those in our centre. More importantly, our data are comparable to those reported by large registries or by other centres recognized for their excellence in CAPD care [611]. Our results were not favourably biased by the ‘rescue’ of particularly ill patients to HD, or by a different inclusion policy compared to HD. In further support of these conclusions, our CAPD-technique survival rate is also comparable with data in published literature [9,11]. A significant drop in the probability of technique survival was recorded by the end of the second year of PD (a long-term technique survival lower than that of the Brescia group [7,8]). This was mainly due to the transfer to HD of patients not meeting response adequacy targets, once the residual renal function disappeared (50% of all dropouts vs 11.5% for the Brescia group [8]). Measures designed to improve technique survival (lowering the percentage of obese patients, earlier initiation of CAPD), will definitely have a favourable influence on survival outcomes. However, an increase of prescription for bags and dialysate volume may increase the drop-out rate due to patient and partner burn-out, minimal at present in our population (only one case). Access to automated peritoneal dialysis has been possible in Iasi only since 1999.

Complication rates were no different in our programme from those of the best results reported in the literature [9,11,13]. CAPD achieved a good overall BP control, with dependence on more antihypertensive medications compared to HD (data not shown). Prevalence of left ventricular dilatation with systolic dysfunction—a condition associated with the worst prognosis—was low. Malnutrition, in a population with a mean income of <100 USD/month, was lower than that recently reported by an Italian multicentre study [14] or by the group of Brescia [7,8].

Thus, dialysis adequacy data assessed according to the DOQI guidelines [12] and by blood pressure control, echocardiographic findings and nutritional status indicate the good overall results of the largest CAPD programme in Romania. Of note is the fact that these results were obtained in a region with the lowest income and least developed social and medical infrastructure in Romania. This development was implemented without logistic problems and with less expenditure than would have been necessary for new HD centres. We believe that, for the success of implementing new CAPD centres in developing countries, a detailed organization of all aspects of the programme, a high quality of nursing and medical input, and strong familial support are all essential.

Clearly in the long-term, a CAPD programme does not represent the ideal renal replacement solution, especially once residual renal function is lost. Transplantation should be provided within the first 3 years (our data support previous evidence that CAPD survival is initially superior to that of HD, and thus CAPD should be the first method of choice for dialysis in Romania). However, in Romania today, there are only two major transplantation centres and cadaveric organ donation is only episodic; in Iasi, renal transplants were first performed in November 2000. Our CAPD programme, from the beginning, aimed to provide, through optimal medical practice, outcomes and complication rates superior (or at least equal) to HD nationwide, and comparable to distinguished centres of CAPD in economically developed countries. It was devised to treat a large and expanding ESRD population, in a region with limited HD resources, until the complete implementation of a nationwide transplantation policy (already in full, marked development). It is our view that an integrated CAPD-transpantation-haemodialysis programme (with an emphasis on live-donor transplantation) is the only long-term solution for our country. Automated PD and HD will increasingly be needed to maintain adequate dialysis if, as in many Western countries, transplantation activity fails to match demand.

Notes

Correspondence and offprint requests to: Dr Adrian Covic MD, PhD, ‘C. I. Parhon’ University Hospital Dialysis and Transplantation Center Medical Director, Blvd. Carol I, No. 50, Iasi 6600, Romania. Email: nefro{at}mail.dnts.ro Back

* No comparable data for other Romanian CAPD populations. Back

References

  1. Briggs JD, Berthoux F, Jones E. Predictions for future growth of ESRD prevalence. Kidney Int2000; 57: S46–S48[ISI]
  2. Schena FP. Epidemiology of end-stage renal disease: International comparisons of renal replacement therapy. Kidney Int2000; 57 [Suppl 74]: S39–S45[ISI]
  3. Rutkowski B, Ciocalteu A, Djukanovic L et al. Evolution of renal replacement therapy in Central and Eastern Europe 7 years after political and economical liberation. Nephrol Dial Transplant1998; 13: 860–864[Abstract]
  4. Ursea N, Mircescu G, Constantinovici N, Verzan C. Nephrology and renal replacement therapy in Romania. Nephrol Dial Transplant1997; 12: 684–690[Abstract]
  5. Capsa D, Ciurea S, Ciobotea R, Dimulescu T, Gheorghiu C. Dializa peritoneala continua ambulatorie. Rezultate dupa 3 ani de aplicare în Spitalul Clinic Fundeni Bucuresti. Nefrologia2000; 14: 79–86
  6. Ross S, Dong E, Gordon M et al. Meta-analysis of outcome studies in end-stage renal disease. Kidney Int2000; 57 [Suppl 74]: 28–38
  7. Maiorca R, Vonesh, Cancarini GC. A six-year comparison of patient and technique survivals in CAPD and HD. Kidney Int1988; 34: 518–524[ISI][Medline]
  8. Cancarini GC, Massimo S, Vizzardi V et al. Long-term peritoneal dialysis outcome in a single center. Perit Dial Int2000; 20: S121–S126[ISI][Medline]
  9. Kurtz SB, Johnson WJ. A four year comparison of continuous ambulatory peritoneal diaysis and center hemodialysis. Arch Intern Med1986; 146: 1138–1143[Abstract]
  10. Gokal R, Jakubowski C, King J. Outcome in patients on continuous ambulatory peritoneal dialysis and hemodialysis: 4-year analysis of a prospective multicentre study. Lancet1987; 14: 1105–1109
  11. Quarello F, Bonello F, Boero R et al. CAPD in a large population: a 7-year experience. Adv Perit Dial1989; 5: 56–62[Medline]
  12. National Kidney Foundation Dialysis Outcomes Quality Initiative. Clinical Practice Guidelines for Peritoneal Dialysis Adequacy. National Kidney Foundation, New York, 1997
  13. Fried L, Pirano B. Peritonitis. In: Gokal R, Khanna R, Krediet RT, Nolph KD (eds.). Textbook of Peritoneal Dialysis, 2nd Edition. Kluwer Academic Publishers, Dordrecht, 2000; 545–564
  14. Ciancciaruso B, Brunori G, Kopple JD et al. Cross-sectional comparison of malnutrition in continuous ambulatory peritoneal dialysis and haemodialysis patients. Am J Kidney Dis1995; 26: 475–486[ISI][Medline]