Integrated conservative-peritoneal dialysis in CKD-stage5 (ICOPE) study: rationale, design and methods

INTRODUCTION: Increasing dialysis use is expected in the next future due to the growing population of CKD patients referred to renal clinics. The high cost, morbidity and mortality of full-dose dialysis, as its negative impact on quality of life, call for new therapeutic strategy to postpone standard dialysis treatment. Adding a low dose of peritoneal dialysis (PD) on the top of usual conservative therapy (CT) in nondialysis CKD-stage 5 may delay the onerous full-dose dialysis; however, no solid evidence has been provided on effectiveness of this combined therapy because the few previous studies on incremental dialysis were limited by retrospective nature, small sample size, absence of control group and undefined selection criteria. Therefore, we designed the ICOPE study to validate safety and efficacy of integrated therapy METHODS: Prospective multicenter controlled study evaluating the effects of add-on therapy with PD at low dose (CAPD 1-2 exchanges/24h or APD ≤4 sessions/week) in adult CKD-stage 5 patients with complications poorly responsive to nephrology treatment (diet and/or drugs). Key inclusion criteria are: age >18 years, CT in the renal clinic from at least three months, eGFR-MDRD 5-15 mL/min/1.73m2. Furthermore, according to current guidelines on dialysis start, presence of ≥2 risk factors uncontro led by CT was required for enrolment. Key exclusion criteria are kidney transplantation and uremic symptoms that make mandatory full-dose dialysis. Patients unwilling to start PD constitute the control group (treated by CT only). Patients are followed according to best clinical practice with data collected every three months. Primary endpoint is time to renal death (full-dose dialysis or death whichever occurs first); secondary endpoints are hypertension status, metabolic abnormalities and nutritional/functional status after six months of integrated therapy. Estimated sample size is 440 RESULTS: Twenty Italian renal clinics have so far recruited 100 patients in the ICOPE arm and 15 controls. Twelve patients have been excluded as they did not meet selection criteria. The analysis planned at 25% recruitment to verify appropriateness of selection criteria, shows the following main basal features: age 63±15 y, males 61%, prior nephrology care 53 months [13-124], diabetes 29%, history of CV disease 36%, eGFR-MDRD 8.4±2.2 and mean of 24-h urea and creatinine clearance 7.8±2.6 mL/min/1.73m2, urinary output 2098±663 ml/24h. Median number of uncontrolled factors is 3 [2-4] and ≥3 in 64% patients; more prevalent complications are: fatigue in 88% patients, hypertension (BP>140/90 mmHg) 52%, worsening of nutritional status 34%, and uncontroled Mineral Bone Disease (30%), anemia (16%), hyperkalemia (14%) and acidosis (11%). These complications have occurred despite multifactorial CT: dietary protein restriction 74%, anti-hypertensive drugs 3/pt [2-4]; diuretics 70%; anti-RAS 46%; antianemic drugs (epoietin and/or iron) 66%; P-binders and/or Vitamin D 78% CONCLUSIONS: ICOPE will be able to verify for the first time effectiveness of combined low PD dose+CT and to provide useful insights for the choice of the best candidate to this integrated therapy