Treatments to slow progression of autosomal dominant polycystic kidney disease: systematic review and meta-analysis of randomized trials.

AIM: Autosomal dominant polycystic kidney disease (ADPKD) is a monogenetic disorder that leads to kidney failure. Our aim was to undertake a meta-analysis of randomized trials of interventions that have been hypothesized to reduce the progression of total kidney volume (TKV) and renal function in ADPKD. METHODS: Relevant trials were identified, and outcomes were: change in TKV, total cyst volume (TCV), renal function and adverse events. Meta-analysis used random effects, with results expressed as mean difference and risk ratio both with 95% confidence intervals (CI). RESULTS: Eleven trials (2262 patients) were included. Compared with placebo, Target of Rapamycin complex 1 (TORC1) inhibitors (5 trials, n = 619), showed no significant change in TKV (P = 0.21), TCV (P = 0.06) or eGFR (P = 0.22). Somatostatin analogues (3 trials, n = 157) reduced TKV by 9% (95% CI -10.33 to -7.58%) but did not alter eGFR. The vasopressin receptor antagonist (n = 1455) attenuated TKV increase to 3%/year (95% CI -3.48 to -2.52) and slowed kidney function decline over a 3-year period. A single trial (n = 41) of eicosapentaenoic acid did not alter the progression of either TKV (P = 0.9) or renal dysfunction (P = 0.78). Adverse events were significant for interventions in all trials compared with placebo. CONCLUSION: These data suggest that somatostatin analogues and vasopressin receptor antagonists attenuate TKV increase. The neutral effects of TORC1 inhibitors on TKV could be true, or due to heterogeneity in study population, drug efficacy and follow-up duration. In the future, further well-designed and powered trials of longer duration using new biomarkers or therapeutic agents with better tolerance are required.

Health-related quality of life of patients awaiting kidney and simultaneous pancreas-kidney transplants.

AIM: Patients undergoing kidney and simultaneous pancreas-kidney (SPK) transplants are younger and fitter than the general dialysis population. Intuitively these patients might have better quality of life (QOL) than the general dialysis population, but their QOL scores are not well characterized. The aim of this study was to compare QOL of patients about to undergo kidney or SPK transplants with Australian dialysis outcomes and practice patterns (DOPPS) data and multiple comorbidity and age-adjusted general population data. METHODS: Patients attending Westmead Hospital for transplants from August 2009 to December 2011 were invited to complete the Kidney Disease QOL-SF(™) 1.3 (KDQOL-SF(™) 1.3) questionnaire regarding their immediate pretransplant QOL. This QOL instrument is predictive of hospitalizations and mortality. The questionnaire was completed within 4 weeks of transplantation. RESULTS: Of 180 patients seen within 4 weeks of transplantation 95 (53%) responded, with no differences from non-responders in age, sex, comorbidities or perioperative complications. Compared with DOPPS, these patients had better physical function and less pain, but significantly lower scores for role physical (CI: -19 to -4, P=0.004) and role emotional (CI: -17 to -2, P=0.018). Patients undergoing SPK transplants reported even poorer general health, energy, social support and function. Patients had lower emotional and social function than people with multiple comorbidities, with whom they shared poor general and mental health and vitality. Scores were markedly lower than the general population except for bodily pain (female). CONCLUSION: Younger, fitter patients are more vulnerable to effects of their illness on social, emotional and physical interactions and may benefit from targeted support.