Range and Heterogeneity of Outcomes in Randomized Trials of Pediatric Chronic Kidney Disease.

OBJECTIVE: To determine the range and heterogeneity of outcomes reported in randomized controlled trials of interventions for children with chronic kidney disease (CKD). STUDY DESIGN: The Cochrane Kidney and Transplant Specialized Register was searched to March 2016. Randomized trials involving children across all stages of CKD were selected. All outcome domains and measurements were extracted from included trials. The frequency and characteristics of the outcome domains and measures were evaluated. RESULTS: From 205 trials included, 6158 different measurements of 100 different outcome domains were reported, with a median of 22 domains per trial (IQR 13-41). Overall, 52 domains (52%) were surrogate, 38 (38%) were clinical, and 10 (10%) were patient-reported. The 5 most commonly reported domains were blood pressure (76 [37%] trials), relapse/remission (70 [34%]), kidney function (66 [32%]), infection (61 [30%]), and height/pubertal development (51 [25%]). Mortality (14%), cardiovascular disease (4%), and quality of life (1%) were reported infrequently. The 2 most frequently reported outcomes, blood pressure and relapse/remission, had 56 and 81 different outcome measures, respectively. CONCLUSIONS: The outcomes reported in clinical trials involving children with CKD are extremely heterogeneous and are most often surrogate outcomes, rather than clinical and patient-centered outcomes such as cardiovascular disease and quality of life. Efforts to ensure consistent reporting of outcomes that are important to patients and clinicians will improve the value of trials to guide clinical decision-making. In our study, non-English articles were excluded.

Losartan and enalapril are comparable in reducing proteinuria in children with Alport syndrome.

BACKGROUND: A previous subgroup analysis of a 12-week, double-blind study demonstrated that losartan significantly lowered proteinuria versus placebo and amlodipine and was well tolerated in children (1-17 years old) with proteinuria secondary to Alport syndrome. The present subgroup analysis of the open-label, extension phase of this study assessed the long-term efficacy and tolerability of losartan versus enalapril. METHODS: Patients who had completed the double-blind study were re-randomized to losartan or enalapril and followed for proteinuria and renal function for up to 3 years. RESULTS: Twenty-seven patients with Alport syndrome were randomized to losartan (0.44-2.23 mg/kg/day; n = 15) or enalapril (0.07-0.72 mg/kg/day; n = 12). The least-squares (LS) mean percent change from week 12 in urinary protein to creatinine ratio (UPr/Cr was +1.1 % in the losartan group versus a further 13.9 % reduction in the enalapril group (GMR [95 % CI] = 1.2 [0.7, 2.0]); the LS mean change from week 12 in estimated glomerular filtration rate (eGFR) was -6.4 ml/min/1.73 m(2) in the losartan group versus -9.1 ml/min/1.73 m(2) in the enalapril group. The adverse event incidence was low and comparable in both treatment groups. CONCLUSIONS: In children with proteinuria secondary to Alport syndrome, losartan maintained proteinuria reduction, and enalapril produced a further proteinuria reduction over the 3-year study period. Both agents were generally well tolerated.