Background: Proteinuria is known to be an independent predictor of progression of chronic renal failure – not only in native kidneys but also in kidney grafts. In adults, proteinuria was shown to impair graft function with different influencing variables i.a. related to the underlying disease, onset and extent of proteinuria and renal histology. However, data in children are scarce and limited to small-scale studies.
Methods: The European CERTAIN Registry evaluates the outcome of pediatric renal allograft (RTx) recipients. Data of 386 participants were analyzed regarding prevalence, extent and origin of proteinuria (24h-proteinuria, urinary protein/creatinine coefficient (UPCR), glomerular/tubular) over a 5-year-observational period. Impact on graft function (GFR, graft loss) and the relevance of potential influencing factors (age, sex, body weight, hypertension, donor/transplant-related variables, immunosuppression) were assessed using multivariate and Kaplan-Meier analysis.
Results: 386 patients (60% male) were included, mean age at RTx was 10.34±5.24 years. 90% of patients presented at least once with urinary protein excretion above the age-related limit (proteinuria) and 22.5% surpassed the fivefold age-related range. Median UPCR decreases over time from 280mg/g creatinine (crea; 1 month after RTx) to 110mg/g crea at 5 years. Severe proteinuria (>5x age-range) within one month after RTx persisted in 43% of patients. In 29% of patients proteinuria was further classified: tubular proteinuria (23%) was predominant within the first month post-transplant, glomerular origin (67%, 10% mixed) increased thereafter with higher UPCR (850mg/g vs. 598mg/g crea (tubular). 8/386 patients lost their grafts (mean 37.5 months post RTx). GFR was negatively correlated with proteinuria (p=0.004, p<0.001 from ≤3.5 years), outcome of patients with persistent proteinuria (>1 and 5x age-range) was significantly worse compared to patients with no or non-persistent proteinuria (difference in GFR p<0.04 at 4.5 and 5 years post RTx). Age <6 years (p<0.001), male gender (p<0.05), low body weight (p<0.001), elevated systolic blood pressure (p<0.001), mTORi-based immunosuppression (p<0.01) were correlated with proteinuria. No impact was detected for donor-related variables, cold ischemia time, HLA mismatch, delayed graft function, or viral infections (EBV, CMV and BKV). Correlation between UPCR and 24h-proteinuria was excellent (p<0.0001, r_rmcorr=0.95).
Conclusion: Proteinuria in children with renal allografts was frequent, exceeding prevalence from adult studies, however, in the majority it was of mild to moderate extent. Despite excellent overall outcome proteinuria impaired graft function in the longterm, especially if persistent and irrespective of its quantity. Male gender, age <6years, low body weight, high blood pressure and mTORi were independent variables. UPCR significantly corresponded with 24h proteinuria demonstrating its applicability in daily routine diagnostics.