POS-435 CHANGE IN eGFR BY CKD STAGE IN PRIMARY HYPEROXALURIA TYPE 1

Abstract

The genetic disorder primary hyperoxaluria type 1 (PH1) is marked by an increased hepatic production of oxalate. The resulting hyperoxaluria leads to recurrent nephrolithiasis and nephrocalcinosis which are commonly observed in childhood. About 50% of PH1 patients develop end stage kidney disease (ESKD) by 33 years of age. Clinical trials of potential therapeutic agents are challenging due to disease rarity and time needed to reach hard clinical endpoints (such as ESKD). Thus, slope of eGFR over time is an attractive surrogate endpoint. However, clinical experience suggests that eGFR decline is not uniform across disease course. Thus we looked at the slope of change in eGFR during sequential stages of CKD in a PH1 cohort. PH1 patients enrolled in the Rare Kidney Stone Consortium (RKSC) registry who were >2 years of age, did not have ESKD at diagnosis, and had ≥2 serum creatinine values between dx their last follow up prior to ESKD were studied. eGFR was estimated using the full age spectrum equation. ESKD was defined as the first occurrence of transplant, initiation of dialysis, or eGFR less than 15 ml/min/1.73m2. Absolute change in eGFR over time was estimated by linear regression within each CKD stage, and estimates across CKD stages were compared using GEE models. A total of 129 PH1 patients met inclusion criteria. Seventy (54.3%) were male and 99 (76.7%) were Caucasian. Median [IQR] age at PH1 dx was 8.6 [3.3, 21.6] years. There were 121 patients with follow-up in CKD stage 2; 72 in stage 3a; 41 in stage 3b; and 14 in CKD stage 4. (Table 1) Absolute annual change in eGFR increased with CKD stage (P=0.007 for trend). (Table 1). As hypothesized, eGFR decline was not uniform across CKD stages in this PH1 population, with a higher rate of eGFR decline at CKD stages 3b and 4. Thus, absolute eGFR and CKD stage need to be accounted for when analyzing eGFR slope in this patient group. These data also suggest that measures to prevent GFR decline to < 45 ml/min/1.73m2 are particularly important, as the disease course accelerates thereafter.