Hyperuricemia and deterioration of renal function in autosomal dominant polycystic kidney disease

Abstract

Background: The role of hyperuricemia in disease progression of autosomal dominant polycystic kidney disease (ADPKD) has not been defined well. We investigated the association of serum uric acid (sUA) with renal function and the effect of hypouricemic treatment on the rate of renal function decline.

Methods: This is a single-center, retrospective, observational cohort study. A total of 365 patients with ADPKD who had estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2 and who were followed up for > 1 year were included in our analysis. Hyperuricemia was defined by a sUA level of ≥ 7.0 mg/dL in male and ≥ 6.0 mg/dL in female or when hypouricemic medications were prescribed.

Results: Hyperuricemia was associated with reduced initial eGFR, independent of age, sex, hypertension, albuminuria, and total kidney volume. During a median follow-up period of over 6 years, patients with hyperuricemia showed a faster annual decline in eGFR (-6.3% per year vs. -0.9% per year, p = 0.008). However, after adjusting for age, sex, hypertension and initial eGFR, sUA was no longer associated with either annual eGFR decline or the development of ESRD. Among 53 patients who received hypouricemic treatment, the annual eGFR decline appeared to be attenuated after hypouricemic treatment (pretreatment vs. posttreatment: -5.3 ± 8. 2 vs. 0.2 ± 6.2 mL/min/1.73 m2 per year, p = 0.001 by Wilcoxon signed-rank test).

Conclusions: Although hyperuricemia was associated with reduced eGFR, it was not an independent factor for renal progression in ADPKD. However, the correction of hyperuricemia may attenuate renal function decline in some patients with mild renal insufficiency.

Figure 1

The association of serum uric acid level with serum creatinine, eGFR, albuminuria and TKV. Relationship between serum uric acid (sUA) level with serum creatinine (sCr) (R² = 0.370, p < 0.001), eGFR (R² = 0.202, p < 0.001), Log albumin-to-creatinine ratio (ACR) (R² = 0.011, p = 0.111) and LogTKV (R² = 0.045, p < 0.001) in ADPKD patients. The sCr and eGFR was measured in 365 patients, ACR in 230 patients and TKV in 278 patients. eGFR, estimated glomerular filtration rate; TKV, total kidney volume; ADPKD, autosomal dominant polycystic kidney disease.

Figure 2

Serial change in sUA and eGFR before and after hypouricemic treatment. After initiation of hypouricemic treatment, mean sUA level decreased from 8.7 ± 0.9 to 5.7 ± 1.4 mg/dL in CKD stage 1-3a group, whereas from 8.8 ± 0.6 to 7.0 ± 0.9 mg/dL in CKD stage 3b-4 group. Mean eGFR level increased from 60.3 ± 16.1 to 62.6 ± 16.4 mL/min/1.73 m² in CKD stage 1-3a group, whereas eGFR decreased from 29.1 ± 7.2 to 26.0 ± 10.0 mL/min/1.73 m² in CKD stage 3b-4 group.