Proteinuria and cholesterol reduction are independently associated with less renal function decline in statin-treated patients; a post hoc analysis of the PLANET trials

Abstract

Background: Statins have shown multiple effects on different renal risk factors such as lowering of total cholesterol (TC) and lowering of urine protein:creatinine ratio (UPCR). We assessed whether these effects of statins vary between individuals, the extent of discordance of treatment effects on both TC and UPCR within an individual, and the association of responses in TC and UPCR with estimated glomerular filtration rate (eGFR) decline.

Methods: The PLANET I and II (Renal effects of Rosuvastatin and Atorvastatin in Patients Who Have Progressive Renal Disease) trials examined effects of atorvastatin and rosuvastatin on proteinuria and renal function in patients with proteinuria. We post hoc analysed 471 therapy-adherent proteinuric patients from the two trials and assessed the individual variability in UPCR and TC response from 0 to 14 weeks and whether these responses were predictive of eGFR decline during the subsequent 9 months of follow-up.

Results: UPCR and TC response varied between individuals: mean UPCR response was -1.3% (5th-95th percentile -59.9 to 141.8) and mean TC response was -93.9 mg/dL (-169.1 to -26.9). Out of 471 patients, 123 (26.1%) showed a response in UPCR but not in TC, and 96 (20.4%) showed a response in TC but not in UPCR. eGFR (mL/min/1.73 m2) did not decrease significantly from baseline in both UPCR responders [0.4; 95% confidence interval (CI) -1.6 to 0.9; P = 0.54] and TC responders (0.3; 95% CI -1.8 to 1.1; P = 0.64), whereas UPCR and TC non-responders showed a significant decline in eGFR from baseline (1.8; 95% CI 0.6-3.0; P = 0.004 and 1.7; 95% CI 0.5-2.9; P = 0.007, respectively). A lack of response in both parameters resulted in the fastest rate of eGFR decline (2.1; 95% CI 0.5-3.7; P = 0.01). These findings were not different for rosuvastatin or atorvastatin.

Conclusions: Statin-induced changes in cholesterol and proteinuria vary between individuals and do not run in parallel within an individual. The initial fall in cholesterol and proteinuria is independently associated with a reduction in eGFR decline. This highlights the importance of monitoring both cholesterol and proteinuria after initiating statin therapy.

Keywords: cholesterol; proteinuria; renal function; response variability; statins.

FIGURE 1

Correlation between U_PCR change and TC change from baseline to Week 14, represented for all treatment groups and per treatment group.

FIGURE 2

Change in eGFR from Weeks 11 to 52 according to U_PCR change and TC change from baseline to Week 14. (A) Mean U_PCR change and subsequent eGFR change in U_PCR responders (ΔU_PCR ≤0%) and U_PCR non-responders (ΔU_PCR >0%). (B) Mean TC change and subsequent eGFR change in cholesterol responders (ΔTC≤−100 mg/dL) and cholesterol non-responders (ΔTC >−100 mg/dL). (C) Least square (LS) means of eGFR change from Weeks 11 to 52 according to combined U_PCR and TC change from baseline to Week 14.

FIGURE 2

Change in eGFR from Weeks 11 to 52 according to U_PCR change and TC change from baseline to Week 14. (A) Mean U_PCR change and subsequent eGFR change in U_PCR responders (ΔU_PCR ≤0%) and U_PCR non-responders (ΔU_PCR >0%). (B) Mean TC change and subsequent eGFR change in cholesterol responders (ΔTC≤−100 mg/dL) and cholesterol non-responders (ΔTC >−100 mg/dL). (C) Least square (LS) means of eGFR change from Weeks 11 to 52 according to combined U_PCR and TC change from baseline to Week 14.