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Kidney Week

Abstract: FR-PO253

Association Between Individual Cholesterol and Albuminuria Response and Exposure to Atorvastatin or Rosuvastatin

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Kroonen, Marjolein, University Medical Centre Groningen, Groningen, Netherlands
  • Stevens, Jasper, University Medical Center Groningen, Groningen, Netherlands
  • de Zeeuw, Dick, University Medical Center Groningen, Groningen, Netherlands
  • L Heerspink, Hiddo Jan, University Medical Center Groningen, Groningen, Netherlands

Group or Team Name

  • Clinical Pharmacy and Pharmacology
Background

The PLANET trials showed that atorvastatin 80 mg (ATOR) but not rosuvastatin at either 10 or 40 mg (ROSU) reduced urinary protein:creatinine ratio (UPCR) while effects on LDL cholesterol were similar. However, individual changes in both UPCR and LDL cholesterol to these statins varied widely between patients. This interindividual variability could not be explained by patients’ physical or biochemical characteristics. We assessed whether the plasma concentration of the statins were associated with LDL cholesterol and albuminuria response.

Methods

the PLANET trials randomized patients with an urine protein:creatinine ratio of 500 – 5000 mg/g, fasting LDL cholesterol >2.3 mmol/L and stable treatment with ACE or ARB to a 52 week treatment period with ATOR 80 mg, ROSU 10 mg or 40 mg. For the current analysis patients with available samples at week 52 and treatment compliance >80% by pill count were included (N=295).
Main outcome measurements were percentage change in UPCR and absolute change in LDL cholesterol (delta LDL), comparing baseline to week 52.

Results

Median (interquartile range) plasma concentration at week 52 for ATOR 80 mg was 3.9 (2.1 – 8.7); for ROSU 10 mg 1.0 (0.7 – 2.0) and for ROSU 40 mg 3.5 (2.0 – 6.8). Higher plasma concentration of statin was associated with larger LDL-cholesterol reductions at week 52 and not with UPCR change nor UACR change (Table). Serum albumin (β = 0.63, p = 0.05) and eGFR per 10 ml/min1.73m2 (β = -0.09; p = 0.04) were independently associated with ROSU plasma concentration. Active metabolites concentration of either ROSU or ATOR did not correlate with LDL and UPCR changes.

Conclusion

Individual variation in plasma concentrations of rosuvastatin and atorvastatin explained the LDL-cholesterol changes of the patients. The individual variation in UPCR change was not explained by the plasma concentration of both statins.

Pearson correlations between plasma concentration of atorvastatin and rosuvastatin and delta LDL-cholesterol (mmol/L) and log Delta UPCR and UACR at week 52.
 LDL changeUPCR changeUACR change
 Pearson correlationP-valuePearson correlationP-valuePearson correlationP-value
Atorvastatin-0.280.0060.160.130.140.16
Rosuvastatin-0.40<0.0010.070.300.030.70