Renal Impairment, Cystatin C Linked

QUEBEC CITY—Early changes in cystatin C levels predict loss of renal  function, according to new findings.

Elevated serum cystatin C concentration is an emerging marker of early renal dysfunction, independent of albuminuria status, said lead investigator Francisco J. Martinez-Martin, MD, PhD, an endocrinologist at University Hospital Dr. Negrin, Las Palmas de Gran Canaria, Spain.

It is thought to be a more sensitive measure than estimated glomerular filtration rate (eGFR), which is based on creatinine.

Dr. Martinez-Martin and his colleagues analyzed data from 91 patients who participated in the OLAS (Olmesartan/Amlodipine vs. Olmesartan/Hydrochlorothiazide in Hypertensive Patients with Metabolic Syndrome) trial.

“We wanted to see the early effect of these treatments on cystatin C in the OLAS trial and their relationship with long-term changes in renal function,” he said. Findings were presented at the 3rd International Congress on Abdominal Obesity.

In the OLAS study, non-diabetic obese, hypertensive patients who had systolic blood pressure (SBP) measurements of 140-179 mm Hg were randomized to receive olmesartan 20 mg/amlodipine 5 mg (60 patients) or olmesartan 20 mg/hydrochlorothiazide (HCTZ) 12.5mg (60 patients).

Patients who did not reach the SBP target of less than 140 mm Hg received a double dose of initial therapy at 13 weeks and thereafter. Doxazosin was added at 26 weeks if necessary. At baseline, no patients had clinical renal failure or albuminuria.

Dr. Martinez-Martin and colleagues measured fasting plasma cystatin C and albumin/creatinine ratio (ACR) in a morning urine specimen at baseline and weeks 13 and 26. The researchers used the Modification of Diet in Renal Disease (MDRD-4) study formula to estimate GFR at  baseline and at every visit, for a total follow-up of 3 years. Early changes in cystatin C significantly predicted decline in renal function and development of stage 3 nephropathy, whereas changes in ACR did not.

Based on study findings, Dr. Martinez-Martin said he encourages the use of cystatin C as a marker of kidney function.

In addition, the olmesartan/amlodipine combination offered greater  renal protection than olmesartan coupled with HCTZ, he said. The olmesartan/amlodipine regimen significantly reduced serum cystatin C by 32.7% at 13 weeks and by 38.4% at 26 weeks, whereas the olmesartan/HCTZ combination reduced serum cystatin C by 3.9% at 13 weeks and 4.6% at 26 weeks. Both combinations reduced ACR in a similar fashion. In addition, the decline in eGFR was significantly slower in the olmesartan/amlodipine arm (1.4 vs. 4.7 mL/min/1.73 m2 per year).

The OLAS trial was funded by Pfizer, and Dr. Martinez-Martin has received fees from Pfizer.

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