Early Clues to Diabetic Kidney Disease

A medical history and measurements of blood pressure (BP), hemoglobin A1c, albumin excretion rate, and serum concentrations of uric acid and cystatin C were obtained; estimated glomerular filtration rate (GFR) was measured by a cystatin C-based formula.

On screening tests, results showed 311 patients had small amounts of the protein albumin--called microalbuminuria--in the urine. The other 364 patients had normal urine albumin levels. None of the patients had even higher levels of albumin (albuminuria), representing more advanced diabetic nephropathy; in contrast, the serum uric acid level was consistently related to kidney function--the higher the uric acid, the lower the kidney function--and one in five had some impairment of kidney function on a standard GFR test. In univariate and multivariate analyses, lower GFR was strongly and independently associated with higher serum uric acid and higher urinary albumin excretion rate, older age, and antihypertensive treatment. The study was published online ahead of print on February 13, 2008, in the Clinical Journal of the American Society of Nephrology.

"The serum uric acid concentration is modifiable by drugs or by decreasing the intake of dietary protein, the main source of uric acid,” said lead author Elizabeth Rosolowsky, M.D. "If follow-up studies, already underway, demonstrate that serum uric acid concentration predicts the course of early decline in kidney function, then clinical trials would be justified to test whether modifying serum uric acid concentration also modifies the course of renal function decline in type I diabetic patients with high normoalbuminuria or microalbuminuria.”

The association between high serum uric acid and insulin resistance has been known since the early part of the 20th century. Nevertheless, recognition of high serum uric acid as a risk factor for diabetes has been a matter of debate. In fact, hyperuricemia has always been presumed to be a consequence of insulin resistance rather than its precursor. On the other hand, it has been shown that high serum uric acid is associated with higher risk of type II diabetes independent of obesity, dyslipidemia, and hypertension.


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