Diabetic hypouricemia as an indicator of clinical nephropathy

We studied the possible association of the low serum uric acid level with incipient diabetic nephropathy in non-insulin-dependent diabetes mellitus (NIDDM). Of 201 NIDDM patients without a diminished glomerular filtration rate, 66 patients (32.8%) showed moderate hypouricemia of less than the mean-1 SD of 201 nondiabetic controls. Thirteen (6.5%) showed marked hypouricemia of less than the mean-2 SD. Hypouricemic patients showed normal daily urinary urate excretion with a markedly elevated urate clearance/creatinine clearance ratio. Most were under poor glycemic control, and presented either negative or intermittent clinical proteinuria. However, neither poor glycemic control, nor the presence of proteinuria or retinopathy alone significantly affected the serum uric acid level of the whole diabetic population. The glomerular filtration rate was determined in comparable groups of diabetic patients with hypouricemia and nonhypouricemic diabetic controls. The hypouricemic group showed a significantly higher endogenous creatinine clearance and lower serum beta-2-microglobulin levels than the nonhypouricemic group. These findings suggest that the hypouricemic group had a higher glomerular filtration rate. Long-term observation of up to 12 years of the above patients revealed that, in most patients, persistent hypouricemia was observed prior to the initial appearance of intermittent proteinuria. We hypothesize that glomerular hyperfiltration also occurs in NIDDM and that it lowers the serum uric acid by increasing the renal clearance of urate. Hypouricemia may also predict the future progression of incipient nephropathy in NIDDM.