Hitoshi Iwamoto

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.

Diffuse Intrapulmonary Hemorrhage and Renal Failure in Adult Henoch-Schönlein Purpura

A 53-year-old woman with Henoch-Schönlein purpura presented with massive intrapulmonary hemorrhage and renal failure. Renal pathology revealed diffuse proliferative glomerulonephritis with granular deposition of immunoglobulin on immunofluorescent staining. Therapy with oral prednisolone resulted in resolution of the pulmonary lesions and renal failure.

Renal tubular hypouricemia: evidence for defect of both secretion and reabsorption.

Two patients had hypouricemia due to increased uric acid clearance. They showed no decrease of urate clearance to creatinine clearance ratio (Cua/Ccr) following pyrazinamide administration, and no increase of Cua/Ccr after probenecid. One patient showed a limited decline in Cua/Ccr after intravenous furosemide. In the other patient, neither acetylsalicylate nor furosemide produced any noticeable change in Cua/Ccr. Both showed a normal diuretic response after intravenous furosemide. The results indicate that they had massive defects in urate transport along the nephron, probably including both secretion and reabsorption.

Hypouricemia Due to Increased Tubular Urate Secretion

A 45-year-old woman had hypouricemia (serum uric acid, 1.0-2.3 mg/dl) with increased uric acid clearance (29.8 +/- 9.3 ml/min/1.73 m2). Uric acid clearance to creatinine clearance ratio (Cua/Ccr) was suppressed markedly by pyrazinamide to 2.3% and surprisingly enhanced by probenecid to 227.8%. No other renal tubular or metabolic abnormalities were detected. This previously unreported high postprobenecid Cua/Ccr suggests that markedly increased urate secretion by the renal tubule is responsible for hypouricemia in this patient.

Long-Term Enalapril Therapy in Patients with Chronic Renal Failure on a Low-Protein Diet

The effect of enalapril (5–10 mg/day) on the progression of chronic renal failure (CRF) was compared with that of metoprolol (40–120 mg/day) in 28 patients for 24 months in a prospective study. Throughout the study, there was no significant difference between the 2 groups in protein intake and urinary sodium excretion. But there was a significant difference between the 2 groups in diastolic and mean arterial blood pressure at 6 months. In the serum creatinine level, there was a significant difference between the 2 groups at 6, 12, 18, and 24 months. In creatinine clearance, there was a significant difference between the 2 groups at 24 months. In addition, the progression of CRF was significantly faster in the metoprolol group than the enalapril group as estimated from the slope of creatinine clearance (p < 0.05) and the slope of glomerular filtration rate (p < 0.0005). In urinary protein excretion, there was a significant difference between the 2 groups at 6 and 18 months (p < 0.05). These findings indicate that enalapril has a suppressive effect on the progression of CRF and also has an antiproteinuric effect by a mechanism independent of its antihypertensive effect.