Since focal glomerulosclerosis is the predominant glomerular lesion in heroin nephropathy and since mesangial expansion is considered to be a precursor of glomerulosclerosis, we have evaluated the effect of opiates on mesangial cell (MC) proliferation and matrix synthesis. We showed, using a fluorometric assay, that MC are not capable of metabolizing heroin to its active metabolite morphine. Cells exposed to morphine (10(-5) M or 10(-4) M) in prolonged cultures either continuously (Group A) or intermittently (Group B) showed enhanced incorporation of [3H]thymidine when compared to control cells (control, 88600 +/- 26303 cpm/well vs. morphine 10(-4) M-Group A, 321203 +/- 52867, P less than 0.001; control vs. morphine 10(-4) M-Group B, 223126 +/- 46866 cpm/well, P less than 0.01; control, 107593 +/- 42284 cpm/well vs. morphine 10(-5) M - Group A, 267108 +/- 41866 cpm/well, P less than 0.001; control vs. morphine 10(-5) M - Group B, 202317 +/- 24325 cpm/well, P less than 0.05). However, MC incubated with a lower concentration of morphine (10(-6) M) enhanced DNA synthesis when exposed intermittently only (control, 107593 +/- 42284 cpm/well vs. Group B, 219164 +/- 15552 cpm/well, P less than 0.05). This growth stimulating effect of morphine (10(-6) M and 10(-5) M) was also observed at earlier time points, that is, one- and one-and-a-half-week old cultures. However, in one-week-old cultures. morphine in a higher concentration (10(-4) M) showed a suppressive effect (P less than 0.05) on MC proliferation (morphine, 3620 +/- 220 cpm/well vs. control, 4668 +/- 410 cpm/well). This effect not only subsided by one and a half weeks but morphine (10(-4) M) treated cells enhanced MC proliferation. An opioid antagonist, naloxone attenuated the effect of morphine in one and half week old cultures. Morphine at 10(-6) M to 10(-4) M concentrations enhanced incorporation of [3H]proline in the extracellular proline pool (a component of mesangial matrix) when compared to control (control, 309661 +/- 3992 vs. morphine 10(-4) M, 363104 +/- 10539 cpm/well, P less than 0.05 or morphine 10(-5) M, 397954 +/- 31008 cpm/well, P less than 0.001 or morphine 10(-6) M, 384630 +/- 26369 cpm/well, P less than 0.01). In addition, MC incubated with morphine (10(-6) M and 10(-4) M) also enhanced (P less than 0.001) synthesis of laminin.(ABSTRACT TRUNCATED AT 250 WORDS)

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Hyperkalemia is a commonly encountered problem in dialysis patients with end-stage renal disease. In this study we evaluated the effect of mineralocorticoid therapy (MCT; fludrocortisone 0.1-0.3 mg per os daily) on serum potassium of hyperkalemic end-stage renal disease patients. Consecutive monthly clinical and biochemical profiles 3-6 months before and after MCT were compared. Twenty-one patients with a mean age ( ± SE) of 54 ± 4 years (11 male and 10 female) were studied. Two patients were dropped from this study because they required a change in prescription of dialysis after starting MCT. Mean serum potassium levels significantly fell (p < 0.001) during the post-MCT period (4.9 ± 0.1 mEq/1) compared with potassium levels during the pre-MCT (5.6 ± 0.1 mEq/1) period. All patients except 1 showed a reduction in serum potassium levels after MCT. Pre- and post-MCT values were not different for body weight, mean blood pressure, blood urea nitrogen, serum glutamic-oxaloacetic transaminase, lactate dehydrogenase, sodium, chloride, bicarbonate, creatinine and albumin. Since the majority of the patients were anuric (n = 15), a decrease in serum potassium values in the post-MCT period was not due to loss of potassium in the urine. MCT appears to decrease serum potassium values in patients with end-stage renal disease by extrarenal mechanisms. We conclude that MCT can be used safely to lower serum potassium in patients with end-stage renal disease.

To evaluate the determinants of rhabdomyolysis in the diabetic state, we compared biochemical and clinical features of diabetic patients with (group 1, 41 patients) and without (group 2, 36 patients) rhabdomyolysis. There was no difference in values for serum potassium, bicarbonate, phosphate and calcium between the two groups. Nineteen patients in group 2 and 21 patients in group 1 were hypokalemic. The mean serum sodium level was higher (p < 0.001) in group 1 patients (148.8 ± 2.1 mEq/l) than in group 2 patients (135.0 ± 1.1 mEq/1). Only 1 patient was hypernatremic in group 2, whereas 24 patients had hypernatremia in group 1. Linear regression of the creatine phosphokinase values versus serum sodium levels suggested a high correlation (p < 0.001). The mean blood glucose level was higher (p < 0.05) in group 1 patients (640.8 ± 80.3 mg/dl) when compared to group 2 patients (436.0 ± 56.7 mg/dl). There was a linear association (p < 0.05) between the levels of blood glucose and creatine phosphokinase values in the patients with rhabdomyolysis. The mean serum osmolality was 350.3 ± 8.2 mosm/kg in group 1 patients as compared to 304.9 ± 3.6 mosm/kg in group 2 patients (p < 0.001). There was also a significant correlation (p < 0.001) between the serum osmolality levels and the serum creatine phosphokinase values in group 1 patients. We conclude that serum sodium, serum osmolality and blood glucose are the major determinants for the occurrence of rhabdomyolysis in the diabetic state.