The prevalence of hyperuricemia was investigated in 214 kidney allograft recipients, 81 were on azathioprine and steroids and 133 on cyclosprine (CyA) and low-dose steroids or on triple therapy. All had stable renal function, serum creatinine < 2.5 mg/dl, and a follow-up between 12 and 120 months. At the time of the study, blood and urine samples were obtained to perform tests of renal function. The renal handling of urate was evaluated by a combined pyrazinamide and probenecid test in 35 selected patients (12 normouricemic on azathioprine, 9 normouricemic on CyA and 14 hyperuricemic on CyA). The prevalence of hyperuricemia was higher in the group of patients on CyA (19.7 vs. 66.9%, p < 0.001), as well as the concentration of serum urate (6.1 ± 1.9vs.7.6 ± 1.7, p < 0.001), and serum creatinine (1.2 ± 0.3 vs. 1.4 ± 0.4, p < 0.001). In patients on CyA, multivariate analysis showed that the most important predictive variables of hyperuricemia were: serum creatinine, FE_urate, diuretic use and CyA blood levels (r = 0.73, p < 0.0001). Thirteen patients on CyA (9.9%) had at least one episode of gouty arthritis. Those patients were older than the hyperuricemic patients without gout (45.7 ± 6.7 vs. 37.1 ± 13.5 years, p < 0.01), had worse renal function (serum creatinine 1.9 ± 0.4 vs. 1.5 ± 0.4 mg/dl, p < 0.01), and higher prevalence of hypertension (100 vs. 63.1%, p < 0.05). The combined pyrazinamide-probenecid test showed a lower FE_urate during the maximal probenecid-induced uricosuria (p < 0.05) and a lower urate secretion (p < 0.05) in hyperuricemic patients on CyA than in normouricemic on azathioprine or normouricemic on CyA. There were no differences either in the presecretory reabsorption or in the postsecretory reabsorption. According to the previous results, 20 hyperuricemic patients (11 with gouty arthritis) were treated with benziodarone (50-100 mg/day). At 1 month, there was a decrease in the serum urate (10.1 ± 1.8 vs. 5.1 ± 1.4 mg/dl, p < 0.01), and a parallel increase in FE_urate (7.1 ± 2.4 vs. 25.4 ± 7.4%, p < 0.001), that persisted after 1 year of follow-up. The drug was well tolerated, and we did not observe side effects. The serum creatinine, CyA dose and CyA blood levels remained unchanged. In conclusion, hyperuricemia is a frequent complication in transplant patients on treatment with CyA. Our data suggest that the disorder could be due to an impairment of the tubular secretion of urate. Benziodarone is an alternative to allopurinol for the treatment of this complication, which does not have important side effects.

In order to ascertain whether there are abnormalities of nonenzymatic glycosylation in uremia, the levels of nonenzymatically glycosylated hemoglobin (GHb), and total plasmatic glycosylated proteins (PGP) were studied using the thiobarbituric acid (TBA) method, a procedure not interfered with by carbamylation. Total hemoglobin A₁ (HbA₁) and the A_1c fraction were also determined by ion exchange chromatographic methods. Sixty-six end-stage renal disease patients (29 nondiabetic and 8 diabetic uremic patients on conservative treatment, 29 non-diabetic hemodialysis patients) and 56 controls (32 nonuremic diabetic patients and 24 healthy controls) were studied. High levels of GHb and total PGP were found in the nondiabetic uremic group on conservative treatment with all the methods used, but the persistence of high chromatographically determined HbA₁ levels in hemodialysis patients contrasts with the results obtained with the other techniques, which showed lower values on hemodialysis. Nondiabetic uremic patients with abnormal oral glucose tolerance curves had significantly higher levels of TBA-determined GHb and PGP. Uremic diabetic patients had the highest glycosylation levels of all the studied groups. We conclude that there is an abnormal nonenzymatic glycosylation of proteins in uremia, independent of carbamylation reactions and partially corrected by hemodialysis.

The contributions of membrane biocompatibility, dialysate temperature and sodium concentration to hemodynamic stability during hemodialysis were studied in 8 patients with a high incidence of hemodialysis-induced symptomatic hypotension. Patients were treated during 8 different periods, randomly ordered in each case, resulting from the combination of the following: the membrane, either Cuprophan or Polyacrylonitrile; the dialysate temperature, 37 or 35 degrees C, and the sodium concentration, 133 or 139 mmol/l. The incidence of symptomatic hypotension was lower at 35 degrees C in the entire study with either membrane and either sodium concentration. It was also lower with a sodium concentration of 139 mmol/l with either temperature and either membrane. There was a lower incidence of symptomatic hypotension when using Polyacrylonitrile, but this difference was not significant. We conclude that changes in physicochemical parameters of dialysate lead to worth-while improvement of symptomatic hypotension in hemodialysis patients, but membrane biocompatibility seems to play a minor role.

A high prevalence of hypercalciuria has been reported in patients with essential hypertension. Nevertheless, the clinical and therapeutic implications of this finding have scarcely been studied. This study was designed to determine the prevalence of hypercalciuria in an unselected population with essential hypertension and to analyze the relationship between the urinary calcium and the clinical and therapeutic status of these patients. This article presents a prospective study of 112 patients with essential hypertension and 49 healthy normotensive control subjects. Urinary excretion rates of calcium, sodium, chloride, potassium, urinary calcium/creatinine index, the fractional excretion of sodium, potassium and uric acid, the creatinine clearance and serum values of creatinine, urea, uric acid, electrolytes, total proteins, parathormone (intact molecule), plasma renin activity, aldosterone, glucose, and insulin (fasting and after an oral glucose load) were performed in every patient and control subject. Untreated hypertensive patients had a higher prevalence of hypercalciuria (35% had a urinary calcium/creatinine ratio > 0.20 versus 20% of treated hypertensives and 2% of control subjects; P < 0.001). Patients on thiazide or beta-blocker monotherapy had lower urinary excretion rates of calcium and urate than patients on calcium-antagonist monotherapy or untreated patients. Urinary calcium, sodium, and urate correlated positively both in treated and untreated essential hypertension patients. Patients with the higher urinary calcium levels also had higher excretion rates of sodium and urate, higher creatinine clearance rates, and lower serum creatinine and serum uric acid levels. It was concluded that hypercalciuria is a frequent finding of untreated essential hypertension. The association of high urinary calcium levels with high urinary urate excretion rates in the same patient may predispose to development of lithiasis in patients with essential hypertension. Antihypertensive drugs have a variable effect on calciuria-uricosuria, which may constitute an additional criterion in the selection and individualization of therapy. Thiazides and beta-blockers can decrease calciuria and uricosuria and, therefore, the lithogenic risk in these patients.

Hyperuricaemia is a frequent side-effect of cyclosporin A (CyA) therapy in renal transplant patients, [1,[5][6][7]11], and gout arthritis is the cause of considerable morbidity among these patients [5,7,8,10,11]. However, neither the potential predisposing factors nor the mechanisms of hyperuricaemia have been clearly elucidated. It has been reported that hyperuricaemia in patients on Cy A is associated with a lowered glomerular filtration rate, or with areduced urate clearance [2,5,7,8,10], due to an increase in the net tubular urate reabsorption or to a decrease in secretion [2, 5]. These conclusions are mostly supported by measurements of the basal clearance rate and fractional excretion of urate, but more precise studies of renal handling of urate by the renal tubule have seldom been performed [2]. The purpose of our study was to investigate the prevalence of hyperuricaemia in our population of renal transplant patients, as well as the risk factors involved. Furthermore, we have evaluated the mechanism of hyperuricaemia by a combined pyrazinamide and probenecid test allowing a better evaluation of urate transport processes than pyrazinamide alone. Patients and methods~or the hyperuricemia prevalence study, 169 renal transplant-patients were selected, all of whom had stable graft function and serum creatinine lower than 2 mgldl. The group comprised 96 males and 73 females, with a mean age of 38 ± 12 years, 80 on azathioprine (Aza) and 89 on CyA. Patient records were reviewed and the following data collected at 12 months: serum and urine urea, creatinine ~nd urate, serum potassium and total C02 and the drugs taken at this time. Hyperuricaemia was considered to be present when serum