Oral contraceptives, hypertension and nephrosclerosis (author's transl)

Five personal cases and many reports in the literature demonstrate the not rare development of hypertension after oral contraceptives or an increase of an existing hypertension. In addition, the drug may also cause vascular changes in the kidneys with development of benign or malignant nephrosclerosis, similar to the increased risk of thrombo-embolic complications of the venous-arterial system. It is, therefore, necessary to check the blood pressure of women on oral contraceptive and, if hypertension exists or develops, discontinue these drugs.     

Circadian hydroxyprolinuria in the early diagnosis of nephrosclerosis in patients with chronic pyelonephritis

The time course of daily urinary excretion of hydroxyproline (HOP) was followed up in patients with chronic pyelonephritis. Manifest hyperhydroxyprolinuria was observed in these patients at the earliest stages of nephrosclerosis, and it augmented with development of renal insufficiency. Measurements of HOP in the urine of patients with chronic pyelonephritis is proposed as an indicator reflecting the metabolic status of renal connective tissue at the early stages of nephrosclerosis. It can be used to assess the activity of the sclerotic process in the kidneys of patients with chronic pyelonephritis, predict the disease course and outcome, and, probably, to develop methods of adequate pathogenetic therapy with biochemical monitoring. The method is not invasive, sufficiently informative, and available for clinical diagnostic laboratories.     

Significance of daily hydroxyprolinuria in the early diagnosis of nephrosclerosis in patients with chronic pyelonephritis

Studies of daily excretion of hydroxyproline with the urine in patients with chronic pyelonephritis (CP) showed manifest hyper-hydroxyprolinuria at the early stages of the disease, which augmented with the development of renal insufficiency. Measurement of hydroxyproline in the urine of CP patients is proposed as a test reflecting the renal connective tissue metabolism at the early stages of the disease. It can be used for assessing the activity of the sclerotic process in the kidneys of CP patients, for predicting the disease course and outcome, and, probably, for developing methods of adequate pathogenetic therapy based on biochemical monitoring. The method is noninvasive, sufficiently informative, and available for clinical diagnostic laboratories.     

Hypertensive nephrosclerosis in the Dahl/Rapp rat. Initial sites of injury and effect of dietary L-arginine supplementation

BACKGROUND: The Dahl/Rapp strains of salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rat were developed to examine pathogenetic mechanisms that produce hypertension in response to an increase in dietary salt. We have shown that providing SS/Jr rats with L-arginine, the metabolic precursor of nitric oxide, acutely prevented salt-sensitive hypertension, suggesting that SS/Jr rats developed hypertension because of inadequate nitric oxide production while on a high-salt diet. EXPERIMENTAL DESIGN: Male 23-day SS/Jr and SR/Jr rats were placed on chow that contained 8% sodium chloride. One group of SS/Jr rats also received L-arginine, 1.25 g/liter, in their drinking water. These three groups were examined at weekly intervals for 4 weeks. RESULTS: SS/Jr rats rapidly developed hypertension when placed on the high-salt chow. After 2 weeks on this diet, inulin clearance dramatically decreased, and albumin excretion rate increased. By the fourth week of study, SS/Jr rats on the high-salt diet had died or were dying. Coincident with the progressive decline in inulin clearance, renal morphologic analysis confirmed development of myointimal thickening, fibrinoid necrosis, and glomerulosclerosis. In contrast, over the 4 weeks of study, SS/Jr rats supplemented with oral L-arginine did not develop hypertension and any of the associated renal complications seen in age-matched SS/Jr rats on the high-salt diet. L-Arginine also corrected hypertension in SS/Jr rats exposed to the high-salt chow for 2 weeks before the inception of L-arginine. L-Arginine administration after 3 weeks on this chow, however, failed to reverse hypertension and the depressed inulin clearance and morphologic renal damage. CONCLUSIONS: Along with previous work (Chen PY, Sanders PW, J Clin Invest 88:1559-67), these studies were consistent with the hypothesis that hypertension and hypertensive nephrosclerosis developed in SS/Jr rats because, while on a high-salt diet, substrate (L-arginine) became a rate-limiting factor in the synthesis of nitric oxide.