Bartter's syndrome--observations on the pathophysiology.

The pathophysiology of Bartter's syndrome affecting seven adults has been investigated. (1) Saralasin infusion caused a fall in blood pressure in all patients, suggesting that angiotensin was contributing to the maintenance of blood pressure. (2) Following a water load, urinary chloride concentrations and osmolality were both low. No positive evidence for a defect in chloride reabsorption in the ascending limb of the loop of Henle was obtained. (3) The effect of high and low dietary sodium on plasma sodium, potassium, chloride, magnesium, renin activity, aldosterone, 6-keto-PGF1a, thromboxane B2, urinary kallikrein, platelet function and erythrocyte membrane cation transport were studied. A variety of responses was observed. Sodium restriction increased (or sodium loading decreased), plasma renin activity, aldosterone, 6-keto-PGF1a, urinary kallikrein and the platelet aggregation abnormality in some, but not all, individuals. (4) Treatment with indomethacin was undertaken in all patients and studied in detail in one patient. There was weight gain, increase in plasma sodium and potassium, decrease in capillary pH, positive sodium and potassium balance, and decrease in plasma renin activity, 6-keto-PGF1a, thromboxane B2 and urinary kallikrein. Hypomagnesaemia and excessive urinary magnesium loss persisted unchanged. (5) A variety of abnormalities of erythrocyte membrane cation transport was found and these persisted during high- and low-sodium, and high-potassium intakes; and during treatment with indomethacin, despite correction of intracellular sodium and potassium concentrations. Bartter's syndrome is associated with an abnormality of erythrocyte membrane sodium and potassium transport. Many of the other metabolic abnormalities may be the consequence of potassium and sodium depletion.

Complement and glomerular disease - a natural history study.

Over a 5-year period we have performed sequential measurements of a range of complement components in 127 patients. Each had a well-characterised glomerular lesion and there was no evidence of an underlying connective tissue disorder. In 17 patients with varied histopathology, who did not have C3 nephritic factor, there was a persisting complement defect which was present during remission in the patients we were able to study. The finding of such defects is consistent with the thesis that primary complement system abnormalities predispose to the development of glomerular lesions. Interestingly, these abnormalities did not influence the prognosis of our patients. In 12 other cases without C3 nephritic factor, complement levels were below the normal range when the glomerular lesion was active but returned to it in remission; these were secondary changes. We showed by discriminant analysis that some circulating complement component levels, assessed in relation to each other and without reference to a statistically derived 'normal' range, discriminated between histological subgroups and had prognostic significance as well. These patterns could not be distinguished until the data were stored and analysed by computer.

Strong association between idiopathic membranous nephropathy and HLA-DRW3.

HLA A, B, and DR antigens were determined in a homogeneous group of patients with idiopathic membranous nephropathy. The frequency of HLA-DRW3 was significantly higher in the patients than in a control population. The frequencies of HLA B8 and B18, which are in linkage disequilibrium with DRW3, were also increased.

The arteriolar lesions of steroid hypertension in rats.

1. The arteriolar lesions of rats with deoxycorticosterone (DOCA)-salt hypertension have been studied by colloidal carbon injection and light- and electron-microscopy. 2. Colloidal carbon particles enter the media of arterioles to form focal deposits when hypertension develops. 3. The focal lesions are similar to those seen after angiotensin infusion or renal artery constriction. They are characterized by endothelial damage and plasma deposition in the media. 4. Heavy deposition of carbon in the glomeruli of DOCA-treated animals was found to be caused by increased mesangial uptake and not by hypertensive vascular damage. 5. Angiotensin II concentrations fell during the development of hypertension and vascular lesions. The renin-angiotensin system was not implicated in the development of vascular damage in this form of hypertension.