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We describe studies in whole kidney, cortical and medullary homogenates and, glomerular cells in culture to determine the relative levels of expression of alpha (Ya, Yc, Yk), mu (Yb1/Yb2), pi (Yf) glutathione S-transferases (GST) and CuZn superoxide dismutase (CuZn SOD) in different regions of the nephron. Immunoblotting and immunohistochemistry were used to demonstrate relatively weak expression of alpha, mu GST and, CuZn SOD in the glomerulus compared to that in particularly distal tubules. Whilst expression of Ya was found within glomerular cells, Yc, Yk and Yf were not detected. Immunofluorescence showed that Ya and Yb1/Yb2 but not Yf were expressed in cultured epithelial and mesangial cells studied between passages 1 and 3. While Ya was distributed in cytosol, Yb1/Yb2 was primarily located in nuclei.

Angiographic and histological studies of the intrarenal circulation have been undertaken in 20 patients following complicated pregnancies: 12 patients had had hypertension of pregnancy (group 1); 7 acute renal failure due to either ante- or post-partum haemorrhage and 1 patient post-partum renal failure (group 2). 3 months after delivery all patients had angiographic evidence of structural and functional abnormalities involving intrarenal blood vessels and cortical blood flow. The severity of the structural changes was related to the degree of microangiopathic haemolytic anaemia noted in the acute obstetric complication but not to the height of the blood pressure at this stage. Histological abnormalities of the cortical blood vessels were minimal. At the time of the renal angiogram and biopsy, 3 of the 12 group 1 patients were hypertensive and 3 had impaired renal function, compared with 5 and 1, respectively, in the 8 group 2 patients. Although during the follow-up period (mean 5 years) no further deterioration in renal function in either group has been observed, hypertension developed in 50% of the group 1 patients compared with only 1 of the patients in group 2. The relationship between the late onset of hypertension and the intrarenal vascular and haemodynamic abnormalities is discussed.

The effect of oestrone acetate (in total doses of 5 and 10 mg) on systemic and renal haemodynamics and the renin-angiotensin system has been studied in adult female rats. The administration of 10 mg of oestrogen resulted in a significant fall in renal blood flow associated with significant rises in both renal vascular resistance and mean arterial pressure. No changes were noted in cardiac output or total peripheral resistance at either dose. Whilst the higher dose of oestrogen induced a significant increase in plasma renin activity, no change was noted in animals receiving 5 mg of oestrogen. Both regimens caused significant reductions in plasma and intrarenal renin concentrations. Although renal blood flow correlated with plasma renin activity in animals with a normal renal blood flow, no such correlation was noted in animals with oestrogen-induced reductions in renal blood flow. The present study demonstrates that oestrogen-induced reductions in renal blood flow result from a rise in intrarenal vascular resistance which cannot be accounted for by simultaneous changes in either plasma renin activity or renal renin concentration.

The effect of oestrogen-containing compounds on platelet factor 3, platelet life span, renal platelet localization and the fibrinolytic activity of forearm venous blood has been studied in eleven women with the renal vascular abnormalities of the loin pain and haematuria syndrome. The results were compared with those obtained in twenty-nine healthy female volunteer subjects. 2. Platelet factor 3 (PF3) availability was found to be increased in patients with the loin pain and haematuria syndrome during normal menstrual cycles. Oestrogens produced an increase in PF3 availability in both patients and control subjects. 3. Platelet life span was shortened and the index of renal platelet localization increased when patients with the loin pain and haematuria syndrome received oestrogens. No change in platelet kinetics was found in the healthy control subjects receiving oestrogens. 4. The fibrinolytic activity of forearm venous blood, both at rest and after venous occlusion, was increased in the healthy control subjects in response to oestrogens. No such response was seen in the patients with the loin pain and haematuria syndrome. 5. It is suggested that the change in platelet function may be causally related to the intrarenal vascular abnormalities. 6. The possible role of oestrogens in causing these disturbances or unmasking pre-existing abnormalities of platelet function or fibrinolysis is discussed.

Nine patients who developed reversible hypertension and/or evidence of impaired renal function whilst taking an oestrogen-progestogen-containing compound have been investigated. Serial haematological and biochemical studies have been carried out on each patient in association with selective renal angiography and renal biopsies. Abnormalities of the peripheral renal vessels have been demonstrated in all patients and a close correlation between the histological and angiographic appearances noted. The presence of microthrombi involving glomerular capillaries or intrarenal arterioles was invariably accompanied by evidence of micro-angiopathic haemolytic anaemia along with stasis of contrast medium in the intra-renal vascular circulation. Although the three different groups of patients studied tended to show their own particular intra-renal angiographic patterns, the definitive diagnosis depended on the haematological and histoligical findings. In the majority of patients, withdrawal of the oestrogen-progestogen-containing compound resulted in clinical improvement.

Clinical features have been correlated with renal function, histology and selective renal angiography in 19 patients with recurrent painless haematuria, recurrent loin pain, or both haematuria and loin pain in whom urinary infection, calculi and anatomical abnormalities of the urinary tract had been excluded. No deterioration in renal function was observed in any patient over periods of up to nine years. Although all patients showed similar glomerular changes histologically, consisting of focal and segmental mesangial thickening and proliferation and periglomerular fibrosis, mild tubular damage was more common in those with loin pain. All patients with loin pain whether or not they had haematuria, had abnormal renal angiograms consisting of focal or generalized vascular lesions sometimes associated with cortical infarcts. The possible aetiological factors are discussed with particular reference to oestrogen-containing compounds.