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Coexistent renal pathology with diabetic glomerulosclerosis was found in 38 of 136 (28%) consecutive renal biopsies performed primarily for proteinuria in individuals with diabetes mellitus. The histological lesions found were glomerulonephritis (14), focal tubulointerstitial disease (23), and amyloidosis (1). Significant microscopic haematuria was present in 66% of all patients and did not help to distinguish non-diabetic disease. The severity of diffuse diabetic glomerular disease was independently associated with duration of diabetes, raised plasma creatinine, the presence of hypertension, clinical retinopathy and neuropathy, but not with type of diabetes, degree of proteinuria or glycosylated haemoglobin at the time of biopsy. Diffuse interstitial fibrosis was related to the severity of glomerular disease and, if severe, also with a significantly (p less than 0.01) higher plasma creatinine. Coexisting renal disease was found to be associated with a significantly higher plasma creatinine (p less than 0.01) independent of the severity of diabetic glomerulopathy. Coexistent pathology is a not uncommon finding in renal biopsies from diabetic patients with proteinuria. These lesions and their underlying causes may not only influence the renal function and natural history of renal disease in diabetic individuals, but may also determine the response of proteinuria to therapy.

Mesangial immunoglobulin A glomerulonephritis does not progress unless microscopic hematuria presents at levels over 100,000/mL, proteinuria presents at levels over 0.5 g in 24 hours, or hypertension is inadequately controlled. Hypertension, microscopic hematuria, and proteinuria all can be controlled; the evidence for control of these three risk factors is reviewed. The evidence for prevention of progression in mesangial immunoglobulin A glomerulonephritis is also reviewed.

The present study examines the effects of dietary potassium (K) on hypertensive glomerular and vascular lesions in deoxycorticosterone acetate and salt induced (DOCA-salt) and two kidney one clip (2K1C) hypertensive as well as normotensive control rats. Animals received a regular (0.28% K), high (1.1% K) or low (0.07% K) potassium diet for 6 weeks. In control rats, low K diet significantly increased systolic blood pressure (SBP) (p < 0.05). In DOCA-salt rats, high K diet did not modify SBP or glomerular and vascular lesions while low K diet significantly increased premature death in these rats. In 2K1C rats, dietary K did not alter the blood pressure, but percentage media area (% media) of intramyocardial arteries, percentage of glomerular lesions, and renal arterial and arteriolar lesion scores were lower in high K diet rats than regular and low K diet rats (p < 0.05). This study is the first demonstration that high K diet can protect against vascular and glomerular lesions in a non salt-loaded hypertensive model. The beneficial effects of dietary K on vascular lesions are at least in part independent of changes in blood pressure, and may be renin related.

To determine the optimal method of measuring uterine artery waveforms with Doppler ultrasound when screening healthy nulliparas for subsequent development of preeclampsia and fetal growth retardation (FGR).Color Doppler ultrasound was used to obtain uterine artery waveforms at 19-24 weeks' gestation in 458 nulliparas. In each uterine artery, the resistance index (RI), the ratio between peak systolic (A) and early diastolic (C) blood flow velocities (AC ratio) (a measure of the early notch in the uterine artery waveform), and placental position were recorded. The predictive values of these uterine artery Doppler measurements were evaluated for pregnancy complications. The major end points were preeclampsia and small for gestational age (SGA) infants.The best screening test for preeclampsia and SGA infants was the placental-side uterine artery RI or AC ratio above the 90th percentile for gestational age when the placenta was located on the left or right, and the highest RI or AC ratio when the placenta was midline. This method identified 51% of women with subsequent preeclampsia or SGA infants and had a positive predictive value of 29%. The test detected women with severe disease requiring delivery before 37 weeks with a sensitivity of 83% and specificity of 88%. However, the results were similar if the placental-side uterine artery RI was above an arbitrary cutoff of 0.56 or the AC ratio was above 2.05. A normal test predicted an uncomplicated pregnancy.Although abnormal uterine artery Doppler is associated with an increased risk of preeclampsia and FGR, the positive predictive values do not support its introduction as a routine screening test in nulliparous women.

Three hundred and forty-five pregnancies in 137 women with reflux nephropathy have been studied. All pregnancies took place after 1971. Overall foetal loss was 48 (14%) of which only 6 (2%) were therapeutic abortions. Maternal complications (urine infection, hypertension, proteinuria, oedema, deterioration in renal function, hematuria or renal stones) occurred alone or in combination in 39% of pregnancies. Fifty-two pregnancies took place in women with plasma creatinine (P.Cr0.11 mmol/l) prior to conception. Foetal loss after 12 weeks gestation (excluding therapeutic abortions) was 18% compared with 8% in the 104 pregnancies where maternal P.Cr was known to beor = o.11 per/l at conception (p0.05). Maternal complications were also more common in the impaired renal function group (p0.001). Comparison of pregnancies in women with unilateral versus bilateral renal scarring revealed no significant difference in foetal loss but an increased incidence of over 50% maternal complications in the bilateral renal scar group (p0.01). The incidence of pre-eclampsia was higher in women with bilateral renal scars, 50 (24%) than in women with unilateral scars 8 (7%) (p0.001). Persistent vesicoureteric reflux was not associated with increased foetal loss or maternal risk. Impaired renal function prior to conception is associated with increased foetal and maternal complications in pregnancy. Bilateral renal scarring is associated with increased maternal complications during pregnancy.

From our perspective, Priscilla Kincaid-Smith's major achievement in the field of hypertension relates to the pathogenesis of vascular lesions. Our own studies of the hypertension of renal parenchymal disease have suggested a role for impairment of the cortisol-cortisone shuttle and decreased activity of the enzyme complex 11-beta-hydroxy-steroid dehydrogenase. We have defined the renal functional consequences of steroid-induced hypertension and shown that the rise in blood pressure produced by steroids with predominant glucocorticoid activity is not dependent on volume shifts or sodium status, although the magnitude of the rise is modulated by dietary sodium content. We have shown that normal pregnant women adapt readily to extremes of sodium intake while women with pre-eclampsia retain sodium, and have shown enhanced capillary permeability. Recent studies have defined an abnormal aldosterone:renin ratio, dopaminergic inhibition of aldosterone, elevations of plasma atrial natriuretic peptide and reduced urinary prostacyclin:thromboxane ratios in women with pre-eclampsia.

Antibodies directed against endothelial cells (AECA) have been described in IgA nephropathy. We have previously measured AECA of the IgA subclass (AECA-IgA) in the sera of patients with glomerulonephritis by an ELISA method, and have shown that patients with IgA nephritis (IgA N) and lupus nephritis (LN) had significantly greater AECA-IgA activity compared with normal controls [1]. In the current study, on Western blotting of the EC membrane components, 6 of 18 (33%) IgA N sera positive for AECA-IgA bound to molecules of 135 and 116 kDa and 10 of 18 (56%) to a molecule of 205 kDa. These EC membrane components recognized by AECA-IgA may be of importance in the pathogenesis of IgA nephropathy.

Antibodies directed against endothelial cells (AECA) have been described in IgA nephropathy. We have previously measured AECA of the IgA subclass (AECA-IgA) in the sera of patients with glomerulonephritis by an ELISA method, and have shown that patients with IgA nephritis (IgA N) and lupus nephritis (LN) had significantly greater AECA-IgA activity compared with normal controls [1]. In the current study, on Western blotting of the EC membrane components, 6 of 18 (33%) IgA N sera positive for AECA-IgA bound to molecules of 135 and 116 kDa and 10 of 18 (56%) to a molecule of 205 kDa. These EC membrane components recognized by AECA-IgA may be of importance in the pathogenesis of IgA nephropathy.

The clinical and pathological data were compared between 88 Chinese and 88 Australian patients with IgA nephropathy, whose age, sex and course of disease identified by renal biopsy were matched. Statistical differences showed: More Chinese patients had edema and loin pain, while more Australian patients had hypertension, glomerular sclerosis and arterial and/or arteriolar abnormalities; impairment of renal function correlated with crescent body formation and loin pain with severe hematuria were only found in Chinese patients, While correlations between severe hematuria and histological changes, hypertension and glomerular sclerosis, impaired renal function and glomerular sclerosis were only seen in Australian patients. Differences between the two groups in symptoms, histological changes and clinico-pathological correlations suggest that IgA nephropathy is a heterogeneous disease, it may result from more than one factor.

Ureaplasma urealyticum has previously been shown to be capable of persisting in the rat kidney for up to 6 months following a single reflux challenge. We examined kidney tissue from infected animals for evidence of renal damage by using standard cytochemical and immunoenzyme methods. We also monitored changes in renal function during a 6-month study period with standard biochemical assays of plasma and urine. Histologic examination showed tubular atrophy, interstitial fibrosis, and a mononuclear infiltrate in proportion to ureaplasma counts from renal tissue. The most severe damage was accompanied by hyaline cast formation within tubules which gave rise to the typical thyroidlike appearance of chronic pyelonephritis involving conventional urinary pathogens. Macroscopic renal scarring occurred in some animals. Although damage to the renal medulla was moderate to severe, only minor changes were seen in the cortex, and glomeruli were invariably spared. Biochemical tests of renal function showed similar changes in infected and uninfected animals during the study period. Interstitial inflammation was characterized by a mononuclear cell infiltrate in which polymorphonuclear leukocytes were not conspicuous. It is evident that U. urealyticum is capable of producing chronic pyelonephritis in the rat after a single reflux challenge. The results of this study have obvious implications for the pathogenicity of these bacteria in human pyelonephritis.

Of 52 patients with mesangial IgA nephropathy, 25 were allocated to treatment with cyclophosphamide (6 months), and dipyridamole and warfarin (2 years) and 27 to no treatment in a randomized prospective 2-year study. At entry, the treated and untreated groups of patients did not differ in mean serum creatinines, urinary protein excretions, quantitative urinary erythrocyte counts or blood pressure readings. At the end of the trial mean (+/- SEM) serum creatinine values had gone from 0.12 +/- 0.01 to 0.13 +/- 0.01 mmol/l (p less than 0.05) in untreated patients and from 0.10 +/- 0.01 to 0.12 +/- 0.01 mmol/l (p less than 0.05) in treated patients. Mean (+/- SEM) log values of urinary erythrocyte (rbc) counts had not changed significantly from 5.47 +/- 0.09 to 5.21 +/- 0.14 log rbc/ml in untreated patients, from 5.45 +/- 0.11 to 5.49 +/- 0.19 log rbc/ml in treated patients. However, in treated patients, mean (+/- SEM) urinary protein excretions decreased from 1.67 +/- 0.35 to 1.15 +/- 0.31 g/24 h (p less than 0.01) whereas in untreated patients urinary protein was unchanged between initial values of 1.76 +/- 0.34 and follow-up at 1.89 +/- 0.45 g/24 h. No significant changes in blood pressure occurred in either group. This study supports the observation that treatment of IgA nephropathy with cyclophosphamide, dipyridamole and warfarin is associated with a reduction of urinary protein excretion but a significant effect on preservation of renal function, at least as determined by serum creatinine values, could not be confirmed over this two-year study.

The chronic nephrotoxicity associated with excessive use of over-the-counter analgesic mixtures and compounds was recognized some 25 years before the documentation of the acute syndromes of renal failure and the nephrotic syndrome attributed to pharmacological doses of non-steroidal anti-inflammatory drugs (NSAIDs). Spuhler and Zollinger’ description1 in 1953 of chronic interstitial nephritis in patients taking excessive amounts of phenacetin-containing mixtures was the first documentation of what has become known as analgesic nephropathy. Papers describing the acute nephrotoxicity of NSAIDs first appeared in the late 1970s although they have increased considerably in number over the past 10 years.