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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.

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.

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.

Twenty-two patients with crescentic anti-GBM nephritis or Goodpasture's syndrome with renal impairment were reviewed. All patients were treated with a combination of plasma exchange and immunosuppression. Sixteen patients (73 per cent) showed improvement in renal function (greater than 30 per cent reduction in serum creatinine level) apparently in response to treatment, and nine patients (41 per cent) made long-term recoveries in renal function. The most important features carrying a bad prognosis were total anuria, and/or a very high percentage of glomeruli showing crescents (greater than 85 per cent) in the initial renal biopsy. Some patients with other so-called 'bad' prognostic features, including severely impaired renal function at presentation, oliguria and the need to institute dialysis had unexpected marked improvement in renal function and/or recovered renal function in the long term provided treatment with plasma exchange was begun promptly and maintained for a sufficient period to allow resolution of the disease process. Renal biopsies at the beginning and later proved to be an extremely valuable guide for the progress and outcome of the disease.

Circulating platelet aggregate ratios (CPAR) and plasma beta-thromboglobulin (B-TG) concentrations were determined in 53 patients with chronic progressive glomerulonephritis [mesangiocapillary glomerulonephritis (15) and focal and segmental hyalinosis and sclerosis (38)] and compared with those from both normal subjects and patients with no evidence of renal disease. The mean B-TG concentration was higher in patient controls [32.6 +/- 6.2 ng/ml (SEM)] than in normal subjects [19.0 +/- 2.0 ng/ml (SEM)] but this did not reach significance (P0.100.05). Nephritic patients had markedly elevated levels [49.8 +/- 4.0 ng/ml (SEM)], but B-TG was significantly correlated with renal impairment. Elevated B-TG levels in patients with nephritis may thus reflect renal impairment or ill-health. The mean CPAR of the nephritic patients [0.75 +/- 0.02 (SEM)] was lower than that of both normal [0.86 +/- 0.03 (SEM), P0.001] and patient controls [0.87 +/- 0.02 (SEM), P0.001]. CPAR was not correlated with renal function or platelet concentration. Low CPAR in nephritic subjects provides further evidence for in-vivo activation of platelets in patients with glomerulonephritis.

The clinical courses of 33 pregnancies in 24 patients with biopsy proven membranous glomerulonephritis have been analyzed. Twenty-four percent (8) of pregnancies resulted in fetal loss, 43% (14) in premature delivery and 33% (11) in a live birth after 36 weeks gestation. Maternal renal function declined during pregnancy in 9% (3) of the pregnancies and in 46% (15) hypertension developed. In 55% (18) proteinuria increased significantly during pregnancy. In 30% (10) nephrotic range proteinuria was recorded in the first trimester. Presence of nephrotic range proteinuria during the first trimester correlated with both poor fetal and poor maternal outcome (p less than 0.0004 and p less than 0.0002, respectively). It is concluded that pregnancy in patients with membranous glomerulonephritis is associated with increased fetal loss and, in some instances, a worsening in maternal renal function. The literature on this topic is reviewed in relation to these findings.

Clinical data in 244 patients with IgA nephropathy and biopsy findings in 519 biopsies (107 patients had at least two biopsies) were analysed. Males predominated (73 per cent) and had more severe disease and a worse prognosis than females. The most frequent symptom was macroscopic haematuria, often with associated loin pain; however, this was typical only in young males. Hypertension was the major presenting feature in 23 per cent of patients. Urinary erythrocyte counts correlated with the presence of crescents on biopsy (p less than 0.0001). Serum IgA levels wer elevated in only 21 per cent, while IgM levels were raised in 43 per cent of patients. Two hundred and seventeen patients were followed for at least one year (mean 59.7 months, range 12-255 months). In 82 patients five-year follow-up and in 33 patients ten-year follow-up data were available. Five- and 10-year survival figures were 91.5 and 87.5 per cent respectively. Clinical resolution occurred in only 6 per cent of patients but in those who had biopsies following clinical resolution, diffuse mesangial cell proliferation and IgA deposits persisted in all. The rate of clinical deterioration correlated with proteinuria, hypertension, impaired renal function, crescents and sclerosed glomeruli on biopsy. Continuing high urinary erythrocyte counts were the strongest predictor of a progressive course.

Four elderly patients developed nephrotic syndrome while receiving sulindac. Sulindac treatment had commenced 4-12 months prior to presentation with the nephrotic syndrome. Two patients also developed oliguric renal failure. Renal biopsy in one showed minimal change nephropathy and in three cases membranous nephropathy. Interstitial nephritis was present on renal biopsy in all cases. The nephrotic syndrome and renal failure resolved in all cases after withdrawal of sulindac. Two patients received steroid therapy and improvement in renal function and disappearance of proteinuria seemed to be temporarily related to steroid therapy in both cases. Despite the fact that sulindac is less likely to cause renal failure due to inhibition of renal prostaglandin secretion this report shows that sulindac treatment can be associated with renal failure and the nephrotic syndrome.

Renal involvement is uncommon in the hydralazine induced systemic lupus erythematosus syndrome. Six women with hypertension are described who developed an immune complex glomerulonephritis after taking 50-300 mg hydralazine daily for 6 months to 7 years. Associated features were anemia (100%), hypocomplementemia (50%), a positive antinuclear antibody test (100%) and antibodies to double-stranded DNA (66%). All patients were slow acetylators and four had HLA-DR 4 genotype. Renal function deteriorated in all cases. Cessation of hydralazine combined with immunosuppressive therapy resulted in amelioration of the disease. It is likely that the patients had a hydralazine induced lupus glomerulonephritis, or alternatively had an unmasking of an inherent tendency to idiopathic lupus nephritis by hydralazine.

The effect of acebutolol (Sectral) was compared with that of placebo in 30 patients with mild to moderate hypertension who were receiving a thiazide diuretic. Ten patients did not complete the study. In the remaining 20 patients, acebutolol (mean dose, 910 +/- 408 mg/day) produced significantly greater reduction both in supine and in erect systolic and diastolic blood pressure over 16 weeks than placebo plus chlorothiazide P less than 0.005). Pulse rate also fell significantly. Four patients did not have a consistent reduction in blood pressure. Acebutolol was found to be an effective hypotensive agent with relatively few side effects.

One hundred and sixteen pregnancies in 70 women with a biopsy-proven diagnosis of IgA glomerulonephritis have been analysed. Thirty percent (35) of the fetuses died, 22% (26) were premature and 44% (52) were full term. Maternal renal function declined during pregnancy in 26% (30) and in 2% (2) this was irreversible post-partum. Hypertension developed in 52% (61) of the pregnancies and in 13% (15) this was irreversible. Increased proteinuria was recorded in 62% (74) of the pregnancies. Fetal loss in pregnancies taking place after biopsy diagnosis was lower (16%) than those in which biopsy was performed either during or following the pregnancy (36%).

It has recently been proposed that renal cortical interstitial fibrosis is causally related to progressive decreases in glomerular filtration rate in a variety of renal diseases including glomerulonephritis. One hundred and eighty-eight renal biopsies in 81 patients with mesangial IgA nephropathy were analyzed for the percentage of relative interstitial volume by a point-counting technique. These data were correlated with serum creatinine, endogenous creatinine, endogenous creatinine clearance, and from age-matched donors were used as controls for the interstitial volume measurement. There was a negative nonlinear correlation between percentage of interstitial volume measurement. There was a negative nonlinear correlation between percentage of interstitial volume and creatinine clearance (r = 0.601, p less than 0.001). These correlations were not explained by age. However, serial biopsies in 39 patients clearly demonstrated that the percentage of interstitial volume could be dissociated from creatinine clearance. The prognosis in individual patients for progression to chronic renal failure could not be predicted from the relative interstitial volume at initial biopsy. Patients with mesangial IgA nephropathy demonstrated higher interstitial volumes than age-matched cadaver donors (p less than 0.001). Although interstitial volume and creatinine clearance are inversely related, the ability to dissociate these two variables in serial biopsies draws into question the hypothesis that interstitial fibrosis is causally related to changes in creatinine clearance. Studies to validate this hypothesis should involve patients followed with serial biopsies and renal function studies. In mesangial IgA nephropathy, interstitial changes are most likely secondary to the activity of the glomerular process.

Thirty-one pregnancies and post partum clinical course of 21 women with a diagnosis of primary focal and segmental hyalinosis and sclerosis have been analyzed. Forty-five percent (14) of pregnancies resulted in fetal loss, 39% (12) in premature delivery and 16% (5) in a term infant. Of 17 fetuses for whom birthweight was recorded, 29% (5) were small for gestational age. Maternal renal function deteriorated in 49% (15) of pregnancies, in 13% (4) irreversibly. Three of these patients (15%) subsequently progressed to end-stage renal failure, and one to progressive chronic renal impairment, by the end of follow-up (median 4 years, range 1-25 years). In 74% (23) of pregnancies hypertension was recorded and this frequently developed early (61%) and was severe (45%). Nephrotic range proteinuria developed in 42% (13) of pregnancies. Increased proteinuria was recorded in 22 (17%) pregnancies. It is concluded that pregnancy in women with primary focal and segmental hyalinosis and sclerosis is associated with increased fetal loss and maternal complications.

Thirty patients have been treated with heparin during pregnancy or in the immediate postpartum period. Twenty had severe preclamptic toxemia. Five presented before 30 weeks and in addition had low estriol levels and high blood ureas. The chance of a successful pregnancy in such patients is very low indeed; however 3 of these 5 patients had living babies. Even in patients presenting after 30 weeks of gestation, if severe preeclampsia is accompanied by low estriol levels and high blood urea levels, the anticipated fetal survival is poor. However, all 5 patients in this group were treated with heparin and had living babies. In the small group of patients with glomerulonephritis, there was a suggestion that heparin treatment may have been of value. Biopsy studies suggested that heparin may help to prevent lesions in arteries and arterioles which have been noted to develop in association with preeclamptic toxemia. In four patients treated in the postpartum period, there was possible benefit in terms of renal function, intravascular coagulation, vessel lesions, and subsequent successful pregnancies.

Expression of C3 receptors (CR1 and CR3) on neutrophils (PMN) was measured in 26 patients with IgA nephropathy (IgA N), 17 normal persons, and 8 patients with non-IgA glomerulonephritis (non-IgA GN) by fluorescence activated cell sorting after labeling with monoclonal antibodies. Mean channel fluorescence for both CR1 and CR3 on PMN was significantly higher in IgA N patients than in either control group (p less than 0.01). (CR1 mean +/- SD 42.5 +/- 10.4 in IgA N, 31.7 +/- 11.5 in normal controls, 27.8 +/- 9.0 in non-IgA GN; CR3 94.0 +/- 16.5, 75.0 +/- 16.6 and 76.7 +/- 15.6, respectively.) No differences were found between the two control groups or between IgA N patients with normal and impaired renal function. These results imply that PMN are activated in IgA N patients. The expression of CR1 and CR3 of PMN may be upregulated by immune complexes (ICs), enhancing both phagocytosis of C3b- or iC3b-coated particles, and absorptive pinocytosis of soluble ICs containing C3b or iC3b. Erythrocyte CR1 and CR3 expression was measured by ELISA and found to be slightly but significantly lower in IgA N patients than in the other 2 groups (CR1 85.3 +/- 28.4 in IgA N, 113.1 +/- 28.8 in normal controls, 109.4 +/- 28.2 in non-IgA GN, p less than 0.02; CR3 80.9 +/- 20.0, 100.4 +/- 19.9, 101.2 +/- 24.9, respectively, p less than 0.05).

The concentration of cross-linked fibrin degradation products (XLFDP) in urine were determined by enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA) in patients with several types of glomerulonephritis with crescents (CrGN). In patients with "active" cellular crescents, increased levels of XLFDP correlated with the percentage of glomeruli containing crescents. Dysmorphic erythrocytes, suggestive of glomerular bleeding, were observed in all of the patients with CrGN, and the urinary red cell counts (URCC) also correlated with percentage of glomeruli containing crescents. The absence of correlation between urinary XLFDP and URCC or urinary protein suggested that lysis of fibrin within crescents may contribute to the urinary excretion of XLFDP in CrGN. The measurement of urinary XLFDP in CrGN is likely to be of value in assessing the activity of glomerular lesions but not renal function.

Loin pain may be a major presenting symptom in patients with glomerulonephritis. Most of these patients show an underlying focal and segmental proliferative glomeruloneyphritis and there may be associated deposits of IgA and Igg in the mesangium. In this group of patients, vascular lesions are often prominent in the absence of hypertension. Episodes of recurrent macroscopic hematuria also occur, but the pain cannot be attributed to colic due to blood clots in the ureter.

To determine the effects of long-term lithium therapy, we have studied the renal histology and the renal function of 47 patients with affective disorders who were either currently receiving or had previously received maintenance lithium therapy (lithium patients), and we have compared the results with those of 32 other psychiatric patients with similar affective illnesses who had never taken lithium (prelithium patients). The renal biopsy samples, analyzed by a point-counting technique for interstitial fibrosis, were not different in degree between the lithium and the prelithium patients. Interstitial fibrosis was also not different between prelithium patients and age-matched transplant donor kidney controls, but it was greater in lithium patients when compared with the donor kidney controls (P less than 0.01). The specific distal tubular lesion associated with lithium therapy was present in all the biopsy samples of the patients who were currently receiving lithium therapy. Marked distal nephron dysfunction, as measured by urinary concentrating ability (P less than 0.0001) and urinary acidification (P less than 0.0001), was evident in lithium patients compared with the prelithium patients. These defects were correlated with the duration of lithium therapy. Serum creatinine estimations (P less than 0.01), serum beta-2 microglobulins (P less than 0.01), and 51Cr-EDTA clearances (P less than 0.01) suggested some impairment of GFR in lithium patients compared with prelithium patients. These defects did not correlate with the duration of lithium therapy. From these studies we concluded that the marked distal nephron dysfunction induced by lithium might produce prerenal impairment of GFR because the renal function abnormalities have no structural basis when the degree of interstitial fibrosis of other psychiatric patients is used as a control. Prospective studies are needed to answer the controversial question of whether stable maintenance lithium therapy produces chronic nephrotoxicity.

Three hundred and ninety-five pregnancies undertaken by 238 women with primary glomerulonephritis between 1962 and 1987 were analysed to record fetal and maternal outcome and identify risk factors for a poor outcome. Of 398 fetuses, 26 per cent were lost (including therapeutic abortions), 24 per cent surviving infants were premature (less than or equal to 36 weeks gestation) and 51 per cent were term. Excluding therapeutic abortions, 20 per cent of fetuses were lost, 15 per cent after 20 weeks gestation. Fifteen per cent of 237 fetuses whose birth weight was recorded were small for gestational age: Deterioration in maternal renal function was seen in 15 per cent of pregnancies and in 5 per cent of women failed to resolve post partum. Only four women had impaired renal function recorded in the first-trimester and two of these were known to have renal impairment before pregnancy. Hypertension was recorded in 52 per cent of pregnancies, developed early (less than or equal to 32 weeks gestation) in 26 per cent and was severe in 18 per cent. Treated hypertension pre-dated 12 per cent of pregnancies and in 7 per cent (included in the overall incidence of hypertension) exacerbation occurred during pregnancy despite continued antihypertensive medication. Forty-four women (18 per cent) who developed de novo hypertension in pregnancy had permanent hypertension postpartum. Increased proteinuria was recorded in 59 per cent of pregnancies and was irreversible in 15 per cent of women. Comparison of pregnancies which occurred before or after renal biopsy revealed a significantly higher fetal loss rate after 20 weeks gestation in those pregnancies undertaken before the diagnosis of renal disease, and a significantly higher incidence of hypertension and increased proteinuria. Impaired renal function, early or severe hypertension or nephrotic range proteinuria was significantly associated with increased fetal loss, prematurity and fewer full-term infants. There was no significant difference in fetal outcome or maternal complications in pregnancy in patients with treated hypertension before pregnancy and those who were normotensive in the first-trimester. The highest incidence of fetal and maternal complications occurred in patients with primary focal and segmental hyalinosis and sclerosis and the lowest in non-IgA diffuse mesangial proliferative glomerulonephritis. The presence of severe vessel lesions on renal biopsy was associated with a significantly higher total fetal loss and fetal loss after 20 weeks gestation.

The clinical course of 135 patients with lupus nephritis was examined long-term as part of a prospective study. Biopsies were classified according to modified WHO criteria and showed 17 per cent of patients had mild mesangial lesions, 10 per cent focal lesions, 21 per cent mild diffuse proliferative lesions, 37 per cent severe diffuse proliferative lesions and 15 per cent membranous lesions. Overall patient survival of 83 and 65 per cent at five and 10 years respectively from onset of nephritis was similar to other recently published series. In contrast to the latter, the severe proliferative group had a significantly worse outcome than the other proliferative groups (p less than 0.01) and only patients in this group progressed to end-stage renal failure. Haematuria was more common (p less than 0.05) in the severe group and there was a striking correlation between histologic activity assessed semiquantitatively (Table 1) and urinary red cell count (p less than 0.001). There was no correlation between serum creatinine, proteinuria or chronic lesions with urinary red cell count. In contrast to a previous study there was no correlation between the presence of hyaline thrombi on initial biopsy and subsequent development of glomerular sclerosis. Although the value of renal biopsy has been questioned, we suggest that it remains a most important investigation in the management of lupus nephritis. Determination of urinary red cell count provides a most useful monitor of disease activity and response to treatment.

Nucleated nonsquamous cells in urine of patients with crescentic glomerulonephritis (CN), noncrescentic glomerulonephritis (NCN), acute tubular necrosis (ATN) and drug related acute interstitial nephritis (AIN) were identified using monoclonal antibodies and immunoperoxidase stain. Cell viability was determined by trypan blue permeability. CN was distinguishable from NCN by total cell numbers exceeding 30,000/ml (p less than 0.001) and counts of granulocytes exceeding 10,000/ml (p less than 0.05), monocytes exceeding 3,000/ml (p less than 0.001), T4 lymphocytes exceeding 1,500/ml (p less than 0.001), T8 lymphocytes exceeding 1,500/ml (p less than 0.001), glomerular epithelial cells exceeding 4,000/ml (p less than 0.001), proximal tubular cells exceeding 8,000/ml (p less than 0.001), loop of Henle cells exceeding 1,500/ml (p less than 0.01) and urothelial cells exceeding 1,500/ml (p less than 0.05). AIN was distinguishable from ATN by total cell numbers exceeding 75,000/ml (p less than 0.001) and counts of granulocytes exceeding 150,000/ml (p less than 0.001), monocytes exceeding 5000/ml (p less than 0.001), T4 lymphocytes exceeding 3,000/ml (p less than 0.01), T8 lymphocytes exceeding 2,500/ml (p less than 0.01) and cell viability exceeding 60% (p less than 0.05). Proximal tubular, loop of Henle, distal tubular/collecting duct and urothelial cells were present in high numbers in CN, ATN and AIN. CN can be distinguished from NCN, and ATN can be distinguished from AIN by identifying and quantifying the nucleated cells present in the urine.

The clinical course of 168 pregnancies in 91 women with non-IgA diffuse mesangial proliferative glomerulonephritis has been analyzed. Twenty percent (33) of pregnancies resulted in fetal loss, 18% (31) in premature delivery and 62% (105) in a term infant. Maternal renal function declined, reversibly, in 3% (5) of pregnancies and in 48% (80) hypertension developed. In 53% (89) a significant increase in proteinuria occurred in pregnancy. Fetal and maternal complications of pregnancy occurred more frequently in patients with pre-existing hypertension although differences failed to reach statistical significance (p greater than 0.01). The presence of severe vessel lesions on the diagnostic renal biopsy was associated with a significantly higher fetal loss and prematurity rate (p less than 0.0005 and p less than 0.005, respectively).

To study the effects of continous low doses of antibacterial agents after eradication of bacteriuria in patients with recurrent urinary tract infection, 31 patients with documented recurrent urinary tract infection were allocated alternately to treatment with either co-trimoxazole (400 mg of suphamethoxazole and 80 mg of trimethoprim each night) or methenamine hippurate (1 g each night). The majority of patients (79%) had underlying radiological abnormalities of the renal tract, but normal renal function (the mean serum creatinine level was 1.05 mg per 100 ml). During the study the incidence of bacteriuria and pyuria was significantly lower in the co-trimoxazole-treated group. Patients receiving co-trimoxazole also had fewer acute clinical episodes of urinary tract infection than patients receiving methenamine hippurate. There were no significant side effects from either drug. Two patients with frequent recurrences of infection developed renal calculi. No change in creatinine clearance or maximum urinary concentrating ability was observed over a follow-up period of four to 30 months (mean 10.4 months). Co-trimoxazole is an effective agent in the prophylaxis of urinary tract infection in this highly susceptible group of patients, and in the doses used was superior to methenamine hippurate.

155 patients were referred for treatment of irreversible renal failure between Jan. 1, 1970, and Oct. 31, 1974. 8 (5%) patients were not accepted for treatment. An integrated programme of dialysis and transplantation (based on finding a cadaver transplant for every patient) has achieved an actuarial survival-rate of 88% at 1 year and 79% at 4 years. Of those surviving at 4 years, 85% are maintained by a functioning transplant. Only 4/122 transplants have been from living related donors. It is suggested that these results demonstrate that cadaveric transplantation, closely integrated with dialysis, offers an acceptable chance of life and full rehabilitation while not demanding from the community an unacceptable percentage of health resources.

116 pregnancies undertaken by 70 women with IgA glomerulonephritis and their diagnostic renal biopsies have been reviewed. An IgA diffuse mesangial proliferative lesion with superimposed focal and segmental proliferative lesions (IgA FSP) on diagnostic renal biopsy was associated with a greater incidence of maternal complications than IgA diffuse mesangial proliferative glomerulonephritis with no superimposed lesions (IgA DMP) and IgA diffuse mesangial proliferative glomerulonephritis with superimposed focal and segmental hyalinosis and sclerosis (IgA FSHS) (p less than 0.025). Patients with severe vessel lesions had a significantly greater incidence of fetal loss than those with only mild to moderate lesions (p less than 0.025).

Diazoxide, clonidine and labetalol, administered intravenously in fixed doses, were used to treat 30 episodes of severe hypertension in 27 patients. Labetalol in a fixed dose of 100 mg proved ineffective treatment. Diazoxide 300 mg and clonidine 300 micrograms were comparable in effectiveness. Drowsiness was a common side effect with administration of clonidine (in six of 10 patients) and severe hypotension occurred in one patient who was given diazoxide.

Thirty-seven patients with biopsy proven mesangial IgA nephropathy were prospectively allocated to either two years of treatment with eicosapentanoic acid (EPA) 10 g per day or no treatment. At entry treated and untreated patients with renal dysfunction (Group A) or patients with normal serum creatinine less than 0.12 mmol/l (Group B) did not differ in serum creatinine, creatinine clearance, urinary protein excretion, or quantitative urinary red cell counts. Compliance with EPA therapy was excellent as assessed by plasma fatty acid profiles. At the end of the trial creatinine clearance in treated patients had gone from 80 +/- 16 to 57 +/- 17 ml/min (p less than 0.05) and in untreated patients from 76 +/- 18 to 55 +/- 14 (p less than 0.05). There were no beneficial effects in either Group A or Group B patients. The only two patients who had improvement in renal function were in the EPA treatment group. Although no side effects of treatment were noted, EPA does not alter the course of established mesangial IgA nephropathy.

The use of prazosin, a new antihypertensive agent, in combination with other conventional antihypertensive agents, in a hospital outpatient clinic setting, was studied in a mixed group of 104 hypertensive patients. Prazosin effectively lowered the lying and standing blood pressure in the majority of patients whose blood pressure was uncontrolled or poorly controlled before the introduction of prazosin. Blood pressure control was adequately maintained in patients who were given prazosin because of the occurrence of side effects of other antihypertensive medication. No significant change in renal function attributable to prazosin was found in patients with normal or impaired renal function.

The adult population of a small Victorian town was interviewed for current analgesic consumption and the replies were validated by urine testing. One thousand four hundred and fifty-six subjects were ranked by stated analgesic consumption, and the 50 highest consumers matched for age and sex with non-consumers. Early morning urine specimens were collected and no significant difference in osmolality or white cell excretion rates was found between the two groups. It was concluded that the absolute risk of renal impairment on chronic analgesic consumers is low, and that patients on therapeutic regimens, including analgesics, may be reassured that any risk is minimal.

The duration of action of a single dose of prazosin and hydrallazine on blood pressure and heart rate was studied in 16 hypertensive patients whose blood pressure was not adequately controlled by a combination of a thiazide diuretic and a beta-adrenergic blocking agent, and had required the addition of either prazosin or hydrallazine. Observations over an eight-hour period, after a single dose of either 3 mg of prazosin, or 75 mg of hydrallazine, in identical capsules, with cross-over study one week later, showed significant reductions in blood pressure within the first hour after oral administration of either agent. This reduction in blood pressure persisted for four to six hours after hydrallazine and six to seven hours after prazosin administration. Tachycardia was more pronounced and prolonged after hydrallazine administration and side effects were more common.