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Although ultrasound is commonly used for screening subjects at risk of polycystic kidney disease 1 (PKD1), there has been no evaluation of ultrasonographic diagnostic criteria. We used DNA linkage among subjects from 128 sibships within 18 PKD1 families as the basis for an assessment of ultrasound sensitivity. Positive and negative predictive values were calculated to allow assessment of different diagnostic cut-off points in previously undiagnosed cases. Currently used criteria (bilateral cysts with at least two in one kidney) provided good sensitivity (88.5% at age 15-29 years and 100% at 30 years and above) but performance could be improved by less stringent criteria in subjects aged 15-29 years and more stringent criteria in older family members, in whom simple renal cysts are frequent. The presence of at least two renal cysts (unilateral or bilateral) in individuals at risk and younger than 30 years may be regarded as sufficient to establish a diagnosis; among those aged 30-59 years, the presence of at least two cysts in each kidney may be required, and among those aged 60 years and above, at least four cysts in each kidney should be required.

It is now clear that mutations of at least two genetic loci can lead to autosomal dominant polycystic kidney disease (ADPKD). We have compared the clinical features of ADPKD caused by mutations at the PKD1 locus (linked to the alpha-globin complex on chromosome 16) with those of disease not linked to the locus (non-PKD1). We identified 18 families (285 affected members) with mutations at PKD1 and 5 families (49 affected individuals) in which involvement of this locus could be dismissed. Non-PKD1 patients lived longer than PKD1 patients (median survival 71.5 vs 56.0 years), had a lower risk of progressing to renal failure (odds ratio 0.35, 95% CI 0.13-0.92), were less likely to have hypertension (odds ratio adjusted for age and family of origin 0.29, 0.11-0.80), were diagnosed at an older age (median 69.1 vs 44.8 years), and had fewer renal cysts at the time of diagnosis. Although most of the PKD1 families were ascertained through clinics treating patients with renal impairment, no non-PKD1 family was identified through this source. Non-PKD1 ADPKD has a much milder phenotype than that linked to PKD1. Partly as a result of this difference in severity, the reported prevalence of this genotype is probably an underestimate.

In a study to determine the proportion of unrecognised cases and the prevalence of treatable complications of autosomal dominant polycystic kidney disease (ADPKD), 46 probands were identified through genetics and renal clinics in Melbourne, Australia. 321 offspring of the probands who were older than 15 years and had not been previously diagnosed as having ADPKD were identified. 68 (21%) had ultrasound evidence of polycystic kidney disease. Of this previously undiagnosed group, 25 (37%) had one or more treatable complications at the time of diagnosis. The complications included 20 cases of hypertension (diastolic blood pressure 95 mm Hg or above), 7 cases of impaired renal function (serum creatinine 0.12 mmol/l or above), and 4 cases of bacterial urinary tract infection. 8 people had several complications. ADPKD has an important treatable component which is not being treated in a substantial proportion of affected individuals, because the disease is not being diagnosed despite the presence of a positive family history.

Polymeric IgA (PIgA) and immune complex concentrations in IgA-related renal disease were measured in cross sectional and longitudinal studies to establish the relationship between these parameters and both mucosal infection and renal dysfunction. These studies were performed in 50 patients with IgA nephropathy (IgAN), 17 patients with Henoch Schönlein purpura nephritis (HSPN), 11 control patients with IgA negative, diffuse mesangial proliferative glomerulonephritis (DMPGN) and 50 healthy controls. Total PIgA (PIgAT) and PIgA subclass concentrations were measured using a secretory component binding enzyme immunoassay and isotype specific immune complex concentrations were measured using conglutinin (K) binding immunoassays. In cross sectional studies patients with IgAN were found to have increased concentrations of PIgAT, PIgA1, K-IgA1 and K-IgA2 compared to controls. In the longitudinal studies controls and patients had significant increases in PIgAT and PIgA1 concentrations during infection. However, in patients with IgAN, the increases were greater, persisted for longer, and PIgA2 concentrations were also increased. K-IgA1 and K-IgA2 concentrations increased significantly during episodes of infection in IgAN patients in contrast to controls. Patients with HSPN had results similar to those of IgAN patients. No significant correlation was found between PIgA or K-IgA concentrations, and either serum creatinine concentrations or the degree of hematuria. The results indicate that patients with IgA-related renal disease have abnormal regulation of PIgA and immune complexed IgA, and that these abnormalities are exaggerated during mucosal infection.

One hundred and eighty-six renal biopsy specimens from 79 adult patients with mesangial IgA nephropathy were examined and correlated with clinical data at the time of biopsy. Forty patients (group 1) with a history of macroscopic hematuria were compared with 39 patients (group 2) without such a history. Group 1 patients had a higher serum creatinine, 240 +/- 20 mumoles/liter vs. 140 +/- 10 mumoles/liter (P less than 0.01), lower creatinine clearance 69 +/- 36 ml/min vs. 87 +/- 30 ml/min (P less than 0.05), and a higher percentage of patients presenting with serum creatinine greater than 300 mumoles/liter, 22.5% vs. 5.1% (P less than 0.05). Fourteen biopsies were performed in 11 patients during an episode of macroscopic hematuria (group 1A). One hundred percent of these biopsy specimens showed crescents. Ninety-one percent of 11 biopsy specimens from ten patients (group 1B), taken 3 to 27 days following an episode but at a time when urinary red cells were less than 1,000,000/ml, also showed crescent formation. Of 14 biopsy specimens from 13 patients without macroscopic hematuria, but with greater than 1,000,000 red cells/ml in the urine just prior to biopsy (group 2A), 79% had crescents. In conclusion, macroscopic hematuria in adult patients with mesangial IgA nephropathy is associated with a high likelihood of crescents on renal biopsy specimens and worse renal function. Careful quantitative assessment of the urine for renal bleeding may help to better define the activity of disease in these patients.

New Zealand white rabbits, eight fed lithium (Li) (50 to 250 mmole LiCl/kg food) and seven controls (C) had sequential open renal biopsies at zero, one, three, six, and 12 months. A distinctive histological lesion, consisting of cytoplasmic vacuolation and accumulation of glycogen in cells lining distal convoluted tubules and collecting ducts, was present in Li (one, three, six, and 12 months), but was absent in Li prior to lithium (zero months) and in C (zero, one, three, six, and 12 months). Histological changes of chronic focal interstitial nephropathy namely, interstitial fibrosis, (quantitated by point counting), tubular atrophy and cast formation (quantitated by digitization), and glomerular sclerosis (determined as the percent of sclerosed glomeruli) showed significant differences between Li and C from as early as one month (interstitial fibrosis, P less than 0.02; tubular atrophy, P less than 0.05; casts, P less than 0.05), and up to 12 months (glomerular sclerosis, P less than 0.05). Distal tubular dilatation and microcyst formation, (quantitated by digitization) was also marked in Li compared with C from one month (P less than 0.05). The degree of distal tubular dilatation and other changes of interstitial nephropathy tended to progress with duration of lithium exposure. Macroscopically, Li kidneys (12 months) were pale, granular, and exhibited microcysts. Raised blood urea (P less than 0.02) and serum creatinine levels (P less than 0.05) were also late features (12 months) of lithium-induced nephropathy. The data support the view that lithium induces chronic renal lesions. The precise relationship between the distinctive distal tubular lesion, distal tubular dilatation and focal interstitial nephropathy remains speculative.

Ten rabbits with transparent ear chambers were grafted with small pieces of kidney. The resulting vessel anastomosis and restoration of renal blood flow allowed continuous microscopic observations of functioning renal tissue in vivo. When the grafts were well established, acute renal failure was induced in the rabbit by glycerol injection. All cases showed similar changes. Within minutes the brisk blood flow within the renal grafts became progressively more sluggish until complete stasis was established. The initial change was a blanching of intertubular and glomerular capillaries with progressive dilation and stasis of renal veins. Only after almost complete cessation of blood flow in most graft vessels, generally after a further 10 minutes, was any change in arteries or arterioles observed. The afferent arterioles and then larger arteries showed constriction followed by complete stasis. The ear chamber vessels (nonrenal) continued to flow normally. Blood flow was slowly re-established in the grafts and by the next day was normal in the surviving rabbits. These studies provided visual in vivo evidence that the mechanism of glycerol-induced acute renal failure is mediated by a reversible renal ischemia and that the factors responsible act particularly on renal vasculature. However, the mechanism whereby blood flow ceases is obscure and it cannot be attributed to arterial or arteriolar constriction.

Renal biopsies from ten patients presenting with macroscopic or heavy microscopic hematuria, shown to be glomerular in origin, were examined by light and electron microscopy. All biopsies showed erythrocytes within tubules by light microscopy and, in five cases, there were morphologic features of acute tubular necrosis. In four biopsies there was clear evidence by electron microscopy of uptake of erythrocytes by renal tubular epithelial cells, associated with some blunting of epithelial microvilli, vacuolar change and increased lysosomal content. Associated with erythrophagocytosis, the subsequent pathway of erythrocyte destruction within renal tubular epithelial cells closely resembled the hemolytic pathway described in macrophages of the reticuloendothelial system.

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.

During episodes of macroscopic hematuria, patients with IgA nephropathy commonly have polymorphonuclear neutrophils (PMNs) as well as fibrin and mononuclear cells in glomerular capillaries. We quantitated PMN and macrophage infiltration in glomeruli of 54 patients with IgA nephropathy in whom renal biopsies were obtained within 30 days of macroscopic hematuria. Control biopsies (N = 22) were from patients with IgA nephropathy and urinary erythrocyte counts below 50,000/ml. PMN monocyte/macrophages were quantitated using the monoclonal antibodies FMC10 and HAM56, respectively. In patients with heavy hematuria, 45.9 +/- 3.4% (mean +/- SE) of glomeruli were positive for PMNs (control 10.5 +/- 2.8%, P = 0.001) with a mean PMN count/glomerulus of 1.10 +/- 0.20 (control 0.13 +/- 0.03, P = less than 0.001). 65.6 +/- 9.7%. Of the glomeruli were positive for monocytes in the heavy hematuria group (control 40.0 +/- 8.4, P less than 0.05) with the mean monocyte count per glomerulus being 1.6 +/- 0.2 (control 0.6 +/- 0.1, P less than 0.01). We conclude that, in the acute phase of mesangial IgA nephropathy, PMN and monocytes are present and presumably participate in glomerular injury.