Detection of kidney reactive antibodies at crossmatch in renal transplant recipients.

We have investigated retrospectively sera from 70 renal allograft recipients for the presence of antibodies binding to a preanastomosis biopsy of the donor kidney by an indirect immunoperoxidase technique. All recipients had a negative T cell lymphocytotoxic crossmatch. A positive immunoperoxidase crossmatch for kidney-reactive antibodies was seen in 13/70 (18.6%) recipients--6 reacting with endothelium, 4 with epithelium, and 3 with both cell types. Neither the presence of these antibodies nor their pattern of staining correlated with recipient graft outcome. Following transplantation endothelial reactive antibodies developed in 15/43 (35%) patients, whereas tubular epithelial antibodies occurred in 5/43 (12%). The antibodies were persistent and accompanied graft failure in 10/14 (71%) patients, while transient antibodies were only associated with graft failure in 2/12 (17%) recipients. Development of lymphocytotoxic antibodies did not correlate with the presence of renal reactive antibodies or eventual graft outcome. Smooth muscle and antinuclear antibodies in recipient sera prior to transplantation were associated with improved graft survival. Eluates of 8/14 rejected grafts confirmed the presence of renal reactive antibodies, with patterns of staining similar to those observed in recipient sera. Antibodies in 7/8 recipients were shown by absorption studies to have HLA class I and/or II specificity, the remaining recipient having proximal tubular brush border antibodies.

Clinical features and outcome of patients with thin and ultrathin glomerular membranes.

There is considerable disagreement regarding the natural history of renal disease associated with thin glomerular basement membranes (TGBM). We followed 43 patients (19 male), mean age 41.6 years (range 19-73) for a mean of 88 months (48-140). TGBM was recognized in adults when glomerular basement membrane thickness, measured from multiple sites in electronmicrographs of renal biopsy tissue as the harmonic mean, was < 320 nm. At presentation, 95% had microscopic haematuria, 12% macroscopic haematuria, 14% loin pain, 28% proteinuria, and 14% hypertension. There was no difference in GBM width between the sexes (male 258 nm vs. female 251 nm) but there was a significant negative correlation between age and GBM width (r = -0.53, p < 0.001), with older patients having the thinnest membranes. Twenty six patients had ultrathin GBM (< 270 nm), of whom 54% had 3+ haematuria vs. 12% of the group with BM > 270 nm (p < 0.01). In the ultrathin group, 71% had loss of anionic charge from the GBM, vs. 17% in those with membranes which were thin but > 270 nm (p < 0.05). Proteinuria occurred more frequently in those with GBM > 270 nm, 65% vs. 8% in the ultrathin group (p < 0.01). Thin GBM were associated with a benign prognosis, as after a mean follow-up of 85 months (48-140), there was no significant change in either serum creatinine or mean arterial blood pressure. Patients with ultrathin GBM had greater loss of GBM anionic charge, which might result in both an alteration of flow characteristics within the glomerular capillaries and also increased fragility of the glomerular basement membrane with likelihood of rupture and resultant macroscopic haematuria.

Do mesangial immune complex deposits affect the renal prognosis in membranous glomerulonephritis?

Patients with rheumatoid arthritis who develop membranous glomerulonephritis associated with gold or penicillamine therapy have been shown to get better when the drugs are discontinued, whereas up to 50% of patients with idiopathic membranous glomerulonephritis develop renal failure. A feature of the lesion in rheumatoid disease is the presence of mesangial immune complex deposits in addition to the basement membrane deposits of classical idiopathic membranous glomerulonephritis. To determine whether the presence of mesangial immune complexes indicates a different renal outcome in membranous glomerulonephritis we studied 3 groups: group A 10 patients with rheumatoid arthritis and drug induced membranous glomerulonephritis with mesangial immune complex deposits, group B 14 patients with idiopathic membranous glomerulonephritis with additional mesangial immune complex deposits and group C 25 patients having classic idiopathic membranous glomerulonephritis with deposits solely in the glomerular basement membrane. After median follow up of 72 months, nephrotic range proteinuria resolved in all cases in group A after drug withdrawal, 93% of group B, but only 60% of group C (groups A + B vs C, X2 = 7.8, p < 0.01). Serum creatinine remains less than 500 mumol/l in all patients in group A, 93% of group B, but only 64% of group C (groups A + B vs C, X2 = 7.6, p < 0.01). Mesangial immune complex deposits were predominantly of the IgM isotype in both the rheumatoid and idiopathic membranous group. The presence of mesangial immune complex deposits suggests either a different pathogenesis or host responsiveness to that found in classic idiopathic membranous glomerulonephritis, and predicts a more favourable renal outcome.

Presence of immunoreactive tissue kallikrein in human polymorphonuclear (PMN) leucocytes.

The presence of tissue kallikrein in polymorphonuclear (PMN) leucocytes from normal human blood and from patients with rheumatoid arthritis and pyelonephritis was investigated. Immunoreactive tissue kallikrein was specifically detected in neutrophil leucocytes. PMN leucocytes displayed a granular staining. In the synovial membrane and kidney, the cells were aggregated into pockets as part of an inflammatory infiltrate. The presence of immunoreactive tissue kallikrein in human PMN leucocytes may provide a new insight into the importance of this enzyme in inflammation.

Fibrillary glomerulonephritis and pulmonary haemorrhage in a Woolly monkey (Lagothrix lagotricha).

Fibrillar deposits, distinct from amyloid deposits, were demonstrated by electron microscopy in the glomeruli and lung of an Amazonian Woolly monkey (Lagothrix lagotricha) which had died with extensive pulmonary haemorrhage. The renal lesions were typical of fibrillary glomerulonephritis in man, and IgG deposition was also demonstrated in the kidney. The association of renal and pulmonary lesions has been reported previously in man, but this is the first report of fibrillary glomerulonephritis, and a pulmonary-renal syndrome, in non-human animals.

The monocyte/macrophage population of the normal human kidney.

There is continuing controversy over the role of mononuclear phagocytes in glomerulonephritis. It is, therefore, important to know their distribution in normal subjects. Normal kidneys (34) were assessed using three cytoplasmic markers for macrophages employing a trypsin-immunoperoxidase (PAP) technique with antibodies to alpha-1-antitrypsin, muramidase (lysozyme) and a further oligoclonal antibody, serum 22, developed against highly purified preparations of blood monocytes. Serum 22 detected twice as many monocytes/macrophages as anti-muramidase and four times as many as anti-alpha-1-antitrypsin. Most cells that showed positive staining lay in glomerular and intertubular capillaries and were considered to be blood monocytes. There was wide variation in monocyte numbers throughout different glomeruli and up to 14 monocytes could be present in a glomerulus. Not more than 1 per cent lay within the mesangium. Macrophages were virtually never seen in the interstitium, except in areas of scarring. No macrophages were present in the tubules. Monocytes and macrophages are demonstrated in greater numbers within the kidney by antisera to muramidase than to alpha-1-antitrypsin.

Renal cell carcinoma: comparison of morphological and flow cytometric parameters of primary tumour and invasive tumour lying within the renal vein.

Histological assessment and DNA flow cytometry have been performed on 15 kidneys containing primary adenocarcinomas which had invaded the renal vein. Comparison of morphological variables showed that samples of the intravenous tumour were more commonly composed of granular cells (53 per cent) than were samples from the main tumour mass (16 per cent), and were also of higher nuclear grade. In 7 of 14 kidneys, DNA studies showed either a higher S-phase fraction (five cases) or DNA aneuploidy (two cases) in tumour cells lying within the renal vein. The mean S-phase fraction was also shown to increase in higher nuclear grades. Thus, both morphological and biological differences exist between invasive tumour cells lying within the renal vein and those in the main tumour. This is a useful model for the investigation of venous invasion and may give a better prediction of the metastatic potential of renal cell carcinoma.

Protein AA amyloidosis in Nigeria.

Eight cases of multi-system amyloid have been found in 4235 autopsies (0.2%) performed at University College Hospital, Ibadan, Nigeria between 1970 and 1979. Blocks and sections of seven cases showed the organ distribution associated with secondary amyloid, involving kidney, spleen and liver. Potassium permanganate oxidation prior to Congo Red staining showed that all seven cases contained protein AA amyloid. Five patients had tuberculosis but in two patients there was no recognized cause, idiopathic AA amyloid. Patients usually presented with nephrotic syndrome or renal failure and hypertension was absent. There appears to be a low incidence of amyloidosis in Africans, despite the occurrence of a large number of potential amyloidogenic stimuli, indicating the importance of individual host reactivity and failure of amyloid degradation in the causation of amyloidosis.

An immunohistological study of granulomatous prostatitis.

Granulomatous prostatitis may result from tuberculosis and fungal infection and has been described following prostatic surgery. In most cases, however, the aetiology is unknown, although it may be due to a reaction to extravasated or altered prostatic secretions. We have investigated cells (macrophages, lymphocytes), serum proteins (fibrinogen, alpha 1-antitrypsin) and prostatic epithelial products (prostatic-specific antigen and prostatic acid phosphatase) in diffuse granulomatous prostatitis (3 cases), focal periacinar prostatic granulomas (9) and focal prostatic infarcts (5), using an immunohistological technique. T-lymphocytes and macrophages are present in diffuse and focal granulomatous prostatitis, but few B-lymphocytes occur. Fibrinogen-related antigen is absent from granulomas, but a small amount is present within infarcts, whereas plentiful alpha 1-antitrypsin was detected both in granulomas and infarcts. Significant reduction in prostatic-specific antigen and acid phosphatase reactivity occurs in granulomatous prostatitis. This suggests that cytokines derived from activated macrophages and T-lymphocytes may be exerting a cell regulatory effect and altering cell secretions, as well as causing destruction of the prostatic epithelium.

Immunoperoxidase techniques in human renal biopsy.

Immunoperoxidase techniques can be easily performed on formalin fixed renal tissue after incubation in trypsin. The sensitivity of the PAP technique on fixed tissue is as good as immunofluorescence methods using frozen sections. The method provides permanent preparations with clear localization of deposited immunoproteins giving accurate classification of renal disease and assessment for treatment. The availability of this technique for retrospective and centralized studies is a major advantage. Infectious agents are rendered harmless and can be specifically identified. The development of the trypsin-immunoperoxidase technique is an important and exciting advance in renal immunopathology.

Zollinger-Ellison syndrome in a child: medical treatment with cimetidine.

A 12-year-old boy presented with intestinal obstruction associated with duodenal and oesophageal ulceration. At laparotomy he was found to have an islet cell tumour in the right lobe of the liver. Gastroenterostomy was performed. Raised levels of serum gastrin were detected. Treatment with cimetidine has produced satisfactory control of his symptoms for 16 months, and is an acceptable alternative to total gastrectomy in childhood.

C1q nephropathy: do C1q deposits have any prognostic significance in the nephrotic syndrome?

C1q deposits are usually found in association with other complement components and immunoglobulins in proliferative glomerulonephritis and may predominate in systemic lupus erythematosus (SLE). We report the clinical outcome of four patients who developed a nephrotic syndrome associated with C1q nephropathy unrelated to SLE. On presentation the mean urinary protein loss was 6.8 g/24 h (range 4-10), and renal function impaired, mean serum creatinine 201 mumol/l (150-400). Over a mean follow up period of 6.5 years (1.7-19), all four patients improved, three spontaneously and one treated with steroids and cyclosporin, to a current urinary protein loss of 0.3 g/24 h (less than 0.2-0.9) and serum creatinine 98 mumol/l (68-115). C1q nephropathy was confirmed in each biopsy by conventional immunohistology. C1q deposits were demonstrated within the glomerular basement membrane of three biopsies and the mesangium in two samples. One patient had been categorized on light- and electron-microscopy as having mesangiocapillary glomerulonephritis, one membranous glomerulonephritis, one proliferative glomerulonephritis with focal segmental glomerulosclerosis, and one diffuse proliferative glomerulonephritis with both subendothelial and mesangial dense deposits. In view of the expected progressive nature of the underlying renal histopathological appearance, the presence of predominant C1q deposits would appear to be associated with a better clinical outcome.