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Twenty-two living related renal transplant operations have been performed at Prince Henry's Hospital over the last seven years. Donors have been accepted for nephrectomy only after exhaustive examination of their health and serach for renal disease. The one and three year graft survival rates have been 85% and 64% respectively. Only two recipients have died, and recipient morbidity has been low. Donors have not suffered any serious complication from nephrectomy. It is concluded that living related renal transplantation has many advantages over cadaveric renal transplantation and is a relatively safe procedure for the donor, provided that rigid criteria are used in donor selection.

Our experience of 54 patients with end-stage renal failure, who were treated with intermittent peritoneal dialysis and compared with patients maintained by haemodialysis over the years 1972 to 1978, has been reviewed. All patients received peritoneal dialysis for more than six weeks. The total experience was 32.8 patient dialysis-years, 48% as home dialysis. Peritoneal dialysis was used as an interim procedure in 19 patients who were waiting for haemodialysis. However, in 35 patients (particularly in the very young and elderly, and in situations of poor social support), recurrent peritoneal dialysis was chosen as the definitive dialysis therapy. Dialysis was assessed as "adequate" in all, but two, patients. The major complication of peritoneal dialysis was peritonitis, although its over-all incidence of 1.31 episodes per patient dialysis-year was low. An attack of peritonitis occurred every nine months of patient exposure, though the incidence of bacterial peritonitis averaged only once every 26 months. Fifty per cent of patients never had an episode of peritonitis. Intermittent peritoneal dialysis was associated with greater morbidity and mortality than haemodialysis, perhaps due, in part, to the older age of the peritoneal dialysis group. Intermittent peritoneal dialysis is a valuable adjunct to haemodialysis and transplantation in the treatment of end-stage renal failure.

Tissue culture of isolated glomeruli from patients with glomerulonephritis. To study aspects of glomerular cell response in varying types of glomerulonephritis, we evaluated isolated glomeruli from 101 normal and diseased adult human renal biopsy specimens in tissue culture. Glomerular cell outgrowths from normal glomeruli consisted of large stellate cells (type I) and smaller fusiform cells (type II). A very occasional cell (type III), which had the features of a macrophage, was seen. The cellular outgrowth from isolated glomeruli reflected the numbers and types of cells present in the diseased glomeruli. Reduced numbers of cells were found in the outgrowth of sclerotic, hypocellular glomeruli. Glomeruli from biopsy specimens with altered morphologic appearances but no increase in cellularity (minimal change nephropathy, membranous nephropathy) produced the same growth pattern as from glomeruli isolated from normal kidneys. In mesangial proliferative nephritis, increased numbers of type II cells were detected in the outgrowth. Large numbers of macrophages were found in the glomerular outgrowth of patients with crescentic glomerulonephritis. Macrophages were absent when crescentic glomeruli were sclerosed, indicating the importance of macrophages in the acute hypercellular phase of crescent formation. Cultures tissulaires de glomerules isoles de malades atteints de glomerulonephrite. Afin d'evaluer les aspects de la reponse des cellules glomerulaires dans differents types de glomerulonephrites, des glomerules isoles de 101 biopsies d'adultes normaux ou malades ont ete etudies en culture de tissu. Les cellules glomerulaires cultivees a partir de glomerules normaux etaient de grandes cellules etoilees (type I) et des cellules fusiformes plus petites (type II). Plus rarement des cellules ayant les caracteres de macrophages (type III) ont ete observees. Pour les glomerules pathologiques, la culture cellulaire a reflete le nombre et le type des cellules initialement presentes. Le nombre de cellules etait diminue dans les cultures de glomerules sclerotiques. Les glomerules modifies mais sans hypercellularite (modifications minimes, extra-membraneuses) donnent issue aux memes cultures cellulaires que les glomerules normaux. Les glomerules de nephrite mesangiale proliferative donnent un nombre accru de cellules de type II. Les macrophages en grand nombre ne sont observes qu'a partir de glomerules obtenus chez des malades atteints de glomerulonephrites proliferatives. Les macrophages sont absents quand les glomerules avec des croissants sont scleroses, ce qui indique l'importance des macrophages dans la phase hypercellulaire aigue de la formation des croissants.

In about 30% of cases of glomerulonephritis. there is little or no evidence that humoral immunity has a role in the pathogenesis of the disease. There is now mounting evidence that cell-mediated immunity (CMI) plays a role in this group of glomerulonephritides, particularly in minimal lesion glomerulonephritis. Moreover, there is some evidence that CMl may also augment injury in glomerulonephritis, primarily induced by a humoral mechanism.

A modified sieving technique has been developed to isolate pure glomeruli from monkey, sheep, dog, rabbit and rat kidney. Glomeruli from all these species have been grown in tissue culture and the glomerular cell outgrowth studied by light microscopy and time-lapse cinemicroscopy. The pattern of growth was the same for all the species studied. In all species, three cell populations have been identified with the features of epithelial cells, mesangial cells and macrophages, although the latter population is only rarely observed. The morphology and culture characteristics of each cell type in all species were similar, including the relative numbers present and rates of division.

The in vitro response of human lymphocytes to phytohaemagglutinin was inhibited in a dose-related fashion by methylprednisolone added to the cell culture. The inhibition by steroid was 100-fold less than expected from published values of human lymphocyte receptor affinity. The dose response curve for inhibition was complex, frequently featuring a plateau region suggestive of a heterogeneous system, possibly caused by the presence of more than one subpopulation of cells. When lymphocytes were separated by unit velocity sedimentation, slow sedimenting lymphocytes were found to be highly steroid sensitive whereas rapidly sedimenting lymphocytes were steroid resistant. However, the addition of cultured macrophages rendered the steroid-sensitive fractions relatively steroid resistant. Similarly, unseparated peripheral blood lymphocytes at low concentrations were found to be highly steroid sensitive despite the addition of 2-mercaptoethanol. This sensitivity was lost by the addition of culture macrophages. Thus, macrophages play a vital role in the relative steroid resistance of human lymphocytes. No evidence was found that macrophages actually reduced steroid concentration in culture, and it is suggested that a cellular interaction is required to increase resistance to steroids.

Reproducible patterns of cell outgrowth have been observed from isolated normal adult, human glomeruli grown in tissue culture. Three morphologically distinct cell populations designated Types I, II, and III have been observed in culture from 15 normal human kidneys. Assessment of the morphology and behaviour of these cells has been made by phase contrast, time-lapse cinemicroscopic, transmission and scanning electron microscopic examination. The phagocytic capacity of these cells has been determined. The Type I cell appears in culture by migration from the capillary loops, its branched cytoplasm and ultrastructural features confirming its origin as a visceral epithelial cell. In keeping with the highly specialised nature of this cell, division was rare, movement was not observed, and differentiation was progressively lost in culture. The Type II cell was mobile and capable of active division. Ultrastructural features were those of mesangial cells. The Type III cell which was seen only rarely, had the features of a macrophage. Endothelial outgrowth was not observed.

A review of 28 cases of biopsy-proven lupus nephritis seen in Prince Henry's Hospital, Melbourne, in the last 12 years from 1971 to 1982 is reported. The mean follow-up period was 51 months. Renal histopathological changes were categorized according to the WHO classification of lupus nephritis. The majority of our patient population fell into two of the seven possible histological subgroups - Class IV (diffuse proliferative) disease (53.6%) and Class IIb (mesangial proliferative) disease (28.5%). Treatment with prednisolone alone or with a prednisolone/azathioprine combination resulted in an equal five-year survival (82%) and a similar overall preservation of renal function. The major single cause of death was opportunistic infection (60%). Despite overrepresentation of the more severe forms of lupus nephritis in a nephrology-unit population, there was a satisfactory outcome from therapy with either prednisolone alone or with a prenisolone /azathioprine combination. However, there were significant rates of morbidity and death associated with immunosuppressive therapy, primarily from opportunistic infection.

Glomerular cells have been grown in a reproducible manner from 5 normal human kidneys. A technique is described which combined mechanical disruption of renal cortex and microdissection, and provides large numbers of pure glomeruli within 30--45 mintues. Histological examination shows this technique produces intact glomeruli without cell disturbance. During tissue culture, glomeruli attach to the flask and the intrinsic cells migrate onto the flask and divide. Variations of culture conditions have shown that glomeruli are robust without fastidious culture requirements. Intact kidney tissue can be left at 4 degrees C for perios up to 24 hours prior to isolated of individual glomeruli without affecting subsequent cellular growth in culture. They grow in most commonly used media although the cells require 20% foetal calf serum for optimum growth. Their pH optimum is between 7.0 and 7.4 with temperature optimum of 37 degrees C. as glomeruli must attach prior to cell growth, minimum movement is critical to promote optimum growth. Under these optimum conditions a regular and predictable growth of cells of two distinct types, has been observed over 14 days; one of these types is probably epithelial.

Preservation of cadaveric renal allografts by ice storage and by machine perfusion after a preliminary flush with a hypertonic citrate solution has been compared in a prospective clinical trial between matched pairs of kidneys from the same cadaver donor. Over a two-year period, ice storage after flushing with the new solution gave results comparable with machine perfusion. Times of warm ischaemia and total times of storage were similar in ice-stored and machine-perfused kidneys and averaged about 16 hours. In each group of recipients, more than half of the kidneys had good early function and one-year survival times were also similar.

Alterations in blood and tissue concentrations of trace elements in the uremic patient have been investigated extensively over the last few years. These studies have largely been undertaken in patients with chronic renal failure (CRF) who were not on dialysis or with endstage renal failure (ESRF) on recurrent hemodialysis (HD). The most outstanding abnormality detected was the blood and tissue accumulation of aluminum [1–13]. High concentrations of aluminum have been linked with the development of dialysis dementia [2, 4, 5, 7, 8, 11, 13] and bone disease [1, 12, 13]. In patients with CRF who were not on dialysis increased tissue concentrations of zinc (bone and heart) [6], arsenic (bone and brain) [6], lead (bone, brain, and spleen) [6], and aluminum were described [6, 10, 11], although rubidium was found to be reduced [6]. In patients on hemodialysis normal or increased plasma and tissue concentrations of magnesium, aluminum, calcium, iron, strontium, molybdenum, cesium, and cadmium were detected although some patients exhibited reduced concentrations of selenium and rubidium [6, 14, 15]. However, various serum concentrations of zinc have been reported as low [16–19], normal [15], or high [14, 20–22]. Serum and tissue copper concentrations have been reported usually as normal or elevated [9, 15, 22, 23]. On the other hand, cases of acute zinc [24, 25], nickel [6], and copper [26] toxicity due to a leaching of these metals from dialysis plumbing have been described.

Defibrination with ancrod in nephrotoxic nephritis in rabbits. In rabbits with nephrotoxic nephritis, defibrination with ancrod provided protection when administered during the autologous phase, after extensive glomerular fibrin deposition had occurred and crescents and renal failure were developing. When further glomerular fibrin deposition was prevented by defibrination, deposited fibrin was rapidly removed, indicating that glomerular fibrin-clearing mechanisms are retained in crescentic nephritis. Defibrination had no effect on the extent of glomerular C3 deposition or on the amount of proteinuria.

In a series of 271 transplantations of renal allografts, performed over 10 years, the rates of graft survival, patient survival, and morbidity in the recipients of allografts from living related donors (47 allografts) have been compared with those in the recipients of cadaveric allografts (224 allografts). The one-year graft survival rates were 88% for allografts from living related donors (100%, if these were HLA-identical) and 55% for cadaveric allografts, while the patient survival rates were 97% and 87%, respectively, in the same period. Morbidity rates (expressed as the number of days spent in hospital) for recipients of allografts from living related donors were approximately 50% of those for recipients of cadaveric grafts. Complications in the living related donors were minimal, and acceptable. It is concluded that transplantation of allografts from living related donors has many advantages over transplantation of cadaveric kidneys, and is a valuable adjunct to a cadaveric renal transplantation programme. Greater use of living related kidney donors should be encouraged in Australia.

Normal human serum also contains the lymphotoxin found in minimal change nephropathy. We have studied serum–borne lymphotoxic activity in a large patient group with various forms of glomerulonephritis (GN). A potent inhibitor of lymphocyte blastogenesis was frequently demonstrable not only in patients with active minimal change nephropathy as has been previously described, but also in other forms of GN. The inhibitor was resistant to heating and prolonged storage but rendered ineffective by normal serum. We have been able to show for the first time, using gel filtration, that normal serum also contains the inhibitor. The inhibitor was shown to be highly avid for a receptor on leucocytes as judged by dose response experiments and by the ability of cell pellets to remove this activity. Gel filtration demonstrated a molecular weight in the range 60 to 160 kilodaltons. The combination of information regarding the biological properties of the inhibitor, its clinical occurrence and molecular weight suggests it to be distinct from any other well–described lymphotoxin. It's presence in normal serum in association with a self-regulatory factor and the known proclivity of minimal change nephropathy patients to infection, also indicate that the inhibitor may play an important role in immunoregulation.

Immunohistological studies indicate that T cells and macrophages are the major components of human kidney allograft infiltrates. Recent work has demonstrated a division of T lymphocytes into 2 subpopulations with distinct functions on the basis of their expression of the CD45R antigen (CD45R+ "naive" and CD45R- "memory" T cells). This study analyzes CD45R expression on circulating T cells and T cells infiltrating renal allografts in patients undergoing rejection and/or cyclosporine nephrotoxicity. The percentage of circulating T cells that expressed CD45R in patients with rejecting (63 +/- 4) or stable grafts (66 +/- 3) was not different from values obtained for normal donors (62 +/- 3). In contrast, the percentage of T cells expressing CD45R infiltrating rejecting grafts was 21 +/- 2 and was not affected by the stage of rejection; in patients with CsA toxicity the value was 22 +/- 6. The reduced proportion of T cells that expressed CD45R in the allograft may reflect a change in status from the naive state due to alloantigenic stimulation (which can be demonstrated in vitro) and/or a propensity of memory T cells to enter or be retained in an allograft.

As a means of studying mechanisms of response to injury in glomerulonephritis, glomeruli from normal sheep and rabbits and from sheep and rabbits with experimental crescentic glomerulonephritis have been isolated and grown in tissue culture. The cellular outgrowths from the normal and diseased glomeruli have been compared. The outgrowth of glomeruli from normal animals contained only two cell populations whose microscopic and ultrastructural appearances were of epithelial and mesangial cells. The same cells were also observed in the outgrowths of glomeruli from animals with crescenti nephritis but in addition a third population of cells was present in large numbers. These cells were identified as macrophages by their mobility, ultrastructure, phagocytic capacity, and presence of Fc receptors. Glomerular outgrowth from sheep with crescentic glomerulonephritis contained 170 +/- 20 (SEM) macrophages and outgrowths from rabbits with crescentic nephritis contained 64 +/- 6 (SEM) macrophages per glomerulus. We have previously observed large numbers of macrophages in the outgrowth of isolated glomeruli from humans with rapidly progressive crescentic glomerulonephritis. The predominance of the macrophage in cultures of glomeruli from both human and animal crescentic glomerulonephritis suggests that this is an important cell in the inflammatory reaction occurring in crescentic glomerulonephritis and may comprise a substantial proportion of the cells forming the crescent.

A histochemical enzyme profile has been used to determine the origin of the cells of glomerular crescents in rabbit and sheep models of rapidly progressive crescentic glomerulonephritis. Crescentic glomeruli were examined for beta-glucuronidase, esterase and acid phosphatase, the characteristic phagolysosomal enzymes of the monocyte-macrophage series and its transformed tissue counterpart, the epithelioid cell. More than 50% of the cells of the glomerular crescents of animals with experimental crescentic glomerulonephritis contained large amounts of all the enzymes, whereas the cells of normal glomeruli contained only trace amounts of acid phosphatase and esterase and no glucuronidase. These findings support the hypothesis that the major proportion of the cells of glomerular crescents are monocytes which have accumulated in Bowman's space rather than intrinsic glomerular cells which have proliferated.

Serial renal biopsies for glomerular culture, histochemical staining for beta-glucuronidase, electron microscopy (EM) and light microscopy, were used to study macrophage involvement in experimental chronic immune complex (IC) glomerulonephritis (GN) induced in rabbits by daily intravenous injections of bovine serum albumin (BSA). In the 26 animals studied, proliferative GN of variable severity was induced, with mild disease in 5 animals, moderate proliferation in 15 and crescentic GN in 6. Macrophages first appeared in glomerular culture outgrowths during the 2nd and 3rd weeks, coincident with the onset of proteinuria and rising serum creatinine concentration. Large numbers of macrophages (in excess of 20 per glomerulus) were seen by the 5th weeks and persisted to the 9th week. The number of macrophages in outgrowths was not significantly greater in animals with crescentic disease. EM demonstrated macrophages in capillary loops, and in glomeruli with crescents, macrophages could be seen in the urinary space. Histochemical staining for beta-glucuronidase also demonstrated macrophages in the glomerular tuft and in crescents when present. These results indicate that macrophages constitute a considerable proportion of the glomerular hypercellularity seen in chronic IC glomerulonephritis.

Graft and patient survival in 37 patients receiving a renal allograft while on CAPD have been compared to that in 102 hemodialysis patients transplanted in the same period. Graft and patient survival was similar in both groups. Blood transfusion prior to transplantation was associated with better graft survival in both CAPD and hemodialysis patients. Although peritonitis occurred in 6 of 30 patients in whom the peritoneal catheter was left in situ at transplantation, the peritonitis rapidly subsided with antibiotics without sequelae. Thus renal transplantation may be safely and effectively performed in patients on CAPD and the catheter left in situ and used if necessary for postoperative dialysis.

The incidence of cytomegalovirus (CMV) infection was established, using laboratory criteria, in 298 patients receiving 362 renal allografts (164/298 = 55%). The incidence of CMV infection did not differ between azathioprine/prednisolone-treated and cyclosporine-treated patients (55% vs. 57% NS). The use of antithymocyte globulin (ATG) increased the incidence of CMV infection (78% vs. 51%: P less than 0.01). Donor and recipient CMV status, known for 116 allografts, did not correlate with the incidence of CMV infection (recipient CMV-positive = 50%; recipient CMV-negative = 54%: NS). CMV infection was responsible for 8 patients' deaths (2.7% mortality). Thirty-three patients with acute transplant glomerulopathy were identified (11%). There was no correlation between acute transplant glomerulopathy and CMV infection. Glomerulopathy was associated with poor graft survival (22/33 patients with a graft survival of less than 6 months). Thus CMV infection, although a common complication of renal transplantation with significant morbidity and mortality, is not closely associated with acute transplant glomerulopathy. Further, the lack of correlation of donor-recipient CMV serologic status with graft outcome limits the usefulness of pretransplantation donor screening.

A 53-year-old female was admitted to hospital one hour after taking an overdose of 60 g of paracetamol and 960 mg of codeine. Two hours after ingestion of the drug, the plasma concentration of paracetamol was 3040 mumol/l. In view of the enormous, and potentially fatal, plasma concentration of the drug, charcoal haemoperfusion was undertaken as well as cysteamine therapy. Charcoal haemoperfusion and cysteamine therapy led to the rapid removal of the paracetamol from the body and consequently prevented the development of severe hepatic necrosis. It is suggested that charcoal haemoperfusion as well as cysteamine has a role in the management of severe overdosage with paracetamol. This is the first report on the use of charcoal haemoperfusion for acute poisoning in Australia.

The spectrum of liver disease in a population of 293 patients receiving 353 renal transplants (1971–1984) was reviewed. This study looked retrospectively at the histological features of liver disease in this population, and prospectively at the clinical and biochemical features of liver disease associated with renal transplantation. In all patients, infection with hepatitis B was excluded. Six deaths, primarily attributable to hepatic failure have occurred: one, acute herpes simplex infection; one, subacute massive hepatic necrosis of uncertain etiology; two, pretransplant liver disease; and two, posttransplantation cirrhosis of uncertain etiology. Review of the hepatic histology of 26 patients with known liver disease following transplantation revealed a wide range of pathologies with few specific correlations with their clinical status or biochemical tests of liver function. The prevalence of hepatic dysfunction following transplantation in our patient population was assessed by prospective biochemical screening of 111 transplant recipients over a 6-month interval. During this time period, 27 patients (24%) displayed biochemical evidence of hepatic dysfunction. Liver disease was known to have predated transplantation in only three of 27. Episodes of abnormal liver function occasionally occurred during an identifiable acute illness (six of 27), although the majority (21 of 27) had chronic hepatic dysfunction. Transplant recipients with abnormal liver function could not be differentiated from a cohort with normal liver function on the basis of age, sex, duration of graft function, or alcohol/drug intake. The possible etiologies of nonhepatitis B liver dysfunction following renal transplantation are discussed, and the high prevalence of biochemical evidence of hepatic dysfunction in this populatinn free of hepatitis B infection is emphasized.

We report a case of a 59 year old woman who presented in end-stage renal failure with lambda (lambda) light-chain myeloma (LLCM). Despite a large tumour burden, and refusal to accept cytotoxic chemotherapy, she was commenced on continuous ambulatory peritoneal dialysis (CAPD). With dialysis therapy alone she has shown considerable hematological improvement and remains well 18 months after diagnosis. The extremely poor prognosis attributed to light-chain myeloma is largely due to death from uremia. As the natural history of this disease in patients offered dialysis therapy is unknown, dialysis should not automatically be withheld from patients with LLCM.

• Subacute cutaneous lupus erythematosus has been heralded as a marker of relatively benign subset of systemic lupus erythematosus. In this article, we describe two cases with severe visceral disease and suggest that it may be less reliable as a predictor of benign disease than was previously accepted. ( Arch Dermatol 1987;123:638-640)