Pulmonary renal syndrome due to anti-GBM and IgM C-ANCA disease requiring the use of novel therapeutic agents.

There are several known causes for the clinical syndrome of pulmonary hemorrhage and acute renal failure. Here, we report a unique case of a 50-year-old man presenting in this manner. The initial diagnosis was one of antiglomerular basement membrane (anti-GBM) disease that responded well to steroids, cyclophosphamide, and plasma exchange (PE). The pulmonary hemorrhage resolved, but he remained dialysis dependent. However, despite falling anti-GBM titers, the symptoms relapsed and standard therapy was reinitiated with limited success. The anti-GBM antibody titer fell to zero despite clinical deterioration, prompting a search for an alternative diagnosis. He was found to be IgM anti-proteinase-3 antineutrophil cytoplasmic antibody (C-ANCA) positive. The pulmonary hemorrhage responded successfully to the use of intravenous immunoglobulin and the antilymphocyte monoclonal antibody CD52. To our knowledge, this is the first known case of IgM C-ANCA in association with anti-GBM disease. As such, it highlights the predominance of pulmonary hemorrhage in this condition, as well as the need to consider alternative therapies in refractory cases.

Clinical and biochemical outcome of hepatorenal transplantation for hereditary systemic amyloidosis associated with apolipoprotein AI Gly26Arg.

BACKGROUND: Treatment of systemic amyloidosis comprises measures to support failing organ function coupled with attempts to reduce the supply of the respective amyloid fibril precursor protein. Orthotopic hepatic transplantation is effective in familial amyloid polyneuropathy associated with variant transthyretin, because this protein is produced almost exclusively in the liver. Hepatic transplantation has not been performed in hereditary apolipoprotein AI (apoAI) amyloidosis, and the liver's contribution to plasma apoAI levels has not been determined in vivo. METHODS: A 57-year-old Irish man with hereditary systemic amyloidosis associated with apoAI Gly26Arg, which had led to end-stage renal failure and progressive liver dysfunction, underwent hepatorenal transplantation. His outcome was followed clinically and his amyloid deposits were monitored with serum amyloid P component scintigraphy. The proportion of variant apoAI in the plasma was estimated by quantitative isoelectric focusing before and after liver transplantation. RESULTS: Plasma levels of variant apoAI decreased by 50% after liver transplantation, and the patient was asymptomatic 2 years after surgery. Subclinical amyloid deposits that were present in his spleen and heart preoperatively have regressed and stabilized respectively. CONCLUSIONS: Orthotopic liver transplantation substantially reduces the supply of the amyloid fibril precursor protein in hereditary apoAI amyloidosis, and the excellent outcome in this patient probably reflects the balance between deposition and turnover of amyloid having been altered in favor of the latter. These findings support the use of liver transplantation in patients with hereditary apoAI amyloidosis who develop hepatic dysfunction.

The use of diagnostic radiology to detect shell irregularities in the New Zealand paua (abalone) Haliotis iris.

A method is described for the non-destructive, non-invasive, detection of shell lesions in the New Zealand paua, a marine gastropod Haliotis iris using diagnostic radiology. The X-ray method reliably detected the presence of shell lesions in 96% of the cases examined once lesion dimensions exceeded 6.2 x 7.1 mm. The extent of lesions above this size can be reliably and accurately determined from X-ray images viewed on a video display unit (VDU). Biofouling on the outside of the shell can cause misdiagnoses. This method is a significant animal welfare refinement in the identification of marine gastropods with shell lesions, when compared with traditional techniques which kill the animals.

Von Hippel-Lindau disease: an important differential diagnosis of polycystic kidney disease.

Von Hippel Lindau disease is a dominantly inherited familial cancer syndrome, characterized by retinal, spinal, and cerebellar haemangioblastomas, renal cell carcinomas, and phaeochromocytomas. Cysts of the kidney and pancreas may also occur. We describe a large three-generation Irish family with VHL disease who initially presented with features typical of autosomal dominant polycystic kidney disease. Eight clinically affected individuals were found. Visceral complications were particularly prominent within the family. There were no cases of retinal angiomata or phaeochromocytoma. The diagnosis was confirmed by genetic linkage analysis in this family, although the exact mutation has yet to be defined.

Skin cancer in an Irish renal transplant population.

One hundred and forty-nine renal transplant patients attending 2 centres in Dublin were examined. Twelve patients (8.1%) were found to have cutaneous malignancy while dysplastic lesions (premalignant and/or malignant) were identified in 34 (22.8%). The prevalence of cutaneous malignancy in this study is substantially greater than that of previous Irish studies. The introduction of cyclosporin A (CyA) as a new and more effective immunosuppressive agent in renal transplantation may in part explain this increase.

Reduction of proteinuria with captopril therapy in patients with focal segmental glomerulosclerosis and IgA nephropathy.

Angiotensin-1 converting enzyme inhibitors (ACEI) have been shown to reduce proteinuria in azotaemic diabetics and in other glomerulopathies, and such treatment has also slowed the development of experimentally-induced glomerulosclerosis in animals. We have treated 13 patients with focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN) with Captopril 12.5 mg twice daily for six months and assessed their response in terms of 24 hour urinary protein excretion, blood pressure, glomerular filtration rate, effective renal plasma flow and derived values for filtration fraction and renal vascular resistance. A mean fall of 29 per cent in urinary protein excretion was observed over the six months treatment schedule. No significant changes were observed in other parameters of renal haemodynamics measured. We conclude that Captopril therapy in patients with FSGS and IgAN reduces urinary protein excretion consistently over a six month period, and that this may in the longer term retard the progression of their renal failure.

The effect of peritoneal dialysate on pulmonary function and blood gasses in C.A.P.D. patients.

There have been many reports showing diminished vital capacity (VC), total lung capacity (TLC), and functional residual capacity (FRC), after the infusion of peritoneal dialysate in patients on continuous ambulatory peritoneal dialysis (C.A.P.D.) for chronic renal failure. We also examined the effects of the infusion of two litres of dialysate on airways resistance (Raw) using total body plethysmography and on arterial blood gasses. Ten patients on C.A.P.D. were selected. The mean results of dialysate infused (in) and dialysate drained (out) are as follows: FVC 3.66 l (in) and 3.73 l (out) (not significant); VC 3.81 l (in) and 3.99 l (out) (p less than 0.05); FEV1 3.02 l (in) and 2.94 (out) (n.s.); TLC 5.89 l (in) and 6.33 l (out) (p less than 0.05); FRC 3.56 l (in) and 3.78 l (out) (p less than 0.05); Raw 4.79 cmsH21/l/s (in) and 4.72 cmsH20/l/s (out) (n.s.); Pa02 11.03 kPA (in) and 11.35 kPA (out) (p less than 0.001). We conclude that two litre dialysate causes significant reduction of TLC, VC and FRC, and a reduction in Pa02 and A-a02 but has no effect on airways resistance.

Haemolytic uraemic syndrome with shigella.

A 49-year-old male developed bloody diarrhoea whilst on a visit to India. Sigmoidoscopy and rectal biopsy showed acute colitis. Shigella dysentery type I was isolated from stool culture. Cytotoxin production by the organism was demonstrated. The patient developed acute renal failure, thrombocytopaenia and microangiopathic haemolytic anaemia. He required mechanical ventilation, haemodialysis, blood transfusion and antibiotic therapy and achieved a complete recovery. This is an unusual case of haemolytic uraemic syndrome complicating shigellosis in an adult.

Immune complex glomerulonephritis secondary to tuberculosis.

A 63 year old man with pulmonary tuberculosis developed nephrotic syndrome secondary to immune complex nephritis. The nephrotic syndrome and renal lesion resolved with standard chemotherapy.

Acute epidemic aluminium osteomalacia secondary to water supply contamination.

When the aluminium content of the water supply to our Haemodialysis Unit rose from less than 0.5 mumol/l to 6 mumol/l over a two month period, we carried out bone biopsies and desferrioxamine infusion tests on twelve (12) patients who had been on haemodialysis for less than one year (mean 8 months) and had normal serum aluminium levels. The patients had no bone symptoms. Eight patients had positive aluminium bone stains. The aluminium osteomalacia group (n = 8) had a mean PTH of 1.4 ng/ml s.e. 0.3 whereas the non-ALO group had a mean PTH of 2.9 ng/ml s.e. 0.7. The difference in mean PTH is significant (p less than 0.05). There was no evidence of encephalopathy, fractures or microcytic anaemia in the ALO positive group. The aluminium contamination of the water supply occurred because of a change in the reservoir purification system from sand-filtration to alum.

Aluminium osteomalacia in chronic renal failure patients neither on dialysis nor taking aluminium containing phosphate binders.

The incidence of aluminium osteomalacia (ALO) in patients with chronic renal failure neither on dialysis nor taking aluminium-containing phosphate binders (ACPB) is not well documented. Biochemical and histological bone investigations were performed in 35 patients fulfilling the above conditions, among whom we found an incidence of ALO of 17%. In the ALO group, salient findings were PTH level (mean +/- s.d.) of 3.1 +/- 1.4 ng/ml (normal less than 0.5 ng/ml); elevated home tap-water aluminium levels of 6.5 +/- 1.2 umol/l (normal less than 2 umol/l); and a GFR of 20.5 mls/min/1.73m, (range 2-50 mls/min/1.73m). We conclude that the aetiology of ALO in this group involves the absorption of toxic home water aluminium in the presence of an elevated PTH level and a GFR less than 50 mls/min/1.73m.