Patients returning to haemodialysis or peritoneal dialysis after a failed kidney transplantation sometimes have a renal allograft left in situ for some urine production. Low-dose immunosuppressive medication is often continued in such patients. To evaluate the morbidity and mortality between patients in time periods with (group A) or without (group B) low-dose maintenance immunosuppression, the present study was initiated. In a multi-centre cohort study we analysed data from patient files, which showed failure after at least 3 months graft function between 10 August 1972 and 4 April 1996, including 197 kidney transplantations. A total of 1.7 versus 0.51 infections per patient year was found in groups A and B, respectively (odds ratio [OR]: 3.4, 95% confidence interval [CI]: 2.5-4.5). There was an increased mortality in group A compared to group B (OR 3.4, 95% CI: 1.8-6.3), both from infectious disease (OR 2.8, 95% CI: 1.1-7.0), and cardiovascular disease (OR 4.9, 95% CI: 1.8-13.5). Continuation of immunosuppressive medication did not lead to fewer rejections (defined as a painful, tender graft and/or haematuria and/or low-grade non-infectious fever). Transplantectomy-related morbidity and mortality were acceptable. The increase in morbidity and mortality associated with low-dose maintenance immunosuppression argues in favour of stopping these medicaments when failed renal allograft patients return to dialysis.

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1. To elucidate the mechanisms by which cyclosporin A diminishes proteinuria, we studied 20 patients with severe nephrotic syndrome. Biopsy-established pathologies included minimal change disease (n = 5), membranous glomerulopathy (n = 6), membranoproliferative glomerulonephritis (n = 5) and focal segmental glomerulosclerosis (n = 4). Before, at the end of a 90 day course of cyclosporin A, and finally 1 month after stopping cyclosporin A we determined 24 h protein excretion. Measurements of glomerular filtration rate, effective renal plasma flow, fractional clearance rates of albumin and immunoglobulins with different charges and the transglomerular sieving of uncharged dextrans of broad size distribution were used to study the effects of cyclosporin A on renal perfusion and the glomerular filtration barrier. The findings were analysed with a theoretical model of solute transport. 2. Among the different forms of glomerulopathy the response to low-dose cyclosporin A (trough levels 32.0-36.9 ng/ml) varied markedly. In minimal change disease, proteinuria decreased from 9.5 +/- 3.1 to 1.3 +/- 0.2 g/24 h (mean +/- SEM, P less than 0.01). This response was due to restoration of the charge selectivity of the glomerular barrier. The depressed value of the glomerular permeability coefficient also returned to normal. Glomerular filtration rate, effective renal plasma flow and renal vascular resistance did not change. Proteinuria returned after stopping cyclosporin A, although it did not reach pretreatment levels. In membranous glomerulopathy, proteinuria fell from 9.9 +/- 1.5 to 1.8 +/- 0.3 g/24 h (P less than 0.01). Changes in protein excretion and dextran sieving were compatible with an increase in glomerular permselectivity and a decrease in filtrate flow through the 'shunt' pathway. Glomerular filtration rate was maintained, although effective renal plasma flow fell significantly. Proteinuria relapsed after stopping cyclosporin A. In membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis proteinuria did not respond to cyclosporin A, although cyclosporin A exerted important haemodynamic effects. 3. In minimal change disease and membranous glomerulopathy cyclosporin A exerts its beneficial effects on proteinuria through changes in the properties of the glomerular barrier, resulting in increased charge and size selectivity, respectively.

One hundred and one patients on haemodialysis, 21 patients on peritoneal dialysis and 30 healthy controls received a trivalent split vaccine containing 15 micrograms haemagglutinin of a recent influenza A-H3N2, influenza A-H1N1 and influenza B strain, respectively. Antibody production after four weeks was determined by the haemagglutination-inhibition test and expressed as response rate, protection rate and overall mean fold increase. The patients on haemodialysis revealed a diminished seroresponse, as compared to patients on peritoneal dialysis and controls. For influenza A-H3N2, this was less distinct than for the other two antigens. In patients on haemodialysis the protection rate was 66% against the A-H3N2 vaccine component (versus 85% in controls, not significant), but only 25% against A-H1N1 and 27% against B (versus 84 and 77% in controls, p less than 0.001). Duration of haemodialysis up to eight years did not affect seroresponse. Patients on haemodialysis who were primed for influenza A-H1N1 in the period 1947-1957, reacted markedly better to the A-H1N1 vaccine component than subjects of other priming periods. A booster injection of the same vaccine dosage four weeks after the first immunization, performed in 98 patients on haemodialysis, was of little value: it had virtually no effect with regard to influenza A-H1N1 and influenza B, and showed, though significantly better, still poor results for A-H3N2. The differences in seroresponse between the A-H3N2 and A-H1N1 vaccine component suggest a major defect of primary, and a minor defect of secondary humoral response in patients on haemodialysis. The consequences for vaccine policy in these patients are discussed.

The increase in serious and life-threatening infections associated with even low-dose immunosuppression argues in favor of discontinuation of these drugs. The removal of failed renal allografts should be considered.