A chromosomal event resulting in possession and expression of multiple HLA-B and Cw genes in a renal patient.

Routine HLA typing of a renal patient for purposes of registration for transplantation revealed an unusual human leucocyte antigen (HLA)-B and Cw genotype, with three specificities detected. Results were confirmed in a second sample, and in a second laboratory. The possibility of these results reflecting a chimaeric state was rejected following short tandem repeat (STR) analysis. Although cytogenetic analysis has failed to detect a chromosomal abnormality, these findings support the view that the aberrant expression of HLA in this patient resulted from an unequal crossover event, occurring during meiosis in a previous generation.

Influence of recipient and donor IL-1alpha, IL-4, and TNFalpha genotypes on the incidence of acute renal allograft rejection.

AIMS: To determine whether polymorphisms of the genes encoding donor or recipient interleukin 1alpha (IL-1alpha), tumour necrosis factor alpha (TNFalpha), or IL-4 have any impact on the incidence of acute rejection after renal transplantation. METHODS: All donors and recipients were genotyped for three polymorphisms in the three cytokine genes: IL1A -889, TNFA -308, and IL4 -590. RESULTS: Statistical analysis of the data obtained revealed no association between the cytokine gene polymorphisms tested and the incidence of post-transplant acute rejection. After stratification for human leucocyte antigen (HLA) matching, it was found that kidneys from donors positive for the TNFA-A allele had a significantly increased incidence of acute rejection in HLA-DR mismatched transplants. CONCLUSIONS: This finding argues for prospective TNFA genotyping of renal donors, with avoidance of allocation of kidneys from donors positive for the TNFA-A allele to HLA-DR mismatched recipients.

Technological advances in renal care.

The first systems for treating kidney failure were developed in the 1940's, when it was found that blood could be successfully cleared of toxins and returned to the body using a relatively simple device based on artificial sausage skin wrapped around a wooden frame. This process was used to replace the function of the kidney, allowing patients to recover from conditions such as poisoning or crush injuries that temporarily stop the kidneys working. In the 1960's, advances in technology made long-term replacement of renal function using haemodialysis machines possible and allowed surgeons to carry out kidney transplants between people who were not identical twins. Long-term peritoneal dialysis became a viable treatment option two decades later. There are now over 1.1 million people world-wide receiving regular dialysis treatment and around 340,000 people living with a donated kidney. This paper reviews the pioneering work in the treatment of kidney failure and looks at some of the recent advances in equipment design, materials science, immunosuppression and information technology that aim to improve the quality of life and the life expectancy for patients living on renal replacement therapy.

Laboratory investigations following an unexpectedly positive crossmatch result in a patient awaiting renal transplantation.

In the preparation of patients for renal transplantation tests of human leucocyte antigen (HLA) sensitisation are performed to detect "unacceptable" HLA antigens that, if present on donor cells, would be expected to result in a positive crossmatch. Individuals bearing such specificities may then be excluded from consideration as donors. Unexpected positive crossmatch results are sometimes obtained when a serum specificity has not been detected on screening. Failure to identify a donor relevant HLA antibody in a recipient at the time of crossmatch may result in hyperacute rejection of the graft. This report describes laboratory investigations performed after a positive crossmatch result in a live donor situation. The pattern of crossmatch results indicated that reactivity resulted from HLA class I antibody. Previously performed serum screening using a standard complement dependent cytotoxicity technique had failed to identify donor relevant antibody specificities in the recipient. Retrospective flow cytometric screening of the same serum samples identified an HLA-A24 specificity of donor relevance. The lower sensitivity of methods used for routine serum screening compared with those used for crossmatching accounts for the findings in this case. The laboratory has amended its serum screening protocol to include flow cytometric analysis.

Specialist follow up of patients before end stage renal failure and its relationship to survival on dialysis.

The high mortality rate of patients with end stage renal failure (ESRF) treated by dialysis is determined principally by irreversible factors such as age and comorbidity. In this single centre retrospective study of all 1260 ESRF patients who started dialysis between 1980 and 1999 it has been demonstrated that a short duration of specialist predialysis follow up is associated with a worse long term outcome on dialysis. Kaplan-Meier survival curves were plotted according to duration of predialysis follow up (group A, < or = 90 days; group B > 90 days), censoring for first transplant, and compared using a log rank test. Differences between groups were examined using an unpaired t test. Cox regression analysis was performed to examine the influence of selected variables on survival. Group A had the worst mortality (survival proportions of 87%, 74%, and 31% in A and 94%, 87%, and 55% in B at four months, one year, and five years respectively, p < 0.001). The increased risk of death was seen principally during the first few months of dialysis. ESRF associated with systemic disease was more prevalent in A. There were small but significant differences in predialysis clinical data, including age and serum albumin (p < 0.001). Fewer patients in A were suitable for transplant listing (p < 0.01). In the regression analysis, age, diabetes, predialysis serum albumin, suitability for transplant work-up and listing ("transplantability"), and the interval between referral and dialysis were significant predictors of survival. In summary, this study strengthens the previously reported association between late referral of ESRF patients and subsequent poor survival on dialysis. This important message is relevant to all potential referring physicians.

A randomized study of oral vs intravenous iron supplementation in patients with progressive renal insufficiency treated with erythropoietin.

BACKGROUND: Correction of anaemia as a result of renal failure improves cardiovascular function and also provides significant cognitive and emotional benefits. The most appropriate route for iron supplementation has not been determined for patients with chronic renal failure who are not yet on dialysis. METHODS: Forty-five anaemic patients with progressive renal insufficiency (PRI) were prospectively randomized to receive oral (ferrous sulphate 200 mg tds) or intravenous (300 mg iron sucrose monthly) iron treatment. Erythropoietin (rHuEpo) was simultaneously commenced and the dose adjusted according to a pre-established protocol. RESULTS: There were no significant differences in baseline patient characteristics between the two groups. The average follow-up was 5.2 months. Three patients suffered possible allergic reactions to iron sucrose. Haemoglobin response and changes in red cell hypochromasia were similar in the two groups, but serum ferritin was significantly higher in the intravenous group. The starting dose of rHuEpo could be temporarily discontinued in 43% of patients on oral iron and 33% of patients receiving iron sucrose (NS). rHuEpo was increased after 3 months in 9% of patients on oral iron and 19% of patients receiving iron sucrose (NS). Final doses of rHuEpo were 33.5 (0-66) and 41.6 (0-124) U/kg/week respectively in the oral and intravenous groups (NS). Although gastro-intestinal symptoms were more commonly reported in patients taking oral iron, these were mild according to scores on visual analogue scales. Dietary protein and energy intake were not significantly different in the two groups at 0, 3 and 6 months. CONCLUSIONS: In pre-dialysis patients, the efficacy of monthly 300 mg iron sucrose given intravenously is not superior with regard to haemoglobin response and rHuEpo dose as compared with a daily oral dose of 600 mg of ferrous sulphate or equivalent. Where intravenous iron is preferred, lower doses may help to reduce the incidence of allergic or "free iron" reactions, especially in patients with low body mass.

The bradykinin response and early hypotension at the introduction of continuous renal replacement therapy in the intensive care unit.

We assessed the relationship of certain clinical variables (including bradykinin [BK] release and dialysis membrane) to initial mean arterial pressure (MAP) reduction in 47 patients requiring continuous renal replacement therapy (CRRT) in an intensive care unit. The pretreatment MAP was 84 +/- 14 mm Hg for the group as a whole. The initial MAP reduction was 11.5 (7-20) mm Hg, occurring 4 to 8 min after connection. MAP reduction was 9 (6-15) mm Hg with polyacryonitrile (PAN) membranes versus 14 (5-19) mm Hg with polysulfone (PS) (not significant). There were positive correlations between MAP reduction and BK concentration at 3 (BK3; r = 0.58, p < 0.01) and 6 (BK6; r = 0.67, p < 0.001) min with PAN but not with PS. A greater reduction in MAP was seen in patients who were not receiving inotropic support (Mann-Whitney test, p < 0.01). BK3 and BK6 values for the PAN and PS groups were not significantly different. However, BK concentrations greater than 1,000 pg/ml were only seen with PAN (6 patients, MAP reduction 27 [17-31] mm Hg). There were positive (albumin) and negative (age; acute physiology, age, and chronic health evaluation score; C-reactive protein [CRP]; calcium) correlations with BK3/BK6 in the PAN and PS groups, some of which (albumin, CRP) reached statistical significance. In summary, MAP reduction at the start of CRRT correlates with BK concentration. The similarity of response with PAN and PS suggests an importance for other clinical factors. In this study, hemodynamic instability was more likely in patients with evidence of a less severe inflammatory or septic illness.

Aluminium release from the Sorbsystem D-3160 and D-3260 cartridges.

Recent clinical information indicates that the aluminium level of patients' serum can rise while they are being treated with the Sorbsystem haemodialysis system. Further evidence suggests that the quality of aluminium removed from the dialysing fluid by the sorbent cartridge utilized in this equipment is time-dependent. Evaluation of the sorbent cartridges D-3160 and D-3260 has shown that ultimately aluminium is satisfactorily removed from the dialysing fluid. However, the time taken to achieve the safe condition of less than 30 micrograms/litre of aluminium is dependent on the quantity of aluminium washed out from a new cartridge before being reabsorbed, and the highly variable quantity contained in the diluting water. The results have also shown that the level of aluminium recommended by the DHSS in April 1982 (30 micrograms/litre) is not reliably attained following the manufacturer's recommended pretreatment, and a further 60 min of operation in the 'dialyse' mode is necessary. It should be noted that, as a result of evaluation of the Sorbsystem, the DHSS have issued guidelines on the use of this equipment.