Plasma ascorbic acid in patients undergoing chronic haemodialysis.

OBJECTIVE: Patients with renal disease receiving dialysis therapy are susceptible to a deficit in ascorbic acid (AA) caused by loss during dialysis and a restricted dietary AA intake. In previous studies, in such patients, the methods generally used for AA determination are non-specific and insensitive, and control of the easily deteriorating AA in the samples is often disregarded. The purpose of this work was to study the AA plasma levels and dialyser clearances as well as the kinetics of administered AA in a group of dialysis patients, using selective and sensitive methodology and a procedure preserving the AA sample content. METHODS: Using an analytical method based on high-performance liquid chromatography and electrochemical detection, we have examined the dialyser clearance of AA as well as the pre- and post dialysis plasma levels of AA in patients on chronic dialysis therapy. The plasma AA levels were further measured after single and multiple dose supplementation of 200 mg p.o. per day. RESULTS: The majority of the patients (16 of 19) had pre-dialysis plasma levels below the normal range. The dialyser clearance of AA was 212 ml/min (median value). Following dialysis, the plasma AA concentrations were reduced by a median of 33%. AA supplementation significantly increased these levels; however, they dropped soon after supplementation was stopped. AA in uraemic whole blood and plasma was, on average, less stable than in samples from healthy subjects. CONCLUSION: This study, using selective analytical method with adequate stability control, confirms that AA is readily removed by conventional haemodialysis membranes. Patients on chronic haemodialysis have remarkably low plasma AA levels unless given AA supplementation.

Serum amyloid A protein is a clinically useful indicator of acute renal allograft rejection.

BACKGROUND: Early diagnosis of acute rejection after renal transplantation is important. There is evidence that measurement of the acute phase proteins, C-reactive protein (CRP) and serum amyloid A protein (SAA) is helpful. METHODS: In 64 consecutive patients, CRP was measured in a routine clinical system (Technicon RA1000, Bayer) and SAA in a new sensitive automated immunoassay on the Abbott IMx instrument, daily or on alternate days for 30 days after renal transplantation. RESULTS: Patients all received triple immunosuppression with cyclosporin, azathioprine, and prednisolone and all mounted a post-surgical acute phase response of SAA, but the CRP response was reduced or absent. Serum creatinine rose significantly in 36 patients, leading to treatment for first rejection. Thirty of these episodes were confirmed rejection, three were definitely not and three were uncertain. SAA. normally < 10 mg/l, rose to more than 100 mg/l in all episodes except when rejection was definitely absent. In six cases SAA rose above 100 mg/l 1-3 days before the rise in creatinine leading to antirejection therapy, and only twice did creatinine rise 1 day before SAA. In contrast, CRP responses to rejection were modest or absent. In four patients there were SAA and CRP responses unrelated to rejection, three associated with intercurrent infection and one with administration of antilymphocyte globulin. There were also two unexplained isolated spikes of SAA. CONCLUSIONS: SAA is a sensitive marker of acute renal allograft rejection. It is not specific, but the differential behaviour of CRP in patients receiving cyclosporin helps to distinguish infection from rejection. Availability of rapid assays for these analytes should facilitate management of renal allograft recipients.

Half dose of OKT3 is efficient in treatment of steroid-resistant renal allograft rejection.

Rejection episodes in renal allograft recipients are usually efficiently treated with high doses of intravenous methylprednisolone. Rejection therapy with OKT3 is often reserved for steroid-resistant episodes. However, the optimal dose of OKT3 in the treatment of steroid-resistant rejection is not known. Therefore, we randomized renal transplant recipients with steroid-resistant rejection to treatment with a standard daily intravenous dose of either 5 mg of OKT3 (n=15) or 2.5 mg of OKT3 (n=15) for 10 days. Circulating T cells (measured as CD2+ cells) were adequately and equally depleted in the two groups. Three grafts were lost due to rejection within the first 3 months following OKT3 administration, one in the 2.5 mg OKT3 group and two in the 5 mg OKT3 group. Two nonimmunologic graft losses occurred in the 2.5 mg OKT3 group. Median serum creatinine values were not different between the two groups, neither at the start (median values: 200 micormol/L in the 5 mg OKT3 group vs. 188 micromol/L in the 2.5 mg group) nor immediately after OKT3 rescue therapy (202 micromol/L vs. 185 micromol/L, respectively). Eight cytomegalovirus infections occurred in each group. Two re-rejection episodes occurred in the 5 mg OKT3 group and one occurred in the 2.5 mg OKT3 group. All responded to treatment. Function of the remaining grafts estimated by serum creatinine after a mean long-term follow-up of 18 months (range, 6-36 months) revealed no differences (185 micromol/L in the 5 mg OKT3 group vs. 170 micromol/L in the 2.5 mg OKT3 group). We conclude that OKT3 treatment of steroid-resistant rejections in renal transplant recipients is equally effective in daily doses of 2.5 mg and 5 mg with respect to reversal rate and long-term outcome.