Digoxin-like immunoreactive substance in renal transplant patients.

Digoxin-like immunoreactive substance (DLIS) has been detected in several patient populations that were not receiving digoxin, including those patients with end-stage renal disease. The structure and physiologic significance of this compound are unknown, and the fate of DLIS after renal transplantation has not been studied. The authors prospectively evaluated 163 patients (not receiving digoxin) before and after transplantation for the presence of DLIS. Three different assays were used: radioimmunoassay (RIA), affinity mediated immunoassay (ACA), and fluorescence polarization immunoassay (TDX I). Depending on the assay method used, 11% (RIA), 6% (ACA), and 9% (TDX) of patients had detectable DLIS pretransplant. Using all 3 assays, a total of 34 patients (21%) were found to have DLIS. The mean serum digoxin concentration was 0.41 +/- 0.13 ng/mL (range: 0.2-1.2 ng/mL) and DLIS was detectable by greater than 1 assay method in seven patients. DLIS persisted longer in patients who had delayed allograft function (13.7 +/- 7 days) than in those who did not (3 +/- 1.9 days), P less than .05. In summary, detection of DLIS in renal transplant recipients appears to be an infrequent occurrence when using a single digoxin assay method. When detected, the concentration of DLIS is often below the usual therapeutic range for digoxin and disappears once allograft function is established. The authors conclude that the presence of DLIS is unlikely to be clinically significant in the renal transplant population.

Low-dose oral acyclovir for prevention of herpes simplex virus infection during OKT3 therapy.

This report evaluates the incidence of clinically significant HSV infection among 23 renal allograft recipients receiving OKT3 for treatment of steroid- or ALG-resistant acute rejection. No HSV infections occurred among the five HSV seronegative patients studied; three of 11 HSV seropositive patients (27%) treated with a ten-day course of low-dose acyclovir prophylaxis developed HSV infection. All three occurred after acyclovir was stopped. Five of six evaluable seropositive patients (83%) who did not receive acyclovir prophylaxis suffered HSV infection. We conclude that low-dose oral acyclovir may be effective in the prevention of HSV infection during OKT3 treatment of seropositive patients. Continuation of acyclovir prophylaxis for two to four weeks following the conclusion of OKT3 therapy may prevent occurrence of delayed infections.

The natural history of and therapy for perirenal fluid collections following renal transplantation.

Fluid collections following renal transplantation are not rare and may be associated with serious complications. We studied the incidence, clinical features, pathology and treatment outcome of perirenal fluid collections after kidney transplantation. Between January 1977 and June 1985, 386 consecutive renal transplants were performed at our university. All allografts were studied with B-mode ultrasonography together with a renal scan in the immediate post-transplant period, at 6-month intervals or when clinically indicated. Symptomatic fluid collections, those associated with rejection episodes and those containing more than 50 to 100 ml. fluid were aspirated under sonographic control via aseptic techniques. There were 190 fluid collections (49 per cent) observed during followup (2 to 11 years). Of these collections 98 (51 per cent) were estimated to be less than 50 ml. in volume, were clinically insignificant and resulted in no morbidity. A total of 92 collections was aspirated with 1 aspiration being diagnostic and therapeutic in 57 instances (serous or serosanguinous fluid). The 35 collections remaining were revealed to be lymphoceles on biochemical grounds. Of 13 lymphoceles associated with rejection episodes 8 resolved on initial aspiration. Of the recurrent lymph collections 27 were treated with repeated aspiration, tetracycline sclerotherapy or an operation (10 were treated with marsupialization into the peritoneal cavity). No large collections of urine or blood were detected and 1 infected lymphocele required external drainage. No renal allograft was lost as a result of a fluid collection and over-all graft survival was not affected by the development of perirenal fluid collections. We conclude that perirenal fluid collections are detected commonly in the post-transplant period using B-mode ultrasonography. The majority of these collections are small and will require careful observation only or they will resolve with a single aspiration. Aggressive diagnostic and therapeutic measures are used only for those collections that are symptomatic or result in allograft dysfunction. A rational approach to the diagnosis and treatment of peritransplant fluid collections is described in the form of an algorithm.

Alternative antirejection treatment with steroids or antilymphoblast globulin in renal transplant patients receiving cyclosporine.

An alternative antirejection protocol using corticosteroids or ALG for reversal of initial acute rejections was studied during a 2-year period in 112 mismatched renal transplant recipients receiving CsA. The majority of patients were cadaver transplant recipients. Thirty-five initial episodes of acute rejection occurred; twelve patients with early or histologically severe rejection were treated with ALG and 23 patients with late, nonsevere rejection received corticosteroid therapy. The overall success rate was approximately 90%, with 21 of 23 corticosteroid-treated patients and ten of 12 ALG-treated patients responding to therapy. The two treatment modalities did not differ with respect to subsequent hospital admissions for fever, second rejections, graft survival, or patient survival. Corticosteroid-treated patients realized significant cost savings and required a shorter hospital stay when compared to ALG-treated patients. An alternative antirejection treatment protocol may be highly effective, safe, and cost beneficial.

Conversion from cyclosporine to azathioprine improves renal function without increased risk of graft failure.

Thirty of 110 HLA-mismatched renal allograft recipients were converted from CsA to Aza due to CsA nephrotoxicity or side effects, persistent posttransplant ATN, noncompliance, or patient desire to reduce the cost of maintenance immunosuppression. The majority of patients studied were cadaver transplant recipients. Renal function improved significantly in all patients following conversion. Converted patients did not demonstrate an increased incidence of rejection or hospitalization for fever or infection when compared with nonconverted, matched controls. The rate of allograft loss in converted patients did not differ from that of all nonconverted patients during the study period. The monthly cost of maintenance immunosuppression was significantly less in converted patients, resulting in an annual savings of $2,489 per patient. Posttransplant conversion from CsA to Aza appears to be safe and cost-beneficial.

Optimizing cyclosporine use in pediatric patients by measuring pretransplant blood levels.

A method for measuring pretransplant CsA levels to predict posttransplant pharmacokinetic behavior was studied in a total of seven pediatric patients. Comparison of drug levels and single-dose pharmacokinetic characteristics in the pretransplant and posttransplant study periods suggest that this method (1) is useful in predicting early posttransplant blood levels and beta-phase half-life; (2) may prevent early episodes of acute allograft rejection associated with subtherapeutic cyclosporine immunosuppression; and (3) may identify those patients who should not be empirically treated with only cyclosporine and prednisone in the early posttransplant period.