No abstract

Cinacalcet appears to be an effective drug for the treatment of posttransplant hypercalcemia due to persistent secondary hyperparathyroidism. Further studies with more patients and longer follow-up will be needed to better elucidate the efficacy/safety profile for this agent, particularly with regard to long-term bone histology and renal outcomes.

The results of our study suggest that the choice of induction agent may not have a major impact on graft outcomes in AA renal-allograft recipients.

Influenza infection in renal transplant recipients may cause either morbidity and mortality or acute allograft rejection; thus, routine annual influenza vaccination should be considered. We have studied the humoral and cellular immune responses to influenza virus antigens before and after trivalent vaccine administration in 13 patients and 16 control subjects. The patients, nine of whom were either on alternate-day or low-dose daily steroid therapy, showed highly significant serum hemagglutination-inhibition antibody responses to each influenza virus strain, There was no significant change in mean lymphocyte stimulation index to any influenza virus strain after vaccination in either group. There was no correlation in the patient group between hemagglutination-inhibition antibody titer or response, or lymphocyte stimulation index or response, and the degree of allograft function or dose or duration of immunosuppressive therapy. The vigorous antibody response and the evidence of cellular immunity support the efficacy of influenza vaccination in these patients.

Sirolimus (SRL) is a macrolide immunosuppressantthat has gained widespread use in organ transplantation. Its full spectrum of side-effects is yet to be defined. We describe herein three cases of SRL-induced angioedema (AE) in African-American (AA) primary renal allograft recipients who received SRL in combination with mycophenolate mofetil and steroids. In two cases, AE manifested after SRL was restarted after a period of discontinuation. The third case presented upon initial exposure to the drug. None of the patients was receiving any drug that has been previously associated with AE. Complete resolution occurred only after SRL was withdrawn. AE has not recurred in any of the patients during a follow-up period of up to 21 months. We conclude that AE is a previously unrecognized adverse event associated with SRL use. Close monitoring for this side-effect, especially in AA patients, is warranted.

From February 1988 through October 1988, 23 samples of peritoneal dialysis fluid from 20 patients with end-stage renal disease were cytologically analyzed in an attempt to determine the effect of the dialysate on the mesothelial cells lining the peritoneal cavity. The patients, five female and 15 male, ranging in age from 26 to 75 yr, had been on continuous ambulatory peritoneal dialysis (CAPD) from 1 mo to 6 yr, 4 mo. The patients had no history of cirrhosis, neoplastic disease, radiation and/or chemotherapy, or current findings of infection. Smears and cytosieve filter preparations were made. Smear analysis included the mesothelial cell pattern, the degree of mesothelial cell atypia, and the presence of atypical multinucleated cells and mitoses. In the majority of the fluid samples, reactive mesothelial cells were arranged singly and in sheets. Moderately and severely atypical mesothelial cells were glandular and papillary in configuration. All samples contained at least a few reactive mesothelial cells; in six, the highest degree of cellular atypia was moderate; in 17, it was severe. The development of severe cellular atypia did not appear to be time dependent (a finding noted in samples from patients on dialysis for 6 mo up to 6 yr). When present, multinucleated mesothelial cells showed moderate to severe atypia. In four cases mitotic figures were present. On the basis of these findings, it is proposed that peritoneal dialysis plays a role in the development of mesothelial cell atypia.

The HLAMatchmaker program is based on the donor/recipient comparison of the polymorphic triplet amino-acid sequences of the antibody-accessible regions on the human leucocyte antigen (HLA) molecule. The previous reports on its predictive value for renal allograft outcomes are conflicting. We conducted a retrospective study in a predominantly African-American (AA) cohort (N = 101, 94% AA). HLA typing was performed by molecular methods and triplet matching using HLAMatchmaker. Study end points included graft survival and incidence of acute rejection. The relationship between the number of triplet mismatches (TMM) and the degree of HLA antigen MM was evaluated using Pearson's correlation coefficient. Logistic regression models were used to examine the association between triplet matching and the study end points. Kaplan-Meier and Cox proportional hazard models were used for graft survival analysis. The strongest relationship between the number of TMM and HLA antigen MM was observed for HLA-DQ (r = 0.88). The association between triplet matching at HLA-A, -B, -DR and -DRw HLA loci and the study end points was not statistically significant. However, after grouping, the unadjusted estimates of graft survival for those with more than 10 Class I TMM were significantly worse than the others (p = 0.03). Adjusting for the effect of donor source, recipient characteristics and the immunosuppressive regimen did not change this association (hazard ratio = 0.2, confidence interval = 0.04-1.1). We conclude that triplet matching using HLAMatchmaker can provide useful prognostic information in kidney transplantation and that more than 10 donor/recipient Class I HLA TMM is predictive of worse graft outcome.

Zinc clearance studies in anesthetized dogs were performed during hydropenia, mannitol infusion, and infusion of mannitol plus ZnSO4, ZnCL2, or cysteine. Mannitol expansion caused no significant change in Zn clearance. ZnSO4 infusion increased filtered Zn 13-fold without changing clearance. Zn excretion increased only sixfold, indicating increased net Zn reabsorption. Cysteine infusion increased urinary Zn excretion 86-fold, indicating net tubular Zn secretion, some of which derived from nonplasma sources. Stop-flow studies localized Zn reabsorption to the distal nephron during infusion of mannitol and mannitol plus ZnSO4 or ZnCl2. Net Zn secretion was shown to occur in the proximal tubule during cysteine infusion with reversal of the distal reabsorption pattern seen during ZnSO4 and ZnCl2 infusion. Despite increased urinary Zn excretion during ZnSO4 infusion, calcium excretion was unaltered. During cysteine infusion dissociation of tubular handling of CA2+ and Zn occurred in both the proximal and distal tubule. These experiments demonstrate that the nephron under these experimental conditions is capable of both proximal secretion and distal reabsorption of Zn.