Late low-dose steroid withdrawal in renal transplant recipients increases bone formation and bone mineral density.

Corticosteroids have been the most widely used immunosuppressive agents since the first clinical transplantation in the 1950s. There are few studies of late steroid withdrawal in renal transplantation and none have prospectively assessed bone mineral density (BMD). The study aim was to assess the impact of corticosteroid withdrawal, in stable renal transplant recipients, on BMD and bone turnover. BMD, osteocalcin (OC) and cross-linked telopeptide of type I collagen (CTx) were measured in 92 patients randomized into a trial of steroid withdrawal. Patients with functioning renal transplants for more than 1 year with a serum creatinine below 200 micromol/L entered the trial. All patients were on triple immunosuppression (Cyclosporin microemulsion, Azathioprine and prednisolone), corticosteroids were withdrawn at 1 mg/month. BMD was measured twice annually with serum CTx and OC. One year following withdrawal of glucocorticoids there was no significant difference in creatinine. BMD increased in the withdrawal group (2.54% per year L1-L4, p < 0.01), there was a slight reduction in the control group. Mean OC increased from 5.3 to 12.2 ng/mL (p < 0.05) in the withdrawal group, but was unchanged in the controls. No change was seen in CTx. Corticosteroid withdrawal in renal transplant recipients results in an increase in BMD with a corresponding increase in serum OC.

Noninvasive imaging of living related kidney donors: evaluation with CT angiography and gadolinium-enhanced MR angiography.

OBJECTIVE: This study was performed to determine whether noninvasive imaging with CT angiography and MR angiography in the preoperative investigation of living, related kidney donors provides sufficient information for the surgeon. MATERIALS AND METHODS: Eighty consecutive potential living kidney donors were investigated. Fifty patients underwent CT angiography and 30 underwent MR angiography before donor nephrectomy. CT was performed using 3-mm collimation with a pitch of 1.6 after the injection of 150 mL of nonionic contrast medium. The axial data, multiplanar reconstructions, and maximum intensity projections were reviewed. MR angiography was performed on a 1-T magnet using a contrast-enhanced three-dimensional gradient echo technique. Maximum intensity projections and axial reformations were reviewed. Imaging findings were compared with the surgical results in 54 patients. RESULTS: CT angiography and MR angiography were 100% sensitive in identifying the main renal arteries and renal veins. CT angiography visualized 37 of the 40 arteries identified at surgery, for a detection rate of 93%. MR angiography visualized 18 of the 20 arteries identified at surgery, a detection rate of 90%. CONCLUSION: CT angiography and MR angiography are suitable for the noninvasive investigation of living kidney donors and provide all the information required by the surgeon. Both methods may miss small accessory renal arteries. MR angiography does not use potentially toxic contrast material or radiation and is the preferred investigation, with CT angiography reserved for patients unable to tolerate MR imaging.

Contribution of individual drugs to gingival overgrowth in adult and juvenile renal transplant patients treated with multiple therapy.

Drug regimens for transplantation often consist of multiple therapeutic agents and may result in drug-induced gingival overgrowth (DIGO). The aim of this study was to investigate the contribution of individual drugs in renal transplant patients. 147 adults (19-84 years) and 60 juveniles (3-18 years) were scored for DIGO and other clinical variables. Duration of treatment, dosage of drugs per kg body weight and serum cyclosporin levels were recorded. 44% of adults and 27% of children had DIGO. All patients were receiving prednisolone. More adults than children were administered cyclosporin, the reverse was true of azathioprine (p<0.01). Explanatory models were evaluated by stepwise ordinal polynomial logistic regression. Statistically significant explanation (p<0.05) of DIGO was afforded by prednisolone, nifedipine and azathioprine concentrations in adults and by cyclosporin, nifedipine and azathioprine concentrations in juveniles. Prednisolone and azathioprine were inversely related to the degree of DIGO. Plaque and irregularity scores, lip coverage and mouthbreathing status showed significant additional explanation in adults, replacing nifedipine and azathioprine in the final model. Irregularity was additionally explanatory in children, but no other clinical variables. A larger proportion of the variance of DIGO was explained by the available variables in children than in adults (pseudo r2=0.50 versus 0.25). The degree of DIGO in renal transplant patients is influenced by the dosage of a number of individual components of multiple drug therapy independently of the presence of local clinical factors.

The asystolic donor syndrome: transaminitis and thrombocytopenia after non-heartbeating renal transplantation.

BACKGROUND: The use of kidneys from non-heartbeating donors (NHB) remains controversial. An increased incidence of delayed primary function and primary nonfunction is common. We report a characteristic syndrome of transaminitis and thrombocytopenia after NHB renal transplantation, which may be predictive of graft outcome. METHODS: Two case histories are presented, followed by a retrospective analysis of 38 NHB renal grafts performed at Guy's Hospital from 1988 to 1994. Changes in alanine aminotransferase (ALT) and platelet count were compared between recipients of kidneys from NHB and heartbeating donors (HB). To control for possible effects of antilymphocyte globulin (ALG), two matched control groups receiving HB kidneys with (n=32) and without (n=32) ALG were also compared. RESULTS: ALT was elevated in 32 of 38 (84%) of NHB recipients and 19 of 64 (30%) controls (P<0.001). Mean peak ALT was 172+/-20 U/L in NHB and 42+/-6 U/L in HB kidneys (P<0.001). Use of ALG did not influence mean peak ALT. Elevated ALT predicted impaired graft function (P<0.02) and was associated with an increased length of delayed primary function (P<0.001) and risk of transplant nephrectomy (P<0.05). Thrombocytopenia (<100 x 10(9) cells/L) occurred in 18 of 38 (47%) NHB recipients and in 20 of 64 (31%) controls (P<0.05). Mean nadir platelet count (x 10(9) cells/L) was 113+/-10 in NHB, 128+/-9 in HB with ALG, and 164+/-9 in HB without ALG (both P<0.05 vs. NHB). Patients who underwent graft nephrectomy (n=9) had a disproportionate fall in platelet count (mean nadir, 80+/-11 x 10(9) cells/L; P<0.05). CONCLUSIONS: Transaminitis and thrombocytopenia occur commonly after NHB kidney transplantation and are predictive of graft outcome. Recognition of these changes may assist the early management of NHB renal recipients, and also reduce investigation of "anomalous" results in this setting.

Antibody removal and subsequent transplantation of a highly sensitised paediatric renal patient.

We report a successful renal transplant in a highly sensitised paediatric recipient following removal of HLA-specific antibodies by extracorporeal immunoadsorption. The immediate pretransplant cytotoxic titre against the donor was greater than 1:512; this was reduced to negativity by two immunoadsorption sessions prior to transplant surgery. We also describe the presence of unexpected non-HLA-specific antibody activities in this immunoadsorbed patient.

Is cystoplasty a safe alternative to urinary diversion in patients requiring renal transplantation?

The study aimed to assess the methods of urinary drainage in patients requiring renal transplantation in whom the native lower urinary tract was unsuitable. Twenty-one patients had a transplant into an abnormal urinary tract. Eight of them into a cystoplasty, 8 into an ileal conduit and 5 had a cutaneous ureterostomy. All patients transplanted into an ileal conduit (mean follow-up 4.6 years) and into a cutaneous ureterostomy (mean follow-up 3.2 years) have had a satisfactory outcome. Five of 8 patients transplanted into a cystoplasty have had a satisfactory outcome, 2 patients suffered graft loss due to rejection and 1 developed necrosis of cystoplasty following transplantation. In terms of graft survival, excellent results in the medium term were obtained for transplantation with an ileal conduit or cutaneous ureterostomy. Cystoplasty was less successful but was not the direct cause of graft loss in any patient and as such is as safe a technique in patients with end-stage renal failure so long as care is taken to avoid the vascular pedicle at the time of transplantation.

Sparing of first dose effect of monovalent anti-CD3 antibody used in allograft rejection is associated with diminished release of pro-inflammatory cytokines.

The murine monoclonal antibody OKT3 is the best known of the anti-CD3 antibodies used for the prevention and treatment of renal allograft rejection. Use of this antibody is associated with improved graft outcome but it has a number of adverse effects thought to result from the massive release of pro-inflammatory cytokines. It has been postulated that OKT3 causes cytokine release because of cross-linking of CD3 molecules on the cell surface by bivalent anti-CD3 antibodies, such as OKT3, and the simultaneous binding of the Fc regions of these monoclonal antibodies to Fc receptors on other cells resulting in cell activation. Monovalent antibodies directed against the CD3 antigen should not, in theory, cause cell activation and cytokine release by this postulated mechanism. This study details the use of a monovalent anti-CD3 monoclonal antibody in the treatment of allograft rejection in five renal transplant recipients and documents the degree of TNF, IFN-g and IL6 release generated after antibody injection. Monovalent anti-CD3 monoclonal antibody reversed the rejection episode for which it was used and was well tolerated in all patients. TNF, IFN-g and IL6 measurement showed that little pro-inflammatory cytokine release occurred after this drug. It is likely that the relative lack of side-effects of monovalent anti-CD3 reflects the blunted release of pro-inflammatory cytokines. Monovalent anti-CD3 monoclonal antibody may be a useful addition to the reagents available to treat allograft rejection.

The negative influence of delayed renal allograft function on longer-term graft survival in a pediatric population.

The influence of delayed graft function on renal allograft survival has been studied in a review of 322 renal transplants performed at one pediatric institution. The appearance of the first radionuclide renal scan was used to indicate early function in patients receiving their first cadaveric allograft. Patients whose first radionuclide renal scan showed both good renal perfusion and good function (n = 52) were compared with those whose scans demonstrated good perfusion but no function (n = 32). the actuarial graft survival of those with no function was significantly worse (P < .05). The difference in graft survival was not solely due to grafts lost in the early posttransplant period. Analysis of serial serum creatinine estimations suggests a process of continued inexorable nephron loss in some patients whose grafts showed a delay in achieving function.

Primary use of a double J silicone ureteric stent in renal transplantation.

Vesicoureteric leakage and obstruction are the commonest urological complications after renal transplantation. A retrospective analysis of our initial experience using a double J silicone ureteric stent showed that primary splinting of the vesicoureteric anastomosis eliminated these complications, whereas their combined incidence was 13.6% in the non-stented patients. The presence of the stent was not associated with increased risks of urosepsis.