Martin Jacobs

The Effect Of Body Mass Index On Long-term Renal Allograft Survival

BACKGROUND A number of factors have been implicated in decreasing long-term renal graft survival. Factors such as living versus cadaveric donor status, acute rejection, and HLA matching have been studied in detail. Mild obesity defined as a body mass index (BMI) of >25 has been found to have a deleterious effect on a number of physiologic processes. We studied the effect of a BMI >25 on long-term renal transplantation outcome. METHODS A total of 405 patients who underwent transplantation at Saint Barnabas Medical Center from 1990 to 1997 were evaluated. All known variables impacting on long-term graft function were collected. Multivariate analysis utilizing the Cox-proportional hazard model and Kaplan-Meier actuarial survival were applied to these risk factors. RESULTS BMI >25 was isolated as an independent risk factor for both decreased graft survival and patient survival (relative risk 2.0 for each). Cadaveric donor status, acute rejection, and use of azathioprine versus mycophenolate mofetil were the only other significant risk factors. CONCLUSIONS Mild obesity before transplantation has a negative impact on long-term renal graft and patient survival.

Hypercoagulable states in renal transplant candidates: impact of anticoagulation upon incidence of renal allograft thrombosis.

INTRODUCTION Although multiple studies of demographic variables have been associated with allograft thrombosis, these results are not routinely reproducible. Are ESRD patients with hypercoagulable states (HCS) (antithrombin III deficiency, protein S or C deficiency, activated protein C resistance, and anticardiolipin antibodies) at predictably greater risk for allograft thrombosis? METHODS Between 1996 and 1999, all renal transplant candidates were screened for hypercoagulability risk factors [HRF] (multiple arteriovenous access thromboses, prior deep vein thrombosis, prior allograft thrombosis, collagen vascular disease, multiple miscarriages, diabetes, autoimmune disease, and Fabrys disease). HRF(+) candidates were then tested for HCS status. We administered preemptive posttransplant i.v. Heparin in HCS(+) patients and observed the impact of this intervention upon the incidence of allograft thrombosis. We compared demographic data and incidence of allograft thrombosis in an historic control (346 patients transplanted between June 31, 1992, and March 5, 1996) not tested for HCS and a study cohort (502 patients transplanted between March 6, 1996, and June 31, 1999) prospectively screened for HRF. HRF(+) patients who were HCS(+) in the study cohort received i.v. heparin immediately after transplant and p.o. warfarin as outpatients. RESULTS Demographic characteristics previously implicated in allograft thrombosis were equivalently distributed in both cohorts with the exceptions that more living-donor transplants (33.1% vs. 15.3%) were performed in study cohort, CIT>24 hr occurred in more control patients (37.3% vs. 22.1%) and more study patients (16.7% vs. 0%) received tacrolimus. Hypercoagulable states were found upon reevaluating five of seven controls (71.4%), who lost prior allografts to thrombosis. Hypercoagulable states were prospectively detected in 10 study patients with hypercoagulability risk factors. Most (9 of 10) study patients receiving anticoagulation have achieved long-term allograft function. Study group allograft thrombosis incidence was reduced (1.59% vs. 4.05%). Hypercoagulable states were demonstrated in most episodes of allograft thrombosis. Control patients who lost prior allografts to thrombosis were anticoagulated after retransplantation and 100% achieved long-term allograft function. CONCLUSIONS Long-term allograft function has been achieved in 90% of study patients when prophylactically anticoagulating study patients with hypercoagulable states. A 2.6-fold reduction in the expected incidence of allograft thrombosis was observed in anticoagulated patients with hypercoagulable states.

Infectious complications in geriatric renal transplant patients: comparison of two immunosuppressive protocols.

BACKGROUND It has been well documented that a regimen of mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisone (Pred) reduces the incidence of acute rejection in renal transplant recipients, as compared with previous regimens based on azathioprine (AZA), CsA, and Pred. In the general renal transplant patient population, immunosuppressive regimens that include MMF are usually well tolerated. It is not clear whether this holds true for older transplant recipients, who may be more susceptible to complications from the greater immunosuppression conferred by MMF. METHODS We retrospectively analyzed our geriatric renal transplant population (age >60 years, 1990-1998) and compared a cohort of 46 patients treated with AZA, Pred, and CsA to a cohort of 45 patients treated with MMF, Pred, and CsA. RESULTS There were no significant differences between the groups with regard to pretransplantation demographics. Patient and graft survival during the first year was not significantly different between the groups. During the first year of follow-up, we observed 27 infections requiring hospitalization in 15 patients in the MMF-treated group as compared with 10 infections in 7 patients in the AZA-treated group. A Cox proportional hazard model accounting for the above mentioned covariates isolated MMF versus AZA as a significant risk factor for the occurrence of serious infectious events (all: P<0.01; cytomegalovirus, fungal: P<0.01). CONCLUSION We conclude that an immunosuppressive regimen of MMF, CsA, and Pred seems to be correlated with an increased incidence of infectious adverse events as compared with AZA, CsA, and Pred in elderly patients.

Prevalence of cytomegalovirus in the gastrointestinal tract of renal transplant recipients with persistent abdominal pain.

Abdominal pain occurs frequently in renal transplant recipients receiving mycophenolate mofetil (MMF) therapy. The cause of this abdominal pain has not been fully elucidated, but may involve local irritation, as well as inhibition of rapidly dividing cells of the gastrointestinal (GI) tract. This milieu of inflammation and added immunosuppression is conducive to activation of cytomegalovirus (CMV). We therefore sought to find the prevalence of active CMV in patients presenting with abdominal pain on maintenance MMF therapy. All patients receiving a renal transplant at our center from March 1, 1997, to September 1, 1997, were studied. Any patient presenting with midepigastric pain for greater than 3 days underwent esophagogastroduodenoscopy (EGD) with biopsy. CMV was diagnosed by the presence of inclusion bodies and immunohistochemical studies. Ten patients presented with persistent midepigastric pain; nine of these patients had evidence of GI CMV. Patients who were CMV negative and received an allograft from CMV-positive donors and those with leukopenia were at significantly increased risk for the development of abdominal pain. In our study population, the majority of patients on maintenance MMF therapy who presented with persistent midepigastric pain had evidence of active CMV infection in the upper gastrointestinal tract.

Potential interaction of troglitazone and cyclosporine

BACKGROUND Troglitazone (Rezulin) is a promising new oral hypoglycemic agent recently approved by the Federal Drug Administration for use in type II diabetes mellitus. Although troglitazone is not metabolized by the cytochrome p450 3A isozyme family, it is a potential inducer of this system. Other medications, e.g., rifampin and phenobarbital, which also induce p450 3A activity, have been reported to significantly decrease cyclosporine (CsA) concentrations. METHODS We report a case of a stable renal transplant patient who had a decrease in CsA concentration after beginning troglitazone and who subsequently developed an acute rejection episode. We then reviewed all stable renal patients begun on troglitazone over the previous 6 months. RESULTS The seven transplant patients who had been started on troglitazone therapy experienced a statistically and clinically significant decrease in CsA 12-hr trough levels immediately after the institution of troglitazone therapy. CONCLUSION A potential interaction exists between troglitazone and CsA. Transplant patients on CsA who receive troglitazone therapy should be monitored closely.

Allograft loss in renal transplant recipients with Fabry's disease and activated protein C resistance.

INTRODUCTION Fabrys disease is associated with an increased incidence of thrombotic events and rejection. Spontaneous thrombosis of a functioning cadaveric renal allograft in a recipient with Fabrys disease prompted prospective evaluation of all transplant candidates with Fabrys disease for hypercoagulability. MATERIALS AND METHODS Transplant candidates with Fabrys disease were tested for hypercoagulability, analyzed for HLA-type and ABO group, and comorbid conditions suggestive of hypercoagulability. RESULTS A unique association of Fabrys disease with activated protein C Resistance was documented in a cohort of Caucasian male renal transplant recipients with Fabrys disease. Four of five patients were blood group A and had no significant comorbid conditions suggestive of hypercoagulability. The resistance to activation of protein C (APCR)(+) patients shared HLA loci-B8 and Dr3, although the APCR(-) patients shared HLA loci-B27 and -B38. CONCLUSIONS Due to the observed increase in the incidence of APCR in our Fabrys cohort, we suggest screening all patients with Fabrys disease for APCR. Because factor V and factor Va receptors are found on vascular endothelium and peripheral blood monocytes, APCR in the presence of Fabrys disease may be a nonimmunological stimulus for rejection. Analysis of HLA typing in patients with Fabrys disease may further elucidate HLA-based association of Fabrys disease and resistance to activated protein C with the risk of thrombosis and rejection.

Withdrawal of mycophenolate mofetil in stable renal transplant recipients.

BACKGROUND Mycophenolate mofetil (MMF) has been demonstrated to decrease episodes of acute rejection in renal transplant recipients during the first year after transplantation. The utility of MMF after 1 year is less clear. METHODS Forty-five stable renal transplant recipients on maintenance therapy of cyclosporine microemulsion, MMF, and prednisone had MMF withdrawn at approximately 1 year after transplantation. A matching concurrent group of 45 stable renal transplant recipients served as the case control group. RESULTS Two of 45 patients in the MMF withdrawal group suffered an acute rejection episode as opposed to 1 of 45 in the control group. Both patients who rejected in the withdrawal group had adequate cyclosporine levels and had no recent decrease in prednisone dose. There was no evidence of an increased incidence of proteinuria or increased creatinine levels in the MMF withdrawal group. CONCLUSION In general, withdrawal of MMF in stable renal transplant recipients is well tolerated. No increased risk of rejection could be demonstrated in this patient group. A larger study will be needed to confirm our result.

Evaluation of voiding cystourethrography prior to renal transplantation

In many centers, voiding cystourethrography is a routine part of pretransplantation assessment of the lower urinary tract. To assess the value of this investigation, a retrospective review of transplant candidates evaluated in our center over 2 years was undertaken. A total of 517 patients were fully evaluable. Only 13 voiding cystourethrograms (VCUGs) (2.5%) of 517 were found to be abnormal. Three patients with reflux alone did not require intervention before transplantation. Four patients with decreased bladder capacity underwent hydrodistention. Two patients increased their capacity to over 150 ml and two patients failed distention, one requiring an ileal conduit and the other requiring an augmentation cystoplasty. Three patients had increased postvoid residual (PVR). Two patients started clean intermittent catheterization. One required prostate resection for benign prostatic hypertrophy. One patient with reflux and decreased bladder capacity refused treatment. One patient with reflux combined with increased PVR started clean intermittent catheterization and was cleared for transplant surgery. One patient with decreased bladder capacity and increased PVR had a stroke and was excluded from transplantation. All 13 patients with abnormal VCUGs had a prior urologic history. In total, only 56 of 517 patients evaluated had a prior urological history. Each VCUG costs approximately

Laparoscopic Internal Drainage of Lymphocele in Renal Transplant

500. Limiting VCUG studies to those patients with a prior urological history would have resulted in a significant cost savings. Hence, we recommend that only patients with a prior urological history should undergo this costly and often distressing examination.

Mitomycin-induced hemolytic-uremic syndrome. Successful treatment with corticosteroids and intense plasma exchange.

Lymphoceles frequently develop following renal transplant surgery. The conventional methods used to drain lymphoceles are invasive and can be associated with complications. Laparoscopic drainage of posttransplant lymphoceles provides a safer alternative.