Michael S. Rohr

Effects of tacrolimus on hyperlipidemia after successful renal transplantation: A southeastern organ procurement foundation multicenter clinical study

BACKGROUND Tacrolimus has been shown to have a less adverse effect on the lipid profiles of transplant patients when the drug is started as induction therapy. In order to determine the effect tacrolimus has on lipid profiles in stable cyclosporine-treated renal transplant patients with established hyperlipidemia, a randomized prospective study was undertaken by the Southeastern Organ Procurement Foundation. METHODS Patients of the 13 transplant centers, with cholesterol of 240 mg/dl or greater, who were at least 1 year posttransplant with stable renal function, were randomly assigned to remain on cyclosporine (control) or converted to tacrolimus. Patients converted to tacrolimus were maintained at a level of 5-15 ng/ml, and control patients remained at their previous levels of cyclosporine. Concurrent immunosuppressants were not changed. Levels of total cholesterol, triglycerides, total high-density lipoprotein, low-density lipoprotein (LDL), very-low-density lipoprotein, and apoproteins A and B were monitored before conversion and at months 1, 3, and 6. Renal function and glucose control were evaluated at the beginning and end of the study (month 6). RESULTS A total of 65 patients were enrolled; 12 patients failed to complete the study. None were removed as a result of acute rejection or graft failure. Fifty-three patients were available for analysis (27 in the tacrolimus group and 26 controls). Demographics were not different between groups. In patients converted to tacrolimus treatment, there was a -55 mg/dl (-16%) (P=0.0031) change in cholesterol, a -48 mg/dl (-25%) (P=0.0014) change in LDL cholesterol, and a -36 mg/dl (-23%) (P=0.034) change in apolipoprotein B. There was no change in renal function, glycemic control, or incidence of new onset diabetes mellitus in the tacrolimus group. CONCLUSION Conversion from cyclosporine to tacrolimus can be safely done after successful transplantation. Introduction of tacrolimus to a stable renal patient does not effect renal function or glycemic control. Tacrolimus can lower cholesterol, LDL, and apolipoprotein B. Conversion to tacrolimus from cyclosporine should be considered in the treatment of posttransplant hyperlipidemia.

Increased Kidney Transplantation Utilizing Expanded Criteria Deceased Organ Donors with Results Comparable to Standard Criteria Donor Transplant

Objective:To compare outcomes in recipients of expanded criteria donor (ECD) versus standard criteria donor (SCD) kidneys at a single center using a standardized approach with similar immunosuppression. Summary Background Data:Expanded criteria deceased organ donors (ECD) are a source of kidneys that permit more patients to benefit from transplantation. ECD is defined as all deceased donors older than 60 years and donors older than 50 years with 2 of the following: hypertension, stroke as the cause of death, or preretrieval serum creatinine (SCr) greater than 1.5 mg/dl. Methods:We retrospectively studied 90 recipients of adult deceased donor kidneys transplanted from October 1, 2001 to February 17, 2003, including 37 (41%) from ECDs and 53 (59%) from SCDs. ECD kidneys were used by matching estimated renal functional mass to recipient need, including the use of dual kidney transplants (n = 7). ECD kidney recipients were further selected on the basis of older age, HLA-matching, low allosensitization, and low body mass index. All patients received a similar immunosuppressive regimen. Minimum follow up was 9 months. Results:There were significant differences in donor and recipient characteristics between ECD and SCD transplants. Patient (99%) and kidney graft survival (88%) rates and morbidity were similar between the 2 groups, with a mean follow-up of 16 months. Initial graft function and the mean 1-week and 1-, 3-, 6-, 12-, and 18-month SCr levels were similar among groups. Conclusions:The use of ECD kidneys at our center effectively doubled our transplant volume within 1 year. A systematic approach to ECD kidneys based on nephron mass matching and nephron sparing measures may provide optimal utilization with short-term outcomes and renal function comparable to SCD kidneys.

Intermediate-Term Outcomes With Expanded Criteria Deceased Donors in Kidney Transplantation: A Spectrum or Specter of Quality?

Objective:To compare intermediate-term outcomes in adult recipients of expanded criteria (ECD) versus concurrent standard criteria (SCD) deceased donor kidney transplants at a single center using a standardized approach. Summary Background Data:Expanded criteria donors (ECDs) are a source of kidneys that increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns regarding diminished survival and predicted poorer intermediate-term outcomes. Methods:Over a 47-month period, we performed 244 deceased donor kidney transplants into adult recipients, including 143 from SCDs and 101 from ECDs. Management algorithms were implemented to preserve nephron function, and recipient selection for an ECD kidney transplant was based on low immunologic risk. All patients received depleting antibody induction in combination with tacrolimus and mycophenolate mofetil. A total of 188 patients (77%) had at least a 1-year follow-up. Results:ECDs were older, had a higher BMI, had an increased incidence of cerebrovascular brain death and preexisting donor hypertension, and had a lower estimated creatinine clearance (CrCl, all P < 0.01) compared with SCDs. Cold ischemic times were similar between groups, but more ECD kidneys were preserved with pulsatile perfusion (P < 0.01). ECD kidney recipients were older, less sensitized, had a lower BMI, had fewer 0-antigen mismatches, and had a shorter waiting time (all P < 0.01) compared with SCD kidney recipients. Actual patient (93%) and kidney graft (83%) survival rates were similar between groups with a mean follow-up of 24 months. The rates of delayed graft function (DGF), acute rejection, readmissions, operative complications, major infections, and resource utilization were comparable between groups. Renal function followed longitudinally was consistently better in SCD patients (P < 0.05). Black recipients had higher rates of DGF, acute rejection, and graft loss (P < 0.05), but the effects were less pronounced in the ECD group. Conclusions:By appropriate donor and recipient profiling and the use of management algorithms to project and protect renal function, excellent intermediate-term outcomes can be achieved with ECD kidney transplants that are comparable to SCD kidney transplants.

Reversal by Liver Transplantation of the Complications of Primary Hyperoxaluria as Well as the Metabolic Defect

LIVER transplantation reverses a number of inborn errors of metabolism that result from the genetically determined absence of an enzyme.1 The earliest enzyme-deficiency disorders to be treated by l...

Dual kidney transplantation: a case-control comparison with single kidney transplantation from standard and expanded criteria donors.

Background. The purpose of this study was to perform a case-matched cohort analysis of dual kidney transplantation (DKT) from expanded criteria donors (ECDs) compared to single kidney transplantation (SKT) from concurrent ECDs and standard criteria donors (SCDs, defined as non-ECD). Methods. Deceased donor (DD) kidney transplants (KTs) performed at a single center between October 2001 and February 2006 were reviewed retrospectively. If the calculated DD creatinine clearance (CrCl) was <65 mL/min, then the kidneys were transplanted dually into a single patient. In the case of DKT and SKT from ECDs, low risk patients were chosen and informed consent was obtained. Patients in each group were matched for age, gender, race, transplant number, and time of transplant. Results. Of 294 adult DD KTs performed, 16 (5%) were DKTs, which were matched with 16 concurrent SCD and 16 ECD SKT patients. Mean donor age in years (65 DKT vs. 33 SCD vs. 61 ECD; P<0.0001) and mean donor CrCl in ml/min (54 DKT vs. 91 SCD vs. 76 ECD; P=0.002) were different between groups. Patient survival was 100% in the DKT and SCD SKT groups and 94% in the ECD SKT group (mean follow up 23–28 months); graft survival rates in the DKT, SCD, and ECD groups were 81%, 81%, and 94%, respectively (P=NS). Graft function, rejection, and morbidity were similar between groups. Conclusions. DKT using kidneys from marginal ECDs is a viable option to counteract the growing shortage of available organs. Excellent short-term results and renal function can be achieved with older, low nephron mass donors provided that both kidneys are transplanted into a single recipient.

External ureteroneocystostomy and ureteroureterostomy in renal transplantation.

“External” ureteroneocystostomy is a method of reconstructing the urinary tract for renal transplantation. As performed by us, it is a modification of the technique of Witzel, Sampson, and Lich. It has the advantages of requiring a very short length of ureter, avoiding a separate and large cystotomy, and retaining the antireflux mechanism. This technique is described in detail. Ureteroureterostomy has been used as the preferred procedure when the bladder wall is very thin or when the vascular attachments are such that a ureteral length of greater than 6–7 cm would be required for bladder implantation. Since using these techniques we have reduced the early complication rate of ureteral implantation from 11.9% in a consecutive series of 126 transplants to 0% in the last 88 consecutive transplants. A review of the literature which led to the adoption of these techniques is also presented.

Conversion to sirolimus-based maintenance immunosuppression using daclizumab bridge therapy in renal transplant recipients

Abstract:  Introduction:  Conversion from calcineurin inhibitor (CI)‐based maintenance immunosuppression to sirolimus (SRL)‐based immunosuppression may be beneficial in selected renal transplant recipients. The purpose of this study was to evaluate the safety and efficacy of a daclizumab (DAC) bridge protocol in patients converted from CI‐ to SRL‐based maintenance immunosuppression.

Recent experiences with autotransplantation of the kidney, jejunum, and pancreas.

Ten autotransplants are presented. Renal autografts were performed in the correction of renal artery stenosis, renal artery aneurysm, and intrarenal arteriovenous fistula. All were successful. Jejunal autografts were used to replace the cervical esophagus twice and the entire esophagus once. All grafts were successful, although one patient with advanced cancer died. Pancreatic segmental autografts were used to prevent diabetes following three subtotal pancreatectomies for chronic pancreatitis and one total pancreatectomy for carcinoma. Two patients have functioning grafts, require no insulin, and are free of disease at present. One patient is free of pancreatitis but is diabetic, and one patient died of probable pulmonary embolus. These experiences suggest that organ autografts can be used with greater frequency in clinical surgery and may alter standard therapy for several problems.

Renal allograft acute tubular necrosis. II. A light and electron microscopic study of biopsies taken at procurement and after revascularization.

The light and electron microscopic morphology of 57 cadaver renal allografts was assessed at the time of procurement and again after revascularization. Twenty-two kidneys (39%) did not function immediately after transplantation and 19 of these (86%) contained morphologic evidence of acute tubular necrosis (ATN) in the procurement biopsy. The morphology of the post-transplant biopsy was abnormal in all 22 kidneys with delayed function. There was a wide spectrum of morphologic change between the time of procurement and revascularization in all kidneys with normal function. These changes were mild in nature, were usually confined to proximal tubules, and were of unknown clinical significance. The morphology of kidneys that were damaged by the time of procurement was surprisingly different after storage with simple hypothermia (ice) than after storage with hypothermic pulsatile perfusion. The changes attributed to ice storage included endothelial swelling and vac-uolation with obliteration and collapse of capillary lumens, fracture and splitting of peritubular basement membrane, and hyalinization of the renal interstitium. It was unknown whether these morphologic abnormalities were associated with delayed recovery of function of the injured kidneys.

Biopsy-proven resolution of immune complex-mediated crescentic glomerulonephritis with mycophenolate mofetil therapy in an allograft

We report biopsy-proven resolution of immune-complex-mediated crescentic glomerulonephritis (ICMCGn) using mycophenolate mofetil (MMF). Therapy with steroids and cyclophosphamide failed twice in a 39-year-old white man who developed ICMCGn in his native kidneys, and subsequently in a human lymphocyte antigen-identical renal allograft. When he developed ICMCGn in a second, now cadaver, allograft, he was treated with steroids and MMF instead. His serum creatinine (Cr) improved from 4.4 mg/dL to 2.1 mg/dL. A biopsy 21 months later showed him to be free of glomerular disease. MMF is known to be an effective immunosuppressant. In our patient, ICMCGn, a notoriously difficult entity to treat effectively, seemingly resolved with MMF therapy. We suggest that MMF may be effective in the treatment of immunologically mediated pre-end-stage renal disease (ESRD). It should be considered in any posttransplantation setting where the original cause of organ failure is known to be immunologically mediated and likely to recur.