William Carlos Nahas

Augmentation cystoplasty in renal transplantation: A good and safe option: Experience with 25 cases

OBJECTIVES To assess the surgical and long-term results of renal transplantation in 25 patients with bladder dysfunction and augmentation cystoplasty. METHODS We retrospectively reviewed the evolution and surgical outcome of 25 renal transplants in 24 recipients with augmentation cystoplasty. The mean patient age at transplantation was 27.6 years. The etiology of bladder dysfunction was neurogenic bladder with detrusor hyperreflexia (11 patients), tuberculosis (5 patients), vesicoureteral reflux (4 patients), posterior urethral valves (3 patients), and interstitial cystitis (1 patient). Seventeen transplants were from living donors. Augmentation cystoplasty was performed before transplantation in 21 patients. The bowel segments used in the augmentation cystoplasty included ileum in 16, ileocecal segments in 2, and sigmoid in 5 patients. The donor ureter was anastomosed to the native bladder in 16 patients, to the bowel segment in 6, and to the native ureter in 3. RESULTS Twenty kidneys (80%) were functioning at a mean follow-up of 53.2 months (range 6 to 118). The mean serum creatinine was 1.56 mg/dL (range 0.7 to 2.6). Three patients died of unrelated causes and 1 of adenocarcinoma that originated at the vesicointestinal anastomosis. The actuarial graft survival at 1, 2, and 5 years was 96%, 92%, and 78%, respectively. Complications included symptomatic urinary infection, ureteral stenosis, and lymphocele. CONCLUSIONS Augmentation cystoplasty is a safe and effective method to restore function in noncompliant bladders. Renal transplantation can be performed safely after augmentation cystoplasty.

The dynamics of glucose metabolism under calcineurin inhibitors in the first year after renal transplantation in nonobese patients

Background. The incidence of glucose metabolism disturbances after transplantation often is based on the use of hypoglycemic agents and not on the results of glucose tolerance tests (GTTs), which may camouflage the real incidence. A lack of information also exists regarding the profile of glucose metabolism during the first year after transplant. Methods. Oral GTT along with insulin measurements and drugs pharmacokinetics were prospectively performed at days 30, 60, 180, and 360 after transplant to diagnose disturbances of glucose metabolism after renal transplantation, in nonobese patients receiving either tacrolimus (n=55) or cyclosporine (n=29), along with mycophenolate mofetil and steroids. Results. The incidence of impaired glucose tolerance or diabetes mellitus reached a peak at 60 days and decreased at 1 year. It could not be adequately diagnosed using fasting plasma glucose in a decreased abnormal (>99 ng/mL) range. In both groups, insulin secretion, evaluated by the Homeostasis Model Assesment (HoMA-β), decreased (P<0.005) from the condition of normal GTT (101±56%) to impaired glucose tolerance (72±35%) and diabetes mellitus (54±25%). In the cyclosporine group, insulin secretion was normal and stable throughout the study period, but in the tacrolimus group, insulin secretion recovered over time and was inversely correlated with tacrolimus exposure. Insulin resistance (HoMA-IR) did not change. Conclusions. This study shows the need to perform an oral GTT at 60 days and at the end of the first year of renal transplantation to adequately diagnose impaired glucose metabolism.

Incisional hernia and its repair with polypropylene mesh in renal transplant recipients.

PURPOSE We evaluate the incidence of incisional hernia after kidney transplantation, predisposing factors and the results of surgical repair with polypropylene mesh. MATERIALS AND METHODS We reviewed the records of 371 consecutive kidney transplants performed between April 1995 and February 2000. Patients with clinical signs of hernia at the transplant incision site were included in the study. Predisposing factors for incisional hernia were also reviewed. A prospective protocol of surgical correction was established using polypropylene mesh and patient outcome was studied. RESULTS We identified 14 patients (3.8%) with an incisional hernia at the transplant incision site. Hernias developed 3 to 840 days after transplant surgery and were significantly more common in white (p = 0.019) and cadaveric graft (p = 0.02) recipients. Predisposing factors in 11 cases included complications of transplant surgery in 7, bladder obstruction in 2, large polycystic kidneys in 1 and chronic pulmonary disease in 1. Surgical repair was performed by primary fascial approximation and polypropylene mesh reinforcement in 13 cases and by pre-peritoneal mesh placement in 1. Minor subcutaneous wound infection developed in 1 patient. No relapses were noted at a mean followup of 17.8 months. CONCLUSIONS In the majority of cases incisional hernia develops in the first 3 months after transplant surgery. The incidence is significantly higher in white patients and after cadaveric donor transplantation. Surgical complications of transplant surgery are important predisposing factors for incisional hernia after kidney transplantation. Surgical repair using polypropylene mesh is safe and effective in this group of patients.

C4d-Positive Chronic Rejection : A Frequent Entity With a Poor Outcome

Background. Chronic rejection (CR) is an important cause of kidney graft loss. Some studies have suggested the role of antibodies mediating chronic graft dysfunction. In this context, C4d identification is an important tool to evaluate antibody-mediated rejection. Method. This is a retrospective study that analyzed 80 patients with histological diagnosis of chronic allograft nephropathy (CAN) according Banff 97 and no evidence of transplant glomerulopathy. These patients had renal biopsies available for C4d immunoperoxidase staining at the time of diagnosis. Cases were reclassified by the presence of C4d in peritubular capillaries. Results. C4d was negative in 30 cases (37.5%) and positive in 50 (62.5%). C4d+ group had more female and highly sensitized patients (PRA) at transplant. All variables were similar between C4d- and C4d+ cases at diagnosis time, but more C4d+ patients presented proteinuria (>0.3 g/L). Patients were submitted to various immunosuppression regimens after the CAN diagnosis. Four years after the diagnosis, death-censored graft survival was 87% for C4d- and 50% for C4d+ (P=0.002). In the multivariate Cox regression analysis, C4d+, PRA>10%, and vascular intimal proliferation were the variables that present higher relative risk for graft loss. Conclusion. These data indicate that C4d positive chronic rejection is very common, associated with proteinuria, and has a poor outcome. A larger study is warranted to identify which immunosuppressive regimen may modify the poor course of this entity.

KIDNEY TRANSPLANTATION: THE USE OF LIVING DONORS WITH RENAL ARTERY LESIONS

PURPOSE A shortage of organs for transplantation has forced surgeons to optimize the use of marginal organs, such as kidneys with arterial disease. We present a retrospective study of the outcome of donors with renal artery disease and recipients of kidneys from living related and unrelated donors. MATERIALS AND METHODS Kidneys with vascular abnormalities from healthy living donors were grafted into 11 recipients. These kidney transplants comprised 1.8% of those performed at our institution. The vascular abnormalities were aneurysms in 3 cases, atherosclerotic lesions in 4 and fibromuscular dysplasia in 4. After nephrectomy all abnormalities were corrected under hypothermic conditions during bench surgery except in 3 cases of ostial atherosclerotic plaque, which was left in the donors. The renal artery was anastomosed to the external iliac artery in 5 cases and to the internal iliac artery in 6. The ureter was reimplanted using an extravesical technique. RESULTS All patients had immediate diuresis and no delayed post-transplant graft dysfunction was observed. One patient died of an unrelated cause and 3 had post-transplant graft function loss due to acute vasculopathy in 1, post-diarrhea with acute arterial thrombosis in 1 and recurrence of the hemolytic-uremic syndrome in 1. All remaining patients are well with median serum creatinine of 1.4 mg./dl. (normal 0.4 to 1.4). All donors are well and normotensive with normal renal function. CONCLUSIONS The use of kidneys with arterial disease from living donors with unilateral disease is safe. Complete informed consent regarding the risks and benefits by donor and recipient is mandatory.

A strategy to calculate cyclosporin A area under the time–concentration curve in pediatric renal transplantation

Abstract: The complete area under the time–concentration curve (AUC) is considered the gold standard for cyclosporin A (CsA) monitoring, particularly in pediatric kidney graft recipients who have great absorption and drug clearance variability. However, complete AUC is time‐consuming and expensive. For this reason, we retrospectively reviewed 131 complete 4‐h AUC (AUC0−4) performed in 34 children (mean age 10.6 ± 2 yr) in order to construct an equation to calculate AUC0−4. The median time after transplantation was 540 (range: 247–1,358) days. Multiple regression analysis was performed either with a single variable or with a combination of two variables. CsA blood concentration at the second hour after the oral morning dose (C2) was the best predictor of AUC0−4, where 
AUC0−4 = 424 + (2.65 × C2), R2 = 0.81, p < 0.001. Only the combination of C1 and C2 offered mathematical improvement over the C2 equation. The same analysis was made for pharmacokinetic curves performed earlier than 6 months (79 ± 55 days, range 8–169 days) and after 1 yr of transplantation. In both time‐periods, C2 was the best parameter to use to calculate AUC0−4. The equations obtained during these two time‐periods were very close to the one for the whole population. Our data shows that C2 can be safely used to estimate AUC0−4. However, for values above 4,000 ng/h/mL, the formula overestimates the trapezoidal AUC0−4. The C2 equation simplifies the CsA monitoring as a result of its high predictive value and clinical feasibility.

Introduction of mycophenolate mofetil and cyclosporin reduction in children with chronic transplant nephropathy.

Abstract: Chronic transplant nephropathy (CTN) is the most important cause of kidney graft dysfunction. Studies in adult populations have reported a beneficial effect of non‐nephrotoxic mycophenolate mofetil (MMF) on graft function in this setting. However, few studies were reported in children in this setting. We therefore reviewed the charts/medical records of renal transplanted patients < 18 yr of age at a single center who had switched from azathioprine to MMF as a result of progressive loss in graft function, for which vascular, infectious, and urological causes were excluded. Serum creatinine (SCr) and calculated creatinine clearance were compared prior to and after MMF introduction. Thirteen patients (nine male/four female), followed‐up for 59.3 ± 35.4 months after transplantation, were analyzed. Age at MMF introduction was 14.2 ± 3.6 yr. In 11 patients a previous biopsy had shown features of CTN and four patients also presented signs of chronic cyclosporin A (CsA) nephrotoxicity. MMF was started at a dose of 1211 ± 351 mg/day, and the CsA dose was decreased from 6.69 ± 3.15 mg/kg/day 6 months before MMF to 4.8 ± 2.3 mg/kg/day at the time of MMF introduction. CsA was withdrawn in four patients. The median (25–75%) SCr value increased from 1.60 mg/dL (range 1.3 to 1.87 mg/dL) 6 months before MMF to 2.2 mg/dL (range 1.87–2.32 mg/dL) when MMF was introduced. Six months after introduction of MMF, the SCr level had decreased to 1.5 mg/dL (range 1.2–1.8 mg/dL) and remained stable until the last follow‐up (17.5 ± 9.2 months after MMF was started). A similar pattern occured with calculated SCr clearance. There were no acute rejections after changes in immunosuppression. The safety of MMF was also analyzed and in only one patient was the drug stopped as a result of intractable diarrhea. These findings suggest that MMF is sufficiently powerful to allow a decrease/withdrawal of CsA without the burden of acute rejection in a pediatric population with CTN.

Prosthetic repair of incisional hernia in kidney transplant patients. A technique with onlay polypropylene mesh

The employment of synthetic mesh for incisional hernia repair in kidney-transplanted patients is rarely reported in the present literature. Many authors believe that mesh employment in such conditions is not safe due to fear of mesh related complications. From 1965 through 1999, a total of 1685 kidney transplants were performed at our Kidney Transplant Unit and 19 patients developed eventrations in the kidney transplant incision, an incidence of 1.1%. From September 1996 eight of these patients had prosthetic repair of the abdominal wall with onlay polypropylene mesh. All patients were under immunosuppressive therapy with prednisone, ciclosporine and azathioprine. Mean age was 48.8 years, mean body mass index was 22.5 and mean number of previous abdominal operations was 2.5. A large polypropylene mesh (Marlex® mesh) was fixed over the aponeurosis after primary closure of the aponeurotic borders, as an onlay graft. There was neither morbidity nor mortality associated to the surgical procedure. No recurrences or long-term complications associated with mesh employment were verified after a follow-up ranging from one year to three years. We concluded that prosthetic repair of incisional hernia in transplanted patients can be performed routinely.

Surgical aspects of third and subsequent renal transplants performed by the extraperitoneal access

Background. We reviewed our experience with third, fourth, and fifth renal transplants performed by the extraperitoneal access. Methods. The charts of 21 third and subsequent transplants performed extraperitoneally were reviewed. Surgical aspects, the occurrence of rejection episodes, delayed graft function (DGF), graft and patient survival were evaluated and compared with 1560 first transplants in adults with nonmanipulated fossa performed in the same period. Results. Transfusion was necessary in 52% of the retransplants and in 5.7% of the first transplants (P<0.0001). Mean operative time was 327 min for retransplants and 212 min for first transplants (P<0.0001). Surgical complications occurred in 4 patients (19%): two arterial thrombosis and two ureteral obstructions. DGF occurred in 11 patients (52%) among retransplants and in 453 (29%) among first transplants (P=0.028). Acute rejection occurred in 7 (33.3%) retransplants and in 530 first transplant patients (33.9%). The mean serum creatinine among retransplant patients 30 days and one year after transplantation was 2.5 mg/dl and 1.8 mg/dl. One-year graft survival was 57.1% (75% for live and 46% for cadaver donors) for retransplants and 86% for first transplant patients (P<0.0001). Conclusion. Third and subsequent transplants performed extraperitoneally are more time-consuming and require more transfusions in the perioperative period. A higher but acceptable incidence of arterial thrombosis and urinary obstruction were observed. One-year graft survival was better with live donor grafts, but was still lower when compared with first transplants using the same surgical technique.

Radical Retropubic Prostatectomy for Localized Prostate Cancer in Renal Transplant Patients

OBJECTIVE To investigate the feasibility of radical retropubic prostatectomy (RRP) in renal transplant recipients with clinically localized prostate cancer. METHODS A prospective protocol was established between August 2004 and November 2007. In that period, 8 patients diagnosed with localized prostate cancer were submitted to RRP, and their clinicopathologic data were reviewed. RESULTS The mean age (+/- standard deviation) at surgery was 59.6 +/- 6.7 years (range, 49-67 years). All patients had T1C tumors, except for 1 with a T2A tumor. The mean preoperative prostate-specific antigen value was 4.5 +/- 1.8 ng/mL (range, 1.6-7.0 ng/mL). The mean interval between renal transplantation and RRP was 89.9 +/- 65.1 months (range, 40-209 months). The procedure was well tolerated without major complications, and all patients were discharged on the fifth postoperative day. There was no impairment to bladder descent caused by the presence of the allograft or the ureteroneocystostomy. Urethrovesical anastomosis was easily performed in all cases in the standard manner. Blood transfusion was needed in 2 patients (1 received 2 U and another 5 U of blood). The mean operative duration was 183 +/- 29.7 minutes (range, 150-240 minutes), the mean estimated blood loss was 656 +/- 576 mL (range, 100-2000 mL), and no deterioration of graft function was observed. All patients were followed, and the mean follow-up was 10.5 months (range, 2-30 months). Prostate-specific antigen was undetectable in all cases during this time frame. CONCLUSIONS Radical retropubic prostatectomy in renal transplant patients is safe, effective, and can be easily performed in the same manner as described by Walsh, regardless of the presence of the allograft. The only necessary technical modification is the avoidance of ipsilateral lymphadenectomy to prevent damage to the transplanted organ.