Luiz Estevam Ianhez

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.

A MULTI-FACTORIAL BIOLOGICAL MODULATION PROTOCOL THAT AMELIORATES ISCHEMIA-REPERFUSION INJURY SIMULTANEOUSLY REDUCES BILESALT TOXICITY IN PORCINE LIVER TRANSPLANTATION FROM NON-HEART BEATING DONORS

Plasma clearance of 51Cr‐EDTA (51Cr‐EDTA‐Cl) is an alternative method to evaluate glomerular filtration rate (GFR). This study aimed to investigate the concordance between 51Cr‐EDTA‐Cl and renal inulin clearance (In‐Cl) in renal transplant recipients as well to determine the repeatability of 51Cr‐EDTA‐Cl in kidney donors. Forty four kidney recipients and 22 kidney donors were enrolled. Simultaneous measurements of 51Cr‐EDTA‐Cl and In‐Cl were performed. A single dose of 3.7MBq of 51Cr‐EDTA was injected and the plasma disappearance curve was created by taking blood samples at 2, 4, 6 and 8 h after injection. Bland and Altman statistical approach was used to quantify the agreement between In‐Cl and 51Cr‐EDTA‐Cl and to determine the better concordance between all possibilities of measure for the 51Cr‐EDTA‐Cl. The mean of In‐Cl was 44.5 ± 17.9 ml/min/1.73 m2. There was a positive correlation between In‐Cl and all possible measurements of 51Cr‐EDTA‐Cl. 51Cr‐EDTA‐Cl with two samples taken at 4 and 8 h or at 4 and 6 h presenting the narrow limits of agreement and a difference (bias) of 2.8 and 2.7 ml/min, respectively. Two plasma sampling for 51Cr‐EDTA‐Cl was a reliable method to measure GFR compared with In‐Cl and comprises a suitable method to be used in kidney transplanted patients.

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.

Acitretin and skin cancer in kidney transplanted patients. Clinical and histological evaluation and immunohistochemical analysis of lymphocytes, natural killer cells and Langerhans' cells in sun exposed and sun protected skin.

Abstract:  Background:  Renal transplanted recipients have an increased incidence of actinic keratosis and skin cancer.

Polycythemia after Kidney Transplantation

3 patients with renal transplantation who developed polycythemia presented normalization of the hemoglobin levels immediately after nephrectomy of the native kidneys. This observation induced the authors to study the role of the native kidneys in the genesis of polycythemia in recipients of renal allografts. Comparison was made among 32 patients submitted to renal transplantation, with maintenance of native kidneys (group I) and among 31 under the same conditions, but without the native kidneys (group II). Both groups were comparable according to age, sex, rejection crisis incidence and immunosuppressive therapy. It was observed that the hemoglobin levels of group I were significantly higher (p 59Fe), was higher in patients of group I. The authors concluded that the native kidneys are responsible for the observed polycythemia after a kidney transplantation.

The need of mycophenolic acid monitoring in long-term renal transplants.

Abstract:  Background:  There is little information regarding the 12‐h mycophenolic acid (MPA) pharmacokinetics (PK), a way to monitor the drug and the need of frequent monitoring, in stable patients.

Mycophenolate mofetil may protect against Pneumocystis carinii pneumonia in renal transplanted patients

Pneumocystis carinii pneumonia (PCP) is usually prevented in transplanted patients by prophylactic trimethoprim-sulfamethoxazol (TMS). Mycophenolate mofetil (MMF) has been shown to have a strong protective effect against PCP in rats. This effect is also suggested in humans by the absence of PCP in patients receiving MMF. After January 1998 MMF has been used with no TMS prophylaxis in renal transplanted patients. In azathioprine (AZA) treated patients TMS prophylaxis was maintained. The incidence of PCP was analyzed in both groups. Data were collected in order to have a minimum 6-month follow-up. Two hundred and seventy-two patients were eligible for analysis. No PCP occurred either in patients under MMF without TMS prophylaxis nor in patients under AZA. MMF may have an effective protective role against PCP as no patient under MMF, despite not receiving TMS coverage, developed PCP. A larger, controlled, trial is warranted to consolidate this information.

Sampling Strategy to Calculate the Cyclosporin‐A Area Under the Time‐Concentration Curve

The complete area under the time‐concentration curve (AUC) is considered to be the gold standard for cyclosporin‐A (CyA) monitoring. However, complete AUC is time‐ and cost‐consuming. For this reason, we reviewed 259 4‐h AUC (AUC0−4 ) performed in 74 renal transplanted patients in order to construct an equation to calculate AUC0−4. All samples were drawn from one adult population 13 days following transplantation, in order to allow the cyclosporin metabolism to stabilize. Regression analysis was done either with each or with a combination of two variables. Cyclosporin‐A blood concentration at the second hour after the oral dose (C2) was the best predictor of AUC0−4, where AUC0−4= 451 + (2.73 × C2), R2 = 0.87, p < 0.001. The combination of C1 and C2 only, offered a better mathematical improvement to the C2 equation. This equation was further validated in 33 other CyA pharmacokinetic profiles performed in eight patients who had not participated in the equation development. In this new population, the C2 equation excellently predicted the trapezoidal AUC0−4 (R2 = 0.81). Our data shows that C2 can be safely used to estimate AUC0−4. The C2 equation simplifies CyA monitoring because of its high‐predictive value and clinical feasibility.