F.J. Burgos

Influence of immunosuppression on the prevalence of cancer after kidney transplantation.

The prevalence of cancer in renal transplant patients is greater than in the general population. It is influenced by demographic and ethnic characteristics. We performed a retrospective study of 793 patients who received 872 kidney transplants at our center during 23 years. The age at transplantation was 41.4+/-14.0 years, the follow up 75.4+/-69.4 months. The cohorts include 203 patients treated with azathioprine-prednisone; 510, cyclosporine-based therapy; and 159, tacrolimus-based therapy. There were 95 patients (10.9%) who developed at least one neoplasm with 9 having more than one type of tumor. The incidence was of 17.3 cases per 1000 patients-years. Forty-four (46.3%) had skin cancer, 8 (8.4%) Kaposi sarcoma and 43 (45.3%) a non-skin cancer. Seven of eight patients with Kaposi sarcoma were on CsA therapy. The risk of developing a neoplasm at 5, 10, and 15 years was 8%, 17%, and 30% respectively. In a multivariate analysis, the risk factors associated with neoplastic diseases were older age (OR=1.061; 95% CI 1.039-1.084; P=.000), male sex (OR=2.658; 95% CI 1.536-4.599; P=.000), length of follow-up (OR=1.121; 95% CI 1.073-1.172; P =.000), and immunosuppression with CsA (OR=4.448; 95% CI 1.334-14.764; P=.015). Cancer was the cause of death in 26 patients, the fourth most common cause after cardiovascular disease, infection, and liver failure. We conclude that malignancies are an important cause of morbidity and mortality among transplant patients. Special attention must be devoted to older male patients with a long-term follow up to develop preventive and surveillance strategies.

Outcome of cadaveric renal transplant patients treated for 10 years with cyclosporine : Is chronic allograft nephropathy the major cause of late graft loss?

Background. The introduction of cyclosporine (CsA) has improved the short-term outcome of renal transplantation, but its effect on the long-term survival is not well known. Methods. We analyzed 128 cadaveric first renal transplant recipients with CsA and prednisone as basal immunosuppression followed for at least 10 years, and we have compared them with a group of 185 historical patients treated with azathioprine (Aza) and prednisone. Results. The 1-year graft survival was 83% in the CsA-treated patients and 68% in the Aza-treated patients (P <0.025), and the differences were significant for 3 years. Acute rejection accounted for the 10.9% of losses in CsA-treated patients and for 23.8% of losses in Aza-treated patients (P =0.046). Chronic allograft nephropathy was the cause of graft losses in 40.6% and 16.8% of cases (P =0.008). Patient survival at 5 years was 88% in CsA-treated patients and 79% in the Aza-treated patients (P <0.025). When analyzing the data of the 64 CsA-treated patients and the 84 Aza-treated patients with one functioning graft at 10 years, mean serum creatinine values were significantly higher in the CsA-treated patients at all time points but the increases were not significantly different. At 10 years, mean blood pressure was higher (P =0.002), and hypercholesterolemia (P =0.011) and hyperuricemia (P =0.000) were more prevalent in the CsA-treated patients. Conclusions. CsA resulted in a better short-time patient and graft survival that was not maintained in the long-term outcome. Chronic allograft nephropathy was the leading cause of graft loss in CsA-treated patients. Graft function was poorer in the CsA-treated patients, but its decline was similar in the two groups.

Lumbar bone mineral density in renal transplant patients on neoral and tacrolimus: a four-year prospective study.

Background. This prospective study was designed to investigate the long-term evolution of bone mineral density (BMD) in kidney transplant recipients. Methods. In 86 patients with functioning grafts, 65 on tacrolimus-based immunosuppression and 21 on cyclosporine-based immunosuppression, laboratory parameters and BMD measurements in lumbar spine (L2–L4) and femoral neck (FN) were performed by DEXA in the first month after transplantation (baseline) and yearly thereafter up to the fourth year. Results. BMD did not change at 12 months in lumbar spine nor in the FN. Detailed analysis identified three patterns of BMD in lumbar spine at 12 months: BMD remained stable in 27 patients (31.4%), decreased >2% in 31 (36.0%) and increased >2% in 28 (32.6%). Patients with no change or gain presented a parallel increase of BMD in FN (P<0.001 in both groups). On multivariate analysis, the variables associated with no change or lumbar BMD loss were total prednisone dose in grams at 12 months (OR 1.402; 95% CI 1.038–1.893; P=0.028), calcitriol levels at 12 months (OR 0.936; 95% CI 0.892–0.982; P=0.007) and lumbar BMD at baseline (OR 1.006; 95% CI 1.002–1.010; P=0.002). Late treatment with calcium supplements and calcitriol did not improve osteopenia. Conclusions. One third of patients had bone loss mainly during the first year of follow-up. Bone loss was associated to higher baseline BMD, high steroid dose, and lower calcitriol levels at 1 year. Late administration of calcitriol and calcium supplements did not improve posttransplant osteopenia. More than 50% of patients were osteopenic 4 years after transplantation.

Development of urologic de novo malignancies after renal transplantation.

OBJECTIVES The incidence of neoplasms in renal transplant recipients is higher than in general population. The increasing age of donors and recipients also increases the risk of developing malignancies, including genitourinary. The aim of this study is to analyze clinical aspects and management of this complication. MATERIALS AND METHODS We conducted a retrospective analysis of 1365 patients who underwent renal transplantation between 1977 and 2010 who were 44.6 ± 14.9 years old at the time of transplantation. The median follow-up was 95.6 months (range, 18.0-236.0). Data were analyzed for sex, age, time from transplant to diagnosis, location, clinical stage, immunosuppression, treatment, follow-up, and evolution. RESULTS We diagnosed 25 de novo urologic neoplasms (25/1365; 1.8%) in 24 patients, with a median follow-up of 32 months (range, 12.5-51.8) from the diagnosis. Sixteen were male (66.7%) and 8 female (33.3%), with a median age at diagnosis of 59 years (range, 56.0-65.5). The median time between the transplant and the diagnosis of the malignancy was 69 months (range, 40.0-116.5). There were 11 renal cell carcinomas (RCC; 11/25; 44%), 8 in native kidney and 3 in renal allograft; 9 prostate cancers (PCa; 9/25; 36%), 8 localized and 1 metastatic; and 5 transitional cell carcinomas (TCC; 5/25; 20%), 3 in bladder and 2 in renal allograft pelvis. Treatments performed were similar to those used in the nontransplanted population. RCC were treated with radical nephrectomy when affecting the native kidney, partial nephrectomy when affecting the allograft, or immunotherapy when metastatic. Patients with localized PCa were treated with radical prostatectomy, radiotherapy, or androgenic deprivation if there were comorbidities, and those metastatic with hormonal deprivation. Bladder TCCs were treated with transurethral resection or radical cystectomy. Pelvis TCCs affecting the allograft were treated with radical nephroureterectomy of the allograft including bladder cuff and pelvic lymphadenectomy. CONCLUSIONS There exists an increased incidence of urologic tumors in kidney transplant recipients. Conventional treatments of these tumors are technically feasible. The risk of developing these tumors remains even in the long term. Because of their suitability for curative treatments, it is advisable to perform periodic screening for urologic cancers to achieve an early diagnosis.

Endourologic implants to treat complex ureteral stenosis after kidney transplantation.

OBJECTIVE To evaluate the safety and efficacy of nitinol stents and the Detour extra-anatomical ureteral bypass graft in treatment of ureteral stenosis after kidney transplantation. PATIENTS AND METHODS Eighteen kidney transplant recipients with complex stenosis caused by failure of primary treatment or with high surgical risk or a poorly functioning graft (serum creatinine concentration >2.5 mg/dL) were treated using antegrade percutaneous implantation of nitinol stents (n = 16) or extra-anatomical ureteral bypass grafts (n = 3); 1 patient was treated with both techniques. RESULTS Mean (range) follow-up of ureteral stents was 51.2 (3-118) months. Patency rate at last follow-up, resumption of dialysis therapy, or death was 75% (12 of 16 patients). In 4 patients (25%), stent occlusion developed, which was treated using a double-J catheter in 2 patients, stent removal and pyeloureterostomy using the native ureter in 1 patient, and implantation of an extra-anatomical bypass graft in 1 patient. Mean follow-up in patients with extra-anatomical ureteral bypass grafts was 32 (8-64) months. One patient developed a urinary tract infection, and another had encrustation with obstruction. CONCLUSIONS Use of nitinol ureteral stents and extra-anatomical ureteral bypass grafts is a safe and effective alternative to surgery for treatment of post-kidney transplantation ureteral stenosis in patients with chronic graft dysfunction, those at high surgical risk, and those in whom previous surgical treatment has failed.

Effects of the new immunosuppressive agents on the occurrence of malignancies after renal transplantation.

INTRODUCTION The risk of malignancies in renal transplant recipients is considerably greater than in the general population. The purpose of the present study was to investigate the effects on the appearance of malignancies of 3 immunosuppressive periods: azathioprine (AZA), cyclosporine (CsA), and tacrolimus (TAC). PATIENTS AND METHODS This study included 1029 first renal transplant recipients of mean age at transplantation of 44.6±14.9 years with a mean follow-up of 95.6±84.2 months. Initial immunosuppression was AZA-based (n=198), CsA-based (n=524), and TAC (n=307). A total of 280 recipients were also treated with mycophenolate mofetil or mycophenolic acid. RESULTS There were 157 patients (15.3%) who displayed≥1 malignancy; there were 95 skin (9.2%) and 74 (7.8%) non-skin malignancies with presentations at 74±62 and 107±77 months, respectively (P=.003). The skin malignancies included squamous cell carcinomas (n=41), basal cell carcinomas (n=41), Kaposi sarcomas (n=7), and melanomas (n=4). Among the solid tumors, lymphoproliferative disorders (n=15), digestive tract (n=14), kidney and urinary tract (n=11), lung (n=10), and breast (n=3) carcinomas. The cumulative incidences at 5, 10, and 15 years were 6%, 10%, and 18% for skin and 3%, 7%, and 14% for non-skin malignancies, respectively. Multivariate analysis showed that age at transplant in years (P=.000) and male gender (P=.000) were the only variables associated with skin malignancies; age at transplant in years (P=.004) and treatment with OKT3 (P=.000) were associated with non-skin malignancies. Malignancies were the cause of death in 18% of recipients who died with functioning grafts. CONCLUSION Malignancies are an important cause of morbidity and mortality among renal transplant recipients. The new immunosuppressive agents do not increase the risk of malignancies. Special surveillance is needed for older, male recipients.

Influence of laparoscopic live donor nephrectomy in ischemia–reperfusion syndrome and renal function after kidney transplantation: an experimental study

The increase of intra-abdominal pressure during laparoscopic techniques provokes oliguria and reduction of the renal blood flow (RBF). The aim of this study is to evaluate this effect during living donor nephrectomy and its influence in the ischemia-reperfusion syndrome and renal function after kidney transplantation. Autotransplantation was performed using 22 pigs (15 after conventional open nephrectomy and 7 after laparoscopic nephrectomy). During donor nephrectomy a significant reduction in RBF was observed in the laparoscopic group (70 mL/min) vs the open group (260 mL/min) (P<.05). After a cold ischemia period of 24 hours an autotransplantation was performed. During the first hour after revascularization RBF was lower for the laparoscopic than for the open group: 60 vs 180 mL/s at 1 minute and 160 vs 400 mL/s at 60 minutes (P<.05). The decrease of creatinine was slower for the laparoscopic than for the open group during the first posttransplant week (2 vs 1.3 mg/dL on the first day and 1.4 vs 0.8 mg/dL on the seventh day posttransplant, respectively) (P<.05).

Renal transplant recipient outcome after losing the first graft

Renal transplantation is the optimal therapy for end-stage renal failure and considerable attention has been given to graft and patient survival and the effectiveness of immunosuppressive regimens. However, little attention has been given to outcome for patients who lose their grafts. We retrospectively reviewed the outcomes of the 793 first renal transplants performed at our institution between November 1979 and December 2001. A total of 348 patients lost their grafts, 116 by death with a functioning graft (33.3%) and 232 patients for other causes (66.7%). Eighty-six patients (37.1%) received a second transplant 3.5+/-2.4 years after returning to dialysis and the remainder continued on dialysis. Retransplanted patients were younger at the time of the first transplant (P=.000), and both time on dialysis (P=.012) and duration of graft function (P=.057) were shorter than for those remaining on dialysis. Therefore, retransplant patient survival at 1, 5, and 10 years was better than among those patients on dialysis not included on the waiting list (P<.001), but when compared with the relisted patients the survival rate was almost identical (96%, 85%, and 67% vs 97%, 82%, and 67%; P=NS). Almost 40% of patients who lost their first grafts were retransplanted. We did not observe differences in patient survival between retransplant and relisted patients. Because the number of cases is limited, our results need to be confirmed by larger series.

Risk Factors for Early Renal Graft Thrombosis: A Case-Controlled Study in Grafts From the Same Donor

Renal graft thrombosis is an important cause of early graft loss. In a case-controlled analysis including only thrombosed kidneys and their counterparts from the same donors, we found that the right kidney as opposed to the left kidney was the only risk factor for early graft vascular thrombosis. No other recipient, donor, or perioperative factor was significantly associated with the complication. Our findings suggested that implantation of a right kidney might be followed by prophylactic anticoagulant or antiaggregant therapy.

Cytomegalovirus infection after renal transplantation: selective prophylaxis and treatment

We have reviewed our experience in selective cytomegalovirus (CMV) infection prophylaxis and treatment in our renal transplant population. Between 1996 and 2001, 263 cadaveric renal transplant recipients had at least 6 months follow up. Immunosuppression was based on cyclosporine Neoral (n=108) or tacrolimus (n=155). CMV infection prophylaxis (oral acyclovir or gancyclovir at half usual doses) was only prescribed in recipients receiving a CMV positive ve kidney and in recipients treated with OKT3. CMV infection was diagnosed by a positive pp65 antigenemia upon appearance of CMV-related symptoms, leading to specific treatment (IV ganciclovir) only if symptoms were intense or there was visceral involvement. Thus, no preemptive treatment or programmed or periodic antigenemia was performed in any case. Nineteen episodes of symptomatic CMV infection were diagnosed (prevalence 7.2%). The frequency was similar for all immunosuppressive regimens. Only 9 of 19 (47%) of patients were given IV ganciclovir; the others were not treated. All patients survived without apparent complications, relapses, or recurrences. No oral gancyclovir was delivered after IV treatment. Our CMV prophylaxis protocol was limited to high-risk patients, using lower gancyclovir dosages than those usually advocated. It does not include programmed or scheduled search for CMV antigenemia in asymptomatic renal transplant patients. Despite these factors, our CMV infection rate and severity were similar to those reported with more aggressive protocols, with extended prophylaxis, preemptive therapy, or intense surveillance.