R. Marcén

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.

Evolution of Serum Erythropoietin after Androgen Administration to Hemodialysis Patients: A Prospective Study

A prospective study of the evolution of serum erythropoietin level after androgen therapy was carried out in a group of 25 male patients on chronic hemodialysis treatment with nonferropenic anemia (serum ferritin > 50 ng/ml). The androgen used was nandrolone decanoate (200 mg/week intramuscularly, for 6 months). There was an increase of serum erythropoietin, that reached statistical significance in the 2nd week of treatment (8.6 +/- 6.4 vs. 14.2 +/- 9.8 mIU/ml, p < 0.05), and a stabilization after 1 month (1 month: 17.8 +/- 11.2 mIU/ml, 6 months: 19.6 +/- 14.9 mIU/ml). The hemoglobin also experienced a parallel increase to that observed in serum erythropoietin (basal value: 8 +/- 0.9 g/dl; at 1 month postandrogen: 9.2 +/- 1.3 g/dl, p < 0.001; at 6 months: 10.7 +/- 1.8 g/dl, p < 0.001). According to their response of serum erythropoietin the patients were divided into responders (15 patients) and nonresponders (10 patients). There were no differences between them concerning age, basal levels of serum erythropoietin and hemoglobin, and dose of nandrolone decanoate in relation to body weight. The evolution of hemoglobin was similar in both groups, and a correlation between serum erythropoietin and hemoglobin was not observed in the responder group. Fourteen patients were studied after androgen was discontinued. The serum erythropoietin returned to basal levels 6 weeks after the last dose of nandrolone decanoate (7.7 +/- 5.4 mIU/ml). However, hemoglobin was above the basal levels 16 weeks after discontinuing androgen (9.5 +/- 1.1 g/dl, p < 0.05), with no differences between the responder and nonresponder group.(ABSTRACT TRUNCATED AT 250 WORDS)

Endourologic implants to treat complex ureteral stenosis after kidney transplantation.

OBJECTIVEnTo evaluate the safety and efficacy of nitinol stents and the Detour extra-anatomical ureteral bypass graft in treatment of ureteral stenosis after kidney transplantation.nnnPATIENTS AND METHODSnEighteen 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.nnnRESULTSnMean (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.nnnCONCLUSIONSnUse 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.

INTRODUCTIONnThe 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).nnnPATIENTS AND METHODSnThis 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.nnnRESULTSnThere 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.nnnCONCLUSIONnMalignancies 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.

Differences between Blood Flow as Indicated by the Hemodialysis Blood Roller Pump and Blood Flow Measured by an Ultrasonic Sensor

Background/Aim: The ultrasonic transit time is currently the best method for measuring the blood flow rate in the extracorporeal hemodialysis circuit. The purpose of this study was to analyze the differences between blood flow as indicated by the hemodialysis blood roller pump (prescribed blood flow) and by an ultrasonic flowmeter (delivered blood flow). Methods: The ultrasonic blood flow was measured in 20 patients on chronic hemodialysis who were dialyzed through an arteriovenous fistula. During each dialysis session the ultrasonic blood flow was measured at three different blood roller pump flow rates (300, 350, and 400 ml/min). In order to analyze the influence of inflow and outflow pressures on blood flow, this study was conducted during nine consecutive dialysis sessions during which needles of different sizes were used. Results: The ultrasonic flow was always lower than indicated by the blood roller pump: 265 ± 12, 304 ± 15, and 341 ± 19 ml/min for blood roller pump flow rates of 300, 350, and 400 ml/min, respectively (variability: –11.6, –13.1, and –14.8%, respectively). An univariate regression analysis showed that the reduction in flow recorded ultrasonically correlated with both venous blood line pressure (r = –0.2679, p < 0.001) and negative arterial blood line pressure (r = 0.6773, p < 0.001). By multivariate analysis, only the arterial blood line pressure has a predictive value. When all measurements were grouped by arterial blood line pressure ranges, the variability between ultrasonic blood flow and blood roller pump flow was found to be similar in those groups with the same arterial blood line pressure, regardless of the blood roller pump flow rate. Conclusions: The blood flow indicated by the dialysis blood roller pump is always greater than the delivered blood flow, and this difference is in turn conditioned by the negative pressure induced by the blood roller pump in the arterial blood line.

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.

Comparison of C0 and C2 cyclosporine monitoring in long-term renal transplant recipients

Recent data show that monitoring cyclosporine A (CsA) concentrations with 2-hour postdose levels (C2) correlates with the incidence of rejection and graft outcome in de novo renal transplant patients. The purpose of the present work was to evaluate the advantage of C2 monitoring after the first year of kidney transplantation. We studied 161 patients, 96 on CsA-prednisone and 65 on triple therapy (Aza or MMF) who had been transplanted for a mean of 103+/-44 months. Mean serum creatinine (SCr) was 1.65+/-0.69 mg/dL, mean C0 was 174+/-44, and C2 was 667+/-194 ng/mL. Patients were classified according to C2 values: >850 (n=29), between 850 and 450 (n=109), and <450 (n=23) ng/mL. Patients with C2 <450 ng/mL displayed higher SCr values (1.97+/-0.99; 1.59+/-0.51; 1.52+/-0.4 mg/dL; P<.001), received lower CsA doses (172+/-54; 207+/-54; 227+/-56 mg/d, P<.01), showed lower C0 levels (155+/-48; 172+/-41; 199+/-45 ng/mL; P< .001), and included more patients on triple therapy (54.5%; 44%; 17.2%; P<.05). We found weak correlations between C0 and C2 (r=0.37), between C2 and CsA dose (r=0.36), and between C0 and SCr (r=-0.37). Among 117 patients followed up for 1 year with several C0 and C2 measurements, the coefficient of variation of C0 was 17% and of C2 was 21%. Graft functional deterioration occurred in 16 patients independent of the differences among the C2 groups, but 7 recipients (43.7%) had C0 <150 ng/mL and C2/C0 >5. We conclude that C2 in monitoring stable patients needs further evaluation.