Julio Pascual

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.

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.

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.

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.

Necrotizing Myositis Secondary to Serratia marcescens in a Renal Allograft Recipient

We describe a fatal case of spontaneous necrotizing myositis due to a highly resistant strain of Serratia marcescens in a renal transplant recipient. Though Staphylococcus aureus and Clostridium are the usual agents which cause either pyomyositis or necrotizing myositis, gram-negative bacteria are a dangerous and rarely suspected possibility. Such an aggressive disease should be promptly recognized because immunosuppression in susceptible hosts makes conservative management unsuccessful. The prognosis for myositis in immunodepressed hosts is poor and wide excision of all the necrotic muscles, leaving the wound open, and intensive antibiotic therapy are required.

A low incidence of new-onset insulin-dependent diabetes mellitus using tacrolimus in kidney recipients in Europe.

Employing tacrolimus (Tac) for routine immunosuppression in renal transplantation (RT), produced an incidence of new-onset, insulin-treated, diabetes mellitus (newDM) as high as 20%. More recently, several large multicenter kidney studies using Tac as the primary immunosuppressant have been reported in Europe. Between 1997 and 2001, we performed 155 RTs using Tac (0.2 mg/k/per day, targeting whole blood trough levels <15 ng/mL) with a rapid steroid taper. The acute rejection rate was 13%, and 89% of grafts are still functioning. Only 5 Tac-treated patients not previously requiring insulin needed insulin therapy for > or =30 days (3.2%). Eight separate studies employing Tac in at least one arm (N=2728) have been reported between 1997 and 2002. Tac was combined with azathioprine or MMF, and/or steroids. The incidence of new DM at study end ranged from 2.3% to 8.3%. The only trial with >6% incidence was the first one, using an initial dose of 0.3 mg/kg per day. The most recent studies utilized an initial dose of 0.2 mg/kg per day, targeting whole blood trough levels of <15 ng/mL and a steroid taper, with newDM at <6%. On the basis of these data, we confirm in that the use of Tac as a first-line immunosuppressant in renal transplant patients affords protection against acute rejection with a low level of newDM. The tendency to employ lower oral doses of Tac, lower blood target levels, and a reduced steroid dose appear to minimize glucose disturbances in RT.

One-center comparison between primary immunosuppression based on neoral cyclosporine and tacrolimus for renal transplantation.

TACROLIMUS is a well-established basic immunosuppressive drug in renal transplantation (RT), but the efficacy and safety comparisons with the new formulation of microemulsified cyclosporine, Neoral, come only from a multicenter study. In the only published 3-month multicenter trial, tacrolimus triple therapy with azathioprine and steroids was associated with less acute rejection episodes (in number and severity) than was triple therapy with Neoral. However, these large multicenter international trials are frequently quite heterogeneous and include too short follow-up. Consequently, they may not reliably reflect the impact of new immunosuppressive regimens on routine clinical practice. We have reviewed the 5-year experience in our unit with RT treated with Neoral or tacrolimus.

Changes in visceral flow induced by laparoscopic and open living-donor nephrectomy: experimental model.

Increased intra-abdominal pressure during laparoscopy changes visceral flow. The objective of the present study was to analyze the changes in peripheral and intra-abdominal flow induced by laparoscopic living-donor nephrectomy in an experimental model. Twenty pigs underwent left-sided nephrectomy, 10 at laparoscopy and 10 in an open approach. Renal blood flow (RBF), hepatic arterial flow (HAF), portal flow (PF), and carotid flow (CF) were measured using an electromagnetic probe placed around these vessels. Comparative analysis between the groups demonstrated increased CF (mean [SD], 125.73 [41.69] vs 291.70 [51.52] mL/min; P < .001) and decreased PF (973.67 [131.70] vs 546.83 [217.53] mL/min; P = .001) and HAF (278.00 [94.71] vs 133.33 [112.32] mL/min; P = .03) in pigs that underwent laparoscopy compared with those who underwent open surgery; no significant differences were observed in RBF. In conclusion, laparoscopic nephrectomy induces increased CF and decreased total hepatic flow, at the expense of PF and HAF. With adequate intravascular volume expansion, no differences were observed in RBF between the laparoscopic and open approaches.

Effects of urodilatin on renal graft blood flow during ischemia-reperfusion syndrome in a pig autotransplant model

FTER KIDNEY PROCUREMENT, during the period of renal ischemia, vasoactive substances are released. During reperfusion of the graft, oxygen free radicals are formed and renal resistances increased. The kidney suffers ischemia-reperfusion injury and intrarenal vasoconstriction. This vascular situation is probably a major cause of delayed graft function, which may increase postoperative morbidity. Alterations in microvascular perfusion are particularly important. Urodilatin is a natriuretic peptide isolated from human urine with a major role in regulation of renal sodium and water excretion. 1 Additional microvascular renal effects, mainly dilatation of afferent renal arterioles and constriction of efferent ones, could be beneficial in the prevention of the ischemia-reperfusion syndrome. 2 We have evaluated the effects of urodilatin administration on main renal graft artery flow just after revascularization. METHODS Eleven male hybrid commercial pigs underwent right nephrectomy on day 0. Kidneys were flushed with Wisconsin solution and stored at 4°C for 24 hours. Contralateral nephrectomy with orthotopic renal transplantation (with the graft previously preserved) was performed on day 1. The period of warm ischemia time was around 40 minutes and the urinary tract was restituted with ureteroureteral suture. Monitoring included continuous arterial pressure through femoral probe and continuous renal graft blood flow (RGBF), with an electromagnetic probe placed on main renal graft artery at the time of revascularization. Urodilatin (HaemoPep Pharma GmbH, Hannover) was infused IV through an ear vein in six animals (bolus just after revascularization and infusion over 45 minutes thereafter) on a dose-finding fashion: bolus 4 ug/kg/min and infusion 1 ug/kg/min (n 1), 2 ug/kg/min and infusion 0.5 ug/kg/min (n 2), and 1 ug/kg/min and infusion 0.3 ug/kg/min (n 3). In control pigs, normal saline was infused in a similar amount.