Sublingual administration of tacrolimus in a renal transplant patient.

Tacrolimus is used in renal and other organ transplantations for immunossupression therapy. Bioavailability of enterally administered tacrolimus is poor, and further reduced by gastrointestinal failure or enteral nutrition. In these situations, intravenous administration is necessary to prevent treatment failure. However, intravenous administration should be done in a continuous manner and it has been implicated in anaphylaxis, torsades de pointes, cardiac arrhythmia and other serious adverse events. Also it is more expensive than other routes of administration. Sublingual administration of tacrolimus has been used in some cases, and literature reports show that it provides therapeutic tacrolimus levels in lung and liver transplant recipients. Here, we report a first case of sublingual administration of tacrolimus in kidney transplantation.

Renal function in patients with cadaveric kidney transplants treated with tacrolimus or cyclosporine.

INTRODUCTION: Renal function predicts graft survival in kidney transplant patients. This study compared the 2-year evolution of renal function in patients treated with cyclosporine or tacrolimus in combination with mycophenolate mofetil (MMF) and prednisone. METHODS: We studied 1558 cadaveric renal transplant recipients from 14 Spanish hospitals between January 2000 and December 2002. Of these, 1168 were treated with tacrolimus and 390 with cyclosporine. The primary efficacy endpoint was long-term renal function. Renal function was measured by serum creatinine and glomerular filtration rate (GFR) by creatinine clearance calculated from the Cockcroft-Gault formula. This report summarizes the 2-year results. RESULTS: At 24 months the tacrolimus group showed significantly better serum creatinine (1.5 +/- 0.7 vs 1.8 +/- 0.8 mg/dL, P < .001) and GFR (60.5 +/- 20.9 mL/min vs 47.9 +/- 10.0, P < .001) than the cyclosporine group. Additionally, recipients with ideal graft donors (23.5 +/- 2.8 vs 24.0 +/- 2.9 years) had a better serum creatinine at 2 years (1.23 +/- 0.2 vs 1.5 +/- 0.4 mg/dL, P < .05). Multivariate analysis showed that tacrolimus was an independent factor associated with better renal function: odds ratio 1.6, 95% confidence interval (1.2 to 2.2), P < .001. CONCLUSIONS: Patients with a renal transplant treated with tacrolimus in combination with MMF and prednisone displayed better renal function at 2 years than those who received cyclosporine.

[Intravenous immunoglobulin: another therapeutic application]. / Inmunoglobulina intravenosa: una nueva aplicación terapéutica.

Intravenous immunoglobulin (IVIG) has immunoregulatory functions. In renal transplant, IVIG has been used as an immunosupressor agent only during short period of time and frequently associated to others immunosupressor drugs. In renal transplant IVIG has been used to treat refractory rejection but not as maintenance immunosupressor treatment. We report a case in which IVIG was used as principal immunosupressor agent close to low doses of iv methylprednisolone. The patient could not receive anything by oral way during three months, so she only could be treated by intravenous way. It is the first time that IVIG is used as maintenance immunosupressortreatment for a long time (three months) without secondary effects.

[Orthotopic renal transplant: our experience]. / Revision del trasplante renal ortotópico en nuestro centro.

UNLABELLED: Orthotopic renal transplant (ORT) is useful in cases of severe atherosclerosis, heterotopic bilateral transplant, unsuitable pelvic vessels and in aortic thrombosis, but it is not available in all the institutions and it is only realized of exceptional form. AIM: To review the indication, surgical technique and outcome of the ORT at our hospital. MATERIAL AND METHODS: The studied included five cases between January 1990 and December 2005. We analyzed several variables: demographic characteristics, characteristics of the donor, ischemia times, evolution of renal function and morbi-mortality associated. RESULTS: Left ORT was performed in three men and two women. Mean patient age was 52+/-5 years, all the patients received kidneys from cadaveric donors. Mean creatinine and urea one month postoperative were 2.2+/-0.72 mg/dl and 103+/-17.2 mg/dl and at 6 months postoperative were 1.8+/-0.59 mg/dl and 78+/-14 mg/dl respectively. Immediately all patients received prophylaxis with low molecular weight heparin but it was indicated antiaggregation to two patients when they left the hospital, anticoagulation to two patients and to one of them was decided to anticoagulation nor antiagregation for history of bled digestive. A patient died for bleeding episode at level of the renal graft six months after the transplant, she was in treatment with dicumarinics, they were indicated by venous deep thrombosis in right leg. The survival a year is 80 % of the graft and the patient. Only two patients returned to hospital later, one of them for presenting an episode of diverticulitis and the other one for renal obstructive failure that needed laying of catheter pig-tail. Four patients presented stenosis of renal native vassels detected in control magnetic nuclear resonance, not symptomatic. There are two patients who take more than three years transplanted with renal stable function (creatinina 1.3 mg/dl and 1.4 mg/dl respectively). CONCLUSION: ORT is an excellent option in patients with co-morbidity increased for atherosclerosis and that cannot be placed in the iliac fossaes.

Posttransplant diabetes mellitus in renal allograft recipients: A prospective multicenter study at 2 years.

The purpose of this study was to investigate the incidence and risk factors for the development of diabetes mellitus after kidney transplantation (PTDM). A total of 1783 nondiabetic renal allograft recipients transplanted from January 2000 to December 2002 were included. Diabetes was diagnosed following American Diabetes Association criteria. While 1276 patients were treated with tacrolimus (Tac), mycophenolate mofetil (MMF), and steroids, 507 patients received cyclosporine-ME (CsA), MMF, and steroids. PTDM incidence at 6, 12, and 24 months was 14.2%, 12.8%, and 13.3%, respectively. Cumulative incidence during the follow-up was 21.6%. Only 121 of the diabetic patients (47.6%) at 6 months remained diabetic at 24 months. Furthermore, 60 patients of 116 patients on insulin at 6 months (51.7%) remained on treatment at 24 months. The cumulative incidence of PTDM was similar in the two immunosuppressive treatments (19.7% on CsA-MMF vs 22.3% on Tac-MMF; P = NS). However, at 24 months, 14 of 50 diabetic patients on CsA-MMF (28%) and 74 of 161 patients on Tac-MMF (45.9%) were on insulin treatment (P < .05). By Cox regression analysis, age older than 60 years (RR 1.61; 95%CI 1.28-2.04; P < .001), body mass index (BMI) > 30 kg/m2 at transplantation (RR 1.66; 95%CI 1.27-2.16; P < .001), and immunosuppression with Tac (RR 1.30; 95%CI 1.02-1-66; P = .033) were associated with PTDM. In conclusions, the incidence of PTDM at 24 months in immunosuppressive protocols including MMF is about 22%, and it is associated with older age, increased BMI, and immnunosuppression with Tac.

Vaccination against hepatitis B in renal dialysis units: short or normal vaccination schedule?

Three I.M. injections of hepatitis B vaccine (Merck Sharp & Dohme) were administered, according to the recommended schedule (0, 1, 6 mos), to seronegative individuals of one renal dialysis unit (33 patients, 58 health care personnel) and, according to a shorter regimen (0, 1, 3 mos), in another unit of similar characteristics (30 patients, 53 health care personnel). Staff members and renal patients received, respectively, 20 y 40 mcg of vaccine per injection. In the early vaccination phase, the two regimens did not lead to a difference in seroconversion rates nor in anti-HBs titers. After a 9-month surveillance, lower seroconversion rates, although not significant, were observed with the accelerated regimen among staff members (84.2%) and renal patients (79.2%) as compared with 93% and 87.5%, respectively, following the normal schedule. At the same time, anti-HBs titers were significantly lower (p less than 0.001) in the staff (316 RIA U) and patients (93 U) vaccinated according to the short regimen than in their respective counterparts (4196 and 1047 U) assigned to the normal schedule. A fourth dose of vaccine given to subjects with low and no anti-HBs titers significantly increased seroconversion and anti-HBs levels, although with little success among the former non-responders.

Hemolytic uremic syndrome in a patient with gastric adenocarcinoma: partial recovery of renal function after gastrectomy.

We report on a patient with gastric adenocarcinoma and severe renal failure caused by hemolytic uremic syndrome with predominantly vascular involvement. Evolution was favorable with partial recovery of renal function after tumor excision and administration of fresh plasma. Although microangiopathic hemolytic anemia is frequently associated with solid tumors, the appearance of a typical hemolytic uremic syndrome with carcinoma is exceptional.

Peritoneal functional parameters after five years on continuous ambulatory peritoneal dialysis (CAPD): the effect of late peritonitis.

Functional stability of the peritoneum is essential for patients on long-term continuous ambulatory peritoneal dialysis (CAPD) treatment. Sixteen patients on CAPD treatment for at least 4 years were studied. Their mean age was 47 +/- 15 years, 5 were males, and none were diabetic. Residual creatinine clearance at the beginning was 2.1 +/- 2.6 mL/min. Once yearly since starting CAPD, we have evaluated their peritoneal ultrafiltration (UF) and diffusion capacities by calculating the peritoneal mass transfer coefficient (MTC, mL/min) for urea and creatinine. Patients were categorized so that we could distinguish the effect of peritonitis, betablockers, and hypertension. For all patients the average initial and final MTCs and UF values were not different. Early episodes of peritonitis (those occurring less than 36 months after starting CAPD) did not influence long-term function. However, late peritonitis (occurring greater than 36 months since initiation) induced a decrease in urea-MTC (22.3 +/- 6 to 15.8 +/- 3.9, p less than 0.05), creatinine-MTC (9.4 +/- 3.1 to 7.4 +/- 2.5, p less than 0.05), and a corresponding increase in UF (1.25 +/- 0.4 to 1.4 +/- 0.3, mL/min, p less than 0.05). Age, sex, betablockers and hypertension did not influence the peritoneal parameters followed. After 5 years on CAPD, functional stability of the peritoneum is evident, except for patients who suffer late episodes of peritonitis. We speculate that the peritoneum in patients who have been on long-term CAPD are more susceptible to injuries, such as peritonitis, and that this results in functional deterioration.

Posttransplant CD30 (Ki-1)-positive anaplastic large cell lymphoma. Report of a case with presentation as a pleural effusion.

BACKGROUND: Posttransplant lymphoproliferative disorders (PTLDs) are almost always of B-cell derivation and have a strong association with Epstein-Barr virus (EBV). Only rare cases of CD30 (Ki-1)-positive anaplastic large cell (ALC) lymphomas in transplant recipients have been described. EBV has been studied in few of these cases. Pleural effusion is an uncommon clinical manifestation of both PTLDs and CD30-positive ALC lymphoma. CASE: A 60-year-old, male renal transplant recipient presented with fever and pleural effusion. Cytologic examination of the effusion revealed a large cell lymphoma. Immunocytologic studies disclosed a T-cell phenotype. Subsequently a cutaneous lesion and an accessory spleen were observed, and cervical lymphadenopathies developed. Fine needle aspiration of lymph nodes confirmed the presence of lymphoma. Histologic and immunohistochemical studies of the lymph nodes, skin and accessory spleen revealed the presence of CD30-positive, T-cell, ALC lymphoma. No EBV DNA was detected by polymerase chain reaction analysis. Despite chemotherapy, the patient died seven months after the initial cytologic diagnosis of lymphoma. CONCLUSION: CD30-positive ALC lymphomas are an uncommon variant of PTLDs that should be considered in the differential diagnosis of neoplastic disorders arising in immunosuppressed patients. Cytology and immunocytochemistry are useful diagnostic procedures for their early detection.

[Acute renal failure caused by cholesterol embolism in kidney transplantation from cadaver donor. Is the prognosis more favorable than in native kidneys?]. / Fracaso renal agudo por embolismo de colesterol (EC) en injerto renal de donante cadáver. Pronóstico más favorable que en riñones nativos?

We present the case of a 47 years old women with a third cadaveric kidney transplant. After surgery, she had effective diuresis reaching a serum creatinine of 2.2 mgs% at 19 postoperative day. In the nest few days, the patient was oliguric with worsening of renal function. The ultrasound examination excluded urinary obstruction. With the suspicion of acute rejection, a renal biopsy was performed. The histopathological record disclosed cholesterol emboli with a widespread multifocal ischemic infarct and eosinophilic tubulointerstitial nephritis. The renal function deteriorated in the seven next days and peritoneal dialysis was carmedow. She then recovered diuresis with improvement of renal function, reaching at discharge a serum creatinine of 1.8 mgs%. The renal function remains stable after 3 years. We analysed the etiopathogenic factors of this disease and the possible beneficial effects of immunosuppresive drugs in better prognosis compared with the same entity in native kidneys.

[Calcineurin-inhibitor-free immunosuppression in early renal transplantation]. / Terapia inmunosupresora en trasplante renal de novo sin anticalcineurínicos.

Calcineurin inhibitors are one of the most common drugs used for prevention of acute rejection in recipients of renal allografts. New immunosuppressors have reduced the incidence of acute renal allograft rejection. There have been numerous recent attempts to develop alternative patterns of immunosuppressors for prevention of chronic renal allograft failure, and enhancing its survival. We described a patient who developed numerous complications after the initial postransplant period. He was treated with a calcineurin inhibitors-free immunosuppression in order to avoid nephrotoxicity, but had over 30 ng/ml of sirolimus. Renal function was impaired after cyclosponne withdrawal. Sirolimus was used in association with mycofenolate mofetil and prednisone.

Prophylaxis and treatment of cytomegalovirus infection postrenal transplantation in two Madrid units.

INTRODUCTION: Complete prevention of cytomegalovirus (CMV) disease continues to be an unresolved problem in renal transplantation. MATERIALS AND METHODS: From January 2005 to May 2006, we implemented a protocol for early detection and preemptive treatment of CMV infection as detected by antigenemia or polymerase chain reaction determined every 2 weeks during the first 3 months posttransplant and monthly thereafter. Prophylaxis was given to all CMV-negative patients who received CMV-positive kidneys and to those who received polyclonal or monoclonal antibody induction therapy. RESULTS: Among 100 transplants, 15 subjects received prophylaxis due to poly- or monoclonal antibody induction and/or negative recipient serology using a mean valgancyclovir dose of 485 +/- 276 mg/d for an average duration of 129 days. After completion of the prophylaxis four patients (26.6%) required preemptive therapy for asymptomatic virus reactivation; the mean dose of drug in these patients had been 450 +/- 275.56 mg, with a treatment time that was significantly shorter than those not suffering reactivation (91.75 vs 143.45 days). In addition, preemptive therapy was given for virus reactivation in seven patients, for illness with mild viral syndrome in two, with moderate illness and positive pretransplantation serology in one. The average treatment time was 79 days and the mean dose was 375 mg. CONCLUSION: In those not at risk, CMV infections occurred among 11.7% of patients in our early detection program. Prophylaxis for at-risk patients should continue for more than 3 months to prevent reactivation.

The fibroblastic nature of dermatofibrosarcoma protuberans. A tissue culture and ultrastructural study.

Dermatofibrosarcoma protuberans has been considered to be of fibrohistiocytic or fibroblastic origin. The purpose of this paper is to identify the original cell strain from which this neoplasm derives, using tissue culture and electron microscopic methods. Thirteen cases of DFSP characterised by clinical, topographical, histological and behavioral criteria were explanted. The emigrating cells were bipolar with two opposed processed and showed a radial arrangement in respect to the explants. After the second week the distal processes tended to curve back towards the cell body forming flame-like structures. This cell morphology and cellular orientation persisted during the whole life of the culture. Electron microscopy was performed in three cases; the newly grown cells maintained an electron microscopic picture similar to that found in the original tumors. This pattern of behaviour is characteristic of fibroblastic tumors and has been found in explants of normal fibroblasts, of fibromatosis and of fibrosarcomas used as controls. On this basis, we believe that DFSP is a fibrosarcoma of the skin of low grade malignancy.

Mycobacterium chelonei peritonitis due to hematogenous dissemination in a continuous ambulatory peritoneal dialysis patient.

Renal failure patients have been found to have a special susceptibility to Mycobacterium infections. In patients undergoing peritoneal dialysis, Mycobacterium chelonei peritonitis, due to penetration through the peritoneal catheter lumen, has been described. In our report, we described a case of disseminated M chelonei infection that began in a Thomas hemodialysis prosthesis and finally resulted in peritonitis of hematogenous origin. The diagnostic and therapeutic peculiarities are discussed.

The influence of hepatitis B and hepatitis C virus infection in the recipient on late renal allograft failure.

BACKGROUND: Chronic liver disease is one of the most important complications after renal transplantation. Hepatitis B and mainly hepatitis C are the more frequent causes of liver disease. Although there are controversial results, in some series, hepatitis B and hepatitis C are associated with lower graft and patient survival. PATIENTS AND METHODS: A total of 3365 adult patients who received a renal transplant in 1990 (N = 824), 1994 (N = 1075) and 1998 (N = 1466) with a functioning graft after the first year were included. Fifty-one (2.1%) with positive HbsAg were diagnosed with hepatitis B at transplantation; 488 (16.9%) presented positive anti-hepatitis C antibodies and were diagnosed with hepatitis C virus (HCV) infection and 25 patients (0.8%) were diagnosed with concomitant hepatitis B virus (HBV) and HVC infection. Demographic, immunosuppression, survival figures and post-transplant and follow-up data of these patients and negative HBV and HVC patients were recorded. RESULTS: The overall prevalence of HBV in the recipients was 2.1%. Patient survival was lower and liver disease was the main cause of death in HBV-positive patients. However, in the multivariate analysis the presence of positive HbsAg did not have an independent risk factor for graft loss and patient death. This finding was similar in patients with concomitant HBV and HVC infection. Graft and patient survival were lower in HCV-positive patients and liver disease was the main cause of death. Interestingly, proteinuria and serum creatinine were risk factors for graft loss and patient death. Fortunately, prevalence of HCV in the recipients significantly decreased from 29% in 1990 to 10% in 1998. CONCLUSIONS: In the last decade in Spain, HBV infection in the recipients, showing an overall prevalence approximately 2%, did not influence graft and patient survival. However, HCV infection in the recipient was associated with lower graft and patient survival, although the prevalence of HCV clearly decreased from 29% in 1990 to 10% in 1998.