E. Rodrigo

Creatinine Reduction Ratio on Post-Transplant Day Two as Criterion in Defining Delayed Graft Function

Delayed graft function (DGF) is a common complication after renal transplant, affecting its outcome. A common definition of DGF is the need for dialysis within the first week of transplantation, but this criterion has its drawbacks. We tried to validate an earlier and better defined parameter of DGF based on the creatinine reduction ratio on post‐transplant day 2 (CRR2). We analyzed the clinical charts of 291 cadaver kidney recipients to compare the outcome of patients with immediate graft function (IGF), dialyzed patients (D‐DGF) and nondialyzed CRR2‐defined DGF patients (ND‐DGF) and to identify risk factors for D‐DGF and ND‐DGF.

ImmuKnow as a diagnostic tool for predicting infection and acute rejection in adult liver transplant recipients: A systematic review and meta‐analysis

Immune status monitoring of transplant recipients could identify patients at risk of acute rejection, infection, and cancer, which are important sources of morbidity and mortality in these patients. The ImmuKnow assay provides an objective assessment of the cellular immune function of immunosuppressed patients. Inconclusive results concerning the ability of the ImmuKnow test to predict acute rejection and infection have raised concerns about the predictive value of ImmuKnow in liver transplant recipients. We conducted a systematic literature review to identify studies published up to March 2012 that documented the use of ImmuKnow for monitoring immune function in liver transplant recipients. The study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 score. We identified 5 studies analyzing ImmuKnow performance for infection and 5 studies analyzing ImmuKnow performance for acute rejection. The pooled sensitivity, specificity, positive likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 83.8% [95% confidence interval (CI) = 78.5%‐88.3%], 75.3% (95% CI = 70.9%‐79.4%), 3.3 (95% CI = 2.8‐4.0), 14.6 (95% CI = 9.6‐22.3), and 0.824 ± 0.034, respectively, for infection and 65.6% (95% CI = 55.0%‐75.1%), 80.4% (95% CI = 76.4%‐83.9%), 3.4 (95% CI = 2.4‐4.7), 8.8 (95% CI = 3.1‐24.8), and 0.835 ± 0.060, respectively, for acute rejection. Heterogeneity was low for infection studies and high for acute rejection studies. In conclusion, the ImmuKnow test is a valid tool for determining the risk of further infection in adult liver transplant recipients. Significant heterogeneity across studies precludes the conclusion that ImmuKnow identifies liver transplant patients at risk for rejection. Liver Transpl 18:1245–1253, 2012.

Assessment of glomerular filtration rate in transplant recipients with severe renal insufficiency by Nankivell, Modification of Diet in Renal Disease (MDRD), and Cockroft-Gault equations

Measurement of glomerular filtration rate (GFR) is time consuming and cumbersome. Several formulas have been developed to predict creatinine clearance (CrCl) or GFR using serum creatinine (Cr) concentrations and demographic characteristics. However, few studies have been performed to discern the best formula to estimate GFR in kidney transplantation. In this study, Cockroft-Gault (CG), Nankivell, and Levey (MDRD) formulas were tested to predict GFR in 125 cadaveric renal transplant patients with severe renal insufficiency (GFR less than 30 mL/min per 1.73 m2). The GFR was estimated as the average Cr and urea clearances. The mean GFR estimated by averaged Cr and urea clearances (22.18+/-5.23 mL/min per 1.73 m2) was significantly different from the mean values yielded by the MDRD formula (20.42+/-6.65 mL/min per 1.73 m2, P=.000), the Nankivell formula (30.14+/-11.98 mL/min per 1.73 m2, P=.000), and the CG formula (29.42+/-8.64 mL/min per 1.73 m2, P=.000). The MDRD formula showed a better correlation (R=0.741, P=.000) than the CG (R=0.698, P=.000) and the Nankivell formulas (R=0.685, P=.000). Analysis of differences using the Bland-Altmann method demonstrated that MDRD gave the lowest bias (MDRD: -1.65+/-4.4 mL/min per 1.73 m2; CG: 7.33+/-6.24 mL/min per 1.73 m2; Nankivell: 8.05+/-9.23 mL/min per 1.73 m2) and narrower limits of agreement (Nankivell: -10.41-26.51 mL/min per 1.73 m2; CG: -5.15-19.81 mL/min per 1.73 m2; MDRD: -10.61-7.31 mL/min per 1.73 m2). In transplant patients with severe renal insufficiency, the MDRD equation seems better than the other formulas to estimate GFR.

Posttransplant diabetes is a cardiovascular risk factor in renal transplant patients

POSTTRANSPLANT DIABETES mellitus (PTDM) is a serious complication that is grossly under recognized. Prior to the advent of cyclosporine, immunosuppression with high doses of steroids caused PTDM in up to 40% of patients. With modern regimens, the incidence of PTDM has been shown to decrease. Depending on the criteria used to define PTDM and the immunosuppressive treatment regimen, the reported incidence varies from 3% to 20%. The relationship between glycemic control and microvascular and macrovascular complications of diabetes is well established. The aim of this study is to analyze the clinical impact of PTDM on the development of posttransplant cardiovascular disease (CVD).

Evolution of tacrolimus blood levels and concentration-dose ratios in patients who develop new onset diabetes mellitus after kidney transplantation

New onset diabetes mellitus (NODM) affects kidney transplantation outcome. Several risk factors, including immunosuppressive drug levels, are related with NODM development. This analysis evaluates the incidence and risk factors of NODM in kidney transplant patients receiving tacrolimus, taking into account 6‐month blood levels and concentration‐dose ratios (CDRs). Seventy‐six patients under tacrolimus therapy who received a cadaveric renal transplant in our centre and with graft survival higher than 1 year were included in the study. NODM was defined as two fasting plasma glucose values ≥126 mg/dl or symptoms of diabetes plus casual plasma glucose concentrations ≥200 mg/dl throughout the first year. We examined previously reported variables related with NODM development. The incidence of NODM at 12 months was 27.6%. Risk factors for NODM included older age, higher first tacrolimus level, higher body mass index and lower first year weight gain. In multivariate analysis, the first year occurrence of NODM was significantly determined by the first tacrolimus blood level >20 ng/ml and age older than 50 years. CDR remains significantly higher in NODM throughout the 6 months. Older age and a high first tacrolimus blood level are associated with the development of NODM during the first year after kidney transplantation. NODM patients show higher CDR during the first 6 months.

ANCA-associated pauci-immune crescentic glomerulonephritis complicating Sjögren's syndrome

Although ocular and oral dryness are the hallmarks of Sjogrens syndrome (SS), SS patients can develop a variety of complications, affecting organs such as the liver, kidneys, lungs, muscles, and nervous system [1]. Renal involvement has been described in 25-30% of patients with SS, usually as a tubulointerstitial nephritis. However, glomerulonephritis (GN) is rare in primary SS and fewer than 25 cases have been reported. Most patients had membranous or membranoproliferative GN [2-7]. We report a patient with primary SS who developed a crescentic glomerulonephritis (CGN) associated with perinuclear antineutrophil cytoplasmic autoantibodies (ANCA). To our knowledge, this association has not been previously described in the literature.

Correlation of C0 and C2 Levels With Cyclosporine Side Effects in Kidney Transplantation

Cyclosporine has a narrow therapeutic window requiring close monitoring to ensure adequate immunosuppression while avoiding nephrotoxicity and other side effects. Pharmacokinetic studies have suggested that cyclosporine levels at 2 hours postdose (C2) is the best single time point to predict area under the concentration curve (AUC) in kidney transplant recipients. C2 also predicted acute rejection episodes and nephrotoxicity better than trough levels (C0). Targeting cyclosporine levels to minimize side effects while maintaining adequate immunosuppressive effects is of clinical interest. There are conflicting evidence and few reports about whether cyclosporine-related side effects are a dose-dependent phenomenon. The aim of this single center study was to ascertain whether cyclosporine side effects were dose-dependent and which single time point level (C0 or C2) was more closely related to them. We analyzed 225 patients on Neoral-based immunosuppression with C0 and C2 levels measured on the same day of 2 different visits. Serum creatinine, glucose, uric acid, potassium, total cholesterol, triglycerides, and 24-hour urinary sodium elimination were measured by routine biochemical analyses. Blood pressure was measured at each visit. A significant positive correlation was observed between C2 and C0 concentrations and levels of potassium (P < .001), total cholesterol (P < .001), systolic blood pressure (P < .001), and pulse pressure (P < .01). There was a significant negative correlation between C2 and uric acid (P < .001). AUCs of receiver operating characteristic (ROC) curves for both C2 and C0 levels were significant as predictors of hyperkalemia (P < .001), hyperuricemia (P = .001), hypercholesterolemia (P < .05), and high systolic blood pressure (P < .05). There were no significant differences between the capacities of C2 or C0 to predict these variables. In conclusion, potassium, total cholesterol, uric acid, and systolic hypertension were influenced by cyclosporine in a dose-dependent manner. Both C2 and C0 were useful to predict cyclosporine side effects.

Posttransplant Kaposi’s Sarcoma Restricted to the Site of a Previous Deep Venous Thrombosis: Abrupt Onset after Withdrawal of Sirolimus

Kaposi’s sarcoma (KS) is an angioproliferative neoplasia associated with human herpesvirus 8 (HHV-8) infection. HHV-8 generates KS by means of the secretion of vascular endothelial growth factor (VEGF) andup-regulation of VEGF receptor, KDR, in endothelial cells. We report a case of KS in a 72-year-old male with a renal transplant who had received immunosuppressant drugs including sirolimus, mycophenolate mofetil, tacrolimus and steroids. KS developed 11 months after transplantation, in relation to deep venous thrombosis and withdrawal of sirolimus due to toxicity. Multiple purple papules and nodules were observed exclusively in the limb affected by thrombosis. Diagnosis of KS was confirmed by biopsy. Progressive withdrawal of prednisone was accompanied by full remission of the tumour. The thrombosis and withdrawal of sirolimus may have acted as cofactors in the development of KS, favouring the activation of the VEGF/KDR autocrine loop. Our experience contributes to further evidence that sirolimus may protect against KS.

Improving the Outcomes of Organs Obtained From Controlled Donation After Circulatory Death Donors Using Abdominal Normothermic Regional Perfusion

The use of donation after circulatory death (DCD) has increased significantly during the past decade. However, warm ischemia results in a greater risk for transplantation. Indeed, controlled DCD (cDCD) was associated with inferior outcomes compared with donation after brain death. The use of abdominal normothermic regional perfusion (nRP) to restore blood flow before organ recovery in cDCD has been proposed as better than rapid recovery to reverse the effect of ischemia and improve recipients’ outcome. Here, the first Spanish series using abdominal nRP as an in situ conditioning method is reported. A specific methodology to avoid restoring circulation to the brain after death determination is described. Twenty‐seven cDCD donors underwent abdominal nRP during at least 60 min. Thirty‐seven kidneys, 11 livers, six bilateral lungs, and one pancreas were transplanted. The 1‐year death‐censored kidney survival was 91%, and delayed graft function rate was 27%. The 1‐year liver survival rate was 90.1% with no cases of ischemic cholangiopathy. Transplanted lungs and pancreas exhibited primary function. The use of nRP may represent an advance to increase the number and quality of grafts in cDCD. Poor results in cDCD livers could be reversed with nRP. Concerns about restoring brain circulation after death are easily solved.

Prediction of Delayed Graft Function by Means of a Novel Web‐Based Calculator: A Single‐Center Experience

Renal failure persisting after renal transplant is known as delayed graft function (DGF). DGF predisposes the graft to acute rejection and increases the risk of graft loss. In 2010, Irish et al. developed a new model designed to predict DGF risk. This model was used to program a web‐based DGF risk calculator, which can be accessed via http://www.transplantcalculator.com . The predictive performance of this score has not been tested in a different population. We analyzed 342 deceased‐donor adult renal transplants performed in our hospital. Individual and population DGF risk was assessed using the web‐based calculator. The area under the ROC curve to predict DGF was 0.710 (95% CI 0.653–0.767, p < 0.001). The “goodness‐of‐fit” test demonstrates that the DGF risk was well calibrated (p = 0.309). Graft survival was significantly better for patients with a lower DGF risk (5‐year survival 71.1% vs. 60.1%, log rank p = 0.036). The model performed well with good discrimination ability and good calibration to predict DGF in a single transplant center. Using the web‐based DGF calculator, we can predict the risk of developing DGF with a moderate to high degree of certainty only by using information available at the time of transplantation.