Allograft Dysfunction In Patients Research Articles

Impact of Long-Term Atorvastatin Therapy on the Development of Chronic Lung Allograft Dysfunction in Patients with Azithromycin Prophylaxis after Lung Transplantation

ObjectiveTo assess the impact of long-term atorvastatin (ATO) therapy on reducing recipient inflammation and immune response, thus lowering the risk of chronic lung allograft dysfunction (CLAD) in lung transplant recipients. This study aimed to investigate the effects of ATO on overall survival, lung function recovery, and its influence on inflammatory factors alongside azithromycin (AZI) prophylaxis. MethodsThis retrospective single-center study included lung transplant recipients from January 2017 to December 2022. Patients who survival >1 year after lung transplantation and who were receiving AZI prophylaxis for >6 months were selected. Outcome measures involved pulmonary function assessments at various time points after AZI treatment, complete blood cell analysis, and inflammatory factor evaluations. ResultsThe incidence of CLAD was significantly lower in the long-term ATO group compared with those not on ATO (P = .011). Long-term ATO treatment significantly delayed CLAD onset after lung transplantation (850 days vs. 630 days; P = .041), with patients showing notably enhanced lung function recovery within 6 months of AZI therapy compared with the non-ATO group. Neutrophil levels decreased in patients with CLAD, and interleukin-6 concentrations significantly decreased in the AZI + ATO group compared with the AZI group. Overall patient survival was significantly better in the AZI+ATO group than in the AZI group (P = .02). ConclusionIn cases where CLAD develops despite AZI prophylaxis, long-term ATO treatment may lead to short-term improvements in lung function. It could also decrease inflammation levels in lung transplant recipients and enhance overall survival. The combination of AZI and long-term ATO therapy may be beneficial for CLAD prevention.

Phase-Resolved Functional Lung MRI for Pulmonary Ventilation and Perfusion (V/Q) Assessment.

Fourier decomposition is a contrast agent-free 1H MRI method for lung perfusion (Q) and ventilation (V) assessment. After image registration, the time series of each voxel is analyzed with regard to the cardiac and breathing frequency components. Using a standard 2D spoiled gradient-echo sequence with a temporal resolution of ~300 ms, an image-sorting algorithm was developed to produce phase-resolved functional lung imaging (PREFUL) with an increased temporal resolution. Thus, it is feasible to evaluate regional flow volume loops (FVL) during tidal volume breathing and depict the propagation of the pulse wave during the cardiac cycle. This method can be applied at 1.5T or 3T with standard MR hardware without the necessity for sequence programming, as the described protocol can be implemented with the default SPGRE sequence on most systems. PREFUL ventilation MRI has been validated using 129Xe and 19F gas imaging with good regional agreement. Perfusion-weighted PREFUL MRI has been validated using SPECT as well as dynamic contrast enhanced (DCE) MRI. PREFUL has been tested in a dual center dual vendor setting and is currently applied in several ongoing multicenter trials. Furthermore, it is feasible across a range of field strengths (0.55T-3T) and different age groups, including newborns. Quantitative V/Q PREFUL MRI has been used in patients with cystic fibrosis, chronic obstructive pulmonary disease, chronic thromboembolic pulmonary hypertension, and corona virus disease-2019 to quantify disease and monitor treatment change after therapy. Furthermore, PREFUL V/Q imaging has been shown to predict transplant loss due to chronic lung allograft dysfunction in patients after lung transplantation. In summary, PREFUL MRI is a validated technique for quantitative ventilation and pulmonary pulse wave/perfusion imaging for regional pulmonary disease detection, quantification, and treatment monitoring with potential added value to the current clinical routine.

Usefulness of Picture Archiving and Communication System-Based Quantitative Ultrasound Measurements in Evaluation of Allograft Dysfunction in Patients With Liver Transplantation.

The aim of this study was to assess the usefulness of picture archiving and communication system (PACS)-based quantitative grayscale ultrasonography (US) measurements in detecting allograft dysfunction in posttransplant patients. In this retrospective study, 116 patients with liver transplantation who underwent biopsy for allograft evaluation were recruited from the database. All participants had US images prior to procedure. Normal, acute cellular rejection (ACR), recurrent hepatitis (Hep), or combined (ACR/Hep) groups were generated based on pathology results. Region of interests were drawn for liver and rectus abdominus muscle to perform quantitative US analysis. The liver/muscle mean ratio (L/M) and heterogeneity index (HI; liver standard deviation/liver mean) were obtained. The ratios of groups were compared, and receiver-operating-characteristic analysis was performed. There was a significant difference between normal (n = 16) and each of other groups (ACR, 39; Hep, 36; combined, 25) for L/M and HI (P < 0.05). No significant difference was detected between ACR, Hep, and combined groups. The areas under the curve for L/M and HI were 0.755 (moderate) and 0.817 (good), respectively. To differentiate abnormal (ACR, Hep, and combined) from normal allografts sensitivity, specificity, PPV, and NPV were 50.0%, 87.5%, 96.2%, and 21.9% for cut point of L/M ≥1 and 84.0%, 68.8%, 94.4%, and 40.7% for cut point of HI ≥0.2 with odds ratios of 7.52 (for L/M ≥1) and 13.10 (for HI ≥0.2), respectively (P < 0.01). L/M has moderate and HI has good discrimination of normal from abnormal allograft in liver transplant patients. PACS-based quantitative US measurements is an objective, easy to use, noninvasive auxiliary tool to discriminate hepatic allograft dysfunction.

Risk Factors of Early Allograft Dysfunction in Patients With Hepatitis B Virus-Related Acute-on-Chronic Liver Failure After Deceased Donor Liver Transplant

Hepatitis B virus-related acute-on-chronic liver failure remains a life-threatening syndrome, and transplant is the definitive treatment. Early allograft dysfunction is a postoperative complication and affects morbidity and mortality. We studied the risk factors associated with early allograft dysfunction in livertransplantrecipients with hepatitis B virus-related acute-on-chronic liver failure. This single-center retrospective study of early allograft dysfunction is based on data from January 2015 to June 2020 for 323 recipients with hepatitis B virus-related acute-on-chronic liver failure and 445 with only hepatitis B virus infection (control group). Data that correlated with early allograft dysfunction and outcome were analyzed. Incidence of early allograft dysfunction in patients with hepatitis B virus-related acute-on-chronic liver failure was significantly higher versus the control group (39.3% vs 21.1%; P < .001). Transplant recipients with hepatitis B virus-related acute-onchronic liver failure who developed early allograft dysfunction had lower 90-day, 180-day, and 360-day patient survival rates versus patients with no early allograft dysfunction (89.0% vs 98.0%, 82.7% vs 97.5%, and 80.3% vs 96.4%, respectively; P < .001). Pretransplant kidney failure (odds ratio, 2.644; 95% CI, 1.019-6.864; P = .046), pretransplant coagulation failure (odds ratio, 2.162; 95% CI, 1.291-3.621; P = .003), and operative time (odds ratio, 1.005; 95% CI, 1.002-1.008; P = .003) were independent risk factors for early allograft dysfunction in liver transplant recipients with hepatitis B virus-related acute-onchronic liver failure. There was a synergistic effect of early allograft dysfunction and preoperative kidney/coagulation failure on survival rates of liver transplant recipients with hepatitis B virus-related acute-on-chronic liver failure. Preoperative kidney/coagulation failure and operative time were independent risk factors of early allograft dysfunction in deceased donor liver transplant recipients with hepatitis B virus-related acute-on-chronic liver failure. The combination of early allograft dysfunction and preoperative kidney/coagulation failure was significantly associated with lower survival of these recipients.

Elevated levels of circulating mitochondrial DNA predict early allograft dysfunction in patients following liver transplantation.

The role of circulating mitochondrial DNA (cmtDNA) in transplantation remains to be elucidated. cmtDNA may be released into the circulation as a consequence of liver injury; yet recent work also suggests a causative role for cmtDNA leading to hepatocellular injury. We hypothesized that elevated cmtDNA would be associated with adverse events after liver transplantation (LT) and conducted an observational cohort study. Twenty-one patients were enrolled prospectively prior to LT. Postoperative complications were observed in 47.6% (n=10). Seven patients (33.3%) had early allograft dysfunction (EAD), and six patients (28.5%) experienced acute cellular rejection within 6months of LT. cmtDNA levels were significantly elevated in all recipients after LT compared with healthy controls and preoperative samples (1361937 copies/mL [IQR 586781-3399687] after LT; 545531 copies/mL [IQR 238562-1381015] before LT; and 194562 copies/mL [IQR 182359-231515] in healthy controls) and returned to normal levels by 5days after transplantation. cmtDNA levels were particularly elevated in those who developed EAD in the early postoperative period (P<0.001). In all patients, there was initially a strong overall positive correlation between cmtDNA and plasma hepatocellular enzyme levels (P<0.05). However, the patients with EAD demonstrated a second peak in cmtDNA at postoperative day 7, which did not correlate with liver function tests. The early release of plasma cmtDNA is strongly associated with hepatocellular damage; however, the late surge in cmtDNA in patients with EAD appeared to be independent of hepatocellular injury as measured by conventional tests.

Prognostic role of levels of extracellular histones H3 for diagnosis of early dysfunction of transplant after hepatic transplantation

Objective. The aim of this study was to determine the prognostic role of extracellular histones in the diagnosis of early graft dysfunction after liver transplantation..&#x0D; Materials and methods. The 93 recipients undergoing LDLT were enrolled in this prospective study. Blood samples of patients were collected on postoperative day 1 and histone levels in the plasma samples were measured with Total Histone H3 sandwich ELISA kits. 19 (20.4%) subjects had early graft dysfunction (EAD) which was diagnosed on postoperative day 7 according to Ol-thoff’s criteria, based on liver function tests and coagulation profiles. Other 74 (79.6%) recipients did not have EGD.&#x0D; Results. Levels of circulating histones were depressed in patients with EGD (0,808±0.026, 95% (CI) 0.752-0.864) than in patients without EGD (0.820±0.017, 95% (CI) 0.786-0.854) (P=0.727). These differences were not significant. The sources of histones in the circulation are not etiologies specific and levels of total histone H 3 after 24 h of operation had not stronger predictive value with AUC 0.477 (95 % CI 0.329 to 0.625) for liver dysfunction. The AUC value of the total bilirubin (AUC 0.685, 95 % CI 0.546 to 0.825) in predicting early graft dysfunction outperformed other LFTs and was less than CRP (AUC 0.705, CI 0.573 to 0.838).&#x0D; The optimal cutoff value of total bilirubin obtained from the analysis of ROC curves was 4,5 and surpassed all other parameters with a sensitivity of 94.4% and a specificity of 40.7% respectively for prognoses of EGD (P=0.012). The univariate analysis determined that postoperative neutrophils level and CRP were identified as independent risk factors for early graft dysfunction. Neutrophils had a higher predictive value for liver dysfunction than any other parameter within 24 h (Odds ratio (OR) 16.3; 95% CI: 1.7-156.3, P = 0.016). &#x0D; Conclusion. Collectively, extracellular histone H3 levels were depressed, total bilirubin and CRP levels were elevated in patients with EGD, which can be used as early predictors for liver tissue damage and early allograft dysfunction in patients after liver transplantation.

Characteristics, Survival, and Outcomes of Lung and Heart-Lung Transplantation for Pulmonary Sarcoidosis in a Multicenter European Study Characteristics, Survival, and Outcomes of Lung and Heart-Lung Transplantation for Pulmonary Sarcoidosis in a Multicenter European Study

In the context of sarcoidosis, lung transplantation is often performed in patients with irreversible advanced lung disease unresponsive to medical therapy. The clinical phenotypes and posttransplant survival remain unclear, due primarily to the recurring nature of the disease and extrapulmonary involvement. The objective of this study in a large multicenter European cohort was to describe the clinical characteristics and outcomes of patients with pulmonary sarcoidosis treated by lung transplantation. We retrospectively reviewed the data of 147 patients with pulmonary sarcoidosis who underwent lung or heart-lung transplantation between 1990 and 2019 at 15 European centers. Inclusion criteria were sarcoidosis meeting international diagnostic criteria and availability of data from pretransplantation right heart catheterization, lung function testing, and chest computed tomography (CT) staged using a standardized system. At transplantation, mean age was 50±8 years, 62% were male, and 20% had extrapulmonary manifestations. Mean values before transplantation were as follows: FVC (%pred), 46±17%; FEV1 (%pred), 38±19; FVC/FEV1 (%), 55±32; DLCO (%pred), 31±13; mPAP (mmHg), 36±13; PCWP (mmHg), 10±5; cardiac index (L/min/m²), 3.0±0.8; and pulmonary vascular resistance (dyn·s·cm-5), 480±340; furthermore, 60% of patients had severe pulmonary hypertension. Posttransplant survival rates after 1, 3, and 5 years were 85%, 69%, and 63%, respectively. During the median [range] follow-up of 43 [17-79] months, 38% of patients developed chronic lung allograft dysfunction. Factors significantly associated with outcomes were high emergency transplantation, era of transplantation, preoperative extrapulmonary sarcoidosis, and extent of fibrosis by CT. Posttransplant survival rates and freedom from chronic lung allograft dysfunction in patients with pulmonary sarcoidosis were similar to those in patients with other reasons for lung transplantation. Factors associated with worse outcomes were high emergency transplantation, earlier transplantation era, preoperative extrapulmonary sarcoidosis, and greater burden of fibrosis by CT.

Association between AT1R Autoantibody with Adverse Outcomes in Patients Bridged to Heart Transplant Using Continuous Flow Ventricular Assist Device

Purpose Antibody to angiotensin-II type 1 receptor (AT1R-Ab) may be implicated in allograft dysfunction in patients who are bridged to heart transplant (BTT) with a continuous flow left ventricular assist device (VAD). We studied AT1R-Ab level following VAD implantation on event-free survival in BTT patients and whether AT1R-Ab elevation is independent from inflammation as measured through C-reactive protein (CRP). Methods Sera of 77 BTT patients from 2009 to 2017 were tested for AT1R-Ab and CRP prior to and after VAD placement. Elevated AT1R-Ab level was defined as greater than 10.0 U/mL. For statistical analysis, the value of 40 U/mL was assigned to AT1R-Ab level greater than 40 U/mL. Events were defined as acute cellular rejection, antibody-mediated rejection, cardiac allograft vasculopathy, reduced EF, and death. Results Median follow-up time after transplant was 3.3 years (range 0.4-9.0 years). After VAD implantation, AT1R-Ab was increased as compared to baseline (Fig 1A). Univariate regression analysis revealed that age, female gender, African-American race, time to transplant, type of VAD, HLA sensitization, and positive donor specific antibodies were not risk factors for AT1R-Ab sensitization. The elevated post-VAD AT1R-Ab cohort had more events than the normal AT1R-Ab group (61% vs 29%, Fig 1B). On Kaplan Meier analysis, there was a statistically decrease in 5-year event-free survival in patients who had elevated AT1R-Ab levels (Fig 1C). Multivariate Cox regression analysis showed increased post-VAD AT1R-Ab as an independent risk factor for developing events. Though CRP was high before and after VAD implantation, CRP had no statistically significant correlation with AT1R-Ab level (Fig 1D). Conclusion Increase in AT1R-Ab was seen in BTT patients after VAD implantation and was associated with adverse outcomes after heart transplant. The AT1R-Ab elevation does not appear to be an epiphenomenon related to CRP, a marker of inflammation.

Lung transplantation for scleroderma lung disease: An international, multicenter, observational cohort study

Due to its multisystemic nature, scleroderma is considered a relative contraindication to lung transplantation at many centers. However, recent studies suggest similar post-transplant outcomes in patients with scleroderma compared to those with other causes of interstitial lung disease (ILD). Furthermore, it remains unknown whether scleroderma-associated pulmonary arterial hypertension (PAH) influences post-transplant outcomes. Our objective in this study was to assess the indications, survival, and prognostic factors of lung or heart-lung transplantation for scleroderma lung disease. We retrospectively reviewed the data of 90 patients with scleroderma who underwent lung or heart-lung transplantation between 1993 and 2016 at 14 European centers. International criteria were used to diagnose scleroderma. Pulmonary hypertension (PH) was diagnosed during right heart catheterization based on international guidelines. Survival rates after 1, 3, and 5 years were 81%, 68%, and 61%, respectively. By univariate analysis, borderline-significant associations with poorer survival were found for female gender (hazard ratio 2.11; 95% confidence interval [CI] 0.99 to 4.50; p = 0.05) and PAH as the reason for transplantation (hazard ratio 1.90; 95% CI 0.96 to 3.92; p = 0.06). When both these factors were present in combination, the risk of death was 3-fold that in males without PAH. The clinical and histologic presentation resembled veno-occlusive disease in 75% of patients with PAH. Post-transplant survival rates and freedom from chronic lung allograft dysfunction in patients with scleroderma were similar to those in patients with other reasons for lung transplantation. Female sex and PAH in combination was associated with lower survival.

An unusual cause of allograft dysfunction

A 41-year-old man, who received a living-donor kidney transplant in 2005, presented 9 years after surgery with recurrent renal allograft dysfunction. Physical examination revealed slightly diminished femoral and distal pulses. Lower extremity claudication was reported on questioning the patient. The serum creatinine was 2.0 mg/dl (baseline 1.4 mg/dl), showing an increase. Renal duplex ultrasonography showed decreased resistance indices (0.3–0.4, normal: 0.6–0.8). Intra renal blood flow profiles were suggestive of renal artery stenosis (tardus parvus waveform) but without increased maximal systolic flow velocities (vmax) within the graft artery. Iliac artery-flow pattern in the vicinity of the anastomosis showed moderately reduced peak flow. Graft biopsy showed borderline rejection and moderate interstitial fibrosis and tubular atrophy (Banff III/V). Creatinine decreased (1.6 mg/dl) after corticosteroid pulse therapy and the patient was discharged. Three days later, he was readmitted with worsening kidney function (creatinine 2.7 mg/dl) and biopsy indicated borderline rejection again. Magnetic resonance angiography was performed and revealed an occlusion of the distal abdominal aorta at the bifurcation into the common iliac arteries (‘Leriche syndrome’, Figure 1). After surgical revascularization using prosthesis with aortoiliac (right) and aortofemoral (left) bypasses kidney function improved (creatinine 1.7 mg/dl) and claudication resolved. Proximal vascular occlusion should be suspected as a cause of allograft dysfunction in patients with fluctuating renal function when renal histology is inconclusive or mild.

Utility of Iron Staining in Identifying the Cause of Renal Allograft Dysfunction in Patients with Sickle Cell Disease.

Sickle cell nephropathy (SCN) is associated with iron/heme deposition in proximal renal tubules and related acute tubular injury (ATI). Here we report the utility of iron staining in differentiating causes of renal allograft dysfunction in patients with a history of sickle cell disease. Case 1: the patient developed acute allograft dysfunction two years after renal transplant. Her renal biopsy showed ATI, supported by patchy loss of brush border and positive staining of kidney injury molecule-1 in proximal tubular epithelial cells, where diffuse increase in iron staining (2+) was present. This indicated that ATI likely resulted from iron/heme toxicity to proximal tubules. Electron microscope confirmed aggregated sickle RBCs in glomeruli, indicating a recurrent SCN. Case 2: four years after renal transplant, the patient developed acute allograft dysfunction and became positive for serum donor-specific antibody. His renal biopsy revealed thrombotic microangiopathy (TMA) and diffuse positive C4d stain in peritubular capillaries. Iron staining was negative in the renal tubules, implying that TMA was likely associated with acute antibody-mediated rejection (AAMR, type 2) rather than recurrent SCN. These case reports imply that iron staining is an inexpensive but effective method in distinguishing SCN-associated renal injury in allograft kidney from other etiologies.

Relationship between European mitochondrial haplogroups and chronic renal allograft rejection in patients with kidney transplant.

Mitochondrial DNA variants may contribute to differences in mitochondrial function, leading to an altered immune system. The aim of this study was to analyze the relationship between mtDNA haplogroups and the development of chronic allograft dysfunction in patients with kidney transplant. A retrospective observational study was carried out on 261 patients who received kidney transplant (114 had stable transplant and 147 patients developed chronic allograft dysfunction). DNA samples were genotyped for 14 mtDNA polymorphisms by using Sequenom's MassARRAY platform (San Diego, CA, USA). Only European white patients within the N macro-cluster were included. Patients with haplogroups V (odds ratio (OR)=0.32; p=0.037) and J (OR=0.36; p=0.038) showed lower odds for developing CRAD than patients with haplogroup H. After adjusting for the most significant variables, haplogroups V and J tended to statistical significance (p=0.091 and p=0.067 respectively). This is a preliminary study in which mtDNA haplogroups seem to be implicated in susceptibility or protection for developing chronic allograft dysfunction.

Risk factors for graft loss and mortality after renal transplantation according to recipient age: a prospective multicentre study.

BackgroundTo describe the causes of graft loss, patient death and survival figures in kidney transplant patients in Spain based on the recipient's age.MethodsThe results at 5 years of post-transplant cardiovascular disease (CVD) patients, taken from a database on CVD, were prospectively analysed, i.e. a total of 2600 transplanted patients during 2000–2002 in 14 Spanish renal transplant units, most of them receiving their organ from cadaver donors. Patients were grouped according to the recipient's age: Group A: <40 years, Group B: 40–60 years and Group C: >60 years. The most frequent immunosuppressive regimen included tacrolimus, mycophenolate mofetil and steroids.ResultsPatients were distributed as follows: 25.85% in Group A (>40 years), 50.9% in Group B (40–60 years) and 23.19% in Group C (>60). The 5-year survival for the different age groups was 97.4, 90.8 and 77.7%, respectively. Death-censored graft survival was 88, 84.2 and 79.1%, respectively, and non death-censored graft survival was 82.1, 80.3 and 64.7%, respectively. Across all age groups, CVD and infections were the most frequent cause of death. The main causes of graft loss were chronic allograft dysfunction in patients <40 years old and death with functioning graft in the two remaining groups. In the multivariate analysis for graft survival, only elevated creatinine levels and proteinuria >1 g at 6 months post-transplantation were statistically significant in the three age groups. The patient survival multivariate analysis did not achieve a statistically significant common factor in the three age groups.ConclusionsFive-year results show an excellent recipient survival and graft survival, especially in the youngest age group. Death with functioning graft is the leading cause of graft loss in patients >40 years. Early improvement of renal function and proteinuria together with strict control of cardiovascular risk factors are mandatory.

Serum cytokine profiles associated with early allograft dysfunction in patients undergoing liver transplantation

Early allograft dysfunction (EAD) occurring in the first week post-liver transplantation is associated with increased graft failure and mortality and is believed to be largely due to ischemia/reperfusion injury. We anticipated that the presence of EAD would be reflected by alterations in expression of serum proteins associated with an inflammatory response in the peri-operative period, and hypothesized that a specific pattern of expression might correlate with the development of EAD. The serum levels of 25 cytokines, chemokines, and immunoreceptors were measured by Luminex multiplex assays pre- and post-liver transplantation. Levels of each cytokine biomarker were compared in adult recipients with or without EAD at serial time points using samples collected pre-operatively and at 1, 7, 14, and 30 days post-transplant. EAD was defined according to standard criteria as maximum alanine transferase (ALT) or aspartate transferase (AST) levels on days 1-7 of >2000 U/ml, day 7 bilirubin level ≥10 mg/dl, or a day 7 international normalized ratio (INR) ≥1.7. Multivariable analyses showed that patients experiencing EAD had lower pre-operative IL-6 and higher IL-2R levels. Patients with EAD also showed higher MCP-1 (CCL2), IL-8 (CXCL8), and RANTES (CCL5) chemokine levels in the early post-operative period, suggesting up-regulation of the NF-kB pathway, in addition to higher levels of chemokines and cytokines associated with T cell immunity, including MIG (CXCL9), IP-10 (CXCL10) and IL-2R. These findings identify several possible biomarkers and pathways associated with EAD, that may guide future validation studies and investigation of specific cellular and molecular mechanisms of graft dysfunction. Furthermore, if validated, our findings may contribute to perioperative prediction of the occurrence of EAD and ultimately lead to identification of potential interventional therapies.

180: Early Fundoplication Reduces the Incidence of Chronic Allograft Dysfunction in Patients with Gastroesophageal Reflux Disease

376 (93-442) vs. 363 (156-369) days (p NS). BAL BA levels, but not pepsin levels, as well as IL-8 and neutrophils were elevated in C patients (figure 1). Generally, BA levels, but not pepsin levels, positively correlated with BAL IL8 and neutrophilia (figure 2). Conclusions: Bile acid aspiration seems to be associated with P.aeruginosa airway colonization after LTx. Their possible role for inducing neutrophilic airway inflammation in the development of BOS after LTx should be further elucidated. Research funded by Research Foundation-Flanders (FWO) and GSK Belgium.

Fenofibrate-associated reversible acute allograft dysfunction in 3 renal transplant recipients: Biopsy evidence of tubular toxicity

Renal transplant recipients are susceptible to hyperlipidemia and the development of atherosclerosis as a consequence of the immunosuppressive agents they require, which include corticosteroids, calcineurin inhibitors, and sirolimus. Fibric acid derivatives and 3-hydroxymethylglutaryl-coenzyme A reductase inhibitors are prescribed commonly to optimize lipid profiles and reduce the risk of cardiovascular events in this type of setting. The authors describe 3 cases of reversible acute renal allograft dysfunction in patients treated with fenofibrate. Serum levels of monitored immunosuppressant agents remained therapeutic throughout the time period. Discontinuation of the fenofibrate resulted in the resolution of renal dysfunction. The pathologic changes to the proximal tubules in all 3 biopsy specimens were in keeping with a toxic rather than an ischemic etiology. Although the control of hyperlipidemia is crucial in the transplant patient population, the authors suggest that caution be exercised and serum creatinine levels be closely monitored in patients started on fibrates.

Fenofibrate-associated reversible acute allograft dysfunction in 3 renal transplant recipients: Biopsy evidence of tubular toxicity

Renal transplant recipients are susceptible to hyperlipidemia and the development of atherosclerosis as a consequence of the immunosuppressive agents they require, which include corticosteroids, calcineurin inhibitors, and sirolimus. Fibric acid derivatives and 3-hydroxymethylglutaryl-coenzyme A reductase inhibitors are prescribed commonly to optimize lipid profiles and reduce the risk of cardiovascular events in this type of setting. The authors describe 3 cases of reversible acute renal allograft dysfunction in patients treated with fenofibrate. Serum levels of monitored immunosuppressant agents remained therapeutic throughout the time period. Discontinuation of the fenofibrate resulted in the resolution of renal dysfunction. The pathologic changes to the proximal tubules in all 3 biopsy specimens were in keeping with a toxic rather than an ischemic etiology. Although the control of hyperlipidemia is crucial in the transplant patient population, the authors suggest that caution be exercised and serum creatinine levels be closely monitored in patients started on fibrates.

Tc-99m DTPA scans in renal allograft rejection and cyclosporine nephrotoxicity.

Renal allograft dysfunction arising from rejection or cyclosporine (CsA) nephrotoxicity can currently only be distinguished reliably by allograft biopsy. We have assessed Technetium (Tc)-99m diethylamine pentacetic acid (DTPA) scanning in 30 CsA-treated patients with allograft dysfunction. Scintigrams were performed during 20 biopsy-proved episodes of rejection and during 14 episodes of CsA nephrotoxicity. These results were compared with the scintigrams of 15 allografts showing stable function. Quantitative indices expressing allograft perfusion (flow index) and function (uptake index) derived from the DTPA scintigrams showed no significant differences between the groups of patients with rejection, CsA nephrotoxicity, or stable or improving function. Similarly, the flow and uptake indices of individual allografts obtained during periods of stable or improving function and then during episodes of dysfunction due to rejection or CsA nephrotoxicity did not significantly change. We conclude that Tc-99m DTPA scintigrams are of limited value in the management of allograft dysfunction in patients immunosuppressed with CsA.