Pretransplant Glomerular Filtration Rate Research Articles

Simultaneous heart-kidney transplant in patients with borderline estimated glomerular filtration rate without dialysis dependency.

Appropriate patient selection for simultaneous heart-kidney transplantation (sHK) in patients with moderate renal dysfunction remains challenging. From the United Network for Organ Sharing database (2003-2020), we identified 5678 adults with an estimated pre-transplant glomerular filtration rate (eGFR) between 30 and 45mL/min/1.73m2 and no pre-transplant dialysis. Patients undergoing sHK (n=293) were compared with those undergoing heart transplantation alone (n=5385) using 1:3 propensity score matching. The sHK utilization rate increased from 1.8% in 2003 to 12.2% in 2020 (p<.001). After matching, 1 and 5-year survival was 87.7% (95% confidence interval [CI] 83.3-91.0) and 80.0% (95% CI 74.2-84.6) after sHK, and 87.3% (95% CI 85.2-89.1) and 71.8% (95% CI 68.4-74.9) after heart transplant alone (p=.04). In the subgroup analysis, sHK was associated with a 5-year survival benefit only in patients with 30<eGFR≤35mL/min/1.73m2 (p=.05) but not in those with 35<eGFR<45mL/min/1.73m2 (p=.45). Patients who underwent heart transplants alone also had a higher incidence of becoming chronic dialysis-dependent after transplant within 5-year follow-up (10.2%, 95% CI 8.0-12.6 vs. 3.8%, 95% CI 1.7-7.1, p=.004). The 5-year incidence of subsequent kidney waitlisting and transplants after heart transplants alone was 5.6% and 1.9%, respectively. Among propensity-matched patients without pre-transplant dialysis, compared to heart transplants alone, sHK had improved 5-year survival in those with 30<eGFR≤35 but not in those with 35<eGFR<45mL/min/1.73m2 . One-year survival was similar irrespective of eGFR. Receiving a kidney after a heart transplant alone is rare under the current allocation system.

Abstract 15126: Hybrid Supervised and Unsupervised Machine Learning Model Improves Prediction of New-Onset Dialysis in Orthotopic Heart Transplant Patients

Introduction: Machine learning (ML) approaches to clinical risk prediction have demonstrated improved performance over traditional statistical approaches. New-onset dialysis following isolated orthotopic heart transplantation (OHT) is an important contributor to mortality risk and quality of life in recipients, yet traditional approaches to predicting its occurrence have performed only modestly. This study sought to develop and evaluate a hybrid supervised and unsupervised ML approach to estimating the risk of new-onset dialysis following OHT. Methods: This was a retrospective study of patients (n = 26,505) with no history of dialysis undergoing primary, isolated OHT between 2000 and 2022 as identified in the United Network for Organ Sharing (UNOS) database. The study cohort was split randomly into training (80%) and validation sets (20%) and under-sampling using K-Nearest Neighbors clustering was used to account for class imbalance. ML models, including a Multilayer Perceptron Classifier, a Support Vector Classifier, and a Logistic Regression Model were developed and compared. Sensitivity, accuracy, precision, and F 1 score were measured, and discriminatory performance was assessed using the area under the receiver-operating-characteristic curve (AUC). Results: The rate of new dialysis was 11.3% following OHT with comparable rates in the training and validation cohorts. In the validation cohort, the support vector classifier had the highest AUC Score (0.774 (95% CI, 0.748 - 0.800), sensitivity (0.74), F 1 Score (0.72), accuracy (0.70), and precision (0.70). All other models yielded poorer performance by every metric. Predictive risk factors that were common across models included congenital heart disease, pre-transplant glomerular filtration rate, and human leukocyte antigen mismatch. Conclusions: This study demonstrates that an ML approach using a support vector model was associated with improved model performance metrics including discriminatory capability compared to other modeling approaches in predicting new-onset dialysis risk after OHT. The use of ML models in OHT may have utility in patient selection, modification of risk factors, and programmatic evaluation.

Need for improvements in simultaneous heart-kidney allocation: The limitation of pretransplant glomerular filtration rate.

The incidence of simultaneous heart-kidney transplant (SHK) has increased markedly in the last 15years. There are no universally agreed upon indications for SHK vs. heart alone (HA) transplant, and center evaluation processes vary widely. We utilized Scientific Registry of Transplant Recipients data from 2003 to 2017 to quantify changes in the practice of SHK, examine the survival of SHK vs. HA, and identify patients with marginal benefit from SHK. We used Kaplan-Meier curves and Cox proportional hazards to assess differences in survival. The incidence of SHK increased more than fourfold between 2003 and 2017 from 1.6% to 6.6% of total hearts transplanted, while the proportion of dialysis-dependent patients undergoing SHK has remained constant. SHK was associated with increased survival in dialysis-dependent patients (Median Survival SHK: 12.6 vs. HA: 7.1years p<.0001) but not with nondialysis-dependent patients (Median Survival SHK: 12.5 vs. HA 12.3, p=.24). The marginal effect of SHK in decreasing the hazard of death diminished with increasing eGFR. Delayed graft function occurred in 26% of SHK recipients. Posttransplant chronic dialysis was similar for both operations (6.4% of HA and 6.0% of SHK). Further study is needed to define patients who benefit from SHK.

Pre-Heart Transplant Glomerular Filtration Rate and Outcome

Heart transplantation remains the optimal treatment for end-stage heart failure. Renal insufficiency has long been considered a significant risk factor for post-heart transplant morbidity and mortality. The International Society of Heart and Lung Transplantation has suggested glomerular filtration rate (GFR) cutoffs of <40mL/min and <30mL/min in 2006 and 2016 respectively. We sought to assess our transplant patients with respect to baseline pre-transplant GFR METHODS: Between 2010 and 2018 we assessed 534 heart transplant patients and divided them based on the GFR directly before transplant. Groups were divided into GFR<30 (n=53), GFR 30-60 (n=299) and GFR>60 (n=182). All combined heart-kidney transplantations were excluded from this study. Endpoints included 1 and 5 year survival, freedom from the development of cardiac allograft vasculopathy (CAV) (as defined by stenosis ≥ 30% by angiography), non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), any treated rejection (ATR), acute cellular rejection (ACR), antibody-mediated rejection (AMR). There is no overall significant difference between the groups in terms of 1,3 or 5 year survival, 1-year freedom from CAV, NF-MACE and all rejection. However, the GFR<30 group had a significantly lower 5-year survival than the GFR>60 group, 73.6% vs. 86.8%. GFR did not greatly improve at 1-year post-transplant for any group. Heart transplantation in patients with pre-transplant GFR <30 appears to have acceptable 1-year outcomes. However, these patients have worse long-term survival and should be considered for combined heart-kidney transplant.

Prevalence of BK Virus Infection in a Large Heart Transplant Population

In heart transplant (HT) patients, prevalence of BK virus (BKV) infection and its clinical significance are unknown. We sought to understand rates of BKV infection in a large HT cohort and to evaluate risk factors and effects of infection. Consecutive HT patients at a single institution were evaluated for BKV infection in blood and urine in the 1st year post-transplant. Titers were collected 1-month post-transplant and then every 6 months, with additional testing if needed. Rates of infection were compared between HT and combined organ transplant. In the HT group, patients with no infection, viruria with no viremia, and viremia with or without viruria were compared. Measures of immunity and kidney function were collected with titers in blood to evaluate Spearman rank correlations using log10 transformation. 104 patients were enrolled: 89 HT, 12 heart/kidney transplant (HKT), 1 heart/liver transplant, 2 heart/liver/kidney transplant. Viruria and viremia were highly prevalent in HT (42% and 30%, respectively). Compared to HT patients without infection, those with viremia were older (57.8 vs 50.8 yrs, p=0.04), and tended to have lower pre-transplant glomerular filtration rate (GFR) (63.3 vs 71.4 mg/dL/1.73m2, p=0.14). There were no significant differences between patients with viruria compared to viremia. 1-year freedom from viruria was 55% in HT vs 46% in HKT. 1-year freedom from viremia was 67% in HT vs 56% in HKT (Figure). Viremia titers in HT strongly correlated with immunoglobulin (IgG) levels (R= -0.60, p=0.001), but not other immunity measures. Viremia titers were not correlated with GFR (R= 0.05, p=0.70). When comparing GFR before transplant to 1-year post-transplant, there was no significant difference found in the groups with no infection, viruria, and viremia (-22.4 vs -23.7 vs -23.4 mg/dL/1.73m2, p=0.98). BK viremia is very common in HT patients. BK viremia correlated with IgG, but not kidney function. Longer surveillance studies are needed to evaluate effects of BKV infection.

Factors Associated with Post-Transplant Renal Replacement Therapy in Lung Recipients with Normal Pre-Operative Kidney Function

Kidney failure after lung transplantation is associated with worse outcomes. In clinical practice, precautions are taken in patients with preoperative kidney disease to minimize the risk of post-transplant renal failure. A subset of patients with normal pre-operative kidney function require renal replacement therapy (RRT) after transplant and may benefit from similar precautions. The Scientific Registry for Transplant Recipients (SRTR) database was queried for all adult, primary, lung only transplantations performed between 05/2005 and 03/2019. Patients with normal pre-transplant glomerular filtration rate (I.e. GFR >= 90mL/min/1.73 m2) were included in the analysis. Multivariable logistic regression identified factors associated with post-transplant RRT. 14, 101 adult lung recipients with normal GFR were included in the analysis. 812 patients (5.76%) required RRT post-transplantation. Patients who required RRT had higher lung allocation scores (47.1 vs. 40.9, p<0.001) and received organs with longer ischemic times (5.6 hours vs. 5.0 hours, p < 0.001). Long term survival was significantly lower in patients who required post-transplant RRT (HR 3.92, 95% CI 3.64-4.34, Figure 1). Logistic regression identified several factors associated with post-operative renal failure including double lung transplantation (HR 1.31, 95% CI 1.06-1.62), recipient history of diabetes mellitus (HR 1.19, 95% CI 1.01-1.42) and ICU level needs at the time of lung transplantation (HR 1.56, 95% CI 1.14-2.14). Post-transplant renal failure is associated with significantly worse survival in lung recipients. In patients with normal pre-operative renal function, particular precautions should be taken to prevent renal decline in those undergoing bilateral lung transplantation, who have diabetes mellitus and who are in the ICU at the time of transplantation.

Staging System to Predict the Risk of Relapse in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.

Over the last decade autologous stem cell transplantation (ASCT) has emerged as the standard of care in the management of Multiple Myeloma (MM). However, the cases of early relapse (within 36 months) after the stem cell rescue remains a significant challenge. For a lot of practical purposes, it is crucial to identify whether a patient undergoing ASCT falls into the high-risk group (likely to relapse within 36 months) or a low risk one. Our analysis showed that existing MM staging systems (International Staging System or ISS and Durie Salmon Staging or DSS) are not sufficient to discriminate between the risk groups significantly. To address this, we gathered a total of 39 clinical and laboratory parameters of 347 patients from the Department of Medical Oncology of All India Institute of Medical Sciences (AIIMS). We employed a stacked machine learning model consisting spectral clustering and Fast and Frugal Tree (FFT) technique to come up with a 3-factor multivariate 2-stage staging scheme, which turns out to be extremely decisive about the outcome of the stem cell rescue. Our model comes up with a three-factor (1. if patients has relapsed following remission, 2. response to induction, 3. pre-transplant Glomerular Filtration Rate or GFR) staging scheme. The resulting model stratifies patients into high-risk and low-risk groups with markedly distinct progression-free (median survival—24 months vs. 91 months) and overall survival (median survival—51 months vs. 135 months) patterns.

Association of pretransplant kidney function with outcomes after lung transplantation.

There is a lack of data regarding the independent association of pretransplant kidney function with early and late outcomes among lung transplant (LT) recipients. We queried the United Network for Organ Sharing database for adult patients (≥18years of age) undergoing LT between 1987 and 2013. Glomerular filtration rate (GFR) was estimated using the modification of diet in renal disease (MDRD) and the Chronic kidney disease epidemiology collaboration (CKD-EPI) equations. The study population was split into four groups (>90, 60-90, 45-59.9, and <45mL/min/1.73m2 ) based on the estimated GFR at the time of listing. Overall, there was a good correlation between the GFR estimated from the two equations (n=17884, Pearson r=.816, P<.001). There was a consistent and independent association of worse early and late outcomes with declining GFR throughout the spectrum including those above 60mL/min/1.73m2 (P<.001 for overall comparisons). Although GFR<45mL/min/1.73m2 was associated with worse early and late survival, patients with GFR 45-59.9mL/min/1.73m2 do not appear to have survival advantage beyond 3years post-transplant. There is a good correlation between GFR estimated using MDRD and CKD-EPI equations among patients being considered for LT. Early and late outcomes after LT worsen in a linear fashion with progressively lower pretransplant GFR.

Determining eligibility for lung transplantation: A nationwide assessment of the cutoff glomerular filtration rate

Historical concerns about lung transplantation in patients with a glomerular filtration rate (GFR) ≤ 50 ml/min/1.73 m(2) have not been validated. We hypothesize that a pre-transplant GFR ≤ 50 ml/min/1.73 m(2) represents a high mortality risk, especially in the setting of acute GFR decline. In addition, we explore the potential for improved risk stratification using a statistically derivable alternative cutoff. Adult, primary, lung recipients in the United Network for Organ Sharing database were analyzed (October 1987 to December 2011). Recursive partitioning identified the GFR value that provides maximal separation in 1-year mortality. Survival over/under the cutoffs was compared using stratified log-rank, Cox, and Kaplan-Meier methods, before and after 1:2 propensity score matching. Median GFR at time of transplant for 19,425 study patients was 94.2 ml/min/1.73 m(2) (quartile 1-quartile, 2 76.9-105.9 ml/min/1.73 m(2)). Recursive partitioning identified a GFR of 40.2 ml/min/1.73 m(2) as the ideal inflection point for predicting 1-year survival. Cutoffs demonstrated statistically significant effects on survival after 840 patients with a GFR ≤ 50 ml/min/1.73 m(2) (hazard ratio, 1.28; 95% confidence interval, 1.15-1.43) and 401 patients with a GFR ≤ 40.2 ml/min/1.73 m(2) (hazard ratio, 1.57; 95% confidence interval, 1.36-1.83) were matched with high GFR controls (p < 0.001). In 13,509 patients with available GFR at the time of listing and transplant, a pre-transplant GFR decline of ≥ 50% from baseline was associated with worse survival (p < 0.001). A pre-transplant GFR ≤ 50 ml/min/1.73 m(2) is associated with decreased survival. However, patients with GFR between 40 and 50 ml/min/1.73 m(2) do not suffer excessive post-transplant mortality and should not be automatically excluded from listing. Notably, outcomes are worse in patients with poor renal function and concomitant pre-transplant GFR decline. Strategies should be devised to detect and manage interval renal deterioration before lung transplantation.

Does Renal Dysfunction and Method of Bridging Support Influence Heart Transplant Graft Survival?

Renal insufficiency is common in status 1B patients supported with inotropes or a continuous flow left ventricular device (CF-LVAD) as a bridge to heart transplantation. We evaluated the association of renal function and inotrope versus CF-LVAD support on posttransplant graft survival in status 1B patients. The Scientific Registry for Transplant Recipients database was analyzed for posttransplant survival in status 1B patients bridged with inotropes or CF-LVAD who underwent transplantation between 2003 and 2012. Pretransplant renal function was measured by estimating glomerular filtration rate (GFR) and was stratified as less than 45 mL · min(-1) · 1.73 m(-2), 45 to 59, and 60 or greater. Univariate Kaplan-Meier and multivariate Cox regression models were used to evaluate the main effects of GFR strata and inotropes versus CF-LVAD, and the interaction effect of GFR strata by CF-LVAD, on graft survival. This study included 4,158 status 1B patients (74% male, aged 53 ± 12 years). Of those, 659 patients had a CF-LVAD (HeartMate-II [Thoratec, Pleasanton, CA], n = 638; HVAD [HeartWare, Framingham, MA], n = 21), and 3,530 were receiving inotropes (31 CF-LVAD patients were also receiving inotropes). Kaplan-Meier analyses demonstrated reduced graft survival (p = 0.022) in patients with pretransplant GFR less than 45 versus GFR 45 to 59 (p = 0.062) and versus GFR 60 or greater (p = 0.007), and no effect of inotrope versus CF-LVAD support on graft survival (p = 0.402). Multivariate analysis demonstrated that, after adjusting for the main effects of GFR stratum, CF-LVAD, and inotropes, status 1B patients bridged with a CF-LVAD and GFR in the lowest stratum had reduced graft survival (interaction effect p = 0.040). Pretransplant renal insufficiency was associated with reduced posttransplant graft survival in status 1B patients. This risk is increased for patients bridged with a CF-LVAD (versus inotropes) who have GFR in the lowest stratum.

Estimated versus Measured Glomerular Filtration Rate in Children before Hematopoietic Cell Transplantation

An accurate assessment of kidney function before hematopoietic cell transplantation (HCT) can help to properly dose conditioning chemotherapy and follow patients for the development of chronic kidney disease. We cross-sectionally examined 94 children and young adults before HCT to compare formal nuclear glomerular filtration rate (GFR) testing with estimated GFR using creatinine and cystatin C–based equations, including the original Schwartz formula and the more recent formulas developed in the Chronic Kidney Disease in Children (CKiD) cohort. The median age of the cohort was 5.9 years (range, .26 to 30.5 years). The mean cohort nuclear GFR was 107.4 ± 24.7 mL/min/1.73 m2, with 18 of 94 subjects (19.1%) having abnormal kidney function (GFR < 90 mL/min/1.73 m2) before HCT. The creatinine-based original Schwartz and bedside CKiD formulas showed significant bias, overestimating the nuclear GFR by 57.4 (95% confidence interval [CI], 49.0 to 65.8) and 14.1 (95% CI, 7.1 to 21.1) mL/min/1.73 m2, respectively. Cystatin C formulas had less mean bias and improved accuracy but also had decreased sensitivity to detect abnormal kidney function before HCT. The Full CKiD equation showed the best performance, with a mean bias of −3.6 mL/min/1.73 m2 (95% CI, −8.4 to 1.2) that was not significantly different from the measured value and 87.7% of estimates within ±30% of the nuclear GFR. Although the more recent bedside CKiD formula performed better than the original Schwartz formula, both formulas had poor sensitivity for detecting a low GFR. An abnormal pretransplant nuclear GFR was not associated with post-HCT acute kidney injury, the need for dialysis, or death in the first 100 days. In conclusion, we observed cystatin C–based equations outperformed creatinine-based equations in estimating GFR in children before HCT. However, all formulas had decreased sensitivity to detect impaired GFR. Formal measurement of kidney function should be considered in children and young adults who need an accurate assessment of kidney function before HCT.

Belatacept Based Immunosuppression For Renal Dysfunction Post Intestinal Transplantation.

Calcineurin inhibitors have been linked to a higher incidence of acute renal failure due to its nephrotoxic effects, which may be related to its erratic area under the curve immediately after intestinal transplantation in patients with caval drainage of the grafts. We identified the patients demonstrating a significant decline in their pre-transplant glomerular filtration rate (eGFR) after transplantation. The decline was quantified using the MDRD equation. EBV status of the patient was documented before the switch. Any episodes of rejection after the switch were recorded. From October 2008 to November 2013, 24 patients underwent intestinal transplantation. All had Campath induction and Tacrolimus monotherapy. Six (25%) demonstrated a mean decline of 45mls/min (range 25-70mls/min) in their eGFR from pre-transplant values. Decline was noted at a mean of 45 days (range 7-720 days) post transplantation. All 6 patients were switched to Belatacept. All patients had a positive EBV serology at the time of the switch. Mean time post-transplant to switch was 208 days (range 23-1195 days). The switch was accompanied with Azathioprine (50mg OD) and Prednisolone (10mg OD) n=2, Low dose tacrolimus (levels<3) n=2, No other maintenance therapy n=2. One patient (17%) demonstrated moderate rejection, 15 days post switch to Belatacept. This patient was switched to Belatacept monotherapy at 5mg/kg. This patient later succumbed to an Aspergillus brain abscess related to the step up in immunosuppression to treat rejection. Majority of patients demonstrated a significant improvement of their eGFR. One patient demonstrated moderate rejection. Belatacept may be a valid option for patients demonstrating significant decline in their eGFR after transplantation. Belatacept as monotherapy may be a high-risk strategy for rejection.

The 24 Hour Urine Creatinine Clearance for Prediction of Glomerular Filtration Rate in Liver Cirrhosis Patients: Have We Considered All Elements?

Dear Editor, The correct estimation of renal function in patients with liver cirrhosis and chronic kidney disease (CKD) is difficult (1, 2). Direct measurement of glomerular filtration rate (GFR) using exogenous markers (iohexol or iothalamate) is considered the reference to assess renal function in cirrhotic patients (1, 2). However, direct measurement of GFR is not available at all transplant centers. The 24 hour urine creatinine clearance (CrCl) is widely used to measure GFR, and is calculated by multiplying the ratio of urine creatinine (Cr) to plasma Cr by 24 hours urine volume. However CrCl has several limitations. Besides the problem with accurately timed urine collection, CrCl is reported to overestimate the true GFR in liver cirrhosis patients compared with the direct measurement of GFR (1, 2). A low plasma Cr secondary to liver disease and poor muscle mass may overestimate GFR using CrCl. In addition, the GFR overestimation is also reported to be due to over-secretion of Cr from renal tubules in proportion to glomerular filtration, especially at low GFR (1, 2). Conversely, we have found that the total amount of Cr excreted in cirrhotic patients is lower than the minimum expected Cr excretion in 24 hours urine (20 mg/kg/day in males and 15 mg/kg/day in females). Hence, when urine Cr excretion is low, CrCl may also on the contrary underestimate the true GFR. In a retrospective study, we evaluated the charts of 160 consecutive patients who underwent liver transplantation alone (LTA) at our center from January 2002 to December 2012. Out of these, 25 patients had CKD with pre-transplant estimated GFR values ≤ 60 ml/min/ 1.73 m2 calculated using 4-variable and 6-variable modification of diet in renal disease (MDRD) equations. The 24-hour urine CrCl was available in all 25 patients within a month pre-transplant. Ten patients were excluded from analysis as their collected urine volumes were either 3000 ml suggesting under- or over- collection of urine. In remaining 15 patients, mean observed urine Cr excretion was significantly lower than the minimum expected Cr excretion in 24 hour urine (1.28 ± 0.62 grams/day vs. 1.69 ± 0.43 grams/day; P = 0.04). In these 15 patients with CKD, there was no significant difference between CrCl and MDRD-4 (49.6 ± 23.5 vs. 41.7 ± 11.6 respectively, P = 0.63), and between CrCl and MDRD-6 (49.6 ± 23.5 vs. 37.2 ± 9.5, respectively, P = 0.19) pre-transplant. However, GFR values at three months post-transplant were significantly higher compared with their corresponding values pre-transplant (see Table 1). The lower urine Cr excretion in these patients is probably secondary to decreased Cr production due to poor muscle mass and liver disease. The improvement in e-GFR early post-transplant suggests that there is likely some hemodynamic component to CKD pre-transplant. It is reported that the CKD eventually gets worse overtime post-LTA due to calcineurin inhibitor therapy and other risk factors (3, 4). In our study, although we did not measure GFR directly, the improved GFR values early post-LTA likely reflect true pre-transplant GFR values. In conclusion, although CrCl has been reported to overestimate GFR in liver cirrhosis patients with CKD, a lower than expected 24 hour urine creatinine excretion may also cause underestimation of GFR. Table 1. Pre- and Post-Liver Transplant (LT) e-GFR Values in 25 Study Patients

Outcomes of liver transplantation for patients with alagille syndrome: The studies of pediatric liver transplantation experience

Alagille syndrome (ALGS) is a multisystem disorder that manifests as childhood cholestasis. Reports of liver transplantation (LT) for patients with ALGS have come largely from single centers, which have reported survival rates of 57% to 79%. The aim of this study was to determine LT outcomes for patients with ALGS. We performed a retrospective analysis of the Studies of Pediatric Liver Transplantation database, which contains information about 3153 pediatric LT recipients. Data were available for 91 patients with ALGS and for 236 age-matched patients with biliary atresia (BA). The frequency of complex cardiac anomalies was lower in the LT group with ALGS versus published ALGS series (5% versus 13%). The pretransplant glomerular filtration rate (GFR) was <90 mL/minute/1.73 m(2) in 18% of the LT patients with ALGS and in 5% of the LT patients with BA (P < 0.001). The height deficit at listing was worse for the ALGS patients (66%) versus the BA patients (22%). The 1-year patient survival rates were 87% for the ALGS patients and 96% for the BA patients (P = 0.002). The deaths in the ALGS group mostly occurred within the first 30 days. No pretransplant factors associated with death were identified in the ALGS group. A survival analysis revealed that biliary (P = 0.02), vascular (P < 0.001), central nervous system (CNS; P < 0.001), and renal complications (P < 0.001) after LT were associated with death in the ALGS group. Renal insufficiency in the ALGS patients worsened after LT, and at 1 year, GFR was <90 mL/minute/1.73 m(2) in 22% of the LT patients with ALGS but in only 8% of the patients with BA (P = 0.0014). More LT pediatric patients with ALGS either were currently receiving special education (50% versus 30% for BA patients, P = 0.02) or had received special education in the past (60% versus 36%, P = 0.01). Vascular, CNS, and renal complications were increased in the ALGS patients after LT, and this reflected multisystem involvement. Although the 1-year survival rate was modestly lower for the ALGS patients versus the BA patients, the clustering of deaths within the first 30 days is notable and warrants increased vigilance and further investigation.

Long-Term (5 Years) Efficacy and Safety of Pancreas Transplantation Alone in Type 1 Diabetic Patients

Although combined pancreas and kidney transplantation is an established procedure for the treatment of type 1 diabetes (T1D) in patients with end-stage renal disease, the role of pancreas transplant alone (PTA) in the therapy of T1D subjects with preserved kidney function is still matter of debate. We report our single-center experience of PTA in 71 consecutive T1D patients all with a posttransplant follow-up of 5 years. Patient and pancreas (normoglycemia in the absence of any antidiabetic therapy) survivals were determined, and several clinical parameters (including risk factors for cardiovascular diseases) were assessed. Cardiac evaluation and Doppler echocardiographic examination were also performed, and renal function and proteinuria were evaluated. Actual patient and pancreas survivals at 5 years were 98.6% and 73.2%, respectively. Relaparotomy was needed in 18.3% of cases. Restoration of endogenous insulin secretion was accompanied by sustained normalization of fasting plasma glucose concentrations and HbA1c levels as well as significant improvement of total cholesterol, low-density lipoprotein-cholesterol, and blood pressure. An improvement of left ventricular ejection fraction was also observed. Proteinuria (24 hours) decreased significantly after transplantation. One patient developed end-stage renal disease. In the 51 patients with sustained pancreas graft function, kidney function (serum creatinine and glomerular filtration rate) decreased over time with a slower decline in recipients with pretransplant glomerular filtration rate less than 90 mL/min. PTA was an effective and reasonably safe procedure in this single-center cohort of T1D patients.

Transforming Growth Factor-β1-Gene Polymorphism in the Development of Kidney Disease After Liver Transplantation

The development of kidney dysfunction is one of the most important after liver transplantation (LT). Genetic variants of pathogenetically relevant cytokines may influence the development and course of the disease. The aim of our study was to evaluate the role of transforming growth factor-β1 (TGF-β1) polymorphism in this context. Four hundred eighty-six liver graft recipients were genotyped for TGF-β1 codon 25 (guanine → cytosine, G → C) by polymerase chain reaction. Renal function before and after LT was characterized by estimation of glomerular filtration rate (GFR) using four-parameter-modification of diet in renal disease formula on defined dates. GFR was compared among TGF-β1-genotype groups of the entire cohort within the median observation period of 7 years. For the assessment of renal function recovery after LT, patients were divided into three groups by GFR difference (ΔGFR = ± 10 mL/min). Mean pretransplant GFR differed significantly among TGF-β1-genotype groups (GG: 85.0 mL/min vs. GC/CC: 75.3 mL/min; P=0.016). The significance disappeared in the follow-up period. Although GG genotype demonstrated higher mean GFR levels, patients with GC/CC genotype tended to improve kidney function compared with GG genotype (P=0.013). Interestingly, lower mean GFR rates were observed among female compared with male recipients before (P=0.002), separately at all dates and cumulatively after LT (P<0.001). Genetic variants of one of the most important cytokine TGF-β1 at codon 25 may have an impact on kidney function, suggesting an unfavorable effect of C allele in pretransplant setting and serve as marker for the recovery of renal function after LT. The identification of further confounders seems to be promising.

Pre-transplant Kidney Function Predicts Chronic Kidney Disease After Liver Transplant: Meta-Analysis of Observational Studies

Chronic kidney disease is a common problem in long-term survivors after liver transplantation. Several studies to clarify the risk factors for incidence of chronic kidney disease among liver transplant recipients, including preoperative kidney function, have yielded conflicting results. The aim of this study was to conduct a systematic review of the published medical literature on the impact of pre-transplant kidney function on the occurrence of chronic kidney disease after liver transplantation. Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effects pooled estimates for incidence of chronic kidney disease across the published studies. The relative risk of chronic kidney disease after liver transplantation according to pre-transplant glomerular filtration rate was regarded as the most reliable outcome end-point. We identified seven studies (38,036 unique liver transplant recipients). A stratified analysis including only studies provided with glomerular filtration rate at transplant reported that the summary estimate of relative risk and 95% confidence intervals (CIs) for developing chronic renal failure among liver transplant recipients with diminished renal function at transplant was 2.12 (95% CI, 1.01; 4.46) (random-effects model). The p value for study heterogeneity was significant (p = 0.0001). Post-transplant chronic kidney disease shows impact on survival; the summary estimate for the adjusted relative risk of all-cause mortality with chronic kidney disease after liver transplant was 4.35 (95% confidence Intervals, 3.34; 5.66), p = 0.0001 (random-effects model). An increased risk of chronic kidney disease frequently exists among liver transplant recipients with reduced renal function at transplant. The occurrence of chronic kidney disease after liver transplantation has a major impact on mortality. Additional studies are needed to understand better the natural history of chronic kidney disease among liver transplant recipients.

Results of Pancreas Transplantation Alone with Special Attention to Native Kidney Function and Proteinuria in Type 1 Diabetes Patients

We report on our single-center experience with pancreas transplantation alone (PTA) in 71 patients with type 1 diabetes, and a 4-year follow-up. Portal insulin delivery was used in 73.2% of cases and enteric drainage of exocrine secretion in 100%. Immunosuppression consisted of basiliximab (76%), or thymoglobulin (24%), followed by mycophenolate mofetil, tacrolimus, and low-dose steroids. Actuarial patient and pancreas survival at 4 years were 98.4% and 76.7%, respectively. Relaparatomy was needed in 18.3% of patients. Restored endogenous insulin secretion resulted in sustained normalization of fasting plasma glucose levels and HbA1c concentration in all technically successful transplantations. Protenuria (24-hour) improved significantly after PTA. Renal function declined only in recipients with pretransplant glomerular filtration rate (GFR) greater than 90 ml/min, possibly as a result of correction of hyperfiltration following normalization of glucose metabolism. Further improvements were recorded in several cardiovascular risk factors, retinopathy, and neuropathy. We conclude that PTA was an effective and reasonably safe procedure in this single-center experience.

The Evolution of Kidney Function After Lung Transplantation: A Retrospective Cohort Study

Background Little information exists regarding the rate of kidney functional loss after lung transplantation. The aim of this study was to assess the evolution of kidney function after lung transplantation, seeking to identify a pretransplant glomerular filtration rate (GFR) threshold under which dual lung-kidney transplantation should be considered. Patients and methods We performed a single-center, retrospective cohort study among patients who received a first lung transplant. GFR was measured with the MDRD7 equation immediately before and up to 10 years after transplantation. A hierarchical model of linear regression was used to determine the evolution of GFR over time. Results We studied 241 subjects whose mean GFR was 92 ± 33 mL/min/1.73 m 2 immediately before transplantation. The GFR declined quickly during the first posttransplant month (−24 mL/min/1.73 m 2 vs baseline; 95% confidence interval [CI]: −27, −21 mL/min/1.73 m 2). It decreased slightly between 1 and 12 months (−34 mL/min/1.73 m 2 at 12 months vs baseline; 95% CI: −37, −31 mL/min/1.73 m 2) and then stabilized up to 10 years after transplantation. GFR loss varied according to the baseline GFR. In patients with baseline GFR ≤ 60 mL/min/1.73 m 2, the GFR declined by 9 mL/min/1.73 m 2 (95% CI = 6–15) at 1 year and was stable there after. Conclusion GFR declines rapidly in the first month and at 1 year after lung transplantation, stabilizing thereafter. Because they are likely to develop eligibility for kidney transplantation in the 1 to 2 years following lung transplantation, we believe that dual lung-kidney transplantation should definitely be considered for subjects with a baseline GFR ≤ 35 mL/min/1.73 m 2.

Earlier Is Not Necessarily Better in Preemptive Kidney Transplantation

While preemptive (before chronic dialysis) transplantation is associated with improved graft survival, it is unclear whether higher versus lower pretransplant kidney function is associated with even better graft survival after preemptive transplantation. We examined 671 first, preemptive, kidney-only transplantations at Hennepin County Medical Center and the University of Minnesota Medical Center 1984-2006. We estimated pretransplant glomerular filtration rate (eGFR, mL/min/1.73 m(2)) using the Modification of Diet in Renal Disease (MDRD) equation with Group 1: <10.0 (7.3 +/- 1.7, N = 324), Group 2: 10.0-14.9 (12.0 +/- 1.4, N = 217) and Group 3: >or=15.0 (21.1 +/- 10.0, N = 130). The mean difference in eGFR for Group 1 versus 3 was 13.8 pretransplant, 16.3 on day 1 and 13.9 on day 2 posttransplant. By week 1 and year 1 posttransplant, the differences between Groups 1 and 3 reduced to 6.3 and 4.5 mL/min/1.73 m(2), respectively. The adjusted relative risk (RR; Cox analysis) for graft failure was not significantly lower with higher pretransplant eGFR (reference eGFR <10.0); RR = 0.99 (95% confidence interval = 0.68-1.44, p = 0.9432) for eGFR 10.0-14.9; RR = 1.35 (0.89-2.05, p = 0.1588) for eGFR >or=15. Thus, early preemptive transplantation with higher eGFR does not necessarily improve graft survival after kidney transplantation, compared to preemptive transplantation with lower pretransplant eGFR.