1-year Glomerular Filtration Rate Research Articles

Lower Time in Therapeutic Range Relates to a Worse Kidney Graft Outcome

Tacrolimus has a narrow therapeutic margin. Maintaining tacrolimus blood levels in the appropriate range is difficult because of its intrapatient variability. In fact, greater blood level variability has been related to worse kidney graft outcome, but only measuring variability does not consider the therapeutic range goal. Determining the time in therapeutic range (TTR) using the Rosendaal method allows dose optimization by considering the adverse events associated with both supratherapeutic and subtherapeutic doses. Some previous studies in kidney and lung transplantation have shown that the measurement of TTR has been related to the subsequent graft outcome. We performed a single-center, observational study including 215 consecutive kidney transplants performed in our center. The percentage of time that the patient remained with levels above 6 ng/mL between months 3 and 12 (%TTR3-12) was calculated using the Rosendaal method. A lower %TTR3-12 was associated with a higher risk of acute rejection (area under the receiver operating characteristic curve, 0.614; 95% confidence interval [CI], 0.513-0.714; P=.018) and with a higher risk of having a 1-year glomerular filtration rate < 30 mL/min/1.73 m2 (area under the receiver operating characteristic curve, 0.676; 95% CI, 0.542-0.811; P=.014). The lowest tertile of %TTR3-12 was independently associated with a higher risk of death-censored graft loss (hazard ratio, 10.773; 95% CI, 1.315-88.264; P=.027) after adjusting by 1-year glomerular filtration rate, expanded criteria donation, and acute rejection throughout the first year. To conclude, measuring TTR after kidney transplant is an easy way to estimate the time of exposure to adequate levels of tacrolimus and relates to kidney graft outcome.

Textbook Outcome as a Quality Metric in Living and Deceased Donor Kidney Transplantation.

BACKGROUND:Quality in kidney transplantation is measured using 1-year patient and graft survival. Because 1-year patient and graft survival exceed 95%, this metric fails to measure a spectrum of quality. Textbook outcomes (TO) are a composite quality metric offering greater depth and resolution. We studied TO after living donor (LD) and deceased donor (DD) kidney transplantation.STUDY DESIGN:United Network for Organ Sharing data for 69,165 transplant recipients between 2013 and 2017 were analyzed. TO was defined as patient and graft survival of 1 year or greater, 1-year glomerular filtration rate of greater than 40 mL/min, absence of delayed graft function, length of stay of 5 days or less, no readmissions during the first 6 months, and no episodes of rejection during the first year after transplantation. Bivariate analysis identified characteristics associated with TO, and covariates were incorporated into multivariable models. Five-year conditional survival was measured, and center TO rates were corrected for case complexity to allow center-level comparisons.RESULTS:The national average TO rates were 54.1% and 31.7% for LD and DD transplant recipients. The hazard ratio for death at 5 years for recipients who did not experience TO was 1.92 (95% CI 1.68 to 2.18, p ≤ 0.0001) for LD transplant recipients and 2.08 (95% CI 1.93 to 2.24, p ≤ 0.0001) for DD transplant recipients. Center-level comparisons identify 18% and 24% of centers under-performing in LD and DD transplantation. High rates of TO do not correlate with transplantation center volume.CONCLUSION:Kidney transplant recipients who experience TO have superior long-term survival. Textbook outcomes add value to the current standards of 1-year patient and graft survival.

Predictors of Renal Outcomes in Sclerotic Class Anti-Neutrophil Cytoplasmic Antibody Glomerulonephritis

Background: The prognostic value of the anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN) classification has been demonstrated in several cohorts with sclerotic class having the worst renal outcome. Relevant published data on factors predicting outcomes in sclerotic ANCA GN is limited. Methods: Sclerotic ANCA GN patients were recruited from 5 centers worldwide for this retrospective cohort study. We describe the clinical characteristics of this cohort and evaluate predictors of 1-year glomerular filtration rate (GFR) and end-stage renal disease (ESRD). Kidney function at 12 months as measured by Modification of Diet in Renal Disease estimated GFR (eGFR) was modeled by simple and multiple linear regression analyses. We used Cox proportional hazards regression modeling to evaluate ESRD-free survival. Results: Of the 50 patients, 92% were Caucasian and 60% male with a mean age of 61 years. While 72% had renal limited disease, 82% were MPO ANCA positive. Kidney biopsies contained a median of 20 (interquartile range [IQR] 15–34) glomeruli with 96% showing moderate to severe interstitial fibrosis. Overall, 96% of patients received immunosuppressive drug therapy and 16% received plasmapheresis. Treatment response was achieved in all but 1 patient. The median (IQR) eGFR at entry was 14.5 (9–19) mL/min/1.73 m². Over a median (IQR) follow-up of 33.5 (17–82) months, 26 patients reached ESRD. Ten patients died with 6 of the deaths occurring within the first year of diagnosis. The hazard of progression to ESRD was significantly higher in those with lower GFR at study entry (p = 0.003) and with higher degree of tubular atrophy (p = 0.043). Conclusions: Renal recovery is rare among sclerotic ANCA GN patients requiring dialysis at entry and 12% of patients died in the first year. Entry GFR and tubular atrophy were significant predictors of GFR at 12 months and renal survival in patients with sclerotic class ANCA GN.

Contrast-induced nephropathy after peripheral vascular intervention: Long-term renal outcome and risk factors for progressive renal dysfunction

ObjectiveContrast-induced nephropathy (CIN) is a frequently used quality outcome marker after peripheral vascular interventions (PVIs). Whereas the factors associated with CIN development have been well documented, the long-term renal effects of CIN after PVI are unknown. This study was undertaken to investigate the long-term (1-year) renal consequences of CIN after PVI and to identify factors associated with renal function deterioration at 1-year follow-up. MethodsFrom 2008 to 2015, patients who had PVI at our institution (who were part of a statewide Vascular Interventions Collaborative) were queried for those who developed CIN. CIN was defined by the Collaborative as an increase in serum creatinine concentration of at least 0.5 mg/dL within 30 days after intervention. Preprocedural dialysis patients or patients without postprocedural creatinine values were excluded. Preprocedural, postprocedural, and 1-year serum creatinine values were abstracted and used to estimate glomerular filtration rate (GFR). ΔGFR was defined as preprocedural GFR minus 1-year GFR. Univariate and multivariate analyses for ΔGFR were performed to determine factors associated with renal deterioration at 1 year. ResultsFrom 2008 to 2015, there were 1323 PVIs performed; 881 patients met the inclusion criteria. Of these, 57 (6.5%) developed CIN; 47% were male, and 51% had baseline chronic kidney disease. CIN resolved by discharge in 30 patients (53%). Using multivariate linear regression, male sex (P = .027) and congestive heart failure (P = .048) were associated with 1-year GFR decline. Periprocedural variables related to 1-year GFR decline included percentage increase in 30-day postprocedural creatinine concentration (P = .025), whereas CIN resolution by discharge (mean, 13.1 days) was protective for renal function at 1 year (P = .02). A post hoc analysis was performed with 50 PVI patients (randomly selected) who did not develop CIN, comparing their late renal function with that of the CIN group stratified by the periprocedural 30-day variables. Patients with CIN resolution at discharge had similar 1-year renal outcomes to non-CIN patients, whereas the CIN-persistent (at discharge) patients had greater renal deterioration at 1 year compared with non-CIN patients (P = .016). ConclusionsMale sex and congestive heart failure are risk factors for further renal function decline in patients developing CIN after PVI. The magnitude and duration of increase in creatinine concentration (CIN persistence at discharge) correlated with late progressive renal dysfunction in CIN patients, suggesting that early-resolving CIN is relatively benign.

Experience With Hypothermic Machine Perfusion in Expanded Criteria Donors: Functional Outcomes

Hypothermic machine perfusion (HMP) decreases delayed graft function (DGF) and improves 1-year graft survival in expanded criteria donors (ECDs). Time of HMP could be associated with incidence of DGF. ObjectiveTo analyze functional outcomes of ECD grafts preserved totally (local grafts) or partially (imported grafts) with HMP. Materials and MethodsWe analyzed prospectively collected data from a cohort of first ECD graft receptors, with a minimum follow-up of 6 months. A total of 119 imported and 74 local grafts were included. Local ECD kidneys were preserved with HMP after retrieval. Imported ECD kidneys were preserved with simple cold storage and HMP. Vascular thrombosis, acute rejection, DGF, 1-year glomerular filtration rate, and 1-year graft survival were assessed. Univariate and estimative multivariate logistic regression was applied for analysis of DGF. A Cox proportional hazards model was applied to estimate graft survival. ResultsDGF occurred in 14 recipients of local grafts and in 33 recipients of imported grafts (28.0 vs 18.1%, P = .13); 1-year graft survival was better in the group of local grafts (80.3 vs 91.9%, P = .03). No differences in vascular thrombosis (5.9 vs 5.4%, P = .88), acute rejection (12.3 vs 9.8%, P = .91), or 1-year glomerular filtration rate (41.2 vs 40.5 mL/m/1.73m2, P = .87) were observed. In multivariate analysis, adjusted odds ratio for DGF was 1.20 (P = .79) and adjusted hazard ratio for graft survival was 1.93 (P = .31). ConclusionsThere is a trend that complete HMP reduces the risk of DGF and improves 1-year graft survival in ECD kidneys.

Renal Allograft Outcome After Simultaneous Heart and Kidney Transplantation

Chronic kidney disease frequently accompanies end-stage heart failure and may result in consideration of simultaneous heart and kidney transplantation (SHKT). In recent years, there has been a significant increase in SHKT. This single-center cohort consisted of 35 patients who underwent SHKT during 1996 to 2015. The aim of this study was to review factors that may predict better long-term outcome after SKHT. Thirteen patients (37%) had delayed graft function (DGF) after transplant (defined as the need for dialysis during the first 7days after transplant), which was significantly associated with mechanical circulatory support device therapy and high right ventricular systolic pressure before transplant. Most of the recipients had glomerular filtration rate (GFR) ≥50ml/min/1.73m2 at 1 and 3years after transplant (21 of 26 [81%] and 20 of 21 [95%], respectively). Higher donor age was associated with reduced 1-year GFR (p= 0.017), and higher recipient pretransplant body mass index was associated with reduced 3-year GFR (p= 0.008). There was a significant association between DGF and reduced median GFR at 1 and 3years after transplant (p<0.005). Patient survival rates at 6months, 1, and 3years after transplant were 97%, 91%, and 86% respectively. In conclusions, our data support good outcomes after SHKT. Mechanical circulatory support device therapy and pulmonary hypertension before transplant are associated with DGF, which is a risk factor for poor long-term renal allograft function.

Comparison of early neonatal valve ablation with vesicostomy in patient with posterior urethral valve

Background:To compare the results of final renal function by two methods of treatment in patients diagnosed as posterior urethral valve (PUV) (valve ablation vs. vesicostomy).Materials and Methods:Fifty-four boys diagnosed with PUV participated in this study. They were divided into top two groups. Thirty-one of the total were treated with primary valve fulguration (Group 1) and 23 were treated with vesicostomy (Group 2). One-year-creatinine level and glomerular filtration rate (GFR) were measured. Also, they were taken ultrasonography detecting hydronephrosis. Data analysed in IBM SPSS21 with t-test and Chi-square test. Presented with 95% of confidence intervals.Results:Fifty-four boys diagnosed with PUV participated in this study. The mean age of patients in Group 1 was 3.8 ± 1.48 days and Group 2 was 4.7 ± 1.85 days. One-year Cr level was 1.57 ± 1.45 in Group 1 and 1.57 ± 1.45 in Group 2 which was not statistically significant (P < 0.8). Also 1-year GFR level was 31.1 ± 4.4 in Group 1 and 33 ± 4.7% in Group 2 (P < 0.10/23) in Group 2 (43.47%) had severe hydronephrosis and 14/31 (45.16%) in Group 1 had severe hydronephrosis. Graded ultrasound results were not significantly different (P = 0.24).Conclusion:The results showed no significant difference. Vesicostomy might be a more favourable method due to less complication and follow-up in early neonatal life. Hence, the condition of the patients and decision of the surgeon are effective parameters in choosing an optimal method in patients diagnosed with PUV.

Impairment of Renal Function at One Year After Liver Transplantation Is a Prognostic Factor for Mortality.

Renal dysfunction/failure are risk factors for poor outcome after liver transplantation (LTX). Our aim is to determine if renal dysfunction has impact on the long term outcome after LTX. We used multiple cutoffs for GFR at 1 year post LTX to look for association with later mortality. 985 primary LTX transplant recipients from a single institution were studied. All included survived >1 year after LTX and underwent iothalamate glomerular filtration rate (GFR) testing. Patients were stratified by GFR at 1 year post LTX [GFR≤40 (n=140), 41-60 (n=290), >60 ml/min (n=555)]. 37 patients had GFR≤30, of which 13 had GFR≤20. The GFR≤40 group had significantly more patients >60 years old, female gender, cyclosporine maintenance, anemia, but did not differ by HTN, DM, liver disease etiology. The 5-year Kaplan Meier survival (6 years post LTX) was 81.6%, 89.1%, and 91.6% for 1-year GFR of ≤40, 41-60,>60 respectively (p=0.01), and dropped to 75.6% if GFR ≤30, compared to 90.1% for GFR>30 (p<0.001), and further to 53.8% if GFR≤20 compared to 84.5-91.6% for GFR>20 (p<0.001). Recurrence of liver disease did not correlate with GFR. Multivariate Cox regression analysis showed statistically significant increased risk of mortality for African American recipients [risk ratio (RR) 2.35,p=0.0002), GFR≤40 (RR 1.95, p=0.0009). Analysis for GFR≤30 showed a RR for mortality of 2.91 (p=0.009). Kaplan Meier 5-year graft survival was 81% for GFR≤40, compared to 88.7% with GFR>40 (p=0.024), and 72.7% if GFR≤30 (p=0.005). In conclusion, a GFR of 40 ml/min or lower at 1 year post LTX is associated with higher mortality and graft loss and therefore requires more agressive follow-up and intervention and thus has therapeutic implications. This GFR threshold is higher than previously anticipated. An accurate GFR measurement is essential for intermediate and long-term prognosis after LTX.

Prediction of Kidney Transplant Outcome by Donor Quality Scoring Systems: Expanded Criteria Donor and Deceased Donor Score

Due to disparity between organ supply and demand, use of kidneys from suboptimal donors has become increasingly common. Several donor quality systems have been developed to identify kidneys with an increased risk for graft dysfunction and loss. The purpose of our study was to compare the utility of Deceased Donor Score (DDS) and expanded criteria donor (ECD) status to predict kidney transplant outcomes in a single center. We analysed 280 deceased donor renal transplantation procedures, collecting data from the prospectively maintained institutional database. Kidney transplant outcome variable included delayed graft function, 1-year glomerular filtration rate (GFR1y), and death-censored graft loss (DCGL). Kidneys were obtained from marginal donors in 45.7% of transplant recipients by DDS and in 24.9% by ECD. DDS-defined marginal donors suffered delayed graft function (DGF) more frequently than nonmarginal donors (40.8% vs 25.0%; P = .006), whereas ECD did not develop DGF at a greater rate. GFR1Y was significantly worse among patients receiving kidneys from marginal donors: DDS 40.3 ± 12.9 vs 57.7 ± 19.4 mL/min/1.73 m2 (P < .001) and ECD 39.4 ± 14.1 vs 53.8 ± 19.1 mL/min/1.73 m2 (P < .0001). The most severe donor category defined by DDS (grade D) showed an independently worse death-censored graft survival hazard rate [HR] 2.661, 95% confidence interval [CI], 1.076–6.582; P = .034). DDS and ECD scoring systems are based on donor information available at the time of transplantation that predict 1-year graft function. Moreover in our center, DDS was better to predict DGF and death-censored graft survival than ECD.

Outcome of pregnancies complicated by oligohydramnios or anhydramnios of renal origin

To evaluate the outcome of fetuses with oligohydramnios due to kidney anomalies. A retrospective study was performed of all pregnancies diagnosed with oligohydramnios and associated kidney anomalies during the period 2000-2008. Outcome included pregnancy outcome, mortality, and morbidity. Morbidity included renal function based on the glomerular filtration rate (GFR) during follow-up. A total of 71 pregnancies were evaluated; 36 fetuses presented on ultrasound with cystic dysplasia, 15 with polycystic kidney disease (PKD) and 20 with hydronephrosis. Twenty-three (32%) had associated anomalies. In 49 fetuses (69%), the diagnosis had been made before 24 weeks of gestational age (GA); 41 of those pregnancies were terminated. Twenty-five neonates were live born: 10 survived, 15 died. Prognostic factors for survival included GA at diagnosis (32.2 weeks for survivors vs 28.1 weeks for non-survivors; P = 0.02), diagnosis of hydronephrosis (7 in the survivors vs 4 in the non-survivors: P = 0.05), isolated anomaly (9 in the survivors vs 7 in the non-survivors: P = 0.04). Severity of oligohydramnios (1 case of anhydramnios in the survivors vs 7 in the non-survivors: P = 0.08) was not significant. The 1-year GFR was below 50 mL/min.1.73 m(2) in four of the ten survivors. The prognosis of early onset renal oligohydramnios is poor. Predictive determinants of survival are: GA at diagnosis, nature of renal anomaly (hydronephrosis vs other), and presence of associated anomalies.

Chronic Kidney Disease Following Liver Transplantation: A South Australian Experience

The incidence of chronic kidney disease (CKD) and its impact on survival have not been widely studied in the Australian liver transplant (OLT) population. The aims of this study were to evaluate the prevalence of CKD stages at various time points, calculate the cumulative incidence of progression to severe CKD, and study the impact of CKD stages on patient survival and risk factors for severe CKD in a single-center post-OLT population. We studied retrospectively 130 patients who underwent OLT in South Australia with a minimum of 6 months of follow-up from 1992 to 2008. CKD was staged according to Kidney Diseases Outcome Quality Initiative Guidelines. Glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease equation. Multiple pre- and post-OLT variables were examined for their association with severe CKD. Log-rank tests and Cox regression analysis were performed to evaluate the survival data. The cumulative incidences of severe CKD (stages 4 and 5) at 2, 5, and 15 years were 3.8%, 12.7%, and 14.8%, respectively. Severe CKD was associated with an increased mortality (hazard ratio 6.5; 95% confidence interval = 2.5–17.0; P < .001). Mild and moderate CKD stages were not associated with increased mortality. Risk factors for severe CKD were: female gender, hepatitis C infection, pre-OLT diabetes, acute renal failure post-OLT, and low 1-year GFR. Mild and moderate CKD are common post-OLT. The development of severe CKD, which can be predicted early in the post-OLT period, is strongly associated with an increased mortality rate.

Percutaneous Radiofrequency Ablation Does Not Affect Glomerular Filtration Rate

To study short- and intermediate-term global renal function in patients undergoing a single percutaneous radiofrequency ablation (pRFA) for a solitary renal parenchymal tumor. We reviewed the records of 62 patients who underwent a single pRFA for solitary renal parenchymal tumor. We used the abbreviated Modified Diet for Renal Disease equation to calculate baseline, 1-month, and 1-year glomerular filtration rate (GFR). We defined normal as >60, moderately diminished as 45-60, and severely diminished GFR as <45 cc/minute/1.73 m². We used the Wilcoxon paired rank sum method to compare 1-month and 1-year GFR to baseline. We fit a linear regression model to test the association of lesion size to GFR controlling for lesion location and baseline GFR. There was no difference in GFR from baseline at 1 month or 1 year (55 vs. 58 cc/minute/1.73 m², p=0.24 and 55 vs. 57 cc/minute/1.73 m², p=0.8, respectively). Tumor size did not affect GFR at 1 month or 1 year after controlling for lesion location and baseline GFR. A single application of pRFA does not affect GFR in the short or intermediate term.

Combined Posttransplant Prophylactic IVIg/Anti-CD 20/Plasmapheresis in Kidney Recipients With Preformed Donor-Specific Antibodies: A Pilot Study

This study assesses the immunologic, functional, and histologic course of kidney recipients with preformed donor-specific alloantibodies (DSA) receiving deceased donor kidneys according to two prophylactic strategies that have been sequentially applied posttransplant. The first strategy combined posttransplant quadritherapy/intravenous immunoglobulin (group 1, n=36) and the second added to the above protocol anti-CD20/plasmapheresis (group 2, n=18). All patients had a concomitant evaluation of glomerular filtration rate, protocol biopsies, and DSA mean intensity of fluorescence (MFI) at 3 month and 1 year posttransplant. Peak and day-0 class-I or II DSAmax-MFI were similar in both groups. The rate of acute antibody-mediated rejection (AMR) was similar in both groups (19.6% vs. 16.6%, respectively). At 1 year posttransplant, group 2 was characterized by lower microcirculation inflammation lesions (glomerulitis+capilaritis score of 1.8+/-0.2 vs. 2.7+/-0.2, respectively, P=0.03), a lower rate of transplant glomerulopathy (7% vs. 38%, P=0.02), and a lower rate of chronic AMR (41.3% vs. 13.3%, respectively, P=0.03). The decline in DSA-MFI from day 0 to 1 year was 44%+/-13% in group 1 compared with 80%+/-8% in group 2 (P=0.02). Finally, the 1-year glomerular filtration rate was 43+/-16 vs. 54+/-16 mL/min/1.73 m(2) in groups 1 and 2, respectively (P=0.04). This study raises the possibility that a more intensive day 0 prophylactic immunosuppressive strategy combining intravenous immunoglobulin/anti-CD20/plasmapheresis in this high-risk population, despite similar rates of early acute clinical humoral rejection, is associated with significant differences in long-term function and chronic AMR rate. Future prospective randomized studies are needed to assess the best strategies to be applied in light of the pretransplant immunologic risk stratification.

Effect of Pretransplantation Body Mass Index on Allograft Function and Patient Survival After Renal Transplantation

We evaluated the effects of pretransplantation recipient body mass index (BMI) on allograft survival and on kidney function. Kidney transplant recipients were grouped according to their pretransplantation BMIs: Group I (BMI <18.5 kg/m2; n = 10); Group II (BMI 18.5–24.9 kg/m2; n = 62); Group III (BMI 25.0–29.9 kg/m2; n = 47); and Group IV (BMI >30.0 kg/m2; n = 16). Excellent 1-year patient and graft survival rates were observed in all groups. Increased BMI was associated with increased hypertension and longer hospital stays. The incidence of acute rejection episodes, slow graft function, and delayed graft function, as well as the need for antithymocyte globulin Fresenius (ATG-F) rescue therapy were comparable between the 4 patient groups. The 1-year glomerular filtration rate was markedly different between the 4 patient groups. The 1-year posttransplantation glucose level was higher among obese patients compared with the other groups. A multivariate regression analysis confirmed the association of a higher 1-year GFR with obesity (BMI >30.0 kg/m2). Overweight and obese recipients showed excellent long-term patient and graft survival rates. Accordingly, denying patients renal transplantation because of obesity may not be justified.

Tacrolimus/Sirolimus Versus Tacrolimus/Mycophenolate in Kidney Transplantation: Improved 3-Year Graft and Patient Survival in Recent Era

Registry analyses suggest that tacrolimus (TAC)/mycophenolate (MPA) immunosuppression is associated with superior kidney graft survival versus TAC/sirolimus (SRL). Large single-center experience can assist in clarifying these findings, by examining outcomes related to specific utilization practice. We retrospectively examined the outcomes of 518 consecutive first renal transplants at a single center treated with TAC/SRL (n=307) or TAC/MPA (n=211) with prednisone. Graft and patient survival, acute rejection, and 1-year glomerular filtration rate (GFR) were analyzed by era of transplant (2000-2002 vs. 2003-2006). Changes in TAC/SRL utilization between eras included elimination of the SRL loading dose and a reduction in TAC target trough concentrations. Three-year graft survival with TAC/SRL was lower when first used (2000-2002) because of a higher incidence of patient death, primarily due to cardiovascular causes. Survival improved from 85.3% to 95.9% between 2000 to 2002 and 2003 to 2006 (P=0.001), with comparable graft and patient survival between TAC/SRL and TAC/MPA cohorts, confirmed following multivariable analysis controlling for donor and recipient factors. Rates of BK virus and acute rejection were comparable, but a higher incidence of hyperlipidemia, anemia, posttransplant diabetes, and a lower 1-year GFR (57.6 vs. 63.1 mL/min, P=0.008) was noted in the TAC/SRL cohort. These data, as the largest long-term single-center report comparing TAC/SRL with TAC/MPA in kidney transplantation, demonstrate worse patient survival initially with TAC/SRL, with improved outcomes in a later era that were temporally associated with reduced TAC exposure. Differences in cardiovascular risk factors and 1-year GFR highlight the need for further investigation of the optimal utilization of SRL in kidney transplantation.

Factors influencing renal function after liver transplantation. Results from the MOST, an international observational study

Renal failure, both acute and chronic, is a common complication after liver transplantation and can seriously jeopardise long-term outcome. Given organ shortage it should be essential to determine which patients will experience progressive and severe renal dysfunction after liver transplantation (LT). To correlate pre-transplant renal function and risk factors for renal failure after liver transplantation with occurrence of renal failure at 1 and 5 years after LT, with particular attention to hepatitis C virus (HCV) infection. Data from patients enrolled in the liver section of Neoral MOST (Multinational Observational Study in Transplantation) study were used for the analysis. HCV status, pre-transplant serum creatinine level, recipient gender, recipient age, pre-transplant arterial hypertension, pre-transplant diabetes mellitus, pre-transplant antiviral therapy, the time of the transplant (before or after 2000) and immunosuppressive regimen were collected for each patient. Post-transplant occurrence of renal failure at 1 and 5 years was defined as a GFR<60 mL/min/1.73 m(2) (Stage III of the National Kidney Foundation). Data from 1948 patients enrolled in the study were considered. Glomerular filtration rate (GFR) was evaluated in 406 patients at 1 year and in 233 patients at 5 years after LT. The prevalence of HCV infection was 35% in the former and 37% in the latter. The median GFR was 70 mL/min/1.73 m(2) after 1 year and 69 mL/min after 5 years, significantly lower in HCV-positive (HCV+) than in HCV-negative (HCV-) patients both 1 and 5 years after LT (p<0.001). GFR before transplant correlated with GFR at 1 month, 1 and 3 years (p<0.0001 for all correlations). Multivariate analysis confirmed HCV status, pre-LT serum creatinine levels and recipient gender as significant predictors of 1-year GFR (p<0.001 for all three). Further analysis of the effect of recipient gender indicated that the only significant risk factor observed in both male and female patients was HCV positivity. Only 1-year GFR was an independent predictor of 5-year GFR (p<0.001). HCV+ status, cyclosporine (CsA) exposure, antiviral therapy and diabetes mellitus had no significant influence on 5-year GFR. HCV status and pre-LT serum creatinine levels were independent predictors of renal function a year after LT, together with GFR before transplant. The negative impact of HCV positivity on renal function was not confirmed in the long term, whereas the prognostic influence of an abnormal renal function in the early post-transplant period was more persistent.

Low 1-Year Cyclosporine Microemulsion Doses Are Associated With Better 5-Year Renal Graft Function: An Insight From MOST, a Multinational Observational Study

Background In earlier registry analyses, cyclosporine at doses of < 3 mg/kg/d at 1 year post–renal transplantation has been associated with significant graft loss or reduction in renal function. Improvements in cyclosporine formulation with increased bioavailability, plus the use of more efficient comedications, may now confer better outcomes. To determine the effect of the 1-year cyclosporine microemulsion (CsA-ME) dose on renal allograft function at 5 years, we analyzed data collected from 2889 patients with documented graft survival to year 5 in a prospective, multinational, observational study—Neoral MOST. Results Glomerular filtration rate (GFR) at year 1 was 63 ± 20 mL/min and 59 ± 22 mL/min at year 5. The multivariate analysis including year 1 CsA-ME dose as factor and GFR at 1 year as covariate revealed the most significant factors affecting GFR at year 5 were 1-year GFR, donor age > 60 years, and CsA-ME dose at 1 year. Risk factors associated with reduction in 5-year GFR (<65 mL/min) included donor or recipient age >60 years, delayed graft function, cadaveric donor, previous graft, and acute rejection. CsA-ME dose <3 mg/kg/d was found to protect GFR. Analysis of GFR at each year posttransplantation (Wilcoxon model) found 1-year CsA-ME (cutoff 3 mg/kg/d) had a significant effect at each time point. Conclusions Compared to higher doses, CsA-ME <3 mg/kg/d at year 1 posttransplantation is associated with increased preservation of renal allograft function at year 5.

Estimated One-Year Glomerular Filtration Rate is the Best Predictor of Long-term Graft Function Following Renal Transplant

Long-term success of renal transplantation depends upon the quality of the donor organ, avoidance of peritransplant and early posttransplant damage (rejection), and optimal maintenance of graft function after the first 6-12 months. Glomerular filtration rate (GFR) at 1 year is a standard way to evaluate short-term success, whereas calculated GFR at 5 years gives a better appreciation of long-term outcomes. The objective of this study was to assess the effect of various demographic and transplant-related parameters on renal function via GFR at 1 year and 5 years post transplantation, using univariate and multivariate data analysis. Data on 1-year GFR were available from 10,397 patients, whereas 2,889 patients provided data on both 1-year and 5-year GFR. All patients were enrolled in the Neoral Multinational Observational Study in Transplantation (Neoral-MOST), an ongoing, prospective, observational study of adult renal transplant recipients. One-year GFR was the most relevant predictor for 5-year GFR. In a multifactorial analysis (ANCOVA) using 1-year GFR as a continuous variable, the effects of several highly relevant parameters from univariate analysis (such as acute rejection and delayed graft function) on 5-year GFR appeared to be fully mediated by their influence on 1-year GFR, whereas immunological risk factors like HLA match or previous transplantation had an ongoing effect on graft function beyond year 1. The findings of this study corroborate and augment data from previous registry surveys, and confirm the importance of observational studies in investigating the role of peritransplant parameters on long-term graft outcome.