Decline In Graft Function Research Articles

220-OR: Is There Any Prognostic Value of Diabetes-Associated Autoantibody Levels for Predicting Islet Graft Function in Patients with Long-Standing Type 1 Diabetes Mellitus?

Introduction: Correlation between increasing titers for GADA, IA-2A, and ZnT8A and graft loss due to recurrent autoimmunity has been reported, but not confirmed in other studies. Here, we assessed the prognostic value of DAA levels for predicting graft function in our cohort of islet transplant recipients. Methods: Twelve patients with T1DM with hypoglycemic unawareness underwent islet allotransplantation (ITx). Eight of those patients were randomly assigned to receive Reparixin (CXCR1/2 inhibitor) and remaining 4 to placebo in addition to thymoglobulin, tacrolimus and mycophenolate mofetil for immunosuppression. Titers of DAAs were monitored before IT and 0, 7, and 75 days and every 3 months post-operatively. Results: IA-2A and ZnT8A levels were undetectable prior to and after IT in all 12 T1DM patients at any time points, median follow-up of 56 months (24-66) so had no value in islet monitoring. No difference was observed for trends of GADA titers between 4 patients with long-term insulin independence after IT and the remaining 8 who experienced a decline in islet graft function. Prior to and after IT, GADA levels did not vary between patients receiving Reparixin and placebo with most GADA negative (65% and 50%, respectively). Most patients converted from GADA seronegative to seropositive or increased antibody titers [5/8 (62.5%) and 4/4 (100%), respectively] and converted back to seronegative by 1 year post-transplant and maintained partial or complete islet function over 4 years. Conclusion: We found no correlation between trends of anti-GAD65 autoantibody levels and IT outcome in our 12-patient cohort. Levels of DAAs targeting IA-2 and ZnT8 were not detectable in all patients prior to and after IT and did not correlate with IT outcome. Differences in immunosuppression and anti-inflammatory regimens and patient characteristics between studies may contribute to inconsistency among reported results. Disclosure P.J. Bachul: None. J.E. Golebiewska: None. F. Antic: None. M. Para: None. L. Basto: None. A.C. Lucander: None. K. Golab: None. L. Perea: None. M.L. Tibudan: None. L. Wang: None. C.C. Thomas: None. P. Witkowski: None. Funding State of Illinois; Dompé

Multicentre randomised controlled trial protocol of urine CXCL10 monitoring strategy in kidney transplant recipients

IntroductionSubclinical inflammation is an important predictor of death-censored graft loss, and its treatment has been shown to improve graft outcomes. Urine CXCL10 outperforms standard post-transplant surveillance in observational studies, by...

The effect of maintaining high hemoglobin levels on long-term kidney function in kidney transplant recipients: a randomized controlled trial.

BackgroundPosttransplant anemia may be a major determinant of chronic allograft nephropathy. However, the impact of correcting anemia on graft function remains controversial.MethodsA 3-year follow-up of an open-label, multicenter, randomized controlled trial involving kidney transplantation recipients examined whether sustained maintenance of target hemoglobin (Hb) concentrations at a high level (12.5–13.5 g/dL, n = 64) with either darbepoetin alfa or epoetin beta pegol would slow the graft function decline rate as the primary efficacy endpoint, compared with maintenance of a low Hb concentration (10.5–11.5 g/dL, n = 63).ResultsThe mean blood pressures in the two groups were well controlled throughout the study. In the high Hb group, mean Hb concentrations increased to >12 g/dL at 3 months, reaching the target range at 18 months. At the end of this study (36 months), the mean Hb concentration was 12.8 ± 0.7 g/dL in the high Hb group and 11.5 ± 1.2 g/dL in the low Hb group. The decline rate of the estimated glomerular filtration (eGFR) rate was considerably greater in the low Hb group (ΔeGFR, −5.1 ± 9.5 mL/min/1.73 m2) than in the high Hb group (−1.0 ± 8.4 mL/min/1.73 m2) (P = 0.02). Of note, only a few high Hb patients developed cardiovascular events and returned to hemodialysis, but the low Hb patients did not.ConclusionThis prospective study suggests that correcting anemia to the target Hb level range (12.5–13.5 g/dL) slows renal function deterioration by >3 years in the chronic phase of allograft nephropathy.

Effects of the strict control of blood pressure in pediatric renal transplant recipients-ESCORT trial.

Strict BP control can retard progression of CKD in children. This prospective 3-year randomized controlled trial is aimed to investigate whether strict BP control can retard progression of chronic allograft dysfunction. Twenty-three pediatric patients were randomly selected to the standard BP group (STAND, target 24-hour MAP 50-95th percentile, n=11) or the intensified BP group (INTENS, target 24-hour MAP <50th percentile, n=12). The primary endpoint was an annual reduction in eGFR (Schwartz formula, mL/min/1.73m2 /y), secondary graft survival, BP, proteinuria, and safety. A total of 21 children (age at entry 11.2 (range 6.2-16.8) years) completed the study, with 73% of children in INTENS and 70% of children in STAND group reached their goal BP. Ambulatory indexed 24-hour MAP decreased significantly in INTENS group (from 0.94 (range 0.86-1.17) to 0.85 (range 0.79-1.01, P<0.01)) but not in STAND group (from 0.93 (range 0.85-1.07) to 0.90 (range 0.84-1.01)). Proteinuria did not change significantly in either group (22.1mg/mmol creatinine to 15.3 in STAND group vs 25.7 to 11.8 in INTENS group). The annual reduction in eGFR did not differ between the INTENS and STAND groups (-1.9mL/min/1.73m2 /y (range +6.4 to -14.3) vs -0.9 (range +4.0 to -8.5)). This first randomized controlled trial on strict BP control has demonstrated that strict BP control is feasible in 73% of children but the strict BP control does not lead to retardation of graft function decline in comparison with standard BP control. However, the results need to be interpreted with caution keeping the major limitation of the study, that is, small sample size in mind.

Donor-specific Antibody Surveillance and Graft Outcomes in Pediatric Kidney Transplant Recipients.

The development of de novo donor-specific antibodies (dnDSA) has been associated with rejection and graft loss in kidney transplantation, and DSA screening is now recommended in all kidney transplant recipients. However, the clinical significance of dnDSA detected by screening patients with a stable creatinine remains unclear. One hundred three patients younger than 18years receiving a first, kidney alone transplant between December 1, 2007, and December 31, 2013, underwent DSA screening every 3months for 2years posttransplant, with additional testing as clinically indicated. No treatment was given for DSAs in the absence of biopsy-proven rejection. Twenty (19%) patients had dnDSA first detected on a screening test, and 13 (13%) patients had dnDSA first detected on a for-cause test. Mean follow-up time posttransplant was 4.4years. Screening-detected dnDSA was associated with an increased risk of rejection within 3years, microvascular inflammation, and C4d staining on a 2-year protocol biopsy. In a Cox proportional hazards regression, screening-detected dnDSA was not associated with time to 30% decline in estimated glomerular filtration rate (adjusted hazard ratio, 0.88; 95% confidence interval [CI], 0.30-2.00; P=0.598) or graft loss. dnDSA first detected on for-cause testing was associated with a 2.8 times increased risk of decline in graft function (95% CI, 1.08-7.27; P=0.034) and a 7.34 times increased risk of graft loss (95% CI, 1.37-39.23 P=0.020) compared with those who did not develop dnDSA. The clinical setting in which dnDSA is first detected impacts the association between dnDSA and graft function. Further research is needed to clarify the role of dnDSA screening in pediatric kidney transplantation.

Prospective Assessment of Adenovirus Infection in Pediatric Kidney Transplant Recipients.

Adenovirus infection is associated with graft dysfunction and graft loss in pediatric cardiac, lung, and liver transplants in prior retrospective studies, but data in pediatric kidney transplant recipients is limited. We conducted a prospective single-center cohort study of 75 consecutive pediatric kidney transplant recipients who underwent monthly screening for adenovirus viremia and symptom assessment for 2 years posttransplant. Adenovirus viremia was detected in 11 (14.7%) patients at a median onset of 173 days (interquartile range, 109-310 days) posttransplant, 6 (8%) had asymptomatic viremia, and 5 (6.7%) had symptomatic disease (2 with hematuria and 3 with an acute febrile respiratory illness). Viremic patients did not differ from nonviremic patients in age, immunosuppression management, or cytomegalovirus or Epstein-Barr virus serostatus, but were more likely to develop cytomegalovirus viremia during the first 2 years posttransplant. No patient had an increase in creatinine from baseline during the time of adenovirus viremia. In a Cox proportional hazards regression, subclinical adenovirus viremia was not associated with a faster time to a 30% decline in estimated glomerular filtration rate. Adenovirus infection is common among pediatric kidney transplant recipients and frequently causes symptomatic disease; however, symptoms are often mild and are not associated with a decline in graft function. Routine monitoring for adenovirus viremia in pediatric kidney transplant recipients may not be warranted.

Dietary Approach to Stop Hypertension (DASH) diet and risk of renal function decline and all-cause mortality in renal transplant recipients.

Renal transplant recipients (RTR) are at risk of decline of graft function and premature mortality, with high blood pressure as an important risk factor for both. To study the association of the Dietary Approach to Stop Hypertension (DASH) diet with these adverse events, we conducted a prospective cohort study of adult RTR. Dietary data were collected using a validated 177‐item food frequency questionnaire and an overall DASH‐score was obtained. We included 632 stable RTR (mean ± standard deviation age 53.0 ± 12.7 years, 57% men). Mean DASH score was 23.8 ± 4.7. During median follow‐up of 5.3 (interquartile range, 4.1‐6.0) years, 119 (18.8%) RTR had renal function decline, defined as a combined endpoint of doubling of serum creatinine and death‐censored graft failure, and 128 (20.3%) died. In Cox‐regression analyses, RTR in the highest tertile of the DASH score had lower risk of both renal function decline (hazard ratio [HR] = 0.57; 95% confidence interval [CI], 0.33‐0.96, P = .03) and all‐cause mortality (HR = 0.52; 95%CI, 0.32‐0.83, P = .006) compared to the lowest tertile, independent of potential confounders. Adherence to a DASH‐style diet is associated with lower risk of both renal function decline and all‐cause mortality. These results suggest that a healthful diet might benefit long‐term outcome in RTR.

Glomerulopatí del trasplante. Resultados clínicos y seguimiento de casos.

We describe the evolution of graft function in patients with transplant glomerulopathy measure by levels of serum creatinine, proteinuria and estimated glomerular filtration rate. Cross-sectional study conducted in the Regional General Hospital No. 46 IMSS. Included patients with kidney allograft and diagnosis of renal biopsy of transplant glomerulopathy grafting between January 1, 2006 to April 31, 2013 serum creatinine, proteinuria and estimated glomerular filtration rate at diagnosis, 6, 12 and 24 was recorded months. The results are shown with numbers, percentages and standard deviations. 42 patients were included. At 6 months of diagnosis, 14% decline in graft function and 7.1% graft loss. At 12 months, 17.9% graft loss, and at 24 months 36.3% had chronic graft dysfunction and graft loss as return to dialysis. Evolution in our patients seems to be better to other series of cases reported in the literature.

Controversies in the management of the haemodialysis-related arteriovenous fistula following kidney transplantation.

ABSTRACTArteriovenous fistula (AVF) is regarded as the best vascular access for chronic haemodialysis (HD). Still, AVF inherently causes significant haemodynamic changes. Although the necessity for vascular access despite its putative cardiovascular complications favours AVF creation in patients under chronic HD, one may question whether sustaining a functional AVF after successful kidney transplantation extends the haemodynamic threat. Small prospective series suggest that AVF ligation causes rapid and sustained reduction in left ventricular hypertrophy. Still, the benefits of such a cardiac remodelling in long-terms of cardiovascular morbi-mortality still need to be proven. Furthermore, the elevation of diastolic blood pressure and arterial stiffness caused by AVF ligation may blunt the expected cardio-protection. Finally, the closure of a functioning AVF may accelerate the decline of kidney graft function. As a whole, the current management of a functioning AVF in kidney transplant recipients remains controversial and does not rely on strong evidence-based data. The individual risk of graft dysfunction and a return to chronic HD also needs to be balanced. Careful pre-operative functional assessments, including cardio-pulmonary testing and estimated glomerular filtration rate slope estimation, may help better selection of who might benefit the most from AVF closure. Large-scale prospective, ideally multi-centric, trials are essentially needed.

IL-6 production by monocytes is associated with graft function decline in patients with borderline changes suspicious for acute T-cell-mediated rejection: a pilot study

Although borderline changes (BL) suspicious for acute T-cell-mediated rejection represent a diagnostic category, its clinical relevance is questioned leading to heterogeneous therapeutic management. We hypothesized that measuring IL-6 secretion by peripheral blood mononuclear cells identifies patients with ongoing graft damage. We examined the association between secreted IL-6 and the change in estimated glomerular filtration rate at 6 months after the biopsy (ΔeGFR). We then conducted phenotypic and functional studies on patient and mouse innate immune cells in the blood and the kidney. In a training set, ΔeGFR was strongly associated with IL-6 levels, showing a clinically meaningful decline of 4.6 ± 1.5 ml/min per increase in log10 IL-6 (P = 0.001). These results were consistent after adjustment and were reproduced in a validation cohort. Phenotyping of peripheral blood cells revealed that the main source of IL-6 was CD14+ CD16- CCR2+ HLA-DR+ CD86+ CD11c+ inflammatory monocytes. There was a significant correlation between IL-6 secretion and interstitial dendritic cell density in the biopsy. Finally, characterization of mouse kidney dendritic cells revealed that they share features with macrophages and function as effector cells secreting IL-6. In conclusion, measuring IL-6 secreted by peripheral blood cells can be useful in the management of patients with BL in the absence of a concurrent inflammatory condition.

Posttransplantation anemia in kidney transplant recipients: A retrospective cohort study.

We sought to assess the frequency and predictors of early and late posttransplantation anemia (PTA). In addition, we aimed to assess the outcomes of patients with anemia and to assess the impact of anemia on mortality, graft function, and graft failure.Patients who underwent kidney transplantation in a single center during a 4-year period were included. Predictors associated with the development of anemia at 6 months (early PTA) or 2 years (late PTA) were evaluated in a univariate and multivariate analyses. The effects of anemia and other variables on mortality and graft function were assessed.A total of 266 kidney transplant recipients were included. The prevalence of PTA at 6 months (early PTA) was 51.3% and at 2 years (late PTA) was 36.6%. Female sex was significantly associated with early PTA. Patients with early PTA proceeded to late PTA. Patients with both early and late PTA had a higher mortality rate at 4 years compared to patients without anemia. On multivariable analysis, lower Hb at 2 years posttransplantation (hazard ratio [HR] 0.716, 95% confidence intervals [CI] 0.541–0.948, for every increment of 1 g/dL) was significantly associated with mortality. Patients with late PTA suffered a decline in eGFR compared to patients without anemia (P = .026). Furthermore, a lower Hb at 2 years posttransplantation was also associated with graft failure (HR 0.775, 95% CI 0.619–0.969, for every increment of 1 g/dL).Post-transplantation anemia is significantly associated with late mortality, with a decline in graft function and with an increased incidence of graft failure.

Effects of DNA Methylation on Progression to Interstitial Fibrosis and Tubular Atrophy in Renal Allograft Biopsies: A Multi-Omics Approach.

Progressive fibrosis of the interstitium is the dominant final pathway in renal destruction in native and transplanted kidneys. Over time, the continuum of molecular events following immunological and nonimmunological insults lead to interstitial fibrosis and tubular atrophy and culminate in kidney failure. We hypothesize that these insults trigger changes in DNA methylation (DNAm) patterns, which in turn could exacerbate injury and slow down the regeneration processes, leading to fibrosis development and graft dysfunction. Herein, we analyzed biopsy samples from kidney allografts collected 24 months posttransplantation and used an integrative multi-omics approach to understand the underlying molecular mechanisms. The role of DNAm and microRNAs on the graft gene expression was evaluated. Enrichment analyses of differentially methylated CpG sites were performed using GenomeRunner. CpGs were strongly enriched in regions that were variably methylated among tissues, implying high tissue specificity in their regulatory impact. Corresponding to this methylation pattern, gene expression data were related to immune response (activated state) and nephrogenesis (inhibited state). Preimplantation biopsies showed similar DNAm patterns to normal allograft biopsies at 2 years posttransplantation. Our findings demonstrate for the first time a relationship among epigenetic modifications and development of interstitial fibrosis, graft function, and inter-individual variation on long-term outcomes.

Associations Between Posttransplantation Diabetes Mellitus and Renal Graft Survival.

Previous reports indicate that posttransplantation diabetes mellitus (PTDM) is associated with overall renal graft loss, but not death-censored graft loss. In this single-center retrospective cohort study of 2749 adult Norwegian renal transplant recipients, transplanted between 1999 and 2011, we estimated overall and death-censored renal graft loss hazard ratios in patients diagnosed with PTDM, impaired glucose tolerance and diabetes before transplantation, using multivariable Cox proportional hazard regression analysis. A total of 893 renal grafts were lost during the study period, either due to recipient death (n = 540) or death-censored graft loss (n = 353).When the observational time started at time of transplantation, diabetes before transplantation was associated with both overall and death-censored graft loss. Pretransplantation diabetes was also associated with a steeper decline in renal graft function, a higher risk of acute rejections and more renal grafts lost due to acute rejection.In patients with a functional renal graft 1 year after transplantation, PTDM was associated with overall graft loss (hazard ratio, 1.46; 95% confidence interval, 1.13-1.88; P < 0.001), but not death-censored graft loss (hazard ratio, 1.25; 95% confidence interval, 0.80-1.96; P = 0.33). We found no significant associations between PTDM and change in renal function during the first 5 years or acute rejection risk during the first year after renal transplantation.Impaired glucose tolerance was not associated with either overall or death-censored graft loss. The present study confirms previous findings of an increased risk of overall but not death-censored renal graft loss in renal transplant recipients with PTDM. Longstanding diabetes might increase the risk of acute rejections.

Rejection of the Renal Allograft in the Absence of Demonstrable Antibody and Complement.

Recent literature has stressed the prominent role of antibodies in graft loss. This study was designed to assess a growing perception that T cell-mediated rejection (TCMR) is no longer clinically relevant. Five hundred forty-five renal allograft recipients over a 3-year period were screened for biopsies with: (a) TCMR including borderline change (BL), (b) negative complement protein C4 degradation fragment, and (c) absence of donor-specific antibody at time of transplant, within 30 days of the biopsy, and up to 4 measurements at later time points. These stringent requirements identified 28 "pure" cases of late TCMR/BL. Low-grade glomerulitis, peritubular capillaritis, or chronic transplant glomerulopathy were found in 9/28 (32%) biopsies. Serum creatinine showed complete short-term remission in 7/10 (70%) BL and 9/18 (50%) TCMR patients 1 month postbiopsy. Yet, both treated and untreated patients demonstrated further decline in graft function as assessed by serum creatinine and estimated glomerular filtration rate. Late TCMR seen in 7.9% of biopsies can contribute to significant deterioration of graft function in patients in whom the dominant contribution of antibody-mediated injury has been reasonably excluded. Our data also reinforce existing literature showing that microvascular lesions do not have absolute specificity for a diagnosis of antibody-mediated rejection.

Immune monitoring in renal transplantation: The search for biomarkers.

It is now widely accepted that in order to improve long-term graft function and survival, a more personalized immunosuppressive treatment of transplant patients according to the individual anti-donor immune response status is needed. This applies to the identification of potentially "high-risk" patients likely to develop acute rejection episodes or display an accelerated decline of graft function, patients who might need immunosuppression intensification, and operationally tolerant patients suitable for immunosuppression minimization or weaning off. Such a patient stratification would benefit from biomarkers, which enable categorization into low and high risk or, ideally, identification of operational tolerant patients. Here, we report on recent developments regarding identification and performance analysis of noninvasive biomarkers such as mRNA and miRNA expression profiles, chemokines, or changes in immune cell subsets in either blood or urine of renal transplant patients. We will also discuss which future steps are needed to accelerate their clinical implementation.

Urinary MicroRNA as Biomarker in Renal Transplantation.

Urine represents a noninvasive source in which proteins and nucleic acids can be assessed. Such analytes may function as biomarkers to monitor kidney graft pathology at every desired frequency, thereby providing a time window to prevent graft damage by therapeutic intervention. Recently, several proteins have been measured in urine as markers of graft injury. However, the specificity is limited, and measuring urinary proteins generally lacks the potential to predict early kidney graft damage. Currently, urinary mRNA and microRNA are being investigated to evaluate the prognostic value of changes in gene expression during the initial stages of graft damage. At such time point, a change in treatment regimen and dosage is expected to have maximum potency to minimize future decline in graft function. Both mRNA and microRNAs have shown promising results in both detection and prediction of graft injury. An advantage of microRNAs compared to mRNA molecules is their stability, a characteristic that is beneficial when working with urine samples. In this review, we provide the current state of urinary biomarkers in renal transplantation, with a focus on urinary microRNA. In addition, we discuss the methods used to study urinary microRNA expression.

Is HRQOL in dialysis associated with patient survival or graft function after kidney transplantation?

BackgroundHealth related quality of life (HRQOL) is patient-reported, and an important treatment outcome for patients undergoing renal replacement therapy. Whether HRQOL in dialysis can affect mortality or graft survival after renal transplantation (RTX) is not determined. The aims of the present study were to investigate whether pretransplant HRQOL is associated with post-RTX patient survival or graft function, and to assess whether improvement in HRQOL from dialysis to RTX is associated with patient survival.MethodsIn a longitudinal prospective study, HRQOL was measured in 142 prevalent dialysis patients (67 % males, mean age 51 ± 15.5 years) who subsequent underwent renal transplantation. HRQOL could be repeated in 110 transplant patients 41 (IQR 34–51) months after RTX using the self-administered Kidney Disease and Quality of Life Short Form (KDQOL-SF) measure. Kaplan-Meier plots were utilized for survival analyses, and linear regression models were used to address HRQOL and effect on graft function.ResultsFollow-up time was 102 (IQR 97–108) months after RTX. Survival after RTX was higher in patients who perceived good physical function (PF) in dialysis compared to patients with poorer PF (p = 0.019). Low scores in the domain mental health measured in dialysis was associated with accelerated decline in graft function (p = 0.048). Improvements in the kidney-specific domains “symptoms” and “effect of kidney disease” in the trajectory from dialysis to RTX were associated with a survival benefit (p = 0.007 and p = 0.02, respectively).ConclusionHRQOL measured in dialysis patients was associated with survival and graft function after RTX. These findings may be useful in clinical pretransplant evaluations. Improvements in some of the kidney-specific HRQOL domains from dialysis to RTX were associated with lower mortality. Prospective and interventional studies are warranted.

Cytomegalovirus Infection in Pediatric Renal Transplantation and the Impact of Chemoprophylaxis With (Val-)Ganciclovir.

Cytomegalovirus (CMV) replication and disease, with its associated morbidity and poor transplant outcome, represents a serious threat to transplant recipients. The pediatric kidney transplant population is at a particularly increased risk of CMV infection. We therefore analyzed CMV epidemiology in a large cohort of pediatric renal transplant recipients (n = 242) and assessed the impact of antiviral chemoprophylaxis with valganciclovir (VGCV) or ganciclovir (GCV) on CMV replication and morbidity. While antiviral chemoprophylaxis with VGCV or GCV in patients with a high (D+/R-) or intermediate (D+/R+) CMV risk (n = 82) compared to preemptive therapy (n = 47) had no significant effect on the incidence of CMV syndrome or tissue-invasive disease, chemoprophylaxis was associated with a better preservation of transplant function at 3 years posttransplant (loss of estimated glomerular filtration rate in the chemoprophylaxis cohort, 16.0 ± 3.4 vs. 30.1 ± 4.7 mL/min per 1.73 m(2) in the preemptive therapy cohort, P < 0.05).CMV replication was associated with a more pronounced decline of graft function (difference in estimated glomerular filtration rate of 9.6 mL/min per 1.73 m(2) at 3 years) compared to patients without CMV replication. However, patients undergoing VGCV or GCV chemoprophylaxis had more leukocytopenia. Antiviral chemoprophylaxis with VGCV or GCV in recipients with a high or moderate CMV risk is associated with a better preservation of transplant function. Hence, the prevention of CMV replication in this patient population has the potential to improve transplant outcome.

Decreased chronic cellular and antibody-mediated injury in the kidney following simultaneous liver-kidney transplantation

In simultaneous liver-kidney transplantation (SLK), the liver can protect the kidney from hyperacute rejection and may also decrease acute cellular rejection rates. Whether the liver protects against chronic injury is unknown. To answer this we studied renal allograft surveillance biopsies in 68consecutive SLK recipients (14 with donor-specific alloantibodies at transplantation [DSA+], 54 with low or noDSA, [DSA-]). These were compared with biopsies of a matched cohort of kidney transplant alone (KTA) recipients (28 DSA+, 108 DSA-). Overall 5-year patient and graft survival was not different: 93.8% and 91.2% in SLK, and 91.9% and 77.1% in KTA. In DSA+ recipients, KTA had a significantly higher incidence of acute antibody-mediated rejection (46.4% vs. 7.1%) and chronic transplant glomerulopathy (53.6% vs. 0%). In DSA- recipients at 5years, KTA had a significantly higher cumulative incidence of T cell-mediated rejection (clinical plus subclinical, 30.6% vs. 7.4%). By 5 years, DSA+ KTA had a 44% decline in mean GFR while DSA+SLK had stable GFR. In DSA- KTA, the incidence of a combined endpoint of renal allograft loss or over a 50% decline in GFR was significantly higher (20.4% vs. 7.4%). Simultaneously transplanted liver allograft was the most predictive factor for a significantly lower incidence of cellular (odds ratio 0.13, 95% confidence interval 0.06-0.27) and antibody-mediated injury (odds ratio 0.11, confidence interval 0.03-0.32), as well as graft functional decline (odds ratio 0.22, confidence interval 0.06-0.59). Thus, SLK is associated with reduced chronic cellular and antibody-mediated alloimmune injury in the kidney allograft.

Factors Influencing Graft Outcomes Following Diagnosis of Polyomavirus -Associated Nephropathy after Renal Transplantation.

BackgroundPolyomavirus associated nephropathy (PVAN) is a significant cause of early allograft loss and the course is difficult to predict. The aim of this study is to identify factors influencing outcome for PVAN.MethodsBetween 2006 and 2014, we diagnosed PVAN in 48 (7.8%) of 615 patients monitored for BK virus every 1–4 weeks after modification of maintenance immunosuppression. Logistic or Cox regression analysis were performed to determine which risk factors independently affected clinical outcome and graft loss respectively.ResultsAfter 32.1±26.4 months follow-up, the frequencies of any graft functional decline at 1 year post-diagnosis, graft loss and any graft functional decline at the last available follow-up were 27.1% (13/48), 25.0% (12/48), and 33.3% (16/48), respectively. The 1, 3, 5 year graft survival rates were 100%, 80.5% and 69.1%, respectively. The mean level of serum creatinine at 1 year post-diagnosis and long-term graft survival rates were the worst in class C (p<0.05). Thirty-eight of 46 (82.6%) BKV DNAuria patients reduced viral load by 90% with a median time of 2.75 months (range, 0.25–34.0 months) and showed better graft survival rates than the 8 patients (17.4%) without viral load reduction (p<0.001). Multivariate logistic regression analysis showed that extensive interstitial inflammation (OR 20.2, p = 0.042) and delayed fall in urinary viral load (>2.75 months for >90% decrease) in urine (OR 16.7, p = 0.055) correlated with worse creatinine at 1 year post-diagnosis. Multivariate Cox regression analysis showed that extensive interstitial inflammation (HR 46988, p = 0.032) at diagnosis, and high PVAN stage (HR 162.2, p = 0.021) were associated with worse long-term graft survival rates.ConclusionsThe extent of interstitial inflammation influences short and long-term graft outcomes in patients with PVAN. The degree of PVAN, rate of reduction in viral load, and viral clearance also can be used as prognostic markers in PVAN.