Renal Allograft Function Research Articles

Tertiary Hyperparathyroidism: Why the Delay?

To evaluate the reason for delay of surgical referral in tertiary hyperparathyroidism (THPT) and its impact on renal allograft function. Persistent hyperparathyroidism after renal transplant has been shown to negatively impact allograft function, yet referral for definitive treatment of THPT is often delayed. A retrospective review was performed of patients undergoing parathyroidectomy for THPT (n = 38) at a single institution from May 2016 to June 2018. The first elevated serum calcium after transplant and time to referral for parathyroid surgery were recorded. Baseline creatinine post-transplant and the most recent creatinine level were used to assess allograft function. Thirty-eight patients were included, with mean age 53 ± 2 years and 66% male. Mean preoperative calcium and parathyroid hormone were 10.8 ± 0.1 mg/dL and 328 ± 48 pg/mL, respectively. THPT after renal transplant was diagnosed at a median of 15 days (range of 1-4892 days). Median time to parathyroidectomy referral was 320 days (range 16-6281 days). In over 50% of patients, the cited reason for referral to an endocrine surgeon was difficulty with cinacalcet - either cost, poor calcium control, and poor compliance or tolerance. In comparing renal function between patients referred early (<278 days, n = 19) versus later (>278 days, n = 19) for parathyroidectomy, those referred early had an improvement in creatinine (27.6% vs -5%, P = 0.007). Patients with THPT wait approximately a year, on average, before referral to an endocrine surgeon for curative parathyroidectomy; earlier referral was associated with improvement in serum creatinine.

P1429EVALUATION OF PARATHYROIDECTOMY IN PERSISTENT HYPERARATHYROIDISM AFTER RENAL TRANSPLANTATION: A SINGLE-CENTER RETROSPECTIVE STUDY

Abstract Background and Aims To investigate the efficacy of parathyroidectomy (PTX) in the treatment of persistent hyperparathyroidism (PHPT) after renal transplantation and the effect of PTX on renal allograft function. Method This single-center retrospective study enrolled 31 patients who underwent PTX for the treatment of PHPT after renal transplantation in the Kidney Disease Center of the First Affiliated Hospital of Zhejiang University from May 2010 to Oct. 2018. The changes of serum calcium, serum phosphorus, alkaline phosphatase, parathyroid hormone(PTH), serum creatinine, and estimated glomerular filtration rate (eGFR) in the preoperative and postoperative periods (1w, 1m, 3m, 6m,12m) were compared. The operative successful rate (12 m) and postoperative complications were calculated. Results The serum calcium before PTX was (2.78±0.18) mmol/L, which decreased significantly to (2.19±0.34) mmol/L at 1 week postoperatively (P&amp;lt;0.01). The serum phosphorus before PTX was (0.76±0.16) mmol/L, which decreased significantly to (0.97±0.26) mmol/L at 1 week postoperatively (P&amp;lt;0.01). The PTH before PTX was (276.00±200.60) pg/mL, which decreased significantly to (46.62±104.36) pg/mL at 1 week postoperatively (P&amp;lt;0.01). The alkaline phosphatase before PTX was (261.59±236.95) U/L, which decreased significantly to (154.90±117.37) U/L at 3 months postoperatively (P&amp;lt;0.01). No significant difference was found in postoperative serum creatinine or eGFR levels compared with the baseline. The operative successful rate was 90.3% at 12 months postoperatively. The incidence rates of postoperative transient hypocalcemia, persistent hypoparathyroidism, and hoarseness were 35.5%, 3.2% and 3.2% respectively. No persistent hypocalcemia, incision hemorrhage, incision infection, or surgery-related death happened. Conclusion PTX can quickly and effectively alleviate high calcium, low phosphorus, high PTH and high alkaline phosphatase after renal transplantation. PTX is effective and safe in the treatment of PHPT after renal transplantation, and has no effect on renal allograft function.

P1781CONVERSION TO SIROLIMUS IN ADVANCED STAGES OF CHRONIC ALLOGRAFT NEPHROPATHY. A RANDOMIZED CLINICAL TRIAL

Abstract Background and Aims Some studies have shown that proteinuria more than 800 mg per day and glomerular filtration rate (GFR) less than 40 ml/min are the most important relative contraindications for mTOR inhibitors prescription. There is no pathophysiologic reason to put aside mTOR inhibitors in more advanced stages of chronic allograft nephropathy(CAN). To clarify the safety of conversion to mTOR inhibitors in more advanced stages of CAN we conduct a randomized clinical trial Method Among 1911 renal transplant recipients which was performed from May 1989 to May 2016, patients (pts) with CAN included to the study. CAN was defined by pathology results and rule out of other causes of renal dysfunction and GFR less than 60 ml/min. pts with recent acute rejection, chronic Ab mediated rejection, active viral infection, malignancy, advanced cardiac, liver and respiratory diseases, obstructive uropathy and non-adherence were excluded from the study. After exclusion there were 211 pts with CAN. Among CAN pts 112 pts have GFR less than 40 ml/min. These patients were assigned in two group randomly. Group 1 continued their immunosuppression which consists of mycophenolate mofetil/myfortic, Cyclosporin A /Tacrolimus and prednisolone. Group B which received Sirolimus 2 mg daily instead of CyclosporinA / tacrolimus. All pts followed for 18 months. allograft function and pts morbidity and mortality were monitored every two months. results were recorded in clinic sheets and were analyzed using SPss version 22 Results G1 consist of 53 and G2 59 pts. There were no differences in two group in respect to sex (M/F was 0.89 and 0.84 in G1 and G2 respectively), and age (mean age was 41 6 9.5 and 43 6 8.23 in G1 and G2 respectively). there were no differences in admission rate for medical reasons (0.43 and 0.39 admission per pts per year in G1 and G2 respectively p=0.23). There was no difference between two group in respect to cardiovascular events (0.23 and 0.27 events per pts per year in G1 and G2 respectively p=0.31). The average trough level of SRL was 8.38± 3.12 ng/mL at 18 months. At 18 months, the incidence of acute rejection was not higher in G2 (21% vs. 18.8 %, p = 0.21) and renal function was superior in patients converted to SRL (eGFR 32.3 vs. 23.4 mL/min/ 1.73 m2, p = 0.019) compared to those maintained on CsA/TAC. There were no significant differences in pts survival (one death in each group) Graft loss was higher in G1( 5 versus 2 at 18 months p= 0.014). there were no significant differences in respect to liver, respiratory, GI, hematologic and infectious complications. pts in G2 group had lower BP and uric acid levels. Conclusion Conversion to mTOR inhibitors in more advanced stages of CAN is safe and has beneficial effect on renal allograft function with no more side effect.

P1682POST-TRANSPLANT VISIT-TO-VISIT PULSE PRESSURE VARIABILITY AND RISK OF RENAL ALLOGRAFT FUNCTION DECLINE

Abstract Background and Aims Pulse pressure (PP) is associated with risk of kidney disease. Association between visit-to-visit PP variability (VVPPV) and renal allograft outcomes is unknown. Method VVPPV, variation of PP between each consecutive BP measurement at 4, 12, 24, 36, and 48 weeks after kidney transplantation (KT), was determined by using coefficient of variation (CV = SD/Mean x 100%). VVPPV was then categorized into 12 strata (&amp;lt;5, 5 - &amp;lt;10, 10 - &amp;lt;15, 15 - &amp;lt;20, 20 - &amp;lt;25, 25 - &amp;lt;30, 30 - &amp;lt;35, 35 - &amp;lt;40, 40 - &amp;lt;45, 45 - &amp;lt;50, 50 - &amp;lt;55, and ≥55). Association between the categorized VVPPV and progression of renal allograft function, which was defined by a decrease in estimated glomerular filtration rate (eGFR) after 12-week post-KT, was examined by Cox proportional hazard regression analysis. Results Of all 102 renal transplant recipients from a single kidney transplant center, mean age±SD was 54.16±11.73 years and 63 patients (62%) was female. An incidence rate of worsening renal allograft function after 12-week post-KT was 0.017 person-weeks with a median survival time of 36 weeks (Figure 1). Every 5% increase in CV of PP was associated with a 14% increased risk of worsening post-transplant eGFR (hazard ratio (HR) 1.142431, 95% confidence interval (CI) 0.9999617 to 1.305199, and p value 0.050). After adjusted for age, gender, types of induction immunosuppressive medications, pretransplant body mass index category, every increase in 5% CV of PP was significantly associated with a 16% greater risk of worsening post-transplant eGFR (HR 1.160975, 95% CI 1.007967 to 1.337209, and p value 0.038). Conclusion VVPPV is an independent predictor of worsening renal allograft function.

P1608CXCL13 IS STRONGLY INDUCED BY RENAL ISCHEMIA REPERFUSION INJURY AND CORRELATES WITH SEVERITY OF RENAL INFLAMMATION

Abstract Background and Aims Ischemia reperfusion injury (IRI) is a strong trigger of inflammation and is tightly linked to renal allograft damage and function. CXCL13 or B lymphocyte chemoattractant (BLC) is a chemokine that controls B cell organization in lymphoid tissues and has recently been described as a biomarker for B cell involvement in acute kidney allograft rejection. Method To show, that CXCL13 is already induced by IRI alone we used renal IRI models in mice with different ischemia times and a kidney transplantation model. We measured serum CXCL13 and characterized cell infiltrates by immunohistochemistry and performed single cell RNA sequencing. Allogenic and isogenic kidney transplantation (KTX) in mice was done to evaluate these findings in the transplant setting. Results Systemic CXCL13 levels increased within hours after surgery in a time dependent manner, both after induction of IRI and KTX. Levels of CXCL13 increased with duration of ischemia time and were higher in allogenic than isogenic transplantation with equal duration of ischemia. CXCR5, the receptor for CXCL13, is mainly expressed on B lymphocytes but also on a subset of T lymphocytes and macrophages. CXCR5 positive infiltrates were detected in IRI kidneys seven days after injury. In kidney allografts interstitial B cell infiltrates were observed as early as seven days and increased further towards three weeks after KTX. Conclusion The current findings indicate that IRI is a strong trigger of CXCL13 expression in the kidney and release into the circulation, which is followed by B lymphocyte infiltration into damaged tissue in ischemic and renal allografts.

SO029FIRST YEAR RENAL OUTCOME OF TRANSPLANTATIONS OF KIDNEYS FROM HEPATITIS C INFECTED DONORS TO HEPATITIS C NEGATIVE RECIPIENTS

Abstract Background and Aims Transplant centers in US are increasingly willing to transplant kidneys from hepatitis C infected donors to hepatitis C negative recipients. Long-term renal outcome data from non-prophylactic treatment approach outside clinical trials is missing. Method We compared kidney graft function of 132 hepatitis C negative recipients, who received HCV infected (NAT+ and antibody+/-; HCV+) versus HCV negative (NAT- and antibody-; HCV-) in 2018, in a single center, retrospective, observational study. Categorical variables were compared using χ2 tests and continuous variables were compared using t-tests or Mann–Whitney U-tests, as appropriate. Linear regression was applied to assess independent association between graft function and HCV viremic status. Results The mean±SD age of recipients was 52±11 years, 44% were female, 20% and 79% of recipients were Caucasian and African-American, respectively. Baseline characteristics were similar between HCV+ vs HCV- groups, except dialysis duration, donors race, KDPI and cold ischemic time (Table). The DGF rate, estimated GFRs at post-transplant 3, 6, 9 and 12 months was similar between HCV+ and HCV- groups (Table). HCV viremic status was not a predictor of 3, 6, 9 and 12 months eGFR in our unadjusted model and after adjustment for donor and recipient characteristics. Conclusion Recipients of HCV-viremic kidneys have similar renal allograft function in the first year after transplantation compared to those who received from HCV-non-viremic kidneys.

P1766EFFECT OF EVEROLIMUS AND REDUCED CALCINEURIN INHIBITORS ON BIOPSY PROVEN BK VIRUS ASSOCIATED NEPHROPATHY-

Abstract Background and Aims BK virus-associated nephropathy (BKVAN) is a clinically important entity that results in an allograft loss in kidney transplant recipients (KTRs). Mammalian target of rapamycin inhibitors (mTOR-i) have been proposed as possible immunosuppressive therapy in BK virus infection because of their antiviral capacity. However, the effect on biopsy (bx) proven BKVAN is still unclear. Method This a retrospective single center review of 27 (KTRs) on triple immunosuppression regimen (CNI/MMF/prednisone), who developed BK viremia and had bx proven BKVAN (n=13, 48%). Patients were converted to Everolimus, reduced/or no CNI and prednisone. We present the renal allograft function, BK viremia status and histological data after a mean follow up period of 28.4±17.9 months post-transplant. Results We reviewed 27 KTRs (17 males, 11 AA) transplanted between 2012 and 2019, who developed BK viremia, 23/27 patients (85%) underwent surveillance &amp; for cause bx (n=55). All patients were switched to Everolimus, reduced CNI (one patient was on Cyclosporin) and prednisone regimen. Median time from transplant to BK viremia was 2.5 months (min 0.7-max 76.7). After a mean follow up period of 17.9±12 months post conversion, the mean serum creatinine remained relatively stable (1.54 mg/dl ±0.47; 1.79 mg/dl±0.82; P=0.17). The mean BK viral load was statistically significantly reduced (P=0.045), pre/post conversion median BK levels were (35900 (655-2.5 million copies) and 752 (0-92150) respectively), 13/27 (48%) patients had undetectable BK viral load. 13/27 (48%) had bx proven BKVAN, with 4/13 (31%) had no follow up bx, 4/13 (31%) had follow up bx proven resolved BKVAN and 5/13 (38%) had bx proven persistent BKVAN (figure 1). Post conversion 3/27 (11%) patients were treated for borderline acute cellular rejection with pulse steroids and had negative DSA. Conclusion Conversion to mTOR-i-based therapy could provide an added benefit in BK viremia as well as BKVAN and could be an effective strategy for the decrease of the viremia and increase of graft survival in selected patients. In the medium-term follow up, the BK viral load was statistically significantly lower even in bx proven persistent BKVAN, and almost half (4/9) of the bx proven BKVAN have resolved. The median time for conversion for patients with resolved BK nephropathy was 25 days (range 19-38) vs 263 days (range 17-931) in patients with persistent BK nephropathy (P&amp;lt;0.001), pointing to possible benefit of rapid conversion to mTOR-i based regimen in the setting of BK viremia.

P1687ASSOCIATION OF URINARY MICRORNA-21-5P WITH INTERSTITIAL FIBROSIS AND TUBULAR ATROPHY (IFTA) IN RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims One of the most limiting factors of long-term graft survival is chronic renal allograft dysfunction (CAD). The major hallmarks of CAD are interstitial fibrosis and tubular atrophy (IFTA). MicroRNAs (miRNAs) are 19-25 nucleotides, small, noncoding molecules involved in the regulation of gene expression. MiRNAs have a role in various immunological processes, including inflammation and fibrosis. Particularly, microRNA-21-5p (miR-21) is reported to be strongly associated with pathogenesis regarding tubulointerstitium. The aim of this study was to analyse expression levels of urinary miR-21 in the renal transplant recipients and evaluate their application in the assessment of IFTA and kidney allograft function. Method The expression levels of urinary miR-21 were measured in 31 renal transplant recipients with biopsy-evaluated IFTA (IFTA 0+I: n=17; IFTA II+III: n=14) by quantitative PCR. Protocolar biopsies were performed 1 or 2 years after renal transplantation. Urine samples were collected at the time of biopsy procedure. MicroRNA-191-5p was used as reference gene. Correlations between the clinicopathological parameters and the level of expression of miR-21 were assessed. Results Relative expression level of miR-21 was significantly increased in IFTA II+III group compared to IFTA 0+I group. MiR-21 correlated positively with serum concentration of creatinine and negatively with eGFR. ROC analysis showed diagnostic value of miR-21 with an area under curve (AUC) of 0.80, high sensitivity and specificity. Conclusion MiR-21 is associated with IFTA and dysfunction of kidney allograft. It may be considered as potential non-invasive biomarker of renal allograft function.

A multimodal computer‐aided diagnostic system for precise identification of renal allograft rejection: Preliminary results

Early assessment of renal allograft function post-transplantation is crucial to minimize and control allograft rejection. Biopsy - the gold standard - is used only as a last resort due to its invasiveness, high cost, adverse events (e.g., bleeding, infection, etc.), and the time for reporting. To overcome these limitations, a renal computer-assisted diagnostic (Renal-CAD) system was developed to assess kidney transplant function. The developed Renal-CAD system integrates data collected from two image-based sources and two clinical-based sources to assess renal transplant function. The imaging sources were the apparent diffusion coefficients (ADCs) extracted from 47 diffusion-weighted magnetic resonance imaging (DW-MRI) scans at 11 different b-values (b0, b50, b100, ..., b1000 s/mm ), and the transverse relaxation rate (R2*) extracted from 30 blood oxygen level-dependent MRI (BOLD-MRI) scans at 5 different echo times (TEs=2, 7, 12, 17, and 22ms). Serum creatinine (SCr) and creatinine clearance (CrCl) were the clinical sources for kidney function evaluation. The Renal-CAD system initially performed kidney segmentation using the level-set method, followed by estimation of the ADCs from DW-MRIs and the R2* from BOLD-MRIs. ADCs and R2* estimates from 30 subjects that have both types of scans were integrated with their associated SCr and CrCl. The integrated biomarkers were then used as our discriminatory features to train and test a deep learning-based classifier, namely stacked autoencoders (SAEs) to differentiate non-rejection (NR) from acute rejection (AR) renal transplants. Using a leave-one-subject-out cross-validation approach along with SAEs, the Renal-CAD system demonstrated 93.3% accuracy, 90.0% sensitivity, and 95.0% specificity in differentiating AR from NR. Robustness of the Renal-CAD system was also confirmed by the area under the curve value of 0.92. Using a stratified tenfold cross-validation approach, the Renal-CAD system demonstrated its reproducibility and robustness by a diagnostic accuracy of 86.7%, sensitivity of 80.0%, specificity of 90.0%, and AUC of 0.88. The obtained results demonstrate the feasibility and efficacy of accurate, noninvasive identification of AR at an early stage using the Renal-CAD system.

Conversion to belatacept within 1-year of renal transplantation in a diverse cohort including patients with donor-specific antibodies.

Early conversion from a calcineurin inhibitor to belatacept has the potential to improve long-term renal allograft function; however, there remains limited experience with this strategy among African Americans and patients with preformed donor-specific antibodies (DSA). To examine these subgroups, we performed a single-center review of kidney transplant recipients converted to belatacept within 1-year of transplant between 01/2011 and 10/2017. All patients received lymphocyte-depleting induction with maintenance tacrolimus and mycophenolate +/- corticosteroids. Patients were switched to belatacept for clinical indication and followed from date of conversion until allograft failure or study conclusion. The primary endpoint at 1-year was a composite of allograft loss, biopsy proven rejection, de novo DSA formation, proteinuria, and declining renal function. Thirty-two patients were included in the review. The majority were African American, and 28.1% had DSA at transplant. Patient and allograft survival at 1-year was 96.9% and 93.8%, respectively, and estimated glomerular filtration rate improved from 41.9 to 58.4mL/min. No African Americans or patients with pretreatment DSA developed rejection or allograft failure within 1-year. The only clinical variable correlated with suboptimal allograft function was baseline weight ≥80kg (OR=6.2; 95% CI, 1.2-32.3). Early conversion to belatacept appears safe for select patients with DSA and African Americans receiving lymphocyte-depleting induction.

Establishment of Murine Model of Kidney Failure Induced by Severe Ischemia-Reperfusion Injury Useful to Evaluate Transplantation and Regenerative Therapies

BackgroundSevere ischemia-reperfusion injury (SIRI) seems to be the key factor that can significantly affect the function of both native kidneys and renal allografts. Therefore, the development of a successful strategy is of a paramount importance in both basic and clinical research. MethodsTo determine the effects of SIRI on the native kidney function, a murine model was planned as follows: group 1 (n = 6) mice underwent to nephrectomy plus ischemia-reperfusion injury for 30 minutes; group 2 (n = 6) mice underwent to nephrectomy without ischemia-reperfusion injury and thus served as sham controls for SIRI. The results of serum creatinine (SCr) were analyzed using Mann-Whitney U tests to calculate the significance between mean values. Survival between groups was measured by Kaplan-Meier test. ResultsTo reliably achieve an elevation of SCr levels animals were exposed to a SIRI. The values of SCr increased from 0.35 (SD, 0.09) mg/dL to about 2-fold within 2 days and 3-fold within the following 5 days. Under these given conditions the mice displayed signs and histologic findings of severe kidney damage. The survival rate was about 83% of the animals within a week, and they showed no capacity of complete spontaneous self-regeneration. ConclusionsIn this study, we aim to establish a murine model with extensive structural kidney damage and significant elevation of SCr levels, which could be used in basic and translational research of transplantation and regenerative therapies.

Predonation Single Kidney Glomerular Filtration Rate in Living Kidney Transplantation to Predict Graft Function and Donor Functional Gain

BackgroundThe 2 main objectives regarding living kidney transplant are to provide optimal graft function and to ensure the safety of donation. Our study hypothesized that the glomerular filtration rate of a single kidney (skGFR), when transplanted, might predict graft function and that the skGFR of the remaining kidney could predict donor functional gain. MethodsA prospective monocentric study was conducted at Grenoble-Alpes University Hospital. Twenty couples of donors and recipients were included. Dimercaptosuccinic acid renal scintigraphy and 51Cr-ethylene-diamine tetra-acetic acid clearance were evaluated predonation to calculate skGFR. All patients had renal function according to 51Cr-ethylene-diamine tetra-acetic acid clearance at 1 year post transplant to assess graft function and donor functional gain. All donors had normal renal function predonation. ResultsAt 1 year post transplant, median glomerular filtration rate of the graft was 50 mL/min/1.73 m2 (range, 46-56 mL/min/1.73 m2) and donor median glomerular filtration rate was 59 mL/min/1.73 m2 (range, 55-74 mL/min/1.73 m2). Median functional gain was 20 mL/min/1.73 m2 (range, 12-22 mL/min/1.73 m2). No statistical correlation was found between skGFR of the transplanted kidney and graft function at 1 year (R2 = 0.096, P = .7). For the donor, functional gain was not associated with predonation skGFR of the remaining kidney (R2 = 0.17, P = .5). A statistical difference was found between donor functional gain (18 [SD, 10] mL/min) and recipient gain (delta between skGFR before and after transplant, 7 [SD, 16] mL/min; P = .02). ConclusionPredonation skGFR of the transplanted kidney had no influence on renal allograft function at 1 year post transplant. Similarly, there was no association between measured skGFR of the remaining kidney and donor functional gain at 1 year.

Outcomes After Direct-Acting Antiviral Therapy Based on Donor Hepatitis C Serostatus Among Hepatitis C Virus-Infected Kidney Transplant Recipients.

Renal grafts from hepatitis C virus-positive deceased donors, which were once discarded, can now be transplanted into recipients and treated posttransplant due to the emergence of direct-acting antivirals, significantly improving wait list time and organ shortages. Here, we compared outcomes in hepatitis C virus-positive patients who received kidneys from hepatitis C virus-positive versus -negative donors. In this single-center retrospective study, we divided 52 kidney transplant recipients who were viremic for hepatitis C virus pretransplant into 2 groups based on donors' hepatitis C virus serostatus (positive/negative). Demographics, time to transplant, efficacy of direct-acting antivirals, rejection episodes, immunosuppression adjustments, and renal function were assessed in both groups. Our cohort included 50 patients receiving kidneys from deceased donors and 2 from living donors (1 related, 1 unrelated). Recipients of hepatitis C virus-positive kidneys had significantly less wait list time (36 days) than recipients of hepatitis C virus-negative kidneys (806 days; P < .001). All recipients responded well to direct-acting antivirals, with both groups showing similar sustained virologic response rates that were comparable to the general population. Intention-to-treat analyses showed rates of 91% and 100% in donor seropositive and donor seronegative groups, respectively (P = .273). Four antibody-mediated rejection episodes occurred in the donor seropositive and one mixed rejection in the donor seronegative group. Tacrolimus dose adjustments were required in 54% and 59% of recipients in the donor seropositive and seronegative groups, respectively. Recipients in the donor seropositive group had lower rates of worsening renal function than recipients in the donor seronegative group (11% vs 17.5%; P = .519). In hepatitis C-positive recipients with donor negative or donor positive hepatitis C virus serostatus, response of direct-acting antiviral response was not significantly different and renal allograft function was maintained without any evidence of long-term adverse consequences to the graft.

Diagnostic Performance of Donor-Derived Plasma Cell-Free DNA Fraction for Antibody-Mediated Rejection in Post Renal Transplant Recipients: A Prospective Observational Study.

ObjectiveTo evaluate the diagnostic performance of donor-derived plasma cell-free DNA (cfDNA) in discriminating antibody-mediated rejection (ABMR) or de novo donor-specific antibodies (DSA) without histological lesions in kidney allograft recipients.MethodsIn this prospective single center observational study, we enrolled kidney allograft recipients between November, 2016 and September, 2017 at the First Affiliated Hospital of Sun Yat-sen University. Kidney allograft recipients with ABMR, de novo DSA but no histological lesions or negative DSA, and stable renal function were included. The plasma cfDNA fraction was measured using a targeted, single nucleotide polymorphism (SNP)-based assay. Pathological diagnosis was made according to the 2015 Banff Kidney Rejection Classification. The area under the ROC curve (AUC-ROC) was determined using the bootstrapping method to estimate median and 95% confidence interval (95% CI). The sensitivity, specificity and Youden index, positive predictive value (PPV), and negative predictive value (NPV) were calculated for specific cfDNA fractions.ResultsTotally 37 consecutive patients received kidney allografts, including 18 recipients in the ABMR group and 19 recipients in the stable allograft group (7 DSA-positive and 12 DSA-negative). All patients in the ABMR group were DSA positive and 7 patients in the stable group were DSA positive but had no pathologically proven ABMR. The median donor-derived plasma cfDNA fraction was 2.4% (Q1 1.52% -Q3 3.70%) in the ABMR group, and was significantly higher than that of the stable group (0.65%, Q1 0.57% -Q3 0.97%; P < 0.001), but comparable with that of the DSA-positive patients in the stable allograft group (P = 0.074). The AUC-ROC of cfDNA was 0.90 (95% CI, 0.79–0.98). When a cfDNA threshold of 1% was chosen, it had a sensitivity of 88.9% and a specificity of 73.7%. The PPV was 76.2% and the NPV was 87.5%.ConclusionDonor-derived plasma cfDNA fraction increased in kidney allograft recipients with ABMR. Detection of donor-derived plasma cfDNA fraction may contribute to the discrimination between ABMR and stable renal allograft function and may aid early recognition of earlier stage antibody-mediated injury.

Spectrum and short-term outcome of acute kidney injury in renal allograft recipients: A single-center experience of Northwest India

Introduction: Acute kidney injury (AKI) episodes in postrenal transplant are important determinants of short- and long-term graft survival. Renal allograft recipients (RARs) are more vulnerable for AKI and differ in risk factor, etiology, and outcome compared to community-setting AKI. The aim of this study was to evaluate the spectrum and the impact of AKI episode on RARs. Materials and Methods: This was a single-center, prospective observational study on 72 RARs (live and cadaveric) with a total of 93 AKI episodes, who were admitted with AKI (as defined by Kidney Disease Improving Global Outcome [KDIGO] criteria) between October 2016 and September 2018 and were followed for 3 months after AKI episodes. Results: A total of 93 AKI episodes occurred in 72 RARs during the study period. The mean age was 36.32 ± 12.03 years and mean serum creatinine at AKI episode was 2.59 ± 0.85 mg/dl. The etiologies of AKI were infections (n = 67, 72.04%), biopsy-proven rejection (n = 10, 10.75%), calcineurin inhibitor toxicity (n = 9, 9.67%), biopsy-proven acute tubular necrosis (n = 3, 3.22%), recurrence of native kidney disease (n = 2, 2.15%), and miscellaneous causes (n = 2, 2.15%). The majority (n = 53, 57.98%) of AKI episodes developed in the 1st year of transplant, 14 (15.05%) between 1st and 2nd year posttransplant, while the rest 26 (27.95%) beyond 2 years. Sixty-nine (74.2%) AKI episodes were in the KDIGO Stage 1, 18 (19.4%) were in Stage 2, and 6 (6.5%) episodes were in Stage 3. At 3 months of follow-up, various factors associated with nonrecovery of renal functions, including multiple AKI episode (P = 0.006), AKI requiring dialysis (P = 0.027), AKI Stage II or III (P = 0.003), and noninfectious etiology (P = 0.027). Overall, AKI had significant impact on renal allograft function at 3 months (P = 0.045). Pulmonary infection (P = 0.016) and need for dialysis (P = 0.001) were associated with increased risk of mortality in RARs after AKI. Conclusion: AKI in RARs had significant impact on renal allograft function and recovery.

Alemtuzumab-induced cytokine release syndrome: an under-appreciated risk in treatment of delayed renal allograft function

Alemtuzumab-induced cytokine release syndrome: an under-appreciated risk in treatment of delayed renal allograft function

Utilization of Carbon Dioxide Angiography and Percutaneous Balloon Angioplasty for Treatment of Transplant Renal Artery Stenosis

Transplant renal artery stenosis (TRAS) may lead to graft dysfunction and failure. Progressive deterioration of renal allograft function may be exacerbated by contrast-induced nephrotoxicity during iodine contrast administration for renovascular imaging of allografts. We present our institutional experience of endovascular management for TRAS using CO2 digital subtraction angiography (CO2-DSA) and balloon angioplasty to manage failing renal transplants. Four patients with renal allografts from March 2017-May 2018 were referred for graft dysfunction and pending renal transplant failure. Indications for referral included refractory hypertension, decreasing renal functioning, and elevated renovascular systolic velocities. Median age of the four patients was 41.5 years (22-60 years). There were two male and female patients. Chronic hypertension and type 2 diabetes mellitus were the most common comorbidities. An average total of 75mL of CO2 was used, supplemented with 17.4mL of iodinated contrast. All patients had improvements in renal function following intervention with a mean decrease in systolic and diastolic blood pressure of 25.8% and 21.4%, respectively. We also observed a mean decrease of BUN by 13.6% and creatinine by 37.4%. Additionally, eGFR increased by 37.7%. All allografts survived after surgery, and only one patient required repeat angioplasty for recurrence. CO2-DSA with balloon angioplasty can be successfully utilized to salvage deteriorating kidney allograft function in patients with TRAS.

Donor Plasma Mitochondrial DNA Is Correlated with Posttransplant Renal Allograft Function.

The lack of accurate biomarkers makes it difficult to determine whether organs are suitable for transplantation. Mitochondrial DNA (mtDNA) correlates with tissue damage and kidney disease, making it a potential biomarker in organ evaluation. Donors who had experienced cardiac death and successfully donated their kidneys between January 2015 and May 2017 were included this study. We detected the level of mtDNA in the plasma of the donor using quantitative real-time polymerase chain reaction and then statistically analyzed the relationship between the level of mtDNA and the delayed graft function (DGF) of the recipient. The incidence of DGF or slowed graft function (SGF) increased by 4 times (68% versus 16%, P < 0.001) when the donor mtDNA (dmtDNA) level was >0.114. When dmtDNA levels were >0.243, DGF and primary nonfunction were approximately 100% and 44%, respectively. Moreover, dmtDNA was an independent risk factor for slowed graft function and DGF. A prediction model for DGF based on dmtDNA achieved an area under the receiver operating characteristic curve for a prediction score as high as 0.930 (95% confidence interval 0.856-1.000), and the validation cohort results showed that the sensitivity and specificity of the model were 100% and 78%, respectively. dmtDNA levels were correlated with 6-month allograft function (R=0.332, P < 0.001) and 1-year graft survival (79% versus 99%, P < 0.001). We conclusively demonstrated that plasma dmtDNA was an independent risk factor for DGF, which is valuable in organ evaluation. dmtDNA is a possible first predictive marker for primary nonfunction and worth further evaluation.

Experience of using polymethyl methacrylate membranes for anti-HLA antibodies’ elimination by hemodialysis in renal transplant recipients

Introduction. In recipients with pre-existing sensitization with incompatible antigens of the main histocompatibility complex, the kidney graft survival after retransplantations directly depends on the level of anti-HLA antibodies. Despite many years of experience in using various methods: plasmapheresis, cascade filtration, immunosorption, intravenous administration of immunoglobulins, the use of polyclonal anti-lymphocytic agents, the search for more acceptable ways to reduce the level of anti-HLA antibodies still remains relevant nowadays.The purpose of the study was to assess the effect of polymethyl methacrylate membrane-based dialyzers on the decrease in anti-HLA antibody level in renal transplant recipients.Material and methods. The study included 20 kidney transplant recipients. The main study group consisted of 10 patients who underwent early postoperatoive hemodialysis using polymethyl methacrylate membrane-based dialyzers to decrease anti-HLA antibody level. A total of 53 hemodialysis procedures were performed, an average of 5.3 per patient. The comparison group included 10 recipients in whom plasmapheresis had been performed at similar timing after kidney transplantation aimed at reducing the anti-HLA antibody titers and whose data were studied retrospectively. A total of 38 plasmapheresis sessions were performed, an average of 3.8 per patient.Results. In the main study group, a day after the hemodialysis procedure using polymethyl methacrylate membranebased dialyzers the level of anti-HLA antibodies decreased by an average of 28.3% in 6 of 10 patients (60%), and increased in 4 cases. Meanwhile, in the comparison group, the level of anti-HLA antibodies in venous blood after a plasmapheresis session decreased average by 44.6% in 8 patients of 10 (80%), and increased in 2 cases, on the contrary. Of note, there were no significant differences between the patients of the two compared groups either in the number of positive results (p&gt; 0.05, Fisher's exact test), or in terms of the decrease in anti-HLA antibody level (p&gt; 0.05, Mann – Whitney test). On days 2 and 5, in 50% of cases both after the hemodialysis procedure using polymethyl methacrylate membranebased dialyzers and after the plasmapheresis session, the patients showed an increase in the anti-HLA antibodies level compared to the baseline values. In the remaining cases, the level of anti-HLA antibodies in both groups was recorded at a lower range compared to the baseline values.Conclusion. The use of polymethyl methacrylate membrane-based dialyzers in the renal allograft recipients having a high level of preexisting anti-HLA antibodies seems promising for the period of oligoanuria until the renal allograft function is restored, since both hemodialysis and the sorption of pre-existing (and also newly synthesized) antibodies take place simultaneously.

Abstract 003: Early and Late Post-Kidney Transplant Hypertension and Late Renal Allograft Outcome

Background: Association between pattern of blood pressure (BP) change at different period after kidney transplantation (KTx) and renal allograft function is unclear. We examine the association between changes in BP patterns and long-term allograft function. Methods: Kidney transplant recipients were stratified into 4 groups based on presence (+) or absence (-) of systolic hypertension (SHTN; SBP ≥130 mmHg) both at 1 and 6 mo post-KTx (Gr1 (-,-), Gr2 (-,+), Gr3 (+,-), Gr4 (+,+)). Declined allograft function defined by a decrease in eGFR from baseline eGFR at 1-mo post-KTx during 24 mo of follow-up among 4 different groups is examined by multivariable Cox regression analysis. Results: Of all 70 patients, mean±SD age was 52.7±12 yr and 41% was female. Mean SBP at 1- and 6-mo post-KTx were 130.9±18.3 and 136.2±18.2 mmHg, respectively. Baseline mean eGFR at 1-mo post-KTx was 50.86±18.89 ml/min/1.73 m 2 and were not different among all 4 groups. Among 70 patients, 57 patients (81%) had a decrease in eGFR between 1 and 24 mo post-KTx with a median time to outcome of 6.8 mo (IQR 2.8-19.6) and the incidence rate of 0.075 person-mo. The number of patients (% in each group) with declined eGFR in Gr1, 2, 3 and 4 were 15 (88%), 17 (89%), 7 (78%), and 18 (72%) patients, respectively (x 2 2.8830, p 0.410). Compared to Gr1, Gr2 had higher, but Gr 3 and 4 had lower the risk of declining eGFR but no statistical significance (HR(95% CI): Gr2 1.20 (0.60-2.40); Gr3 0.79 (0.32-1.95); Gr4 0.78 (0.39-1.55)). After adjusted for age, gender, race, types of induction immunosuppression, types of KTx, SBP, DBP, and BMI at the time of KTx, Gr3 became higher risk; otherwise, the direction of the association remains the same for Gr2 and Gr4. Conclusion: Changes in SBP from either normotension to HTN or vice versa between 1 and 6 mo post-KTx appears to be associated with poorer allograft function within 24 mo post-KTx; whereas, maintaining SBP pattern both normotension or HTN from 1 to 6 mo post-KTx may be protective for a decline in allograft function. Very early BP levels during 1 mo post-KTx may be the suitable target SBP for kidney transplant recipients and too liberal or tight BP control in normotensive or hypertensive patients after 1 mo post-KTx may associated with greater risk for worsening long-term allograft outcomes.