Function In Kidney Transplant Recipients Research Articles

#5547 SERUM PERIOSTIN IN KIDNEY TRANSPLANT RECIPIENTS AS A NOVEL BIOMARKER PREDICTING RENAL FUNCTION LOSS

Abstract Background and Aims Experimental studies have shown periostin is expressed throughout organogenesis, particularly within the kidney interstitium. Periostin is enhanced in different tissues of patients with nephropathy and has been considered as a candidate biomarker of kidney injury. Method Retrospective analysis of electronic medical record of one hundred and five kidney transplant recipients (KTRs) was performed. Only patients under sequential ambulatory care, with a history of at least 2 years post-transplant were included. Median (IQR) follow-up and time post-transplant was 4.42 (2.65, 4.58) and 4.29 (3.04, 8.07) years, respectively. Additionally, thirty-two health volunteers (HV) were enrolled. Biochemical testing was performed using commercially-available immunoassays. Results Median [IQR] serum periostin was significantly lower in KTRs as compared with HV (959 [732, 1204] vs. 1176 [997, 1408]; P<0.01). Higher serum periostin was observed in male patients (7.01 [6.84, 7.22] vs. 6.79 [6.64, 7.07], P<0.05) and a significant relationship was noted for interleukin 6 (IL6; r=0.24, P=0.01) and baseline estimated glomerular filtration (eGFR) (r=0.20, P=0.04). Patient age (P=0.60), body-mass index P=0.08), cardiovascular disease (P=0.31), diabetes (P=0.45), current smoker status (P=0.27), nor anemia (P=0.23) were not associated with serum periostin. In a generalized additive model adjusted for baseline renal function and IL-6, serum periostin showed a signficant nonlinear association (P=0.04) with eGFR change over follow-up. Conclusion Previous studies reported an association between periostin expression and the severity of histological injury within the kidney in both inflammatory and non-inflammatory conditions. Serum periostin may be a potential marker aiding in prediction of renal function in KTRs.

Calcification Propensity (T50) Predicts a Rapid Decline of Renal Function in Kidney Transplant Recipients.

Serum creatinine level, proteinuria, and interstitial fibrosis are predictive of renal prognosis. Fractional excretion of phosphate (FEP)/FGF23 ratio, tubular reabsorption of phosphate (TRP), serum calcification propensity (T50), and Klotho's serum level are emerging as determinants of poor kidney outcomes in CKD patients. We aimed at analysing the use of FGF23, FEP/FGF23, TRP, T50, and Klotho in predicting the rapid decline of renal function in kidney allograft recipients. We included 103 kidney allograft recipients in a retrospective study with a prospective follow-up of 4 years. We analysed the predictive values of FGF23, FEP/FGF23, TRP, T50, and Klotho for a rapid decline of renal function defined as a drop of eGFR > 30%. During a follow-up of 4 years, 23 patients displayed a rapid decline of renal function. Tertile of FGF23 (p value = 0.17), FEP/FGF23 (p value = 0.78), TRP (p value = 0.62) and Klotho (p value = 0.31) were not associated with an increased risk of rapid decline of renal function in kidney transplant recipients. The lower tertile of T50 was significantly associated with eGFR decline >30% with a hazard ratio of 3.86 (p = 0.048) and remained significant in multivariable analysis. T50 showed a strong association with a rapid decline of renal function in kidney allograft patients. This study underlines its role as an independent biomarker of loss of kidney function. We found no association between other phosphocalcic markers, such as FGF23, FEP/FGF23, TRP and Klotho, with a rapid decline of renal function in kidney allograft recipients.

Obesity is Associated With Delayed Graft Function in Kidney Transplant Recipients: A Paired Kidney Analysis.

Obesity is increasingly prevalent among candidates for kidney transplantation. Existing studies have shown conflicting post-transplant outcomes for obese patients which may relate to confounding bias from donor-related characteristics that were unaccounted for. We used ANZDATA Registry data to compare graft and patient survival between obese (BMI >27.5kg/m2 Asians; >30kg/m2 non-Asians) and non-obese kidney transplant recipients, while controlling for donor characteristics by comparing recipients of paired kidneys. We selected transplant pairs (2000-2020) where a deceased donor supplied one kidney to an obese candidate and the other to a non-obese candidate. We compared the incidence of delayed graft function (DGF), graft failure and death by multivariable models. We identified 1,522 pairs. Obesity was associated with an increased risk of DGF (aRR = 1.26, 95% CI 1.11-1.44, p < 0.001). Obese recipients were more likely to experience death-censored graft failure (aHR = 1.25, 95% CI 1.05-1.49, p = 0.012), and more likely to die with function (aHR = 1.32, 95% CI 1.15-1.56, p = 0.001), versus non-obese recipients. Long-term patient survival was significantly worse in obese patients with 10- and 15-year survival of 71% and 56% compared to 77% and 63% in non-obese patients. Addressing obesity is an unmet clinical need in kidney transplantation.

Endotrophin Levels Are Associated with Allograft Outcomes in Kidney Transplant Recipients.

Early prediction of kidney graft function may assist clinical management, and for this, reliable non-invasive biomarkers are needed. We evaluated endotrophin (ETP), a novel non-invasive biomarker of collagen type VI formation, as a prognostic marker in kidney transplant recipients. ETP levels were measured with the PRO-C6 ELISA in the plasma (P-ETP) of 218 and urine (U-ETP/Cr) of 172 kidney transplant recipients, one (D1) and five (D5) days, as well as three (M3) and twelve (M12) months, after transplantation. P-ETP and U-ETP/Cr at D1 (P-ETP AUC = 0.86, p < 0.0001; U-ETP/Cr AUC = 0.70, p = 0.0002) were independent markers of delayed graft function (DGF) and P-ETP at D1 had an odds ratio of 6.3 (p < 0.0001) for DGF when adjusted for plasma creatinine. The results for P-ETP at D1 were confirmed in a validation cohort of 146 transplant recipients (AUC = 0.92, p < 0.0001). U-ETP/Cr at M3 was negatively associated with kidney graft function at M12 (p = 0.007). This study suggests that ETP at D1 can identify patients at risk of delayed graft function and that U-ETP/Cr at M3 can predict the future status of the allograft. Thus, measuring collagen type VI formation could aid in predicting graft function in kidney transplant recipients.

Marinobufagenin, Left Ventricular Hypertrophy and Residual Renal Function in Kidney Transplant Recipients.

Left ventricular hypertrophy (LVH), which is a pervasive complication of end-stage kidney disease (ESKD), persists in some uremic individuals even after kidney transplantation (Ktx), contributing to worsening CV outcomes. Marinobufagenin (MBG), an endogenous steroid cardiotonic hormone endowed with natriuretic and vasoconstrictive properties, is an acknowledged trigger of uremic cardiomyopathy. However, its clinical significance in the setting of Ktx remains undefined. In a cohort of chronic Ktx recipients (n = 40), we assessed circulating MBG together with a thorough clinical and echocardiographic examination. Forty matched haemodialysis (HD) patients and thirty healthy subjects served as controls for MBG measurements. Patients were then prospectively followed up to 12 months and the occurrence of an established cardio-renal endpoint (death, CV events, renal events, graft rejection) was recorded. Median MBG plasma levels were lower in Ktx as compared with HD patients (p = 0.02), but higher as compared with healthy controls (p = 0.0005). Urinary sodium (β = 0.423; p = 0.01) and eGFR (β = -0.324; p = 0.02) were the sole independent predictors of MBG in this cohort, while a strong correlation with left ventricular mass index (LVMi), found in univariate analyses (R = 0.543; p = 0.0007), gained significance only in multivariate models not including eGFR. Logistic regression analyses indicated MBG as a significant predictor of the combined endpoint (OR 2.38 [1.10-5.12] per each 1 nmoL/L increase; p = 0.01), as well as eGFR, LVMi, serum phosphate and proteinuria. Ktx recipients display altered MBG levels which are influenced by sodium balance, renal impairment and the severity of LVH. Thus, MBG might represent an important missing link between reduced graft function and pathological cardiac remodelling and may hold important prognostic value for improving cardio-renal risk assessment.

The Protective Role of Protocol Biopsy for Allograft Kidney Maintenance in Kidney Transplantation

Many studies have reported that protocol biopsy (PB) may help preserve kidney function in kidney transplant recipients. Early detection and treatment of subclinical rejection may reduce the incidence of chronic antibody-mediated rejection and graft failure. However, no consensus has been reached regarding PB effectiveness, timing, and policy. This study aimed to evaluate the protective role of routine PB performed 2 weeks and 1 year after kidney transplantation. We reviewed 854 kidney transplant recipients at the Samsung Medical Center between July 2007 and August 2017, with PBs planned at 2 weeks and 1 year after transplantation. We compared the trends in graft function, chronic kidney disease (CKD) progression, new-onset CKD, infection, and patient and graft survival between the 504 patients who underwent PB and 350 who did not undergo PB. The PB group was again divided into 2 groups: the single PB group (n=207) and the double PB group (n=297). The PB group was significantly different from the no-PB group in terms of the trends in graft function (estimated glomerular filtration rate). The Kaplan-Meier curve showed that PB did not significantly improve graft or overall patient survival. However, in the multivariate Cox analysis, the double PB group had advantages in graft survival, CKD progression, and new-onset CKD. PB can play a protective role in the maintenance of kidney grafts in kidney transplant recipients.

Is There Any Association Between Triglyceride–Glucose Index and Graft Function in Kidney Transplant Recipients?

BackgroundAlthough previous studies have illustrated the relationship between chronic kidney disease, coronary artery disease, erectile dysfunction, and the triglyceride–glucose index (TyGi), the relationship between this index and postoperative graft function in patients undergoing renal transplantation has yet to be investigated. In the present study, we aimed to reveal the association between the TyGi and renal graft outcomes in patients who underwent renal transplantation. MethodsWe retrospectively collected data on living and cadaveric kidney donor recipients between May 2019 and April 2022. The recipients’ age, sex, body mass index, preoperative fasting glucose and triglyceride levels, TyGi, estimated glomerular filtration rate (eGFR), and serum creatinine measurement data were recorded. The patients were divided into 2 groups according to their GFR values (group 1: GFR <60 mL/min/1.73 m2; group 2: GFR ≥60 mL/min/1.73 m2). Follow-up serum creatinine–eGFR levels and TyGi measurements were compared between the recipients in group 1 and group 2. ResultsThe mean TyGi measurements of the recipients were 8.79 ± 0.64 in group 1 and 8.83 ± 0.72 in group 2. There was no statistically significant difference in terms of the TyGi measurements between the 2 groups (P >. 05). No statistically significant correlation was found between the recipients’ creatinine, eGFR, and TyGi at 1st, 6th, and 12th postoperative months (P > .05). ConclusionsWe believe that the relationship between the TyGi and renal graft function can be more clearly understood in prospective studies that include a higher number of patients and a longer follow-up period.

Impact of Induction Therapy on Clinical Outcomes of Kidney Transplant Recipients

The purpose of this study was to evaluate long-term efficacy of immunosuppressive drugs based on the type of induction therapy given to kidney transplant recipients, and determine the occurrence of graft dysfunctions or rejections. We compared the safety and efficacy of anti-thymocyte globulin (ATG) and basiliximab (BAS) in high-risk patients and analyzed the cumulative incidence of immediate, slow, and delayed graft function in kidney transplant recipients to determine their initial short-term graft function. Evaluation of the long-term efficacy after 3 years post-transplantation by assessment of patients and graft survival, incidence of infections, and risks of rejection were the primary end-points. Patients with stable graft survival were observed more with ATG (85%) than BAS (70%); in contrast, graft dysfunctions, graft nephrec-tomy, rejection episodes, and patient deaths were more prevalent with BAS than ATG, with statistically significant differences in long-term graft functioning. Patient survival at 3 years in ATG group was 90.4%, compared to 88% in BAS group, and graft survival was 90.4% in the ATG group and 81.3% in the BAS group (P &lt; 0.001). The use of both induction therapies resulted in good patient and graft survival outcomes than placebo, and the results showed that there was a significant difference in both patient and graft survival after 3 years between induction of ATG and BAS, suggesting that ATG can be safer, effective, and preferable drug over BAS for high-risk recipients.

Metabolomic Profiling of Plasma, Urine, and Saliva of Kidney Transplantation Recipients.

Kidney biopsy is commonly used to diagnose kidney transplant dysfunction after transplantation. Therefore, the development of minimally invasive and quantitative methods to evaluate kidney function in transplant recipients is necessary. Here, we used capillary electrophoresis-mass spectrometry to analyze the biofluids collected from transplant recipients with impaired (Group I, n = 31) and stable (Group S, n = 19) kidney function and from donors (Group D, n = 9). Metabolomics analyses identified and quantified 97 metabolites in plasma, 133 metabolites in urine, and 108 metabolites in saliva. Multivariate analyses revealed apparent differences in the metabolomic profiles of the three groups. In plasma samples, arginine biosynthesis and purine metabolism between the I and S Groups differed. In addition, considerable differences in metabolomic profiles were observed between samples collected from participants with T cell-mediated rejection (TCR), antibody-mediated rejection, and other kidney disorders (KD). The metabolomic profiles in the three types of biofluids showed different patterns between TCR and KD, wherein 3-indoxyl sulfate showed a significant increase in TCR consistently in both plasma and urine samples. These results suggest that each biofluid has different metabolite features to evaluate kidney function after transplantation and that 3-indoxyl sulfate could predict acute rejection.

Dynamic changes of neutrophil-to-lymphocyte ratio in brain-dead donors and delayed graft function in kidney transplant recipients

Objectives Neutrophil-to-lymphocyte ratio (NLR) is a simple parameter implying the inflammatory status. We aimed to explore the association of brain-dead donor NLR change with delayed graft function (DGF) in kidney transplant recipients. Methods We retrospectively analyzed the data on 102 adult brain-dead donors and their corresponding 199 kidney transplant recipients (2018 − 2021). We calculated ΔNLR by subtracting the NLR before evaluating brain death from the preoperative NLR. Increasing donor NLR was defined as ΔNLR > 0. Results Forty-four (22%) recipients developed DGF after transplantation. Increasing donor NLR was significantly associated with the development of DGF in recipients (OR 2.8, 95% CI 1.2 − 6.6; p = .018), and remained significant (OR 2.6, 95% CI 1.0 − 6.4; p = .040) after adjustment of confounders including BMI, hypertension, diabetes, and the occurrence of cardiac arrest. When acute kidney injury (AKI) was included in the multivariable analysis, increasing donor NLR lost its independent correlation with DGF, while AKI remained an independent risk factor of recipient DGF (OR 4.5, 95% CI 2.7 − 7.6; p < .001). The area under the curve of combined increasing NLR and AKI in donors (0.873) for predicting DGF was superior to increasing donor NLR (0.625, p = .015) and AKI alone (0.859, p < .001). Conclusions Dynamic changes of donor NLR are promising in predicting post-transplant DGF. It will assist clinicians in the early recognition and management of renal graft dysfunction. Validation of this new biomarker in a large study is needed.

Assessment of Biochemical Parameters, Kidney Function, and Long-term Outcome in Renal Transplant Recipients

Background and Aims: New-onset of diabetes after transplantation (NODAT) is the most significant complications arising post-renal transplantation and affecting the long-term graft outcome and recipient survival. Assessment of renal function in kidney transplant recipients might help in understanding the better outcome of the graft and also the factors associated with NODAT. The present study was aimed to estimate the biochemical parameters, electrolytes, and minerals in the serum among renal transplant recipients and healthy controls (HC) and to evaluate the graft function, graft outcome and patient survival. Materials and Methods: Biochemical parameters (creatinine, urea, and uric acid), electrolytes (sodium, potassium, and chloride), and minerals (calcium and phosphorus) were estimated in serum by enzymatic method using commercially available kits in 100 HC, 80 NODAT, and 80 Non-NODAT subjects. The graft outcome was assessed by comparing serum creatinine levels and urinary creatinine clearance at 0 month and 60 months. The survival rate was evaluated by Kaplan-Meier survival curve. Results: The mean age was significantly higher in NODAT versus non-NODAT at P &lt; 0.0009. Significant gender difference was observed in NODAT and non-NODAT versus HC at P &lt; 0.0001. The levels of creatinine, urea, and uric acid were significantly more in NODAT versus HC at P &lt; 0.0001, P &lt; 0.0001, and P &lt; 0.006. The mean levels of sodium and phosphorus were significantly lower in NODAT versus HC at P &lt; 0.008 and P &lt; 0.029. In multinomial logistic regression analysis, age, male gender, creatinine, and urea significantly predicted the outcome and the Receiver Operating Characteristic analysis revealed creatinine to be better marker for assessing kidney function. The Kaplan-Meier survival curve analysis showed decreased survival rates in NODAT than non-NODAT. Conclusion: Older age (above 40), hyponatremia, and hypophosphatemia could be significant risk factors for NODAT development.

MO977: Circulating CD14++CD16+MONocytes, NK Cells and LYMPHOcyte Subsets Correlate with Conventional and Novel Deformation Related Indices of Left Ventricular Function in Kidney Transplant Recipients with no Established Cardiovascular Disease

Abstract BACKGROUND AND AIMS Kidney transplant recipients (KTRs) carry a significant burden of cardiovascular disease (CVD), despite improvement of patterns of left ventricular (LV) remodeling following kidney transplantation. Kidney allograft dysfunction and the immunosuppressed milieu play a major adverse role in myocardial structural changes in asymptomatic KTRs. An intricate relationship exists between immune system responses with heart failure syndromes, manifesting among others with aberrant activity and counts of proinflammatory CD16+monocytes, of natural killer (NK) cells and T regulatory cells (Tregs). The associations of immune cell subpopulations with subclinical markers of CVD remain to be determined in KTRs. The aim of our study was to investigate potential correlations between blood levels of specific immune cells subsets with conventional and novel deformation related indices of LV function in KTRs. METHOD 31 stable KTRs (mean age 58 ± 9.28 years, 67% males, 13% diabetics) without established CVD were enrolled. Control population included 17 chronic kidney disease (CKD) stage 3 patients without history of CVD. Additional exclusion criteria were history of malignancy, autoimmune disease and active or chronic infections. The peripheral blood immune cell subsets CD14++CD16-, CD14++CD16+and CD14+CD16++ absolute values and percentages out of total monocytes and NK cells (CD3+CD16+56+), CD3-CD19+B lymphocytes, CD3+CD4+T cells, CD3+CD8+T cells and Tregs (CD4+CD25+FoxP3+) absolute values and percentages out of total lymphocytes were measured by flow cytometry. Simultaneously, conventional (left atrial volume index (LAVI), LV mass index (LVMI), E/E’) and novel 2D speckle tracking (2DST) echocardiographic indices of LV function [global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), TWIST AND UNTWIST] were assessed. RESULTS KTRs had a mean eGFR of 58 ± 18 mL/min/1.73 m2 (CKD-EPI) and mean 24-h proteinuria (PER) 707 ± -1185 mg/24 h. Total lymphocytes, B-cells, T-cells and CD8+T cells counts correlated positively with eGFR (P &amp;lt; 0.05). Increased non-classical CD14+CD16++ monocytes were associated with proteinuria levels (P &amp;lt; 0.01) whereas an inverse correlation was observed between the percentage of classical CD14++CD16- monocytes with PER (P &amp;lt; 0.05). When compared with CKD patients, KTRs displayed higher CD14++CD16- and lower CD14+CD16++ monocytes counts, a lower percentage of NK cells and T cells and lower Tregs (significant differences presented in Table 1). Regarding classical indices of LV function, increased total monocytes were associated with elevated LAVI (P &amp;lt; 0.05), whereas an increased percentage of the intermediate CD14++CD16+monocytes correlated positively with an increased E/E’ value. Increased NK cells were associated with more negative GCS values (P &amp;lt; 0.05). No significant correlations were observed between the rest immune cells with the classical or novel LV dysfunction indices. CONCLUSION Alterations of immune cells subsets correlate with subclinical markers of LV dysfunction in KTRs with no established CVD. Future research is required to evaluate the role of immune subpopulations as tools to identify KTRs who are at the highest risk for complications and guide interventions.

MO955: Serum Cystatin C in Renal Transplantation: Beyond GFR Estimation, A Prognosis Marker?

Abstract BACKGROUND AND AIMS In renal transplantation, death with a functioning graft remains one of the main causes of graft loss. In the general population, renal function impairment is strongly associated with cardiovascular and all-cause mortality. Whether this association holds true for kidney transplant recipients (KTR) is unclear. This uncertainty is likely to be due, in part, to the fact that glomerular filtration rate (GFR) estimation based on serum creatinine (SCr) does not always provide an accurate evaluation of the graft function in KTR. As compared to SCr, we have previously shown in a large cohort of KTR that serum cystatin C (SCysC) is a much better marker of GFR. Herein, we sought to study the ability of the 1-year-post-transplant renal function to predict all-cause mortality according to the methods used to assess GFR. METHOD Four hundred and ten consecutive KTR for whom a measurement of GFR by inulin clearance was available at 1 year post-transplant were included. SCr and ScysC were measured with standardized methods. The association of the 1-year inulin clearance value the 1-year MDRD Study equation value and the 1-year CKD-EPI ScysC equation value with all-cause mortality was studied by ROC analysis and Cox model. RESULTS During a median follow-up of 17 years, 131 KTR died. Mean (±SD) inulin clearance at 1-year-post-transplant was 47 (±13) mL/min/1.73 m2. Areas under the ROC curves were similar for inulin and CKD-EPI ScysC equation values (0.62 for both), and were both significantly superior to that of the MDRD equation (0.54, P &amp;lt; 0.01). In Cox analysis, while all types of GFR evaluations were significantly associated to graft loss, only an inulin and a CKD-EPI ScysC equation values below 45 mL/min/1.73 m2 were associated with an excess risk of mortality (HR of 1.55, 1.45 and 1.01 for inulin, CKD-EPI ScysC and MDRD, respectively). CONCLUSION We conclude that ScysC-based GFR estimation might better predict KTR outcome as compared with a traditional SCr-based estimation. The one year-post transplant GFR value given by the CKD-EPI ScysC equation should be further evaluated as a potential surrogate marker for both graft and patient survival.

Perioperative Vasopressors are Associated with Delayed Graft Function in Kidney Transplant Recipients in a Primarily Black and Hispanic Cohort.

Introduction: Negative outcome studies of vasopressors in kidney transplant have not focused on patient populations that are predominantly Black or Hispanic. Project Aims: The evaluation sought to investigate the independent impact of perioperative vasopressors on postoperative renal allograft function in a sample drawn from a primarily Black and Hispanic population. Design: Retrospective, observational, single-center evaluation of patients > 18 years old who underwent kidney transplantation comparing outcomes based on vasopressor exposure. Results: The study included 150 patients of which 60 received vasopressors. The primary outcome differed between groups with delayed graft function occurring in 17(28%) versus 11(12.2%) occurring more often in those that received perioperative vasopressors (P = 0.02). The serum creatinine at postoperative day 7 was higher (2.69 vs1.52 mg/dL, P = 0.004), postoperative day 7 eGFR was worse (27.3 vs 52.9 mL/min/1.73m2, P = 0.002) in patients who received vasopressors. Patients who received perioperative vasopressors experienced more postoperative arrhythmias (15% vs 8%, P = 0.007), insulin infusion therapy (26.7% vs 13.3%, P = 0.04), and increased hospital length of stay (6 days vs 5 days, P = 0.006). Using IPWRA, patients receiving vasopressors were more likely to experience delayed function, relative risk difference of 22% (95% CI:0.08-0.35;P = 0.002) and in multivariate logistic regression modeling, an increased odds ratio of 3.2 (95% CI:1.1-8.62;P = 0.022). Conclusions: The use of perioperative vasopressors was independently associated with worsened early renal allograft function including delayed graft function, increased adverse events such as postoperative arrhythmias, and longer ICU length of stay. Further investigation is needed surrounding vasopressor use in this population.

Urinary Retinol-Binding Protein 4 is Associated With Renal Function and Rapid Renal Function Decline in Kidney Transplant Recipients

Urinary retinol-binding protein 4 (RBP4) has been known as a biomarker of chronic kidney disease. In this study, we evaluated the association of urinary RBP4 with renal function and progression of renal function in kidney transplant recipients (KTRs). A total 50 KTRs were included in this study. Proteomic analysis with liquid chromatography-mass spectrometry and tandem mass spectrometry was performed to discover potential urinary biomarkers. Several urinary proteins including RBP4 were identified and then validated by enzyme-linked immunosorbent assay. Rapid renal function decline was defined as estimated glomerular filtration rate (eGFR) decline of >3 mL/min/1.73 m2/year or initiation of dialysis, and 19 (38%) were included in rapid renal function decline group. Urinary RBP4/creatinine was inversely correlated with allograft function (r=-0.54, P < .001 with eGFR, and r=0.49, P < .001 with serum creatinine, respectively). Urinary RBP4/creatinine was higher in rapid renal function decline group than in stable renal function group (184.9 ± 156.7 vs 83.1 ± 99.9, P=.017). Log-transformed urinary RBP4/creatinine was significantly associated with rapid renal function decline in univariate logistic regression analysis (Odds ratio [OR] 7.59, confidence interval [CI] 2.04-36.70, P=.005). In multivariate logistic regression adjusted with recipient age and sex, donor age, number of HLA mismatch, and acute rejection episode, urinary RBP4/creatinine remained a significant factor for rapid renal function decline (OR 9.43, CI 1.99-65.65, P=.010). Receiver operating characteristic analysis showed that the area under the curve of urinary RBP4/creatinine was 0.747 (CI 0.608-0.886, P < .001) for rapid renal function decline. Urinary RBP4 levels are associated with renal function and might be used to predict rapid renal function decline in KTRs.

Proteinuria is accompanied by intratubular complement activation and apical membrane deposition of C3dg and C5b-9 in kidney transplant recipients.

Proteinuria predicts accelerated decline in kidney function in kidney transplant recipients (KTRs). We hypothesized that aberrant filtration of complement factors causes intraluminal activation, apical membrane attack on tubular cells, and progressive injury. Biobanked samples from two previous studies in albuminuric KTRs were used. The complement-activation split products C3c, C3dg, and soluble C5b-9-associated C9 neoantigen were analyzed by ELISA in urine and plasma using neoepitope-specific antibodies. Urinary extracellular vesicles (uEVs) were enriched by lectin and immunoaffinity isolation and analyzed by immunoblot analysis. Urine complement excretion increased significantly in KTRs with an albumin-to-creatinine ratio of ≥300 mg/g compared with <30 mg/g. Urine C3dg and C9 neoantigen excretion correlated significantly to changes in albumin excretion from 3 to 12 mo after transplantation. Fractional excretion of C9 neoantigen was significantly higher than for albumin, indicating postfiltration generation. C9 neoantigen was detected in uEVs in six of the nine albuminuric KTRs but was absent in non-albuminuric controls (n = 8). In C9 neoantigen-positive KTRs, lectin affinity enrichment of uEVs from the proximal tubules yielded signal for iC3b, C3dg, C9 neoantigen, and Na+-glucose transporter 2 but only weakly for aquaporin 2. Coisolation of podocyte markers and Tamm-Horsfall protein was minimal. Our findings show that albuminuria is associated with aberrant filtration and intratubular activation of complement with deposition of C3 activation split products and C5b-9-associated C9 neoantigen on uEVs from the proximal tubular apical membrane. Intratubular complement activation may contribute to progressive kidney injury in proteinuric kidney grafts.NEW & NOTEWORTHY The present study proposes a mechanistic coupling between proteinuria and aberrant filtration of complement precursors, intratubular complement activation, and apical membrane attack in kidney transplant recipients. C3dg and C5b-9-associated C9 neoantigen associate with proximal tubular apical membranes as demonstrated in urine extracellular vesicles. The discovery suggests intratubular complement as a mediator between proteinuria and progressive kidney damage. Inhibitors of soluble and/or luminal complement activation with access to the tubular lumen may be beneficial.

Soluble Complement Component 1q Receptor 1 (sCD93) Is Associated with Graft Function in Kidney Transplant Recipients.

Cluster of differentiation 93 (CD93), also known as complement component 1q receptor 1 is a transmembrane glycoprotein expressed in endothelial and hematopoietic cells and associated with phagocytosis, cell adhesion, angiogenesis and inflammation. The extracellular part, soluble CD93 (sCD93), is released to body fluids in inflammation. Data on sCD93 in kidney diseases are limited. Our aim was to evaluate serum sCD93 in long-term kidney transplant recipients as a marker of inflammation and endothelial dysfunction that may be potentially useful in early recognition of graft dysfunction. Seventy-eight adult patients with functioning kidney graft and stable clinical state were examined at least one year after kidney transplantation. Serum sCD93 was measured by enzyme immunosorbent assay. Estimated glomerular filtration rate (eGFR) and albuminuria or proteinuria were assessed at baseline and over one-year follow-up. Increased sCD93 was associated with lower baseline eGFR independently of the confounders. Moreover, sCD93 was negatively associated with eGFR during one-year follow-up in simple analysis; however, this was not confirmed after adjustment for confounders. Baseline sCD93 was positively associated with baseline albuminuria and with increased proteinuria during the follow-up. Serum sCD93 was not correlated with other studied inflammatory markers (interleukin 6, C-reactive protein, procalcitonin and C3 and C4 complement components). To the best of our knowledge, this is the first report regarding the concentrations of sCD93 in kidney transplant recipients and one of the first reports showing the inverse association between sCD93 and renal function. Serum sCD93 should be further evaluated as a diagnostic and prognostic marker in renal transplantation.

Evaluation of severity of delayed graft function in kidney transplant recipients.

The most common definition of delayed graft function (DGF) relies on dialysis during the first week post-transplant and does not consider DGF severity. The impact of DGF severity on long-term graft outcome remains controversial. We analysed 627 deceased-donor kidney transplant recipients (KTRs) transplanted in 2005-2015 at our centre for DGF severity, associated risk factors and long-term consequences of DGF. We found 349 (55.7%) KTRs with DGF, which were classified into four groups according to DGF duration (0-1, 2-7, 8-14, >14days) and were compared with KTR with no DGF. A longer duration of DGF was associated with progressive worsening of 10-year death-censored graft survival {no DGF: 88.3% [95% confidence interval (CI) 82.4-94.2]; 0-1 day: 81.3% [95% CI 68.2-94.4], 2-7 days: 61.5% [95% CI 43.1.1-79.9], 8-14 days: 66.6% [95% CI 47.4-85.8], >14days: 51.2% [95% CI 33-69.4]; P<0.001}. In kidneys with a Kidney Donor Profile Index (KDPI) ≥85%, all DGF severity groups demonstrated reduced graft survival. However, inthe <85% KDPIkidneys, only>14days DGF duration showed worse outcomes. DGF had a duration-dependent effect on graft survival, which varied depending on the KDPI. Of note, 0- to 1-day DGF showed comparable results to no DGF in the whole cohort.

IT'S NOT THE HEART

TOPIC: Pulmonary Vascular Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: HOHF is suspected when patients present with clinical symptoms of CHF but have an elevated CI typically above 4L/min/m2 [1]. These patients can exhibit signs and symptoms of CHF and have PH as a result of elevated blood flows through the pulmonary vasculature. CASE PRESENTATION: A 56 year-old male kidney transplant recipient (KTR) presented with shortness of breath, lower extremity edema 3-months after cadaveric renal transplantation. He had a history of chronic mild systolic cardiac dysfunction (EF 50%), pulmonary hypertension (WSPH group II), and diabetes mellitus type 2 prior to kidney transplantation. Physical exam was significant for +3 pitting edema of bilateral lower extremities, crackles at lung bases and a right brachiocephalic AVF with palpable thrill. Serum creatinine was 3.5mg/dL (baseline 2.0mg/dL) and Chest X ray showed pulmonary edema. Diuresis improved the edema and shortness of breath, but worsened renal function. Renal biopsy was negative for rejection. Echocardiography (TTE) revealed an elevated right ventricular systolic pressure (RVSP) and severely dilated right atrium (RA) and ventricle (RV). Right heart catheterization demonstrated elevated right and left sided filling pressures with moderate pulmonary hypertension (PH) and an elevated cardiac output/index (CO/CI). An AVF occlusion in the cath lab resulted in a significant reduction in CO 7.75 L/min and CI 3.10 L/min/m2 by thermodilution. Findings were consistent with PH secondary to high output heart failure (HOHF), likely related to AV fistula. He underwent an AVF revision with improvement of symptoms and renal function. DISCUSSION: PH is common in patients with ESRD undergoing HD via an AVF [2] and HOHF could be an easily addressable cause of PH in ESRD. HOHF can be difficult to diagnose based on echocardiography alone. RHC typically shows an elevated CO (> 8L/min, CI>4L/min/m2), AVF/G flow > 1.5L/min, and a cardiopulmonary recirculation ratio (CPR) > 0.3 [3]. Furthermore, PH prior to transplantation appears to have an adverse impact on allograft function in kidney transplant recipients (KTR) [4]. In a retrospective analysis of KTRs in a single institution, 29/113 (26%) of patients required closure of their AVF due to symptomatic CHF. The mean AVF flow rate was significantly elevated in patients requiring AVF closure compared to those managed conservatively (2197 ml/min vs. 851 ml/min) [5]. High flow rates due to increased arterial blood shunted from left to right circulation increased the preload and stroke volume and resulted in ventricular hypertrophy leading to subsequent heart failure [6]. CONCLUSIONS: In our patient, HOHF and PH secondary to an aneurysmal AVF resulted in acute cardio-renal syndrome type 1(CRS - 1) in the transplanted kidney. The improvement in both cardiac and renal function following the revision of AVF confirmed the diagnosis of cardiorenal injury due to an aneurysmal AVF. REFERENCE #1: Reddy YN, Obokata M, Dean PG, Melenovsky V, Nath KA, Borlaug BA. Long-term cardiovascular changes following creation of arteriovenous fistula in patients with end stage renal disease. Eur Heart J. 2017 Mar 6. REFERENCE #2: Schoenberg NC, Argula RG, Klings ES, Wilson KC, Farber HW. Prevalence and Mortality of Pulmonary Hypertension in ESRD: A Systematic Review and Meta-analysis. Lung. 2020 Jun;198(3):535-45. REFERENCE #3: Wijnen E, Keuter XH, Planken NR, van der Sande FM, Tordoir JH, Leunissen KM, et al. The relation between vascular access flow and different types of vascular access with systemic hemodynamics in hemodialysis patients. Artif Organs. 2005 Dec;29(12):960-4. DISCLOSURES: Advisory Committee Member relationship with Janssen pharmaceutical Please note: 4/2020 - 4/2021 Added 04/27/2021 by Rahul Argula, source=Web Response, value=Consulting fee Advisory Committee Member relationship with United Therapeutics Please note: 2019-2021 Added 04/27/2021 by Rahul Argula, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Breathe Technologies Please note: 2019 Added 04/27/2021 by Rahul Argula, source=Web Response, value=Consulting feeeducational grant relationship with Reata pharmaceuticals Please note: 2018-2019 Added 04/27/2021 by Rahul Argula, source=Web Response, value=Grant/Research Consultant relationship with Accordant health / CVS Please note: 2020 - 2021 Added 04/27/2021 by Rahul Argula, source=Web Response, value=Consulting fee no disclosure on file for mona haj; No relevant relationships by Elena Vlachos, source=Web Response

Killer cell immunoglobulin-like receptor (KIR) gene distribution and allograft kidney function.

The inhibition and activation cycles of the NK cells are mainly regulated by killer cell immunoglobulin-like receptors (KIRs). In this study, we examined KIR genes/genotypes in kidney transplant recipients and healthy subjects. We aimed to determine if there are relations between certain KIR genes and allograft kidney function. Renal transplantation patients (n=131) and healthy controls (n=183) from the same ethnic background were included. Transplant patients with an obvious cause of graft dysfunction (increase in serum creatinine and decrease in estimated glomerular filtration rate) were excluded. Recruited patients were classified as graft dysfunction (GD) (n=38) or functioning graft (FG) (n=93) based on rejection and allograft dysfunction. Isolated DNA of all participants were typed for 16 KIR genes with specific primers using PCR. Patient groups were compared for KIR genes/genotypes and clinical features. Significant differences were observed for KIR2DL3 and KIR3DL1 genes presented with higher frequencies in healthy controls than in kidney transplant recipients (p=0.001, p=0.006 respectively). Comparison between GD and FG groups revealed a protective association for the KIR2DL1 gene (p=0.003, OR=0.148). KIR2DL1 gene was significantly more frequent in renal transplantation patients with FG. We suggest that the presence of KIR2DL1, which is an inhibitor gene for NK cell functions, might be associated with favorable graft function in kidney transplant recipients.