Poor Renal Outcome Research Articles

Long-term renal survival and undetected risk factors of IgA nephropathy in Chinese children-a retrospective 1243 cases analysis from single centre experience.

The long-term renal outcome for IgA nephropathy (IgAN) in large cohorts of children remains unclear. IgAN is a progressive disease, to explore novel biomarkers is necessary for predicting the disease activity and progression of IgAN. In addition, there is a hot debate on when to treat with immunosuppression in children. We aimed to confirm the long-term renal survival, find some undetected risk factors and investigate when to treat with immunosuppression can benefit for renal outcome in Chinese children. 1243 Children with IgAN were enrolled and a follow-up of at least 1year after a biopsy from 2000 to 2017. Long-term renal survival, undetected risk factors and the renal survival of immunosuppressive and non-immunosuppressive therapy were evaluated. The primary endpoint of the study was a combined outcome of either ≥50% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD) or death. The median follow-up time were 86.8months (interquartile range 54.7-140.2months). The 5-, 10- and 15-year renal survival rates were 95.3%, 90.3% and 84%, respectively. Cox multivariate regression and Kaplan-Meier analysis showed that hypertension, hyperuricemia, high 24h urine protein (24h-UP) levels, lower initial eGFR, high urine C3 levels, high retinol-binding protein (RBP) levels, segmental glomerulosclerosis (S) and tubular atrophy and interstitial fibrosis (T) were associated with renal outcome. The statistically significant predictive perfect power for renal outcome was RBP≥0.7µg/ml (AUC = 0.899, sensitivity = 84.00%, specificity = 86.00%), 24h-UP ≥ 1g/24h (AUC = 0.722, sensitivity = 84.20%, specificity = 52.70%), eGFR<60ml/min/1.73m2 (AUC = 0.718, sensitivity = 81.30%, specificity = 39.20%) and S1 lesion (AUC = 0.703, sensitivity = 75.50%, specificity = 65.10%).Children with urinary RBP ≥0.7µg/ml were associated with a 2.513-fold risk than patients with urinary RBP<0.7µg/ml (P = 0.003). Our study suggested that immunosuppressive therapy may reduce the risk of progression in IgAN children had both eGFR>50ml/min/1.73m2 and proteinuria of at least 1g/day. This is the first report that the 15-year renal survival rate of children with IgAN in China was 84%. At the same time, this is the first study to reveal that urinary RBP≥0.7µg/ml may indicate a poor renal outcome. In addition, this study supports immunosuppressive therapy for IgAN children had both proteinuria≥1g/day and initial eGFR>50ml/min/1.73m2.

Lack of EULAR/ERA-EDTA response at 1 year predicts poor long-term renal outcome in patients with lupus nephritis

ObjectivesShort-term predictive endpoints of chronic kidney disease (CKD) are needed in lupus nephritis (LN). We tested response to therapy at 1 year.MethodsWe considered patients with LN who underwent renal biopsy...

P0462HEMODIALYSIS PREDICTORS IN ANCA-ASSOCIATED VASCULITIS AND ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE

Abstract Background and Aims Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and anti-glomerular basement membrane (GBM) disease are autoimmune diseases frequently associated with poor renal outcomes namely hemodialysis. Therefore, the aim of this study was to identify predictors of renal replacement therapy (RRT) at six months in patients with ANCA-associated vasculitis and/or anti-glomerular basement membrane disease. Method We performed a single center observational, retrospective study in 40 patients with ANCA-associated vasculitis and/or anti-GBM disease diagnosed between January 2013 and June 2019. Clinical, analytical and histological variables were included as well as therapeutic regimens and outcomes. The primary endpoint was renal replacement therapy (RRT) at six months. Continuous variables were presented as means or medians, according to normality and categorical variables presented as frequencies. The comparison between subgroups of patients was performed using the Wilcoxon, Fisher exact test or t-test, chi-square test, according to normality. Univariate logistic regression model was fitted to identify variables associated with renal replacement therapy. STATA 14.2 statistical package was used and p &amp;lt;0.05 was considered statistically significant. Results We identified 40 patients, with a mean age of 69 years-old, 18 (45%) were male, 37 (95%) Caucasian. Twenty-seven (68%) had hypertension and 3 (8%) diabetes. The majority (33, 83%) presented with constitutional symptoms. Pulmonary manifestations were seen in 12 (30%) and gastrointestinal in 5 patients (12%). The other symptoms were rare. The mean systolic blood pressure was 140 mmHg and mean diastolic blood pressure 73 mmHg. The mean hemoglobin in hospital stay was 9,4g/dL, albumin 3.0 mg/dL, erythrocyte sedimentation rate 77mm/h, C3 1,11 UQ, C4 0,30 UQ, proteinuria 1,42 gr/24h, hematuria 279 erythrocytes, serum creatinine 3,4 mg/dL, eGFR 14 ml/min/m2, uric acid 7.1 mg/dL. The average ANCA MPO titles were 382 UQ/L, PR3 751UQ/L and GBM 883UQ/L. During hospital stay 11 patients (28%) needed dialysis. Renal biopsy showed interstitial fibrosis and tubular atrophy grade 0 in 5 patients (13%), grade 1 in 13(33%), grade 2 in 8 (20%) and grade 3 in 14 (35%). The majority had no vessel involvement 24 (60%). Acute tubular necrosis was absent in 13 (33%) patients, grade 1 in 9 (23%) and grade 2 in 18 (45%). Inflammatory infiltrate was present in 25 patients (63%). Regarding treatment, 38 (95%) of patients received pulse methylprednisolone and all prednisolone. Rituximab was administered to 15 (38%) patients and Cyclophosphamide to 14 (35%). Eighteen (45%) received azathioprine and 3 (8%) mycophenolate mofetil. Plasmapheresis was performed in 14 patients (35%). The average time from beginning of symptoms to treatment initiation was 119 days. The mean follow-up was 1094 days. At discharge the mean serum creatinine was 2,5 mg/dL, eGFR 23ml/min/m2 and none of the patients died. At six months, mean serum creatinine was 1.6 mg/dL, eGFR 31ml/min/m2 but 15 (38%) patients were dialysis-dependent. Two relapses occurred and 17 (43%) had infections during this period. Five (13%) patients died. At 12 months, mean serum creatinine was 2.0 mg/dL, eGFR 29 ml/min/m2 and (9) 23% patients were dialysis dependent. Six (30%) patients had infections and 5 (13%) died. In the end of follow up 13 (33%) patients had died. On univariate analysis, hemoglobin (OR 0.59 [0.36-0.95], p = 0.031), uric acid (OR 1.85 [1.12-3.05], p = 0.027), hematuria (OR 1.00 [1.00-1.00], p = 0.013), hemodialysis performed during 1st hospital stay (OR 22.9 [2.3-217.9], p = 0.006) and plasmapheresis ( OR 12.0 [2.4-61.0], p = 0.003) were associated with RRT at six months. Conclusion RRT in AAV and anti-GBM disease has decreased over the last decades with the use of immunosuppressive therapies. Clinical presentation and plasmapheresis seem the major predictors for RRT.

P0674DCR2,AS A SENESCENCE MARKER,IS ASSOCIATED WITH DISEASE SEVERITY AND PROGRESSION IN IGA NEPHROPATHY PATIENTS

Abstract Background and Aims Accelerated senescence of renal tubular epithelial cells (RTECs) may contribute to the progression of IgA Nephropathy (IgAN). Our previous studies demonstrated that DcR2 may reflect senescence of RTECs in experimental models and patients with diabetic nephropathy. The objective of this study was to investigate the association of DCR2 with disease severity and progression in IgAN. Method We included a retrospective cohort of 105 patients with biopsy proven IgAN. 15 normal renal tissue specimens displaying insignificant alterations biopsied from patients with renal carcinoma were recruited as controls. Renal biopsies from all patients were scored according to Oxford classification (MEST-C score). We analysed the degree of expression and localization of DCR2 in biopsies from kidneys with IgAN, and correlated their immunostaining levels with various clinical and histological parameters at baseline. Cox regression was performed for the composite renal outcome defined as 30% reduction in initial estimated glomerular filtration rate (eGFR) and/or end-stage renal disease (ESRD), and for the individual components during a follow-up for 60 or more months. Results DCR2 was overexpressed in the cytoplasm of RTECs obtained from kidneys of patients with IgAN [male: 60.9%, age:39.5±13.0 years, mean arterial pressure (MAP): 95.2±18.0 mmHg, proteinuria: 1.9 (0.7, 3.7)g/day, Initial eGFR:89.8±37.2 ml/min/1.73 m2], and were elevated with the increasing T scores. At baseline, DCR2 protein levels in the RTECs was inversely correlated with eGFR (R=−0.597, P=0.000) and positively associated with 24h-proteinuria (R=0.379, P=0.000) and the T score (R=0.632, P = 0.000). During a median follow-up of 80 (60, 125) months, patients with ≥25% tubular DCR2 positive showed worse eGFR slopes (the rate of eGFR decline) than those&amp;lt;25% DCR2 positive group [4.35 (2.17, 5.53) versus 0.36 (-0.96, 1.19) ml/min per 1.73 m2 per year; P=0.000)]. Kaplan–Meier survival analysis revealed that renal survival for the composite outcome was significantly lower in the ≥25% DCR2 positive group than in the&amp;lt;25% DCR2 positive group (P=0.000). In Cox regression models, ≥25% tubular DCR2 positive expression independently associated with poor renal outcome (HR=2.02, P=0.001) after adjustment for multiple known risk factors for IgAN progression, including baseline proteinuria, hypertension, eGFR, Oxford scores, and steroids/immunosuppressive therapy. Moreover, tubular DCR2 expression showed the highest sensitivity and specificity (80.8% and 87.3%, respectively) at a cut-off value of 25.5% DCR2 positive expression over proteinuria and eGFR for the composite outcome. The area under the receiver operating characteristic curve (AUROC) of tubular DCR2 expression was 0.880. Conclusion DCR2 is associated with disease severity and prognosis in IgAN patients and may have additional prognostic value besides established risk markers.

P0365INCREASED LIFETIME RISK OF END-STAGE RENAL DISEASE IN FAMILIAL IGA NEPHROLOGY

Abstract Background and Aims Familial IgA nephropathy (IgAN) has been widely reported around the world. However, it's clinico-histological characteristics and long-term prognosis are not clear. Method In this study, 348 familial IgAN cases from167 independent IgAN families were recruited and their clinico-histological characteristics were compared to 1,116 sporadic IgAN patients from the same geographic region. Inheritance patterns, clinical features, and treatment regimens of all recruited patients were recorded and lifetime risk of end-stage renal disease (ESRD) was compared between familial and sporadic cases. Results Of all familial IgAN patients, 60 (17%) came from 32 single-generation (SG, defined as all affected individuals are siblings) families, while 286 (82%) came from 134 multiple-generation (MG, affected individuals were present in at least two consecutive generations) families. There’re totally 178 transmissions, 79 of which (44%) were paternal transmission and 99 (56%) were maternal transmissions. We observed evidence for incomplete penetrance in 30 (22%) MG families. The lifetime risk of progression to ESRD was significantly higher in familial IgAN patients than sporadic patients after adjusted by gender [HR=1.40, 95%CI: 1.12-1.74, P=0.004], with 5-year younger in median ESRD onset age [median ESRD-free survival of 60 years vs. 65 years in familial and sporadic cases separately]. As expected, compared to the ones without progressive renal failure at disease onset (eGFR≥60ml/min), familial cases with progressive renal failure (eGFR&amp;lt;60ml/min) had higher risk of lifetime ESRD [HR=6.32, 95%CI: 3.73-10.72, P&amp;lt;0.001]. Interestingly, among familial cases, we found cases from SG families [vs MG families: HR=2.62, 95%CI: 1.59-4.31, P&amp;lt;0.001] or with early onset (onset age &amp;lt;30yrs) [vs late onset: HR=4.79, 95%CI: 3.16-7.26, P&amp;lt;0.001] had higher lifetime risk of ESRD. Furthermore, among sporadic patients, compared to females, males had lower eGFR, higher urine protein, higher Oxford T score and resulted in a higher risk for lifespan ESRD (male vs female, 25% vs 17%, P=0.003) while these gender difference was not seen in familial patients. Conclusion In conclusion, familial IgAN cases had poorer renal outcomes and less gender differences compared to sporadic cases. These findings provide evidence that familial disease represent a distinct subtype of more progressive IgAN.

P0207PLASMA CHEMOKINE CXC MOTIF-LIGAND 16 AS A PREDICTOR OF RENAL PROGNOSIS IN IMMUNOGLOBULIN A NEPHROPATHY

Abstract Background and Aims A recognized non-invasive biomarker to improve risk stratification of IgA nephropathy (IgAN) patients is scarce. CXCL16 has been shown to play a key role in inflammatory disease as chemoattractant, adhesion and fibrosis factor. This study assessed the possibility of plasma CXCL16 as a potential biomarker in IgAN patients. Method Plasma CXCL16 was measured in 230 patients with renal biopsied IgAN from 2012 to 2014. The patients were followed for 41.3 months with 50% reduction in eGFR or ESRD as end-points. Results The plasma CXCL16 levels in IgAN patients were significantly correlated with the uric acid, estimated glomerular filtration rate and tubular atrophy/interstitial fibrosis score in multivariate analysis. In addition, the counts of CD4+ T cells, CD8+ T cells and CD20+ B cells in renal biopsies of IgAN patients were significantly correlated with the plasma CXCL16 levels, but not CD68+ macrophage. Finally, we concluded that patients with higher plasma CXCL16 levels had a higher risk of poor renal outcome compared with those with lower. No association was observed between the CXCL16 polymorphisms and clinical parameters including plasma CXCL16 levels and prognosis. Conclusion Plasma CXCL16 levels were associated with clinical parameters, pathological damage, the CD4+ T cells, CD8+ T cells and CD20+ B cells infiltration in renal tissue and renal outcome in IgAN patients. Plasma CXCL16 might be a potential prognosis predictor in Chinese IgAN patients.

P0418LUPUS NEPHRITIS: A MONOCENTRIC STUDY

Abstract Background and Aims Systemic lupus erythematosus is a multi-visceral autoimmune disease. Renal involvement is one of the most common and serious manifestations of this disease. The histological lesions are highly polymorphic and the renal biopsy remains crucial for the therapeutic management of lupus nephritis (LN). The aim of our investigation was to study the epidemiological, clinical, biological and histological characteristics, outcomes and to evaluate the therapeutic protocols used for lupus nephritis’ treatment and to identify predictive factors of renal prognosis in patients with lupus nephritis. Method It was a retrospective study including patients over 16 years old with lupus nephritis proved by kidney biopsy and followed up over a period of 17 years in our department. Results We collected 155 women and 19 men with a sex ratio F / H of 8.2. The mean age at the time of the discovery of LN was 32.6 years with a maximum between 15 years and 45 years. The most frequent extra-renal manifestations were articular and dermatological manifestations (79%). Renal symptomatology was dominated by proteinuria noted in all patients, associated to a nephrotic syndrome in 68% of patients. At the time of diagnosis of LN, hematuria was present in 69% of patients and renal failure was present in half of cases. Immunologically, antinuclear antibody were positive in 89.1% of cases, anti DNA positive in 73.4% of cases, anti Sm positive in 79.8% of cases and Antiphospholipids were positive in 50% of cases, associated with an antiphospholipid syndrome in 14.9% of cases. We performed 243 renal biopsies with 174 initial and 69 iterative biopsies. The histological lesions were polymorphic dominated by LN class IV (36.6%) isolated or associated with LN class V (17.7%). All patients received a corticosteroid for induction or maintenance treatment. It was associated with immunosuppressive treatment according to different treatment regimens. The median duration of follow-up was 81.2 months. Renal outcome was marked by complete and sustained remission in 36.7% of cases, incomplete remission with chronic kidney disease in 34.5% of cases, chronic renal failure in 28.7% of cases. At univariate analysis, we identified the young age below 35 years at the time of the discovery of LN, the male sex, increased serum creatinine at the time of biopsy, proliferative forms, the presence of histological signs of chronicity and lesions of thrombotic microangiopathy as predictive factors of poor renal outcomes. Conclusion Lupus nephritis is one of the most common and serious manifestations of Systemic lupus erythematosus. The generalization of renal biopsy, the use of early codified therapeutic protocols and regular monitoring and evaluation of disease activity according to the appropriate scores can improve management and survival of patients with renal impairment.

P0484CLINICAL FEATURES AND OUTCOME OF LUPUS NEPHRITIS IN MOROCCO: A SINGLE CENTER STUDY OF 207 CASES

Abstract Background and Aims renal involvement is a common and potentially severe complication of systemic lupus erythematosus (SLE). Few data for Lupus nephritis (LN) exist on North Africans, especially those from Morocco. The aim of our study was to report the long-term renal outcome of a cohort of Moroccan patients with LN. Methods the records of 207 patients (191 females, 16 males) with LN (American College of Rheumatology criteria) admitted to the departments of nephrology and internal medicine of Marrakesh University Hospital were reviewed and included in a retrospective analysis. Results the mean age at the time of renal biopsy was 31,7 ± 15,9 years. Time between diagnosis of SLE and the onset of renal disease was 29 ± 10 months. Renal involvement was observed concomitantly with the onset of SLE in 39 patients (18,8%). At presentation, 65 patients (31,4%) had hypertension. Hematuria was seen in 158 patients (76,3%), nephrotic syndrome in 82 patients ( 39,6%) and renal failure in 76 patients (36,7%). The most frequent extarenal manifestations were skin and joint manifestations in 89,3% and 83,6% respectively. The most common histological finding was type IV LN in 96 patients, followed by type III LN in 51 patients. 191patients (92,3%) received corticosteroids as initial therapy followed by immunosuppressive therapy in 127 patients (61,3%). During the follow-up period, partial or total remission was obtained in 56,5% of cases while 61 patients (29,4%) progressed to end stage renal disease (ESRD) and 29 patients (14%) died. Logistic regression detected that hypertension, high serum creatinine at admission and proliferative histological classes were the main risk factors for poor renal outcome. Conclusion Our results showed that LN was particularly severe in our population compared with other published data with predominance of proliferative forms.

P0276SERUM C3 LEVELS AND THE PROGNOSIS OF ANCA-ASSOCIATED VASCULITIS: A SINGLE-CENTER RETROSPECTIVE STUDY

Figure: Background and Aims Despite improved survival, patients affected by ANCA-associated vasculitis (AAV) presenting with rapidly progressive glomerulonephritis (RPGN) still remain at a higher risk of death relative to the general population. Recent findings suggest a role for the activation of the complement alternative pathway in the pathogenesis of the disease. We aimed to retrospectively evaluate the presentation and outcome of a cohort of patients with AAV and RPGN according to ANCA specificity, investigating the role of complement pathways. Method We retrospectively examined 1,547 biopsies performed between 1996 and 2019 in our center, which included 124 patients presenting with paucimmune RPGN. Patients without ANCA serology and/or with missing data (n=44), ANCA negative RPGN (n=15) and anti-GBM disease (n=2) were excluded from our analysis. Seventy-eight patients with AAV and RPGN (63 biopsy proven) were analysed and compared according to ANCA serotype (n=30 MPO, n=21 PR3). Furthermore, data were analysed on the basis of median levels of serum C3 (1.05 g/l). Statistical analysis Data are mean ± SD or median and interquartile range for variables not normally distributed. Groups were compared using ANOVA after logarithmic transformation of skewed variables. Primary endpoint was renal survival defined as need for renal replacement therapy (NRRT); secondary outcome was patient survival. Cumulative and renal survivals were calculated using Kaplan-Meier method and differences between groups were analysed with the log-rank test. Multivariate Cox proportional hazard analysis for time to NRRT was performed to determine the significance of different risk factors in renal outcome. A p value of &amp;lt; 0.05 was considered statistically significant. Results Patients had a mean age of 64± yrs and eGFR ±15 ml/min at diagnosis. Patients with MPO-AAV were older (69±11 vs. 61±14 yrs, p=0.02) and showed lower levels of C3 (1.0±0.22 vs 1.25±0.2 g/l, p=0.009) as compared to PR3 patients. Moreover, those presenting with C3 levels lower than median value had more advanced renal damage at diagnosis (eGFR 7± ml/min vs 15.5± ml/min, p= 0.04). Serum C3, but not C4 levels, significantly correlated with eGFR, proteinuria and serum uric acid at diagnosis. Twenty-seven (39.7%) reached ESRD requiring RRT. The 1-, 5- and 10- yrs patients renal survivals were 81%, 62.9 % and 52.4%. Renal outcome was neither influenced by ANCA serotype nor gender but patients with C3 levels below median value exhibited a worse renal prognosis (Log rank p=0.02) and a 5 times higher risk of NRRT (HR 5.1, 95% CI 1.4-18.7, p=0.01) independently by potential confounding factors. Conclusion Referral to the nephrologist was late, at an advanced stage of disease, indicating the need to improve the awareness of AAV and RPGN in order to favour early treatment. In this cohort, low C3 indicated a more severe renal damage and predicted poorer renal outcome thus suggesting a role of complement activation in the pathogenesis and progression of these nephritides.

Weight-Based Assessment of Fluid Overload in Patients with Acute Kidney Injury

Introduction: Acute kidney injury (AKI) with fluid overload is associated with poor outcomes. While percentage fluid overload (PFO) using intake/output charts (PFO_i/o) has been validated as a marker of overload, accurate PFO_i/o measurements may not be possible in a general ward. We propose an alternative weight-based PFO calculation: PFO_w = [(maximum weight − baseline weight) ÷ baseline weight] × 100%. Methods: This is a prospective, observational pilot study on general ward inpatients with AKI who were referred for nephrology consult. PFO_w was compared with PFO_i/o, and both were evaluated for associations with dialysis requirement, AKI stage 2 or 3, and 90-day mortality. Results: Fifty-eight patients with a median age of 67.5 years (interquartile range 18.0) were recruited. Of which, 33 (56.9%) were males and 41 (70.7%) had preexisting CKD 3 or higher. We found no correlation between PFO_i/o and PFO_w (R² = 0.015, p = 0.531). A higher PFO_w was observed in AKI stage 2 or 3 (p = 0.005) and in patients requiring dialysis (p = 0.001). On multivariate analysis, each percentage increase in PFO_w was associated with increased odds of AKI stage 2 or 3 (odds ratio 1.37 [95% CI 1.05–1.78], p = 0.020) and dialysis need (odds ratio 1.69 [95% CI 1.20–2.39], p = 0.003). Twenty-nine patients had complete quantitative data to calculate PFO_i/o. Multivariate analysis of these 29 patients showed that PFO_w correlated with AKI stage 2 or 3 and dialysis requirement, while PFO_i/o had no correlation with these events. The area under the curve receiver operating characteristics of PFO_w was 0.706 for AKI stage 2 or 3 and 0.819 for AKI requiring dialysis. The optimal PFO_w cutoff was determined at ≥1%. Three deaths occurred within 90 days, and all had PFO_w ≥ 1%, although the log-rank test did not achieve statistical significance (p = 0.050). Conclusion: The proposed PFO_w is a potential prognostic indicator for general ward patients with AKI. PFO_w ≥ 1% is associated with poor renal outcomes.

Comparison of clinicopathological features and prognosis between IgA nephropathy and purpura nephritis in adults with diffuse endocapillary proliferation: a single-center cohort study.

Clinical manifestations and histological lesions of IgA nephropathy and Henoch-Schönlein purpura nephritis (HSPN) are different, but related, and are also correlated with the renal outcomes. This study aimed to compare the features of immunoglobulin A nephropathy (IgAN) and HSPN in adult patients with diffuse endocapillary proliferation (DEP) lesions aiming to clarify the differences and relationships in the clinicopathological findings and outcome. Twelve patients with DEP-IgAN and 10 patients with DEP-HSPN were enrolled. Twenty four patients with IgAN (NDEP-IgAN) and matched 20 patients with HSPN (NDEP-HSPN) were enrolled at the same ratio (1:2). The clinicopathological features, clinical efficacy, and renal outcomes were analyzed in the four groups. DEP patients with IgAN or HSPN had worse clinical manifestations (more severe proteinuria, lower serum ALB, higher incidence of gross hematuria). The proteinuria in the DEP-HSPN group was more severe than in the DEP-IgAN group. There was no significant difference in the serum creatinine among four groups. The incidence of endothelial swelling was significantly higher in the DEP-HSPN group than in the NDEP-HSPN group and DEP-IgAN group. The S1 score of Oxford classification was more common in the DEP-IgAN group than in the DEP-HSPN. None in the DEP-IgAN group reached endpoint events during the follow-up period, while the renal outcomes were significantly poorer in the DEP-HSPN group than in the DEP-IgAN and NDEP-HSPN groups. No significant difference was observed in the cumulative renal survival among four groups (χ 2 =7.264, P=0.064), but patients in the DEP-HSPN group had markedly lower renal cumulative survival rate as compared to the NDEP-HSPN group (χ 2 =4.875, P=0.027). The DEP is significantly associated with more severe proteinuria and hematuria regardless the IgAN and HSPN. Among DEP patients, patients with HSPN have poor therapeutic efficacy and renal outcomes, even under active immunosuppressive therapy, as compared to those with IgAN.

Association between Renal Podocalyxin Expression and Renal Dysfunction in Patients with Diabetic Nephropathy: A Single-Center, Retrospective Case-Control Study.

This retrospective study investigated whether podocalyxin expression in renal biopsies and urine of patients with diabetic nephropathy (DN) is associated with renal function. This retrospective study included 32 patients with nephropathy, secondary to type 2 diabetes treated at the First Hospital of Lanzhou University (January 2010 to January 2015). Compared with the control group, the DN group had a significantly lower renal expression of podocalyxin and higher urinary podocalyxin/creatinine ratio. Patients with DN were divided into the high and low expression groups according to podocalyxin expression in renal tissues. Patients in the low expression group had longer diabetes duration, lower plasma albumin and eGFR, higher glycated hemoglobin (HbA1c), 24 h urinary protein, serum creatinine, and urinary podocalyxin/creatinine ratio, and more severe glomerular, tubulointerstitial, and renal interstitial inflammation than patients in the high expression group (all P < 0.01). The renal survival rate was significantly lower in the low expression group than in the high expression group (P < 0.01). Single-factor Cox regression analysis showed that reduced podocalyxin expression and increased urinary podocalyxin excretion were associated with poor renal outcome. Measuring podocalyxin levels in renal tissues and urine could help evaluate the progression of DN.

Trends in Blood Urea Nitrogen to Creatinine Ratio between Listing and Heart Transplant are Associated with Poor Post-Transplant Outcomes

Non-dialysis dependent patients with renal impairment undergoing heart transplantation (HT) alone are at higher risk of mortality and poor renal outcomes compared to those undergoing heart-kidney transplantation (HKT). It remains unclear what parameters might identify patients who may benefit from HKT compared to HT. We investigated whether interval changes in blood urea nitrogen to creatinine ratio (BCR) between listing and transplant in those with stage 3 chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) 30 - 59 ml/min/1.73 m2) are associated with higher risk of post-HT death or worsening renal function (WRF). We identified 159 patients undergoing HT at our institution between 1/2009 and 2/2018. Absolute changes in BCR between listing and transplant were categorized as improved (BCR decreased) or worsened (BCR increased). Next, the following groups were created: Group 1 - improved BCR and BCR ≤ 21 at HT, Group 2 - worsened BCR but remained ≤21 at HT, Group 3 - worsened BCR and BCR >21 at HT, and Group 4 - improved BCR but remained >21 at HT. WRF was defined as a decrease in eGFR by >25% or need for dialysis between HT and 1-year follow up. One-year composite risk of death or dialysis was our primary outcome of interest; WRF in survivors was our secondary outcome of interest. By 1 year, a total of 14 patients died and 43 had WRF, including 15 who needed dialysis. The BCR improved in 98 patients (62%) and worsened in 61 (38%); BCR was >21 at HT in 25 patients (16%). Group 4 incurred highest risk of both the primary and secondary outcomes (see figure) with adjusted hazard ratio of 3.81 (95% confidence interval (CI): 1.45-10.00; p<0.01) for the primary outcome and odds ratio of 9.21 (95% CI: 2.13-39.76; p<0.01) for the secondary outcome. High BCR at listing that remained >21 at HT despite interval improvement was associated with increased risk of death or dialysis and WRF. These findings warrant further pathophysiologic explanation.

Trends in MELD-XI between Listing and Transplant are Associated with Poor Outcomes in Heart Transplant Recipients with Stage 3 Chronic Kidney Disease

Non-dialysis dependent patients with renal impairment undergoing heart transplantation (HT) alone are at significantly higher risk of mortality and poor renal outcomes compared with those undergoing heart-kidney transplantation (HKT). It remains unclear what parameters might identify patients who may benefit from HKT compared to HT alone. The Model for End-Stage Liver Disease Excluding INR (MELD-XI) score at the time of HT has been shown to predict early post-HT mortality. We investigated whether trends in the MELD-XI score between listing and transplant among those with stage 3 chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) between 30 and 59 ml/min/1.73 m2) are associated with higher risk of post-HT death or dialysis. We identified 159 patients undergoing HT at our institution between 1/2009 and 2/2018. The following groups were created: Group 1 - MELD-XI ≤ 16 at listing and HT, Group 2 - MELD-XI ≤ 16 at listing and > 16 at HT, Group 3 - MELD-XI > 16 at listing and ≤ 16 at HT, Group 4 - MELD-XI > 16 at listing and HT. A cutoff of 16 was chosen based on the 75th percentile in a normal distribution among those without a composite outcome of post-HT death or dialysis at 1 year. Cox-proportional regression and survival analyses were performed to assess risk of this outcome. Average MELD-XI at listing was 14.0 ± 4.9 and at HT was 12.8 ± 4.5 (p < 0.01); MELD-XI >16 was present in 51 (32.1%) at listing and 38 (23.9%) at HT. Group 4 incurred highest risk of composite outcome relative to Group 1 (adjusted hazard ratio 3.67 (95% confidence interval: 1.38-9.76, p < 0.01); see figure). Notably, Groups 2 and 3 had a statistically nonsignificant trend toward higher risk of the composite outcome compared to Group 1. Changes in MELD-XI between listing and transplantation offer additional risk stratification beyond absolute MELD-XI at time of transplant for death or dialysis at 1 year in patients with stage 3 CKD.

Blood Urea Nitrogen to Creatinine Ratio at Listing is Associated with Poor Outcomes in Heart Transplant Recipients with Stage 3 Chronic Kidney Disease

Non-dialysis dependent patients with renal impairment undergoing heart transplantation (HT) alone are at significantly higher risk of mortality and poor renal outcomes compared with those undergoing heart-kidney transplantation (HKT). It remains unclear what parameters might identify patients who may benefit from HKT compared to HT alone. We investigated whether blood urea nitrogen to creatinine ratio (BCR) at time of HT listing among those with stage 3 chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) between 30 and 59 ml/min/1.73 m2) is associated with higher risk of post-HT death or dialysis. We identified 159 patients who underwent HT alone at our institution between 1/2009 and 2/2018. Univariate and multivariate Cox-proportional regression analyses were used to investigate the association between BCR and composite risk of post-HT death or dialysis at 1 year. At listing, average age was 55±10 years (74% male and 28% African American) and eGFR was 47 ± 8. Mean eGFR did not differ between those with the composite outcome (46 ± 8) and those without (47 ± 8; p = 0.60). Overall, 14 patients (9%) died and 25 (16%) needed dialysis by 1 year post-HT. The univariate and multivariate adjusted hazard ratios for continuous variable BCR as a predictor of the composite outcome were 1.05 [95% confidence interval (CI): 1.02, 1.09; p < 0.01) and 1.04 [95% CI: 1.01, 1.09; p = 0.02), respectively. Additional regression analyses and Kaplan-Meier survival curves are shown in the figure. Heart transplant candidates with stage 3 CKD and elevated BCR at time of listing are at increased risk of post-HT mortality or dialysis. Further investigation of HKT outcomes among those with stage 3 CKD and elevated BCR at listing is warranted.

Spondyloarthritis-Associated IgA Nephropathy

IntroductionIgA nephropathy (IgAN) can be associated with spondyloarthritis (SpA). The course of SpA-associated IgAN remains largely unknown due to the absence of large cohorts.MethodsThis retrospective study included patients with biopsy-proven IgAN and definite SpA. Kidney biopsies were centrally examined and scored according to the IgAN Oxford Classification. Thirty-two patients fulfilled the inclusion criteria, with a male:female ratio of 9:1 and median age of 27 and 37 years at SpA and IgAN diagnosis, respectively. HLA-B27 was positive in 90% of cases, and most patients (60%) presented with ankylosing spondylitis. The mean baseline estimated glomerular filtration rate (eGFR) was 84 ± 26 ml/min per 1.73 m2, and the urine protein-to-creatinine ratio was 0.19 g/mmol.ResultsRenal biopsy revealed frequent presence of crescents (33%) and interstitial inflammation (18%). Despite almost constant use of renin-angiotensin system inhibitors, combined with steroids in 13 of 32 patients, renal outcome was particularly poor. After a median follow-up of 5.9 years, 4 patients (12.5%) reached end-stage renal disease and 41% of patients experienced a >50% decrease of eGFR. The mean annual eGFR decline rate was −4.3 ± 6.7 ml/min per 1.73 m2. The risk of reaching class IV or V chronic kidney disease (CKD) stage during follow-up was associated with the presence of hypertension, level of proteinuria, and baseline S- and T-scores of the Oxford.ConclusionSpA-associated IgAN is associated with a poor renal outcome, despite frequent use of steroids. Tumor necrosis factor (TNF)-α blockade did not appear to influence the rate of eGFR decline in this setting.

SAT-429 CMV-ASSOCIATED CONGENITAL NEPHROTIC SYNDROME: CORRELATION OF CLINICAL, HISTOPATHOLOGICAL AND GENETIC FINDINGS

Congenital nephrotic syndrome (cNS), defined by onset during the first three months of life, is a rare clinical disorder with traditionally poor renal outcome. It is caused by homozygous or compound heterozygous mutations of a growing number of genes affecting podocyte and/or glomerular basement membrane integrity, with or without syndromic features. Other potential etiologies include antenatal or perinatal infections, or (other) systemic disorders. Case description and systematic review of the literature in PubMed using the key words "CMV", "congenital” or "infant", and "nephrotic” or "glomerulonephritis". This report describes an ex-preterm baby who had been referred at two weeks corrected gestational age for suspected surgical abdomen in view of progressive abdominal distention, scrotal edema and vomiting. The patient was found to have full-blown nephrotic syndrome with urine protein-to-creatinine ratio of > 6 g/g, hypoalbuminemia <10 g/L, hypercholesterolemia and anemia, and elevated liver transaminases. He had syndromic features. Diagnostic workup revealed an active CMV infection, based on CMV-specific IgM and positive CMV PCR from blood and urine. Routine pregnancy screen for intrauterine infections had been negative. Subsequent maternal diagnostic revealed high maternal anti-CMV IgG (IgM negative) and positive CMV PCR. The infant’s kidney biopsy showed focal mesangial proliferation and sclerosing glomerulonephritis with cellular or fibro-cellular crescents in less than 5% of glomeruli, while global or segmental sclerosis associated with older fibrous crescents was noted in 10% of glomeruli, in addition to interstitial fibrosis and tubular atrophy. Routine immune fluorescence was negative. Electron microscopy revealed diffuse podocyte foot process effacement, but no immune complexes or endothelial tubule-reticular inclusions. Infiltrating (interstitial) lymphocytes stained positive for CD3 and CD20, respectively. Results of the genetic mutation screen are pending. After 6 weeks of treatment with valganciclovir, the CMV PCR has become negative, but the infant continues to demonstrate severe proteinuria and hypoalbuminemia. Review of the available literature reveals an important overlap between cNS due to known monogenic causes and CMV infection. Although the number of defined cases in the literature is scarce, we noted divergent histopathological features in CMV-associated cNS, dependent on the presence or absence of cognate genetic mutations as shown in the Table. CMV is a rare cause of nephrotic syndrome presenting soon after birth. Screening for relevant mutations is essential since congenital infections can complicate or mask an underlying genetic etiology leading to the failure of CMV-directed antiviral therapy and poor renal outcome.

SAT-410 Clinicopathologic Features and Outcomes of Patients with Crescentic Glomerulonephritis with Renal Involvement: A Single-Center, 13-year Retrospective Study from Turkey

Crescentic glomerulonephritis (GN) is a group of the disease spectrum characterized by the presence of glomerular crescent formation as the principal histologic finding. We aimed to investigate the etiologic distribution and clinicopathologic features of the patients with biopsy-proven crescentic GN in the last 13 years in our center according to different percentages of crescents. Patients who had renal biopsy-proven glomerular crescent formation and recorded from 2005 to 2018 were retrospectively reviewed. The baseline clinical and laboratory parameters of all patients were obtained at the time of renal biopsy. Renal histopathological data were reviewed by light and immunofluorescence microscopy. According to the percentages of crescentic glomeruli, the patients were divided into three subgroups: group I (crescents <10%), group II (10%≤ crescents ≤30%) and group III (crescents >30%). The clinical, laboratory and histopathological features of patients, risk factors and outcomes were compared among the three groups. A total of 103 patients with biopsy-proven crescentic GN were included in the analysis and followed up. The results according to different percentages of crescents are presented in Table. As the percentage of crescentic glomeruli increased, it was associated with increased levels of baseline serum creatinine (p=0.018), lower baseline estimated glomerular filtration rate (eGFR) (p=0.002) and decreased macroscopic hematuria (p=0.032). In last outpatient clinic visit, eGFR, serum albumin and amounts of proteinuria were not different among the groups (p=0.096). The most common renal biopsy indications were rapidly progressive glomerulonephritis and nephrotic syndrome in all three groups (p=0.031). The disease spectrum of crescentic GN was as follows: 6 (6%) had anti-GBM GN, 16 (15.5%) had lupus nephritis, 27 (26%) had IgA nephropathy, 3 (3%) had infection-related GN, 5 (5%) had membranoproliferative GN, 42 (40.5%) had pauci-immune GN and 4 (4%) had others. There were no significant differences in the histological findings among the three groups except for mesangial cell proliferation and matrix expansion (p=0.002). Twenty three patients (%22.3) required dialysis on admission, including 6 (15%) patients with group II and 17 (36%) patients with group III (p<0.01). By the end of the follow-up period of 30 months, 35 (34%) patients progressed to end-stage renal disease (ESRD), requiring renal replacement therapy (7 (7%) renal transplantation and 28 (27%) dialysis) and 14 (13.5%) patients died. Cox regression analysis for renal survival showed that serum creatinine levels of 3.5 mg/dl or greater (HR= 1.5, 95% CI: 1.9-10.5, p<0.001) on admission and presence of interstitial fibrosis and tubular atrophy score >25% (HR= 2.7, 95% CI: 2-113, p=0.008) on renal biopsy were risk factors for ESRD. Of the etiologic spectrum of crescentic GN, pauci-immune GN had the poor renal and patient outcomes. This study provides valuable information about the disease spectrum of crescentic GN in our country. In patients with crescentic GN who present with different clinical features, an accurate and early diagnosis is essential for both renal and patient survival. Prognosis mostly depends on the degree of renal failure, histopathologic findings and the type of crescentic GN. Studies with larger sample sizes, including national registry data is still needed.

SUN-414 Renal biopsy in the elderly: indications, outcomes and prognostic factors A retrospective study about 70 patients

Advances in health have led to longer life expectancy in all countries and as life expectancy increases, the number of elderly patients with kidney disease increases. The complexity of kidney damage in the elderly obscures the clinical picture. Without a renal biopsy, establishing a good diagnosis may be impossible, or at least prolonged. In this context fits our study that aims to clarify the main indications of renal biopsy and histological diagnostics in the elderly while specifying the risk factors for end-stage renal disease (ESRD). A retrospective observational study was conducted in elderly patients (≥65 years) who had received renal biopsies over 14 years (between January 2003 and December 2016). Demographic, clinical and pathological data at the time of the biopsy were collected from the medical records. Follow-up records and prognostic factors were studied. Outcomes of the renal biopsy were compared to a control group of patients aged between 40 and 64 years. The elderly accounted for 7.25% of native renal biopsies that were performed for 14 years. We included 70 patients in the study, 48 males (68.6%) and 22 females (31.4%). The most common indications for biopsy were an acute renal failure (72,8%) and nephrotic syndrome (24,3%). Common diagnosis included crescentic glomerulonephritis (27%), diabetic nephropathy (12,9%) and postinfectious acute glomerulonephritis (10%). In at least 48.5% of cases, renal biopsy showed histological lesions that can benefit from a therapeutic intervention. In the multivariate analyses, serum creatinine on admission was the only independent factor of poor renal outcome. Comparing histological outcomes with the control group, we found that crescentic glomerulonephritis was more common in the elderly with a significant difference and membranous nephropathy was more common in adults aged 40 to 64 years without significant difference with the elderly. The results of our study confirm the usefulness of renal biopsy in the elderly. Even in patients whose renal biopsy does not show lesions that can modify the therapeutic attitude, it can inform on the prognosis and /or avoid the prescription of the heavy treatments.

Plasma chemokine CXC motif-ligand 16 as a predictor of renal prognosis in immunoglobulin A nephropathy.

BackgroundThere are few non-invasive biomarkers that have been identified to improve the risk stratification of patients with IgA nephropathy (IgAN). CXCL16 has been shown to play a key role as a chemoattractant, adhesion, and fibrosis factor in inflammatory disease. This study evaluated the potential for CXCL16 plasma as a potential biomarker in patients with IgAN.MethodsPlasma CXCL16 was measured in 230 patients with renal biopsied IgAN enrolled from 2012 to 2014. The patients were followed for 41.3 months, with a 50% reduction in estimated glomerular filtration rate or end-stage renal disease as endpoints.ResultsThe plasma CXCL16 levels in IgAN patients were strongly correlated with the uric acid, estimated glomerular filtration rate and tubular atrophy/interstitial fibrosis score in multivariate analysis. Furthermore, counts of CD4+ T cells, CD8+ T cells, and CD20+ B cells in renal biopsies of IgAN patients were significantly correlated with the plasma CXCL16 levels, but not CD68+ macrophage. Lastly, we concluded that patients with higher levels of plasma CXCL16 had an increased risk of poor renal outcome compared to those with lower levels. There was no association between the polymorphisms and clinical parameters of CXCL16, including the levels and prognosis of plasma CXCL16.ConclusionsPlasma CXCL16 levels were associated with clinical parameters; pathological damage; CD4+ T cell, CD8+ T cell, and CD20+ B cell infiltration in renal tissue; and renal outcome in IgAN patients. Plasma CXCL16 might be a potential prognosis predictor in Chinese IgAN patients.