Kidney Survival Time Research Articles

Prognostic Value of Inflammation Scores and Hematological Indices in IgA and Membranous Nephropathies: An Exploratory Study.

Background and Objectives: Systemic-inflammation-based prognostic scores and hematological indices have shown value in predicting outcomes in various clinical settings. However, their effectiveness in predicting outcomes specifically for IgA nephropathy (IgAN) and membranous nephropathy (MN), the most common primary glomerular diseases diagnosed by kidney biopsy, has not been thoroughly investigated. Materials and Methods: We conducted a retrospective, observational study involving 334 adult patients with biopsy-proven IgAN (196 patients) and MN (138 patients) from January 2008 to December 2017 at a tertiary center. We assessed six prognostic scores [Glasgow prognostic score (GPS), modified GPS (mGPS), prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-C-reactive protein ratio (LCRP)] and two hematological indices [red blood cell distribution width (RDW), platelet distribution width (PDW)] at diagnosis and examined their relationship with kidney and patient survival. Results: End-stage kidney disease (ESKD) occurred more frequently in the IgAN group compared to the MN group (37% vs. 12%, p = 0.001). The mean kidney survival time was 10.7 years in the IgAN cohort and 13.8 years in the MN cohort. After adjusting for eGFR and proteinuria, lower NLR and higher LCRP were significant risk factors for ESKD in IgAN. In the MN cohort, no systemic-inflammation-based scores or hematological indices were associated with kidney survival. There were 38 deaths (19%) in the IgAN group and 29 deaths (21%) in the MN group, showing no significant difference in mortality rates. The mean survival time was 13.4 years for the IgAN group and 12.7 years for the MN group. In the IgAN group, a lower PLR was associated with a higher mortality after adjusting for age, the Charlson comorbidity score, eGFR, and proteinuria. In patients with MN, higher NLR, PLR, and RDW were associated with increased mortality. Conclusions: NLR and LCRP are significant predictors of ESKD in IgAN, while PLR is linked to increased mortality. In MN, NLR, PLR, and RDW are predictors of mortality but not kidney survival. These findings underscore the need for disease-specific biomarkers and indicate that systemic inflammatory responses play varying roles in the progression and outcomes of these glomerular diseases. Future studies on larger cohorts are necessary to validate these markers.

#1644 Prognostic significance of hematuria on kidney survival in podocytopathies

Abstract Background and Aims Hematuria is common in podocytopathies, but its prognostic impact on kidney survival in these proteinuric diseases is not well-established. Our study examines the prevalence of hematuria at podocytopathy diagnosis and its association with renal survival. Method In our retrospective study, we analyzed 236 patients (median age 50 years, 60% male, median eGFR 65.5 mL/min/1.73 m2, median proteinuria 3.9g/g) with biopsy proven podocytopathies—48% membranous nephropathy (MN), 32% minimal change disease (MCD), 20% focal and segmental glomerulosclerosis (FSGS)—diagnosed at a tertiary center from 2010 to 2015. Hematuria was defined as the presence of 5 or more red blood cells (RBCs) per high-power field in 3 of 3 consecutive centrifuged urine specimens obtained at least 1 week apart. The follow-up period extended until the onset of end-stage kidney disease (ESKD: start of kidney replacement therapy or renal transplantation), death, or January 2022, with a median duration of 8.5 (95% CI: 8.1, 8.8) years. Results In our patient cohort, 31% (n = 73) presented with hematuria, having a median of 120 (IQR: 40-220) red blood cells (RBCs). Those with hematuria more frequently exhibited arterial hypertension (55% vs 36%, p 0.007) and had higher levels of proteinuria (5.3 vs 3.2g/g, p 0.01). However, no significant differences were noted in terms of age (53 vs 48 years, p 0.08), Charlson comorbidity score (2 vs 2, p 0.9), type of podocytopathy (MN 52 vs 47%, MCD 27 vs 34%, FSGS 21 vs 19%, p 0.5), eGFR (62.1 vs 68.8 mL/min, p 0.08), serum albumin levels (3.3 vs 3.4g/dL, p 0.6), total renal chronicity score on histology (0 vs 0, p 0.6), and treatment with ACE inhibitors/angiotensin receptor blockers (43% vs 50%, p 0.4) or immunosuppression (81% vs 74%, p 0.4). Thirty-two percent of the patients with hematuria reached ESKD versus 9% in the group without hematuria (p 0.001); there were no differences regarding mortality between the two groups. Mean kidney survival time for the entire cohort was 10.3 (95% CI: 9.9, 10.8) years; renal survival at 1, 3, 5 and 10 years were 97%, 92%, 88% and 82%, respectively. Patients with hematuria at diagnosis had a significant shorter kidney survival time (9.0 (95% CI: 8.0, 10.0) vs 11.0 (95% CI: 10.6, 11.4) years, p 0.001). In a multivariate Cox proportional hazard model (backward Wald), presence of hematuria at diagnosis (HR 3.64, 95% CI: 1.87, 7.07), lower eGFR (HR 0.96, 95% CI: 0.94, 0.97) and higher total renal chronicity score on histology (HR 1.10, 95% CI: 1.00, 1.22) were independent predictors of reduced kidney survival. Conclusion Hematuria is prevalent in the three podocytopathies and independently correlates with poorer kidney survival outcomes. This underscores the possible need for personalized treatment strategies in patients with podocytopathies presenting with hematuria.

#1641 Assessing long-term prognosis in patients with glomerular disease: nephrotic syndrome versus nephrotic range proteinuria comparison

Abstract Background and Aims Although there is considerable research on the role of proteinuria in the progression of chronic kidney disease, a direct comparison between biopsy-diagnosed glomerular disease (GD) patients presenting with nephrotic syndrome (NS) and those with nephrotic range proteinuria (NRP) is lacking. Our study aims to bridge this gap by comparing the long-term outcomes of patients with NS and NRP. Method We conducted a unicentric retrospective study on 240 kidney biopsy-proven GD patients (median age 50 years, 65% men, median eGFR 58 mL/min, median proteinuria 6.0 g/24 h), tracked from 2010-2015 until end-stage kidney disease (ESKD), death, or study end in January 2022. Results The median follow-up was 8.8 years. Diagnoses were predominantly nonproliferative (53%), proliferative (25%) nephropathies, diabetic nephropathy (12%), and paraprotein diseases (10%). NS was observed in 141 (59%) patients, presenting more frequently with arterial hypertension (61 vs 43%, p 0.001), higher eGFR (64.9 vs 51.5 mL/min, p 0.001), increased proteinuria (6.4 vs 5.4g/24 h, p 0.01), and dyslipidemia (serum cholesterol 316 vs 251 mg/dL, p 0.001; serum triglycerides 226 vs 184 mg/dL, p 0.001) than NRP patients. NRP patients more often had proliferative (30 vs 22%) GD and diabetic nephropathy (22 vs 5%) ; their renal chronicity score was higher (2 vs 0, p 0.001). ESKD endpoint occurred in 35% NS and 39% NRP patients (p 0.4). The cohort's mean kidney survival time was 8.2 years. In multivariate analysis, NS (HR 1.79, 95% CI: 1.09, 2.94), lower eGFR (HR 0.97, 95% CI: 0.96, 0.98), higher renal chronicity score (HR 1.12, 95% CI: 1.02, 1.23), and diabetic nephropathy (Ref, p 0.001) were associated with ESKD. 64 patients (27%) died, 73% post-kidney replacement therapy initiation, mostly from cardiovascular disease (63%). Mortality between proteinuria forms showed no difference. Multivariate analysis found lower eGFR (HR 0.98, 95% CI: 0.97, 0.99), higher Charlson comorbidity score (HR 1.38, 95% CI: 1.17, 1.64), and diabetic nephropathy (Ref, p 0.01) associated with mortality. Conclusion Our study found no difference in all-cause mortality between NS and NRP in glomerular diseases. However, adjusted analysis revealed poorer kidney survival for NS patients, emphasizing the need for personalized management to improve renal prognosis.

Circulating alternative pathway complement cleavage factor Bb is associated with vascular lesions and outcomes in IgA nephropathy.

Complement alternative pathway (AP) activation is linked to immunoglobulin A nephropathy (IgAN) prognosis severity, but Bb fragment's role is unclear. We examined the relationship between serum Bb fragment concentration at IgAN diagnosis with disease activity and outcomes. This retrospective study included 125 biopsy-proven IgAN patients (age 39.9 years, 75% male, eGFR 82mL/min, proteinuria 0.5g/day) enrolled from 1984 to 2010 and followed for a minimum of 18 months. Monitoring continued until the last follow-up, end-stage kdiney disease (ESKD), or death. Serum Bb fragment was measured using ELISA at diagnosis. Oxford classification and global optical score (GOS) were utilized for pathology assessment. Patients were followed for a median of 16 years, 42% developed CKD stage 3 or higher, 19% reached ESKD, and 9% died. Serum Bb fragment concentration negatively correlated with eGFR values at last follow-up and positively with vascular and tubular histopathological indices. In univariate Cox regression analyses, higher Bb fragment concentration was associated with ESKD alongside older age, increased body-mass-index, arterial hypertension, lower eGFR, higher proteinuria, E1, S1, T1-2, GOS, and corticotherapy. Patients with Bb levels≥14.3μg/mL had shorter mean kidney survival time (19.5vs 22.7 years, p=0.07); after adjusting for progression risk factors, the association persisted (HR 4.76, 95% CI 1.56-14.43). Serum Bb fragment concentration at diagnosis may predict long-term IgAN outcomes, potentially due to AP activation at the endothelial surface. Further research is needed to confirm these results and evaluate Bb fragment's role in IgAN management.

Prognostic role of glomerular electron microscopy lesions in IgA nephropathy: "the devil is in the details".

Transmission electron microscopy enables examination of ultrastructural glomerular changes; while this tool has already been appliedin IgA nephropathy (IgAN), limited information exists on the prognostic valuein this disease. We aimed to systematically investigate ultrastructural lesions and assess their role in predicting the evolution of IgA nephropathy toend-stage kidney disease. A single-center retrospective study was performed on 107 consecutive IgAN patients (median age 42years, 67% male, estimated glomerular filtration rate 46mL/min, proteinuria 1.0g/g) between 2010 and 2015, who were followed-up until end-stage kidney disease, death, or end of study (January 2021). A pathologist evaluated the Mesangial hypercellularity (M), Endocapillary hypercellularity (E), Segmental glomerulosclerosis (S), and Tubular atrophy/interstitial fibrosis-Crescents (C) (MEST-C) score and transmission electron microscopy lesions according to a comprehensive protocol that encompassed all glomerular structures. Patients were followed up for a median of 7.1years; 32 (43%) reached end-stage kidney disease. Patients who reached kidney failure had higher comorbidity score, more frequent arterial hypertension, lower estimated glomerular filtration rate, and higher MEST-C score. In terms of transmission electron microscopy lesions, patients who progressed to end-stage kidney disease had more frequent podocyte activation, effacement, and presence of microvilli; more frequent signs of endothelial cell activation and fenestration; higher mesangial cell proliferation. In theunivariate Cox proportional hazard regression, higher MEST-C score and lesions detected bytransmission electron microscopy in podocytes, endothelial cells, and mesangial cell proliferation were associated with shorter kidney survival time. In themultivariate Cox proportional hazard regression, only higher MEST-C score, presence of podocytes with microvilli, and mesangial cell proliferation were associated with end-stage kidney disease. This study shows that, besides the MEST-C score, the presence of podocytes with microvilli and mesangial cell proliferation are associated with poor kidney survival in IgAN patients, highlighting the prognostic value of lesions detected bytransmission electron microscopy.

Anti-phospholipase A2 receptor positive membranous nephropathy: investigating the link between electron microscopy stages and clinical outcome

ABSTRACT This retrospective, observational study sought to examine the relationship between Ehrenreich-Churg electron microscopy (EM) stages and long-term outcomes in anti-PLA2R membranous nephropathy (MN). Seventy-one patients with anti-PLA2R MN (median titer 185.7RU/mL) were followed for a median of 46 months, with end-stage kidney disease (ESKD) as the primary endpoint, and response to treatment as a secondary endpoint. Patients were grouped into stages I-II (41 patients) and stages III-IV (30 patients) for analytical purposes. Notably, the III-IV group demonstrated a lower eGFR, lower anti-PLA2R titer, but a higher chronicity score. Kaplan-Meier analysis showed shorter mean kidney survival time in stages III-IV compared to I-II (p 0.03). However, multivariate analysis using Cox regression indicated that Ehrenreich-Churg stages did not significantly influence kidney survival, but lower eGFR at diagnosis and higher histopathological chronicity score did. Remission was achieved by 64% of patients and no relationship between Ehrenreich-Churg stages and treatment response was found. The only identified risk factor for not achieving remission was the severity of hyposerinemia at diagnosis. In conclusion, while EM stages III-IV are associated with more chronic lesions and stages I-II with more active immunologic disease, the histological chronicity score seems to be a stronger predictor of long-term outcomes.

Immunosuppressive therapy versus supportive care in IgA nephropathy patients with stage 3 and 4 chronic kidney disease.

The use of immunosuppressive therapy for immunoglobulin A nephropathy (IgAN) patients with stage 3 or 4 chronic kidney disease (CKD) is controversial. We performed a monocentric retrospective study on 83 consecutive IgAN patients with stage 3 or 4 CKD and proteinuria ≥0.75 g/d (age 41 [33-56] years, 72% male, estimated glomerular filtration rate 36.1 [25.4-47.5] mL/min/1.73 m2) who received uncontrolled supportive care (Supp) (n = 36), corticosteroids/corticotherapy (CS) (n = 14), or CS combined with monthly pulses of cyclophosphamide (CS + CFM) (n = 33) between 2010 and 2017. Patients were followed until composite endpoint (doubling of serum creatinine, end-stage kidney disease (dialysis or kidney transplant) or death, whichever came first) or end of study (January 2020). Patients were followed for a median of 29 (95% confidence interval = 25.2-32.7) months, and 12 (15%) patients experienced the composite endpoint. Within the limitation of a retrospective study, our results suggest no benefit from immunosuppressive therapy in patients with IgAN with stage 3 and 4 CKD as compared with supportive care. There were no differences between the 3 studied groups regarding age, estimated glomerular filtration rate, proteinuria, Oxford classification score, arterial hypertension, and therapy with renin-angiotensin system inhibitors. Mean kidney survival time for the entire cohort was 81.0 (95% confidence interval = 73.1-89.0) months, without significant differences between the 3 groups. In univariate and multivariate Cox regression analysis adjusted for IgAN progression factors, immunosuppressive therapy was not associated with better kidney survival when compared with supportive therapy.

Inflammation-based modified Glasgow prognostic score and renal outcome in chronic kidney disease patients: is there a relationship?

Chronic kidney disease (CKD) progression is presumably related to inflammatory response. The modified Glasgow prognostic score (mGPS), based on a combination of albumin and C-reactive protein, has been derived from oncology and validated in multiple diseases. To evaluate the relationship between the mGPS and CKD progression. The present retrospective unicentric cohort study included 547 CKD patients (age 60.2 years; 53% male; estimated glomerular filtration (eGFR) 42.0 mL/min; mean change -2 mL/min/year) admitted between 1 January 2007 and 31 December 2012. Patients' records were reviewed from the CKD diagnosis to one of the four outcomes: end-stage kidney disease (ESKD), death, loss to follow up or until 31 July 2017. The mGPS score was 0 for 420 (78%), 1 for 110 (19%) and 2 for 17 (3%) patients. More patients with rapid CKD progression were found in the group with the highest mGPS (P = 0.05). mGPS was negatively correlated with baseline eGFR and positively with albuminuria. In the multivariate analysis, mGPS was associated with the eGFR slope. During the study period, 130 (24%) patients died and 109 (20%) reached ESKD. The mean kidney survival time was 8.1 (95% confidence interval 7.9-8.4) years. Patients with zero mGPS had better kidney survival than those with the score of 1 and 2 (Kaplan-Meier, P = 0.02). However, the kidney survival differences were not present after adjusting for CKD progression risk factors. The inflammation-based mGPS score was associated with eGFR decline in CKD patients. Therefore, could prove useful in improving risk stratification of CKD patients.

MO260: Prognostic Role of Electron Microscopy Lesions in IGA Nephropathy

Abstract BACKGROUND AND AIMS The progression of immunoglobulin A nephropathy (IgAN) is currently assessed using the Oxford MEST-C score, which uses five indicators (mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy and the presence of crescents). However, little is known about the prognostic role of the glomerular lesions assessed by transmission electron microscopy (EM). METHOD We performed a unicentric retrospective study on 107 consecutive IgAN patients {age 42 [interquartile range (IQR) 33–54] years}, 67% male, eGFR 46 (IQR 33.3–65.2) mL/min, proteinuria 1.0 (IQR 0.4–2.1) g/g creatinine)—kidney biopsy-proven—between 2010 and 2015. Patients were followed until end-stage kidney disease (ESKD, dialysis or renal transplantation), death or end of study (January 2021), whichever came first. For each biopsy specimen, light microscopy, immunofluorescence and EM were routinely performed. One pathologist (GTB) reviewed independently the slides without knowledge of the original biopsy interpretation and assessed for MEST-C score and EM lesions according to the Mayo Clinic/Renal Pathology Society Consensus in podocytes, endothelial cells, mesangium and glomerular basement membrane (Table 1). RESULTS Patients were followed for a median of 7.1 (95% CI 6.7–7.5) years. The patients who reached ESKD—32 (43%)—had a higher Charlson comorbidity score [CCS 2 (IQR 2–4) versus 1 (IQR 0–3), P = .01)], arterial hypertension more often [88% versus 64%, P = .01)], lower eGFR [33.7 (IQR 22.4–44.3) versus 56.3 (IQR 39.4–72.5) mL/min, P < .001] and higher MEST-C score [2 (IQR 2–4) versus 1 (IQR 1–2), P < .001]. There were no differences regarding proteinuria, hematuria and treatment. In terms of EM lesions, patients who experienced ESKD had more frequent podocyte activation (47% versus 27%, P < 0.01), effacement (100% versus 83%, P = .01) and presence of microvilli (69% versus 35%, P = .001); more often endothelial cells activation (47% versus 27%, P = .04) and fenestration (56% versus 29%, P < 0.01); higher mesangial cells proliferation (91% versus 64%, P < .01). Mean kidney survival time for the entire cohort was 8.2 (95% CI 7.4–8.9) years. In univariate Cox proportional hazard (CPH) regression higher MEST-C score and EM lesions in podocytes, endothelial cells and mesangial cell proliferation were associated with a shorter kidney survival time (Table 1). However, in the multivariate CPH adjusted for CCS, arterial hypertension, eGFR and treatment, only higher MEST-C score, presence of podocytes with microvilli and mesangial cell proliferation were associated with ESKD (Table 1). CONCLUSION To the best of our knowledge, this is the first study to evaluate in depth the prognostic value of EM lesions in IgAN patients in a reasonable large cohort with an appropriate follow-up time. Besides the MEST-C score, we found that the presence of podocytes with microvilli and mesangial cell proliferation are associated with poor kidney survival.

Negative anti-phospholipase A2 receptor antibody status at three months predicts remission in primary membranous nephropathy

Background The value of anti-phospholipase A2 receptor antibody (anti-PLA2R ab) monitoring at 3 months after diagnosis in membranous nephropathy (MN) remains uncertain. Methods We retrospectively examined the outcome on 1 August 2020 of 59 adult patients (age 54 (44, 68) years, 69% male, SCr 1.0 (0.9, 1.3) mg/dL) diagnosed with MN (kidney biopsy, positive serum anti-PLA2R ab). The outcomes were: kidney survival; partial and/or complete remission. Results Most of the studied patients (97%) received immunosuppression, cyclophosphamide regimens were the most frequent (87%), followed by cyclosporine (10%). The median time to remission was 12.0 months and the cumulative remission rates were 34% at 6, 54% at 12, and 73% at 24 months. Forty (69%) patients had negative anti-PLA2R ab at 3 months, they had similar age, serum creatinine, albumin, proteinuria, and treatment with the group with positive ab at 3 months. In the Cox proportional hazard model, three months anti-PLA2R ab negativization (HR 0.4 (95%CI 0.1, 0.9)) was an independent predictor for remission, while baseline hypoalbuminemia (HR 3.0 (95%CI 1.5, 5.7)) was associated with absence of remission. Six (10%) patients died, mostly due to cardiovascular disease and infections. A total of five (9%) patients started dialysis. Mean kidney survival time was 50.3 months and there was no survival difference in relation to baseline anti-PLA2R ab titer (p .09) or 3 months negativization (p .8). Conclusions Three months anti-PLA2R ab negativization seems to be a late predictor of remission, and lower serum albumin at diagnosis is an early marker for remission absence. Abbreviations: anti-P LA2R ab, anti-phospholipase A2 receptor antibody; eGFR, estimated glomerular filtration rate; ESKD, end stage kidney disease; MN, membranous nephropathy; NELL-1, neural epidermal growth factor-like 1 protein; RAAS: renin–angiotensin–aldosterone system; RBC: red blood cells; RRT, renal replacement therapy; T HSD7A, thrombospondin type-1 domain containing 7A

Renal Survival and Validation of Novel International Immunoglobulin a Nephropathy Prediction Tool in Latvian Population: Preliminary Data

Abstract The aim of the study was to determine kidney survival and validate the novel international immunoglobulin A nephropathy (IgAN) prediction tool (PT) in the Latvian population. Adults with morphologically confirmed IgAN were included. Kidney survival was analysed with the Kaplan–Meier method. PT-assigned risk was compared with calculated risk by the Cox regression model. The Kaplan–Meier analysis included 95 patients. The five-year kidney survival Q3 was 24 months. Women had longer median kidney-survival time (> 60 months) than men (58 months). Median kidney survival in participants with MEST T0 was longer than 60 months; T1 and T2 were 40 and 18 months, respectively. Median kidney survival in participants with diastolic blood pressure (DBP) < 99 mmHg was longer than 60 months, whereas in patients with DBP 100–109 and 110 mmHg, it was 40 and 24 months, respectively. Cox regression analysis included 68 patients. A moderate degree of correlation was found between predicted and observed five-year risk (p = 0.001). Gender, tubular atrophy/interstitial fibrosis, DBP are significant factors affecting kidney survival. Since there was statistically significant correlation and reliability between PT and follow-up analysis data, we conclude that PT could be applied for use in the Latvian population.

MO605INFLAMMATION-BASED MODIFIED GLASGOW PROGNOSTIC SCORE AND CHRONIC KIDNEY DISEASE PROGRESSION

Abstract Background and Aims The modified Glasgow prognostic score (mGPS), based on combination between albumin (sAlb) and C-reactive protein (CRP), has been derived from oncology and validated in multiple diseases. Since chronic kidney disease (CKD) progression is related to inflammation, we aimed to evaluate the relationship between the mGPS and CKD outcome. Method The present retrospective unicentric cohort study included 547 CKD patients (age 60.2 years, 53% male, eGFR 42.0 mL/min, mean change -2 mL/min/year) admitted between January 1, 2007 and December 31, 2012. The mGPS assessment: zero points if CRP ≤10 mg/L and sAlb ≥3.5 g/dL; one point if CRP >10 mg/L and sAlb ≥3.5 g/dL, two points if CRP >10 mg/L and sAlb <3.5 g/dL. Patients records were reviewed from the CKD diagnosis to one of the four outcomes: end-stage kidney disease (ESKD), death, loss to follow-up, or until July 31, 2017. Results The mGPS score was 0 for 420 (78%), 1 for 110 (19%), and 2 for 17 (3%) patients. Rapid progression defined as a sustained decline in eGFR of more than 5 mL/min/year was found in 17% of the studied patients. More patients with rapid CKD progression were found in the group with the highest mGPS (30% vs 17%, vs 16%, p=0.05). In the multivariate analysis, mGPS was associated with the eGFR slope (OR 1.42 (95%CI 0.29, 2.55), p 0.01). Moreover, mGPS was negatively correlated with baseline eGFR (OR -3.74 (95%CI 7.8, 0.33), p 0.05) and positively with albuminuria (0.87 (95%CI 0.51, 1.23), p 0.001). During the study period, 130 patients (24%) died and 109 (20%) reached ESKD. The mean kidney survival time was 8.1 (95%CI 7.9, 8.4) years. Kidney survivals at 12, 24, 36, 48, 60, and 72 months were 96, 95, 89, 86, 83 and 82%, respectively. In univariate time-dependent analysis, patients with zero mGPS had better kidney survival than those with the score of one and two (99.9 (95%CI 96.9, 102.9) vs 92.1 (95%CI 85.2, 99.0) vs 78.1 (95%CI 60.4, 95.4) months, log rank p=0.02). However, the kidney survival differences were not present after adjusting for CKD progression risk factors (HR 1.12 (95%CI 0.78, 1.62), p 0.5). Conclusion The inflammation-based mGPS score was associated with eGFR decline in CKD patients. Therefore, could prove useful in improving risk stratification of CKD patients.

MO293NEUTROPHIL-TO-LYMPHOCYTE RATIO AND OUTCOME IN CRESCENTIC GLOMERULONEPHRITIS

Abstract Background and Aims Crescent formation is a nonspecific response to severe injury to the glomerular capillary wall, which may be seen with any form of inflammatory glomerulopathy. Despite improved therapeutic interventions, patients with crescentic glomerulonephritis (CGN) still have a severe kidney prognosis and high mortality. Since neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker linked to worse outcomes in patients with malignancies, chronic kidney disease, myocardial infarction, and other clinical settings, we aimed to assess if NLR can predict kidney outcome and mortality in subjects with CGN. Method Eighty-four adults with biopsy-proven CGN between 1st Jan. 2008 and 31st Dec. 2017 [age 56 (95%CI 53 to 59) years, 50% males, eGFR 9.3 (95%CI 7.8-12.7) mL/min] were retrospectively enrolled in this single-centre study. Subjects were followed for a median of 31 (95%CI 6 to 56) months, until 31st May 2018. Seven subjects with inadequate biopsy sample and insufficient data were excluded. Demographic (age, gender), clinical and laboratory data at the time of biopsy were obtained from medical records. Kaplan-Meier method was used to evaluate kidney and patient survival. Variables related to kidney outcome were evaluated in a multivariate Cox proportional hazard (CPH) model. According to median NLR value (4.3, 95%CI 3.5 to 5.2) subjects were clustered in low NLR group (≤4.3; n=38 pts.) and high NLR group (>4.3; n=38 pts.). The primary endpoints were time to renal replacement therapy (RRT) initiation and all-cause mortality. Results The most common CGN subtype was pauci-immune GN (76.3%; i.e. myeloperoxidase-ANCA vasculitis - 48.7%, PR3-ANCA vasculitis - 15.8% and ANCA-negative vasculitis - 11.8%) followed by. anti-GBM antibody and immune complex related GN, with similar frequencies (11.8% each). According to kidney biopsy (KB) findings, half of the subjects had fibro-cellular crescents (55.3%), while cellular and fibrous crescents were found in 35.5% and 9.2%, respectively. Almost all subjects received corticosteroids (97.4%) and 82.9% received cyclophosphamide. Baseline eGFR was lower in the high-NLR group (8.5 vs. 11.6 mL/min, p=0.04), but no other differences in laboratory findings at baseline between the two groups were found. In bivariate analysis, NLR was negatively associated with serum albumin (rs=-0.26, p=0.02). NLR was not associated with other inflammation markers, Charlson comorbidity score, nor with the type of crescents at KB. During the follow-up period 53.9% started RRT and 19.7% died. There were no differences regarding mortality between the two groups. The mean kidney survival time was 47.6 (95%CI 33.5, 61.7) months. Kidney survival at 12, 24, 48 and 60 months were 44, 41, 38, and 33% respectively. In univariate time-dependent analysis (Figure) patients with low-NLR (68.95%CI 48 to 88 months) had better kidney survival than those with high-NLR (25, 95%CI 13 to 38 months; log rank p=0.004). Moreover, the kidney survival advantage remained (OR 1.06, 95%CI 1.002 to 1.16) after adjusting for eGFR, proteinuria, C reactive protein, immunosuppressive treatment and CGN etiology. Lower eGFR-ul was also associated with poor kidney survival (OR 0.96, 95%CI 0.88 to 0.97). Conclusion In adults with biopsy-proven crescentic glomerulonephritis and advanced kidney function decline, a higher neutrophil-to-lymphocyte ratio seems to predict worse kidney survival, but not the risk of mortality.

Adult-onset minimal change disease: the significance of histological chronic changes for clinical presentation and outcome.

Data on pathologic features with prognostic utility in adults with minimal change disease (MCD) are limited. We assessed the relationship between histologic chronic changes and clinical presentation and outcomes. The consecutive records of 79 patients with MCD and minimum of 6months follow-up were retrospectively reviewed. Kidney survival was the primary endpoint (doubling serum creatinine or dialysis initiation). Secondary endpoints were time to remission and relapse. Total chronicity score was the sum of glomerulosclerosis (0-3), interstitial fibrosis (0-3), tubular atrophy (0-3), and arteriolosclerosis (0/1). The median renal chronicity score was 1; 77% had minimal (0-1), 18% mild (2-4), and 5% moderate (5-7) chronicity. Fifty percent had a null score; they were younger, had higher eGFR, similar proteinuria, better renal survival, and lower mortality. Mean kidney survival time was 5.7 (95% CI 5.2-6.2) years; 89% reached a form of remission at a median of 8weeks; 31% relapsed at a mean of 26months. Chronic changes severity predicted both relapses and kidney survival, each one-point increase in score raised with 27% the risk of relapse and with 31% the risk of dialysis initiation. Acute kidney injury (AKI) was present in 42% of the patients; they had more often mesangial proliferation, interstitial inflammation, tubular atrophy, arteriosclerosis, podocyte villous hypertrophy, and higher chronicity score. Standardized grading of chronicity was a predictor of kidney survival and disease relapse and was related to AKI. Older patients with severe nephrotic syndrome and with increased chronicity score could represent a high-risk category.

Therapeutic effect of tonsillectomy on IgA nephropathy after kidney transplantation

Objective: To observe the clinical effect of tonsillectomy on IgA nephropathy (IgAN) after renal transplantation. Methods: From March 2011 to July 2018, 201 kidney transplantation recipients who were diagnosed of IgAN by transplant renal biopsy in the Department of Organ Transplantation of the First Affiliated Hospital of Sun Yat-sen University were retrospectively reviewed, of which 18 patients underwent tonsillectomy after renal biopsy. The clinical data of the 18 patients were collected, patient and kidney survival time and function of the transplanted kidney were analyzed. Results: Of the 18 recipients, 13 were male and 5 were female, with an average age of (36.0±10.9) years. All 18 patients survived during follow-up. Two patients returned to dialysis treatment 10 months and 14 months after tonsillectomy, respectively. The creatinine was 94 (78, 133) μmol/L, 95 (74, 139) μmol/L, 106 (87, 158) μmol/L and 95(81, 147) μmol/L before tonsillectomy, 3 months, 1 year and 2 years after tonsillectomy, respectively (P=0.206). Urinary protein quantification was 0.31 (0.16, 1.38) g/24 h, 0.34 (0.10, 1.42) g/24 h, 0.33 (0.11, 0.56) g/24 h and 0.25 (0.10, 0.50) g/24 h at the same time points, respectively (P=0.104). The two patients who returned to dialysis were diagnosed of IgAN by transplant renal biopsy because of elevated creatinine, proteinuria and hematuria, 9 years and 4 years after kidney transplant respectively. Renal biopsy suggested that glomerular and segmental sclerosis were 7/24, 5/24 and 1/6, 2/6, respectively. Additionally, interstitial fibrosis and tubular atrophy (IF/TA) were both occupied 30% in the biopsies, and tonsillectomy was performed 461 days and 1 077 days after diagnosis of IgAN, respectively. Conclusions: Tonsillectomy can maintain the stability of renal function and prevent the aggravation of proteinuria in IgAN patients after renal transplantation. However, if pathology suggests obvious glomerulosclerosis or IF/TA, tonsillectomy may not be effective.

P0113STANDARDIZED GRADING OF CHRONIC CHANGES IN MINIMAL CHANGE DISEASE: A VALIDATION STUDY IN NATIVE KIDNEY BIOPSY SPECIMENS

Abstract Background and Aims Recently, a group of pathologists and nephrologists devised a simple scoring system for chronic changes based on the grading of glomerulosclerosis (GS), tubular atrophy (TA), interstitial fibrosis (IF) and arteriosclerosis (AS). We aimed to validate for the first time this score in patients with minimal change disease. Method We included 79 adult patients (age 50.3 (46.3, 54.3) years, 57% male, eGFR 54.7 (44.2, 63.5) mL/min) with biopsy proven MCD between 2010-2015 who were followed up until January 1, 2017. The extent of GS, TA and AS was scored from 0 to 3, 0 to 3 and 0 to 1, respectively. The scores were then added (total renal chronicity score) to grade the overall severity of the chronic lesions into minimal (0–1 total score), mild (2–4 total score), moderate (5–7 total score) and severe (>8 total score). The outcomes were: patient survival; kidney survival defined as doubling of serum creatinine or ESRD; partial (proteinuria 0.3 to 3.5g/24h) or complete remission (proteinuria <0.3g/24h) - whichever came first. Variables related to renal outcome were further evaluated in a multivariate Cox proportional hazard (CPH) model. Results Minimal chronic lesions were found in 77%, mild in 18% and moderate in 5% of the studied patients. Fifty percent had a null score of chronicity; they were younger (44 (29-53) versus 62 (44-66) years, p<0.001), had higher eGFR (65.0 (42.1-83.2) versus 43.4 (25.8-63.9) mL/min, p<0.01) but similar proteinuria (4.8 (1.9-8.2) versus 4.5 (1.1-6.7) g/g, p=0.3). Patients with a score higher than one had higher mortality (18% versus 0%, p<0.001) and started RRT more often (15% versus 0%, p=0.01). There were no differences regarding the presentation as acute kidney injury, and in reaching complete or partial remission. Moreover, there were no clinical or pathology features that predicted remission. 17% of the patients reached the composite endpoint of kidney survival; mean kidney survival time was 5.7 (5.2, 6.3) years. In the CPH analysis the only independent predictors of decreased renal survival were elevated chronicity score (HR 1.56 (95%CI 1.14-2.14), p<0.01), lower serum albumin (HR 0.27 (95%CI 0.08-0.88), p=0.03) and the presence of hypertension (HR 0.18 (95%CI 0.03-0.93), p=0.04). Conclusion To the best of our knowledge, this is the first study to validate the standardized grading of chronic changes as an independent predictor of renal survival in patients with minimal change disease.

Histologic predictors of renal outcome in diabetic nephropathy: Beyond renal pathology society classification.

The prognostic utility of histologic features in patients with diabetic nephropathy (DN) classified according to the Renal Pathology Society (RPS) classification is controversial. Therefore, we aimed to evaluate the relationship between histologic changes and renal outcome in DN patients.We examined the renal outcome at November 30, 2017 of 74 adult patients (median age of 54.6 years, 69% male, 81% diabetes mellitus (DM) type 2, estimated GFR (eGFR) 29.6 mL/min) with biopsy proven DN between 2010 and 2015. The primary endpoint was renal replacement therapy (RRT) initiation.Half of the patients progressed to end stage renal disease (ESRD) during follow-up; they had lower eGFR, increased proteinuria, hematuria and serum cholesterol. Regarding the pathologic features, they were more frequently in class III and IV, had higher interstitial fibrosis and tubular atrophy score (IFTA), increased interstitial inflammation, more frequent arteriolar hyalinosis and higher glomerular basement membrane (GBM) thickness. The mean kidney survival time was 2.7 (95%CI 2.1, 3.3) years. In univariate time-dependent analyses, higher RPS DN class, increased IFTA, the presence of arteriolar hyalinosis and arteriosclerosis were associated with RRT initiation.In the fully adjusted model, the clinical characteristics associated with poor renal survival were longer duration of DM, lower eGFR, increased proteinuria and higher hematuria and the only pathologic lesions to remain significant were the GBM thickness and the IFTA.In conclusion, in this European cohort, the severity of glomerular lesions evaluated with the RPS DN classification had limited utility in predicting RRT initiation. However, IFTA and GBM thickness were significantly associated with renal survival.

Validation study of Oxford Classification of IgA Nephropathy: the significance of extracapillary hypercellularity and mesangial IgG immunostaining.

The Oxford classification (OC) of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as predictors of outcome. We aimed to validate the OC and to investigate the clinical significance of extracapillary hypercellularity and IgG immunostaining. We examined the renal outcome at December 31, 2014, of 121 adult patients with biopsy proven primary IgAN between 2003 and 2013. The primary endpoint was doubling of serum creatinine or renal replacement therapy initiation. The mean observation period was 59.7 months. Thirty-one percent of the patients presented with a grade of extracapillary hypercellularity. In comparison with the group with no crescents, they had higher grade of inflammation, lower eGFR and increased proteinuria. There were no differences between the IgA and IgA&IgG immunostaining groups regarding the disease progression risk factors. Mean kidney survival time for the entire cohort was 10.6 (9.1, 12.0) years. In the Cox regression model, the independent predictors of decreased renal survival were eGFR at time of biopsy, S1 and the presence of crescents. Our study showed that extracapillary proliferation and S1 had the greatest importance in establishing the renal prognosis of patients with IgAN.

Single-nucleotide polymorphism of the UMOD promoter is associated with the outcome of chronic kidney disease patients.

Uromodulin (UMOD) is the most abundant protein secreted in urine and the mutated form of the UMOD gene is associated with UMOD-associated kidney disease (UAKD). Although UMOD accumulates in the kidney of UAKD patients, it is unclear whether this also occurred in the chronic kidney disease (CKD) patients. Therefore, the association of single-nucleotide polymorphisms (SNPs) in the promoter region of UMOD gene with the kidney survival time of CKD was investigated. The promoter region of the UMOD gene was sequenced for 111 CKD patients. The Kaplan-Meier method was used to identify the disease outcome associated with SNPs in the promoter region of the UMOD gene in CKD patients. The Cox proportional hazard model was used to identify risk factors for the kidney survival time of CKD. SNPs in reference to GenBank accession NG-000016 were detected at 23 sites of the 481-bp in the UMOD promoter region from the CKD patients and the healthy controls. The 6 SNPs with minor allele frequency >5% in the CKD patients or controls were used for disease risk and outcome analysis. The frequent allele rs13333226AA was associated with a shorter period of kidney survival time in CKD patients (P=0.005). The length of kidney survival time in CKD patients with the rs13333226AA genotype was significantly shorter than that of patients with the frequent allele rs13333226AG+GG (relative risk, 0.361; 95% confidence interval, 0.171-0.761; P=0.007). In conclusion, analysis of genetic polymorphisms in UMOD may help to identify the CKD patient subgroups at a high risk for a disease outcome, thereby helping to refine therapeutic decisions in CKD patients.

Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA is associated with the kidney survival time in chronic kidney disease patients

Background: The mitochondrial displacement loop (D-loop) is known to accumulate mutations and SNPs at a higher frequency than other regions of mitochondrial DNA (mtDNA). We had identified chronic kidney disease (CKD) risk-associated SNPs in the D-loop of CKD patients previously. In this study, we investigated the association of SNPs in the D-loop of mtDNA with the kidney survival of CKD. Methods: The D-loop region of mtDNA was sequenced for 119 CKD patients from the inpatient of the Fourth Hospital of Hebei Medical University. The Kaplan–Meier method was used to identify disease outcome-associated SNPs in the D-loop of CKD patients. The Cox proportional hazards model was used to identify risk factors for the kidney survival of CKD. Results: In the present study, we identified 20 SNPs with a frequency higher than 5% and assessed the relationship of these SNPs with kidney survival time in CKD patients, a SNP of 146 was identified by log-rank test for statistically significant prediction of the kidney survival time. In an overall multivariate analysis, allele 146 was identified as an independent predictor of kidney survival time in CKD patients. The survival time of kidney in the CKD patients with 146C was significantly shorter than that of kidney in CKD patients with 146T (relative risk, 2.336; 95% CI, 1.319–3.923; p = 0.001). Conclusion: SNPs in the D-loop can predict the kidney survival of CKD patients. Analysis of genetic polymorphisms in the mitochondrial D-loop can help to identify CKD patient subgroup at high risk of a poor disease outcome.