Risk Factor For Renal Outcomes Research Articles

Preditores de progressão da doença renal policística autossômica dominante: uma coorte brasileira de centro único

Abstract Introduction: Identifying risk factors for autosomal dominant polycystic kidney disease (ADPKD) progression is important. However, studies that have evaluated this subject using a Brazilian sample is sparce. Therefore, the aim of this study was to identify risk factors for renal outcomes and death in a Brazilian cohort of ADPKD patients. Methods: Patients had the first medical appointment between January 2002 and December 2014, and were followed up until December 2019. Associations between clinical and laboratory variables with the primary outcome (sustained decrease of at least 57% in the eGFR from baseline, need for dialysis or renal transplantation) and the secondary outcome (death from any cause) were analyzed using a multiple Cox regression model. Among 80 ADPKD patients, those under 18 years, with glomerular filtration rate <30 mL/min/1.73 m2, and/or those with missing data were excluded. There were 70 patients followed. Results: The factors independently associated with the renal outcomes were total kidney length – adjusted Hazard Ratio (HR) with a 95% confidence interval (95% CI): 1.137 (1.057–1.224), glomerular filtration rate – HR (95% CI): 0.970 (0.949–0.992), and serum uric acid level – HR (95% CI): 1.643 (1.118–2.415). Diabetes mellitus - HR (95% CI): 8.115 (1.985–33.180) and glomerular filtration rate - HR (95% CI): 0.957 (0.919–0.997) were associated with the secondary outcome. Conclusions: These findings corroborate the hypothesis that total kidney length, glomerular filtration rate and serum uric acid level may be important prognostic predictors of ADPKD in a Brazilian cohort, which could help to select patients who require closer follow up.

Perinatal risk factors of renal outcome in former extremely low birth weight neonates.

Understanding risk profiles for unfavorable outcomes may help to identify children at increased risk for kidney dysfunction. Poorer eGFR was associated with longer ventilation, male sex, and intra-ventricular hemorrhage but not with blood pressure. This knowledge can lead to safer neonatal therapeutic regimens for ELBW infants, a more intensive follow-up and earlier treatment initiation for children at highest risk. • Extremely Low Birthweight (ELBW) neonates suffer later in life from adverse renal and cardiovascular outcomes. • Perinatal risk factors that further predict the individual risk for adverse outcomes are not well known. • Poorer eGFR in adolescence was associated with male sex, longer ventilation and intra-ventricular hemorrhage at birth but not with blood pressure. • Former ELBW infants had higher blood pressures compared to controls, but no microalbuminuria. • This knowledge can lead to potential precision medicine, safer neonatal therapeutic regimens for ELBW infants, a more intensive follow-up and earlier treatment initiation for children at highest risk.

Significance of the total renal chronicity score in predicting renal outcome in PLA2R-associated membranous nephropathy.

Phospholipase A2 receptor (PLA2R)-associated membranous nephropathy accounts for the majority of membranous nephropathy; however, few studies have determined the prognostic impact and clinicalapplication of renal pathologic change on this disease. A retrospective cohort study of 262 patients with PLA2R-associated membranous nephropathy was conducted. The total renal chronicity score calculatedaccording to the degree ofglomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriosclerosis was applied to evaluate renal chronicity. Baseline bias was adjusted by inverse probability weight whenassessing the prognostic impact of chronicity, and multiple parameters were used to evaluatethe application valueof renalchronicity. During a median follow-up of 24.5 months, renal outcome (kidney function deteriorationand/or end-stage kidney disease) was observed in 22 (8.40%) patients. Not only did a higher total renal chronicity score independently predict renal outcome [odds ratio (OR): 1.562, 95% confidence interval (CI) 1.073-2.273, P = 0.020], but non-minimal chronicity was also an independent risk factor for renal outcome (OR: 3.170, 95% CI 1.040-9.659, P = 0.042). Moreover, the membranous nephropathy risk classification in the Kidney Disease: Improving Global Outcomes (KDIGO) guideline integrated with non-minimal chronicity showed improvements in categorical net reclassification (0.174, 95% CI 0.012-0.335, P = 0.035), continuous net reclassification (0.462, 95% CI 0.087-0.838, P = 0.016), and integrated discrimination (0.019, 95% CI 0.003-0.035, P = 0.020) compared to the original classification. Renal chronicity is closely associated withrenal outcomes in PLA2R-associated membranous nephropathy, and combiningthe KDIGO risk classification with chronicity scoresmay provide amore accurate prognostic prediction.

Hepatitis B Virus Status and Clinical Outcomes in IgA Nephropathy

Immunoglobulin A nephropathy (IgAN) has been reported to coexist with hepatitis B virus (HBV) infection. Despite the clinical significance of this association, there is a lack of comprehensive research investigating the impact of various common conditions following HBV infection and the potential influence of anti-HBV therapy on the progression of IgAN. We investigated 3 distinct states of HBV infection, including chronic HBV infection, resolved HBV infection, and the deposition of hepatitis B antigens in renal tissue, in a follow-up database of 1961 patients with IgAN. IgAN progression was defined as a loss of estimated glomerular filtration rate (eGFR) >40%. Multivariable cause-specific hazards models to analyze the relationship between HBV states and IgAN progression. Chronic HBV infection was identified as an independent risk factor for IgAN progression, supported by both prematching analysis (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.06-2.44; P= 0.024) and propensity-score matching analysis (HR, 1.74; 95% CI 1.28-2.37; P< 0.001). Conversely, resolved HBV infection showed no significant association with IgAN progression (HR, 1.01; 95% CI 0.67-1.52; P= 0.969). Moreover, the presence of HBV deposition in the kidneys and the utilization of anti-HBV therapy did not appear to be significant risk factors for renal outcomes (P > 0.05). Chronic HBV infection is an independent risk factor for IgAN progression, whereas resolved HBV infection is not. In patients with IgAN, management of concurrent chronic HBV infection should be enhanced. The presence of HBV deposition in the kidneys and the use of anti-HBV medications do not impact the kidney disease progression in patients with IgAN with concurrent HBV infection.

The clinicopathological features and renal prognostic factors in pure membranous lupus nephritis-a large series cohort study from China.

Membranous lupus nephritis (MLN) is a subepithelial immune deposition or its morphological sequelae with or without mesangial changes. Previous studies on the prognosis of MLN have shown relatively small sample sizes and short follow-up periods. Our study was a retrospective analysis of biopsy-proven MLN patients from January 2010 to January 2020 at Jinling Hospital in China. The clinical manifestations, pathological features, and renal outcomes of MLN patients were collected. The endpoint was defined as end-stage kidney disease (eGFR≤15mL/min·1.73m2 or need for renal replacement therapy) or a doubling of serum creatinine or an eGFR decline of more than 40%. We used Cox regression to analyze the risk factors for renal outcome and Kaplan-Meier curves were used to analyze renal survival rate. In the total of 2884 lupus patients, we screened 535 MLN patients. 456 MLN patients were recruited with an average age of 34 ± 12years, 87.8% for female patients and 62.1% patients of nephrotic syndrome with proteinuria of 2.67g/24h. After follow-up of 78 (IQR, 47.3-113.0) months, 37 (8.1%) patients reached the renal endpoint. The 5-year and 10-year renal survival rates were 95.8% and 89.4%, respectively. 370 patients (81.1%) achieved complete remission, 43 patients (9.4%) had partial remission, and only 43 had no response. 34.4% MLN experienced a relapse. The Cox regression showed the risk factors that affect the renal prognosis include male, hypertension history, anemia, high uric acid, acute kidney injury, and interstitial fibrosis in the renal pathology. MLN mostly manifested as nephrotic syndrome, with few renal dysfunctions. Although MLN had a high relapse rate, most patients had a response to immunosuppressants and had a good renal outcome.

The Feasibility of Japanese Histological Grade Classification for Predicting Renal Function Deterioration among Taiwanese Individuals with IgA Nephropathy

Background: We aimed to validate the Japanese histological grading classification (JHGC) in our population of IgA immunoglobulin (IgAN) cases. Methods: We conducted a retrospective cohort study at Taichung Veterans General Hospital in Taiwan from January 2011 to December 2023. The process involved assessing JHGC’s clinical, histological, and merged grading system. Composite renal outcomes based on glomerular filtrate rate (eGFR) were considered. Results: The study included 359 IgAN by renal biopsies. Kidney function at the time of biopsy was suboptimal, with average SCr of 1.3 mg/dL, eGFR of 54.0 mL/min/1.732 m2, and urine protein–creatinine ratio (UPCR) of 1.2 mg/mg. JHGC effectively identified different severity levels of histological and clinical aspects in Taiwanese IgAN. Initial 4-histological classification showed significantly higher MEST-C scores (p &lt; 0.001). Merging grade III and IV was reasonable in Japanese and Taiwanese populations. The clinical grading system (3C) was associated with histological status and proteinuria, but there was no significant trend with SCr, eGFR, and blood urea nitrogen. Significant differences were found among the three groups (log-rank p &lt; 0.01), but C-grade I and II lacked significant difference in long-term renal outcomes. We separated UPCR &lt; 0.5 mg/mg into two groups: eGFR≥ and &lt;60 mL/min/1.732 m2. The new grading system effectively differentiated risk factors for renal outcomes (log-rank p &lt; 0.01), suggesting the need for separation in Taiwanese IgAN. Conclusions: Our study externally validated JHGC in non-Japanese IgAN. Despite applicability to our population, we recommend a new classification specifically for Taiwanese IgAN patients with increased case numbers in eGFR ≥ 60 mL/min/1.732 m2 and UPCR &lt; 0.5 g/day group.

Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis: a nationwide retrospective study in China

BackgroundPediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children.MethodsData from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored.ResultsRenal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924–0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010–1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation.ConclusionsRenal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.342BNb9AdCycy4MnMisg3FSupplementary file 2 (MP4 18937 KB)

Unleashing the power of complement activation: unraveling renal damage in human anti-glomerular basement membrane disease.

Anti-glomerular basement membrane (GBM) disease is a rare but life-threatening autoimmune disorder characterized by rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Renal biopsies of anti-GBM patients predominantly show linear deposition of IgG and complement component 3 (C3), indicating a close association between antigen-antibody reactions and subsequent complement activation in the pathogenesis of the disease. All three major pathways of complement activation, including the classical, lectin, and alternative pathways, are involved in human anti-GBM disease. Several complement factors, such as C3, C5b-9, and factor B, show a positive correlation with the severity of the renal injury and act as risk factors for renal outcomes. Furthermore, compared to patients with single positivity for anti-GBM antibodies, individuals who are double-seropositive for anti-neutrophil cytoplasmic antibody (ANCA) and anti-GBM antibodies exhibit a unique clinical phenotype that lies between ANCA-associated vasculitis (AAV) and anti-GBM disease. Complement activation may serve as a potential "bridge" for triggering both AAV and anti-GBM conditions. The aim of this article is to provide a comprehensive review of the latest clinical evidence regarding the role of complement activation in anti-GBM disease. Furthermore, potential therapeutic strategies targeting complement components and associated precautions are discussed, to establish a theoretical basis for complement-targeted therapies.

Roles of mesangial C3 and C1q deposition in the clinical manifestations and prognosis of IgAN

Background and aimImmunoglobulin A nephropathy (IgAN) is regarded as the most common type of glomerulonephritis around the world and has the potential to result in renal failure. Complement activation has been addressed by a great body of evidence in the pathogenesis of IgAN. We aimed to evaluate the predictive value of C3 and C1q deposition for disease progression in IgAN patients in this retrospective study. MethodsWe recruited 1191 biopsy-diagnosed IgAN patients, and they were divided into different groups according to their glomerular immunofluorescence examination of renal biopsy tissues: 1) C3 deposits ≥ 2 + group (N = 518) and C3 deposits < 2 + group (N = 673). 2) C1q deposit-positive group (N = 109) and C1q deposit-negative group (N = 1082). The renal outcomes were end-stage renal disease (ESRD) and/or an estimated glomerular filtration rate (eGFR) decrease greater than 50% from the baseline value. Kaplan–Meier analyses were performed to evaluate renal survival. Univariate and multivariate Cox proportional hazard regression models were used to evaluate the effect of C3 and C1q deposition on renal outcome in IgAN patients. In addition, we compared the predictive value of mesangial C3 and C1q deposition in IgAN patients. ResultsThe median follow-up period was 53 months (interquartile range 36–75 months). During follow-up, 7% (84) of patients progressed to ESRD, and 9% (111) of patients had an eGFR decline ≥ 50%. IgAN patients complicated with C3 deposits ≥ 2 + were associated with more severe renal dysfunction and pathologic lesions at the time of renal biopsy. The crude incidence rates for the endpoint were 12.5% (84 out of 673) and 17.2% (89 out of 518) in the C3 < 2 + and C3 ≥ 2 + groups, respectively (P = 0.022). Of C1q deposit-positive and C1q deposit-negative patients, 22.9% (25 out of 109) and 13.7% (148 out of 1082) reached the composite endpoint, respectively (P = 0.009). Adding C3 deposition to clinical and pathologic models had better predictability of renal disease progression than C1q. ConclusionGlomerular C3 and C1q deposits affected the clinicopathologic features of IgAN patients and emerged as independent predictors and risk factors for renal outcomes. In particular, the predictive ability of C3 was slightly better than that of C1q.

Lower bile acids as an independent risk factor for renal outcomes in patients with type 2 diabetes mellitus and biopsy-proven diabetic kidney disease.

AimsAbnormalities of glucolipid metabolism are critical mechanisms involved in the progression of diabetic kidney disease (DKD). Bile acids have an essential role in regulating glucolipid metabolism. This study investigated the clinicopathological characteristics of DKD patients with different bile acid levels and explored the relationship between bile acids and renal outcomes of DKD patients.MethodsWe retrospectively reviewed and evaluated the histopathological features and clinical features of our cohort of 184 patients with type 2 diabetes mellitus and biopsy-proven DKD. Patients were divided into the lower bile acids group (≤2.8 mmol/L) and higher bile acids group (>2.8 mmol/L) based on the cutoff value of bile acids obtained using the time-dependent receiver-operating characteristic curve. Renal outcomes were defined as end-stage renal disease (ESRD). The influence of bile acids on renal outcomes and correlations between bile acids and clinicopathological indicators were evaluated.ResultsBile acids were positively correlated with age (r = 0.152; P = 0.040) and serum albumin (r = 0.148; P = 0.045) and negatively correlated with total cholesterol (r = -0.151; P = 0.041) and glomerular class (r = -0.164; P =0.027). During follow-up, 64 of 184 patients (34.78%) experienced progression to ESRD. Lower levels of proteinuria, serum albumin, and bile acids were independently associated with an increased risk of ESRD (hazard ratio, R=5.319; 95% confidence interval, 1.208–23.425).ConclusionsBile acids are an independent risk factor for adverse renal outcomes of DKD patients. The serum level of bile acids should be maintained at more than 2.8 mmol/L in DKD patients. Bile acid analogs or their downstream signaling pathway agonists may offer a promising strategy for treating DKD.

Long-Term Outcome of Leptospirosis Infection with Acute Kidney Injury.

Acute kidney injury (AKI) is associated with long-term mortality and morbidity outcomes. Severe leptospirosis usually results in AKI and multiple organ failure, but is associated with favorable short-term outcomes, if treatment is initiated early. However, information on long-term outcomes after leptospirosis-associated AKI is limited. The effects of leptospirosis on resulting chronic kidney disease (CKD), as well as mortality, were evaluated in this study. We studied 2145 patients with leptospirosis from the National Health Insurance Research Database over an 8-year follow-up period. Patient demographics and characteristics were analyzed for AKI and dialysis. The risk factors for renal outcomes were analyzed using multivariate logistic regression. In total, 443 (20.6%) patients had AKI. Among them, 77 (3.6%) patients received replacement therapy (AKI-RRT group). Long-term mortality was higher in the AKI-RRT group than in the AKI group and non-AKI group, based on a multivariate logistic regression model. Similarly, the incidence rate of CKD was highest in the AKI-RRT group, followed by the AKI and non-AKI groups. Leptospirosis, complicated with AKI, may play a critical role in the long-term outcomes, resulting in CKD. The severity of AKI determines the incidence of CKD. Additional prospective investigations for the early detection of AKI in leptospirosis are warranted.

Tubulointerstitial nephritis in cases of lupus nephritis: An experience from a tertiary care referral center of Eastern India

Context: Up to 60% of patients with systemic lupus erythematosus develop lupus nephritis (LN). Tubulointerstitial nephritis (TIN) includes interstitial inflammation, tubulitis, tubular atrophy (TA), and interstitial fibrosis. These are considered independent risk factors for renal outcome. Aims: To evaluate the occurrence of TIN in LN and to correlate it with clinical and histopathological variables and renal outcome. Settings and Design: It was a prospective, single-center study. Subjects and Methods: One hundred and thirty-two LN cases were evaluated. Light microscopic scoring of interstitial inflammation, fibrosis, and TA was done as follows: 0 (nil); 1+ (mild - &lt;25% of the area of observed cortex); 2+ (moderate - &gt;25% to 50% of the area of observed cortex); 3+ (severe - &gt;50% of the area of observed cortex). For direct immunofluorescence study, fluorescein isothiocyanate-conjugated polyclonal rabbit antisera against human IgG, IgA, IgM, C3c, C1q, kappa, and lambda antibodies (DAKO, Germany) were used. Statistical Analysis Used: Statistical software GraphPad Prism version 6.1. Results: Significant TIN was present in 6% of cases associated with high National Institutes of Health activity and chronicity indices irrespective of the modified International Society of Nephrology and Renal Pathology Society class of LN. In the cases where inflammation and fibrosis are marked, significantly raised serum creatinine, low estimated glomerular filtration rate, high 24-h urinary protein excretion, and reduced survival without any complete remission were seen. Severe interstitial and tubular inflammations without chronicity were also associated with low survival rate due to frequent relapse and significant hypertension. Conclusions: Activity and chronicity indices describing TIN components become essential to predict the survival, therapeutic response, and disease prognosis in LN.

Severe 25-Hydroxyvitamin D Deficiency May Predict Poor Renal Outcomes in Patients With Biopsy-Proven Diabetic Nephropathy.

AimsThis study aims to investigate the role of 25-hydroxyvitamin D (25(OH)D) levels in predicting renal survival in biopsy-proven diabetic nephropathy (DN) with type 2 diabetes mellitus (DM).MethodsIn this retrospective study, a total of 161 biopsy-proven DN patients were enrolled and divided into four groups (normal group: 25(OH)D>20ng/ml; mild group: 10<25(OH)D ≤ 20ng/ml; moderate group: 5<25(OH)D ≤ 10 ng/ml; severe group: 25(OH)D ≤ 5 ng/ml). The effect of the 25(OH)D level on renal survival was evaluated by multivariate Cox regression.ResultsA total of 161 type 2 DM patients with biopsy-proven DN were enrolled in this study. Patients with lower 25(OH)D levels had higher serum creatinine, urinary albumin creatinine ratio (UACR), total cholesterol, and parathyroid hormone levels as well as lower estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and calcium levels and were more prone to diabetic retinopathy (DR). Rather than proteinuria and renal function, glomerular class and interstitial fibrosis and tubular atrophy (IFTA) had a significant correlation with 25(OH)D levels. Multivariate Cox regression indicated that severe deficiency of 25(OH)D levels was associated with adverse renal outcomes. Compared to the level in the normal group, after adjusting for clinicopathological characteristics, a lower 25(OH)D level remained a risk factor for renal outcomes. The HRs were 3.446 (95% CI 0.366-32.406, p=0.279) for the mild group, 8.009 (95% CI 0.791-81.102, p=0.078) for the moderate group, and 14.957(95%CI 1.364-163.995, P=0.027) for the severe group.ConclusionLevels of 25(OH)D less than 5 ng/ml were correlated with worse renal function, more pathological injury and poorer renal prognosis in patients with biopsy-proven DN.

Comparison of 24-h Urine Protein, Urine Albumin-to-Creatinine Ratio, and Protein-to-Creatinine Ratio in IgA Nephropathy.

BackgroundProteinuria is a strong risk factor for renal outcomes in IgA nephropathy. Random urine protein-to-creatinine ratio (PCR), random albumin-to-creatinine ratio (ACR), and 24-h urine protein excretion (24-h UP) have been widely used in clinical practice. However, the measurement which is the best predictor of long-term renal outcomes remains controversial. This study aimed to compare the three measurements in IgA nephropathy.MethodsWe conducted a retrospective study of 766 patients with IgA nephropathy. The associations among baseline ACR, PCR, and 24-h UP with chronic kidney disease (CKD) progression event, defined as 50% estimated glomerular filtration rate (eGFR) decline or end stage kidney disease (ESKD), were tested and compared.ResultsIn this study, ACR, PCR, and 24-h UP showed high correlation (r = 0.671–0.847, P < 0.001). After a median follow-up of 29.88 (14.65–51.65) months, 51 (6.66%) patients reached the CKD progression event. In univariate analysis, ACR performed better in predicting the prognosis of IgA nephropathy, with a higher area under the receiver operating curve (ROC) curve than PCR and 24-h UP. After adjustment for traditional risk factors, ACR was most associated with composite CKD progression event [per log-transformed ACR, hazard ratio (HR): 2.82; 95% (95% CI): 1.31–6.08; P = 0.008].ConclusionsIn IgA nephropathy, ACR, PCR, and 24-h UP had a high correlation. ACR performed better in predicting the prognosis of IgA nephropathy.

Nocturnal heart rate rising is a risk factor for poor renal outcomes in patients with chronic kidney disease and hypertension.

The association of heart rate (HR) dipping pattern with renal outcomes in chronic kidney disease (CKD) patients with hypertension has never been investigated. In order to demonstrate if HR dipping pattern is a risk factor for renal outcomes, cardiovascular (CV) diseases, and mortality in hypertensive patients with CKD, we conducted the prospective longitudinal observational study. Patients were divided into three groups according to their nocturnal HR: HR dippers (night–day HR ratio ≤ 0.9), HR non‐dippers (0.9 < night–day HR ratio ≤ 1.0), and HR risers (night–day HR ratio > 1.0). The primary outcome was renal endpoint, a composite outcome of progression to end‐stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) decline ≥ 50%; the secondary outcomes included poor renal outcomes, CV events, and death. A total of 34 (11.3%) patients reached renal endpoint after a follow‐up of 34 ± 17 months. Both HR non‐dippers and HR risers were predictive to renal endpoint (hazard ratio 2.58, 95% confidence interval (CI) 1.04‐ 6.4, P = .04; hazard ratio 3.95, 95% CI 1.33‐ 11.79, P = .01, respectively), while only HR risers was shown to be correlated with a decline in eGFR≥ 50% (hazard ratio 5.28, 95% CI 1.45–19.16, P < .05), and decline in eGFR (β ‐0.17, 95% CI ‐0.33‐ ‐0.01, P = .04). No predictive value was found for HR dipping pattern to mortality and CV events. In conclusion, our study provided the first evidence that HR non‐dippers, especially risers were a risk factor for poor renal outcomes in hypertensive patients with CKD.

T-Lymphocyte Subsets Alteration, Infection and Renal Outcome in Advanced Chronic Kidney Disease.

Background: T-lymphocyte subsets reflect patients' immune status and are associated with adverse outcomes in various diseases. However, the association between T-lymphocyte subsets and major infection and renal outcome in chronic kidney disease (CKD) patients has not been well-addressed.Methods: Patients diagnosed with stage 3–5 of non-dialysis CKD were recruited, and healthy subjects were selected as the controls. T-lymphocyte subsets (CD3+, CD4+, CD8+) were detected by flow cytometry, and the CD4+/CD8+ T cell ratio was then calculated. Patients were divided into the normal-level group and the low-level group according to the clinical reference value. The primary outcomes were the major infection and renal outcome.Results: A total of 410 CKD patients were enrolled; the average age was 47.25 years. Compared to the healthy controls, the level of CD3+, CD4+, CD8+ T cells, and the CD4+/CD8+ T cell ratio were significantly decreased in CKD patients (p < 0.05). During the median follow-up of 2.56 (quartile interval 1.24–3.46) years, major infections occurred in 15.10% of the CKD patients. The incidence of infection was significantly higher in the low-level group of CD3+, CD4+ T cells, and CD4+/CD8+ T cell ratio compared with the normal level groups. Kaplan-Meier analysis showed that the lower level of CD3+, CD4+ T cells, and CD4+/CD8+T cell ratio is associated with a greater risk of infection. Cox regression analysis further confirmed that low CD3+, CD4+ T cells, and CD4+/CD8+ T cell ratio were independent risk factors of infection in CKD patients. Moreover, during the follow-up, renal events occurred in 37.50% of patients. Kaplan-Meier analysis indicated that low levels of CD3+, CD4+, and CD8+ T cells are significantly associated with renal outcome in CKD patients. Cox regression analysis showed that low level of CD3+ T cells (HR = 2.407, 95% CI: 1.664–3.482, p < 0.001), CD4+ T cells (HR = 2.397, 95% CI: 1.633–3.518, p < 0.001) and CD8+ T cells (HR = 2.416, 95% CI: 1.476–3.955, p < 0.001) were independent risk factors for renal outcome after multivariable-adjusted.Conclusion: CKD patients had a defect in T-lymphocyte subpopulation. T-lymphocyte subsets were closely associated with infection and renal outcome in CKD patients. Suggesting T-lymphocyte subsets are independent predictors of infection and renal outcome in CKD patients.

Mesangial C3 deposition and serum C3 levels predict renal outcome in IgA nephropathy.

Complement activation plays an important role in the pathogenesis of IgA nephropathy (IgAN). We aimed to evaluate the relationship between mesangial C3 deposition and histologic lesions and to investigate the role of mesangial C3 deposition and serum C3 reduction in predicting renal outcome in IgAN children. We performed a retrospective cohort study in children with biopsy-proven IgAN. Mesangial C3 deposition (< 2+ vs. ≥ 2+) was detected by the immunofluorescence. Histopathologic kidney grades were determined by the Oxford classification. A decreased serum C3 concentration (hypoC3) was defined when C3 < 90mg/dl. The endpoint was composite kidney outcome with either a 30% decline in glomerular filtration rates from baseline or kidney failure during the follow-up period. A total of 98 children were analyzed. Mesangial hypercellularity (M) was an independent factor associated with mesangial C3 deposition (HR 3.267; 95% CI 1.028-10.389; P = 0.045). After a median follow-up period of 25months (interquartile range 18-36months), 6 (6.1%) children reached the endpoint. Compared with other children, a significantly higher proportion of children with composite kidney outcomes had mesangial C3 deposition ≥ 2+ and hypoC3 (3.4% versus 27.3%, P = 0.002). After adjustment for clinicopathologic risk factors, mesangial C3 deposition ≥ 2+ and hypoC3 were associated with renal outcome (HR 9.772; 95% CI 1.264-75.518; P = 0.029). Mesangial C3 deposition was associated with M in IgAN. Mesangial C3 deposition and hypoC3 were risk factors for renal outcome in children with IgAN.

Association of platelet-to-lymphocyte ratio with kidney clinicopathologic features and renal outcomes in patients with diabetic kidney disease

BackgroundGrowing evidence points to the pivotal role of inflammation in the pathogenesis of diabetic kidney disease (DKD). However, as an inflammation-based prognostic score, the significance of platelet-to-lymphocyte ratio (PLR) in biopsy-proven DKD remains uncertain. Therefore, the current study aimed to evaluate the association of PLR with the clinicopathological features and the progression of DKD. MethodsIn total, 167 patients with biopsy-proven T2DKD were retrospectively recruited. Clinicopathological characteristics were compared according to the tertiles of baseline PLR. Pearson’s or Spearman correlations were used to examine the associations between PLR and baseline characteristics. Assessment of the prospective relationship of PLR with the kidney outcomes defined as a doubling of baseline serum creatinine or onset of end stage renal disease (ESRD), were investigated by Kaplan-Meier survival analysis. Moreover, a cubic spline curve was further calculated to explore the significance of PLR in DKD prognosis. On top of that, identification of the risk factors associated with DKD progression was executed by a model of Cox proportional hazards. ResultsMedian follow-up period was 23.77 months, during which 92 (55.1%) patients confronted DKD progression. Pearson’s correlation indicated that urinary protein increased along with PLR rising (r = 0.193, P = 0.012). Kaplan–Meier survival curves revealed a significantly increased probability of event-free survival in the lowest tertile of PLR compared to those in the highest tertile (P = 0.018). A statistical linear correlation between PLR and DKD development was demonstrated by a restricted cubic spline analysis (P for nonlinear = 0.784). In addition, the analyses of multivariate Cox regression indicated that elevated PLR had an association with a greater risk of DKD progression (HR 1.004, 95%CI [1.000–1.008], P = 0.035), which was verified to be an independent risk factor for renal outcomes. ConclusionsOur findings demonstrated that the PLR was associated with proteinuria and prognosis in DKD patients. It was an independent risk factor for kidney progression in biopsy-proven DKD.

Clinicopathologic characteristic and prognosis in idiopathic membranous nephropathy patients with focal segmental sclerosis lesion: A retrospective observational study.

To explore the clinicopathological characteristics and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental sclerosis lesions (FSL).A total of 70 IMN patients with FSL (FSL+group) were enrolled in this study, and 140 patients were randomly selected by age and sex matching as disease controls (FSL-group). The clinical and renal histopathological data on renal biopsy and clinical data of patients regularly followed were collected. Serum anti-phospholipase A2 receptor (PLA2R) autoantibody, thrombospondin type-1 domain-containing 7A (7A) autoantibody, glomerular PLA2R and 7A expression, and IgG4 deposition were detected. First, the clinical and pathological significance of IMN combined with the FSL group was analyzed. Whether FSL is a risk factor for renal outcomes was further analyzed. 1.Compared with the FSL- group, patients in the FSL+ group had a significantly higher incidence of hypertension and a longer duration of hypertension as well as higher levels of systolic blood pressure, serum creatinine, serum triglycerides, serum cholesterol, 24-hour urinary protein excretion, and lower eGFR and urine osmotic pressure. Patients in the FSL+ group had an increased frequency of Churg stage III and more severe glomerulosclerosis and interstitial fibrosis. The remission rate was significantly lower in the FSL+ group than in the FSL- group (50.0% vs 75.9%, P = .027).2.Multivariate Cox regression analysis showed that FSL (HR = 3.01, 95%CI = 1.07–8.52, P = .038) was an independent risk factor for progression of renal function deterioration, and FSL (HR = 3.25, 95%CI = 1.43–7.38, P = .005) and high levels of serum anti-PLA2R antibody (HR = 1.89, 95%CI = 1.27–2.82, P = .002) were independent risk factors for nonremission of IMN.IMN patients who developed FSL had more severe clinical and pathological characteristics than those without FSL. FSL was an independent risk factor for poorer prognosis. When the appearance of FSL in IMN patients with a high level of serum anti-PLA2R antibody, the treatment needs to be more aggressive to promote remission and to delay the progression of renal function.

Urinary sediments could differentiate endocapillary proliferative lupus nephritis and endocapillary proliferative IgA nephropathy

ObjectiveThis study investigated the differences in urinary sediment findings between patients with endocapillary proliferative lupus nephritis (LN) and patients with endocapillary proliferative IgA nephropathy (IgAN) and further evaluated the associations of leukocyturia with disease activity, pathological features and prognosis. MethodsThe urinary sediments of 126 patients, including 92 with LN and 34 with IgAN, with renal-biopsy-proven endocapillary proliferative glomerulonephritis (EPGN) were examined by a standardized method. The urinary elements investigated included various cells, casts and crystals. The associations of leukocyturia with disease activity, pathological features and prognosis were further analyzed. ResultsIn the patients with EPGN, normal to mild leukocyturia (≤12/HPF) and moderate to severe leukocyturia (>12/HPF) were found in 52 (41.27%) and 74 (58.73%) patients, respectively. The proportion of moderate to severe leukocyturia and the frequencies of urinary white blood cell casts and waxy casts were significantly higher in endocapillary proliferative LN than those in endocapillary proliferative IgAN (P < 0.001, P = 0.020, P = 0.010, respectively). In the endocapillary proliferative LN group, the levels of leukocyturia were significantly correlated with serum creatinine (r = 0.288, P = 0.005), eGFR (r = −0.284, P = 0.006), serum C3 (r = −0.275, P = 0.009), SLEDAI scores (r = 0.383, P ≤ 0.001) and glomerular leukocyte infiltration (r = 0.285, P = 0.002). A multivariate analysis showed that leukocyturia was an independent risk factor for renal outcomes in endocapillary proliferative LN (HR: 1.456, 95% CI: 1.083-1.957, P = 0.013) but not in IgAN. ConclusionsUrinary sediments of LN with EPGN and IgAN with EPGN differed in many aspects. Leukocyturia could reflect the disease activity and prognosis of EPGN, especially in endocapillary proliferative LN.