Combined Effects of the Serum IgA/C3 Ratio and Glomerular C3 Staining on the Renal Outcome in Adult Immunoglobulin A Nephropathy.

INTRODUCTION: The aim of this study was to evaluate the predictive value of the serum IgA/C3 ratio and glomerular C3 deposits in kidney biopsy in adult IgA nephropathy. METHODS: The study included 718 adult IgAN patients diagnosed based on kidney biopsy. Patients without corticosteroids or immunosuppressive drugs >1 month were regularly followed up for at least 1 year or until the study endpoint. The optimum serum IgA/C3 ratio was calculated by the AUROC-based cutoff ratio. Proteinuria, creatinine, eGFR, serum IgA, and serum C3 were evaluated at baseline. Kidney biopsy was categorized using the Oxford classification, with a calculation of the MEST-C score. The degree of glomerular C3 staining was semiquantitatively determined (grade 0, no or trace; grade 1, mild; grade 2, moderate; grade 3, marked) by immunofluorescence microscopy. The patients were divided into four groups by the serum IgA/C3 ratio and glomerular C3 staining. RESULTS: The baseline data suggested that when the serum IgA/C3 ratio was at the same level, patients with a high glomerular C3 staining score (≥2) always had mesangial proliferation, segmental glomerulosclerosis, and tubular atrophy/interstitial fibrosis (group 1 vs. group 2; group 3 vs. group 4). When glomerular C3 staining was at the same level, proteinuria was significantly higher in patients with serum IgA/C3<2.806 (group 1 vs. group 3; group 2 vs. group 4), which was contrary to previous studies that have suggested that the serum level of IgA/C3 was associated with disease severity. Hence, this study set out to investigate the combined effects of the serum IgA/C3 ratio and glomerular C3 staining on the renal outcome in adult IgA nephropathy. Renal survival analysis indicated that serum IgA/C3 ≥2.806 and glomerular C3 staining ≥2 (group 1) may be correlated with a poorer prognosis, especially in different clinicopathological characteristics of IgAN patients based on the subgroup analysis. Multivariate Cox analysis demonstrated that hypertension, serum creatinine, CKD stage, T1/2 and C3 staining were independent predictive factors of renal survival. CONCLUSIONS: The combination of serum IgA/C3 and C3 staining may contribute to improved optimization of the prognostic model in IgAN patients, especially patients with different sexes and degrees of disease. However, further study is required for validation in the future.

Uric acid-based ratios for predicting renal failure in Chinese IgA nephropathy patients.

Objective: The uric acid/albumin ratio (UAR), a novel, simple, and compositive laboratory biomarker, has recently attracted attention for predicting disease prediction and disease prognosis. However, whether uric acid-related biomarkers (especially UAR) could serve as prognostic indicator for IgAN is unclear. Methods: In this retrospective cohort study, biopsy-confirmed IgAN patients from 2009 to 2017 from West China Hospital were evaluated. The optimal cutoff value of UAR for renal outcome was defined using the Youden index by the area under receiver operating characteristic curve (AUC). The patients were then categorized into the high UAR group and the low UAR group. Renal endpoints were defined as progression to ESRD, eGFR decreased ≥50% of the baseline level, or initiation of renal replacement treatment. Kaplan‒Meier survival analysis and Cox regression analysis were used to identify factors influencing IgAN outcomes. Results: A total of 1143 patients with a median age of 33.0 (26.0-42.0) (44.2% men) were included in the study. The best cut-off UAR concerned with renal survival was determined to be 9.94 with a specificity of 77.5% and a sensitivity of 61.5% (J, 0.390; AUC, 0.750). Then, the patients were divided into two groups labelled as low and high UAR ratios (≥ 9.94 and <9.94, respectively). More severe clinical manifestations and pathological lesions were observed in the high UAR group. Multivariate Cox regression analysis after adjusted for important clinicopathological parameters manifested that a high UAR was an independent prognostic biomarker for IgAN. (p = 0.036, HR =2.56, 95% CI: 1.07-6.16). Conclusion: UAR might be a novel predictor for renal progression and contribute to targeted management.

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

BACKGROUND AND AIM: Immunoglobulin 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. METHODS: We 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. RESULTS: The 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. CONCLUSION: Glomerular 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.

Association of obesity with the development of end stage renal disease in IgA nephropathy patients.

Background and aim: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. We aimed to evaluate whether obesity is a risk factor for IgAN patients. Methods: A total of 1054 biopsy-proven IgAN patients were analyzed in this retrospective study. Patients were divided into four groups according to their body weight index (BMI) at the period of renal biopsy: underweight group (BMI< 18.5, N=75), normal weight group (18.5≤BMI<24, N=587), overweight group (24≤BMI<28, N=291) and obesity group (28≤BMI, N=101). The endpoint of our study was end stage renal disease (ESRD: eGFR <15 mL/min/1.73 m2 or having renal replacement treatment). Kaplan-Meier analyses and Cox proportional hazard models were performed to evaluate renal survival. Propensity-score matching (PSM) was performed to get the matched cohort to evaluate the role of obesity in IgAN patients. Besides, the effect modification of obesity and hypertension in IgAN patients was clarified by the synergy index. Results: IgAN patients complicated with obesity had more severe renal dysfunction at the time of renal biopsy than those with optimal body weight. In addition, patients with obesity tended to have higher risk of metabolic disorders, such as hyperuricemia (64.4% vs 37%, p<0.001), hypertriglyceridemia (71.3% vs 32.5%, p<0.001) and hypercholesterolemia (46.5% vs 35.6%, p=0.036). It was observed that obesity patients had higher rate of unhealthy behaviors, such as smoking (27.7% vs 16.4%, p=0.006) and alcohol drinking (29.7% vs 19.9%, p=0.027). Although obesity was not confirmed as an independent risk factor for IgAN patients, we found that IgAN patients with obesity presented with higher incidence of hypertension, as well as lower event-free renal survival rate (log-rank p < 0.001), especially in patients with 24-h urine protein ≥ 1g (log-rank p =0.002). In addition, the synergy index showed that there was positive interaction between obesity and hypertension in IgAN. Conclusion: Obesity is an important risk factor for IgAN patients when combined with hypertension. Hypertension appears to be common in obese IgAN patients.

Oral energy supplementation improves nutritional status in hemodialysis patients with protein-energy wasting: A pilot study.

Background: Protein-energy wasting (PEW) is highly prevalent in hemodialysis (HD) patients, which is associated with poor quality of life, complications, and an increased risk of mortality. A prospective study in HD patients with 2 months of oral energy supplements (OESs) was performed. Methods: A total of 37 HD patients with PEW were finally enrolled in this prospective study and were randomized into the OES group (n = 19), which received oral energy supplementation (300 kcal) and dietary recommendations, while patients in the non-OES group (n = 18) received only dietary recommendations. The study duration was 2 months. The nutritional status of the patients was evaluated by laboratory indexes, body composition parameters, and the modified quantitative subjective global assessment (MQSGA) and malnutrition-inflammation score (MIS). Quality of life was evaluated by the Short Form Health Survey Questionnaire (SF-36). Results: After 2 months of therapy, a significant increase in serum albumin [39.6 (37.6-45.8) vs. 43.4 (39.1-46.7) g/L; p = 0.018], hemoglobin (101.0 ± 13.6 g/L vs. 111.8 ± 11.7 g/L; p = 0.042), and dietary energy intake (29.17 ± 3.22 kcal/kg/day vs. 33.60 ± 2.72 kcal/kg/day, p < 0.001) was observed in the comparisons of baseline in the OES group. Moreover, the OES group demonstrated significant amelioration in MQSGA [9 (8-13) vs. 8 (7-12), p < 0.001] and MIS [5 (3-10) vs. 3 (2-8), p < 0.001], physical functioning (p < 0.001), and mental health (p = 0.046) subsections of SF-36 compared with the baseline. No electrolyte disorders or dyslipidemia were observed in the OES group. Conclusion: OES in HD patients with PEW can significantly ameliorate energy supply, nutritional status, anemia, and quality of life.

Prognostic value of the albumin-to-fibrinogen ratio (AFR) in IgA nephropathy patients.

BACKGROUND: The albumin-to-fibrinogen ratio (AFR), a novel inflammatory marker, has been studied in various diseases. However, whether AFR could act as a prognostic factor for IgAN patients remains unclear. We aimed to investigate the prognostic value of AFR in IgAN. METHODS: A total of 1289 biopsy-confirmed primary IgAN patients from 2008 to 2018 in West China Hospital, Sichuan University, were studied retrospectively. Receiver operating characteristic curve analysis was generated to assess and compare the ability of indicators to predict survival. Based on the cut-off value of AFR, IgAN patients were classified into the low AFR group and the high AFR group. The demographic and clinical-histopathological data were collected. Renal endpoints included eGFR decreased ≥50 % of the baseline level, ESRD, renal transplantation and/or death. Patients were followed up until a composite endpoint. Kaplan-Meier survival curves and Cox proportional hazards models were used to determine independent predictors. RESULTS: The area under the curve (AUC) of AFR was 0.677, with an optimal cut-off value of 12.44. IgAN patients were classified into two groups (low AFR group: AFR < 12.44, n = 541; high AFR group: AFR ≥ 12.44, n = 748) with a median follow-up of 55.3 (36.4-78.6) months. A higher composition of hypertension, worse renal function, higher proteinuria, and more severe pathological lesions were significantly shown in the low AFR group. Further multivariable Cox regression analyses showed that a low AFR was an independent risk factor for renal survival (HR 1.90, 95 % CI 1.29-2.81, p = 0.001). Kaplan-Meier curves showed that the cumulative incidences of both ESRD and composite end point were significantly higher in patients with AFR < 12.44 (both p < 0.001). CONCLUSIONS: Our study demonstrated that a low AFR (<12.44) is an independent prognostic factor of poor renal prognosis in Chinese IgAN patients.

Triglyceride-Glucose Index May Predict Renal Survival in Patients with IgA Nephropathy.

Background: The triglyceride−glucose (TyG) index is a simple, novel and reliable surrogate marker of insulin resistance. However, evidence for the prognostic impact of an elevated TyG index on IgA nephropathy (IgAN) is limited. Therefore, we evaluated the relationship between the TyG index and the risk of renal progression in IgAN. Method: This cohort study involved biopsy-proven IgAN between January 2009 and December 2018 in West China Hospital, in which patients were assigned to two groups based on the cut-off value of TyG using receiver operating characteristic (ROC) curves. A 1:1 matched-pair analysis was established to optimize the bias in IgAN by propensity score matching (PSM). The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The composite endpoint was defined by eGFR decreased ≥50% of the baseline level, end-stage kidney disease (ESKD), renal transplantation and/or death. Univariable and multivariable Cox proportional hazard models were applied to confirm the predictive value of the optimal marker. Results: Before PSM, a total of 1210 participants were ultimately included. During a median follow-up period of 55.8 months (range 37.20−79.09 months), 129 participants progressed to the composite endpoint (10.7%). After PSM, 366 patients were enrolled in the matched cohort, of whom 34 (9.3%) patients reached the endpoints. Based on the cut-off value of the TyG index, patients were divided into the low TyG index group (TyG ≤ 8.72, n = 690) and the high TyG index group (TyG > 8.72, n = 520). Further analysis demonstrated that a higher TyG index was significantly associated with a higher risk of reaching composite endpoints in IgAN patients in both the unmatched and matched cohorts (before PSM: HR 2.509, 95% CI 1.396−4.511, p = 0.002; after PSM: HR 2.654, 95% CI 1.299−5.423, p = 0.007). Conclusion: A high TyG index is associated with a higher risk of renal progression.

Probiotics ameliorate IgA nephropathy by improving gut dysbiosis and blunting NLRP3 signaling.

BACKGROUND: Recently, a few studies have indicated a relationship between the gut microbiota and IgA nephropathy (IgAN). Whether the gut microbiota participates in the pathogenesis of IgAN and whether probiotics are effective in treating IgAN are still controversial. Therefore, this study aimed to identify the differences in the structure of the gut microbiota between IgAN and controls and to evaluate the efficacy and mechanism of probiotics in the treatment of IgAN. METHODS: To address this question, 35 IgAN patients and 25 healthy volunteers were enrolled, and a mouse IgAN model was also constructed. The stool microbes were analyzed by 16S rRNA high-throughput sequencing to identify the differential strains between IgAN and healthy controls. The impact of probiotics on the structure of the intestinal flora and the efficacy of the probiotics in the treatment of IgAN were evaluated. RESULTS: Although the microflora structure of mice and humans was not the same, both patients and mice with IgAN exhibited gut microbiota dysbiosis, with all subjects presenting an evident decrease in Bifidobacterium levels. The Bifidobacterium proportion was negatively correlated with proteinuria and hematuria levels, indicating that the decreased Bifidobacterium abundance could be related to IgAN severity. Probiotic treatment containing Bifidobacterium in IgAN mice could significantly alleviate gut dysbiosis, specifically by increasing the proportion of beneficial bacteria and reducing the abundance of potentially pathogenic bacteria. Moreover, both probiotics and their metabolites, short-chain fatty acids (SCFAs), could attenuate IgAN clinicopathological manifestations by inhibiting the NLRP3/ASC/Caspase 1 signaling pathway. CONCLUSIONS: Supplementation with probiotics mainly containing Bifidobacterium could markedly improve gut dysbiosis in IgAN. Moreover, both probiotics and their SCFA metabolites could attenuate the clinicopathological manifestations of IgAN by inhibiting the NLRP3/ASC/Caspase 1 signaling pathway. Therefore, probiotics have potential as an adjunctive therapy for IgAN.

Prognostic Value of Triglyceride to High-Density Lipoprotein Cholesterol Ratio (TG/HDL-C) in IgA Nephropathy Patients.

Background: The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio is an easy-to-use atherogenic and prognostic marker which has attracted increasing attention these days. However, whether TG/HDL-C correlate with outcomes in IgA nephropathy (IgAN) patients remains unknown. To clarify these issues, we conducted this study. Methods: A total of 1146 patients from West China Hospital of Sichuan University were retrospectively analysed between 2008 and 2018.The demographic, clinical and pathological data of all patients at the time of biopsy were collected. Then, patients were divided into the high TG/HDL group (TG/HDL ≥ 1.495, N=382) and the low TG/HDL group (TG/HDL-C < 1.495, N=764) based on the optimal cut-off value of the TG/HDL-C using receive operating curve. Cox proportional hazard models and Kaplan-Meier curves were used to evaluate the renal outcomes of IgAN. Results: The median age of the patients was 33 (26-42) years, and 44.5% were men. By correlation analysis, we found that the TG/HDL-C ratio was negatively correlated with the eGFR (r = 0.250, P < 0.001) but positively correlated with proteinuria (r = 0.230, P< 0.001), BMI (r=0.380, P<0.001) and serum uric (r =0.308, P< 0.001). Patients with a higher TG/HDL-C ratio tended to have hypertension [odds ratio (OR), 1.987; 95% CI, 1.527-2.587; P<0.001] and more severe pathologic lesions with tubular atrophy/interstitial fibrosis (OR, 1.610; 95% CI, 1.203-2.154; P=0.001). During a median follow-up period of 54.1 (35.6-73.2) months, a high TG/HDL ratio was strongly associated with worse renal survival in IgAN patients (log-rank: P <0.001). Multivariate Cox analysis demonstrated that a high TG/HDL-C ratio (HR 1.775, 95% CI 1.056-2.798; P=0.029) was an independent predictive marker to ESRD. Conclusion: In this study, we addressed the importance of TG/HDL-C ratio as a predictive marker for IgAN progression.

Platelet-to-Albumin Ratio: A Novel IgA Nephropathy Prognosis Predictor.

Background: Chronic inflammation is related to the development of IgA nephropathy (IgAN). Emerging studies have reported that platelet-related parameters including platelet (PLT), platelet-to-albumin ratio (PAR), and platelet-to-lymphocyte ratio (PLR) are proved to be novel prognostic indicators for several inflammatory diseases. Whether platelet-related parameters could serve as predictors for IgAN remains unknown. Methods: A total of 966 IgAN patients were enrolled in this retrospective study and were divided into several groups based on the optimal cut-off value of the platelet-related parameters. End-stage renal disease was used as the renal endpoint. A 1:2 propensity score (PS) match was then carried out to eliminate significant differences at baseline. The area under the receiver operating characteristic curve (AUROC), Kaplan-Meier (K-M) curve, and Cox proportional hazards analyses were performed to evaluate their predictive effect. Results: Without considering the effect of covariates, the K-M curve showed that PLT, PLR, and PAR were strongly correlated with the renal outcomes of IgAN. However, the AUROC revealed that the PAR and PLR had better predictive power than the PLT. Multivariate Cox regression adjusting for demographic data, pathological findings, treatment, and laboratory results indicated that compared with PLR, albumin and PLT, PAR seemed to be a better marker of adverse renal outcome, implying that PAR was the only platelet-related parameter that could be used as an independent risk factor. Notably, high PAR patients seemed to have more severe clinical manifestations and pathological lesions. However, after eliminating the influence of different baselines on outcome variables, the PAR could still predict the poor prognosis of IgAN. To more accurately evaluate the predictive power of the PAR, we analyzed the predictive effect of the PAR on patients with different clinicopathological characteristics through subgroup analysis. It was indicated that the PAR might better predict the prognosis and outcome of patients whose disease was already very severe. Conclusion: PAR might be used as an independent risk factor for IgAN progression.

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 (ß -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.

Arterial-Arteriolar Sclerosis Is Independently Associated With Poor Renal Outcome in IgA Nephropathy Patients.

Aim: This study aimed to investigate the clinicopathological features and prognosis of immunoglobulin A nephropathy (IgAN) with arterial-arteriolar sclerosis (AS). Methods: Patients with biopsy-proven IgAN from the West China Hospital of Sichuan University were retrospectively enrolled. Clinicopathological features were collected. Patients were categorized based on the presence and the severity of the AS. All the patients were regularly followed-up until a composite end point. The correlation between AS and prognosis of IgAN was assessed. Results: A total of 1,424 patients were recruited and followed for 60.0 ± 28.7 months. Patients with AS tended to have older age, higher blood pressure, heavier proteinuria, higher serum creatinine, uric acid, and total triglyceride (TG). Meanwhile, they were more likely to have a lower estimated glomerular filtration rate (eGFR), hemoglobin, and albumin. At the end of follow-up, 126 patients in the AS group and 47 patients in the non-AS group had reached the composite end point (p < 0.001). AS was associated with the renal outcome (log-rank p < 0.001) and was an independent risk factor for the progression of IgAN (p = 0.049). The severity of AS was associated with renal outcomes (log-rank p < 0.001) and there was a trend that it might serve as an independent risk marker for progression of IgAN. In the subgroup analysis, patients presenting with AS and lower eGFR, albumin, and hemoglobin or higher proteinuria, uric acid, and TG had a significant trend for a shorter time to reach the end point (log-rank p < 0.001). Conclusion: AS was commonly seen in patients with IgAN and was independently associated with the poor prognosis.

Association of morning blood pressure surge with chronic kidney disease progression in patients with chronic kidney disease and hypertension.

Blood pressure (BP) usually rise from being asleep to awake, which is named the morning blood pressure surge (MBPS). Researches have reported that elevated MBPS was related with CV events, incident CKD in hypertensive patients. However, there have been no studies that have investigated the association between MBPS and renal or heart outcomes in patients with CKD and hypertension, in these patients, the MBPS is much lower because of high prevalence of night hypertension and reduced BP dipping. In this prospective two-center observational study, we enrolled patients with CKD and hypertension and the 24 h ambulatory blood pressure monitoring (ABPM) was conducted in all patients. Time to total mortality, CKD progression and CV events was recorded; Finally, a total of 304 patients were enrolled and 94 (30.9%) of them had elevated MBPS. After a follow-up for median 30 months, 23 (7.6%), 34 (11.2%), and 95 (31.3%) patients occurred death, CKD progression and new-onset CV events, respectively. The Cox regression analysis suggested the elevated MBPS was a strong predictor of CKD progression (HR 2.35, 95%CI 1.2 -4.63, p = .013), independent of morning BP, while no associations were found between elevated MBPS and CV events (HR 1.02, 95%CI 0.66 -1.57), as well as death (HR 1.08, 95%CI 0.46 -2.55). In conclusion, we provided the first evidence that elevated MBPS was an important risk factor of CKD progression in patients with CKD and hypertension. Appropriate evaluation and management of MBPS may be helpful to postpone CKD progression.

The Association of Morning Hypertension With Target Organ Damage in Patients With Chronic Kidney Disease and Hypertension.

Objectives: To determine the association between morning hypertension and target organ damage (TOD) in patients with chronic kidney disease (CKD) and hypertension. Methods: In this cross-sectional study, 447 patients with CKD and hypertension from two centers were enrolled. Ambulatory blood pressure monitoring was conducted in all patients. Linear regression and logistic regression analysis were used to determine the association between morning hypertension and TOD in patients with CKD and hypertension, including assessments of estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), urine protein/creatinine ratio (UPCR), and left ventricular hypertrophy (LVH). Results: Overall, 194 (43.4%) participants had morning hypertension. Morning hypertension was strongly correlated with LVH [odds ratio (OR), 2.14; 95% confidence interval (CI), 1.3-3.51; p < 0.01], lower level of eGFR (ß = -0.51; 95%CI, -0.95--0.08; p < 0.05), higher LVMI (ß = 0.06; 95%CI, 0.04-0.08, p < 0.001), and UPCR (ß = 0.22; 95%CI, 0.06-0.38, p < 0.01), independent of nocturnal hypertension and elevated morning blood pressure surge. As a continuous variable, both morning systolic blood pressure (SBP) and diastolic blood pressure (DBP) were found to be associated with LVH and higher level of UPCR and LVMI (p < 0.05), whereas only morning SBP was negatively correlated with eGFR (p < 0.01). Conclusion: Morning hypertension was strongly correlated with cardiac damage and impaired kidney function in CKD patients with hypertension, independent of nocturnal hypertension and morning surge in blood pressure. Morning hypertension in CKD patients warrants further attention.

High Neutrophil-To-Lymphocyte Ratio Is an Independent Risk Factor for End Stage Renal Diseases in IgA Nephropathy.

Background: Complex factors are involved in the development and progression of immunoglobulin A nephropathy (IgAN), a common primary glomerulonephritis worldwide. Autoimmunity and inflammation have been considered to be the basic mechanisms; however, the exact pathogenesis remains unclear. As a novel marker of inflammation, the neutrophil-to-lymphocyte ratio (NLR) has been studied in various diseases. Whether the NLR can predict the renal outcome of patients with IgAN remains unclear. We evaluated the relationships between the NLR and renal function, pathologic lesions, renal progression, and prognosis in patients with IgAN. Methods: This retrospective study involved 966 patients with biopsy-proven IgAN. They were divided into two groups based on the cut-off value of the NLR: the high group (NLR ≥ 2.67, n = 384) and the low group (NLR < 2.67, n = 582). The endpoint was end-stage renal disease [estimated glomerular filtration rate (eGFR) of <15 mL/min/1.73 m2 or performance of renal replacement therapy]. A correlation test was conducted to explore the relationship between the NLR and other important parameters (eGFR, serum creatinine, proteinuria, hypertension and renal pathologic lesions). The predictive value was determined by the area under the receiver operating characteristics curve (AUROC). Kaplan-Meier and Cox proportional hazards analyses were performed to evaluate renal progression and prognosis. Results: The NLR had the highest AUROC, which was 0.633 (p < 0.001). The correlation test revealed that the NLR was positively correlated with serum creatinine (r = 0.127, p < 0.001) and 24-hour urine protein (r = 0.18, p < 0.001) and negatively correlated with eGFR (r = 0.14, p < 0.001). Patients with IgAN who had a high NLR were more likely to have hypertension (p = 0.003). Multivariate Cox regression analysis indicated that a high NLR was an independent risk factor for IgAN even after adjustment for important clinical and pathological parameters (p = 0.043, HR = 1.74, 95%CI: 1.02-2.97). Kaplan-Meier analysis showed that a high NLR was significantly associated with the renal prognosis of patients with IgAN (p < 0.001), especially patients with stage 3 to 4 chronic kidney disease (p = 0.028) or 24-hour urine protein of >1 g/day (p < 0.001). Conclusion: An elevated NLR affects the renal progression and prognosis in patients with IgAN and could be a marker for evaluation of renal function and pathologic lesions.

Cigarette smoking may accelerate the progression of IgA nephropathy.

BACKGROUND: Whether cigarette smoking is associated with the progression of immunoglobulin A nephropathy (IgAN) remains uncertain; therefore, we aimed to evaluate the effect of cigarette smoking on the prognosis of IgAN. METHODS: We divided 1239 IgAN patients from West China Hospital of Sichuan University who met the inclusion criteria into smoker (current or former) and non-smoker groups. The endpoint was end-stage renal disease (ESRD: eGFR < 15 mL/min/1.73 m2 or undergoing renal replacement treatment) and/or eGFR decreased by > 50%. Kaplan-Meier, correlation, logistic regression and Cox proportional hazards analyses were performed. The association between cigarette smoking and IgAN was further verified by propensity-score-matched cohort analysis. RESULTS: During the mean follow-up period of 61 months, 19% (40/209) of the smoker group and 11% (110/1030) of the non-smoker group reached the study endpoint (p < 0.001). Multivariate Cox regression analysis revealed that cigarette smoking (hazard ratio (HR) = 1.58; p = 0.043) was an independent risk factor predicting poor renal progression in IgAN, and that IgAN patients with chronic kidney disease (CKD) stage 3-4 were more susceptible to cigarette smoking (p < 0.001). After propensity score matching (PSM), a significant correlation between cigarette smoking and renal outcomes in IgAN patients was seen. Furthermore, Spearman's correlation test revealed that smoking dose was negatively correlated with eGFR (r = 0.141; p < 0.001) and positively related with proteinuria (r = 0.096; p = 0.001). CONCLUSIONS: Cigarette smoking is an independent risk factor for IgAN progression, especially for advanced patients.

Novel Predictors and Risk Score of Treatment Failure in Peritoneal Dialysis-Related Peritonitis.

Objective: Peritonitis is a severe complication in peritoneal dialysis (PD). This study was performed to identify predictors and establish a risk score for treatment failure in peritonitis patients. Methods: A single-center, retrospective observational study was conducted. The basic demographic characteristics, clinical and laboratory data of all patients with peritonitis during the study period were documented and analyzed. Multivariate logistic regression was applied to examine independent predictors of treatment failure, and a risk prediction score was established. Results: Three hundred fourteen episodes experienced by 241 patients were included in the final analysis. Logistic regression analysis indicated that PD duration (OR 1.017; P 0.005), fibrinogen (OR 1.327; P 0.021), high-density lipoprotein (OR 0.443; P 0.032), fungal infection (OR 63.413; P < 0.001), intestinal obstruction (OR 5.186, P 0.007), and diabetes mellitus (OR 2.451; P 0.018), hemodialysis history (OR 2.804, P 0.006) were independent predictors of treatment failure. The risk prediction score system showed a good calibration (P > 0.05) and discrimination (AUROC 0.80, P < 0.001). Conclusions: Fibrinogen, PD duration, fungal infection, hemodialysis history, concurrent intestinal obstruction, or diabetes mellitus were independent risk factors for a poor peritonitis outcome, while the high-density lipoprotein was a protective factor. This novel risk prediction score system may be used to predict a high risk of treatment failure effectively.

Development and validation of a novel score to predict dialysis inadequacy in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: Adequate dialysis is of great importance for continuous ambulatory peritoneal dialysis (CAPD) patients. This study aimed to develop and validate an easily applicable quantitative dialysis adequacy risk scoring system in CAPD patients based on laboratory parameters from a single blood draw. METHODS: A total of 634 CAPD patients from four study centers were enrolled in this study (345 and 289 patients in development and validation groups, respectively). A risk score model for inadequate dialysis was developed based on multivariate regression analysis, which was validated by the area under the receiver operator curve and calibrated by a calibration curve. RESULTS: Seven independent predictors for inadequate dialysis were identified in the development group (male sex, hypoalbuminemia, anemia, being overweight, hyperuricemia, estimated glomerular filtration rate <4.7 mL/min/1.73 m2, and serum creatinine >800 µmol/L). A risk prediction score model was established and validated in the development and validation groups. Further analysis indicated that this model is suitable for CAPD patients with a wide range of clinical manifestations. CONCLUSION: An easily applicable novel risk scoring system was established to detect inadequate dialysis in CAPD patients.

Corticosteroids Improve Renal Survival: A Retrospective Analysis From Chinese Patients With Early-Stage IgA Nephropathy.

Background: The efficacy and safety of corticosteroids and immunosuppressive therapy remain controversial for the treatment of immunoglobulin A nephropathy (IgAN). This study aimed to evaluate the effects of corticosteroid and immunosuppressant therapy in Chinese patients with early-stage IgAN whose estimated glomerular filtration rate (eGFR) was ≥45 ml/min/1.73 m2 and proteinuria was ≥1 g/24 h at biopsy. Methods: Patients with biopsy-proven IgAN were retrospectively enrolled from four study centers between 2007 and 2016. Patients were regularly followed up for at least 1 year or until the study end point. Patients were categorized into three treatment groups: supportive care (SC), steroids alone (CS), and steroids plus immunosuppressants (IT). The observed responses to therapy included complete remission (CR), partial remission (PR), no response (NR), and end-stage renal disease (ESRD). The primary end point of the current study was defined as a 50% decline in eGFR and/or ESRD. Results: A total of 715 patients (male 47% and female 53%) were recruited and followed up for 44.69 ± 24.13 months. The observed CR rate was 81.8% with corticosteroids alone (CS), 62.7% with corticosteroids + immunosuppresants (IT), and 37% with supportive care alone (SC). Renal outcomes were remarkably better in the CS group compared with the SC and IT groups (the percentage of patients reaching the end point in each group was 4.6 vs. 14.4 vs. 11.5%, respectively; p = 0.001). Moreover, 36 and 80-month renal survival were significantly better for the CS group (98.3 and 86.4%) than for the IT (94.2 and 82.4%) and SC (94.0 and 51.6%) groups. Early CKD stage also presented with better kidney survival (p < 0.001). Renal survival of CKD stage 1 patients was relatively good regardless of the specific treatment regimen. CS and IT treatment significantly improved renal survival for CKD stage 2 patients when compared with the SC group (p < 0.001 and 0.007, respectively). However, renal survival of CKD stage 3a patients was not impacted by any of the three treatment regimens. Subgroup analysis also showed that renal survival of patients with proteinuria >3.5 g, M1, E0, S1, T0, and C0 was significantly better in the CS group than in the SC and IT groups. A multivariate model showed that hypertension, serum creatinine, E1 lesion, and T1/T2 lesion remained independent predictors of poor renal survival. Conclusions: Immunosuppressive therapy does not have further benefit beyond that provided by steroids. Corticosteroids plus optimal supportive care may further be beneficial in treating early-stage IgAN patients in that it could significantly improve the short-term renal outcome.

Normalized Protein Catabolic Rate Is a Superior Nutritional Marker Associated With Dialysis Adequacy in Continuous Ambulatory Peritoneal Dialysis Patients.

Introduction: Current knowledge of the relationship between normalized protein catabolic rate (nPCR) and dialysis adequacy is limited. Our study aimed to explore the potential relationship between nPCR and dialysis adequacy. Methods: In this cross-sectional study, we analyzed the association of nPCR with peritoneal dialysis adequacy in 266 continuous ambulatory peritoneal dialysis (CAPD) patients (mean age 48.6 ± 13.1 years; 50.8% male). The patients were divided into two groups: a dialysis inadequacy group (total weekly Kt/V urea < 1.70) and a dialysis adequacy group (total weekly Kt/V urea≥1.70). We then analyzed the correlation between dialysis adequacy and the patients' primary cause of end-stage renal disease, nutritional and inflammatory markers, and biochemical parameters. Multivariable logistic regression analysis was also used to identify risk factors for inadequate dialysis. Results: We observed a significantly higher level of nPCR (0.98 ± 0.22 vs. 0.79 ± 0.18 g/kg/day, p < 0.001) in the dialysis adequacy group, whereas we observed no significant differences among other nutritional markers such as albumin, prealbumin, and transferrin. Correlation analyses revealed that dialysis adequacy was positively associated with residual glomerular filtration rate (rGFR), hemoglobin, serum calcium, and body mass index (BMI), while dialysis adequacy was negatively associated with leak-protein, uric acid, high-sensitivity C-reactive protein, interleukin-6, and serum phosphorus. Furthermore, a logistic regression analysis revealed that gender (male), nPCR <0.815 g/kg/day, higher weight, and rGFR <2.43 mL/min/1.73 m2 were independent risk factors for inadequate dialysis. Conclusion: Nutritional status is closely associated with dialysis adequacy. Among common nutritional markers, nPCR may be superior for predicting CAPD dialysis adequacy. Gender (male), nPCR <0.815 g/kg/day, higher weight, and rGFR <2.43 mL/min/1.73 m2 are independent risk factors for dialysis inadequacy in CAPD patients.