Personalized decision support system for tailoring IgA nephropathy treatment strategies.

BACKGROUND: The ongoing debate surrounding the use of immunosuppressive treatments for IgA nephropathy (IgAN) underscores the demand for personalized and effective strategies. METHODS: Analyzed data from 807 IgAN patients over 5+ years using three methods: Random Forest with molecular biomarkers, network biomarkers with graph engineering, and an auto-encoder model. All models were trained using identical demographic, clinical, and pathological data, employing an 80-20 split for training and testing purposes. RESULTS: In the comprehensive assessment of IgAN prognosis, the Random Forest model, employing molecular biomarkers, demonstrated strong performance metrics (AUC = 0.83, sensitivity = 0.51, specificity = 0.96). However, traditional graph feature engineering on patient-specific networks outperformed these results with an AUC of 0.90, sensitivity of 0.64, and specificity of 0.94. The Auto-encoder model showed the best accuracy (AUC = 0.91, sensitivity = 0.46, specificity = 0.96). The findings highlighted the superior predictive capabilities of network biomarkers over molecular biomarkers for adverse renal outcome prediction in IgAN. Consequently, we integrated Auto-encoder-derived Network Biomarkers with Random Forest Models to enhance prognostic precision in diverse IgAN treatment scenarios. The prediction for the prognosis of patients receiving supportive care, glucocorticoid therapy, and immunosuppressant treatment yielded AUC values of 0.95, 0.96, and 1, respectively, indicating high specificity. Drawing from these insights, we pioneered the development of an innovative decision support model for IgAN treatment. This model demonstrated the ability to make medical decisions comparable to those by experienced nephrologists, enabling the customization of personalized disease management strategies. CONCLUSION: Our system accurately predicted IgAN prognosis and evaluated various treatment efficacies, aiding physicians in devising optimal therapeutic strategies for patients.

Molecular basis of threonine ADP-ribosylation of ubiquitin by bacterial ARTs.

Ubiquitination plays essential roles in eukaryotic cellular processes. The effector protein CteC from Chromobacterium violaceum blocks host ubiquitination by mono-ADP-ribosylation of ubiquitin (Ub) at residue T66. However, the structural basis for this modification is unknown. Here we report three crystal structures of CteC in complexes with Ub, NAD+ or ADP-ribosylated Ub, which represent different catalytic states of CteC in the modification. CteC adopts a special 'D-E' catalytic motif for catalysis and binds NAD+ in a half-ligand binding mode. The specific recognition of Ub by CteC is determined by a relatively separate Ub-targeting domain and a long loop L6, not the classic ADP-ribosylating turn-turn loop. Structural analyses with biochemical results reveal that CteC represents a large family of poly (ADP-ribose) polymerase (PARP)-like ADP-ribosyltransferases, which harbors chimeric features from the R-S-E and H-Y-E classes of ADP-ribosyltransferases. The family of CteC-like ADP-ribosyltransferases has a common 'D-E' catalytic consensus and exists extensively in bacteria and eukaryotic microorganisms.

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.

Altered serum metabolic profile in patients with IgA nephropathy.

BACKGROUND: We investigated alterations in the serum metabolomic profile of IgA nephropathy (IgAN) patients and screen biomarkers of IgA nephropathy based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). METHODS: Serum samples from 65 IgAN patients and 31 healthy controls were analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Univariate and multivariate analysis were performed to screen the differential metabolites. Differential metabolites should meet both the following two criteria: adjusted P < 0.05 in the univariate analysis and VIP value > 1 in the multivariate model. Pathway analysis was performed to reveal the metabolic pathways that were significantly influenced in IgAN. Spearman correlation analysis was applied to explore the correlation between metabolites and between the metabolites and clinicopathological features of IgAN. A random forest model and Logistics regression analysis were conducted to evaluate the predictive ability of the metabolites. RESULTS: The metabolic profile was significantly altered in IgAN patients compared with healthy controls. Thirty-nine metabolites were identified, including glycerophospholipids, sphingolipids, vitamin K1, vitamin K2, bile acids and amino acids. Sphingolipid metabolism, ubiquinone and other terpenoid-quinone biosynthesis, and glycerophospholipid metabolism were found to be significantly disturbed in the pathway analysis. Differential metabolites were found to be associated with the clinical and pathological features of IgAN patients. Lanosterol, vitamin K1, vitamin K2, and ß-elemonic acid were found to have promising predictive ability for IgAN. CONCLUSIONS: We confirmed the differences in the metabolic profiles of IgAN patients and healthy controls and identified the differential metabolites of IgAN, which may help with the further exploration of the pathogenesis and treatment of IgAN.

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.

Association between the triglyceride-glucose index and chronic kidney disease in adults.

BACKGROUND: Chronic kidney disease (CKD) is characterized as a progressive dysfunction of the kidney, and it might have a close relationship with insulin resistance. We utilized the triglyceride-glucose (TyG) index, a reliable marker of insulin resistance, to evaluate the association between the TyG index and CKD in adults from the general population. METHODS: This was a cross-sectional study obtaining data from the 2015-2018 National Health and Nutrition Examination Survey. The estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) served as kidney function indicators. We defined CKD as the existence of either low eGFR (eGFR < 60 mL/min/1.73 m2 BSA) or albuminuria (UACR > 30 mg/g). Multivariate regressions, correlated subgroup analyses, and interaction terms were performed in this study. RESULTS: For 4361 recruited participants, the mean TyG index was 8.60 ± 0.68, and the prevalence of CKD was 13.35%. Participants with a higher TyG index showed a higher UACR level (ß = 25.10, 95% CI: 6.76, 43.44, P = 0.0074) and higher levels of CKD (OR = 1.34, 95% CI: 1.13, 1.59, P = 0.0006). The positive relationship between the TyG index and CKD became stronger and remained significant in the overweight (OR = 1.61, 95% CI: 1.18, 2.20, P = 0.0027) and obese (OR = 2.48, 95% CI: 1.95, 3.15, P < 0.0001) groups and in people with diabetes (OR = 1.94, 95% CI: 1.46, 2.56, P < 0.0001). CONCLUSIONS: Higher TyG index was strongly associated with a higher UACR level and higher values of albuminuria and CKD, which might be useful in kidney function screening especially among people in disadvantageous socioeconomic conditions with no availability for direct measurement of kidney function. However, more well-designed studies are still needed to validate this relationship.

Machine Learned Texture Prior From Full-Dose CT Database via Multi-Modality Feature Selection for Bayesian Reconstruction of Low-Dose CT.

In our earlier study, we proposed a regional Markov random field type tissue-specific texture prior from previous full-dose computed tomography (FdCT) scan for current low-dose CT (LdCT) imaging, which showed clinical benefits through task-based evaluation. Nevertheless, two assumptions were made for early study. One assumption is that the center pixel has a linear relationship with its nearby neighbors and the other is previous FdCT scans of the same subject are available. To eliminate the two assumptions, we proposed a database assisted end-to-end LdCT reconstruction framework which includes a deep learning texture prior model and a multi-modality feature based candidate selection model. A convolutional neural network-based texture prior is proposed to eliminate the linear relationship assumption. And for scenarios in which the concerned subject has no previous FdCT scans, we propose to select one proper prior candidate from the FdCT database using multi-modality features. Features from three modalities are used including the subjects' physiological factors, the CT scan protocol, and a novel feature named Lung Mark which is deliberately proposed to reflect the z-axial property of human anatomy. Moreover, a majority vote strategy is designed to overcome the noise effect from LdCT scans. Experimental results showed the effectiveness of Lung Mark. The selection model has accuracy of 84% testing on 1,470 images from 49 subjects. The learned texture prior from FdCT database provided reconstruction comparable to the subjects having corresponding FdCT. This study demonstrated the feasibility of bringing clinically relevant textures from available FdCT database to perform Bayesian reconstruction of any current LdCT scan.

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.

Emerging trends and focus for the link between the gastrointestinal microbiome and kidney disease.

The clinical value of the relationship between gastrointestinal microbiome imbalance and its corresponding interventions with kidney disease is emerging. This study describes the hotspots and evolution of gastrointestinal microbiome and kidney disease research over the past three decades by scientific collaboration networks and finally predicts future trends in the field through bibliometric analysis and visualization studies. CiteSpace was used to explore the original articles from January 1990 to August 2021 to visualize the knowledge network of journals, countries, institutions, authors, references, and keywords in this field. Publications were extracted from Web of Science Core Collection database using the terms "gastrointestinal microbiome" and "kidney disease" (and their synonyms in MeSH). A total of 2145 publications with 93880 references in 102 journals were included in the analyses. The number of studies combining gastrointestinal microbiomes with kidney diseases has increased significantly over the past two decades. The United States is the leading country in the number of documents, and the leading institution is the Cleveland Clinic. The most landmark articles in the field are on chronic renal failure, L-Carnitin, and cardiovascular disease. The pathogenesis of uremia toxin is an emerging trend in gastrointestinal microbiomes and kidney diseases. In addition, probiotic or synbiotic supplements have strong clinical value in adjusting abnormal intestinal symbiotic environments. This study demonstrates a growing understanding of the interaction between gut microbiota and kidney disease over time. Using microbial supplements to improve the living conditions of kidney disease patients is a promising and hot research focus. Based on publications extracted from the database, this study may provide clinicians and researchers with valuable information to identify potential collaborators and partner institutions and better predict their dynamic progression.

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.

Effectiveness of Microecological Preparations for Improving Renal Function and Metabolic Profiles in Patients With Chronic Kidney Disease.

Background: Determining whether microecological preparations, including probiotics, prebiotics, and synbiotics, are beneficial for patients with chronic kidney disease (CKD) has been debated. Moreover, determining which preparation has the best effect remains unclear. In this study, we performed a network meta-analysis of randomized clinical trials (RCTs) to address these questions. Methods: MEDLINE, EMBASE, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials were searched. Eligible RCTs with patients with CKD who received intervention measures involving probiotics, prebiotics, and/or synbiotics were included. The outcome indicators included changes in renal function, lipid profiles, inflammatory factors, and oxidative stress factors. Results: Twenty-eight RCTs with 1,373 patients were ultimately included. Probiotics showed greater effect in lowering serum creatinine [mean difference (MD) -0.21, 95% confidence interval (CI) -0.34, -0.09] and triglycerides (MD -9.98, 95% CI -19.47, -0.49) than the placebo, with the largest surface area under the cumulative ranking curve, while prebiotics and synbiotics showed no advantages. Probiotics were also able to reduce malondialdehyde (MDA) (MD -0.54, 95% CI -0.96, -0.13) and increase glutathione (MD 72.86, 95% CI 25.44, 120.29). Prebiotics showed greater efficacy in decreasing high-sensitivity C-reactive protein (MD -2.06, 95% CI -3.79, -0.32) and tumor necrosis factor-α (MD -2.65, 95% CI -3.91, -1.39). Synbiotics showed a partially synergistic function in reducing MDA (MD -0.66, 95% CI -1.23, -0.09) and high-sensitivity C-reactive protein (MD -2.01, 95% CI -3.87, -0.16) and increasing total antioxidant capacity (MD 145.20, 95% CI 9.32, 281.08). Conclusion: The results indicated that microbial supplements improved renal function and lipid profiles and favorably affected measures of oxidative stress and inflammation in patients with CKD. After thorough consideration, probiotics provide the most comprehensive and beneficial effects for patients with CKD and might be used as the best choice for microecological preparations. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022295497, PROSPERO 2022, identifier: CRD42022295497.

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.

Efficacy and safety of potassium binders in the treatment of patients with chronic kidney disease and hyperkalemia.

BACKGROUND: Gastrointestinal cation exchangers that can bind potassium in the gut, including sodium polystyrene sulfonate (SPS), calcium polystyrene sulfonate (CPS), patiromer and sodium zirconium cyclosilicate (SZC), are emerging medications for the treatment of hyperkalemia with chronic kidney disease (CKD). However, which might be the best alternative for patients with chronic kidney disease and hyperkalemia remains disputed. METHODS: We performed this systematic review and network meta-analysis with the Bayesian approach to conduct direct and indirect comparisons among potassium binders regarding their efficacy and safety. The surface under the cumulative ranking curve analysis (SUCRA) was used to calculate the best intervention for each outcome. RESULTS: All four potassium binders had a promising effect regarding potassium reduction. SPS had favorable efficacy and safety for short-term use (MD: -0.94; 95% CIs: -1.4 to -0.48; SUCRA = 94.69%), but long-term treatment required strict dose control and assessment of gastrointestinal conditions. CPS had a positive effect on reducing potassium, and could especially maintain the serum potassium concentration in patients receiving renin-angiotensin-aldosterone system inhibitors (RAASi). Patiromer might reduce all-cause mortality in CKD patients with hyperkalemia and have a positive effect on potassium-lowering, though it had significant gastrointestinal adverse effects. SZC had a potassium-lowering effect in both the short-term and long-term, and can be a promising long-term treatment for the hyperkalemia in CKD patients, especially in combination with RAASi. CONCLUSION: These four potassium binders had their own advantages and disadvantages, and the medication should be selected according to the clinical situation of the patient.

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.

Case Report: Adolescent-Onset Isolated Nephronophthisis Caused by a Novel Homozygous Inversin Mutation.

Objective: Nephronophthisis (NPHP) is a rare autosomal recessive inherited kidney disease that can cause cystic enlargement of the kidneys, and lead to end-stage renal disease (ESRD) before the age of 30 years. Herein we describe a case of adolescent-onset NPHP with a novel homozygous mutation in the inversin gene (INVS). Methods: The patient was a 15-year-old Chinese boy who presented with ESRD. Genetic testing was performed via whole exome sequencing and validated via Sanger sequencing. A novel homozygous INVS mutation was identified (c. 1909C > T; p. Gln637Ter). Results: The results of laboratory examinations included urinary protein 1.05 g/24 h, urine erythrocyte count 5/high-power field, serum creatinine 1,026.2 µmol/L, and estimated glomerular filtration rate 5.8 ml/min/1.73 mm2. Extrarenal features included hypertension and moderate anemia, and his parents were consanguineous (first cousins). A homozygous 1-bp substitution resulting in a nonsense mutation (c. 1909C > T; p. Gln637Ter) in exon 15 of INVS was detected via whole exome sequencing, and validated via Sanger sequencing. According to the classification system of the American College of Medical Genetics and Genomics, the mutated gene in INVS is strongly pathogenic (PVS1+PM2+PP3+PP5). His parents and a younger brother were heterozygous carriers. Based on the above results he was diagnosed with juvenile type 2 NPHP. He underwent hemodialysis, and received a kidney transplant after 2 months. He is currently recovering well, with a serum creatinine level of 117 µmol/L and an estimated glomerular filtration rate of 79.6 ml/min/1.73 mm2. Conclusion: Here we have described an extremely rare case of adolescent-onset type 2 NPHP caused by a homozygous INVS mutation. The patient had progressed to ESRD by the age of 15 years. The current report will deepen our understanding of the clinical and genetic basis of this disease.

Clinicopathological characteristics and risk factors in elderly patients with biopsy-proven IgA nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) has been well studied among young people, but few data on clinicopathological characteristics, treatment response and outcomes for elderly IgAN patients are available. METHODS: A cohort study of elderly IgAN patients was performed. The combined endpoints of renal outcome were a 50% decline in eGFR compared with the time of renal biopsy, end-stage kidney disease and/or death. Risk factors associated with poor renal outcomes were then determined. The benefits of immunosuppressant therapies were also evaluated by Kaplan-Meier survival curve analysis. RESULTS: This study ultimately included 126 elderly patients with IgAN. Comparison between the endpoint and non-endpoint groups indicated that patients with poor outcomes had more severe clinical features, such as worse kidney function, severe hematuria and lower albumin levels. Cox regression analysis indicated that age (HR 1.15, 95% CI 1.02-1.29, p = 0.021), male gender (HR 9.71, 95% CI 1.00-97.56, p = 0.050), and urine red blood cells (HR 1.003, 95% CI 1.000-1.006, p = 0.029) were independent risk factors for poor renal outcome in elderly IgAN patients. To explore possible reasons accounting for the predictive value of age and sex, patients were divided into two groups based on these two variables. Patients in the geriatric group had lower serum albumin, estimated glomerular filtration rate, hemoglobin and aspartate aminotransferase levels than those in the quinquagenarian group. Male patients tended to have higher hemoglobin, higher alanine aminotransferase, and lower triglycerides and cholesterol levels than female patients. To investigate different treatment responses, patients were classified into two groups depending on treatment strategies (renin-angiotensin system inhibitors and immunosuppressive therapy), and the survival analysis indicated no significant difference in kidney outcome between the two groups (p > 0.05). This result still holds after adjusting for age, sex, eGFR, hematuria, and proteinuria. CONCLUSION: Advanced age, male, and hematuria might be independently associated with poor kidney outcomes in elderly patients with IgAN. Immunosuppressive therapy might confer no overall benefit to older IgAN patients.

A Proinflammatory Diet May Increase Mortality Risk in Patients with Diabetes Mellitus.

This was an observational study based on the National Health and Nutrition Examination Survey (NHANES) and National Death Index (NDI) 2009-2014 which aimed to validate whether a proinflammatory diet may increase mortality risk in patients with diabetes mellitus. Dietary inflammatory potential was assessed by dietary inflammatory index (DII) based on 24 h dietary recall. Mortality follow-up information was accessed from NDI, which was then merged with NHANES data following the National Center for Health Statistics (NCHS) protocols. For 15,291 participants from the general population, the average DII was 0.37 ± 1.76 and the prevalence rate of diabetes was 13.26%. DII was positively associated with fasting glucose (ß = 0.83, 95% CI: 0.30, 1.36, p = 0.0022), glycohemoglobin (ß = 0.02, 95% CI: 0.01, 0.03, p = 0.0009), and the risk of diabetes (OR = 1.05, 95% CI: 1.01, 1.09, p = 0.0139). For 1904 participants with diabetes and a median follow-up of 45 person-months, a total of 178 participants with diabetes died from all causes (mortality rate = 9.34%). People with diabetes who adhered to a proinflammatory diet showed a higher risk of all-cause mortality (HR = 1.71, 95%CI: 1.13, 2.58, p = 0.0108). In summary, DII was positively associated with diabetes prevalence and a proinflammatory diet may increase mortality risk in patients with diabetes mellitus.