Genotype-Phenotype Correlations in Alport Syndrome-A Single-Center Experience.

BACKGROUND: Alport syndrome (AS) is a common and heterogeneous genetic kidney disease, that often leads to end-stage kidney disease (ESKD). METHODS: This is a single-center, retrospective study that included 36 adults with type IV collagen (COL4) mutations. Our main scope was to describe how genetic features influence renal survival. RESULTS: A total of 24 different mutations were identified, of which eight had not been previously described. Mutations affecting each of the type IV collagen α chains were equally prevalent (33.3%). Most of the patients had pathogenic variants (61.1%). Most patients had a family history of kidney disease (71%). The most prevalent clinical picture was nephritic syndrome (64%). One-third of the subjects had extrarenal manifestations, 41.6% of patients had ESKD at referral, and another 8.3% developed ESKD during follow-up. The median renal survival was 42 years (95% CI, 29.98-54.01). The COL4A4 group displayed better renal survival than the COL4A3 group (p = 0.027). Patients with missense variants had higher renal survival (p = 0.023). Hearing loss was associated with lower renal survival (p < 0.001). CONCLUSIONS: Patients with COL4A4 variants and those with missense mutations had significantly better renal survival, whereas those with COL4A3 variants and those with hearing loss had worse prognoses.

Chronological Changes in the Histology of Infection-Related Glomerulonephritis in Renal Allograft: A Case Report.

We report the histological changes over time for a patient with infection-related glomerulonephritis (IRGN) that developed in a transplanted kidney. A 47-year-old man had undergone renal transplantation 3 years ago for end-stage kidney disease (ESKD). After several episodes of acute rejection, the patient was in a stable CKD condition. The abrupt development of severe microscopic hematuria and renal dysfunction was observed approximately 2 weeks after the onset of a phlegmon in his right leg. An allograft biopsy showed prominent glomerular endocapillary proliferation on light microscopy, granular C3 deposition on immunofluorescent microscopy, and subepithelial electron-dense deposits on electron microscopy, suggesting IRGN accompanied by moderate interstitial fibrosis and tubular atrophy (IFTA). Positive glomerular staining for nephritis-associated plasmin receptor (NAPlr) and plasmin activity, which are biomarkers of bacterial IRGN, supported the diagnosis. Although the infection was completely cured with antibiotic therapy, renal dysfunction persisted. A re-biopsy of the allograft 2 months later revealed resolution of the glomerular endocapillary proliferation and negative staining for NAPlr/plasmin activity, with worsening IFTA. We showed, for the first time, the chronological changes in infiltrating cells and histological markers of IRGN in transplanted kidneys. Glomerular changes, including NAPlr/plasmin activity staining, almost disappeared after the cessation of infection, while interstitial changes continuously progressed, contributing to ESKD progression.

The presence of exudative thickening of Bowman's capsule predict poor prognosis in diabetic kidney disease.

BACKGROUND: The relationship between Bowman's capsule thickening and progression of diabetic kidney disease (DKD) remains uncertain. METHODS: Renal biopsy specimens from 145 DKD patients and 20 control subjects were evaluated for Bowman's capsule thickness. Immunohistochemical staining assessed col4α2, laminin ß1, and albumin expression. In a discovery cohort of 111 DKD patients with eGFR ≥ 30 ml/min/1.73 m2, thickening was classified as fibrotic or exudative. The composite endpoint included CKD stage 5, dialysis initiation, and renal disease-related death. Prognosis was analyzed using Kaplan-Meier and Cox regression analyses. Two validation cohorts were included. RESULTS: Three types of thickening were observed: fibrotic, exudative, and periglomerular fibrosis. Parietal epithelial cell matrix protein accumulation contributed to fibrotic thickening, while albumin was present in exudative thickening. Bowman's capsule was significantly thicker in DKD patients (5.74 ± 2.09 µm) compared to controls (3.38 ± 0.43 µm, P < 0.01). In discovery cohort, the group of exudative thickning had a poorer prognosis(median time 20 months vs 57 months, P = 0.000). Cox multivariate analysis revealed that exudative thickening of Bowman's capsule were associated with a poor prognosis. The validation cohorts confirmed the result. CONCLUSIONS: Various mechanisms contribute to Bowman's capsule thickening in DKD. The proportion of exudative thickening may serve as a valuable prognostic indicator for DKD patients.

G Protein Coupled Receptor 87 (GPR87) in End Stage Kidney and Associated Tumors.

BACKGROUND/AIM: End-stage renal disease (ESRD) and acquired cystic renal disease (ACRD) are characterized by progressive inflammation, structural remodeling and by development of unique cancer types. Eosinophilic-vacuolated and chromophobe-like renal cell carcinoma develop exclusively in ACRD kidney. The aim of the study was to investigate the molecular mechanism of ESRD/ACRD carcinogenesis. MATERIALS AND METHODS: Our previous Affymetrix array analysis detected GPR87 as one of the highly and specifically expressed genes in ESRD/ACRD kidneys. In this study we analyzed normal and ESRD/ACRD kidneys and related tumors for GPR87 expression by PCR, RT-PCR, and immunohistochemistry. RESULTS: Immunohistochemistry revealed a strong GPR87 expression in proliferating epithelial cells in ESRD/ACRD kidneys and in cells of eosinophilic-vacuolated and chromophobe-like renal cell carcinoma. CONCLUSION: GPR87 signaling plays an important role in the structural remodeling of ESRD/ACRD kidney and development of ACRD-associated tumors with unique histology.

Utilization of the corticomedullary difference in magnetic resonance imaging-derived apparent diffusion coefficient for noninvasive assessment of chronic kidney disease in type 2 diabetes.

BACKGROUNDS: Accumulating data demonstrated that the cortico-medullary difference in apparent diffusion coefficient (ΔADC) of diffusion-weighted magnetic resonance imaging (DWI) was a better correlation with kidney fibrosis, tubular atrophy progression, and a predictor of kidney function evolution in chronic kidney disease (CKD). OBJECTIVES: We aimed to assess the value of ΔADC in evaluating disease severity, differential diagnosis, and the prognostic risk stratification for patients with type 2 diabetes (T2D) and CKD. METHODS: Total 119 patients with T2D and CKD who underwent renal MRI were prospectively enrolled. Of them, 89 patients had performed kidney biopsy for pathological examination, including 38 patients with biopsy-proven diabetic kidney disease (DKD) and 51 patients with biopsy-proven non-diabetic kidney disease (NDKD) and Mix (DKD + NDKD). Clinicopathological characteristics were compared according to different ΔADC levels. Moreover, univariate and multivariate-linear regression analyses were performed to explore whether ΔADC was independently associated with estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR). The diagnostic performance of ΔADC for discriminating DKD from NDKD + Mix was evaluated by receiver operating characteristic (ROC) analysis. In addition, an individual's 2- or 5-year risk probability of progressing to end-stage kidney disease (ESKD) was calculated by the kidney failure risk equation (KFRE). The effect of ΔADC on prognostic risk stratification was assessed. Additionally, net reclassification improvement (NRI) was used to evaluate the model performance. RESULTS: All enrolled patients had a median ΔADC level of 86 (IQR 28, 155) × 10-6 mm2/s. ΔADC significantly decreased across the increasing staging of CKD (P < 0.001). Moreover, those with pathological-confirmed DKD has a significantly lower level of ΔADC than those with NDKD and Mix (P < 0.001). It showed that ΔADC was independently associated with eGFR (ß = 1.058, 95% CI = [1.002,1.118], P = 0.042) and UACR (ß = -3.862, 95% CI = [-7.360, -0.365], P = 0.031) at multivariate linear regression analyses. Besides, ΔADC achieved an AUC of 0.707 (71% sensitivity and 75% specificity) and AUC of 0.823 (94% sensitivity and 67% specificity) for discriminating DKD from NDKD + Mix and higher ESKD risk categories (≥50% at 5 years; ≥10% at 2 years) from lower risk categories (<50% at 5 years; <10% at 2 years). Accordingly, the optimal cutoff value of ΔADC for higher ESKD risk categories was 66 × 10-6 mm2/s, and the group with the low-cutoff level of ΔADC group was associated with 1.232 -fold (95% CI 1.086, 1.398) likelihood of higher ESKD risk categories as compared to the high-cutoff level of ΔADC group in the fully-adjusted model. Reclassification analyses confirmed that the final adjusted model improved NRI. CONCLUSIONS: ΔADC was strongly associated with eGFR and UACR in patients with T2D and CKD. More importantly, baseline ΔADC was predictive of higher ESKD risk, independently of significant clinical confounding. Specifically, ΔADC <78 × 10-6 mm2/s and <66 × 10-6 mm2/s would help to identify T2D patients with the diagnosis of DKD and higher ESKD risk categories, respectively.

[Long-term auditory monitoring in children with Alport syndrome based on different degrees of renal injury].

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.

Coexistence of nephrogenic systemic fibrosis and calciphylaxis in a gadolinium-naïve, chronic haemodialysis patient.

We present a case of a man in his 40s who was on haemodialysis for over 20 years presenting with rapidly progressive decline in mobility, associated with fixed flexion deformities of joints and peau d'orange appearance of skin together with areas of ulceration that was concerning for calciphylaxis. Skin biopsies were consistent with both nephrogenic systemic fibrosis and calciphylaxis. He has never had exposure to gadolinium-based contrast agent. His treatment included daily dialysis sessions, which were challenging due to vascular access issues and three times weekly sodium thiosulfate. He rapidly declined in hospital and died within 2 weeks of presentation while being treated for a hospital-acquired pneumonia.

Comparison of Clinico-pathologic features and outcomes of ANCA negative and ANCA positive pauci immune crescentic glomerulonephritis: A single centre study.

Introduction: Pauci-immune crescentic glomerulonephritis (PICN) is an important cause of rapidly progressive renal failure. 10-40% of PICN cases have ANCA (antineutrophil cytoplasmic antibody) negative serology. The present study compared clinico-pathologic features, Brix's renal risk score, Berden's histopathological classes and differences in outcome between ANCAnegative vs ANCA positive PICN patients. Materials and Methods: Sixty-one patients of biopsy-proven PICN were studied. Biochemical findings and ANCA serology were recorded. Renal biopsy slides were reviewed along with direct immunofluorescence. Clinical and histological features were compared between ANCA negative and positive PICN using the Man Whitney U test and Chi-square test. Patients were compared for distribution in Berden's histological classes and Brix's renal risk categories. Patient and renal survival were compared using Kaplan-Meier survival analysis. Results: ANCA negative PICN patients were younger (44.9 ± 16.5 years vs 53.6 ± 15.1 years, P = 0.049). Nasal (0 vs 18%, P = 0.035) and pulmonary involvement (9% vs 38%, P = 0.014) were lower in ANCA negative group. Both ANCA groups had similar renal biochemical profiles, percentage normal glomeruli, 16.3 ± 18.2 vs 21.7 ± 20.4 and percentage glomeruli with crescents, 64.5 ± 28.1 vs 64.3 ± 27.1. Twenty-seven per cent of ANCA negative cases fell in the sclerotic class in Berden's classification vs just 2.5% in ANCA positive group (p = 0.037) without significant difference in Brix's renal risk categories (p = 0.329). Thirteen per cent of ANCA negative patients achieved complete remission on treatment compared to 33% in ANCA positive patients. Patient survival and overall probability of progressing to ESRD were similar in the two groups. Conclusion: ANCA negative PICN cases present at younger ages. Nasal and pulmonary involvement is uncommon in these patients. Patient survival and progression to ESRD are similar in both ANCA groups.

Comparison of the effects of peritoneal dialysis and hemodialysis on spontaneous brain activity in CKD patients: an rs-fMRI study.

OBJECTIVE: To compare the effects of peritoneal dialysis and hemodialysis on spontaneous brain activity in patients with end-stage renal disease. METHODS: A total of 52 dialysis patients with end-stage renal disease, including 25 patients with chronic kidney disease undergoing hemodialysis (HD-CKD) and 27 patients with chronic kidney disease undergoing peritoneal dialysis (PD-CKD), and 49 healthy controls (normal control) were included. All participants underwent neuropsychological testing (Mini-Mental State Examination and Montreal cognitive assessment) and resting-state functional magnetic resonance imaging. Fractional amplitude of low frequency fluctuations and Regional Homogeneity algorithms were employed to evaluate spontaneous brain activity. Statistical analysis was performed to discern differences between the groups. RESULTS: When compared with the normal control group, the PD-CKD group exhibited significant alterations in fractional amplitude of low frequency fluctuations in various cerebellum regions and other brain areas, while the HD-CKD group showed decreased fractional amplitude of low frequency fluctuations in the bilateral pericalcarine cortex. The Regional Homogeneity values in the PD-CKD group were notably different than those in the normal control group, particularly in regions such as the bilateral caudate nucleus and the right putamen. CONCLUSION: Both peritoneal dialysis and hemodialysis modalities impact brain activity, but manifest differently in end-stage renal disease patients. Understanding these differences is crucial for optimizing patient care.

Renal transcriptome analysis of uninephrectomized db/db mice identified a mechanism for the transition to severe diabetic nephropathy.

Diabetic nephropathy (DN), included in diabetic kidney disease (DKD), is a primary driver of end-stage renal disease (ESRD) leading to dialysis treatment. To develop new therapeutic drugs to prevent ESRD and avoid dialysis treatment, insight into DKD pathophysiology and animal models suitable for drug efficacy testing are needed. In this study, transcriptome analysis of kidneys from 26-week-old and 35-week-old uninephrectomized (UNX) db/db mice was used to identify the pathways that affect the deterioration of renal function in db/db mice. Differentially expressed genes suggested that there was increased interferon (IFN)-γ signaling during the 26 to 35-week period. Modules that changed between 26 and 35 weeks of age extracted by weighted gene co-expression network analysis (WGCNA) suggested increased the tumor necrosis factor (TNF)-α and nuclear factor-kappa B (NF-κB) signaling pathway in component cells of glomeruli. The protein-protein interaction (PPI) network analysis identified Cxcl16 as a hub gene for those signaling pathways, and it was shown that the pathways in this module changed when the glomerular filtration rate decreased in patients with DN. These results suggested the possibility that signaling mediated by Cxcl16 induced by IFN-γ and TNF-α between 26 and 35 weeks of age leads to renal fibrosis, resulting in severe disease. Drugs that target such pathways can be options for developing drugs for DN. We also think that the uninephrectomized db/db mouse can be used as an animal model of severe DKD and to evaluate efficacy in patients with DN.

External validation of the pediatric International IgA Nephropathy Prediction Tool in a central China cohort.

BACKGROUND: This study aimed to externally validate the pediatric International IgA Nephropathy (IgAN) Prediction Tool updated from the adult IgAN Prediction Tool. METHODS: 439 children with biopsy-confirmed idiopathic IgAN were enrolled in this external validation study. The primary outcome was a 30% decline in eGFR or end-stage kidney disease. We evaluated the discrimination using Harrell's C-index, the receiver operating characteristic (ROC) curve, and Kaplan-Meier curves for four risk groups (< 16th [low risk], ∼16 to < 50th [intermediate risk], ∼50 to < 84th [high risk], and ≥ 84th percentiles [highest risk] of linear predictor). Calibration was assessed using calibration plots. RESULTS: The median follow-up time of the 439 patients was 4.5 (2.7-6.8) years, and 27 patients reached the primary outcome. Compared with the reported cohorts, our cohort was more contemporary, with milder proteinuria at biopsy, and had lower proportions of S1 and T1 lesions. Harrell's C-index and area under the ROC curve at 5 years were < 0.7 for both the models with and without race. The Kaplan-Meier curves of the risk groups were not well separated for the two models, only separated completely between the highest-risk group and the others for the model without race. The two models generally overestimated the risk of the primary outcome, CONCLUSION: The model without race could accurately distinguish the highest-risk patients from patients with low, intermediate, and high risk for kidney progression. Discrimination and calibration for the full model with or without race were unsatisfactory in this contemporary cohort in central China.

Long-term auditory monitoring in children with Alport syndrome based on different degrees of renal injury / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.

Effects of salt supplementation in uninephrectomized KK-Ay mice: Examining the potential of a diabetic kidney disease model.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD). Although current therapeutic strategies for DKD, including sodium-glucose cotransporter-2 inhibitors and mineralocorticoid receptor antagonists, have shown some degree of efficacy, they have failed to completely halt the progression of DKD to ESRD owing to the complexity of DKD pathogenesis. Elucidating the pathophysiological mechanism of DKD is essential for the development of novel therapeutic strategies. In this study, we investigated the pathophysiological characteristics of uninephrectomized (UNx) KK-Ay mice and examined the effects of salt supplementation on the acceleration of renal injury in these mice. UNx KK-Ay mice exhibited pathophysiological renal abnormalities with glomerular and tubulointerstitial fibrosis. Additionally, salt supplementation exacerbated renal injury, particularly tubular injury. These results suggest that UNx KK-Ay mice are useful models for advanced DKD and that salt exacerbates tubular damage in DKD.

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.

Pharmacokinetic-pharmacodynamic modeling of the active components of Shenkang injection in rats with chronic renal failure and its protective effect on damaged renal cells.

The study aimed to explore the pharmacokinetic and pharmacodynamic alterations of the active components of Shenkang injection (i.e. hydroxy saffron yellow pigment A [HSYA], tanshinol, rheum emodin, and astragaloside IV) in rats with chronic renal failure (CRF), and establish a pharmacokinetic-pharmacodynamic model (PK-PD model) in order to provide a scientific and theoretical basis for the rational clinical use of Shenkang injection. Sprague-Dawley (SD) rats were randomly divided into a normal group, model group, and Shenkang injection group. A rat model of CRF was induced by adenine gavage and then followed by drug administration via tail vein injection. Orbital blood was collected at different timepoints and the blood concentrations of the four active components were measured by UHPLC-Q-Orbitrap HRMS. Serum levels of creatinine (Scr), urea nitrogen (BUN), and uric acid (UA) were determined using an automatic biochemical analyzer. A PK-PD model was established, and DAS 3.2.6 software was used for model fitting as well as statistical analysis. TGF-ß1 was utilized to induce normal rat kidney cells to construct a renal fibrosis model to investigate the protective effect of the pharmacological components on renal fibrosis. The pharmacokinetic analysis of hydroxy saffron yellow pigment A, tanshinol, rheum emodin, and astragaloside IV based on UHPLC-Q-Orbitrap HRMS was stable. The linear regression equations for the four active components were as follows: Y = 0.031X + 0.0091 (R2  = 0.9986) for hydroxy saffron yellow pigment A, Y = 0.0389X + 0.164 (R2  = 0.9979) for tanshinol, Y = 0.0257X + 0.0146 (R2  = 0.9973) for rheum emodin, and Y = 0.0763X + 0.0139 (R2  = 0.9993) for astragaloside IV, which indicated good linear relationships. The methodological investigation was stable, with the interday and intraday precision RSD <10%. Meanwhile, the recoveries ranged between 90% and 120%, in accordance with the requirements for in vivo analysis of drugs. Compared with the model group, the levels of Scr, BUN, and UA were significantly decreased after 20 min in the Shenkang injection group (p < 0.01). The PK-PD model showed that the four active components in the Shenkang injection group could fit well with the three effect measures (i.e. Scr, BUN, and UA), with the measured values similar to the predicted values. The cell model of renal fibrosis showed that the connective tissue growth factor and FN1 protein expression levels were significantly lower in the Shenkang injection group than those in the model group, and the cell fibrosis was improved. The established method for in vivo analysis of Shenkang injection was highly specific, with good separation of the components and simple operation. The total statistical moment could well integrate the pharmacokinetic parameters of the four active components. After treatment with Shenkang injection, all indexes in the administered group improved and showed significant inhibition of renal cell fibrosis in vitro. This study could provide scientific reference ideas for the clinical rational use of traditional Chinese medicine.

Validation of a renal risk score in a cohort of children with ANCA-associated glomerulonephritis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is extremely rare in children. Renal involvement is a common and severe complication of AAV as it can cause end stage kidney disease (ESKD). ANCA renal risk score (ARRS) is helpful in predicting long-term ESKD in patients with ANCA-associated glomerulonephritis (AAGN). This retrospective study included 61 consecutive patients with kidney biopsy specimen-proven AAGN from Clinical Center for Children's Kidney Disease in China. Each patient was assessed by eGFR, normal glomeruli, and tubular atrophy/interstitial fibrosis, and the renal outcome was evaluated using the ARRS. Based on the ARRS, 27 (44.26%), 21 (34.43%), and 13 (21.31%) patients were divided into the low-risk, medium-risk, and high-risk groups, respectively. The median follow-up period was 46.36 (14.58-95.62) months. The high-risk group had worse renal outcomes than the low-risk group (p< 0.05) and the medium-risk group (p < 0.05). COX multivariate regression analysis showed that eGFR ≤ 15 ml/min/1.73 m2 (p = 0.015, Hazard Ratio (HR) = 9.574, 95% CI 4.205-25.187) and ARRS (p = 0.012, HR = 2.115, 95% CI 1.206-4.174) were independent risk factors for ESKD.The area under the curve for ESKD prediction of ARRS was 0.880, and the best cutoff value was 5.50. Delong test result showed that ARRS exhibited better predictive value for ESKD than the Berden classification (p < 0.001) and rapidly progressive glomerulonephritis (p < 0.001). This is the first study to investigate the value of the ARRS for predicting renal prognosis among Chinese children. The ARRS is a preferred index that can predict ESKD in Chinese children with AAGN.

Altered resting-state cerebellar-cerebral functional connectivity in patients with end-stage renal disease.

BACKGROUND: End-stage renal disease (ESRD) patients have functional and structural brain abnormalities. The cerebellum also showed varying degrees of damage. However, no studies on cerebellar-cerebral functional connectivity (FC) have been conducted in ESRD patients. This study aimed to investigate the changes in cerebellar-cerebral FC in ESRD patients and its relationship with neuropsychological and clinical indexes. METHODS: Resting-state functional magnetic resonance imaging and neuropsychological assessment were performed on 37 ESRD patients and 35 control subjects. Seed-based FC analysis was performed to investigate inter-group differences in cerebellar-cerebral FC. In addition, the relations of altered FC with the neuropsychological function and clinical indicators were analyzed in ERSD patients. RESULTS: ESRD patients exhibited alterations in cerebellar-cerebral FC involving the executive control network, default mode network, and affective-limbic network compared to control subjects (False discovery rate-corrected, p < 0.05). The altered cerebellar-cerebral FC was associated with the Montreal Cognitive Assessment Scale score (p < 0.05), and correlated with serum creatinine and uric acid levels within the ESRD group (p < 0.05). CONCLUSIONS: The study indicates that cerebellar-cerebral FC is involved in the neural substrates of cognitive impairment in ESRD patients. The findings may provide clinically relevant new neuroimaging biomarkers for the neuropathological mechanisms underlying cognitive impairment of ESRD.

Disrupted network communication predicts mild cognitive impairment in end-stage renal disease: an individualized machine learning study based on resting-state fMRI.

End-Stage Renal Disease (ESRD) is known to be associated with a range of brain injuries, including cognitive decline. The purpose of this study is to investigate the functional connectivity (FC) of the resting-state networks (RSNs) through resting state functional magnetic resonance imaging (MRI), in order to gain insight into the neuropathological mechanism of ESRD. A total of 48 ESRD patients and 49 healthy controls underwent resting-state functional MRI and neuropsychological tests, for which Independent Components Analysis and graph-theory (GT) analysis were utilized. With the machine learning results, we examined the connections between RSNs abnormalities and neuropsychological test scores. Combining intra/inter network FC differences and GT results, ESRD was optimally distinguished in the testing dataset, with a balanced accuracy of 0.917 and area under curve (AUC) of 0.942. Shapley additive explanations results revealed that the increased functional network connectivity between DMN and left frontoparietal network (LFPN) was the most critical predictor for ESRD associated mild cognitive impairment diagnosis. Moreover, hypoSN (salience network) was positively correlated with Attention scores, while hyperLFPN was negatively correlated with Execution scores, indicating correlations between functional disruption and cognitive impairment measurements in ESRD patients. This study demonstrated that both the loss of FC within the SN and compensatory FC within the lateral frontoparietal network coexist in ESRD. This provides a network basis for understanding the individual brain circuits and offers additional noninvasive evidence to comprehend the brain networks in ESRD.

Rodent models to study type 1 and type 2 diabetes induced human diabetic nephropathy.

INTRODUCTION: Diabetic nephropathy (DN), an outcome of prolonged diabetes, has affected millions of people worldwide and every year the incidence and prevalence increase substantially. The symptoms may start with mild manifestations of the disease such as increased albuminuria, serum creatinine levels, thickening of glomerular basement membrane, expansion of mesangial matrix to severe pathological symptoms such as glomerular lesions and tubulointerstitial fibrosis which may further proceed to cardiovascular dysfunction or end-stage renal disease. PERSPECTIVE: Numerous therapeutic interventions are being explored for the management of DN, however, these interventions do not completely halt the progression of this disease and hence animal models are being explored to identify critical genetic and molecular parameters which could help in tackling the disease. Rodent models which mostly include mice and rats are commonly used experimental animals which provide a wide range of advantages in understanding the onset and progression of disease in humans and also their response to a wide range of interventions helps in the development of effective therapeutics. Rodent models of type 1 and type 2 diabetes induced DN have been developed utilizing different platforms and interventions during the last few decades some of which mimic various stages of diabetes ranging from early to later stages. However, a rodent model which replicates all the features of human DN is still lacking. This review tries to evaluate the rodent models that are currently available and understand their features and limitations which may help in further development of more robust models of human DN. CONCLUSION: Using these rodent models can help to understand different aspects of human DN although further research is required to develop more robust models utilizing diverse genetic platforms which may, in turn, assist in developing effective interventions to target the disease at different levels.