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.

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.

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.

[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.

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.

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.

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.

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.

Long-term survival and renal outcomes of thrombotic microangiopathy in pregnancy: A retrospective cohort study.

OBJECTIVE: Thrombotic microangiopathy (TMA) in pregnancy can rapidly progress, leading to severe morbidities. This study aimed to compare baseline demographics and clinical outcomes between pregnant women with and without TMA. METHODS: Using the National Health Insurance Research Database, 207 patients with pregnancy-related TMA from January 1, 2006 to December 31, 2015 were enrolled. Their data were compared with a 1:4 propensity score-matched cohort of 828 pregnant women without TMA to evaluate mortality and end-stage renal disease (ESRD) risks. Cox proportional hazards models were used to estimate the adjusted hazard ratio and 95% confidence intervals. RESULTS: A total of 1035 participants were included. The risks of mortality and ESRD were 4.46 and 5.97 times higher for the TMA cohort, respectively. Subgroup analysis revealed higher mortality and ESRD risks in patients with TMA aged >40 years with a history of hypertension, stroke, cancer, concomitant stroke, malignant hypertension, or gastroenterocolitis than in the matched cohort. CONCLUSION: Pregnant patients with TMA, especially those older and with comorbidities and organ involvement, faced increased mortality and ESRD risks. Physicians should collaborate with obstetricians throughout the prenatal and postpartum periods for these patients.

One-Step Robot-Assisted Complete Urinary Tract Extirpation in Man with End-Stage Renal Disease on Dialysis: The First Case Report.

Urothelial carcinoma (UC) could be observed in urinary bladder (UBUC) and upper urinary tracts (UTUC). In the National Comprehensive Cancer Network guidelines for bladder cancer, extirpative surgery is indicated in certain cases. However, some extreme cases might also need the extirpation of the majority of the urinary tract, which is called complete urinary tract extirpation (CUTE). We present a patient diagnosed with high-grade UBUC and UTUC. He underwent dialysis for end-stage renal disease (ESRD) at the same time. Considering his non-functional kidneys and removing his high-risk urothelium at the same time, we performed robot-assisted CUTE to extirpate both his upper urinary tracts, urinary bladder, and prostate. In our experience, the console time was not significantly elongated, and the perioperative course was uneventful. To our knowledge, this is the first case report adopting a robotic system in such an extreme case. We conclude that robot-assisted CUTE is worth further study regarding its oncological survival outcomes and perioperative safety in patients with ESRD on dialysis.

Predictors of long-term outcomes in pediatric focal segmental glomerulosclerosis.

BACKGROUND: Available data on primary focal segmental glomerulosclerosis (FSGS) in children usually report on short follow-up and small samples. Furthermore, the application of the Columbia classification for FSGS in children has not yet been fully agreed. We aimed to confirm the prognosis and risk factors of FSGS in a large cohort of Chinese children. METHODS: Two hundred seventy-four children with primary FSGS from a single center were enrolled from 2003 to 2018. Long-term renal survival and related risk factors were evaluated by the Kaplan-Meier method and Cox multivariate regression analysis. Receiver operating characteristic (ROC) curve analysis further tested the effect of various risk factors in predicting renal outcomes. The composite end-point included ≥ 50% reduction in estimated glomerular filtration rate and/or end-stage renal disease or death. RESULTS: One hundred twenty-five children were diagnosed with not otherwise specified (NOS) (45.6%) variant; 79 with tip lesions (28.8%), 32 with collapsing (11.7%), 31 with cellular (11.3%), and 7 with perihilar lesions (2.6%). The renal survival rate was 80.73% at 5 years, 62.58% at 10 years and 34.66% at 15 years. Multivariate analysis showed that chronic tubulointerstitial damage ≥ 25% (HR 4.14, 95% CI 1.49-11.50, P < 0.01), collapsing variant [(reference: NOS) HR 2.16, 95% CI 1.10-4.27, P = 0.03], segmental sclerosis (HR 1.03, 95% CI 1.01-1.04, P < 0.01) and age at biopsy (HR 0.91, 95% CI 0.85-0.98, P = 0.01) were significantly associated with renal outcomes. ROC curve analysis showed an excellent diagnostic yield of the Columbia classification. The combination of Columbia classification, CTI ≥ 25% and segmental sclerosis had the best predictive value for renal outcomes (AUC = 0.867, sensitivity = 77.78%, specificity = 82.27%, P < 0.01). CONCLUSIONS: This study reports a renal survival rate of Chinese children with FSGS of 62.58% at 10 years and 34.66% at 15 years. Prognosis is poorer in patients with collapsing variant or CTI ≥ 25% and good in patients with tip variant. The Columbia classification is confirmed as a valuable tool for predicting prognosis of Chinese children with FSGS.

Palm-Plant Pain, Sign of a Severe Systemic Disease? Case Report and Review of Literature.

Fabry disease is an X-linked lysosomal storage disease, second in prevalence after Gaucher disease. The onset of symptoms occurs in childhood or adolescence with palmo-plantar burning pains, hypo hidrosis, angiokeratomas, and corneal deposits. In the absence of diagnosis and treatment, the disease will progress to the late phase, characterized by progressive cardiac, cerebral and renal damage, and possible death. We present the case of an 11-year-old male boy who was transferred to the Pediatric Nephrology Department for palmo-plantar burning pain and end stage renal disease. Following the evaluations for the etiology of end stage renal disease we excluded the vasculitis, the neurologic diseases, extrapulmonary tuberculosis. Because of suggestive aspect at CT scan and lack of etiologic diagnosis of renal insufficiency we performed lymph node and kidney biopsy, with a surprising result for storage disease. The specific investigation confirmed the diagnosis.

Predicting kidney outcomes among Latin American patients with lupus nephritis: The prognostic value of interstitial fibrosis and tubular atrophy and tubulointerstitial inflammation.

OBJECTIVE: To assess the effect of tubulointerstitial inflammation (TII) and interstitial fibrosis and tubular atrophy (IFTA) on kidney survival in lupus nephritis (LN). METHODS: Two hundred eighty five patients with biopsy-proven LN were retrospectively studied. Kidney survival was defined as the time from initial biopsy to end-stage kidney disease (ESKD), dialysis, or transplant. Kidney survival analysis was performed by the Kaplan-Meier method and the statistical difference between survival curves compared by the log-rank test. Cumulative incidence functions with competing risk of death for kidney survival were also graphed. Multivariable Cox proportional hazards regression and competing-risk analyses were performed to identify independent predictors of ESKD. RESULTS: Fifty-seven patients (20%) progressed to ESKD during a median time of 4.2 (2.0-55.2) months after biopsy. TII was present in 206 (72.3%) biopsies, while IFTA in 99 (34.7%) biopsies. Patients with moderate-to-severe IFTA had worse kidney survival than those with none or mild IFTA in both the Kaplan-Meier (p = 0.018) and the competing-risk analyses (p = 0.017). Patients with class IV ± V LN had worse kidney survival than those with non-class IV LN by the Kaplan-Meier method (p = 0.050), but not in the competing-risk analysis (p = 0.154). Worse kidney survival was also found among those with fibrous crescents than those without, in both the Kaplan-Meier (p = 0.010) and the competing-risk (p = 0.011) analyses. By multivariable Cox regression analysis, older age (HR 1.04, 95% CI 1.01-1.07) and class IV ± V LN (HR 5.06, 95% CI 1.82-14.09) were associated with higher risk of ESKD after adjusting for sex, ethnicity, TII, and IFTA. By competing-risk analyses, class IV ± V LN (SHR 3.32, 95% CI 1.25-8.83) and no response to immunosuppressive therapy (SHR 4.55, 95% CI 1.54-13.41) were associated with a higher risk of ESKD, while eGFR >90 mL/min/1.73 m2 (SHR 0.98 for each ml/min/1.73 m2, 95% 0.97-0.99) with a lower risk. CONCLUSIONS: Patients with moderate-to-severe IFTA had worse kidney survival than those with none or mild IFTA. Worse kidney survival was also found among those with class IV LN and fibrous crescents versus those without IV LN and fibrous crescents, respectively.

Modeling Low Muscle Mass Screening in Hemodialysis Patients.

INTRODUCTION: Computed tomography (CT) can accurately measure muscle mass, which is necessary for diagnosing sarcopenia, even in dialysis patients. However, CT-based screening for such patients is challenging, especially considering the availability of equipment within dialysis facilities. We therefore aimed to develop a bedside prediction model for low muscle mass, defined by the psoas muscle mass index (PMI) from CT measurement. METHODS: Hemodialysis patients (n = 619) who had undergone abdominal CT screening were divided into the development (n = 441) and validation (n = 178) groups. PMI was manually measured using abdominal CT images to diagnose low muscle mass by two independent investigators. The development group's data were used to create a logistic regression model using 42 items extracted from clinical information as predictive variables; variables were selected using the stepwise method. External validity was examined using the validation group's data, and the area under the curve (AUC), sensitivity, and specificity were calculated. RESULTS: Of all subjects, 226 (37%) were diagnosed with low muscle mass using PMI. A predictive model for low muscle mass was calculated using ten variables: each grip strength, sex, height, dry weight, primary cause of end-stage renal disease, diastolic blood pressure at start of session, pre-dialysis potassium and albumin level, and dialysis water removal in a session. The development group's adjusted AUC, sensitivity, and specificity were 0.81, 60%, and 87%, respectively. The validation group's adjusted AUC, sensitivity, and specificity were 0.73, 64%, and 82%, respectively. DISCUSSION/CONCLUSION: Our results facilitate skeletal muscle screening in hemodialysis patients, assisting in sarcopenia prophylaxis and intervention decisions.

Kidney biopsy diagnosis in childhood in the Norwegian Kidney Biopsy Registry and the long-term risk of kidney replacement therapy: a 25-year follow-up.

BACKGROUND: There is scarce information on biopsy-verified kidney disease in childhood and its progression to chronic kidney disease stage 5 (CKD 5). This study aims to review biopsy findings in children, and to investigate risk of kidney replacement therapy (KRT). METHODS: We conducted a retrospective long-term follow-up study of children included in the Norwegian Kidney Biopsy Registry (NKBR) and in the Norwegian Renal Registry (NRR) from 1988 to 2021. RESULTS: In total, 575 children with a median (interquartile range, IQR) age of 10.7 (6.1 to 14.1) years were included, and median follow-up time (IQR) after kidney biopsy was 14.3 (range 8.9 to 21.6) years. The most common biopsy diagnoses were minimal change disease (MCD; n = 92), IgA vasculitis nephritis (IgAVN; n = 76), IgA nephropathy (n = 63), and focal and segmental glomerulosclerosis (FSGS; n = 47). In total, 118 (20.5%) of the biopsied children reached CKD 5, median (IQR) time to KRT 2.3 years (7 months to 8.4 years). Most frequently, nephronophthisis (NPHP; n = 16), FSGS (n = 30), IgA nephropathy (n = 9), and membranoproliferative glomerulonephritis (MPGN; n = 9) led to KRT. CONCLUSIONS: The risk of KRT after a kidney biopsy diagnosis is highly dependent on the diagnosis. None of the children with MCD commenced KRT, while 63.8% with FSGS and 100% with NPHP reached KRT. Combining data from kidney biopsy registries with registries on KRT allows for detailed information concerning the risk for later CKD 5 after biopsy-verified kidney disease in childhood. A higher resolution version of the Graphical abstract is available as Supplementary information.

Genomic features of renal cell carcinoma developed during end-stage renal disease and dialysis.

Patients with end-stage renal disease (ESRD) or receiving dialysis have a much higher risk for renal cell carcinoma (RCC), but carcinogenic mechanisms and genomic features remain little explored and undefined. This study's goal was to identify the genomic features of ESRD RCC and characterize them for associations with tumor histology and dialysis exposure. In this study, we obtained 33 RCCs, with various histological subtypes, that developed in ESRD patients receiving dialysis and performed whole-genome sequencing and transcriptome analyses. Driver events, copy-number alteration (CNA) analysis and mutational signature profiling were performed using an analysis pipeline that integrated data from germline and somatic SNVs, Indels and structural variants as well as CNAs, while transcriptome data were analyzed for differentially expressed genes and through gene set enrichment analysis. ESRD related clear cell RCCs' driver genes and mutations mirrored those in sporadic ccRCCs. Longer dialysis periods significantly correlated with a rare mutational signature SBS23, whose etiology is unknown, and increased mitochondrial copy number. All acquired cystic disease (ACD)-RCCs, which developed specifically in ESRD patients, showed chromosome 16q amplification. Gene expression analysis suggests similarity between certain ACD-RCCs and papillary RCCs and in TCGA papillary RCCs with chromosome 16 gain identified enrichment for genes related to DNA repair, as well as pathways related to reactive oxygen species, oxidative phosphorylation and targets of Myc. This analysis suggests that ESRD or dialysis could induce types of cellular stress that impact some specific types of genomic damage leading to oncogenesis.

[A Rapidly Growing Cardiac Calcified Amorphous Tumor in a Peritoneal Dialysis Patient:Report of a Case].

A calcified amorphous tumor( CAT) is a non-neoplastic cardiac tumor, which has been reported to be associated with hemodialysis dependent end-stage renal disease. We report a case of CAT attached to mitral annular calcification (MAC) in the posterior leaflet annulus of the mitral valve in a 56-year-old man who had been receiving peritoneal dialysis for three years. The CAT grew to 10 mm long in a half year. Peritoneal dialysis dependent end-stage renal disease is associated with MAC. Additionally, MAC-related CAT has been reported growing rapidly. We should perform periodic echocardiography not only for hemodialysis patients but also for peritoneal dialysis patients. When CAT is diagnosed, operation should be performed early to prevent embolism such as cerebral infarction.

Crocodile Oil Disrupts Mitochondrial Homeostasis and Exacerbates Diabetic Kidney Injury in Spontaneously Diabetic Torii Rats.

Diabetic nephropathy is currently the leading cause of end-stage renal disease (ESRD) in type 2 diabetes. Studies have suggested that supplementation with some fatty acids might reduce the risk and delay the progression to ESRD in patient with chronic kidney disease. Crocodile oil (CO) contains a variety of fatty acids, especially omega-3, -6 and -9, that have been reported to be beneficial to human health. This study examined the impact of long-term CO supplementation on the development of diabetic nephropathy in spontaneously diabetic Torii (SDT) rats. After diabetic verification, SDT rats were assigned to receive vehicle or CO at 500 and 1000 mg/kg BW, respectively, by oral gavage. Age-matched nondiabetic Sprague-Dawley rats were given vehicle or high-dose CO. After 28 weeks of intervention, CO failed to improve hyperglycemia and pancreatic histopathological changes in SDT rats. Unexpectedly, CO dose-dependently exacerbated the impairment of kidney and mitochondrial functions caused by diabetes. CO also disturbed the expressions of proteins involved in mitochondrial biogenesis, dynamics, and mitophagy. However, no significant alterations were observed in nondiabetic rats receiving high-dose CO. The findings reveal that CO has deleterious effects that aggravate diabetic kidney injury via disrupting mitochondrial homeostasis, possibly due to its improper omega-6: omega-3 ratio.

The Role of Non-Coding RNAs in Kidney Diseases.

Renal diseases include different pathologies, such as acute kidney injury (AKI), chronic kidney disease (CKD), end-stage renal disease (ESRD), diabetic nephropathy (DN), kidney cancer, polycystic kidney disease, etc [...].