BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) is prevalent in patients with Type 2 Diabetes Mellitus (T2DM) and is associated with chronic kidney disease (CKD). The aim of this cross-sectional study was to determine the association of Fibrosis-4 (FIB-4) index with CKD among T2DM patients with concomitant NAFLD.

A single center, analytical cross-sectional study was conducted among 216 T2DM patients with concomitant NAFLD. Clinical data were obtained via retrospective review of medical charts. The outcome of interest was CKD which was based on self-report obtained from medical charts or estimated Glomerular Filtration Rate (eGFR)RESULTS

Higher FIB-4 index was found to be significantly associated with CKD. Patients with FIB-4 index of 1.45-3.25 (moderate risk) and >3.25 (high risk) have about 3 times higher odds of CKD. However, after controlling for the significant confounders, only those who belong to high-risk group was found to be associated with CKD.

This study has demonstrated that FIB4 index > 3.25, an index of liver fibrosis, is significantly associated with development of CKD in T2DM patients with concomitant NAFLD.

OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

Background and Objective: Gastrointestinal (GI) manifestations among COVID-19 patients are common; however, their relation with patient outcomes remains unclear. The study, therefore, aims to determine the association of GI manifestation with in-hospital mortality among end-stage renal disease patients (ESRD). Methods: This is a retrospective cohort design. All 501 ESRD patients with COVID-19 and admitted to the National Kidney and Transplant Institute from June 2020 to 2021 were included. GI manifestation was defined as the presence of any of the following signs and symptoms on admission: dysgeusia, anorexia, abdominal pain, nausea, vomiting, diarrhea, and jaundice. The outcome of interest was in hospital mortality, defined as death due to any cause during hospital stay. Stata17 was used for data analysis. Results: The overall prevalence of GI manifestation was 58.08% (95% CI: 53.63-62.45). The most common symptoms were abdominal pain (27.15%), loss of appetite (24.35%), and nausea (19.76%). Patients with GI manifestation had a higher proportion of stroke, lower median systolic blood pressure, and a lower proportion of abnormal oxygen saturation and diastolic blood pressure than those without GI manifestation. Across all clinical outcomes, only hospital stay significantly differ between those with and without GI manifestation. In-hospital mortality was 31.14% (95% CI: 27.10-35.39%) and showed no significant association with GI manifestation (OR= 0.94, p=0.749). Conclusions GI manifestation was common among ESRD patients with moderate-to-severe COVID-19. The inhospital mortality rate is also high; however, GI manifestation was not associated with this outcome. Meanwhile, GI manifestation leads to longer hospital stay.
Kidney Diseases ; SARS-CoV-2

BACKGROUND

Chronic kidney disease (CKD) poses a global health threat with significant morbidity and mortality. Despite current therapies, there is a need for innovative interventions to slow CKD progression. Probiotic supplementation shows promise due to its positive effects on gastrointestinal health and inflammation. However, existing research is inconclusive, necessitating a meta-analysis to assess probiotics’ impact on CKD outcomes.

To evaluate the existing scientific literature among probiotic supplementation and the improvement in glomerular filtration rate (GFR) among chronic kidney disease (CKD) patients compared to placebo treatment.

A comprehensive search of electronic databases was conducted to identify relevant studies published up to 2023. Studies that meet the predefined eligibility criteria were included. Data extraction was performed, and methodological quality and risk of bias assessment was conducted for each study. Effect measures, such as mean differences or standardized mean differences, were used to quantify the association between probiotic supplementation and GFR improvement. The random-effects model was applied to estimate the overall effect size, and subgroup analyses were performed to explore potential sources of heterogeneity. Publication bias was assessed, and sensitivity analyses was conducted to evaluate the robustness of the findings.

The meta-analysis encompassed three randomized controlled trials (RCTs) conducted from 2017 to 2023, involving 121 chronic kidney disease (CKD) patients. The analysis focused on the impact of probiotic supplementation on CKD, examining Glomerular Filtration Rate (GFR), Blood Urea Nitrogen (BUN), and Urine Protein Creatinine Ratio (UPCR). While no significant distinctions were found in GFR and BUN changes between probiotics and placebos, there was a statistically significant reduction in UPCR associated with probiotic supplementation in one study. Notably, considerable heterogeneity in GFR and significant heterogeneity in UPCR reduction were observed among the trials. Sensitivity analysis, excluding studies with small sample sizes or high bias risk, remained consistent with overall findings.

The meta-analysis indicated no significant impact of probiotic supplementation on GFR and BUN, but there was a notable reduction in Urine UPCR. The observed heterogeneity among the studies calls for cautious interpretation due to variations in study designs, patient populations, and probiotic formulations. While the results suggest a potential role for probiotics in reducing proteinuria in chronic kidney disease (CKD) patients, the need for further research with larger sample sizes and standardized methodologies is emphasized to establish definitive conclusions.

OBJECTIVE: To observe the therapeutic effect of governor vessel moxibustion combined with wenyang yiqi qiwei decoction on erectile dysfunction (ED) with spleen-kidney deficiency and to explore the possible mechanism. METHODS: A total of 130 ED patients with spleen-kidney deficiency were randomized into an observation group (65 cases, 2 cases dropped off) and a control group (65 cases, 3 cases dropped off). The control group was given wenyang yiqi qiwei decoction orally, one dose daily. On the basis of the treatment in the control group, governor vessel moxibustion was applied from Dazhui (GV 14) to Yaoshu (GV 2) in the observation group, 110 min a time, once a day. The treatment of 4 weeks was required in both groups. Before and after treatment, 5-question international index of erectile function (IIEF-5) score, erection quality scale (EQS) score, erectile hardness assessment (EHS) score, TCM syndrome score, serum testosterone (T) level and vascular endothelial function indexes (prostaglandin I2 [PGI2], endothelin-1 [ET-1] and nitric oxide [NO] levels) were observed respectively, and the clinical efficacy was evaluated in both groups. RESULTS: After treatment, the scores of IIEF-5, EQS, EHS and serum levels of T, PGI2, NO were increased compared before treatment (P<0.01), the TCM syndrome scores and serum ET-1 levels were decreased compared before treatment (P<0.01) in the two groups; the scores of IIEF-5, EQS, EHS and serum levels of T, PGI2, NO in the observation group were higher than those in the control group (P<0.01, P<0.05), the TCM syndrome score and serum ET-1 level were lower than those in the control group (P<0.01, P<0.05). The total effective rate was 88.9% (56/63) in the observation group, which was superior to 74.2% (46/62) in the control group (P<0.05). CONCLUSION Governor vessel moxibustion combined with wenyang yiqi qiwei decoction can improve the erectile function and increase the erection hardness and quality in ED patients with spleen-kidney deficiency, its mechanism may relate to improving serum T level and vascular endothelial function.
Humans ; Male ; Administration, Oral ; Drugs, Chinese Herbal/therapeutic use* ; Erectile Dysfunction/therapy* ; Kidney/pathology* ; Kidney Diseases/complications* ; Moxibustion ; Spleen/pathology* ; Splenic Diseases/complications* ; Testosterone/blood* ; Combined Modality Therapy

This study was designed to evaluate the protective effect of CPD1, a novel phosphodiesterase 5 inhibitor, on renal interstitial fibrosis after unilateral renal ischemia-reperfusion injury (UIRI). Male BALB/c mice were subjected to UIRI, and treated with CPD1 once daily (i.g, 5 mg/kg). Contralateral nephrectomy was performed on day 10 after UIRI, and the UIRI kidneys were harvested on day 11. Hematoxylin-eosin (HE), Masson trichrome and Sirius Red staining methods were used to observe the renal tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of proteins related to fibrosis. HE, Sirius Red and Masson trichrome staining showed that CPD1-treated UIRI mice had lower extent of tubular epithelial cell injury and deposition of extracellular matrix (ECM) in renal interstitium compared with those in the fibrotic mouse kidneys. The results from immunohistochemistry and Western blot assay indicated significantly decreased protein expressions of type I collagen, fibronectin, plasminogen activator inhibitor-1 (PAI-1) and α-smooth muscle actin (α-SMA) after CPD1 treatment. In addition, CPD1 dose-dependently inhibited the expression of ECM-related proteins induced by transforming growth factor β1 (TGF-β1) in normal rat kidney interstitial fibroblasts (NRK-49F) and human renal tubular epithelial cell line (HK-2). In summary, the novel PDE inhibitor, CPD1, displays strong protective effects against UIRI and fibrosis by suppressing TGF-β signaling pathway and regulating the balance between ECM synthesis and degradation through PAI-1.
Animals ; Humans ; Male ; Mice ; Rats ; Extracellular Matrix Proteins ; Fibrosis ; Kidney ; Kidney Diseases ; Phosphodiesterase 5 Inhibitors ; Plasminogen Activator Inhibitor 1

Cobalt/toxicity* ; Computational Biology ; Kidney/drug effects* ; Kidney Diseases/genetics* ; Humans

OBJECTIVE: To explore the clinical characteristics and genetic basis of two Chinese pedigrees affected with Joubert syndrome. METHODS: Clinical data of the two pedigrees was collected. Genomic DNA was extracted from peripheral blood samples and subjected to high-throughput sequencing. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out for a high-risk fetus from pedigree 2. RESULTS: The proband of pedigree 1 was a fetus at 23⁺⁵ weeks gestation, for which both ultrasound and MRI showed "cerebellar vermis malformation" and "molar tooth sign". No apparent abnormality was noted in the fetus after elected abortion. The fetus was found to harbor c.812+3G>T and c.1828G>C compound heterozygous variants of the INPP5E gene, which have been associated with Joubert syndrome type 1. The proband from pedigree 2 had growth retardation, mental deficiency, peculiar facial features, low muscle tone and postaxial polydactyly of right foot. MRI also revealed "cerebellar dysplasia" and "molar tooth sign". The proband was found to harbor c.485C>G and c.1878+1G>A compound heterozygous variants of the ARMC9 gene, which have been associated with Joubert syndrome type 30. Prenatal diagnosis found that the fetus only carried the c.485C>G variant. A healthy infant was born, and no anomalies was found during the follow-up. CONCLUSION The compound heterozygous variants of the INPP5E and ARMC9 genes probably underlay the disease in the two pedigrees. Above finding has expanded the spectrum of pathogenic variants underlying Joubert syndrome and provided a basis for genetic counseling and prenatal diagnosis.
Female ; Humans ; Pregnancy ; Pedigree ; Cerebellum/abnormalities* ; Abnormalities, Multiple/diagnosis* ; Eye Abnormalities/diagnosis* ; Kidney Diseases, Cystic/diagnosis* ; Phosphoric Monoester Hydrolases/genetics* ; Retina/abnormalities* ; East Asian People ; Mutation

The purpose of the present study was to determine the role of inositol 1,4,5-trisphosphate receptor 3 (IP₃R3) in renal cyst development in autosomal dominant polycystic kidney disease (ADPKD). 2-aminoethoxy-diphenyl borate (2-APB) and shRNA were used to suppress the expression of IP₃R3. The effect of IP₃R3 on cyst growth was investigated in Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney specific Pkd1 knockout (PKD) mouse model. The underlying mechanism of IP₃R3 in promoting renal cyst development was investigated by Western blot and immunofluorescence staining. The results showed that the expression level of IP₃R3 was significantly increased in the kidneys of PKD mice. Inhibiting IP₃R3 by 2-APB or shRNA significantly retarded cyst expansion in MDCK cyst model and embryonic kidney cyst model. Western blot and immunofluorescence staining results showed that hyperactivated cAMP-PKA signaling pathway in the growth process of ADPKD cyst promoted the expression of IP₃R3, which was accompanied by a subcellular redistribution process in which IP₃R3 was translocated from endoplasmic reticulum to intercellular junction. The abnormal expression and subcellular localization of IP₃R3 further promoted cyst epithelial cell proliferation by activating MAPK and mTOR signaling pathways and accelerating cell cycle. These results suggest that the expression and subcellular distribution of IP₃R3 are involved in promoting renal cyst development, which implies IP₃R3 as a potential therapeutic target of ADPKD.
Animals ; Dogs ; Mice ; Cysts/genetics* ; Inositol 1,4,5-Trisphosphate Receptors/pharmacology* ; Kidney/metabolism* ; Polycystic Kidney Diseases/metabolism* ; Polycystic Kidney, Autosomal Dominant/drug therapy* ; Madin Darby Canine Kidney Cells

Kidney disease affects a large number of people around the world, imposing a significant burden to people's health and life. If early prediction, rapid diagnosis and prognosis prediction of kidney disease can be carried out, the health of patients will be better protected. Machine learning belongs to the category of artificial intelligence, which can be divided into supervised learning, unsupervised learning and reinforcement learning. With the increasing requirements for the processing and analyzing large-scale and high-dimensional data, machine learning is playing an increasingly important role in the medical domain, and the field of kidney disease is no exception. This article presents a comprehensive overview of the application progress of machine learning in kidney disease, aiming to make medical staff's decision-making in kidney disease more early, accurate and rapid, and better escort the life and health of patients.
Humans ; Artificial Intelligence ; Machine Learning ; Kidney ; Kidney Diseases/diagnosis*