Kidney Diseases最新文献

Introduction: The aim of the study was to investigate the long-term effects of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection and novel coronavirus disease (COVID-19) on prognosis of kidney transplant recipients.

Methods: A 1-year retrospective study was carried out among 362 domestic kidney transplant recipients who were divided into observational (COVID-19) and control groups. Stratification analysis was then carried out to investigate whether repeated infections and infection severity could influence graft prognosis. Kaplan-Meier curves assessed 1-year graft survival, while one-way analysis of variance (ANOVA) compared graft function and laboratory parameters. Generalized estimating equations and repeated-measures ANOVA confirmed the magnitude of the impact of COVID-19 on kidney grafts. Generalized logistic regression and Cox regression established a model for analyzing COVID-19 risk factors. Meta-analysis and subgroup analysis were performed for validation.

Results: Exposure of COVID-19 had a significant effect on graft function within 1 year (p < 0.001), and this kind of effect was mostly brought by severer infections in the stratification analysis regarding graft survival rate (p < 0.001), estimated glomerular filtration rate (eGFR) level (p < 0.001), and 1-year eGFR slope (p = 0.014). Diagnostic model showed tacrolimus patients are less likely to get severe COVID-19 than cyclosporine (p = 0.004). Hyperglycemia (p = 0.004) and low hemoglobin (p = 0.023) are adverse factors for severe pneumonia. Hemoptysis, hypo-lymphopenia, high procalcitonin and ferritin are linked to poor allograft outcomes with SARS-CoV-2 infection.

Conclusions: COVID-19 severity is linked to poor kidney allograft prognosis. Hyperglycemia, low hemoglobin, and drug protocols including cyclosporine rather than tacrolimus are correlated with COVID-19 pneumonia. Hemoptysis, low lymphocytes, high procalcitonin or ferritin were concerned with kidney allograft prognosis post-COVID-19.

Introduction: Fatty acid-binding protein 4 (FABP4) is a novel adipokine that is critically involved in many inflammatory and immune diseases. However, the role of FABP4 in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) remains unclear. The current study aimed to investigate the role of FABP4 in patients with ANCA-GN.

Methods: Plasma and urine samples from 37 patients with active ANCA-GN and kidney biopsy specimens from another group of 56 patients with ANCA-GN were collected. The plasma and urinary levels of FABP4 were measured by enzyme-linked immunosorbent assay and the kidney FABP4 expression was determined by immunohistochemistry and immunofluorescence staining. Associations between FABP4 levels with clinical and pathologic parameters were analyzed. To further elucidate the role of FABP4 in ANCA-GN, a novel FABP4 inhibitor, BMS309403, was employed in a recognized rat model of experimental autoimmune vasculitis (EAV).

Results: Plasma and urinary levels of FABP4 in active ANCA-GN patients were significantly higher than those in normal controls {52.8 ± 23.6 ng/mL vs. 16.9 ± 8.8 ng/mL, p < 0.01; median 126.6 (interquartile range [IQR] 28.4-311.2) ng/g Cr vs. median 0.0 (IQR 0.0-0.0) ng/g Cr, p < 0.01, respectively}. Immunohistochemical analysis revealed higher glomerular and tubular expression of FABP4 in the kidneys of ANCA-GN patients than those in normal controls (0.015 ± 0.012 vs. 0.004 ± 0.003, p < 0.001; 0.053 ± 0.026 vs. 0.011 ± 0.010, p < 0.001, respectively). Moreover, for ANCA-GN patients, urinary FABP4 levels were significantly higher in active ANCA than those in remission (184.3 ± 187.0 ng/g Cr vs. 9.4 ± 23.9 ng/g Cr, p < 0.01). Correlation analysis showed that urinary levels of FABP4 correlated with serum creatinine (r = 0.596, p < 0.0001), urinary albumin/Cr (r = 0.523, p = 0.001), blood neutrophil ratio (r = 0.386, p = 0.018), PT (r = 0.583, p = 0.001), APTT (r = 0.364, p = 0.034), hemoglobin level (r = -0.398, p = 0.015), estimated glomerular filtration rate (r = -0.680, p < 0.0001), crescent proportion (r = 0.661, p = 0.032), and all-cause death of ANCA-GN patients (HR 2.93, 95% CI [1.05-8.19]). Furthermore, FABP4 inhibition by BMS309403 ameliorated renal injury in a rat mole of ANCA-GN.

Conclusions: Urinary FABP4 levels might reflect the disease activity and renal involvement of ANCA-associated vasculitis, and FABP4 might act as a promising therapeutic target against ANCA-GN.

Introduction: VERTIS CV was a placebo-controlled cardiovascular (CV) outcome trial evaluating the sodium-glucose cotransporter 2 inhibitor ertugliflozin in patients with type 2 diabetes and established atherosclerotic CV disease. The aim of the current analyses was to evaluate VERTIS CV cardiorenal outcomes according to baseline use of renin-angiotensin-aldosterone system (RAAS) inhibitors or diuretics, including mineralocorticoid receptor antagonists (MRAs).

Methods: Participants received ertugliflozin 5 mg, ertugliflozin 15 mg, or placebo once daily and were followed for a mean of 3.5 years. Prespecified CV and kidney outcomes were analyzed by Cox proportional hazard modeling in participant subgroups defined by baseline use of RAAS inhibitors (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers) or diuretics (loop diuretics, non-loop diuretics, MRAs), with interaction testing to assess for treatment effect modification.

Results: A total of 8,246 patients were randomized in VERTIS CV. At baseline, 6,686 (81%) participants were being treated with RAAS inhibitors, 3,542 (43%) with diuretics, 1,252 (15%) with loop diuretics, and 674 (8%) with MRAs. No significant interactions were observed for cardiorenal outcomes by baseline use of RAAS inhibitors or MRAs (p _interaction > 0.05 for all). Statistically significant interactions for a first event of hospitalization for heart failure (HHF) or CV death, and of HHF (alone), were observed with baseline use of diuretics, including loop diuretics, with an increased benefit of ertugliflozin treatment versus placebo.

Conclusion: In VERTIS CV, baseline use of diuretics, particularly loop diuretics, identified a subgroup that demonstrated greater benefit with ertugliflozin on first HHF/CV death and HHF outcomes, with no modification of treatment effect observed with baseline use of RAAS inhibitors or MRAs. There was no evidence of treatment effect on the kidney composite outcomes by baseline use of RAAS inhibitors, diuretics, loop diuretics, or MRAs.

Introduction: There were limited data regarding the association between remnant cholesterol (RC), an emerging novel lipid marker, and chronic kidney disease (CKD). This study aimed to investigate the association of baseline and cumulative exposure of RC (cumRC) with kidney function decline (KFD) risk in the general population of China.

Methods: Using data from the physical examination database in the Third Xiangya Hospital of Central South University (Changsha, China), 22,702 participants (age ≥18 years) without KFD, who underwent 3 consecutive annual health examinations between 2012 and 2015, were included. KFD was recorded during the interval between the third examination and the end of follow-up through 2020.

Results: The cumRC was classified into 4 groups according to these cutoff values: 0.92, 1.33, and 1.99 (mmol/L). During a median follow-up of 3.17 years, 1,085 new KFD events were confirmed. Participants in the highest quartile of cumRC had 43% higher risk of KFD (hazard ratio, 1.43 [95% confidence interval, 1.16-1.77]), compared with the lowest quartile. Similarly, restricted cubic spline analysis showed a significant dose-response relationship between cumRC and the risk of KFD (P nonlinearity = 0.0314). However, baseline RC did not show any typical dose-dependent positive relationship with KFD development. In the discordance analysis, high baseline RC/low baseline low-density lipoprotein cholesterol (LDL-C) or high cumRC/low cumLDL-C were all associated with KFD in adjusted models.

Conclusion: These data suggest a significant association between cumRC and risk of KFD independent of traditional CVD risk factors as well as the LDL-C level. Therefore, consistent RC monitoring should be given to individuals for early KFD prevention, especially in population with normal LDL-C levels who are often overlooked.

Introduction: Hydroxychloroquine (HCQ) is recommended for Chinese patients with immunoglobulin A nephropathy (IgAN). This study aimed to investigate the pharmacokinetics of HCQ in the treatment of IgAN and its relationship with therapeutic efficacy.

Methods: This prospective study included 49 IgAN patients treated with HCQ, who were divided into effective and ineffective groups based on HCQ treatment efficacy after 6 months, defined as a reduction in proteinuria of at least 50% from baseline. The concentrations of HCQ and its metabolites were measured by high-performance liquid chromatography-tandem mass spectrometry. The relationships between the concentrations of HCQ and its metabolites and therapeutic efficacy were analyzed using linear correlation analysis and logistic regression. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of HCQ and its metabolite concentrations.

Results: Following 6 months of treatment with HCQ, patients in the effective group exhibited increased concentrations of HCQ (p = 0.022) and desethylchloroquine (DCQ) (p = 0.015). The results of the Spearman's correlation analysis indicated a positive correlation between alterations in proteinuria and concentrations of HCQ (r = 0.328, p < 0.05) and DCQ (r = 0.267, p < 0.05). Univariate and multivariate logistic regression analyses indicated that efficacy was significantly correlated with HCQ (odds ratio 1.008, 95% CI: 1.001-1.014) and DCQ (odds ratio 1.064, 95% CI: 1.010-1.121) concentrations. ROC curves indicated that an HCQ concentration of 442.6 ng/mL and a DCQ concentration of 42.7 ng/mL exhibited the optimal capacity to predict efficacy (p < 0.05).

Conclusion: The blood concentrations of HCQ and its metabolite DCQ may be significant factors for evaluating therapeutic efficacy in IgAN patients.

Introduction: Renal anemia is a common complication among patients with non-dialysis chronic kidney disease (ND-CKD), and there remains an unmet need for more efficient and convenient daily oral medications to improve patient outcomes. This study aimed to evaluate the efficacy and safety of enarodustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, in treating anemia for ND-CKD patients.

Methods: This phase 3 study was conducted at 48 centers across China, enrolling 156 ND-CKD patients. Participants were randomly randomized in a 2:1 ratio to receive either enarodustat or placebo for an initial 8-week double-blind period, followed by a 16-week open-label period during which all patients received enarodustat.

Results: The primary endpoint was the mean change in hemoglobin (Hb) levels from baseline to the average level during weeks 7-9. Secondary endpoints focused on Hb concentration or treatment pattern, while exploratory endpoints assessed iron metabolism-related parameters. The mean (±SD) change in Hb levels from baseline to weeks 7-9 was 15.99 (±9.46) g/L in the enarodustat group, compared to -0.14 (±8.08) g/L in the placebo group, resulting in a mean difference of 16.00 (±1.54) g/L (p < 0.001). During weeks 7-9, 85.3% of patients in the enarodustat group achieved Hb levels ≥100 g/L with 86.0% maintaining this level during weeks 21-25. In the first 4 weeks, the Hb increased by 11.82 (±9.56) g/L in the enarodustat group. By week 9, the mean change in hepcidin level was -42.94 (±37.56) ng/mL in the enarodustat group, compared to +4.58 (±33.34) ng/mL in the placebo group. Enarodustat also improved other iron-related parameters and reduced the need for iron supplements. The safety profile of enarodustat was well tolerable with adverse events comparable to those of the placebo.

Conclusion: Enarodustat effectively corrected renal anemia with a manageable safety profile. Its once-daily oral administration offers convenience that may enhance the adherence. Enarodustat shows the potential as a promising therapy for anemic patients with ND-CKD.

[This corrects the article DOI: 10.1159/000523847.].

Background: Peritonitis is a common and serious complication of peritoneal dialysis that results in considerable morbidity, mortality, and increased healthcare costs. A positive culture-based microorganism test is one of the main criteria for the diagnosis of peritonitis. However, the rates of positive bacterial culture remain quite low.

Summary: Peritonitis is a frequently encountered and consequential complication of peritoneal dialysis that poses a significant clinical burden in terms of morbidity, mortality, and healthcare expenditure. The reliance on culture-positive microbiological tests as a cornerstone of peritonitis diagnosis often results in a relatively low rate of positive results.

Key messages: This article aimed to present a comprehensive synthesis and critical analysis of the most recent diagnostic modalities used to identify peritonitis-associated pathogens in peritoneal dialysis. Emphasis was placed on both direct diagnostic tools for pathogen identification and rapid detection methodologies that facilitate expedited pathogen diagnosis in peritonitis.

Introduction: This study aims to explore the contribution of neutrophil extracellular traps (NETs) to kidney stones.

Methods: The microarray data from GSE73680 and bioinformatic analysis were applied to identify differentially expressed genes in patients with kidney stones. A rat model of kidney stones was established through ethylene glycol and ammonium chloride administration. The plasma was collected for examining cf-DNA, DNase I, MPO-DNA, H3Cit and NE. Superoxide dismutase, malondialdehyde, creatinine, blood urea nitrogen, and calcium were examined through biochemical analysis. MPO, H3Cit, and NE in kidney tissues were detected via immunofluorescence staining. Cell apoptosis was evaluated through TUNEL assays. HE, Periodic Acid-Schiff and Von Kossa staining were applied to determine histological structure, calcium deposits and stone formation in the kidneys. Neutrophil elastase inhibitor Sivelestat (SIVE) was administrated for NET suppression in rats.

Results: A total of 403 differentially expressed genes including 270 upregulated and 133 downregulated genes were identified between renal papillary tissues with Randall's plaque and normal tissues. Gene ontology enrichment, KEGG pathway and protein-protein interaction network analysis of these dysregulated genes were performed. Moreover, increased NET markers including cf-DNA, DNase I, MPO-DNA, H3Cit and NE and calcium deposits were observed in patients with kidney stones. Subsequently, we established a rat model of kidney stones. We found that NET formation was significantly elevated in kidney stone rats, and renal tubular injury and apoptotic cells were enhanced as kidney stones developed. Strikingly, we found that suppression of NETs via SIVE could significantly reduce calcium deposits and apoptotic cells and alleviate tubular injury, thus improving kidney function.

Conclusion: NETs drive the formation of kidney stones, thus aggravating kidney injury. Our study identifies NETs as a potential diagnostic and therapeutic biomarker for nephrolithiasis.

Background: Kidney disease has become a growing public health problem worldwide, and there is an urgent need to develop reliable models for investigating novel and effective treatment strategies. In recent years, kidney organoids, as novel models different from traditional two-dimensional cells and model animals, have attracted more and more attention. Current advances have allowed the generation of kidney organoids from the directed differentiation of induced pluripotent stem cells (iPSCs), which possess similar characteristics to embryonic stem cells, but bypass ethical constraints and have a wide range of sources.

Summary: Herein, the methods of generating renal organoids from iPSCs, the applications of iPSC-derived renal organoids in disease modeling, drug effectiveness detection, and regenerative medicine as well as the challenges were reviewed.

Key messages: iPSC-derived renal organoids can be used to model kidney diseases and are great models for studying kidney injury and toxicity. Many efforts are needed to finally apply organoids into clinical application.