Kidney Diseases最新文献

[This corrects the article DOI: 10.1159/000538106.].

Background: Focal segmental glomerulosclerosis (FSGS) is an increasingly prevalent group of refractory glomerular diseases and a significant aetiology of end-stage renal disease. Podocyte injury and depletion significantly contribute to the pathogenesis and progression of FSGS. MicroRNAs (miRNAs) are noncoding RNAs that regulate the expression of specific genes in relevant cells, thereby playing crucial roles in the pathogenesis of FSGS. Many studies have shown that miRNAs can be secreted from cells into body fluids and that these miRNAs in the circulation are highly stable. The gold standard for FSGS diagnosis is kidney biopsy; however, the clinical heterogeneity of FSGS, along with variations in histology and nonspecific morphological features, can impact its diagnostic accuracy. Thus, the discovery of novel and efficacious biomarkers is crucial in facilitating the diagnosis of FSGS. In addition, the degree of kidney damage in patients with FSGS varies at different stages, necessitating individualized diagnosis and treatment approaches. Considering the side effects of glucocorticoids, determining whether a patient is steroid resistant is vital. Thus, ideal biomarkers should not only be specific and sensitive but also have the ability to accurately reflect the stage or prognosis of the disease to improve the treatment for patients.

Summary: To date, numerous studies have shown that both urinary miRNAs and plasma miRNAs are potential biomarkers for FSGS. In addition, the identification of miRNA biomarkers specific for the FSGS disease state may provide new insights into the underlying pathological mechanism of FSGS.

Key messages: Here we summarize the currently available miRNA biomarkers that could help us better understand the diagnosis, disease activity, prognosis, and clinical features of FSGS.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder that often leads to end-stage renal disease, with disease progression deeply influenced by the renal microenvironment. This study aims to unravel the critical cellular types and their intricate interactions within the ADPKD microenvironment.

Methods: Leveraging single-cell transcriptome data from seven ADPKD and three healthy human kidney samples, we systematically dissected the cellular landscape of the ADPKD microenvironment. Our approach included CellChat for cell-cell communication analysis, VISION for pathway enrichment analysis, pySCENIC for regulon activity calculation, and Monocle V3 for pseudotime trajectory construction.

Results: We identified nine major cell lineages, with a notable increase of mononuclear phagocytes (MNPs), T cells, and fibroblasts in the ADPKD microenvironment. These cells collectively orchestrated a distinctive microenvironment, marked by complex intercellular networks. Notably, a specific subset of macrophages exhibited an "M2-like" phenotype, which was driven by IL-10 signaling from M1-like macrophages and contributed to cyst cell proliferation. Immunosuppression was predominantly mediated by CD4+ T cells, activated by macrophages through immune checkpoint pathways, such as PDL1 signaling. The fibrotic expansion was a cumulative effect of fibroblast activation and proliferation, modulated by macrophages and cyst-lining epithelial cells.

Conclusion: This comprehensive investigation provides valuable insights into the diverse landscapes of the ADPKD microenvironment at single-cell resolution, emphasizing MNPs, T cells, and fibroblasts. The study unveils complex interactions among these cell types, shedding light on an understanding of the immunological aspect of ADPKD and proposing potential therapeutic targets.

Introduction: Whether restless legs syndrome (RLS) and sleep disturbance (SD) in hemodialysis (HD) patients influence all-cause and cardiovascular mortality remains controversial. The aim of this study was to evaluate the association between RLS or SD and 3-year mortality in HD patients.

Methods: A total of 301 patients who underwent HD were examined in April 2021 and were followed up for 3 years. The median follow-up time was 36.0 [33.3, 36.0] months. Fifty-four patients fulfilled the diagnosis of RLS (17.9%), 126 patients complained of SD (41.9%). Demographic parameters, clinical features, laboratory indices, and two questionnaires to assess the diagnosis of RLS and sleep status were collected. All-cause mortality and cardiovascular mortality in this population were evaluated. Cox regression analyses and Kaplan-Meier curves were performed to determine the effect of RLS or SD on 3-year mortality.

Results: The RLS group reported that 29 patients (53.8%) exhibited concurrent symptoms of SD. The presence of RLS or SD alone did not significantly elevate the risk of all-cause mortality (p = 0.053 and p = 0.193). However, the coexistence of RLS and SD was identified as an independent risk factor for all-cause mortality (p = 0.011). Furthermore, the various combinations associated with RLS or SD were found to be independently correlated with the risk of cardiovascular death (p < 0.05).

Conclusion: The combination of RLS and SD in HD patients is associated with an increased risk of cardiovascular and all-cause mortality, underscoring the clinical significance of this association.

Introduction: Membranoproliferative glomerulonephritis (MPGN) is a heterogeneous pattern of glomerular injury. Repeated kidney biopsies may elucidate pathogenic mechanisms and guide diagnostic strategies.

Methods: We included 82 patients diagnosed with MPGN by kidney biopsy who underwent at least two biopsies between 1997 and 2023 at Peking University First Hospital. Clinical and pathological data were analyzed retrospectively.

Results: Of 342 MPGN patients, 95 (28%) had repeated biopsies (0.9-4.0 years apart). This incidence was higher than in other glomerulonephropathies under immunosuppression. Among the 82 patients analyzed (excluding kidney transplants and ≤3-month biopsy intervals), 42 were initially diagnosed with non-MPGN pathology. At the second biopsy, proteinuria increased (from 2.9 to 6.3 g/day), eGFR declined (from 76 to 47 mL/min/1.73 m²), and renal C3 deposition was stronger (p = 0.04). Thirty patients (37%) had etiological reclassification, mostly to monoclonal gammopathy of renal significance (MGRS). Compared to idiopathic MPGN, MGRS patients were older (53 vs. 35 years) and had worse renal function (eGFR 57 vs. 81 mL/min/1.73 m²) but slower eGFR decline (-7 vs. -12 mL/min/1.73 m²/year). Most MGRS patients (64%) remained negative for monoclonal protein in serum or urine immunofixation, necessitating repeat biopsy and clone-directed therapy.

Conclusion: In this study, about half and one-third of patients underwent morphological and etiological reclassification, respectively. Stronger complement deposition may drive morphological changes. Repeated kidney biopsies are crucial for diagnosing MGRS, especially in patients with negative immunofixation.

Introduction: Indications for sodium-glucose cotransporter-2 (SGLT2) inhibitors have expanded to include heart failure and chronic kidney disease after the year 2020. Whether and how the demographic trends in the prescription of SGLT2 inhibitors have changed after the expansion of indications have not been studied extensively.

Methods: This study is a descriptive analysis of serial, cross-sectional data on nationwide prescription of SGLT2 inhibitors between April 2016 and March 2023 obtained from NDB Open Data Japan, which contains more than 95% of total health insurance reimbursement claims in the nation.

Results: The total number of SGLT2 inhibitor tablets prescribed in outpatient settings with prescriptions papers increased from 577,996,158 tablets in fiscal year (FY) 2020 to 904,598,175 tablets in FY 2022. Patients aged 75 years and older accounted for 20.3% of the total prescriptions in FY 2020, and this proportion increased to 27.8% in FY 2022. Among all SGLT2 inhibitors, the tablet that expanded its indications for patients with heart failure and chronic kidney disease the earliest showed the largest percentage increase in the number of prescribed tablets during this period and the highest share of the elderly population in its recipients in both sexes (men, 35.9%; women, 49.4%) in FY 2022. The number of prescribed SGLT2 inhibitor tablets per population was constantly higher in men than in women between FY 2020 and 2022, which is consistent with the sex difference in the prevalence of these diseases.

Conclusion: Prescription of SGLT2 inhibitors to the elderly population is no longer infrequent and accounts for a large portion of the entire prescription of SGLT2 inhibitors in Japan. These findings contribute to updating our perception on the demographics of SGLT2 inhibitor recipients.

Introduction: The global rise in urinary stone prevalence has become a significant health and economic challenge. Linked to metabolic disorders such as obesity and diabetes, urinary stones represent a complex systemic condition that requires a comprehensive understanding of metabolic profiles for effective management.

Methods: The methodological quality of this study was evaluated in accordance with the STROBE-MR checklist. Using genome-wide association study (GWAS) data for 1,091 blood and 1,172 urine metabolites, we conducted a two-sample Mendelian randomization (MR) analysis, validated by meta-analysis, to explore metabolic influences on stone formation. Multivariable and mediation MR analyses were performed to identify independent metabolite influences and their interaction with gut microbiota and metabolism-related genes. Clinical metabolomic analysis and further animal experiments substantiated our findings.

Results: Univariable MR identified 119 blood and 63 urine metabolites associated with urinary stones, with 16 blood and 2 urine metabolites showing robust associations post-correction. Notably, mannose and 3-aminoisobutyrate emerged as independent influencers of stone formation. Mediation MR suggested these metabolites as potential mediators in the gut microbiota's influence on stone formation. Clinical urine sample analysis indicates higher mannose levels in normal renal sides than stone sides. Animal studies confirmed mannose's protective role by reducing renal calcium oxalate crystal deposition.

Conclusion: Our study establishes causal links between specific metabolites and urinary stones, shedding light on the intricate biological mechanisms of stone formation. The discovery of mannose as a protective factor opens avenues for future research and clinical applications, offering promising directions for the prevention and treatment of stones.

Introduction: The aim of the study was to assess the impact of employing the KHA-200 hemoperfusion device in conjunction with hemodialysis therapy in the elimination of serum solutes among maintenance hemodialysis (MHD) patients.

Methods: A total of ninety-two MHD patients from our hospital's hemodialysis center were judiciously chosen and allocated randomly into two groups: the conventional hemodialysis group, serving as the control group, and the group utilizing the KHA-200 hemoperfusion device in combination with hemodialysis, denoted as the experimental group, in a 1:1 ratio. We compared variations in serum solute indices, including blood urea nitrogen, creatinine, potassium, calcium, phosphorus, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), β2-microglobulin (β2-MG), parathyroid hormone (PTH), homocysteine (Hcy), albumin, both prior to and post-treatment. Meanwhile, a comparison of the serum solute clearance rates in the two groups was performed.

Results: Following treatment, both groups exhibited substantial reductions in blood urea nitrogen, creatinine, uric acid, potassium, phosphorus, PTH, and Hcy (p < 0.001). There were no statistically significant distinctions between the two groups in terms of urea nitrogen, creatinine, uric acid, and potassium clearance (p > 0.05). Conversely, the experimental group demonstrated a significant effect on the elimination of IL-6 and β2-MG (p < 0.001). Furthermore, the experimental group's performance in reducing blood phosphorus, PTH, IL-6, β2-MG, and Hcy was significantly superior to that of the control group (p < 0.05). Moreover, the reduction in systolic blood pressure in the experimental group was better than in the control group.

Conclusion: Employing the KHA-200 hemoperfusion device in tandem with hemodialysis excels in removing blood phosphorus and certain medium-sized uremic toxins, including PTH, IL-6, β2-MG, and Hcy, surpassing the performance of conventional hemodialysis.

Introduction: Individuals with end-stage kidney disease frequently grapple with uncontrolled hypertension, which elevates their risk for cardiovascular complications.

Methods: This randomized, controlled, multicenter study, conducted across 10 hospitals, aimed to compare the effectiveness and safety of sacubitril-valsartan versus irbesartan in managing hypertension among dialysis patients. The primary efficacy variable of the present study was the reduction in office blood pressure (BP) after 12 months of treatment. Participants were randomly allocated to receive either sacubitril-valsartan (angiotensin receptor-neprilysin inhibitor [ARNI]) or irbesartan (angiotensin receptor blocker [ARB]) treatment over a 12-month period. We gauged treatment efficacy through office and 24-h ambulatory BP readings, as well as serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP). Safety outcomes were also evaluated.

Results: Baseline office BP averaged 150/82 mm Hg and median NT-proBNP was 6,336 pg/mL. In the intention-to-treat analysis, office systolic BP reduction was significantly greater in the ARNI than ARB group (-10.4 vs. -4.6 mm Hg, p = 0.003) after adjustment for baseline BP. In hemodialysis (HD) patients, the mean systolic/diastolic BP reduction was also greater in the ARNI than ARB group (-15.9/2.4 vs. -6.6/1.1 mm Hg, p < 0.05). While for peritoneal dialysis (PD) patients, there were no significant between-group differences (p = 0.087). Per-protocol analyses in 215 patients on office BP and 137 patients on 24-h BP produced similar results. During the study period, there was no between-group difference in the overall incidence of fatal and nonfatal events and hyperkalemia.

Conclusion: In dialysis patients with hypertension, especially those undergoing HD, ARNI demonstrated superior effectiveness in reducing BP compared to ARB. The safety profiles of both treatments were comparable and acceptable.

Introduction: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a standard treatment for kidney and cardiovascular protection in diabetic kidney disease (DKD). We investigated the effect of SGLT2i on the urinary podocyte-associated molecule levels in DKD.

Methods: We studied 24 DKD patients who were started on SGLT2i treatment and 25 patients who were not treated (control group). Urinary levels of podocyte-associated molecules, their corresponding mRNA levels in urinary sediment, estimated glomerular filtration rate (eGFR), and urine albumin-creatinine ratio (UACR) were measured at baseline and 3 months later.

Results: Urinary levels of podocin, podocalyxin, and synaptopodin increased significantly over 3 months in the control group, while the levels remained static in the treatment group. After 3 months of treatment, urinary podocin (2.95 [0.92-5.45] vs. 9.15 [1.88-24.80] ng/μmol-Cr, p < 0.01), podocalyxin (367.3 [299.5-768.6] vs. 920.6 [369.3-2,060.4] ng/μmol-Cr, p < 0.01), and synaptopodin levels (13.17 [9.86-47.02] vs. 35.56 [17.59-134.08] ng/μmol-Cr, p < 0.05) were significantly lower in the treatment than the control group. Urinary sediment mRNA levels of podocin, podocalyxin, synaptopodin, and nephrin did not change in both groups. However, there was no significant correlation between urinary podocyte-associated marker levels and eGFR or UACR at baseline or after treatment.

Conclusion: SGLT2i prevents the progressive increase in the urinary excretion of podocyte-specific molecules in DKD patients, suggesting that SGLT2 inhibitors have a protective effect on the podocytes.