Acute kidney injury (AKI) and chronic kidney disease (CKD) are significant public health issues associated with a long-term increase in mortality risk, resulting from various etiologies including renal ischemia, sepsis, drug toxicity, and diabetes mellitus. Numerous preclinical models have been developed to deepen our understanding of the pathophysiological mechanisms and therapeutic approaches for kidney diseases. Among these, rodent models have proven to be powerful tools in the discovery of novel therapeutics, while the development of kidney organoids has emerged as a promising advancement in the field. This review provides a comprehensive analysis of the construction methodologies, underlying biological mechanisms, and recent therapeutic developments across different AKI and CKD models. Additionally, this review summarizes the advantages, limitations, and challenges inherent in these preclinical models, thereby contributing robust evidence to support the development of effective therapeutic strategies.
急性肾损伤（acute kidney injury, AKI）和慢性肾脏病（chronic kidney disease, CKD）是日益严重的公共卫生问题，可由肾缺血、败血症、药物中毒和糖尿病等多种因素引起。该文重点介绍了用于研究这些疾病的临床前模型，特别是啮齿类动物模型和新兴的肾脏类器官组织模型。该综述详细总结了各模型的构建过程、基本机制及其在临床前治疗发展中的应用，评估了它们的优势、局限性和挑战，为制定有效的治疗策略提供了科学依据。.

Estimated glomerular filtration rate (eGFR) variation is associated with end-stage kidney disease (ESKD) development in patients with chronic kidney disease; whether annual variations in eGFR at health check-ups is associated with ESKD risk in the general population is unclear. We conducted a retrospective cohort study using Japanese national medical insurance claims from 2013 to 2020. Individuals who had their eGFR levels measured three times in annual health check-ups were included (N = 115,191), and the coefficient of variation of eGFR (CVeGFR) was calculated from 3-point eGFR. The end-point was ESKD as reported in the claims data. We analyzed the association between CVeGFR and ESKD incidence after adjusting for conventional ESKD risk factors. The CVeGFR median distribution was 5.7% (interquartile range: 3.5-8.5%). During a median follow-up period of 3.74 years, 164 patients progressed to ESKD. ESKD incidence was significantly higher in the highest quartile group (CVeGFR ≥ 8.5%) than in the other groups (P < 0.0001). After adjusting for risk factors, individuals with CVeGFR ≥ 8.5% had a significantly high ESKD incidence (adjusted hazard ratio: 3.01; 95% CI 2.14-4.30). High CVeGFR in annual health check-ups was associated with high ESKD incidence, independent of its other conventional risk factors, in the general population.

Chronic kidney disease (CKD) is a prevalent disease among felids; yet its origin is still poorly understood, and the disease often remains asymptomatic for years, underscoring the need for early diagnosis. This study aimed to investigate the diagnostic value of urinalysis in accurately staging CKD, particularly as routine health checks in large felids often overlook its significance. In this research, ultrasound-guided cystocentesis (UGC) was performed on 50 captive nondomestic felids during routine veterinary health checks under general anesthesia. Urinalysis included microscopic examination of the sediment, measurement of urine specific gravity (USG) and protein to creatinine ratio (UPC). Additional serum kidney markers, such as creatinine and symmetric dimethylarginine, were compared with USG and UPC to assess their diagnostic value as urinary biomarkers. The results demonstrated proteinuria (UPC > 0.4) or borderline proteinuria (UPC 0.2-0.4) in 49% of the animals. Among these cases, 62% were of renal origin, and 38% were postrenal causes. USG was significantly higher in felids with borderline proteinuria compared to those with proteinuria. A moderate, but significant negative correlation between serum parameters and USG was observed, emphasizing the importance of assessing both diagnostic parameters during kidney evaluations. Additionally, felids with CKD have an increased risk of urinary tract infections, necessitating microscopic urinalysis and bacterial culture analysis. Abnormalities, including hematuria, pyuria, crystalluria, and bacteriuria, were found in approximately 38% of cases through microscopical examination of urine. No complications associated with UGC were observed and abnormal findings were detected in 60% of the cases. Based on these results, the authors recommend the inclusion of UGC and urinalysis as standard diagnostic tools in general health checks for nondomestic felids. This approach provides valuable insights into the early detection and staging of CKD, supporting early intervention and supportive medical care to prolong renal health in these animals.

UNASSIGNED: Adults experiencing homelessness in the US face numerous challenges, including the management of chronic kidney disease (CKD). The extent of a potentially greater risk of adverse health outcomes in the population with CKD experiencing homelessness has not been adequately explored.
UNASSIGNED: To evaluate the association between a history of homelessness and the risk of end-stage kidney disease (ESKD) and death among veterans with incident CKD.
UNASSIGNED: This retrospective cohort study was conducted between January 1, 2005, and December 31, 2017. Participants included veterans aged 18 years and older with incident stage 3 to 5 CKD utilizing the Veterans Health Administration health care network in the US. Patients were followed-up through December 31, 2018, for the occurrence of ESKD and death. Analyses were performed from September 2022 to October 2023.
UNASSIGNED: History of homelessness, based on utilization of homeless services in the Veterans Health Administration or International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Homelessness was measured during the 2-year baseline period prior to the index date of incident CKD.
UNASSIGNED: The primary outcomes were ESKD, based on initiation of kidney replacement therapy, and all-cause death. Adjusted hazard ratios (HRs) were calculated to compare veterans with a history of homelessness with those without a history of homelessness.
UNASSIGNED: Among 836 361 veterans, the largest proportion were aged 65 to 74 years (274 371 veterans [32.8%]) or 75 to 84 years (270 890 veterans [32.4%]), and 809 584 (96.8%) were male. A total of 26 037 veterans (3.1%) developed ESKD, and 359 991 (43.0%) died. Compared with veterans who had not experienced homelessness, those with a history of homelessness showed a significantly greater risk of ESKD (adjusted HR, 1.15; 95% CI, 1.10-1.20). A greater risk of all-cause death was also observed (HR, 1.48; 95% CI, 1.46-1.50). After further adjustment for body mass index, comorbidities, and medication use, results were attenuated for all-cause death (HR, 1.09; 95% CI, 1.07-1.11) and were no longer significant for ESKD (HR, 1.04; 95% CI, 0.99-1.09).
UNASSIGNED: In this cohort study of veterans with incident stage 3 to 5 CKD, a history of homelessness was significantly associated with a greater risk of ESKD and death, underscoring the role of housing as a social determinant of health.

BACKGROUND: Kidney diseases are a major global health problem affecting millions of people. Despite this, there is as yet no effective drug therapy improving outcome in patients with renal disease. The aim of this study was to examine the nephroprotective effect of α-lipoic acid (ALA) in vitro and to examine the effect of ALA administered in vivo on the production of reactive sulfur species (RSS), including hydrogen sulfide (H2S) and compounds containing sulfane sulfur.
METHODS: The effect of ALA was studied in vitro by determining the viability of human embryonic kidney cells (HEK293) in normoxic and hypoxic conditions as well as in vivo in two groups of chronic kidney disease (CKD) patients: non-dialyzed (ND) and undergoing continuous ambulatory peritoneal dialysis (PD) after 30 days of ALA supplementation.
RESULTS: The results revealed that the viability of HEK293 cells was significantly decreased by hypoxic conditions, while ALA administered during hypoxia increased the viability to the level observed in normoxic conditions. Studies performed in plasma of CKD patients after ALA supplementation suggested that ALA did not affect the parameters of oxidative stress, while significantly increased the level of reactive sulfane sulfur in both ND and PD patients suffering from CKD. The results suggest that ALA can exert nephroprotective effects which are related to sulfane sulfur production.

BACKGROUND: The aim of this study was to investigate the association between systemic immune-inflammation index (SII) and all-cause mortality in individuals with chronic kidney disease (CKD).
METHODS: This prospective cohort study was carried out among 9303 participants with CKD from the National Health and Nutrition Examination Survey cycles spanning 1999 to 2018. The mortality data were ascertained by linking participant records to the National Death Index up to December 31, 2019. Complex sampling-weighted multivariate Cox proportional hazards models were employed to estimate the association between SII level and all-cause mortality, providing hazard ratios (HR) and 95% confidence intervals (CI). A restricted cubic spline analysis was conducted to explore potential nonlinear correlation. Subgroup analyses and sensitivity analyses were also conducted.
RESULTS: During a median follow-up period of 86 months, 3400 (36.54%) all-cause deaths were documented. A distinctive \"J\"-shaped relationship between SII level and all-cause mortality was discerned among individuals with CKD, with the nadir observed at an SII level of 478.93 within the second quartile. After adjusting for potential covariates, the risk of all-cause mortality escalated by 13% per increment of one standard deviation of SII, once SII exceeded 478.93 (HR = 1.13; 95% CI = 1.08-1.18). An elevated SII was associated with an increased risk of all-cause mortality among patients with CKD (Q4 vs. Q2: HR = 1.23; 95% CI = 1.01-1.48). Subgroup analyses indicated that the correlation between SII and CKD mortality was particularly pronounced among participants over 60 years old and individuals with diabetes. Sensitivity analyses revealed a linear positive association between SII and all-cause mortality after removing the extreme 5% outliers of SII.
CONCLUSIONS: A distinctive \"J\"-shaped relationship between SII level and all-cause mortality was identified among individuals with CKD. Further research is warranted to validate and expand upon these findings.

暂无摘要。

UNASSIGNED: G-protein coupled receptors (GPCRs) expressed on neutrophils regulate their mobilization from the bone marrow into the blood, their half-live in the circulation, and their pro- and anti-inflammatory activities during inflammation. Chronic kidney disease (CKD) is associated with systemic inflammatory responses, and neutrophilia is a hallmark of CKD onset and progression. Nonetheless, the role of neutrophils in CKD is currently unclear.
UNASSIGNED: Blood and renal tissue were collected from non-dialysis CKD (grade 3 - 5) patients to evaluate GPCR neutrophil expressions and functions in CKD development.
UNASSIGNED: CKD patients presented a higher blood neutrophil-to-lymphocyte ratio (NLR), which was inversely correlated with the glomerular filtration rate (eGFR). A higher frequency of neutrophils expressing the senescent GPCR receptor (CXCR4) and activation markers (CD18+CD11b+CD62L+) was detected in CKD patients. Moreover, CKD neutrophils expressed higher amounts of GPCR formyl peptide receptors (FPR) 1 and 2, known as neutrophil pro- and anti-inflammatory receptors, respectively. Cytoskeletal organization, migration, and production of reactive oxygen species (ROS) by CKD neutrophils were impaired in response to the FPR1 agonist (fMLP), despite the higher expression of FPR1. In addition, CKD neutrophils presented enhanced intracellular, but reduced membrane expression of the protein Annexin A1 (AnxA1), and an impaired ability to secrete it into the extracellular compartment. Secreted and phosphorylated AnxA1 is a recognized ligand of FPR2, pivotal in anti-inflammatory and efferocytosis effects. CKD renal tissue presented a low number of neutrophils, which were AnxA1+.
UNASSIGNED: Together, these data highlight that CKD neutrophils overexpress GPCRs, which may contribute to an unbalanced aging process in the circulation, migration into inflamed tissues, and efferocytosis.

暂无摘要。

BACKGROUND: The coexistence of cardiovascular disease and chronic kidney disease, termed chronic cardiovascular-kidney disorder (CCV-KD), is increasingly prevalent. However, limited studies have assessed the association between cardiovascular health (CVH), assessed by the American Heart Association\'s Life\'s Essential 8 (LE8), and CCV-KD.
METHODS: We conducted a prospective cohort study using data from UK Biobank. Participants without cardiovascular disease and chronic kidney disease at baseline and having complete data on metrics of LE8 were included (N = 125,986). LE8 included eight metrics, and the aggregate score was categorized as low (< 50 points), intermediate (50 to < 80 points), and high (≥ 80 points), with a higher score indicating better CVH health. Adjusted Cox proportional hazard models were conducted to explore the association of CVH with the risk of CCV-KD. The adjusted proportion of population attributable risk (PAR%) was used to calculate the population-level risk caused by low or intermediate CVH.
RESULTS: During a median follow-up of 12.5 years, 1,054 participants (0.8%) had incident CCV-KD. Participants with intermediate and high CVH had 54% (HR = 0.46, 95% CI: 0.40-0.54, P < 0.001) and 75% (HR = 0.25, 95% CI: 0.18-0.34, P < 0.001) lower risks of incident CCV-KD compared with those in low CVH group. There was an approximately dose-response linear relationship between the overall LE8 score and incident CCV-KD. The risk of incident CCV-KD decreased by 30% (HR = 0.70, 95% CI: 0.67-0.74, P < 0.001) for a 10-point increment of LE8 score. The adjusted PAR% of lower overall CVH was 47.4% (95% CI: 31.6%-59.8%).
CONCLUSIONS: Better CVH, assessed by using LE8 score, was strongly associated with decreased risk of incident CCV-KD. These findings imply optimizing CVH may be a preventive strategy to reduce the burden of CCV-KD.