American Journal of Nephrology最新文献

Introduction: Inhaled fine and ultrafine particulate matter may affect organs other than the lung, including the kidney. Recent studies have consistently shown the possibility of air pollution in highly polluted countries to be nephrotoxic. However, in countries like Australia, where air quality generally adheres to or remains below the WHO standards, the subtle yet consequential impacts of chronic exposure to seemingly safe levels of traffic PM2.5, are a subject of increasing significance. However, how such exposures in the peri-pregnancy period affect kidney health in mothers and the offspring is unclear, which formed the aims of this study.

Methods: Female Balb/c mice were exposed to PM2.5 (5 μg/day) delivered nasally for 6 weeks prior to mating, during gestation and lactation (PM group). In a sub-group, PM2.5 was switched to saline from mating until offspring were weaned to model mothers moving to areas with clean air. Kidneys were analysed in dams and adult offspring at 13 weeks of age.

Results: PM2.5 induced oxidative stress without histological changes in the dam's kidney. However, male PM offspring displayed in-utero underdevelopment, characterised by reduced body weight and kidney-to-body weight at birth compared to control offspring, and lower glomerular numbers, with a marked increase in albuminuria, glomerulosclerosis, inflammation, oxidative stress, and mitochondrial injury. Female PM offspring had delayed postnatal development, lower glomerular numbers, increased glomerulosclerosis and oxidative stress injury markers. Removal of PM2.5 from conception significantly reduced DNA oxidation and kidney damage in the offspring.

Conclusion: There is no safe level of ambient PM2.5 for kidney health when exposed in-utero. Maternal PM2.5 exposure equally impacts the kidney health of male and female offspring. Removal of PM2.5 from conception was overall protective to the offspring.

Introduction: Peritoneal dialysis (PD) is an effective home therapy for end-stage kidney disease. However, continuous exposure to PD fluids with high glucose concentration and recurrent peritonitis may lead to the activation of cellular and molecular processes of peritoneal damage, including inflammation and fibrosis. In particular, recent studies have highlighted the role of neutrophils in chronic inflammation. This study explores how neutrophil extracellular traps (NETs) affect peritoneal membrane function and contribute to technical failures in PD patients.

Methods: We conducted a prospective observational study involving 250 non-infectious and 30 acute peritonitis patients. NETs were measured using nucleosome and myeloperoxidase DNA levels in PD fluids. Monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-8 (MMP-8) were also measured to assess peritoneal inflammation and damage.

Results: A significant increase in peritoneal NETs, as determined by nucleosome and myeloperoxidase DNA levels, was observed in patients with acute peritonitis compared to patients without peritonitis. Even in non-infectious samples, NET levels were widely distributed and closely correlated with levels of MCP-1 and MMP-8. Higher levels of peritoneal NETs were closely associated with increased 4-hour dialysate/peritoneal (D/P) creatinine ratio and 1-hour D/P sodium levels, indicating a higher prevalence of fast transport and limited free water transport. These factors were associated with a higher risk of technical failure. During a mean follow-up of 34 months, 39.2% (98 patients) switched from PD to hemodialysis, with higher NET levels significantly increasing the risk by 1.9 times (95% confidence interval 1.27-2.83, p=0.020).

Conclusions: This study suggests the importance of peritoneal NETs not only as markers of acute inflammation but also as significant immunological predictors of chronic peritoneal membrane inflammation and dysfunction, and as potential risk factors for technical failure.

Background: Sodium glucose co-transporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRAs) reduce the progression of kidney disease. Whether the combination of these agents provides additional benefits compared to SGLT2i alone is worth exploring using data from randomized trials designed for this purpose.

Aims: To assess the randomized treatment effect of MRAs combined with SGLT2i vs SGLT2i alone on markers of kidney and cardiovascular health.

Methods: Random-effects meta-analysis of randomized trials testing the combination of MRAs with SGLT2i vs SGLT2i alone on albuminuria, blood pressure, estimated glomerular filtration rate (eGFR) and serum potassium among patients with chronic kidney disease (CKD).

Results: Four randomized trials were included with a total of 272 patients with CKD: eGFR varying between 30 and 60 mL/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) between 90 and 500 mg/g, with >60% having type 2 diabetes. Treatment with MRAs plus SGLT2i vs SGLT2i alone reduced UACR by -33.6% (-42.6 to -24.7%), P <0.001, I2 =0%. MRAs plus SGLT2i vs SGLT2i alone reduced systolic blood pressure by -6.1 mmHg (-8.9 to -3.3) mmHg, eGFR by -3.4 mmHg (-5.2 to -1.6) mmHg, and increased serum potassium by +0.23 mmol/L (0.15 to 0.34) mmol/L; P <0.001 for all, without significant heterogeneity between trials (I2 <25%).

Conclusion: In this meta-analysis, MRAs plus SGLT2i provided greater reductions in albuminuria and blood pressure compared to SGLT2i alone. Larger randomized trials with longer follow-up should test whether MRA/SGLT2i combination therapies improve cardiovascular and renal outcomes compared to SGLT2i alone.

Introduction: IgA nephropathy (IgAN), a leading cause of kidney failure worldwide, is one of the most common forms of primary glomerulonephropathy with variability by race and ethnicity. Using a diverse cohort within a large integrated health system in the United States (US), we identified and characterized patients with biopsy-proven IgAN and report annual incidence rates across racial/ethnic groups and standardized to the US nationally.

Methods: Cross sectional study between 1/1/2010 through 12/31/2021 within Kaiser Permanente Southern California was performed. Patients (age>/=18years) who underwent a native kidney biopsy and identified as primary IgAN comprised the study population. Laboratory, demographic, and co morbidity information obtained from electronic health records. Annual incidence rates were calculated for biopsy-proven IgAN (per 100,000 person-years) and standardized to 2020 US Census.

Results: Of 9,392 individuals who underwent kidney biopsy, 606 adult patients identified with primary IgAN. Crude annual IgAN incidence rates ranged from 1.3 to 2.2 (per 100,000 person years). US census standardized incidence rate (CI) of IgAN was 1.4 (0.8, 2.0) per 100,000 person years in the 12-year period. Incidence rate (per 100,000 person years) was highest among Asian/Pacific Islanders (4.5) and Hispanics (1.7) and lowest among Whites (1.2) and Blacks (0.6). Median eGFR was 51 ml/min with median uPCR 1.8g/g.

Conclusion: Among a large diverse US population within Southern California, we observed an IgAN incidence rate of 1.7 which estimated to a standardized US incidence of 1.4 (per 100,000 person years) within a 12-year period. Patients appear to be diagnosed at more advanced disease given the eGFR and uPCR at biopsy.

Introduction: Although the prevalence of chronic kidney disease (CKD) is increasing in the aging population, the clinical relevance of the CKD definition (glomerular filtration rate [GFR] <60 mL/min/1.73 m2) in older populations remains debatable. We investigated the clinical outcomes in older populations with mildly to moderately decreased GFR (45-59 mL/min/1.73 m2, CKD stage 3A).

Methods: A total of 7,789,242 participants aged ≥40 years with estimated GFR (eGFR) ≥45 mL/min/1.73 m2 in national health screening examination from 2012 to 2017 were included in this retrospective cohort study using the Korean National Health Insurance Service database. The main outcomes included kidney failure, cardiovascular disease (CVD), and all-cause death. Cox regression hazard models were used to estimate the hazard ratios.

Results: The proportion of participants with eGFR 45-59 mL/min/1.73 m2 was 10.0% and 16.3% in the old (65-74 years) and very old (75≥ years) groups, respectively. Mildly to moderately decreased eGFR was associated with a higher risk of kidney failure, CVD, and all-cause death compared with eGFR 60-89 mL/min/1.73 m2 in the old and very old groups, regardless of proteinuria (adjusted hazard ratio [95% confidence interval] in the very old group without proteinuria: kidney failure 3.048 [2.495-3.722], CVD 1.103 [1.066-1.142], and all-cause death 1.172 [1.144-1.201]).

Conclusion: Mildly to moderately decreased eGFR was associated with an increased risk of kidney failure, CVD, and all-cause death in the older population, regardless of proteinuria, suggesting the importance of appropriate monitoring and management in this population.

Introduction Diabetes, kidney disease, and cardiovascular disease have complex interactions and coexistences that significantly worsen a patient's overall health. Previous research results have shown that SGLT2i hypoglycemic drugs can not only effectively control blood sugar in diabetic patients, but also protect the kidneys and heart. This study further focuses on diabetic patients with kidney disease to explore the effectiveness of using SGLT2i hypoglycemic drugs in avoiding heart-related complications or death. Methods This is a multi-center retrospective cohort study using the Taipei Medical University Clinical Research Database (TMUCRD) as the data source. This study selected patients who suffered from both type 2 diabetes and chronic kidney disease from 2008/01/01 to 2020/12/31 as the research team. Integrated or separate 4P-MACE (4-point major adverse cardiovascular events) and mortality were the outcomes of this study. The Kaplan Meier curves method and Cox proportional hazard regression analysis were used to explore the association between each influencing factor and the outcome. Results A total of 5,005 patients with type 2 diabetes and CKD were included in this study, of which 524 patients were stably treated with SGLT2i, 3,952 patients were treated with DPP4i, and 529 patients were treated with TZD. The results showed that the SGLT2i user group had a significantly lower risk of 4P-MACE compared with the SGLT2i non-user group (HR: 0.68, 95% CI [0.49, 0.95], p=0.024). The SGLT2i group had a significantly lower risk of cardiovascular mortality compared with the DPP4i and TZD groups (HR: 0.37, 95% CI [0.21, 0.65], p<0.001; HR: 0.42, 95% CI [0.20, 0.90], p=0.025). Conclusion This study found that for patients with both diabetes and kidney disease, SGLT2i is a better option than other oral hypoglycemic medications because it can significantly avoid the occurrence of heart-related complications. The results of this study can be used as a reference for clinical medication selection practice.

Introduction: Chronic kidney diseases (CKD) encompass a spectrum of complex pathophysiological processes. While numerous genome-wide association studies (GWASs) have focused on individual traits such as albuminuria, estimated glomerular filtration rate (eGFR), and eGFR change, there remains a paucity of genetic studies integrating these traits collectively for comprehensive evaluation.

Methods: In this study, we performed individual GWASs for albuminuria, baseline eGFR, and eGFR slope utilizing data from non-diabetic individuals enrolled from the Taiwan Biobank (TWB). Subsequently, we employed principal component analysis to transform these three quantitative traits into principal components (PCs) and performed GWAS based on these principal components (PC-based GWAS).

Results: The individual GWAS analyses of albuminuria, baseline eGFR, and eGFR slope identified 10, 13, and 210 candidate loci respectively, with 2, 3, and 99 of them representing previously reported loci. PC-based GWAS identified additional 20 novel candidate loci linked to CKD (p values ranging from 5.8 × 10-7 to 9.1 × 10-6). Notably, 4 of these 20 single nucleotide polymorphisms (rs9332641, rs10737429, rs117231653, and rs73360624) exhibited significant associations with kidney expression quantitative trait loci.

Conclusion: To our knowledge, this study represents the first PC-based GWAS integrating albuminuria, baseline eGFR, and eGFR slope. Our approach found 20 novel candidate loci suggestively associated with CKD, underscoring the value of integrating multiple kidney traits in unraveling the pathophysiology of this complex disorder.

Introduction: Clinical laboratories have replaced conventional manual urine microscopy with automated urinalysis; however, concerns persist regarding its validity in detecting specific elements of urinary sediment crucial for evaluating kidney diseases. This study aimed to assess the accuracy of urinary sediment analysis performed by a large hospital laboratory compared to a standardized microscopic review, focusing on patients both with and without kidney disease.

Methods: Urine samples were randomly selected from routine laboratory specimens at a university hospital. Laboratory analysis was performed using LabUmat 2 and Urised 3 PRO equipment (Abbott Diagnostics). In the automated analysis for sediment examination, technicians have the option to reclassify urinary sediment elements as necessary and, if warranted, conduct manual microscopic evaluations to validate findings. The laboratory's analysis was compared with a "reference" analysis, which was double-blinded and conducted by two experienced technicians using bright-field and phase-contrast microscopy.

Results: 503 samples were selected, with 52.3% originating from nephrology outpatient clinic patients. Overall agreement between the laboratory results and the reference analysis was 42.1%. The sensitivity (SN) of the laboratory examination for detecting pathological casts, lipiduria, and renal tubular epithelial cells was low (<50%), while specificity (SP) was high (>98%). However, for hyaline casts (SN: 50.4%; SP: 80.9%) and dysmorphic red blood cells (SN: 62.3%; SP: 96.2%), accuracy was intermediate. Performance was better for hematuria (SN: 86.1%; SP: 82.3%; intraclass correlation coefficient [ICC]: 0.703; R: 0.828) and leukocyturia (SN: 84.9%; SP: 95.1%; ICC: 0.807; R: 0.861). In patients with kidney disease (N = 248) and in samples manually reviewed by the laboratory (N = 115), accuracy for each urinary element was comparable to the overall sample findings. However, when assessing the ability to identify elements suggestive of nephropathy, only samples manually reviewed by the laboratory showed statistically similar results to those obtained by the reference analysis (p = 0.503, McNemar's test).

Conclusion: Employing automated urinalysis seems to be accurate for detecting hematuria and leukocyturia, as well as for screening patients without kidney diseases. However, clinical laboratories attending complex patients should employ personalized strategies to help decide when to perform manual review, thus avoiding misleading urinalysis results.