American Journal of Nephrology最新文献

Introduction: Kidney injury molecule-1 (KIM-1) expression reflects proximal renal tubular damage, but plasma and urine KIM-1 have not been jointly studied in a CKD cohort.

Methods: Plasma and urine KIM-1 were measured in 2,581 adults from the NURTuRE-CKD cohort, a multicentre, non-dialysis-dependent CKD cohort. Survival analyses, C-statistics, and net reclassification improvement were used to assess associations and predictive performance of plasma and urine KIM-1 for kidney failure (KF), all-cause mortality, and a secondary endpoint of combined CKD progression endpoint (CKE) (KF or >40% decline in eGFR) in the total cohort and in KDIGO albuminuria categories, early CKD (eGFR >45 mL/min/1.73 m2), and four plasma/urine KIM-1 groups, dichotomised above and below the median value.

Results: Median age was 65 years, baseline eGFR 34.8 mL/min/1.73 m2, and urine albumin-to-creatinine ratio (uACR) 22.3 mg/mmol. During median follow-up of 48.8 months, 616 (23.9%) participants developed KF, 817 (32%) experienced CKE, and 344 (13.3%) died. Plasma and urine KIM-1 levels increased with lower eGFR, higher uACR, and diabetes. Plasma KIM-1 was independently associated with KF, while urine KIM-1 was associated with pre-KF death. The combination of high plasma and high urine KIM-1 conferred the greatest hazards of KF and all-cause mortality. Combining plasma and urine KIM-1 led to a 24.1% improvement in net reclassification index for KF. In earlier stages of CKD, both biomarkers were associated with CKD progression and there were large improvements in risk prediction for plasma KIM-1 alone. Increased albuminuria amplified the relationship between plasma and urine KIM-1 and KF risk.

Conclusion: This study highlights distinct prognostic associations of plasma and urine KIM-1 in CKD. Measuring both may be useful in improving risk stratification in people with CKD. For early-stage CKD, the need to use a combined CKE, including decline in eGFR, is emphasised as few of these people developed KF.

Introduction: High blood pressure accelerates chronic kidney disease (CKD) progression, but the optimal intensity of blood pressure control in this population remains unclear. We aimed to determine whether intensive blood pressure control, compared to less-intensive control, improves clinical outcomes in individuals with CKD.

Methods: A comprehensive search of PubMed, Embase, Scopus, and the Cochrane Library was conducted through December 2024. Randomized controlled trials comparing intensive versus standard blood pressure targets in patients with CKD stage 3 or higher were included. Eligible studies reported all-cause mortality and at least one cardiovascular or renal outcome. Risk of bias was assessed using the Cochrane Risk of Bias tool. A random-effects model was used to pool risk ratios (RRs) with 95% confidence intervals (CIs). Subgroup analyses were performed based on the baseline systolic blood pressure, inclusion of diabetic patients versus exclusion, and baseline glomerular filtration rate (GFR).

Results: Eleven randomized controlled trials with 8,740 participants were included. Intensive blood pressure control did not significantly reduce all-cause mortality (6.4% vs. 6.9%; RR, 0.91 [95% CI 0.73-1.13]; p = 0.32), cardiovascular mortality (RR, 0.89 [95% CI 0.69-1.15]; p = 0.3), major adverse cardiovascular events (RR, 0.91 [95% CI 0.69-1.20]; p = 0.27), decline in kidney function (RR, 0.86 [95% CI 0.59-1.25]; p = 0.34), or progression to end-stage kidney disease (RR, 1.00 [95% CI 0.81-1.23]; p = 0.99).

Conclusions: Intensive BP control did not improve overall mortality or renal outcomes in CKD patients. Further large, long-term studies are warranted.

Introduction: Current KDIGO guidelines for IgA nephropathy (IgAN) recommend proteinuria should be maintained at <0.5 g/day. In this study, we aimed to evaluate the association of proteinuria target achievement timing and stability with adverse kidney outcomes.

Methods: A cohort study was conducted with IgAN patients at Peking University First Hospital. We introduced three metrics: the timing of proteinuria first to target (TTT) in part A, time in target range (TTR), and area out of target (AOT) of proteinuria in part B to describe target achievement timing and stability, respectively. The target of proteinuria was less than 0.5 g/day. We analyzed the association between those three metrics and the composite kidney outcome, which was defined as the first occurrence of either end-stage kidney disease or a >50% decrease in estimated glomerular filtration rate from baseline.

Results: In part A, the primary outcome occurred in 166 (18.65%) patients. The 10-year kidney survival probability was 73% in TTT <6 months of group and 64% in TTT ≥6 months of group (p = 0.006). We identified a significant association between the rate of initial target achievement and clinical outcomes. In part B, the primary outcome occurred in 385 (23.21%) patients. The 10-year kidney survival probability was 45% in T1 (TTR = 0%), 60% in T2 (0%< TTR ≤50%), and 86% in T3 (50%< TTR ≤100%) groups (p < 0.001). The corresponding hazard ratios (95% CI) for the respective proteinuria-TTR categories were 0.54 (0.43-0.68) and 0.21 (0.15-0.31), respectively. Our results demonstrate that maintaining stable target-range duration strongly correlated with improved prognosis. Our further analysis using a restricted cubic spline model indicated that the association of TTR and primary outcome generally showed a linear relationship. The analysis of AOT showed consistent results.

Conclusion: Our study supports the importance of rapidly reaching proteinuria remission (<6 months) and maintaining proteinuria within this target range for an extended period.

Introduction: PLA2R-associated primary membranous nephropathy (PMN) was classified as IgG4-associated autoimmune disease, in which anti-PLA2R antibody is predominantly IgG4 subclass. Our objective was to explore the capability of anti-PLA2R IgG4-to-IgG ratio for predicting remission in PLA2R-associated PMN patients.

Methods: A total of 143 patients with anti-PLA2R IgG ≥14 RU/mL were biopsy-confirmed as PLA2R-associated PMN. Serum samples collected at the time of renal biopsy were tested for anti-PLA2R IgG and anti-PLA2R IgG4 using time-resolved fluoroimmunoassay. The anti-PLA2R IgG4-to-IgG ratio was calculated as anti-PLA2R IgG4 (ng/mL) divided by anti-PLA2R IgG (RU/mL). Patients were divided into high-ratio and low-ratio groups by cutoff value of 31.5 ng/RU determined by the maximally selected log-rank statistic. The relationship between anti-PLA2R IgG4-to-IgG ratio and remission was analyzed using Cox proportional hazard regression.

Results: Compared to the low-ratio group, patients in the high-ratio group were significantly younger (52 [40-60] vs. 58 [51-61] years, p = 0.035), had higher estimated glomerular filtration rate (102 [88-111] vs. 94 [72-100] mL/min/1.73 m2, p = 0.004), and obtained higher 6-month partial remission rates (64.6% vs. 30.0%, p = 0.001) and 1-year complete remission rates (38.3% vs. 7.7%, p = 0.003). The higher remission rates with high ratio remained in both moderate-low-risk and high-risk subgroups categorized according to KDIGO 2021 guidelines. The anti-PLA2R IgG4-to-IgG ratio had a significant positive relation with partial remission (hazard ratio [95% confidence interval] = 2.09 [1.27-3.46], p = 0.004), which also persisted across both risk subgroups. Kaplan-Meier survival curves confirmed the significantly higher possibility of partial remission in the high-ratio group.

Conclusion: An elevated anti-PLA2R IgG4-to-IgG ratio may be a supplementary predictor for remission in PLA2R-associated PMN.

Introduction: Obesity is associated with chronic kidney disease (CKD) incidence and progression. We examined whether bariatric surgery is associated with change in eGFR trajectory among patients with and without CKD.

Methods: Patients who underwent bariatric surgery at two health systems were identified using ICD-9/ICD-10 and CPT codes. Linear mixed models were fit on estimated glomerular filtration rate (eGFR) trajectory pre- and post-surgery among patients with or without CKD. Models were adjusted for age, sex, race, ethnicity, body mass index, hypertension, diabetes, follow-up duration, and type of bariatric surgery. Post-surgery, eGFR trajectory among patients with CKD was also compared following 1:2 propensity score matching to (1) patients without CKD who underwent surgery and (2) patients with CKD who did not undergo surgery.

Results: Patients with CKD (n = 139) at Michigan Medicine had a slower annual rate of eGFR decline post-surgery compared to patients without CKD (n = 278) (1.54 [-2.26, -0.81] vs. 3.15 [-3.41, -2.87] mL/min/1.73 m2; p < 0.001), despite adjusting for degree of weight loss. Among patients with CKD, surgery was associated with a slower annual rate of eGFR decline (-0.20 [-0.83, 0.43] post-surgery vs. -1.11 [-1.37, -0.85] mL/min/1.73 m2 for non-surgery patients; p < 0.001). In an external validation study of patients with CKD in the Providence health system, bariatric surgery predicted an average increase in annualized eGFR slope by 1.19 [0.12, 2.25] mL/min/1.73 m2 (p = 0.03).

Conclusion: Bariatric surgery is associated with less eGFR decline and may have weight-independent effects on preserving kidney function among persons living with obesity and CKD.

Introduction: Renal ischemia-reperfusion (I/R) injury can lead to acute kidney injury. SGLT-2 inhibitors, commonly used as hypoglycemic agents, have demonstrated the ability to mitigate cardiac I/R injury. Some studies have indicated that SGLT-2 inhibitors may safeguard renal tubular epithelial cells from damage caused by high glucose levels via mitochondrial mechanisms. SGLT-2 inhibitors alleviate renal hypoxia and cellular stress and enhance nutrient deprivation signaling. These combined effects may account for their inhibition of HIF-1α and activation of HIF-2α, which in turn leads to increased erythropoiesis, while also preventing organelle dysfunction, inflammation, and fibrosis. Our aim is to verify the efficacy of ertugliflozin in alleviating renal ischemia-reperfusion injury and to explore its potential protective mechanism.

Methods: HK-2 cells were exposed to hypoxia for 16 h, followed by a 3 h re-oxygenation period (H16R3), with or without ertugliflozin treatment. The activity and phenotype of HK-2 cells were detected by using detection methods such as CCK-8 assay, mitochondrial membrane potential detection, flow cytometry, and protein electrophoresis. It was determined through cell immunofluorescence staining, RNA interference experiments, and gene overexpression transfection experiments that ertugliflozin alleviated H/R-induced HK-2 cell damage by inhibiting HIF-1α in the HIF-1α-iNOS-NO pathway. In in vivo experiments, the bilateral renal pedicles were occluded using a vascular clamp for 25 min to induce renal ischemia. After 24 h post-operation, the mouse was continuously administered ertugliflozin by gavage until the third day after the operation. The total duration of ertugliflozin administration was 8 days. Blood samples and kidney tissues of the mouse were collected. Qualitative and quantitative analyses of mouse histological specimens were conducted through experiments such as enzyme-linked immunosorbent assay, H&E staining, immunohistofluorescence staining, and immunohistochemical staining.

Results: This study analyzed the effects of ertugliflozin on kidney I/R from both cellular and animal model perspectives. Transcriptome sequencing was used to screen the HIF-1 signaling pathway as the relevant signaling pathway through which ertugliflozin exerts its renal protective effect. RNA interference experiments and gene overexpression plasmid transfection experiments were conducted to clarify that ertugliflozin exerts corresponding renal protective effects in renal tubular epithelial cells and kidney I/R-induced renal injury through the HIF-1α site in the HIF-1α-Inos pathway.

Conclusion: Our study provides compelling preliminary evidence that ertugliflozin may improve I/R-induced acute kidney injury by downregulating HIF-1α. This study provides some reference value for the treatment and management of renal I/R injury.

Introduction: Preeclampsia is associated with acute renal complications during pregnancy, but the risk of renal sequelae later in life is unclear. We determined if preeclampsia was associated with chronic renal complications in the long-term period following pregnancy.

Methods: We conducted a longitudinal cohort study of 1,431,156 pregnant women in QC, Canada with 25,598,024 person-years of follow-up between 1989 and 2023. The main exposure measure was preeclampsia, and outcomes included hospitalization for vascular and nonvascular renal complications up to 34 years after pregnancy. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between preeclampsia and subsequent kidney complications using Cox regression models adjusted for patient characteristics.

Results: Patients with preeclampsia had a higher hospitalization rate for renal complications than patients without preeclampsia (29.4 vs. 19.5 per 10,000 person-years). Preeclampsia was associated with 1.45 times the risk of hospitalization for renal disease during follow-up (95% CI 1.40-1.50). Risks were particularly elevated for renal vascular disease (HR 3.74, 95% CI 3.21-4.37), diabetic kidney disease (HR 3.71, 95% CI 3.18-4.32), and glomerulopathy (HR 3.44, 95% CI 2.92-4.05). Associations were also present with obstructive uropathy (HR 1.44, 95% CI 1.30-1.58). Severe forms of preeclampsia, including early onset preeclampsia (HR 1.90, 95% CI 1.72-2.10) and superimposed preeclampsia (HR 2.52, 95% CI 2.22-2.85), were strongly associated with subsequent renal morbidity.

Conclusion: Preeclampsia, especially severe preeclampsia, is associated with the long-term risk of renal disease. Patients with preeclampsia may benefit from nephrological follow-up in the long-term period after pregnancy.

Background: A comparison of the efficacy of different extracorporeal platforms in reducing free light chain levels in the setting of light chain cast nephropathy has not been discussed in detail.

Summary: Recent advances in treating multiple myeloma have increased overall survival and brought a cure closer to reality. Kidney failure remains one of the most significant factors impacting survival, and the recovery of kidney function is crucial in this aspect. Light chain cast nephropathy is the most common subtype of kidney injury caused by toxic monoclonal proteins in myeloma patients and is closely related to the concentration of the involved serum-free light chain (sFLC). A fast decline in sFLC is associated with improved kidney recovery rates. Negative results in randomized controlled trials of extracorporeal therapies have not yet distracted clinicians from applying these options in light chain cast nephropathy due to the demonstrated efficiency of these modalities in sFLC removal compared to conventional dialytic therapies. This review summarizes the efficiency of sFLC reduction with available extracorporeal methods in patients with multiple myeloma and severe kidney failure when combined with anti-myeloma therapy.

Key messages: Since achieving a hematologic response is crucial in light chain cast nephropathy, it appears tough to demonstrate the possible benefit of extracorporeal FLC removal in cast nephropathy in this setting. High-cutoff hemodialysis reduces serum FLC by about 90% after several sessions when combined with anti-myeloma therapy, albeit with albumin loss. Other options, such as medium cutoff hemodialysis and adsorptive methods, may provide a less efficient removal with lower loss of plasma proteins. The contribution of extracorporeal therapy to renal recovery is still unclear.

Introduction: Tenapanor is currently seen as a promising treatment for hyperphosphatemia in hemodialysis patients. Although previous meta-analysis has investigated its efficacy and safety, the potential impact of tenapanor remained a topic of further investigation. This meta-analysis aimed to provide an updated and thorough assessment of tenapanor efficacy in reducing serum phosphate levels and its safety in hemodialysis patients, integrating new evidence, and refining the analysis of treatment outcomes.

Methods: In this systematic review and meta-analysis, we searched online databases up to August 2024 for studies evaluating the efficacy and safety of tenapanor in hemodialysis patients. Only short-term randomized controlled trials (4-8 weeks) comparing tenapanor with placebo were included. The primary outcome was the change in serum phosphate levels from baseline. Safety was assessed based on data regarding drug-related adverse effects (AEs), including diarrhea and other gastrointestinal AEs.

Results: Among the selected 8 clinical trials with a total of 1,001 patients, tenapanor showed a significant reduction in serum phosphate levels from baseline compared to placebo (mean difference: -1.39 mg/dL; 95% confidence interval [CI]: -1.94, 0.84; p < 0.0001). A greater number of patients in the tenapanor group were able to achieve target serum phosphate levels of ≤5.5 mg/dL (relative risk: 2.80; 95% CI: 1.70, 4.61; p < 0.0001). Drug-related AEs, gastrointestinal AEs, and diarrhea were more severe in the tenapanor group compared to the placebo.

Conclusion: In summary, the results indicate that tenapanor effectively lowers serum phosphate levels in hemodialysis patients and facilitates achievement of target levels, although drug-related side effects were common. However, these findings are based exclusively on short-term trials (4-8 weeks). Further long-term studies are needed to confirm the sustained efficacy and safety of tenapanor.