Kidney360最新文献

Background: Incident atrial fibrillation (AF) is common following kidney transplantation (KTx) and is associated with worse clinical outcomes. Artificial intelligence electrocardiography (AI-ECG) algorithms have demonstrated efficacy in predicting risk of new-onset AF in the general population, however their prognostic value in KTx recipients is relatively unknown.

Methods: Retrospective analysis was conducted on KTx recipients without AF, with at least one pre-transplant ECG between 2011 and 2021 across three tertiary centers in the United States (Mayo Clinic sites in Minnesota, Arizona, and Florida). A previously validated AI-ECG algorithm estimated the probability of incident AF for each patient. Based on AI-ECG probabilities, patients were categorized into high and low risk groups, with the optimal AI-ECG score cut-off determined. The incidence of new-onset AF, allograft failure, and mortality were compared between groups.

Results: Overall, 6246 patients (age 53.5 ± 13.8 years; 58.9% male) were included. Pre-transplant AI-ECG probability of AF ≥5% was the optimal cutoff for high risk of incident AF (sensitivity 72%, specificity 62%). High risk scores were associated with true new-onset AF at 30 days (aHR 2.89, 95%CI 2.05-4.09, p<0.001), three years (aHR 2.54, 95%CI 1.99-3.26, p<0.001), and five years post-transplant (aHR 2.48, 95%CI 1.99-3.09, p<0.001). High risk AI-ECG scores were also associated with increased mortality (aHR 1.56, 95%CI 1.30-1.88, p<0.001) and overall allograft failure (aHR 1.50, 95%CI 1.30-1.75, p<0.001) through five year follow-up.

Conclusions: This pre-transplant AI-ECG parameter identified patients at increased risk of new-onset AF post-KTx and provided prognostic utility. Overall, this easy to obtain tool allows for risk stratification of patients who may benefit from closer monitoring, targeted risk factor modification, and early intervention.

Background: Rhabdomyolysis (RM) is the etiology in 7-10% of cases of AKI and benefits from early, aggressive volume repletion. RM as an etiology of AKI is often missed in clinical setting as it requires specific diagnostic testing (CK testing). We evaluated various criteria that could be applied to urinalysis (UA) to identify individuals at elevated likelihood of RM.

Methods: A retrospective electronic chart review of adult inpatients hospitalized at the Yale New Haven Hospital was performed between January 2020-December 2022. A total of 16 screening criteria were formulated using combinations of heme (≥1+, ≥ 2+, ≥ 3+, and ≥ 4+) and RBCs (≤5, ≤10, ≤20, and ≤30) per high power field (HPF) thresholds from the closest UA prior to AKI. The accuracy was assessed using post-AKI CK>1000 U/L as the definition of rhabdomyolysis diagnosis.

Results: A total of 12,273 patients were included of which 20.5% patients had serum CK levels checked after AKI. Of those, 222 (8.8%) met the diagnostic criteria for rhabdomyolysis. The median time from laboratory AKI diagnosis to CK measurement was 2.7 (0.9-6.5) days. UA criterion 1.4 (≥1 heme and ≤30 RBCs) met by 35.1% demonstrated the highest sensitivity for rhabdomyolysis. UA criterion 3.1 (≥ 3+ heme and ≤5 RBCs) met by 2.0% demonstrated a specificity of 96.7% and sensitivity of 16.7% included the highest proportion of patients with CK measurement (45.3%), and more than a quarter of those tested had levels consistent with rhabdomyolysis.

Conclusions: Rhabdo-suspected patients with greater heme/RBC discrepancy on UA were more likely to be tested for serum CK levels and diagnosed with rhabdo. CK testing was uncommon under all definitions, suggesting missed rhabdomyolysis cases. Automated electronic screening of UA parameters with clinical decision support to order CK may be a viable mechanism to increase the diagnosis of rhabdo among AKI patients.

Background: Decreased skeletal muscle mass is common in hemodialysis patients and contributes to adverse outcomes. However, muscle mass alone does not fully capture muscle health. An imbalance between extracellular and intracellular water (ECW/ICW ratio) may reflect tissue-level integrity of skeletal muscle. This study examined the combined prognostic significance of the skeletal muscle mass index (SMI) and ECW/ICW ratio for mortality and health-related quality of life (HRQoL) in hemodilaysis patients.

Methods: In this multicenter cohort study, 295 maintenance hemodialysis patients (208 men, 87 women) underwent multifrequency bioelectrical impedance analysis. Low SMI was defined according to the Asian Working Group for Sarcopenia (men <7.0 kg/m2, women <5.7 kg/m2), and high ECW/ICW was defined as ≥0.66. Patients were categorized into four groups based on SMI and ECW/ICW status. HRQoL was assessed using the Kidney Disease Quality of Life Short Form, and mortality was recorded through March 2024.

Results: Among the cohort, 93 patients (31.5%) had low SMI, and 38 (12.9%) had both low SMI and high ECW/ICW. These patients were older and demonstrated lower ICW, poorer nutritional status, chronic inflammation, and higher natriuretic peptide levels. During a median follow-up of 3.7 years, 34 patients died. Low SMI (HR 1.82, 95% CI 1.11-3.65) and high ECW/ICW (HR 2.21, 95% CI 1.34-4.08) independently predicted mortality, while their coexistence conferred the highest risk (HR 3.95, 95% CI 2.01-7.72). Both indices were associated with impaired HRQoL across multiple domains, particularly those related to physical functioning.

Conclusions: Combined assessment of SMI and ECW/ICW identifies muscle vulnerability and predicts mortality and HRQoL in hemodialysis patients. This simple, noninvasive approach may improve early detection of high-risk individuals and inform targeted interventions addressing nutrition, inflammation, and fluid management.

Background: Following acute kidney injury, successful regeneration of tubular epithelium is essential to restore normal kidney function. We have previously reported that arginase-1 expressing macrophages in the outer medulla promote tubular proliferation following ischemic injury, however the mechanism of this effect remained unidentified.

Methods: Arginase-1+ macrophage-dependent proliferative signals and their cellular source were determined by cell sorting and single-cell transcriptional profiling at 2 days post injury in mice subjected to ischemia-reperfusion injury (IRI) and in vitro using transwell coculture of macrophages and renal cells.

Results: Quantitative PCR analysis of outer medullary RNA on day 2 post-IRI in wild type and macrophage-specific arginase1 null (Arg1mko) mice identified Insulin-like growth factor -1 (Igf1) as the epithelial growth factor significantly upregulated in an arginase1-dependent manner after kidney injury. Single-cell RNA sequencing analysis of mouse kidneys, human kidney biopsies, and sorted outer medullary cells identified myofibroblasts and endothelial cells as potential cellular sources of IGF-1. In vitro studies showed that myofibroblast and endothelial cell expression of Igf1 was dependent on macrophage arginase-1 expression, and that myofibroblast-secreted IGF1 induced epithelial cell IGF1 receptor activation and proliferation. Consistent with this, in vivo activation of the IGF1 receptor on surviving S3 proximal tubule cells after injury was dependent on macrophage Arg1 expression.

Conclusions: Our results demonstrate that alternatively activated macrophages signal cooperatively with myofibroblasts and possibly endothelial cells to coordinate local IGF1 secretion and proliferative tubule repair at sites of epithelial cell loss after kidney injury. These findings support an important role of activated myofibroblasts in effective tubule repair.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) are effective in managing chronic kidney disease (CKD) and type 2 diabetes (T2D). However, there are concerns about an increased risk of diabetic ketoacidosis (DKA) associated with the use of SGLT2i, particularly in patients with CKD.

Methods: The is a population-based, new-user, active comparator cohort study comparing SGLT2i vs. GLP1RA initiators using three U.S. healthcare databases: Optum's de-identified Clinformatics® Data Mart (2014-2024), Merative MarketScan (2014-2022), and Medicare Fee-for-Service (2014-2020). The exposure is initiation of either SGLT2i or GLP1RA, defined as a new prescription without prior use in 365 days. The primary outcome was hospitalization with DKA identified via inpatient ICD-9/10 codes. Incidence rates (IRs), rate differences (RDs), and hazard ratios (HRs) were calculated.

Results: After 1:1 propensity score matching, the study population included 143,858 patients, 71,929 in the SGLT2i arm and 71,929 in the GLP1RA arm. The mean age (standard deviation) was 71.28 (8.16) years, and 48.8% were female. Patients initiating SGLT2i had higher risk of hospitalization with DKA compared to GLP1RA initiators (IR 4.37 vs. 3.13 events per 1,000 person-years; RD 1.23 [95% CI 0.54, 1.92]; HR 1.40 [95% CI 1.16, 1.68]). The number needed to harm was 813 per 1,000 person-years for SGLT2i compared to GLP1RA initiation. Results remained consistent in subgroup analyses stratified by age (<70 vs. ≥70 years), sex, body mass index (<30 vs. ≥30 kg/m2), frailty status, baseline cardiovascular disease, diabetic retinopathy, hyperglycemia, metformin use, and insulin use.

Conclusions: The incidence rate of DKA among SGLT2i and GLP1RA initiators remained low overall. However, SGLT2i use was associated with a 40% increased risk of hospitalization with DKA compared to GLP1RA use among patients with CKD stages 3-4 and T2D. Clinicians should remain vigilant when monitoring patients with CKD and T2D treated with SGLT2i.

Background: CKD is a risk factor for adverse pregnancy outcomes (APOs) in singleton pregnancies. Little is known about multifetal pregnancies in women with CKD. Due to higher maternal age and the wider use of medically assisted fertilization, multifetal pregnancies are increasing. We aimed to review pregnancy outcomes in the largest multicentre series of multifetal pregnancies in women affected by CKD.

Methods: This retrospective study gathered data from three Italian units with long-standing experience in the follow-up of pregnancy in women with CKD (2000-2023). Propensity-score matched (age, parity, BMI, year of delivery) multifetal low-risk pregnancies and singleton pregnancies served as controls; multifetal pregnancies were also matched for chorionicity, amnionicity and mode of conception. Intrauterine death of at least one fetus, given the low number of events, was explored in the overall multifetal cohorts.

Results: In this propensity score matched-cohort study, 52 multifetal pregnancies in women with CKD were associated with a significantly lower gestational age compared to 104 low-risk non-CKD controls (median 34.0 vs 36.0 gestational weeks - GW) and with lower term-delivery rate (9.6% vs 28.8%). NICU admission was more frequent in multifetal pregnancies with CKD (50.9% vs 25.2%, p=0.003).Cox regression and Kaplan-Meier analyses confirmed the independent impact of CKD on gestation duration. In women with CKD, multifetal pregnancies had a markedly shorter gestation than singletons (median 34 vs 39 GW, p< 0.00001), with significantly higher risk of preterm birth <34 GW (OR 9.733), SGA (OR 5.155), and NICU admission (OR 8.033). The difference was sharper than in low-risk non-CKD pregnancies (35 and 39 GW respectively).

Conclusions: This study, the largest assessing the risks of APOs in women with CKD carrying more than one fetus, suggests that multifetal gestation is a strong additional risk. These findings highlight the need for further investigation and demonstrate the importance of careful counselling, particularly in medically assisted reproduction.