Baseline Chronic Kidney Disease Stage Research Articles

Extended-Release Calcifediol: A Data Journey From Phase 3 Studies to Real-world Evidence Highlights the Importance of Early Treatment of Secondary Hyperparathyroidism.

Early secondary hyperparathyroidism (SHPT) diagnosis and treatment are crucial to delay the progression of SHPT and related complications, in particular, cardiovascular events and bone fractures. Extended-release calcifediol (ERC) has been developed for the treatment of SHPT in patients with stage 3/4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). This review compares baseline characteristics and treatment responses of SHPT patients receiving ERC in Phase 3 studies with those treated with ERC in a real-world study. Mean ± standard deviation baseline parathyroid hormone (PTH) levels were 147 ± 56 pg/mL and 148 ± 64 pg/mL in the Phase 3 ERC cohorts, and 181 ± 98 pg/mL in the real-world study. Other baseline laboratory parameters were consistent between the clinical and real-world studies. ERC treatment increased 25-hydroxyvitamin D [25(OH)D] and significantly reduced PTH levels, regardless of baseline CKD stage, in all studies. In the pooled Phase 3 per-protocol populations, 74% of the ERC cohort were up-titrated to 60 μg/day after 12 weeks at 30 μg/day, 97% attained 25(OH)D levels ≥30 ng/mL, and 40% achieved ≥30% PTH reduction. Despite a much lower rate of uptitration in the real-world study, 70% of patients achieved 25(OH)D levels ≥30 ng/mL, and 40% had a ≥30% reduction in PTH. These data establish a 'continuum' of clinical and real-world evidence of ERC effectiveness for treating SHPT, irrespective of CKD stage, baseline PTH levels, and ERC dose. This evidence supports early treatment initiation with ERC, following diagnosis of SHPT, VDI, and stage 3 CKD, to delay SHPT progression.

Low rate of severe-end-stage kidney disease after SABR for localised primary kidney cancer

BackgroundStereotactic ablative body radiotherapy (SABR) is an emerging treatment for patients with primary renal cell carcinoma (RCC). However, its impact on renal function is unclear. This study aimed to evaluate incidence and clinical factors predictive of severe to end-stage chronic kidney disease (CKD) after SABR for RCC.Methods and materialsThis was a Single institutional retrospective analysis of patients with diagnosed primary RCC receiving SABR between 2012–2020. Adult patients with no metastatic disease, baseline estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73 m2, and at least one post-SABR eGFR at six months or later were included in this analysis. Patients with upper tract urothelial carcinoma were excluded. Primary outcome was freedom from severe to end-stage CKD, determined using the Kaplan–Meier estimator. The impact of baseline CKD, age, hypertension, diabetes, tumor size and fractionation schedule were assessed by Cox proportional hazard models.ResultsSeventy-eight consecutive patients were included, with median age of 77.8 years (IQR 70–83), tumor size of 4.5 cm (IQR 3.9–5.8) and follow-up of 42.2 months (IQR 23–60). Baseline median eGFR was 58 mls/min; 55% (n = 43) of patients had baseline CKD stage 3 and the remainder stage 1–2. By last follow-up, 1/35 (2.8%) of baseline CKD 1–2, 7/27 (25.9%) CKD 3a and 11/16 (68.8%) CKD 3b had developed CKD stage 4–5. The estimated probability of freedom from CKD stage 4–5 at 1 and 5 years was 89.6% (CI 83.0–97.6) and 65% (CI 51.4–81.7) respectively. On univariable analysis, worse baseline CKD (p < 0.0001) and multi-fraction SABR (p = 0.005) were predictive for development of stage 4–5 CKD though only the former remained significant in multivariable model.ConclusionIn this elderly cohort with pre-existing renal dysfunction, SABR achieved satisfactory nephron sparing with acceptable rates of severe to end-stage CKD. It can be an attractive option in patients who are medically inoperable.

Early-Stage Chronic Kidney Disease and Related Health Care Spending

The global burden of chronic kidney disease (CKD) is substantial and potentially leads to higher health care resource use. To examine the association between early-stage CKD and health care spending and its changes over time in the general population. Cohort study using nationwide health checkup and medical claims data in Japan. Participants included individuals aged 30 to 70 years with estimated glomerular filtration rates (eGFR) of 30 mL/min/1.73 m2 or greater at the baseline screening in 2014. Data analyses were conducted from April 2021 to October 2023. The CKD stages at baseline, defined by the eGFR and proteinuria, were as follows: eGFR of 60 mL/min/1.73 m2 or greater without proteinuria, eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. The primary outcome was excess health care spending, defined as the absolute difference in health care spending according to the baseline CKD stages (reference group: eGFR ≥60 mL/min/1.73 m2 without proteinuria) in the baseline year (2014) and in the following 5 years (2015 to 2019). Of the 79 988 participants who underwent a health checkup (mean [SD] age, 47.0 [9.4] years; 22 027 [27.5%] female), 2899 (3.6%) had an eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, 1116 (1.4%) had an eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and 253 (0.3%) had an eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. At baseline, the presence of proteinuria and an eGFR less than 60 mL/min/1.73 m2 were associated with greater excess health care spending (adjusted difference, $178; 99% CI, $6-$350 for proteinuria; $608; 99% CI, $233-$983 for an eGFR of 30-59 mL/min/1.73 m2; and $1254; 99% CI, $134-$2373 for their combination). The study consistently found excess health care spending over the following 5 examined years. In this cohort study of nationwide health checkup and medical claims data in Japan, early-stage CKD was associated with excess health care spending over the 5 examined years, and the association was more pronounced with a more advanced disease stage.

Abstract 12444: Pulse Pressure and Cardiovascular and Renal Outcomes by Age in the Chronic Renal Insufficiency Cohort

Pulse pressure (PP) is associated with cardiovascular events and the progression of chronic kidney disease (CKD) to end stage kidney disease (ESKD). While PP is known to widen with age, it is less clear what other clinical factors affect PP and whether the risks associated with wide PP are the same across all ages. We used Cox proportional hazards models to investigate the association of PP with development of 1) atherosclerotic cardiovascular disease (ASCVD) events (congestive heart failure hospitalization, myocardial infarction, stroke and peripheral artery disease) or death and 2) 50% reduction in estimated glomerular filtration rate (eGFR) or ESKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. In sensitivity analyses, we evaluated the association of time-updated PP with these outcomes, accounting for potential time-updated confounders using inverse probability of treatment weighting. We evaluated for effect modification by age (divided into tertiles), apparent treatment-resistant hypertension (HTN), baseline diabetes mellitus (DM) status, baseline CKD stage and baseline cardiovascular disease (CVD). Among 5,621 participants with CKD followed for ~5.4 years, mean PP was 57±19 mmHg, 1,396 (25%) had an ASCVD event, 1,186 (21%) died and 1,783 (32%) participants experienced the composite renal outcome. Every 10 mm Hg wider PP was associated with 6% higher risk of an ASCVD event or death (time-updated adjusted hazard ratio [HR]=1.06, 95% CI 1.04, 1.08) and 17% higher risk of the composite renal outcome (time-updated adjusted HR=1.17, 95% CI 1.16, 1.18). Wider PP was associated with a higher risk of ASCVD events or death among participants in the lowest age tertile (21-61 years; Figure 1A ), but a higher risk of the composite renal outcome in the oldest age tertile (71-79 years; Figure 1B ), suggesting PP may be associated with different pathophysiology across ages.

Changes in renal blood flow after surgically induced weight loss: can bariatric surgery halt the progression of chronic kidney disease?

BackgroundWe previously demonstrated how kidney injury in patients with morbid obesity can be reversed by bariatric surgery (BaS). Objective(s)Based on previous experience, we hypothesize patients’ potentially reversible kidney injury might be secondary to reduction in renal blood flow (RBF), which improves following BaS. SettingAcademic Hospital. MethodsWe conducted a retrospective analysis of patients who underwent BaS at our institution from 2002 to 2019. We identified patients with chronic kidney disease (CKD) using the estimated glomerular filtration rate (eGFR) from the CKD Epidemiology Collaboration Study (CKD-EPI) classification system. We used the BUN/Creatinine (Cr) ratio pre- and postoperatively to determine a prerenal (decreased RBF) versus intrinsic component as the responsible cause of CKD in this patient population. Decreased RBF was defined as BUN/Cr > 20 preoperatively. ResultsOur analysis included n = 2924 patients, of which 11% (n = 325) presented decreased RBF. From our original sample, only n = 228 patients had the complete data necessary to assess both eGFR and RBF (BUN/Cr). Patients with baseline CKD stage 2 demonstrated preoperative BUN/Cr 20.85 ± 10.23 decreasing to 14.99 ± 9.10 at 12-month follow-up (P < .01). Patients with baseline CKD stage 3 presented with preoperative BUN/Cr 23.88 ± 8.75; after 12-month follow-up, BUN/Cr ratio decreased to 16.38 ± 9.27 (P < .01). Patients with CKD stage 4 and ESRD (eGFR < 30) did not demonstrate a difference for pre- and postoperative BUN/Cr 21.71 ± 9.28 and 19.21 ± 14.58, respectively. Conclusion(s)According to our findings, patients with CKD stages 1–3 present improvement of their kidney function after BaS. This amelioration could be secondary to improvement of the RBF, an unstudied reversible mechanism of kidney injury in the bariatric population.

Health-related Quality of Life in 10 years Long-term Survivors of Chronic Kidney Disease: A From-J Study

ObjectiveThe Chronic Kidney Disease (CKD) practice facilitation program in the Frontier of Renal Outcome Modifications in Japan (FROM-J) study reduced cardiovascular disease (CVD) events in patients with CKD. 10-year long-term survivors with CKD lived with serious complications, including end-stage kidney disease (ESKD) and CVD. This study aimed to measure health-related quality of life (HRQOL) in 10-year long-term CKD survivors and examine the predictors and determinants of clinical indices for measured QOL scores. MethodsThe EQ-5D-5L, a generic preference-based instrument, was administered to 1,473 CKD survivors enrolled in the FROM-J study. The 10th-year data collection was performed by either primary care physicians or participants who filled out questionnaires from October 2018 to March 31, 2019. ResultsThe response rate was 38.2% (423/1,473). The mean QOL score was 0.893 (95% confidence interval (CI), 0.880–0.906), and the median QOL score was 1.000 (interquartile range (IQR), 0.806–1.000). The mean QOL score in participants with renal replacement therapy was 0.824 (95% CI, 0.767–0.881), and the median was 0.828 (IQR, 0.755–1.000). The mean QOL score in participants with CVD was 0.877 (95% CI, 0.811–0.943), and the median was 1.000 (IQR, 0.723–1.000). The mean QOL score in participants with 50% decline in eGFR was 0.893 (95% CI, 0.860–0.926), and the median was 0.889 (IQR, 0.825–1.000). The decrease in QOL scores with baseline CKD stages was significant according to the Jonckheere–Terpstra test for trend (P = 0.002). Baseline age, systolic blood pressure, and history of hyperuricemia were significant predictors of 10th-year QOL scores. ConclusionWe suggest that CKD complications negatively affect the QOL scores in 10-year long-term survivors with CKD. CKD guideline-based practices, prevention of ESKD/CVD and management of hypertension, diabetes and hyperuricemia, might contribute to future HRQOL in patients with CKD.

A new machine-learning model to predict long-term renal function impairment after minimally invasive partial nephrectomy: the Fundació Puigvert predictive model.

To provide a new model to predict long-term renal function impairment after partial nephrectomy (PN). Data of consecutive patients who underwent minimally invasive PN from 2005 to 2022 were analyzed. A minimum of 12 months of follow-up was required. We relied on a machine-learning algorithm, namely classification and regression tree (CART), to identify the predictors and associated clusters of chronic kidney disease (CKD) stage migration during follow-up. 568 patients underwent minimally invasive PN at our center. A total of 381 patients met our inclusion criteria. The median follow-up was 69 (IQR 38-99) months. A total of 103 (27%) patients experienced CKD stage migration at last follow-up. Progression of CKD stage after surgery, ACCI and baseline CKD stage were selected as the most informative risk factors to predict CKD progression, leading to the creation of four clusters. The progression of CKD stage rates for cluster #1 (no progression of CKD stage after surgery, baseline CKD stage 1-2, ACCI 1-4), #2 (no progression of CKD stage after surgery, baseline CKD stage 1-2, ACCI ≥ 5), #3 (no progression of CKD stage after surgery and baseline CKD stage 3-4-5) and #4 (progression of CKD stage after surgery) were 6.9%, 28.2%, 37.1%, and 69.6%, respectively. The c-index of the model was 0.75. We developed a new model to predict long-term renal function impairment after PN where the perioperative loss of renal function plays a pivotal role to predict lack of functional recovery. This model could help identify patients in whom functional follow-up should be intensified to minimize possible worsening factors of renal function.

Association of Baseline Chronic Kidney Disease Stage With Short- and Long-Term Outcomes After Fenestrated Endovascular Aneurysm Repair

Fenestrated endovascular aneurysm repair (FEVAR) is a well-established treatment approach for juxtarenal and short-neck infrarenal aortic aneurysms. Recommendations and clinical outcomes are lacking for offering FEVAR in patients with chronic kidney disease (CKD). We aimed to compare short- and long-term outcomes for patients with none-to-mild versus moderate-to-severe CKD undergoing FEVAR. We retrospectively reviewed consecutive patients undergoing standard FEVAR with Cook devices at a single institution. The cohort was stratified by preoperative CKD stage none-to-mild or moderate-to-severe (CKD 1-2 and CKD 3-5, respectively). The primary outcome was postoperative acute kidney injury (AKI). Secondary outcomes included 30-day perioperative complications, 1- and 5-year rates of overall survival, dialysis, renal target artery patency, endoleak, and reintervention assessed by the Kaplan-Meier method. Aneurysm sac regression, number of surveillance computed tomography (CT) scans, and CKD stage progression were assessed at latest follow-up. Multivariate Cox proportional hazards modeling was used to evaluate the association of CKD stage 3 and stage 4-5 with all-cause mortality, controlling for differences in baseline characteristics. From 2012- to 2022, 184 patients (of which 82% were male) underwent FEVAR with the Cook ZFEN device (mean follow-up 34.3months). Group CKD 3-5 comprised 77 patients (42%), was older (75.2 vs. 73.0years, P=0.04), had increased preoperative creatinine (1.6 vs. 0.9mg/dL, P<0.01), and demonstrated increased renal artery ostial calcification (37.7% vs. 21.5%, P=0.02) compared with Group CKD 1-2. Perioperatively, CKD 3-5 sustained higher estimated blood loss (342 vs. 228ml, P=0.01), longer operative times (186 vs. 162min, P=0.04), and longer length of stay (3 vs. 2days, P<0.01). Kaplan-Meier 1- and 5-year survival estimates were lower for CKD 3-5 (82.3% vs. 95.1%, P<0.01 and 55.4% vs. 70.8%, P=0.02). Fewer CKD 3-5 patients remained free from chronic dialysis at 1year (94.4% vs. 100%, P=0.015) and 5years (84.7% vs. 100%, P<0.01). There were no significant differences in postoperative AKI rate (CKD 1-2 6.5% vs. CKD 3-5 14.3%, P=0.13), long-term renal artery patency, reinterventions, type I or III endoleak, mean sac regression, or total follow-up CT scansbetween groups. CKD stage progression occurred in 47 patients (31%) at latest follow-up but did not differ between stratified groups (P=0.17). On multivariable modeling, age (hazardratio 1.05, 95% confidence interval 1.01-1.09, P=0.02) and CKD stage 4-5 (hazard ratio 6.39, 95% confidence interval 2.26-18.05, P<0.01) were independently associated with mortality. Preoperative CKD status did not negatively impact the durability or technical success related to aneurysm outcomes after FEVAR. Worsening CKD stage was associated with lower 1- and 5-year overall survival and freedom from dialysis after FEVAR with no statistically significant differences in 30-day or long-term technical aneurysm outcomes.

#3259 ARTEMIS: A PHASE 3 STUDY OF RAVULIZUMAB TO PROTECT PATIENTS WITH CKD UNDERGOING CARDIAC SURGERY FROM AKI AND SUBSEQUENT MAJOR ADVERSE KIDNEY EVENTS

Abstract Background and Aims In patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), pre-existing chronic kidney disease (CKD) confers a substantial risk for poor outcomes, including the development of cardiac surgery-associated acute kidney injury (CSA-AKI). CSA-AKI occurs in ≥50% of patients with CKD undergoing cardiac surgery with CPB vs ∼20–25% of patients without CKD1,2. The risk of subsequent Major Adverse Kidney Events (MAKE; a composite of sustained kidney dysfunction, initiation of dialysis, and death) is also elevated in patients with CKD. Causes of CSA-AKI are multifactorial and complex, and may include inflammation, oxidative stress, renal congestion, and ischaemic injury (such as ischaemic-reperfusion injury [IRI]). IRI is a common cause of AKI and typically results from early hypoperfusion while on bypass, followed by kidney injury upon reperfusion. There are currently no approved therapies that reduce the risk of AKI and associated poor outcomes after cardiac surgery with CPB3. Preclinical and clinical studies suggest that damage and inflammation caused by IRI and CPB is amplified by complement activation3; early treatment with C5 inhibitors, especially before onset of ischaemia, may lower the risk of damage. Method ARTEMIS is a Phase 3, randomised, double-blind, placebo-controlled, multicentre study of ravulizumab in adults with CKD and stable cardiac disease undergoing non-emergent sternotomy with CPB, to reduce the risk of post-operative AKI and subsequent MAKE 90 days post-surgery. Key inclusion and exclusion criteria can be found in Figure 1 and a study schematic in Figure 2. Briefly, the study consists of an up to 28-day screening period, randomisation and dosing 1–7 days prior to surgery with CPB (Day 1), a 90-day primary evaluation period post-CPB, and a survival follow-up at day 365 post-CPB. Approximately 736 participants will be randomised 1:1 to receive a single weight-based dose of ravulizumab or placebo; randomisation will be based on baseline CKD stage (3A, 3B, 4) and surgery type (mitral valve replacement or combined procedures vs other single procedures). The primary objective of this study is to assess the efficacy of ravulizumab in reducing the risk of MAKE90, defined as meeting ≥1 of the following by day 90 post-CPB: ≥25% sustained decrease from baseline in estimated glomerular filtration rate (calculated using the Chronic Kidney Disease Epidemiology Collaboration equation, based on serum Cystatin C); initiation of renal replacement therapy; death from any cause. The safety of ravulizumab in participants with CKD undergoing non-emergent CPB will also be evaluated. Other secondary objectives include assessment of ravulizumab efficacy for reducing AKI (based on serum creatinine) and MAKE risk at earlier timepoints following CPB, alongside any effects it may have on healthcare resource utilisation and health-related quality of life – as well as treatment immunogenicity – in participants with CKD undergoing non-emergent CPB. Results The final analysis will be conducted when all participants have completed the primary evaluation period. Conclusion The aim of this study is to assess whether terminal complement inhibition with ravulizumab is safe and effective in reducing kidney injury and improving outcomes in patients with CKD undergoing cardiac surgery with CPB.

A retrospective database analysis of erythropoiesis-stimulating agent treatment patterns and associated healthcare resource use in patients with non-dialysis-dependent chronic kidney disease-related anaemia in Japan.

This study was conducted to evaluate clinical characteristics, treatment patterns, and healthcare resource use (HCRU) for patients in Japan with non-dialysis-dependent chronic kidney disease (CKD) and anaemia. This retrospective, longitudinal, epidemiological database extraction study used the JMDC Claims Database, comprising ~9.4 million unique beneficiaries. The observation period for anaemia and erythropoiesis-stimulating agent (ESA)/iron treatment was 1 January 2015 to 31 December 2018, and for HCRU and costs was 1 April 2016 to 31 March 2018. The non-dialysis-dependent CKD anaemia population, and the ESA treatment, iron treatment, and no-treatment cohorts were evaluated. Patient characteristics, treatment patterns, and outcomes were summarised descriptively. The non-dialysis-dependent CKD anaemia population included 5908 patients (7.9%), with 464 patients in the ESA treatment cohort, 809 patients (13.7%) in the iron treatment cohort (13.7%), and 4405 (74.6%) patients in the no-treatment cohort. The prevalence of patients prescribed an antihypertensive, antidiabetic, and/or antihyperlipidaemic medication generally increased with increasing baseline CKD stage. Proportions of no treatment for anaemia decreased while ESA treatment increased with increasing CKD stage; ESA treatment increased with decreasing baseline haemoglobin levels. Patients in the ESA treatment cohort generally had more frequent events associated with HCRU and higher costs from HCRU-associated activities (e.g., inpatient and outpatient care, pharmacy). As CKD severity increased, anaemia management changed from iron use or no treatment to ESA use; however, anaemia may be undertreated across all CKD stages. ESA-treated patients incurred greater HCRU-associated costs relative to other patients with non-dialysis-dependent CKD anaemia in Japan.

Association of polygenic scores with chronic kidney disease phenotypes in a longitudinal study of older adults

Risk of chronic kidney disease (CKD) is influenced by environmental and genetic factors and increases sharply in individuals 70 years and older. Polygenic scores (PGS) for kidney disease-related traits have shown promise but require validation in well-characterized cohorts. Here, we assessed the performance of recently developed PGSs for CKD-related traits in a longitudinal cohort of healthy older individuals enrolled in the Australian ASPREE randomized controlled trial of daily low-dose aspirin with CKD risk at baseline and longitudinally. Among 11,813 genotyped participants aged 70 years or more with baseline eGFR measures, we tested associations between PGSs and measured eGFR at baseline, clinical phenotype of CKD, and longitudinal rate of eGFR decline spanning up to six years of follow-up per participant. A PGS for eGFR was associated with baseline eGFR, with a significant decrease of 3.9 mL/min/1.73m2 (95% confidence interval -4.17 to -3.68) per standard deviation (SD) increase of the PGS. This PGS, as well as a PGS for CKD stage 3 were both associated with higher risk of baseline CKD stage 3 in cross-sectional analysis (Odds Ratio 1.75 per SD, 95% confidence interval 1.66-1.85, and Odds Ratio 1.51 per SD, 95% confidence interval 1.43-1.59, respectively). Longitudinally, two separate PGSs for eGFR slope were associated with significant kidney function decline during follow-up. Thus, our study demonstrates that kidney function has a considerable genetic component in older adults, and that new PGSs for kidney disease-related phenotypes may have potential utility for CKD risk prediction in advanced age.

Triglycerides and Renal Outcomes According to Albuminuria and in Consideration of Other Metabolic Syndrome Components in Diabetic US Veterans

Introduction: Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Previous studies have shown that the relationship of triglycerides (TGs) with outcomes changes across stages of CKD. Our objective was to examine the association of TG independent of other metabolic syndrome components with renal outcomes in diabetic patients with or without CKD. Methods: This retrospective cohort study included diabetic US veteran patients with valid data on TGs, estimated glomerular filtration rate (eGFR), and albuminuria (urinary albumin/creatinine ratio) between fiscal years 2004 and 2006. Using Cox models adjusted for clinical characteristics and laboratory markers, we evaluated the relationship of TG with incident albuminuria (stratified by eGFR category) and based on eGFR (stratified by baseline albuminuria categories). To evaluate the relationship of TG with time to end-stage renal disease (ESRD), we stratified models by baseline CKD stage (eGFR category) and baseline albuminuria stage ascertained at time of TG measurement. Results: In a cohort of 138,675 diabetic veterans, the mean ± SD age was 65 ± 11 years old and included 3% females and 14% African Americans. The cohort also included 28% of patients with non-dialysis-dependent CKD (eGFR <60 mL/min/1.73 m²), as well as 28% of patients with albuminuria (≥30 mg/g). The median (IQR) of serum TG was 148 (100, 222) mg/dL. We observed a slight positive linear association between TG and incident CKD after adjustment for Case-Mix and Laboratory variables among non-albuminuric and microalbuminuric patients. The relationship of high TG trended towards a higher risk of ESRD in CKD 3A non-albuminuric patients and in CKD 3A and 4/5 patients with microalbuminuria. Conclusion: In a large cohort, we have shown that elevated TGs are associated with all kidney outcomes tested independently of other metabolic syndrome components in diabetic patients with normal eGFR and normal albumin excretion rate, but the association is weaker in some groups of diabetic patients with preexisting renal complications.

Long-term follow-up of HCV-infected patients with end-stage chronic kidney disease after sustained virological response with direct-acting antiviral therapy

Background and aimPatients with chronic kidney disease (CKD) and hepatitis C infection can be safely and effectively treated with direct-acting antivirals (DAAs). However, there is scarce data on the long-term impact of hepatitis C cure on CKD. The aim of this study was to assess the long-term mortality, morbidity and hepatic/renal function outcomes in a cohort of HCV-infected individuals with CKD treated with DAAs. Methods135 HCV patients with CKD stage 3b-5 who received ombitasvir/paritaprevir/ritonavir±dasabuvir in a multicenter study were evaluated for long-term hepatic and renal outcomes and their associated mortality. Results125 patients achieved SVR and 66 were included. Prior to SVR, 53 were under renal replacement therapy (RRT) and 25 (37.8%) had liver cirrhosis. After a follow-up of 4.5 years, 25 (38%) required kidney transplantation but none combined liver–kidney. No changes in renal function were observed among the 51 patients who did not receive renal transplant although eGFR values improved in those with baseline CKD stage 3b-4. Three (5.6%) subjects were weaned from RRT. Eighteen (27.3%) patients died, mostly from cardiovascular events; 2 developed liver decompensation and 1 hepatocellular carcinoma. No HCV reinfection was observed. ConclusionsLong-term mortality remained high among end-stage CKD patients despite HCV cure. Overall, no improvement in renal function was observed and a high proportion of patients required kidney transplantation. However, in CKD stage 3b-4 HCV cure may play a positive role in renal function.

Abstract 10208: Troponin Frequency for Diagnosis of NSTEMI Across Estimated Glomerular Filtration Rate: A Nationwide Sample From US Veterans Health Administration

Introduction: Recent data suggest comparable diagnostic performance of cardiac specific troponin (cTn) in chronic kidney disease (CKD) compared to those without CKD, including when shorter time interval between tests is considered for high sensitivity (hs) assays. Objective: We performed a descriptive analysis of the adherence to recommended testing frequency across CKD stages in a large nationally representative dataset from the US Veterans Health Administration (VHA). Methods: The Loma Linda VA IRB approved the study under expedited review. Unique admissions for non-ST elevation myocardial infarction (NSTEMI) between 1999 and 2022in the VHA system with available cTn lab values (n=104, 390) were evaluated. ANOVA was utilized to compare time between first and second cTn values across CKD groups. After 2012, criteria for cTn interval reduced from 6-9 hours to 3-6 hours for hs-cTn. Criteria were considered met if time interval between cTn checks was &amp;lt; 9 hours before 2012, &amp;lt; 6 h after 2012. All analyses performed using R statistical software. Results: Troponin I was the assay utilized in 80% of the sample; high-sensitivity (hs) assays made up the minority (&amp;lt;1%) and were primarily used after 2012. Average time interval between first and second cTn checks (across all assays over entire observation period) was 8.1, 8.4, 8.5, 9.3, 9.6, 7.9, 8.1 hours for CKD G1, G2, G3a, G3b, G4, G5, ESKD, respectively (p = 0.001, for trend) (Figure). When cardiac catheterization is performed, cTn criteria met was associated with shorter time to cardiac catheterization (48.5h vs. 52.4h, p &lt; 0.001), irrespective of baseline CKD stage. Conclusions: Consistent application of guideline supported practices in NSTEMI care was noted across CKD stages in VHA hospitals, associated with timely diagnostic measures.

Real-World Effects of Biologics on Renal Function in Psoriatic Patients: A Retrospective Study.

Patients with severe psoriasis are prone to deterioration of renal function. Whether biologics with potent anti-inflammatory action can prevent deterioration of renal function in psoriatic patients was unclear. To investigate the effects of different biologics on renal function in patients with severe psoriasis. By using the Chang Gung Research Database in Taiwan during 2006-2018, we analyzed the changes in renal function of psoriatic patients from 2 years before biologic treatments to baseline (start of biologic treatment) to after 2 years' treatment with different classes of biologics (anti-TNF, anti-IL-12/23, and anti-IL-17 agents). The renal function was evaluated by estimated glomerular filtration rate (eGFR) and the staging of chronic kidney disease (CKD). We further analyzed the risk factors of progression on the staging of CKD during biologics treatment. We included 601 patients with severe psoriasis receiving continuous use of biologics for ≥ 2 years. We detected no significant differences between pre-biologic treatment with conventional systemic treatment and post-biologic treatment in the levels of eGFR and progression of CKD staging among psoriatic patients receiving different classes of biologics. Most patients (97.8%) remained at stable CKD stage, while progression of CKD stage over time occurred in 13 patients (2.2%), with seven treated with anti-TNF biologics and six treated with anti-IL-12/23 biologics. Of note, all 52 patients receiving anti-IL-17 biologics had stable CKD. Progression of CKD during biologics use was associated with lower baseline levels of eGFR, higher baseline CKD stage, older age, diabetes, and dyslipidemia. Further multiple logistic regression analysis showed diabetes as an independent factor for the deterioration of renal function during biologic treatment. Biologic treatments failed to improve but did not worsen renal function of psoriatic patients during a 2-year follow-up period. Diabetes is an important risk factor for the deterioration of renal function.

Sleeve gastrectomy in patients with severe obesity and baseline chronic kidney disease improves kidney function independently of weight loss: a propensity score matched analysis.

In the last 10 years, severe obesity and the associated metabolic syndrome have reached pandemic proportions and consequently have significantly increased the prevalence of related co-morbidities such as chronic kidney disease (CKD). One in 7 people in the United States have CKD, and 90% of those are not aware of it. Following sleeve gastrectomy (SG) in patients with severe obesity and baseline CKD stage ≥2, to determine improvement of glomerular function and analyze the relationship between kidney function and weight loss. US Hospital, Academic Institution. We retrospectively reviewed the charts of all patients who underwent SG at our institution from 2010 to 2019. Kidney function assessment using the Chronic Kidney Disease Epidemiology Collaboration Study (CKD-EPI) equation and classification was carried out preoperatively and postoperatively at 12-months follow-up. Propensity score matching (1:1 ratio) was used to balance the distribution of covariates between patients with a baseline estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 and patients with normal kidney function. We calculated the eGFR of 1330 bariatric patients who underwent SG. Of these patients, 18.79% (n = 250) met the criteria for CKD-EPI eGFR calculation preoperatively and at 12-months follow-up after SG. From the 250 patients included in the analysis, 42% (n = 105) were classified as CKD stage ≥2. When comparing the baseline preoperative eGFR at 12-months follow-up after SG, we observed an improvement of 8.26 ± 11.89 mL/min/1.73 m2 in CKD stage ≥2 (eGFR <90 mL/min/1.73 m2) as compared with 1.98 ± 10.25 mL/min/1.73 m2 in patients with eGFR >90 mL/min/1.73 m2 (P < .001). There is short-term improvement of the eGFR in patients with severe obesity following SG. This improvement is significant in CKD stages ≥2 and seems unrelated to weight loss.

Estimating the causal effect of treatment with direct-acting antivirals on kidney function among individuals with hepatitis C virus infection.

BackgroundDirect-acting antivirals (DAA) are highly effective at treating Hepatitis C virus (HCV) infection, with a cure rate >95%. However, the effect of DAAs on kidney function remains debated.MethodsWe analyzed electronic health record data for DAA-naive patients with chronic HCV infection engaged in HCV care at Boston Medical Center between 2014 and 2018. We compared the following hypothetical interventions using causal inference methods: 1) initiation of DAA and 2) no DAA initiation. For patients with normal kidney function at baseline (eGFR>90 ml/min/1.73m2), we estimated and compared the risk for reaching Stage 3 chronic kidney disease (CKD) (eGFR≤60 ml/min/1.73m2) under each intervention. For patients with baseline CKD Stages 2–4 (15<eGFR≤90 ml/min/1.73m2), we estimated and compared the mean change in eGFR at 2 years after baseline under each intervention. We used the parametric g-formula to adjust our estimates for baseline and time-varying confounders.ResultsFirst, among 1390 patients with normal kidney function at baseline the estimated 2-year risk difference (95% CI) of reaching Stage 3 CKD for DAA initiation versus no DAA was -1% (-3, 2). Second, among 733 patients with CKD Stage 2–4 at baseline the estimated 2-year mean difference in change in eGFR for DAA initiation versus no DAA therapy was -3 ml/min/1.73m2 (-8, 2).ConclusionsWe found no effect of DAA initiation on kidney function, independent of baseline renal status. This suggests that DAAs may not be nephrotoxic; furthermore, in the short-term, HCV clearance may not improve CKD.

A multiple 24-hour urine collection study indicates that kidney function decline is related to urinary sodium and potassium excretion in patients with chronic kidney disease

Multiple 24-hour urine collections are necessary to adequately assess sodium and potassium intake. Here, we assessed kidney function decline for four years after baseline in relation to seven-time averaged 24-hour urinary sodium and potassium excretion (UNaV, UKV), their UNaV/UKV ratio, and their categorical combination in outpatients with chronic kidney disease (CKD). This retrospective cohort study was based on 240 outpatients with baseline CKD stages 3-5, baseline age 20 years or more (median age 72.0 years), and a median follow-up (with interquartile range) of 2.9 (1.4-4.0) years. Outcome was the percentage change in annual slope of estimated glomerular filtration rate (delta eGFR per year). In linear mixed models, percentage changes in delta eGFR per year were -3.26% (95% confidence interval -5.85 to -0.60),+5.20% (2.34 to 8.14), and -5.20% (-7.64 to -2.69), respectively, per one standard deviation increase in the seven-time averaged UNaV and UKV, and their UNaV/UKV ratio. Additionally, percentage changes per year in delta eGFR per year were -16.27% (-23.57 to -8.27) in the middle-to-high UNaV and low UKV group, compared with the low UNaV and middle-to high UKV group. Thus, our study reinforces the observation of opposite associations between GFR decline and urinary excretion rates of sodium (positive) and potassium (negative), respectively. Whether changes in dietary sodium and potassium intake slow GFR decline still requires further study.

Renal safety and biochemical changes for 2years after switching to tenofovir alafenamide from long-term other nucleotide analog treatment in patients with chronic hepatitis B.

Long-term use of nucleotide analogs such as adefovir (ADV) or tenofovir disoproxil fumarate (TDF) may cause renal impairment. Tenofovir alafenamide (TAF) has less systemic exposure than TDF did. The aims were to examine longitudinal changes in renal function and biochemical parameters for 2years after switching from long-term ADV and TDF to TAF, and to explore factors associated with improved renal function after TAF in patients with chronic hepatitis B. The prospective observational cohort study included 306 patients with chronic hepatitis B who underwent switching from long-term TDF or ADV to TAF. The primary outcome was the changes in estimated glomerular filtration rate (eGFR) after TAF. Among 306 patients, 190 (65.3%) and 106 (34.7%) had chronic kidney disease (CKD) stages 1-2 and 3a-4 at baseline. In patients with CKD stages 3a-4, the mean eGFR significantly increased until week 12 and plateaued from week 12 to year 2 (adjusted slope using linear mixed effect models: +9.01ml/min/1.73m2 /year until week 12; p<0.001). In contrast, the mean eGFR plateaued from baseline to year 2 in the CKD stages 1-2 subgroup. Multivariate logistic regression showed that baseline CKD stage ≥3a, steeper decline in eGFR 1year before TAF, and shorter duration of any nucleotide analog use was significantly associated with ≥10% improvement in eGFR in year 1. Switching from TDF or ADV to TAF resulted in favorable renal safety for 2years. In CKD stage 3a-4 subgroup, eGFR after TAF was recovered in the first 12weeks and subsequently stabilized.

Risk of Atherosclerotic Cardiovascular Disease and Nonatherosclerotic Cardiovascular Disease Hospitalizations for Triglycerides Across Chronic Kidney Disease Stages Among 2.9Million US Veterans.

BackgroundHigh triglycerides are associated with atherosclerotic cardiovascular disease (ASCVD) risks. Among patients with advanced chronic kidney disease (CKD), the association of elevated triglycerides with mortality is diminished and, thus, we investigated the relationship of triglycerides with ASCVD and non‐ASCVD hospitalizations across CKD stages.Methods and ResultsThe cohort comprised 2 963 176 veterans who received care in 2004 to 2006 (baseline) and were followed up to 2014. Using Cox models, we evaluated baseline and time‐varying triglycerides with time to ASCVD or non‐ASCVD hospitalizations, stratified by baseline CKD stage, and adjusted for demographics and baseline or time‐updated clinical characteristics. The cohort mean±SD age was 63±14 years, with a baseline median (interquartile range) triglycerides level of 127 (87–189) mg/dL, and a quarter had prevalent CKD. There was a linear association between baseline triglycerides and ASCVD risk; however, the risk with high triglycerides ≥240 mg/dL attenuated with worsening CKD stages (reference: triglycerides 120 to <160 mg/dL). Baseline triglycerides were associated with a U‐shaped relationship for non‐ASCVD events in patients with CKD 3A to 3B. Patients with late‐stage CKD had lower to null relationships between baseline triglycerides and non‐ASCVD events. Time‐varying triglycerides associations with ASCVD were similar to baseline analyses. Yet, the time‐varying triglycerides relationship with non‐ASCVD events was inverse and linear, where elevated triglycerides were associated with lower risks.ConclusionsAssociations of higher triglycerides with ASCVD and non‐ASCVD events declined across advancing CKD stages, where a lower to null risk was observed in patients with advanced CKD. Studies are needed to examine the impact of advanced CKD on triglycerides metabolism and its association with outcomes in this high‐risk population.