Moderate CKD Research Articles

Machine learning identifies individuals at higher risk of incident cardio-renal-metabolic diseases and cardiovascular death who have unrealised opportunities to reduce future cardiovascular risk

Abstract Background Machine learning may be able to identify individuals at risk of cardio-renal-metabolic events using routinely-collected data, and these individuals may be suitable for targeted preventative strategies.(1, 2) Purpose To train and test a machine learning algorithm to identify individuals at higher risk of incident cardio-renal-metabolic diseases and cardiovascular death, and then establish if there are opportunities to reduce their future cardiovascular risk. Methods We trained a random classifier (OPTIMISE) in UK primary care EHR data from 2 081 139 individuals aged ≥30 years (Jan 2, 1998, Nov 30, 2018), randomly divided into training (80%) and testing (20%) datasets. We calculated the cumulative incidence rate for ten cardio-renal-metabolic diseases and death. Fine and Gray’s models with competing risk of death were fit for each outcome between higher and lower predicted risk. In a multi-centre pilot interventional single arm study consenting individuals aged ≥30 years at higher predicted risk received cardio-renal-metabolic phenotyping and assessment for guideline target attainment. Results In the testing dataset (n = 416 228), individuals at higher predicted risk had higher long-term risk of heart failure (HR 12.54), aortic stenosis (HR 9.98), AF (HR 8·75), stroke/TIA (HR 8.07), CKD (HR 6.85), PVD (HR 6.62), valvular heart disease (HR 6.49), MI (HR 5.02), diabetes (HR 2.05) and COPD (HR 2.02) (Figure 1). This cohort were also at higher risk of death (HR 10.45), accounting for 74% of cardiovascular deaths (8 582 of 11 676) during 10-year follow up. Of 82 higher risk patients in the pilot study (mean age 71.6 years (SD 7.5), 50% women), the prevalence of cardio-renal-metabolic disease was high (Table 1), and there were opportunities to reduce future cardiovascular risk. Of higher risk patients with hypertension, 58.5% (31/53) of those aged <80 years had a systolic blood pressure (SBP)>140mmHg, and 54.5% (6/11) of those aged ≥80 years had a SBP >150mmHg. Of those with type 2 diabetes and co-existent ASCVD, only 23.1% (3/13) were on SGLT2 inhibitor therapy. Of higher risk patients on statin therapy, 37.0% (20/54) had LDL-cholesterol >1.8 mmol/L, and 52.0% (12/25) of patients with previous ASCVD had an LDL-cholesterol >1.4mmol/L. Furthermore, 19.5% (16/82) of the higher risk cohort had undiagnosed moderate or high risk CKD; who were infrequently prescribed a statin (41.7%; 5/12), ACE-i/ARB therapy with co-existent hypertension (61.5%. 8/13), or SGLT2 inhibitor with co-existent diabetes (83.3% (5/6)). Obesity was present in 49%, and 17% (14/82) were eligible for GLP-1 RA therapy. Conclusions The machine learning OPTIMISE algorithm can identify people at higher risk of cardio-renal-metabolic diseases and death using routinely collected data. On prospective evaluation higher risk individuals have unrecorded and undertreated cardio-renal-metabolic diseases, which are actionable targets for preventative care.Figure 1

#2775 ERCOS multicenter Spanish study: clinical profile of patients with chronic kidney disease G3a-G5D and osteoporosis

Abstract Background and Aims Fracture risk evaluation has recently been integrated into the 2017 KDIGO CKD-MBD (Chronic Kidney Disease- Mineral and Bone Disorder) guideline and its 2021 Spanish endorsement. It is now suggested to test bone mineral density (BMD) to assess fracture risk “if results will impact treatment decisions”. In fact, multiple new prospective studies have now documented that lower BMD predicts incident fractures in patients with CKD G3a–G5D. However, we scarcely know current real clinical practice in this population. Thus, the aim of the ERCOS (“Enfermedad Renal Crónica OSteoporosis”) study was to describe the clinical profile of patients with CKD who had been diagnosed of osteoporosis in outpatient Nephrology and Rheumatology clinics in Spain. Method ERCOS is a descriptive, observational, and multicenter Spanish study. Patients were recruited by consecutive sampling from 15 different Spanish hospitals. Osteoporosis characteristics (history of fragility fracture, BMD and other fracture risk factors), associated comorbidities, biochemical parameters and treatment were analyzed. Results A total of 163 patients (median age 77 years old) were included. Most were women (71.2%) and 98.3% of them were postmenopausal. Hypertension was the most frequent comorbidity (87.1%) and “attributed” cause of CKD (43.2%). Diabetes mellitus and cardiovascular disease were present in 35.6% and 29.4% of patients, respectively. Median estimated glomerular filtration rate was 36 ml/min/1.73 m2 [creatinine 1.48 mg/dl (95% CI 1,2-2)]. 38% of patients were G5D CKD patients (95.2% undergoing hemodialysis). 37.7% of patients had had a fragility fracture after the diagnosis of CKD (vertebral 52.5%, hip 24.6%, wrist 21.3%, humerus 16.4%, among others). Importantly, despite the diagnosis of osteoporosis, only 60.1% of the patients received specific treatment (mainly bisphosphonates or denosumab). Moreover, antiosteoporotic treatment was much more frequently prescribed by rheumatologists (46.9%), internal medicine physicians (23.5%), and only 13.3% was prescribed by nephrologists. 19.4% of patients suffered from fragility fractures even after initiating specific treatment. Conclusion Most patients with moderate and severe CKD with osteoporosis were old postmenopausal women with a high prevalence of diabetes or cardiovascular disease. Although about 40% had even suffered a fragility fracture, there is a high treatment gap, especially relevant among nephrologists. A call to action and to avoid existing therapeutic nihilism seems necessary, expanding the knowledge of the new more proactive guidelines and homogenizing the care and therapeutic approach in these patients.

Mitral Valve Repair in Patients with Chronic Kidney Disease: Long-Term Outcomes and Cardiac Remodeling

Objectives: Literature examining mitral valve repair (MVr) outcomes on CKD patients is largely limited to short term outcomes and percutaneous approaches. This study is the first to present long-term outcomes of mortality and morbidity with paired cardiac remodelling data on CKD patients undergoing surgical MVr.Design: A retrospective, observational, comparative study.Setting: Single-center university hospital.Participants: Patients with varying stages of CKD undergoing MVr from 2004-2018.Interventions: Patients were grouped by estimated glomerular filtration (eGFR) rate and followed for a maximum of 15 years. Long term outcomes and measures of cardiac remodelling were then compared between the groups.Measurements and Main Results: The primary outcome was all-cause mortality. Secondary outcomes included measures of postoperative morbidity and cardiac remodelling. Every 10 unit increase in eGFR was associated with a significant reduction in all-cause mortality at 5 years (HR 0.81 95% CI 0.67-0.98) p=0.028), 10 years (HR 0.82 CI 0.72-0.94 p=0.004), and at 15 years (HR 0.78 CI 0.69-0.88 p<0.001) Moderate CKD group had a significantly higher rates of all-cause mortality at 15 years (HR 3.38 CI 1.28-8.98 p=0.014). eGFR was a significant predictor for residual moderate to severe mitral regurgitation (MR) at 1 year (HR 0.74 CI 0.57-0.96 p=0.024). There was positive cardiac remodelling following MVr for CKD patients with significant reduction in LV size and LA volume.Conclusions: In patients with CKD undergoing MVr, eGFR is a predictor of decreased long-term survival and residual MR at 1 year. Further investigation is required for optimizing postoperative outcomes in this patient population.

Stroke, mortality, and major bleeding among patients with atrial fibrillation and chronic kidney disease; insights from a contemporary large-scale population study

Abstract Introduction Chronic kidney disease (CKD) and atrial fibrillation (AF) frequently coexist, sharing a complex interplay. Although both conditions are prothrombotic, the prognostic role of CKD in AF remains uncertain, and anticoagulation effect on clinical outcomes is unclear. Methods A historical population-based study based on the "Clalit" health organization computerized database, including patients &amp;gt;21 years first diagnosed with AF between January 1st, 2010, and January 1st, 2020. The study population was stratified according to the estimated glomerular filtration rate (eGFR) at baseline to: No or mild CKD (eGFR≥60mL/min/1.73m2), moderate-CKD (eGFR above 30 and below 60 mL/min/1.73m2) and advanced-CKD (eGFR≤30 mL/min/1.73m2). Multivariable Cox-regression analyses were performed to evaluate the association between CKD stages and the 5-year risk of death, stroke, intracranial hemorrhage (ICH), and gastrointestinal bleeding (GIB). The association of anticoagulation treatments and possible interaction with CKD with the risk for the study outcomes were also examined. Results We identified 87,804 patients with incident AF. Of them, 3.2% had advanced CKD, and 25% had moderate CKD. 39,421 patients (45%) received anticoagulation. In multivariable models, moderate and advanced CKD were associated with increased risk for death in an incremental manner (moderate CKD: adjusted-hazard ratio (aHR) 1.17; 95% CI 1.14-1.20, p&amp;lt;0.001) (advanced CKD: aHR 1.85; 95% CI 1.76 -1.96; p&amp;lt;0.001). Both moderate CKD (aHR 1.1; 95% CI 1.00-1.20, p&amp;lt;0.05) and advanced CKD (aHR 1.37; 95% CI 1.13-1.67; p=0.001) were associated with increased risk of stroke. Renal function was not associated with increased risk for ICH, yet it was associated with increased risk of GIB. DOAC therapy reduced the risk of stroke (aHR 0.7; 95% CI 0.57-0.86, p=0.001) and death (aHR 0.83; 95% CI 0.77-0.78, p&amp;lt;0.001) while warfarin treatment did not. The association of anticoagulation treatment with reduced risk for stroke was consistent across CKD strata (p-for-interaction=0.19). Conclusions In this contemporary registry of AF patients, worse CKD was incrementally and independently associated with an increased risk of death, stroke and gastrointestinal bleeding among patients with AF. DOAC therapy was associated with a reduced risk for stroke and death without evident increase in ICH or GI bleeding. The inverse association between DOACs and stroke was consistent across all CKD categories. If confirmed by others, CKD ought to be added to stroke risk scores in AF.5 year stroke risk5 year death risk

Effects of a Low Phosphorus Diet on Phosphorus and Calcium Whole-Body Balance and Intestinal Absorption: Results of a Pilot Study in Adults with Moderate CKD

Effects of a Low Phosphorus Diet on Phosphorus and Calcium Whole-Body Balance and Intestinal Absorption: Results of a Pilot Study in Adults with Moderate CKD

A Novel Titratable Pig Model of Mild, Moderate, and Severe CKD

A Novel Titratable Pig Model of Mild, Moderate, and Severe CKD

Clopidogrel-Related High Residual Platelet Reactivity Associated with Estimated Glomerular Filtration Rate in Patients with Acute Ischemic Stroke

Introduction: There are few studies on the relationship between the occurrence of clopidogrel-related high residual platelet reactivity (HRPR) and estimated glomerular filtration rate (eGFR) at admission in patients with ischemic stroke. The aim of this study was to investigate the possible relationship between the two. Methods: Patients who were hospitalized and diagnosed with acute ischemic stroke were recruited from July 1, 2017, to June 30, 2018, at Shanghai TCM-Integrated Hospital. Renal function was measured within 24 h of enrollment and eGFR was calculated. Patients were tested for platelet reactivity using the VerifyNow system after 7 days of antiplatelet therapy with clopidogrel 75 mg/d alone, and patients with P2Y12 reaction unit values ≥230 were diagnosed with HRPR. The association between HRPR and eGFR was analyzed. Results: A total of 274 patients were enrolled in the study, of whom 91 (33.21%) had HRPR. Multivariate logistic regression analysis suggested that an increased risk of HRPR was independently associated with female sex and reduced eGFR (female sex: OR = 2.24, 95% CI: 1.26–3.99, p = 0.006; mild chronic kidney disease [CKD]: OR = 2.95, 95% CI: 1.47–5.93, p = 0.002; moderate CKD: OR = 3.07, 95% CI: 1.08–8.75, p = 0.04). Conclusion: Decreased eGFR is an independent risk factor for the occurrence of HRPR in patients with ischemic stroke.

Health effects of the New Nordic Renal Diet in patients with stage 3 and 4 chronic kidney disease, compared with habitual diet: a randomized trial

BackgroundChronic kidney disease (CKD) leads to an accumulation of waste products and causes adverse cardiometabolic effects. ObjectivesWe investigated the health effects of the New Nordic Renal Diet (NNRD), a novel meal pattern reduced in phosphorus, protein, and sodium. MethodsA 26-wk randomized trial compared the NNRD with a habitual diet. The NNRD group received weekly home deliveries of food and recipes. Monthly study visits included fasting blood samples, 24-h urine samples, blood pressure, and anthropometric measurements. Intention-to-treat analysis used linear mixed-effects models. ResultsSixty patients, mean estimated glomerular filtration rate (eGFR) 34 mL/min/1.73 m2 and body mass index of 25–27 kg/m2, were included and 58 completed. Metabolic syndrome was present in 53% (NNRD group) and 57% (control group). The NNRD group (n = 30) reduced their 24-h urine phosphorus excretion by 19% (−153 mg; 95% confidence interval [CI]: −210, −95), control group (n = 30) (no change), between-group difference −171 mg (95% CI: −233, −109; P < 0.001). Proteinuria was reduced by 39% in the NNRD group (−0.33 g/d; 95% CI: −0.47, −0.18), control group (no change), between-group difference −0.34 g/d (95% CI: −0.52, −0.17; P < 0.001). Plasma urea was reduced by −1.5 mmol/L in the NNRD group (95% CI: −2.1, −0.9), control group (no change), between-group difference −1.4 mmol/L (95% CI: −2.0, −0.7; P < 0.001). Systolic blood pressure fell by −5.2 mmHg in the NNRD group (95% CI: −8.4, −2.1), control group (no change), between-group difference −3.9 mmHg (95% CI; −7.6, −0.2; P = 0.04). The NNRD group lost −1.7 kg (95% CI: −2.6, −0.8), control group (no change), between-group difference −2.0 kg (95% CI: −3.0, −1.0; P < 0.001). There were no effects on eGFR during the 26-wk intervention. ConclusionNNRD in moderate CKD reduces phosphorus excretion, proteinuria, systolic blood pressure, and weight, mainly by reducing abdominal fat.This trial was registered at clinicaltrials.gov as NCT04579315.

Physiologically-based pharmacokinetic modeling for single and multiple dosing regimens of ceftriaxone in healthy and chronic kidney disease populations: a tool for model-informed precision dosing.

Introduction: Ceftriaxone is one of commonly prescribed beta-lactam antibiotics with several label and off-label clinical indications. A high fraction of administered dose of ceftriaxone is excreted renally in an unchanged form, and it may accumulate significantly in patients with impaired renal functions, which may lead to toxicity. Methods: In this study, we employed a physiologically-based pharmacokinetic (PBPK) modeling, as a tool for precision dosing, to predict the biological exposure of ceftriaxone in a virtually-constructed healthy and chronic kidney disease patient populations, with subsequent dosing optimizations. We started developing the model by integrating the physicochemical properties of the drug with biological system information in a PBPK software platform. A PBPK model in an adult healthy population was developed and evaluated visually and numerically with respect to experimental pharmacokinetic data. The model performance was evaluated based on the fold error criteria of the predicted and reported values for different pharmacokinetic parameters. Then, the model was applied to predict drug exposure in CKD patient populations with various degrees of severity. Results: The developed PBPK model was able to precisely describe the pharmacokinetic behavior of ceftriaxone in adult healthy population and in mild, moderate, and severe CKD patient populations. Decreasing the dose by approximately 25% in mild and 50% in moderate to severe renal disease provided a comparable exposure to the healthy population. Based on the simulation of multiple dosing regimens in severe CKD population, it has been found that accumulation of 2g every 24h is lower than the accumulation of 1g every 12h dosing regimen. Discussion: In this study, the observed concentration time profiles and pharmacokinetic parameters for ceftriaxone were successfully reproduced by the developed PBPK model and it has been shown that PBPK modeling can be used as a tool for precision dosing to suggest treatment regimens in population with renal impairment.

#5399 VONAFEXOR AS A NOVEL THERAPY FOR CHRONIC KIDNEY DISEASE

Abstract Background and Aims Chronic kidney diseases (CKD) are characterized by the progressive loss of renal function. The molecular mechanisms underlying this progression are still poorly characterized and probably multifactorial. Therefore, there is a real need to expand the very limited number of therapies able to slow down the rate of CKD progression. Recent findings indicate that NR1H4, a druggable nuclear receptor, might play an important role in CKD. The aim of this study was to investigate the benefit of Vonafexor, a novel small molecule and specific NR1H4 agonist in acquired and genetic models of CKD. Method Two complementary experimental models of CKD (the 75% excision of total renal mass (Subtotal Nephrectomy; Nx) and the Col4a3−/− mice, a model of Alport disease) were studied. NR1H4 and the expression of some of its downstream targets were evaluated by quantitative RT-PCR, western blot and immunohistochemistry. In the Nx model, mice were treated with Vonafexor by daily oral gavage from 5 to 8 weeks after the surgery. The possible beneficial effect was compared to that of Losartan and other NR1H4 agonists. In the Alport model, mice were treated by Vonafexor from 5 to 8 weeks after birth. In both models, group of mice were sacrificed at 5 weeks to evaluate the extent of renal lesions at baseline. Renal lesions were quantified using image J. Renal inflammation, myofibroblast activation and podocyte number were quantified after specific staining. Human biopsies were also studied. RNAseq was performed using Illumina NovaSeq6000. Results We observed that NR1H4 expression and OSTA and OSTB, two downstream targets of NR1H4, were significantly reduced in remnant kidneys of Nx FVB/N mice compared to sham-operated animals 8 weeks after surgery. Co-localization staining revealed that NR1H4 is mainly expressed in proximal tubules and, to a minor extent, in Henle loops. Renal lesions were already present at 5 weeks in both experimental models. Remarkably, Vonafexor stopped the progression of renal lesions, in terms of glomerulosclerosis and tubular dilatations and, more importantly, induced a regression of interstitial fibrosis 8 weeks after nephrectomy as compared to the 5-week baseline. Lymphocytes and macrophage infiltration, as well as activated myofibroblasts, were also significantly reduced. Similarly, podocyte loss was stopped by Vonafexor treatment. Of note, the beneficial effect of Vonafexor was unique compared to other classes of NR1H4 agonists and also higher than that of Losartan. The same beneficial curative effect was found in Col4a3−/− mice. RT-PCR confirmed the activation of several NR1H4 downstream targets in mice treated with Vonafexor, while RNAseq analysis revealed that Vonafexor impacted the pathological activation of pathways involved in cell cycle, cell signaling and metabolism. These results may be relevant to humans, since NR1H4 expression was significantly reduced in biopsies from patients with CKD of different etiologies as compared to control kidneys. Conclusion Altogether our results identified in Vonafexor a novel key drug to control CKD. This is consistent with recent results obtained in LIVIFY phase 2 clinical trial in which Vonafexor has already demonstrated beneficial effects on eGFR in NASH patients with mild to moderate CKD.

P330 MANAGEMENT OF HYPERKALEMIA IN A PATIENT WITH HFREF

Abstract Hyperkalimia (HK) is a condition that occurs very frequently in patients with heart failure (HF). HK often limits and discourages the implementation and optimization of RAASI therapy in patients with HFrEF. The introduction of the new K–binders drugs has made it possible to overcome this obstacle by allowing optimization of therapy even in patients with persistent hyperkalemia. Mr. AB aged 83 years cognitively intact and autonomous ( Katz‘s BADL and Lawton‘s IADL preserved; MMSE 29/30). February 2022 accessed DEA for aggravating exertional dyspnea; at that time echocardiogram finding reduced left ventricular systolic function, FE 35%. March 2022 performed elective coronarography: coronary tree free of critical lesions, confirmed on echocardiogram reduced FE. Post indication to undertake Sacubitril/Valsartan, beta blocker and SGLT2i therapy. For moderate CKD (eGFR 33 ml/min) with tendency to hyperkalemia not initiated MRA. April 2022 the patient was taken to our Heart Failure Outpatient Clinic–UTIG– AOU Careggi. June 2022 considered improvement in renal function and Kaliemia in optimized range GDMTs therapy with Potassium Canreonate 25 mg/day. At control EEs in July 2022 found hyperKalemia with K values 5.5 mEq/L but stability of renal function. Reduced therefore the dosage of Potassium Canreonate (25 mg every other day) with indication to repeat blood tests soon. September 2022 despite reduction in MRA dosage further increase in Kaliemia values to 5.8 mEq/L. Suspended Potassium Canreonate and started Sodium Zirconium Cyclosilicate therapy initially at loading dosage of 10 g three times daily for two days then continued with maintenance dosage of 5 g. At follow–up performed the following week K 4.5 mEq/L. Re–introduced Potassium Canreonate 25 mg/day with initial tight control of potassium values that remained stably at optimal values. Hyperkalemia is an obstacle in titrating HFrEF, especially in elderly patients with CKD. However, we have new drugs available that may allow the implementation of guideline–recommended treatments by controlling potassium values.

Pre-Pregnancy eGFR and the Risk of Adverse Maternal and Fetal Outcomes: A Population-Based Study.

Pregnancies in women with CKD carry greater risk than pregnancies in the general population. The small number of women in prior studies has limited estimates of this risk, especially among those with advanced CKD. We report the results of a population-based cohort study in Ontario, Canada, that assessed more than 500,000 pregnancies, including 600 with a baseline eGFR < 60 ml/min per 1.73 m 2 . The investigation demonstrates increases in risk of different adverse maternal and fetal outcomes with lower eGFR and further risk elevation with baseline proteinuria. CKD is a risk factor for pregnancy complications, but estimates for adverse outcomes come largely from single-center studies with few women with moderate or advanced stage CKD. To investigate the association between maternal baseline eGFR and risk of adverse pregnancy outcomes, we conducted a retrospective, population-based cohort study of women (not on dialysis or having had a kidney transplant) in Ontario, Canada, who delivered between 2007 and 2019. The study included 565,907 pregnancies among 462,053 women. Administrative health databases captured hospital births, outpatient laboratory testing, and pregnancy complications. We analyzed pregnancies with serum creatinine measured within 2 years of conception up to 30 days after conception and assessed the impact of urine protein where available. The risk of major maternal morbidity, preterm delivery, and low birthweight increased monotonically across declining eGFR categories, with risk increase most notable as eGFR dropped below 60 ml/min per 1.73 m 2 . A total of 56 (40%) of the 133 pregnancies with an eGFR <45 ml/min per 1.73 m 2 resulted in delivery under 37 weeks, compared with 10% of pregnancies when eGFR exceeded 90 ml/min per 1.73 m 2 . Greater proteinuria significantly increased risk within each eGFR category. Maternal and neonatal deaths were rare regardless of baseline eGFR (<0.3% of all pregnancies). Only 7% of women with an eGFR <45 ml/min per 1.73 m 2 received dialysis during or immediately after pregnancy. We observed higher rates of adverse pregnancy outcomes in women with low eGFR with concurrent proteinuria. These results can help inform health care policy, preconception counseling, and pregnancy follow-up in women with CKD.

Feasibility of the NIH Toolbox Cognitive Battery for Children With Mild to Moderate CKD

Feasibility of the NIH Toolbox Cognitive Battery for Children With Mild to Moderate CKD

Association of combined fractional excretion of phosphate and FGF23 with heart failure and cardiovascular events in moderate and advanced renal disease.

High levels of FGF23 associate with adverse events in CKD. The urinary fractional excretion of phosphate (FePi) might modify this association, although data are limited in moderate and advanced CKD. We investigated the association of combined FePi and serum FGF23 with incident heart failure, cardiovascular events and mortality in patients withCKD stages2-4. Patients from the Chronic Renal Insufficiency Cohort were divided into four groups according to the median of FePi and FGF23: low-FePi/low-FGF23, reference group; high-FePi/low-FGF23; low-FePi/high-FGF23; high-FePi/high-FGF23. Primary outcomes were: the composite of cardiovascular death or hospitalization for heart failure; cardiovascular death; hospitalization for heart failure; and death from any cause. Survival analysis and adjusted regression analyses were performed. We analyzed 3684 patients with a mean age of 58 ± 11years of whom 45% were male. Mean eGFR was 44 ± 15ml/min/1.73m2. The median time of follow-up was 12 (IQR 7-13) years. The risk of the composite of cardiovascular death or hospitalization for heart failure was increased in the low-FePi/high-FGF23 group (HR 1.35; 95%CI 1.09-1.67) and in the high-FePi/high-FGF23 group (HR 1.50; 95%CI 1.20-1.86), compared to the low-FePi/low-FGF23 group. Cardiovascular death and hospitalization for heart failure were also increased in both groups with high FGF23. Death from any cause was increased in the low-FePi/high-FGF23 group (HR 1.56 (95%CI 1.30-1.89) and in the high-FePi/high-FGF23 (HR 1.57 (95%CI 1.29-1.90)). High FGF23 was associated with heart failure and cardiovascular death in patients with low FePi and high FePi with moderate to advanced CKD. This contrasts with reports in mild CKD.

Cardiac Biomarkers and Risk of Atherosclerotic Cardiovascular Disease in Patients with CKD.

Several cardiac biomarkers of cardiac stress, inflammation, and fibrosis (N-terminal pro brain-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T [hsTnT], growth differentiation factor 15 [GDF-15], and soluble ST2 [sST2]) have been associated with atherosclerotic disease in the general population. We hypothesized that these cardiac biomarkers may also be associated with the atherosclerotic cardiovascular disease in patients with CKD. We analyzed levels of NT-proBNP, hsTnT, GDF-15, and sST2 in a cohort of 2732 participants with mild to moderate CKD from the Chronic Renal Insufficiency Cohort (CRIC) study. Outcomes included incident atherosclerotic disease, defined as the first instance of myocardial infarction, stroke, or peripheral vascular disease. We used Cox proportional hazard models to the test the association of each cardiac biomarker with risk of incident atherosclerotic disease, adjusting for multiple possible confounders. When modeled continuously (per SD increase in the log-transformed biomarker), NT-proBNP, hsTnT, GDF-15, and sST2 were significantly associated with incident atherosclerotic disease after adjustment for multiple potential confounders: (NT-proBNP HR, 1.51; 95% CI, 1.27 to 1.81; hsTnT HR, 1.61; 95% CI, 1.38 to 1.89; GDF-15 HR, 1.44; 95% CI, 1.19 to 1.73; and sST2 HR, 1.19; 95% CI, 1.04 to 1.36). NT-proBNP, hsTnT, GDF-15, and sST2 were significantly associated with incident atherosclerotic cardiovascular disease in patients with CKD. These associations may highlight important mechanisms for the development of atherosclerotic disease in CKD.

MO475: Dapa-CKD Patient Profile: Transposability Assessment in Real-Life Through the CKD-Rein French Cohort

Abstract BACKGROUND AND AIMS The objective of this observational study was to describe the `DAPA-CKD-like’ population and to assess the burden of illness (comorbidities, cardiovascular (CV) and renal events) and prognosis in patients with CKD in France, compared with those randomized in the DAPA-CKD RCT [1]. METHOD The CKD-REIN cohort study enrolled 3033 patients with moderate or advanced CKD from 40 nationally representative nephrology clinics in France [median age of 68 (IQR: 60–76), min-max: 19–94, 65% men, CKD stage 3 (60%) or 4 (40%)]. Inclusions started in July 2013 and ended in July 2016. The analysis describes baseline characteristics of patients with DAPA-CKD inclusion criteria (75 ≥ eGFR ≥ 25 mL/min/1.73 m2 and 5000 ≥ UACR ≥ 200 mg/g) and CV and renal outcomes &amp;gt;3-year follow-up. RESULTS Among the 3033 adult patients included in CKD-REIN cohort, 503 met the inclusion and exclusion criteria of the DAPA-CKD RCT. The characteristics of these 503 French `DAPA-CKD-like’ patients and those of the DAPA-CKD RCT were similar in terms of age (63.9 ± 13.6 versus 61.8 ± 12.1), gender (74% men versus 67%), eGFR (36.5 ± 9.1 mL/min/1.73 m2 versus 43.1 ± 12.4 mL/min/1.73 m2) and SBP (145 ± 21 mmHg versus 137 ± 17 mmHg). The CV and renal event rates/100 patient-year (PY) were similar between the two populations, both for the main composite outcome (eGFR decline ≥50% or end-stage kidney disease (defined as eGFR &amp;lt;15 mL/min/1.73 m2 long-term dialysis or kidney transplantation) or CV or renal deaths), 7.9/100 PY versus 7.5/100 PY, but also for each outcome of the main endpoint and secondary endpoints. CONCLUSION In conclusion, the DAPA-CKD RCT patient profile appears to be similar to a real-life French CKD patient profile based on the French CKD-REIN cohort meeting the inclusion and exclusion criteria of the DAPA-CKD RCT.

Effects of ferric citrate and intravenous iron sucrose on markers of mineral, bone, and iron homeostasis in a rat model of CKD-MBD.

Anemia and chronic kidney disease-mineral and bone disorder (CKD-MBD) are common and begin early in CKD. Limited studies have concurrently compared the effects of ferric citrate (FC) versus intravenous (IV) iron on CKD-MBD and iron homeostasis in moderate CKD. We tested the effects of 10 weeks of 2% FC versus IV iron sucrose in rats with moderate CKD (Cy/+ male rat) and untreated normal (NL) littermates. Outcomes included a comprehensive assessment of CKD-MBD, iron homeostasis and oxidative stress. CKD rats had azotemia, elevated phosphorus, parathyroid hormone and fibroblast growth factor-23 (FGF23). Compared with untreated CKD rats, treatment with FC led to lower plasma phosphorus, intact FGF23 and a trend (P=0.07) toward lower C-terminal FGF23. FC and IV iron equally reduced aorta and heart calcifications to levels similar to NL animals. Compared with NL animals, CKD animals had higher bone turnover, lower trabecular volume and no difference in mineralization; these were unaffected by either iron treatment. Rats treated with IV iron had cortical and bone mechanical properties similar to NL animals. FC increased the transferrin saturation rate compared with untreated CKD and NL rats. Neither iron treatment increased oxidative stress above that of untreated CKD. Oral FC improved phosphorus homeostasis, some iron-related parameters and the production and cleavage of FGF23. The intermittent effect of low-dose IV iron sucrose on cardiovascular calcification and bone should be further explored in moderate-advanced CKD.

Qualitative approach to better understand the trajectory of patients with early and moderate stage CKD.

Qualitative approach to better understand the trajectory of patients with early and moderate stage CKD.

Abstract TP163: Effect Of Renal Impairment On Clinical Outcomes Among Acute Ischemic Stroke Patients Treated With Endovascular Therapy- A Bi-center Study.

Objective: To investigate the effect of renal impairment on clinical outcomes among acute ischemic stroke (AIS) patients treated with endovascular therapy (EVT). Methods: We performed a retrospective analysis from January to December 2020 involving AIS patients with CKD and premorbid modified Rankin Scale (mRS) ≤2, undergoing EVT in two large academic comprehensive stroke centers. Our primary efficacy outcome of interest was mRS at 90 days. Secondary outcomes included: inpatient mortality, length of hospitalization and reperfusion status based on Thrombolysis in Cerebral Infarction (TICI) score. CKD was defined as estimated glomerular filtration rate (eGFR) ranging from mild (eGFR 60-89 mL/min), moderate (eGFR 30-59 mL/min) or severe (eGFR 15-29 mL/min). We performed ordinal regression, multinomial logistic regression and binomial logistic regression analyses. In our subgroup analysis, we compared outcomes among AIS patients diagnosed with mild, moderate and severe CKD. We additionally performed a sensitivity analysis comparing patients with treated with combined intravenous thrombolysis (IVT) and EVT vs EVT only. Results: A total of 484 AIS patients underwent EVT at both stroke centers during the study period. After excluding patients for missing data and baseline mRS &gt;2, total of 300 AIS patients who underwent EVT (176 CKD and 124 patients with normal renal function) were included. Patients with CKD was associated with worse clinical outcomes [4 (2-6) vs 3 (1-6)]; adjusted odds ratio [aOR] 1.70, 95% confidence interval [CI] 1.10 - 2.61, p =0.02] based on 90-day mRS shift analysis and increased odds of in-hospital mortality (aOR 2.63, 95% CI; 1.08-6.38, p =0.03). Rates of TICI 2b/3 reperfusion ( p =0.84) and length of stay ( p =0.42) were similar between the two groups. Subgroup analyses found no difference between CKD and normal renal function groups for primary and secondary outcomes (all p &gt;0.05). Similarly, sensitivity analyses demonstrated no difference in clinical outcomes between patients receiving combined IVT and EVT compared to EVT only (all p &gt;0.05). Conclusion: Among AIS patients undergoing EVT, renal impairment was independently associated with worsening functional outcomes at 90 days and a higher rate of inpatient mortality.

Apolipoprotein A-IV concentrations and clinical outcomes in a large chronic kidney disease cohort: Results from the GCKD study.

BackgroundChronic kidney disease (CKD) represents a chronic proinflammatory state and is associated with very high cardiovascular risk. Apolipoprotein A‐IV (apoA‐IV) has antiatherogenic, antioxidative, anti‐inflammatory and antithrombotic properties and levels increase significantly during the course of CKD.ObjectivesWe aimed to investigate the association between apoA‐IV and all‐cause mortality and cardiovascular outcomes in the German Chronic Kidney Disease study.MethodsThis was a prospective cohort study including 5141 Caucasian patients with available apoA‐IV measurements and CKD. The majority of the patients had an estimated glomerular filtration rate (eGFR) of 30–60 ml/min/1.73m2 or an eGFR >60 ml/min/1.73m2 in the presence of overt proteinuria. Median follow‐up was 6.5 years. The association of apoA‐IV with comorbidities at baseline and endpoints during follow‐up was modelled adjusting for major confounders.ResultsMean apoA‐IV concentrations of the entire cohort were 28.9 ± 9.8 mg/dl. Patients in the highest apoA‐IV quartile had the lowest high‐sensitivity C‐reactive protein values despite the highest prevalence of diabetes, albuminuria and the lowest eGFR. Each 10 mg/dl higher apoA‐IV translated into lower odds of prevalent cardiovascular disease (1289 cases, odds ratio = 0.80, 95% confidence interval [CI] 0.72–0.86, p = 0.0000003). During follow‐up, each 10 mg/dl higher apoA‐IV was significantly associated with a lower risk for all‐cause mortality (600 cases, hazard ratio [HR] = 0.81, 95% CI 0.73–0.89, p = 0.00004), incident major adverse cardiovascular events (506 cases, HR = 0.88, 95% CI 0.79–0.99, p = 0.03) and death or hospitalizations due to heart failure (346 cases, HR = 0.84, 95% CI 0.73–0.96, p = 0.01).ConclusionsThese data support a link between elevated apoA‐IV concentrations and reduced inflammation in moderate CKD. ApoA‐IV appears to be an independent risk marker for reduced all‐cause mortality, cardiovascular events and heart failure in a large cohort of patients with CKD.