Non-diabetic Chronic Kidney Disease Patients Research Articles

#1432 Prevalence, risks and treatment of incident chronic kidney disease stage 3-4: an observational study in Finland between 2016-2022

Abstract Background and Aims The rising burden of chronic kidney disease (CKD) calls for early detection and targeted interventions. Kidney-protective treatments (renin–angiotensin system inhibitors [RASis] and sodium-glucose co-transporter-2 inhibitors [SGLT2is]) can delay chronic kidney disease (CKD) progression, cardiovascular events and death. However, contemporary differences between CKD patients with and without type 2 diabetes (T2D) is limited. This study aimed to describe the prevalence, patient characteristics, the use of kidney protective treatments (RASi or SGLT2i) and event risks among patients with incident stage 3-4 CKD in Finland. Method We used comprehensive real-world clinical data from electronic health records from primary and hospital care in five municipalities in Finland between 1st January 2016 to 31st December 2022 to identify stage 3-4 CKD patients aged ≥18 years, defined as having either one estimated glomerular filtration rate (eGFR) measurement between 15 to 60 ml/min/1.73 m2 followed by a second one ≥90 days apart, or a registered CKD diagnosis. Two cohorts from primary care were identified: a prevalent cohort indexed at a fixed date, 1st Jan 2022 and an incident cohort indexed at the date of new CKD. The incident CKD patients were followed from CKD incident index date until death, emigration, or end of study on 31 December 2022. Analyses were also stratified by CKD patients with T2D and non-diabetes (T1D and gestational diabetes excluded), respectively. Risks were estimated as event rates per 1000 patient-years. The proportion of patients on/off treatment were estimates as a function of time and divided into pre- vs. post-index. Results In 2022 the prevalent cohort of 16,380 CKD stage 3-4 patients, represented a prevalence of 6.2% in the total background population of 263,383 individuals. The 12,129 incident Stage 3-4 CKD patients had a median eGFR of 55 ml/min/1.73 m2, similar in both non-T2D and T2D. Most patients were non-T2D; 73% (n = 8859). At index, 1.7% had a CKD diagnosis, lower in non-T2D (1.0%) vs T2D (3.5%) patients. The use of urine albumin creatinine ratio (UACR) was generally very low (21% had a measurement), 9% in the non-T2D and 53% in the T2D patients. Non-T2D, compared to T2D patients, were similar in age (76 vs 75 years) and had slightly less comorbidities like HF (12% vs 18%), myocardial infarction (9% vs 14%), stroke (15% vs 16%), atrial fibrillation (21% vs 25%) and less treated with statins (38% vs 64%). During follow-up, 10% had died within 1-year (97 deaths per 1000 patient years), similar in non-T2D (95 deaths per 1000 patient years) and T2D patients (104 deaths per 1000 patient years). One year risk of any hospitalization was also high, 49% and 64%, respectively. The use of kidney-protective treatments (renin angiotensin system inhibitor [RASi] or SGLT2i) at index (date of incident CKD) was lower in patients without T2D (47%) compared to those with T2D (69%). No change was observed in their use in the 12 months after incident CKD (Fig.). Finally, when studying the proportion of all non-T2D patients receiving SGLT2i after approval for CKD treatment, less than 1% of all CKD patients in the study group were treated with SGLT2i on 31st December 2022. Conclusion This study shows that CKD stage 3-4 is highly prevalent in Finland. Newly detected CKD stage 3-4 patients were little diagnosed and the use of UACR was low, especially among those who were non-diabetic. More than 2 out of 3 CKD patients were non-diabetic. Importantly, these non-diabetic CKD patients had similarly high disease burden, similar high risk of dying and had less kidney/cardiovascular prevention compared to those with T2D. The high mortality risks, substantial kidney-protective treatment inertia and UACR underutilization in stage 3-4 CKD patients all call for an urgent need for improved awareness and risk management, especially in the larger group of non-T2D.

Sodium-Glucose Cotransporter 2 Inhibitors for Chronic Kidney Disease: A Comprehensive Review

Chronic Kidney Disease (CKD) is a major global health burden. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated potential in slowing CKD progression. We evaluated the expanding role of SGLT2 inhibitors, emphasizing their renoprotective benefits in diabetic and non-diabetic CKD patients. We also investigated the underlying mechanisms, including the reduction of glomerular hypertension via modulation of tubuloglomerular feedback. Our study critically analyzed current indications for SGLT2 inhibitor therapy based on recent clinical trial data. To optimize patient outcomes, we present a comprehensive analysis of practical considerations for the prescription of SGLT2 inhibitors, including the potential initial decline in the estimated glomerular filtration rate and a review of adverse events.

Assessing care quality: impact on renal outcomes in non-diabetic chronic kidney disease patients

Abstract Background Chronic kidney disease (CKD) is a major global noncommunicable disease, with significant burden on healthcare systems. Quality indicators (QIs) are useful tools for evaluating healthcare quality, but existing QIs for renal care mainly focus on dialysis population. This study aims to explore the association between quality of renal care and outcomes in non-diabetic CKD patients. Methods This study utilized Taiwan's National Health Insurance claims data and death registries to enroll non-diabetic adults with advanced CKD (stage 3B-5) from 2016 to 2019, following them through 2020. QIs evaluated included prescription of renin-angiotensin system (RAS) inhibitors, testing for proteinuria, and avoidance of nonsteroidal anti-inflammatory drugs (NSAIDs). An overall quality score was calculated by summing scores of each QI. The primary outcome was long-term dialysis, and secondary outcomes included death, acute kidney injury (AKI), hyperkalemia, and acidosis. Univariate and multivariate Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the effects of QIs on outcomes. Results Among 27,842 patients, 59.8% received RAS inhibitors, 56.5% underwent proteinuria testing, and NSAIDs were avoided in 97.9% of cases. Only 33.5% received the highest QI score of 3. Multivariate Cox proportional hazard models showed that higher overall quality scores were associated with a lower risk of long-term dialysis (HR 0.87, 95% CI 0.83-0.92), death (HR 0.90, 95% CI 0.86-0.94), and acidosis (HR 0.87, 95% CI 0.79-0.96). Additionally, higher overall quality scores were borderline associated with a lower risk of AKI and hyperkalemia. Conclusions QIs for renal care were associated with better outcomes in non-diabetic patients with advanced-stage CKD, particularly in long-term dialysis, death, and acidosis. More patients need to be prescribed RAS inhibitors and tested for proteinuria to achieve better quality of renal care. Key messages • Our study shows quality of renal care can impact outcomes for non-diabetic CKD patients, with higher quality indicator scores associated with lower risk of long-term dialysis, death, and acidosis. • Prescription of RAS inhibitors had the most significant protective effect, but more patients need to be prescribed RAS inhibitors and tested for proteinuria to achieve better renal care quality.

Abstract 103: Combined Dapagliflozine And Eplerenone Treatment Improve Cardiorenal Function In Rats With Chronic Kidney Disease.

Background: Patients with chronic kidney disease (CKD) present higher risk of cardiovascular (CV) complications as well as renal function decline. The DAPA-CKD trial showed reduced CV events in diabetic and non-diabetic CKD patients treated with Dapagliflozine (DAPA). Mineralocorticoid Receptor Antagonists (MRAs) have shown similar beneficial effects in diabetic CKD patients (FIDELIO-CKD & FIGARO-CKD trials) but impact in non-diabetic CKD patients is unkown. The aim of this study was to compare DAPA and Eplerenone (EPLE), alone or in combination on renal and CV functions in a non-diabetic rat CKD model. Methods: CKD was induced in Sprague Dawley rats by 5/6 nephrectomy. Rats were treated with DAPA (10 mg/kg/day PO), EPLE (100 mg/kg/day PO) or the combination during 3 months. Results: After 3 months kidney fibrosis is decreased in the 3 treated groups compared to untreated CKD. No changes of creatinine clearance were observed while albuminuria increased in the DAPA groups with no significant effects of EPLE. The fractional shortening and the cardiac output were not modified by the treatments (not shown). Cardiac hemodynamic was improved with reduced LV end diastolic pressure (LVEDP) in the CKD rats treated with EPLE or a combination of EPLE and DAPA while LV end diastolic pressure volume relationship (LVEDPVR) was decrease by both DAPA and EPLE and further decreased by DAPA + EPLE. Decreased cardiac perfusion was prevented with EPLE alone or with the combination. Conclusion: The use of DAPA + EPLE appears to be more effective than DAPA or EPLE alone on diastolic function in non-diabetic CKD rats while cardiac perfusion is improved by EPLE only.

Pharmacological Nephroprotection in Non-Diabetic Chronic Kidney Disease-Clinical Practice Position Statement of the Polish Society of Nephrology.

Chronic kidney disease (CKD) is a modern epidemic worldwide. Introducing renin-angiotensin system (RAS) inhibitors (i.e., ACEi or ARB) not only as blood-pressure-lowering agents, but also as nephroprotective drugs with antiproteinuric potential was a milestone in the therapy of CKD. For decades, this treatment remained the only proven strategy to slow down CKD progression. This situation changed some years ago primarily due to the introduction of drugs designed to treat diabetes that turned into nephroprotective strategies not only in diabetic kidney disease, but also in CKD unrelated to diabetes. In addition, several drugs emerged that precisely target the pathogenetic mechanisms of particular kidney diseases. Finally, the role of metabolic acidosis in CKD progression (and not only the sequelae of CKD) came to light. In this review, we aim to comprehensively discuss all relevant therapies that slow down the progression of non-diabetic kidney disease, including the lowering of blood pressure, through the nephroprotective effects of ACEi/ARB and spironolactone independent from BP lowering, as well as the role of sodium-glucose co-transporter type 2 inhibitors, acidosis correction and disease-specific treatment strategies. We also briefly address the therapies that attempt to slow down the progression of CKD, which did not confirm this effect. We are convinced that our in-depth review with practical statements on multiple aspects of treatment offered to non-diabetic CKD fills the existing gap in the available literature. We believe that it may help clinicians who take care of CKD patients in their practice. Finally, we propose the strategy that should be implemented in most non-diabetic CKD patients to prevent disease progression.

#3642 SERUM APELIN AND RENAL PROGNOSIS IN PATIENTS WITH NON-DIALYSIS DEPENDENT CHRONIC KIDNEY DISEASE

Abstract Background and Aims The apelin/APJ system is a novel pleiotropic system with an essential role in renal and cardiovascular physiology and disease. A role for the apelin/APJ system in diverse pathological states, including disorders of sodium and water balance, hypertension, heart failure, pre-eclampsia, acute kidney injury, sepsis and diabetic nephropathy, has recently been reported. Especially, the impact of apelin/APJ system on cardiovascular system has been attracting attention, but scarce data is available in chronic kidney disease (CKD). Method We measured serum apelin-36 by ELISA in 411 outpatients with non-dialysis dependent (NDD) CKD and analyzed factors associated with serum apelin. Furthermore, we examined the association of serum apelin with renal outcome (renal replacement therapy, RRT) using multivariate Cox proportional hazards model. Results Median age and eGFR were 71 years and 21.7 ml/min/1.73 m2, respectively and the prevalence of male gender and diabetes was 26.8% and 50.8%, respectively. Median serum apelin was 0.81pg/ml. There was no significant difference in serum apelin level between male and female patients, or those with and without diabetes. Moreover, serum apelin level had no significant association with age and eGFR; however, there was a significant relationship between serum apelin and brain natriutetic peptide. During the follow-up period of 38 months, 126 patients started RRT. eGFR and age were associated with the time to RRT induction. Serum apelin was not associated with renal outcome (HR, 1.05; 95%CI, 0.64-1.71; P,0.86); however, this association was interacted by diabetes and gender (P for interaction, 0.073 and 0.070, respectively). Conclusion Serum apelin could be a predictive marker of renal prognosis in male and non-diabetic CKD patients.

Relationship between High-density Lipoprotein Cholesterol and Insulin Resistance in Non-diabetic Chronic Kidney Disease Patients.

Insulin resistance is linked to cardiovascular disease (CVD), even in non-diabetic patients. Therefore, insulin resistance contributes to the development of CVDs, which are the most important cause of morbidity and mortality in chronic kidney disease (CKD) and patients receiving dialysis replacement therapy. Furthermore, CKD greatly affects the enzyme activities responsible for the metabolism of high-density lipoprotein (HDL), causing an abnormal composition and function of HDL, which results in the loss of the anti-inflammatory effect of HDL and its protective effect against CVD. The study aimed to find the relationship between HDL-C, inflammation, and insulin resistance in nondiabetic CKD patients undergoing different modalities of treatment. This prospective cross-sectional comparative study included 80 subjects divided into the control group (20 healthy participants), Group 1 (15 predialysis CKD patients on conservative treatment), Group 2 (10 peritoneal dialysis patients), and Group 3 (35 hemodialysis patients). A full history, medical examination, and a laboratory investigation were carried out on all subjects from June 2018 to June 2019. The patient groups had significantly lower HDL and higher serum insulin than the control group. HDL was negatively correlated with the Homeostatic Model Assessment of Insulin Resistance. There was a strong negative association between HDL and insulin resistance in CKD patients. Therefore, lifestyle modifications and dyslipidemia treatment in CKD might help to prevent cardiovascular events even in nondiabetic nonobese CKD patients.

S-41-5: NEW INSIGHTS INTO THE OPTIMAL ANTIHYPERTENSIVE THERAPY IN CKD PATIENTS

Chronic kidney disease (CKD) is defined as continuous existence of reduced renal function, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2, and/or proteinuria including microalbuminuria. CKD patients are not only prone to progress to renal failure but also at high risk for developing cardiovascular diseases (CVD) as the concept of cardio-renal syndrome is assumed. As the cause of CKD, diabetic kidney disease and nephrosclerosis are dominating and their progression is promoted by aging and lifestyle-related diseases (LSD) such as hypertension and diabetes. Therefore, in order to maximally prevent renal failure and CVD in CKD patients, aggressive intervention achieving strict control of LSD starting at its earliest stage is important. Renal function is generally evaluated by eGFR, however, the fundamental aspect of renal function is renal blood flow or renal plasma flow (RPF), and the decrease of RPF is compensated by the increase in filtration fraction yielding the maintenance of GFR value. Accordingly, if eGFR is less than 60, it should be recognized that the extent of renal injury is not mild but moderate or worse. However, the measurement of RPF requires laborious and invasive procedure. Albuminuria may reflect the increase in glomerular capillary pressure (glomerular hypertension) elicited by reduced nephron number but the urinary albumin excretion is highly variable and is not necessarily parallel to the degree of renal injury. Among LSD, hypertension plays a pivotal role as the risk factor for renal failure and CVD, and the strict blood pressure control targeting < 130/80mmHg is recommended in the guidelines. As antihypertensive agents, renin-angiotensin system inhibitors such as ARB and ACE inhibitors are preferred because of dilating the efferent arterioles resulting in the alleviation of glomerular hypertension and the reduction in albuminuria. Calcium channel blockers have advantage in preserving RPF and GFR by dilating the afferent arterioles. In addition, recent randomized controlled trials have demonstrated that sodium-glucose cotransporter 2 inhibitors retard the GFR decrease in diabetic and non-diabetic CKD patients. Angiotensin receptor neprilysin inhibitor, now used for hypertension, has also been shown to reduce the risks of GFR decrease and worsening of renal function in heart failure patients. Nonsteroidal mineralocorticoid receptor antagonists are expected to provide renoprotective effects such as albuminuria reduction with affordable risk of hyperkalemia. Thus, in future strategy of antihypertensive therapy for CKD aiming maximum renal and cardiovascular protection, practical evaluation of renal injuries at early stages and incorporation of drugs with new evidence are the key issues.

Effect of Vitamin D Supplementation on Serum Hepcidin Levels in Non-Diabetic Chronic Kidney Disease Patients.

Vitamin D deficiency and anemia frequently coexist. Moreover, vitamin D deficiency is found to play a role in chronic kidney disease (CKD)-associated anemia. We investigated the effect of cholecalciferol on serum hepcidin levels in vitamin D-deficient, non-diabetic individuals with CKD in a randomized, double-blind, placebo-controlled trial. This study was performed on stored samples of our previously published randomized, double-blind, placebo-controlled trial of cholecalciferol supplementation in non-diabetic patients with stage III-IV CKD and vitamin D deficiency. Stable patients of either sex, aged 18-70 years, with non-diabetic stage III-IV CKD (estimated glomerular filtration rate between 15 and 60 ml/min/1.73 m2), and having serum 25-hydroxyvitamin D3 [25(OH) D] levels ≤20 ng/ml were included. Participants received either two directly observed oral doses of cholecalciferol (300,000 IU) or matching placebo at baseline and at eight weeks. Follow-up was done at 16 weeks. Serum hepcidin levels were analyzed at baseline and at 16 weeks. A total of 120 CKD patients were enrolled. Serum 25(OH) D levels were similar in the placebo and cholecalciferol groups at baseline (13.21 ± 4.78 ng/ml and 13.40 ± 4.42 ng/ml; P = 0.88). After 16 weeks, the serum 25(OH) D levels were found to be increased in the cholecalciferol group but not in the placebo group (between-group difference in mean change 23.40 ng/ml; 95% CI: 19.76 to 27.06; P < 0.001). Serum hepcidin levels were similar at baseline (median [IQR]: 33.6 [8.6-77.8] ng/ml vs. 24.6 [9.3-70.7] ng/ml, P = 0.903) and did not vary between groups at 16 weeks (median [IQR]: 41.5 [10.9-75.0] ng/ml vs. 34.8 [12.3-63.75] ng/ml, P = 0.703). Our study provides preliminary data based on which a larger adequately powered clinical trial can be conducted to conclusively assess the impact of vitamin D supplementation on hepcidin levels and anemia in patients with CKD and vitamin D deficiency.

Intrarenal and Urinary Glycogen Synthase Kinase-3 Beta Levels in Diabetic and Nondiabetic Chronic Kidney Disease

Background: Renal glycogen synthase kinase-3 beta (GSK3β) overactivity has been associated with a diverse range of kidney diseases. GSK3β activity in urinary exfoliated cells was reported to predict the progression of diabetic kidney disease (DKD). We compared the prognostic value of urinary and intrarenal GSK3β levels in DKD and nondiabetic chronic kidney disease (CKD). Methods: We recruited 118 consecutive biopsy-proved DKD patients and 115 nondiabetic CKD patients. Their urinary and intrarenal GSK3β levels were measured. They were then followed for dialysis-free survival and rate of renal function decline. Results: DKD group had higher intrarenal and urinary GSK3β levels than nondiabetic CKD (p r = −0.335, p = 0.006) and remained an independent predictor after adjusting for other clinical factors. Conclusion: Intrarenal and urinary GSK3β levels were increased in DKD. The intrarenal pY216-GSK3β/total GSK3β ratio was associated with the rate of progression of DKD. The pathophysiological roles of GSK3β in kidney diseases deserve further studies.

Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and Nuclear Factor-Kappa B (NF- κB) Expression in Chronic Kidney Disease Patients (CKD) from South India

Aim: The present study elucidated the expression level of Nrf2 and NF-κB, in chronic kidney disease (CKD) patients from South India. Further, the expression levels of these genes are analyzed for cytokines TNF-α and IFN-γ and various subgroups of cases including dialysis, non-dialysis, diabetic and non-diabetic CKD patients, and correlation analysis performed. Methods: 133 CKD patients and 133 healthy individuals were enrolled for the evaluation of NF-κB and Nrf2 expression by qPCR. Results: Upregulated Nrf2 mRNA expression (as fold change) was observed in diabetic (Fc: 1.13), and non-diabetic (Fc: 1.30) patients. Inversely, Nrf2 mRNA expression was down regulated in non-dialysis groups (Fc: 0.80). NF-κB expression was significantly upregulated in non-diabetic (Fc:1.92), non-dialysis (Fc:1.59), dialysis (Fc: 1.36) and CKD patients (pooled) (Fc: 1.27). A dysregulated NF-κB expression was observed in diabetic groups (Fc: 0.69). Nrf2 mRNA expression were positively correlated with IFN-γ expression in diabetes (r = 0.28, p = 0.05) and non-diabetic CKD patients (r = 0.37, p &lt; 0.002). Likewise, TNF-α expression was positively correlated with Nrf2 expression in CKD (pooled) patients (r = 0.33, p &lt; 0.000). A negative correlation was observed in Nrf2 and NF-κB expression in CKD (pooled) (r = -0.028, p = 0.833). Conclusion: The study concluded the down regulated Nrf2 and upregulated NF-κB expressions in non-dialysis patients. On the contrary, in diabetic CKD patients, the expression level of NF-κB was downregulated and Nrf2 was upregulated. Thus, a negative correlation was observed between Nrf2 and NF-κB genes with respect to their expression patterns.

Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and Nuclear Factor-Kappa B (NF- κB) Expression in Chronic Kidney Disease Patients (CKD) from South India

Aim: The present study elucidated the expression level of Nrf2 and NF-κB, in chronic kidney disease (CKD) patients from South India. Further, the expression levels of these genes are analyzed for cytokines TNF-α and IFN-γ and various subgroups of cases including dialysis, non-dialysis, diabetic and non-diabetic CKD patients, and correlation analysis performed. Methods: 133 CKD patients and 133 healthy individuals were enrolled for the evaluation of NF-κB and Nrf2 expression by qPCR. Results: Upregulated Nrf2 mRNA expression (as fold change) was observed in diabetic (Fc: 1.13), and non-diabetic (Fc: 1.30) patients. Inversely, Nrf2 mRNA expression was down regulated in non-dialysis groups (Fc: 0.80). NF-κB expression was significantly upregulated in non-diabetic (Fc:1.92), non-dialysis (Fc:1.59), dialysis (Fc: 1.36) and CKD patients (pooled) (Fc: 1.27). A dysregulated NF-κB expression was observed in diabetic groups (Fc: 0.69). Nrf2 mRNA expression were positively correlated with IFN-γ expression in diabetes (r = 0.28, p = 0.05) and non-diabetic CKD patients (r = 0.37, p &lt; 0.002). Likewise, TNF-α expression was positively correlated with Nrf2 expression in CKD (pooled) patients (r = 0.33, p &lt; 0.000). A negative correlation was observed in Nrf2 and NF-κB expression in CKD (pooled) (r = -0.028, p = 0.833). Conclusion: The study concluded the down regulated Nrf2 and upregulated NF-κB expressions in non-dialysis patients. On the contrary, in diabetic CKD patients, the expression level of NF-κB was downregulated and Nrf2 was upregulated. Thus, a negative correlation was observed between Nrf2 and NF-κB genes with respect to their expression patterns.

A Study of Cardiac Autonomic Neuropathy among Non-Diabetic Chronic Kidney Disease Patients

A Study of Cardiac Autonomic Neuropathy among Non-Diabetic Chronic Kidney Disease Patients

Chronic Kidney Disease is Associated With Attenuated Plasma Metabolome Response to Oral Glucose Tolerance Testing

Chronic kidney disease (CKD) is associated with decreased anabolic response to insulin contributing to protein-energy wasting. Targeted metabolic profiling of oral glucose tolerance testing (OGTT) may help identify metabolic pathways contributing to disruptions to insulin response in CKD. Using targeted metabolic profiling, we studied the plasma metabolome response in 41 moderate-to-severe nondiabetic CKD patients and 20 healthy controls at fasting and 2hours after an oral glucose load. We used linear mixed modeling with random intercepts, adjusting for age, gender, race/ethnicity, body weight, and batch to assess heterogeneity in response to OGTT by CKD status. Mean estimated glomerular filtration rate among CKD participants was 38.9±12.7mL/min per 1.73m2 compared to 87.2±17.7mL/min per 1.73m2 among controls. Glucose ingestion induced an anabolic response resulting in increased glycolysis products and a reduction in a wide range of metabolites including amino acids, tricarboxylic acid cycle intermediates, and purine nucleotides compared to fasting. Participants with CKD demonstrated a blunted anabolic response to OGTT evidenced by significant changes in 13 metabolites compared to controls. The attenuated metabolome response predominant involved mitochondrial energy metabolism, vitamin B family, and purine nucleotides. Compared to controls, CKD participants had elevated lactate:pyruvate (L:P) ratio and decreased guanosine diphosphate:guanosine triphosphate ratio during OGTT. Metabolic profiling of OGTT response suggests a broad disruption of mitochondrial energy metabolism in CKD patients. These findings motivate further investigation into the impact of insulin sensitizers and mitochondrial targeted therapeutics on energy metabolism in patients with nondiabetic CKD.

Predictive Value of HbA1c and Metabolic Syndrome for Renal Outcome in Non-Diabetic CKD Stage 1-4 Patients.

Glycated hemoglobin (HbA1c) levels are commonly used to indicate long-term glycemic control. An HbA1c level of 6.5–5.7% is defined as pre-diabetes and is proposed as a criterion for diagnosing metabolic syndrome (MetS). However, HbA1c levels can be affected by chronic kidney disease (CKD). Whether HbA1c is associated with clinical outcomes in nondiabetic CKD patients with or without MetS is still unknown. This study included 1270 nondiabetic CKD stage 1–4 Asian patients, divided by HbA1c and MetS. Through linear regression, HbA1c was positively associated with age, waist circumference, hemoglobin levels, and C-reactive protein and was negatively associated with malnutrition–inflammation. HbA1c levels were 5.5% (0.6%) and 5.7% (0.6%) in non-MetS and MetS, respectively (p < 0.001). In Cox regression, higher-level HbA1c was associated with worse composite renal outcome in MetS patients, but with better renal outcome in non-MetS patients: Hazard ratio (HR) (95% confidence interval [CI]) of HbA1c ≥5.7%, compared with HbA1c <5%, was 2.00 (1.06–3.78) in MetS and 0.25 (0.14–0.45) in non-MetS. An association between HbA1c and all-cause mortality was not found. In conclusion, higher HbA1c levels are associated with worse renal outcomes in nondiabetic CKD stage 1–4 patients modified by the presence of MetS.

The non-steroidal mineralocorticoid receptor antagonist finerenone is a novel therapeutic option for patients with Type 2 diabetes and chronic kidney disease.

Despite strong preclinical data supporting the use of mineralocorticoid receptor antagonists (MRAs) to provide cardiorenal protection in rodent models of diabetes, the clinical evidence of their utility in treating chronic kidney disease (CKD) has been limited. Two major clinical trials (FIDELIO-DKD and FIGARO-DKD) including more than 13,000 patients with albuminuric CKD and Type 2 diabetes randomized to placebo or finerenone (MRA) have recently provided exciting results showing a significant risk reduction for kidney and cardiovascular outcomes. In this review, we will summarize the major findings of these trials, together with post-hoc and pooled analyses that have allowed evaluation of the efficacy and safety of finerenone across the spectrum of CKD, revealing significant protective effects of finerenone against kidney failure, new-onset atrial fibrillation or flutter, new-onset heart failure, cardiovascular death, and first and total heart-failure hospitalizations. Moreover, we will discuss the current evidence that supports the combined use of MRAs with sodium-glucose co-transporter-2 inhibitors, either by providing an additive cardiorenal benefit or by decreasing the risk of hyperkalemia. Although the mechanisms of protection by finerenone have only been partially explored in patients, rodent studies have shed light on its anti-inflammatory and anti-fibrotic effects in models of kidney disease, which is one of the main drivers for testing the efficacy of finerenone in non-diabetic CKD patients in the ongoing FIND-CKD trial.

MO387: Dapagliflozin and Kidney Outcomes in CKD Patients with and without Type 2 Diabetes: Real Life Data (Precursor Announcement)

Abstract BACKGROUND AND AIMS Globally, diabetes mellitus is a leading cause of kidney disease, with a critical % of patients approaching end-stage kidney disease. At the same time, chronic kidney disease (CKD) is a major contributor to illness and is associated with impaired quality of life. Until recently, the only classes of medication that have been shown to slow a decline in kidney function were angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs). Sodium-glucose cotransporter 2 (SGLT2) inhibitors leading to a reduction in intraglomerular pressure may also preserve kidney function in persons with kidney diseases due to causes other than type 2 diabetes. We investigated the impact of Dapagliflozin on kidney function in CKD patients with and without type 2 diabetes. METHOD We monitored kidney function and proteinuria in 10 CKD patients (6 male) with and without type 2 diabetes that received Dapagliflozin. All the participants were required to be receiving a stable dose of an ACE inhibitor or ARB for the study period. All of our patients were clinically stable and there was no need for hospitalization for any reason. RESULTS A total of 9/10 patients were diabetic. One patient had focal segmental glomerulosclerosis (FSGS). The mean age of our patients was 70 years (range: 50–80 years) and were monitored for an average period of 21 months (range: 3–72 months). A total of 5 of them were receiving an ACE inhibitor and the other 5 an ARB. The mean eGFR of our patients at the initiation of the study was 49.62 ± 24.35 mL/min, turned to be 41.42 ± 11.34 mL/min (P = NS) after a year and 54.2 ± 26.97 mL/min after 24 months (P = NS). Mean proteinuria of our patients at the initiation of the study was 1573.33 ± 959 mg/24-h, which turned to be 800.33 ± 575.33 mg/24-h (P = 0.122) after a year and 953.25 ± 1062.93 mg/24-h after 24 months (P = NS). No major kidney event happened in any of our patients. CONCLUSION Dapagliflozin preserved and slightly increased kidney function in our study population for the duration of our noticing period. Proteinuria, on the other hand, showed downward trends. Our study is in progress, but for sure long-term clinical studies in evaluating the potential benefit of SGLT2i, especially, in non-diabetic CKD patients are required before reaching a meaningful and solid conclusion.

MO569: Assessment of Inflammation Using Neutrophil-Lymphocyte Ratio Among Non-Dialyzed Chronic Kidney Disease Patients—A Prospective Observational Study

Abstract BACKGROUND AND AIMS Persistent low-grade inflammation is intimately linked to the pathophysiology of chronic kidney disease and contributes grossly to poor nutritional status and mortality. There is insufficient evidence on inflammation in relation to diabetic status, stages of CKD among chronic kidney disease patients before the commencement of dialysis. This study has characterized the prevalence and factors of inflammation among pre-dialysis chronic kidney disease patients at a tertiary care public teaching hospital. METHOD This longitudinal observational study adopted neutrophil–lymphocyte ratio (&amp;gt;3.53) to evaluate the inflammatory status among pre-dialysis chronic kidney disease patients. Glomerular filtration rate (eGFR) calculated by CKD-EPI equation from National Kidney Foundation was used as a measure of renal function. Multiple/multinomial regression analysis was also performed to determine the predictors of inflammatory status. RESULTS A total of 450 non-dialysis chronic kidney disease patients with or with diabetes were recruited during the period of study, consisting of 265 males and 185 females. Patients were aged 53.9 ± 14.2 years. According to neutrophil–lymphocyte ratio, the prevalence of inflammation among chronic kidney disease patients was found to be 91 (20.2%). The chronic kidney disease patients with diabetes 51(11.3%) were found to have higher rates of inflammation than non-diabetic chronic kidney disease patients 40 (8.9%). The adult age group 57 (12.7%) suffered more with inflammation than the elderly 34 (7.6%). Patients with severe malnutrition 42 (9.3%) were noted to have higher prevalence of inflammation followed by well-nourished 27 (6.0%) and mild/moderately malnourished population 22 (4.9%). The extent of inflammation was found to increase {CKD stage 1–2 (0.6%), CKD stage 3a-3b 34 (7.6%), CKD stage 4–5 54 (12.0%)} with decrease in renal residual function. Serum albumin, nutritional status and serum phosphorous have shown a significant association with the inflammatory status among chronic kidney disease patients. CONCLUSION The current findings demonstrate that the inflammation should be regarded as a familiar comorbid condition in chronic kidney disease. The intensity of inflammation is greater in patients with poorer renal function, comorbid diabetes and higher age. Future work needs to be aligned with respect to comprehensive understanding of inflammation mechanisms among patients with chronic kidney disease.

MO392: Mildly Impaired Kidney Function May Be Associated With the Risk of Hippocampal Atrophy in Young and Midlife Adults

Abstract BACKGROUND AND AIMS To date, associations between kidney function and brain structural abnormalities have been described in several studies [1]. Reports of renal function in relation to hippocampal atrophy have been scarce and the majority of studies have been focussed on older end-stage renal disease populations [2]. Particularly, with the ageing process, the hippocampus has a greater propensity to atrophy than other cerebral structures.The purpose of this study was to evaluate the relationship between kidney function assessed by estimated glomerular filtration rate (eGFR) and the degrees of hippocampal atrophy among young and midlife adults. METHOD In this cross-sectional study, the risk factors for hippocampal atrophy were evaluated in a cohort of 219 non-diabetic chronic kidney disease (CKD) patients, age ≤ 55 years, who had undergone magnetic resonance imaging (MRI) of the brain. The eGFR was calculated using the CKD-EPI formula. Hippocampal volume (HV) was assessed in brain MRIs with the Scheltens’ Medial Temporal Atrophy score, including a 5-stage escalation—0: no atrophy, 1: only widening of choroid fissure, 2: also widening of the temporal horn of lateral ventricle, 3: moderate loss of HV (decrease in height) and 4: severe loss of HV [3]. RESULTS In our group, the median and interquartile ranges (IQR) of age was 45 (14) years, 57.53% (126 patients) being males. The median eGFR was 100.6 (34.7) mL/min/1.73m2 and 46.75% (102 patients) presented with mild reduction in eGFR (eGFR between 60 to 89 mL/min/1.73m2). In univariable regression analysis, eGFR (R2 = 0.207, P &amp;lt; 0.001), arterial hypertension (R2 = 0.018, P = 0.045), dyslipidaemia (R2 = 0.044, P = 0.002), haematocrit (R2 = 0.021, P = 0.032), natrium levels (R2 = 0.018, P = 0.047), and potassium levels ( R2 = 0.019, P = 0.042) were associated with smaller HV. In multivariable regression analysis, eGFR [odds ratio (OR), 0.95; 95% confidence interval (CI), 0.94–0.97; P &amp;lt; 0.001) and serum natrium (OR, 0.91; 95% CI, 0.83–0.98; P = 0.027) were significantly associated with hippocampal atrophy. CONCLUSION This cross-sectional study shows that mild decrease in eGFR is independently associated with hippocampal atrophy. Our results suggest that brain imaging tests should be routinely performed in patients with mild reduction of eGFR, as the hippocampal atrophy process appears to be due, in part, to the mild renal dysfunction itself.

Comparison of peripapillary retinal nerve fiber layer and macular thickness in non-diabetic chronic kidney disease and controls.

ObjectiveThis study aimed to compare the peripapillary retinal nerve fiber layer (pRNFL) thickness and macular thickness (MT) between patients with non-diabetic chronic kidney disease (NDCKD) and controls, as well as between different stages of NDCKD. We also evaluated the correlation between pRNFL thickness and MT with duration of NDCKD.MethodsThis was a comparative cross-sectional study. Subjects were divided into NDCKD and control groups. Both pRNFL thickness and MT, including center subfield thickness (CST), average MT as well as average ganglion cell-inner plexiform layer (GC-IPL) were measured using spectral-domain optical coherence tomography. One-way ANCOVA test was used to compare the differences in pRNFL and MT between NDCKD and controls, as well as between the different stages of NDCKD. Spearman rank-order correlation coefficients were employed to determine the effects of NDCKD duration on pRNFL thickness and MT.ResultsA total of 132 subjects were recruited, 66 with NDCKD and 66 controls. There was a statistically significant difference in superior (110.74 ± 23.35 vs 117.36 ± 16.17 μm, p = 0.022), nasal (65.97 ± 12.90 vs 69.35 ± 10.17 μm, p = 0.006), inferior quadrant (117.44 ± 23.98 vs 126.15 ± 14.75 μm, p = 0.006), average pRNFL (90.36 ± 14.93 vs 95.42 ± 9.87 μm, p = 0.005), CST (231.89 ± 26.72 vs 243.30 ± 21.05 μm, p = 0.006), average MT (268.88 ± 20.21 vs 274.92 ± 12.79 μm, p = 0.020) and average GC-IPL (75.48 ± 12.44 vs 81.56 ± 6.48, p = 0.001) values between the NDCKD group and controls. The superior quadrant (p = 0.007), nasal quadrant (p = 0.030), inferior quadrant (p = 0.047), average pRNFL (p = 0.006), average MT (p = 0.001) and average GC-IPL (p = 0.001) differed significantly between different stages of NDCKD. There was no correlation between pRNFL thickness and MT with duration of NDCKD.ConclusionCST, average MT, average GC-IPL thickness, average pRNFL and all quadrants of pRNFL except the temporal quadrant were significantly thinner in NDCKD patients compared to controls. These changes were associated with the severity of CKD, but not its duration.