Progression Of Chronic Kidney Disease In Patients Research Articles

Longitudinal Patterns of Ankle-Brachial Index and Their Association With Progression of CKD in Patients With Type 2 Diabetes and Elevated Body Mass Index

Rationale & ObjectiveAnkle-brachial index (ABI) is used to screen for vascular complications in the setting of diabetes. This study sought to examine the relationship of longitudinal ABI data and chronic kidney disease (CKD) progression in patients with type 2 diabetes (T2D) and elevated body mass index (BMI). Study DesignA post-hoc analysis of the Look AHEAD trial. Setting & ParticipantsThis study included 3,631 participants in the Look AHEAD trial with a baseline glomerular filtration rate (eGFR) >60 ml/min/1.73 m2. ExposuresAverage ABI and average annual change in ABI were calculated based on annual ABI measurements during the first 4 years of the study. OutcomeCKD progression, defined as kidney failure requiring maintenance dialysis or the occurrence of eGFR<60 ml/min/1.73 m2 with a drop of ≥30% at a follow-up visit relative to the first eGFR measurement. Analytical ApproachRestricted cubic spline and Cox proportional hazards models were fit to estimate associations and to explore non-linearity. ResultsOver a median follow-up of 10.1 years, 1,051 participants developed CKD progression. There was a reversed J-shaped relationship of CKD progression with average ABI (when ABI <1.17: HR (per SD decrement), 1.23; 95%CI, 1.06-1.42; when ABI ≥ 1.17: HR (per SD increment), 1.10; 95%CI, 1.00-1.22) and average annual change in ABI (when change in ABI <-0.007: HR (per SD decrement), 1.37; 95%CI, 1.12-1.66; when change in ABI ≥-0.007: HR (per SD increment), 1.13; 95%CI, 1.03-1.24). LimitationsObservational study, potential unmeasured confounding. ConclusionsLow and high average ABI, even at clinically normal values, as well as decreasing and increasing average annual ABI, were associated a higher risk of CKD progression in patients with T2D and elevated BMI. Monitoring ABI and its changes over time may facilitate CKD risk stratification in patients with T2D.

SGLT2-Inhibition in Patients With Alport syndrome

IntroductionLarge-scale trials showed positive outcomes of sodium–glucose cotransporter-2 inhibitors (SGLT2i) in adults with chronic kidney disease (CKD). Whether the use of SGLT2i is safe and effective in patients with the common hereditary CKD Alport syndrome has not yet been investigated specifically in larger cohorts. MethodsThis observational, multi-center, international study (NCT02378805) assessed 112 patients with Alport syndrome after start of SGLT2i. The study’s primary endpoint was change of albuminuria in albumin/gram creatinine from start of therapy. ResultsCompared to randomized trials investigating the effect of SGLT2i in CKD, the adult patients in this study were younger (38±14 years) and had a better estimated glomerular filtration rate, eGFR, (63±35 ml/min/1.73m2; n=98). Maximum follow up was 32 months. Compared to baseline, at the first three follow-up visits (months 1 to 3, 4 to 8 and 9 to 15) after initiation of SGLT2i-therapy, a significant reduction of albuminuria in milligrams albumin/gram creatinine (>30%) was observed. Mean loss of eGFR was 9±12 ml/min/1.73 m2 almost one year after initiation of SGLT2i-therapy (n=35). At a total of 71 patient-years at risk, 0.24 adverse events per patient year on SGLT2i were reported. ConclusionThis study indicates that, additive to RAS-inhibition, SGLT2i have the potential to reduce the amount of albuminuria in patients with Alport syndrome. Future studies are needed to investigate the long-term effects of SGLT2i on CKD progression in patients with Alport syndrome to assess whether the observed reduction in albuminuria translates to a delay in kidney failure.

A Urine pH-Ammonium Acid/Base Score and CKD Progression.

Acidosis is associated with exacerbated loss of kidney function in chronic kidney disease (CKD). Currently, acid/base status is assessed by plasma measures, although organ-damaging covert acidosis, subclinical acidosis, may be present before reflected in plasma. Low urine NH4+ excretion associates with poor kidney outcomes in CKD and is proposed as a marker for subclinical acidosis. However, low NH4+ excretion could result from either a low capacity or a low demand for acid excretion. We hypothesized that a urine acid/base-score reflecting both the demand and capacity for acid excretion would better predict CKD progression. 24-hour urine collections were included from three clinical studies of patients with CKD stage 3 and 4: A development cohort (n=82), a variation cohort (n=58), and a validation cohort (n=73). A urine acid/base-score was derived and calculated from urinary pH and [NH4+]. Subclinical acidosis was defined as an acid/base-score below the lower limit of the 95% prediction interval of healthy controls. Main outcomes were change in measured GFR after 18 months and CKD progression (defined as ≥50% decline in eGFR, initiation of long-term dialysis or kidney transplantation) during up to 10 years of follow-up. Subclinical acidosis was prevalent in all cohorts (n=54/82, 48/73, and 40/58, ∼67%). Subclinical acidosis was associated with an 18% (95% CI: 2-32) larger decrease of measured GFR after 18 months. During a median follow-up of 6 years, subclinical acidosis was associated with a markedly higher risk for CKD progression. Adjusted hazard ratios were 9.88 (95% CI 1.27-76.7) in the development cohort and 11.1 in the validation cohort (95% CI: 2.88-42.5). The acid/base-score had a higher predictive value for CKD progression than NH4+ excretion alone. Subclinical acidosis, defined by a new urine acid/base-score, was associated with a higher risk of CKD progression in patients with CKD stage 3 and 4.

#3004 Serum miRNAs as novel biomarkers and modulators of rapidly progressing chronic kidney disease in patients with diabetes

Abstract Background and Aims Chronic kidney disease (CKD) is very common in diabetes, occurring in around 40% of patients. Without treatment, CKD can lead to end stage renal disease (ESRD), which requires costly dialysis and transplantation. Current treatments aim to prevent CKD or slow down its progression to ESRD. The speed of CKD progression is patient-specific, and at present there are no biomarkers which can predict which patient with diabetes will develop CKD; level of albuminuria is an important but variably reliable biomarker of speed of CKD progression. The current methods for rapid identification of patients prone to accelerated CKD progression are limited, as they are based on measuring estimated glomerular filtration rate (eGFR) over prolonged periods of time, as well as albuminuria. Therefore, there is a clinical need for novel biomarkers that can predict early potential rapid CKD progression in patients. The aim of this project is to determine whether serum microRNAs (miRs) can be used as biomarkers to predict the speed of CKD progression in diabetes patients, and to identify potential treatment targets associated with such dysregulated miRs. Method miRs were isolated from sera of 34 patients with type 2 diabetes classed with either slow or fast progressing CKD by their eGFR (n = 17; obtained from the Salford Kidney Study sample collection). Several miRs were found to be significantly dysregulated in fast progressing patients by using Next Generation Sequencing (NGS) of miRs in individual serum samples. An additional 49 diabetic CKD patient serum samples (slow (n = 29) or fast progressors (n = 20)) were used to validate the potential miR biomarker panel by qPCR. Results The NGS miR analysis of the initial 34 CKD patient sera produced a panel of 16 miRs that were either significantly upregulated or downregulated in the fast-progressing patients compared to slow progressors. The qPCR validation of this initial panel in 49 additional CKD patient serum samples demonstrated that 6 miRs were significantly upregulated in the fast-progressing patients. The levels of these miRs correlated with demographic and clinical parameters. ROC curve analysis revealed that the individual predictive power of each of those 6 miRs to define either a slow or fast progressing CKD patient was between 63-75%. Determination of a miR combination the strongest predictive power is ongoing. Conclusion A potential biomarker panel of 6 miRs has been identified and validated by qPCR, with each miR having a predictive power of between 63-75% for fast progression of CKD. A panel of miRs that could accurately predict progression speed of CKD patients could lead to faster and earlier diagnosis of patients to enable better treatment. Work is ongoing to explore the predictive power of this miR biomarker panel, and potential novel therapeutic targets to prevent CKD or delay its progression to ESRD.

#1200 Coronary artery calcium modifies the relationship between blood pressure and adverse kidney outcome: results from KNOW-CKD

Abstract Background and Aims Previous studies evidenced that elevated coronary artery calcium (CAC) score is associated with higher chronic kidney disease (CKD) progression. However, the use of CAC score to guide CKD management has not been adequately evaluated. Here, we evaluated whether presence of CAC modify the association between systolic blood pressure (SBP) and CKD progression in patients with CKD. Method We analyzed 1693 participants with CKD stages G1 to G5 from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Key exclusion criteria were kidney failure with replacement therapy (KFRT) and missing data for CAC and SBP information. We categorized participants according to baseline SBP and CAC score (Controlled BP, SBP &amp;lt; 120 mmHg; Elevated BP without CAC, SBP 120-140 mmHg and CAC score = 0; Elevated BP with CAC, SBP 120-140 mmHg and CAC score &amp;gt;0; Uncontrolled BP, SBP &amp;gt;140 mmHg) and compared the CKD progression. The CKD progression was defined as a composite of halving eGFR from baseline value or onset of KFRT. Results During 10,023 person-years of follow-up (median 6.2 years), the composite outcome occurred in 689 (40.7%) participants, and 108 (6.4%) participants died among the KNOW-CKD participants. There was significant interaction between CAC score and SBP for CKD progression (P &amp;lt; 0.001). There were 181/568 (31.9%), 167/424 (39.4%), 128/314 (40.8%) 213/387 (55.0%), composite outcomes in controlled BP, elevated BP without CAC, elevated BP with CAC, uncontrolled BP group, respectively. In crude Cox regression, compared to controlled BP, elevated BP with CAC group showed similar CKD progression risk (Hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.95-1.44), whereas other strata group showed increased risk of CKD progression (elevated BP with CAC; HR, 1.59; 95% CI 1.31-1.94 and uncontrolled BP, HR, 1.94; 95% CI 1.56-2.41). Similar elevated risk in elevated BP with CAC was observed even after adjustment of age, sex, diabetes mellitus, estimated glomerular filtration ratio, and proteinuria (HR, 1.26; 95% CI, 1.02-1.56). However, the risk of CKD progression in elevated BP without CAC group was comparable to controlled BP group (HR, 1.20; 95% CI, 0.87-1.66). Conclusion Elevated SBP was more strongly associated with an increased risk of adverse kidney outcomes in patients with coronary calcification.

Association of serum 25-hydroxyvitamin D with cardiovascular mortality and kidney outcome in patients with early stages of CKD.

While serum 25-hydroxyvitamin D (25[OH]D) deficiency is prevalent in chronic kidney disease (CKD), the effects of 25(OH)D deficiency on cardiovascular mortality and kidney outcomes in patients with early-stage CKD remain incompletely understood. This multicenter retrospective cohort study included adult patients with stages 1-3 CKD from 19 medical centers across China between January 2000 and May 2021. The primary outcome was cardiovascular mortality. The secondary study outcome included CKD progression (defined as a sustained > 40% eGFR decrease from baseline or progress to end-stage kidney disease), and annual percentage change of eGFR. Of 9229 adults with stages 1-3 CKD, 27.0% and 38.9% had severe (< 10ng/mL) and moderate (10 to < 20ng/mL) serum 25(OH)D deficiency, respectively. Compared with patients having 25(OH)D ≥ 20ng/mL, a significantly higher risk of cardiovascular mortality (hazard ratio [HR] 1.90, 95% CI 1.37-2.63), CKD progression (HR 2.20, 95% CI 1.68-2.88), and a steeper annual decline in eGFR (estimate - 7.87%; 95% CI - 10.24% to - 5.51% per year) was found in those with serum 25(OH)D < 10ng/mL. Similar results were obtained in subgroups and by sensitivity analyses. 25(OH)D deficiency is associated with increased risks of cardiovascular mortality and CKD progression in patients with early-stage CKD. Studies are needed to determine whether early intervention for 25(OH)D deficiency could improve the prognosis of patients with early-stage CKD.

Changes in the Progression of Chronic Kidney Disease in Patients Undergoing Fecal Microbiota Transplantation.

Chronic kidney disease (CKD) is a progressive loss of renal function in which gut dysbiosis is involved. Fecal microbiota transplantation (FMT) may be a promising alternative for restoring gut microbiota and treating CKD. This study evaluated the changes in CKD progression in patients treated with FMT. Patients with diabetes and/or hypertension with CKD clinical stages 2, 3, and 4 in this single-center, double-blind, randomized, placebo-controlled clinical trial (NCT04361097) were randomly assigned to receive either FMT or placebo capsules for 6 months. Laboratory and stool metagenomic analyses were performed. A total of 28 patients were included (15 FMT and 13 placebo). Regardless of CKD stages, patients responded similarly to FMT treatment. More patients (53.8%) from the placebo group progressed to CKD than the FMT group (13.3%). The FMT group maintained stable renal function parameters (serum creatinine and urea nitrogen) compared to the placebo group. Adverse events after FMT treatment were mild or moderate gastrointestinal symptoms. The abundance of Firmicutes and Actinobacteria decreased whereas Bacteroidetes, Proteobacteria and Roseburia spp. increased in the FMT group. CKD patients showed less disease progression after FMT administration. The administration of oral FMT in patients with CKD is a safe strategy, does not represent a risk, and has potential benefits.

MORPHO-FUNCTIONAL PROPERTIES OF ERYTHROCYTES AS A MARKER OF THE PROGRESS OF KIDNEY INJURIES IN PATIENTS WHO HAD CORONAVIRUS DISEASE

Pathology of the morpho-functional state of erythrocytes affects the rheological properties of blood and various regulatory processes that ensure microcirculation in the kidneys. Changes in the morpho-functional state of erythrocytes are the cause of pathological effects on the membranes and receptors of kidney cells. It leads to adverse disorders of vital activity and functioning of the kidneys.Aim. The paper aims to investigate the morpho-functional state of erythrocytes in patients with kidney damage who were sick with COVID-19. Material and methods. 75 patients aged 45-65 years with kidney damage who suffered from moderate COVID 8-12 months ago were examined. Research groups and control groups were formed (patients with appropriate nosology who did not suffer from COVID): I – glomerulonephritis; II – pyelonephritis; ІІІ – diabetic nephropathy of the 4th century. All patients had a protocol examination of nephrological patients, and we also examined the morpho-functional properties of erythrocytes (the deformability index of erythrocytes, peroxide hemolysis of erythrocytes and the relative viscosity of the erythrocyte suspension using filtration methods.Results. Changes in the morpho-functional properties of erythrocytes may indicate the progressive course of kidney diseases in patients who have undergone COVID. It manifested by a decrease in the deformability index of erythrocytes, by more than 40% in patients with glomerulonephritis and twice in patients with diabetic nephropathy, as well as a probable increase in the relative viscosity of the erythrocyte suspension, which was 2 times higher in the group with glomerulonephritis and 3 times higher in the group with diabetic nephropathy compared with pyelonephritis. An inverse correlation between daily proteinuria and the index of deformability of erythrocytes in patients with chronic kidney disease (CKD) after COVID (r=-0.59) (р=0.041), as well as a direct correlation between peroxide hemolysis of erythrocytes and daily proteinuria (r=0.68) ( p=0.038) and between the relative viscosity of the erythrocyte suspension with daily proteinuria (r=0.76) (p=0.035) were detected.Conclusions. Changes in the morpho-functional properties of erythrocytes were more profound in patients with diabetic nephropathy and glomerulonephritis after experiencing COVID than in patients with pyelonephritis. A correlation was found between indicators of morpho-functional properties of erythrocytes and daily proteinuria. Indicators of the morpho-functional properties of erythrocytes can be markers of the progression of CKD in patients who have experienced moderate COVID.

Effectiveness of a Disease Management Program (DMP) in controlling the progression of Chronic Kidney Diseaseamong hypertensives and diabetics.

The occurrence rate of stage 5 chronic kidney disease (CKD) will be 151 per million population in India in the coming years. Comorbidities like diabetes mellitus and hypertension are the usual triggers of CKD. Hence this study aimed to control the progression of CKD and to note the effectiveness of a structured education program that would help in the prevention of complications related to diabetes and hypertension. This quasi-experimental study was conducted among 88 participants who had hypertension, diabetes mellitus, or both for five or more years. The study objective was to find the effect of a Disease Management Program on delaying progression of CKD in patients with hypertension or diabetes mellitus.The baseline data were obtained from demographic proforma, and the clinical data collected were the blood pressure, serum creatinine, and random blood sugar (RBS) of the participants. The management of hypertension and diabetes mellitus was taught to them. In the fourth and the eighth month, blood pressure and blood sugar were reassessed. At one-year blood pressure, blood sugar, and serum creatinine were tested. Baseline and one-year follow-up blood pressure, blood sugar, and estimated Glomerular Filtration Rate were compared. Descriptive statistics and "Wilcoxon signed-rank test" were used to analyze the data. In one year, the mean systolic blood pressure reduced by six mm of Hg and mean blood sugar by 24 mg/dl. The prevalence of CKD stage three and above (< 60 ml/min/m2) was nine (10.22%). The median decline in eGFR was 5 ml/min/m2 (Z= 5.925, P< 0.001). The Disease Management Program led to improvements in blood pressure and diabetes control and median progression of CKD was estimated at five ml/min/m2/year.

The role of inflammatory markers and growth factors in progression of chronic kidney disease in patients with diabetes mellitus

Introduction: A Diabetes mellitus (DM) and chronic kidney disease (CKD) are two chronic non-communicable diseases that have exceeded epidemic thresholds in all countries of the world. The problem of early diagnosis, prevention and treatment of CKD continues to be relevant for modern medicine, and assessment of the severity of CKD and associated cardiovascular complications is of great practical importance for primary and secondary prevention. Objectives: The aim of the study was to assess the role of proinflammatory cytokines, chemokines and growth factors in progression of CKD in patients with DM. Patients and Methods: We screened 155 type 2 DM patients aged 65.00 (55.00-71.00) years. Control group included 21 healthy people with the same age. Renal function was assessed based on the levels of serum creatinine, cystatin C, estimated glomerular filtration rate (eGFR), which was calculated according to the CKD-EPI (chronic kidney disease epidemiology collaboration) equation, and albuminuria, which was assessed as albumin/creatinine ratio (A/C). The analysis of serum and urine biomarkers was carried out by enzyme immunoassay using commercial test systems. Results: Patients with DM had significantly higher levels of proinflammatory cytokines in comparison with the control group. The levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor-23 (FGF-23), regulated upon activation, normal T cell expressed and presumably secreted (RANTES), MIG, CRP, kidney injury molecule-1 (KIM-1) and homocysteine gradually increased with decreasing GFR. According to the results of univariate linear regression analysis, there were significant relationships between the levels of VEGF-A, FGF-23, RANTES, tumor necrosis factor alpha (TNF-alpha), MIG, CRP, hs-CRP, IL-6 and renal function. By multiple linear regression analysis adjusted for confounding factors, serum creatinine was significantly correlated with FGF-23 (β=0.40, P&lt;0.001) and Il-6 (β=0.29, P&lt;0.001). Conclusion: Our study demonstrated the important role of growth factors and proinflammatory cytokines in the development and progression of CKD in DM. However, despite these data, the pathogenesis of diabetic changes in the kidneys remains not fully understood and, in order to clarify the possibility of pathogenetic influences on the progression of diabetic nephropathy, it is necessary to study various aspects of its development, including genetic factors.

Findings from the KNOW-CKD Study indicate that higher systolic blood pressure time in target range is associated with a lower risk of chronic kidney disease progression

Time-in-target range (TTR) of systolic blood pressure (SBP) is determined by the proportion of time during which SBP remains within a defined optimal range. TTR has emerged as a useful metric for assessing SBP control over time. However, it is uncertain if SBP-TTR can predict the progression of chronic kidney disease (CKD). Here, we investigated the association between SBP-TTR during the first year of enrollment and CKD progression among 1758 participants from the KNOW-CKD (KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease). Baseline median estimated glomerular filtration rate (eGFR) was 51.7 ml/min per 1.73 m2. Participants were categorized into four SBP-TTR groups (0%, 1–50%, 51–99%, and 100%). The primary outcome was CKD progression defined as 50% or more decline in eGFR from baseline measurement or the initiation of kidney replacement therapy. During the follow-up period (9212 person-years over a median 5.4 years), the composite outcome occurred in 710 participants. In the multivariate cause-specific hazard model, a one-standard deviation increase in SBP-TTR was associated with an 11% lower risk of the composite outcome with hazard ratio, 0.89 (95% confidence interval, 0.82–0.97). Additionally, compared to patients with SBP-TTR 0%, the respective hazard ratios for those with SBP-TTR 1–50%, 51–99%, and 100% were 0.85 (0.68–1.07), 0.76 (0.60–0.96), and 0.72 (0.55–0.94), and the respective corresponding slopes of eGFR decline were –3.17 (–3.66 to –2.69), –3.02 (–3.35 to –2.68), –2.62 (–2.89 to – 2.36), and –2.33 (–2.62 to –2.04) ml/min/1.73 m2 . Thus, higher SBP-TTR was associated with a decreased risk of CKD progression in patients with CKD.

DYNAMICS OF β2-MICROGLOBULIN CONTENT IN BLOOD AND URINE IN PATIENTS WITH KIDNEY DAMAGE WHO HAD CORONAVIRUS DISEASE

The purpose of the work – to study the content of beta-2-microglobulin in the bloodand urine of patients with kidney damage who suffered from coronavirus disease, and tointerpret the results.Material and methods. 95 patients with kidney damage who suffered from coronavirusdisease were examined. In all patients, the content of beta-2-microglobulin in blood andurine was examined by the immunoenzymatic method.The results. The most significant increase in the content of beta-2-microglobulin inboth blood and urine was noted in patients who contracted the coronavirus diseaseagainst the background of chronic kidney disease (CKD) of the III-IV stage, includingin patients undergoing hemodialysis. In patients with stage I-II CKD with pyelonephritisand glomerulonephritis, an increase in the level of beta-2-microglobulin only in theblood was observed. In CKD patients with type II diabetes, an increase in the content ofbeta-2-microglobulin in the blood and urine was noted even in the presence of CKD-II stage.Conclusions. The coronavirus disease has a negative effect on the course of chronickidney disease and accelerates its progression due to a significant acceleration of thedevelopment of renal (tubular) dysfunction. This is indicated by the increase in thecontent of beta-2-microglobulin in the blood and urine of patients who have suffered fromthe coronavirus disease. Patients with type II diabetes with kidney damage who haveexperienced coronavirus disease are a separate group at risk of rapid progression ofCKD. This method of monitoring the dynamics of beta-2-microglobulin content in bloodand urine can be used for early diagnosis of the progression of CKD in patients who havesuffered from the coronavirus disease.

Association of the dietary inflammation index (DII) with the prevalence of chronic kidney disease in patients with type-2 diabetes mellitus

Chronic kidney disease (CKD) is a major complication of diabetes mellitus (DM). Inflammation is an essential component in the process of CKD progression in patients with DM. Diet is a significant determinant of systemic inflammation levels. However, the association between the dietary inflammatory index (DII) and CKD in individuals with DM remains largely unknown; therefore, the aim of this study was to explore whether the DII is linked to the prevalence of CKD in patients with DM. The research method was as follows: first, data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018 were obtained. There were 7,974 participants in our study. These individuals were then classified into three groups according to DII tertiles (T1-T3), with each group consisting of 2,658 participants. Logistic regression analysis was employed to examine whether there was a connection between the DII and CKD. We observed a significant association between the DII and the prevalence of CKD in individuals with DM. After full adjustment for age, sex, ethnicity, smoking, drinking, body mass index (BMI), triglyceride (TG), total cholesterol (TC), metabolic equivalents (METs), energy intake, hypoglycemic medications, hypertension, and cardiovascular disease (CVD), the group with a higher DII had a greater frequency of CKD (T2 group: OR: 1.40; 95% CI: 1.10–1.76; p = 0.006; T3 group: OR: 1.67; 95% CI: 1.29–2.17; p < 0.001). The implementation of an anti-inflammatory diet could serve as an intervention strategy for patients with DM to prevent the onset of CKD.

β2-Adrenergic receptor agonists as a treatment for diabetic kidney disease.

We have previously shown that the long-acting β2-adrenergic receptor (β2-AR) agonist formoterol induced recovery from acute kidney injury in mice. To determine whether formoterol protected against diabetic nephropathy, the most common cause of end-stage kidney disease (ESKD), we used a high-fat diet (HFD), a murine type 2 diabetes model, and streptozotocin, a murine type 1 diabetes model. Following formoterol treatment, there was a marked recovery from and reversal of diabetic nephropathy in HFD mice compared with those treated with vehicle alone at the ultrastructural, histological, and functional levels. Similar results were seen after formoterol treatment in mice receiving streptozotocin. To investigate effects in humans, we performed a competing risk regression analysis with death as a competing risk to examine the association between Veterans with chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), who use β2-AR agonists, and Veterans with CKD but no COPD, and progression to ESKD in a large national cohort of Veterans with stage 4 CKD between 2011 and 2013. Veterans were followed until 2016 or death. ESKD was defined as the initiation of dialysis and/or receipt of kidney transplant. We found that COPD was associated with a 25.6% reduction in progression from stage 4 CKD to ESKD compared with no COPD after adjusting for age, diabetes, sex, race-ethnicity, comorbidities, and medication use. Sensitivity analysis showed a 33.2% reduction in ESKD in Veterans with COPD taking long-acting formoterol and a 20.8% reduction in ESKD in Veterans taking other β2-AR agonists compared with those with no COPD. These data indicate that β2-AR agonists, especially formoterol, could be a treatment for diabetic nephropathy and perhaps other forms of CKD.NEW & NOTEWORTHY Diabetic nephropathy is the most common cause of ESKD. Formoterol, a long-acting β2-adrenergic receptor (β2-AR) agonist, reversed diabetic nephropathy in murine models of type 1 and 2 diabetes. In humans, there was an association with protection from progression of CKD in patients with COPD, by means of β2-AR agonist intake, compared with those without COPD. These data indicate that β2-AR agonists, especially formoterol, could be a new treatment for diabetic nephropathy and other forms of CKD.

New possibilities of nephroprotection in type 2 diabetes using finerenone Consensus of the board of experts

Patients with chronic kidney disease (CKD) belong to the category of patients with diabetes mellitus (DM), which are the most difficult to treat. They require a multidisciplinary, multifactorial approach to slow disease progression, reduce glomerular filtration rate (GFR), and prevent cardiovascular morbidity and mortality. Modern treatment of CKD in patients with type 2 diabetes involves influencing various links of its pathogenesis. The use of finerenone is a fundamentally new approach in treatment of CKD. Inflammation and fibrosis, which develop as a result of excessive activation of mineralocorticoid receptors, are key pathophysiological mechanisms of the development and progression of CKD in patients with type 2 DM. Therefore, the blocking of mineralocorticoid receptors (MCR) with the innovative nonsteroidal selective MCR antagonist finerenone is a promising way to improve the clinical course of CKD, and has a favorable prognostic effect on the rate of progression of CKD and on the risk of cardiovascular events. The feasibility of adding finerenone to the treatment regimens of patients with CKD and type 2 diabetes in order to reduce the rate of progression of CKD and reduce the frequency of cardiovascular events is substantiated by convincing data from clinical studies and reflected in the recommendations of the American Diabetes Association, 2023. The innovative drug finerenone has a direct nephroprotective effect, which reliably slows down the progression of CKD in patients with type 2 diabetes. Therefore, finerenone should be considered for prescribing from the initial stage of kidney damage. When using finerenone, the risk of developing hyperkalemia is low, which minimizes the risk of withdrawal of the drug during treatment. Despite the available modern methods of treatment, which are primarily aimed at the hemodynamic and metabolic factors of the development of CKD in type 2 diabetes mellitus, the introduction of the specified new pathogenetic approach using finerenone, as a means whose mechanism of action is due to a direct effect on inflammation and fibrosis, is considered necessary from the point of view of improving the clinical course of CKD and the prognosis.

#5365 T2DM MODIFIES THE RELATIONSHIP BETWEEN CAC AND ADVERSE KIDNEY OUTCOME IN PATIENTS WITH CKD

Abstract Background and Aims Kidney function decline faster in patients with type 2 diabetes mellitus (T2DM) than in those without. We previously showed that coronary artery calcification (CAC) is a strong risk of adverse kidney outcome. Here, we examined whether T2DM could modify the relationship between CAC and the progression of chronic kidney disease (CKD). Method 2067 participants from the KoreaN Cohort Study for Outcome in Patients With CKD were enrolled. The main exposures were T2DM and CAC. The primary outcome was CKD progression defined as a composite of a 50% decline in estimated glomerular filtration rate or kidney failure with replacement therapy. Multivariable cause-specific hazard function was employed to determine the association between the main exposures and the primary outcome. Results During 8633 person-years of follow-up, the primary outcome occurred in 565 (27.3%) participants. In the multivariable cause-specific hazard model, both T2DM and CAC Agatston score (CACS) &amp;gt;0 were associated with a 1.80- and a 1.41-fold increased risk of CKD progression compared with counterparts. There was a significant interaction between T2DM and CAC for the primary outcome. In patients without T2DM, CACS &amp;gt;0 was not associated with the primary outcome compared with CACS of 0. However, in patients with T2DM, CACS &amp;gt;0 was associated with a significantly higher risk of CKD progression (adjusted hazard ratio, 2.12; 95% confidence interval, 1.64-2.75). In addition, a 1-SD increase in CACS was associated with 1.11-fold higher risk of CKD progression. Notably, this association was also significant in patients with T2DM who had CACS of 0. The slope of eGFR decline was steeper in patients with T2DM and the magnitude of decline was greater when CACS &amp;gt;0. Conclusion CAC were more strongly associated with risk of CKD progression in patients with T2DM than in those without. Thus, clinical implication of CAC may differ depending on the presence of T2DM.

#3556 ASSOCIATION OF SERUM 25-HYDROXYVITAMIN D WITH ALL-CAUSE MORTALITY AND KIDNEY OUTCOME IN PATIENTS WITH EARLY STAGES OF CKD

Abstract Background and Aims Although serum 25-hydroxyvitamin D (25(OH)D) deficiency is prevalent in all stages of chronic kidney disease (CKD), the effects of 25(OH)D deficiency on all-cause mortality and kidney outcomes in patients with early-stage CKD remain incompletely understood. Method This nationwide retrospective cohort study included 9840 adults with stages 1–3 CKD from 19 medical centers across China. The study outcomes included all-cause mortality, cardiovascular mortality, and kidney disease progression. The associations between serum 25(OH)D concentrations and the risks of mortality and CKD progression were evaluated using a Cox proportional hazard model. A mixed-effects model was used to estimate the slopes of estimated glomerular filtration rate (eGFR). Results Of 9840 adults with stages 1–3 CKD, 26.9% had severe (&amp;lt;10 ng/ml) and 38.7% had moderate (10–20 ng/ml) serum 25(OH)D deficiency. Compared with patients having 25(OH)D &amp;gt;20 ng/ml, patients with serum 25(OH)D &amp;lt;10 ng/ml were at significantly higher risks of all-cause mortality (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.53–2.28), cardiovascular mortality (HR 1.80, 95% CI 1.33–2.44), and CKD progression (HR 2.28, 95% CI 1.74–2.99), and had a steeper decline in eGFR slope (estimate -0.07; 95% CI -0.10 to -0.05 mL/min/1.73 m2 per year). Similar results were obtained in subgroups and by sensitivity analyses. Conclusion 25(OH)D deficiency is associated with increased risks of all-cause mortality and CKD progression in patients with early-stage CKD. Studies are needed to determine whether early intervention for 25(OH)D deficiency could improve the prognosis of patients with early-stage CKD.

Kidney function in cachexia and sarcopenia: Facts and numbers.

Cachexia, in the form of unintentional weight loss >5% in 12months or less, and secondary sarcopenia in the form of muscle wasting are serious conditions that affect clinical outcomes. A chronic disease state such as chronic kidney disease (CKD) often contributes to these wasting disorders. The purpose of this review is to summarize the prevalence of cachexia and sarcopenia, their relationship with kidney function, and indicators for evaluating kidney function in patients with CKD. It is estimated that approximately half of all persons with CKD will develop cachexia with an estimated annual mortality rate of 20%, but few studies have been conducted on cachexia in CKD. Hence, the true prevalence of cachexia in CKD and its effects on kidney function and patient outcomes remain unclear. Some studies have highlighted the concept of protein-energy wasting (PEW) which usually include sarcopenia and cachexia. Several studies have examined kidney function and CKD progression in patients with sarcopenia. Most studies use serum creatinine levels to estimate kidney function. However, creatinine may be influenced by muscle mass, and creatinine-based glomerular filtration rate may overestimate kidney function in patients with reduced muscle mass or muscle wasting. Cystatin C, which is least affected by muscle mass, has been used in some studies, and creatinine-to-cystatin-C ratio has emerged as an important prognostic marker. A previous study incorporating 428320 participants reported that participants with CKD and sarcopenia had a 33% higher hazard of mortality compared with those without (7% to 66%, P=0.011), and that those with sarcopenia were twice as likely to develop end-stage kidney disease (hazard ratio: 1.98; 1.45 to 2.70, P<0.001). Future studies on cachexia and sarcopenia in patients with CKD are needed to report rigorously defined cachexia concerning kidney function. Moreover, in studies on sarcopenia with CKD, it is desirable to accumulate studies using cystatin C to accurately estimate kidney function.

Effectiveness of a Disease Management Program (DMP) in controlling the progression of Chronic Kidney Disease among hypertensives and diabetics.

Background: In India, the number of patients with type II diabetes mellitus in 2006 was 40.9 million and is expected to increase by 2025 to 69.9 million. The occurrence rate of stage 5 CKD was 151 per million population in India. Diabetes Mellitus and hypertension were the usual triggers of Chronic Kidney Disease (CKD). A structured education program helps in the prevention of diabetes and hypertension related complications. Methods: This quasi-experimental study was conducted among 88 participants who had hypertension, diabetes mellitus, or both for five or more years with an objective to find the effect of a Disease Management Program on delaying progression of CKD in patients with hypertension or diabetes mellitus. The baseline data were collected on demographic proforma, serum creatinine, blood pressure, and random blood sugar, and the patients were taught the management of hypertension and diabetes mellitus. In the fourth and the eighth month, blood pressure and blood sugar were reassessed. At one-year blood pressure, blood sugar, and serum creatinine were tested. Baseline and one-year follow-up blood pressure, blood sugar, and estimated Glomerular Filtration Rate were compared. Descriptive statistics and "Wilcoxon signed-rank test" were used to analyze the data. Results: In one year, the mean systolic blood pressure reduced by six mm of Hg and mean blood sugar by 24 mg/dl. The prevalence of CKD stage three and above (&lt; 60 ml/min/m2) was nine (10.22%). The median decline in eGFR was 5 ml/min/m2 (Z= 5.925, P&lt; 0.001). Conclusion: The Disease Management Program led to improvements in blood pressure and diabetes control and median progression of CKD was estimated at five ml/min/m2/year.

PS-C27-5: ASSOCIATION BETWEEN ANKLE-BRACHIAL INDEX AND KIDNEY OUTCOMES IN PATIENTS WITH HYPERTENSION

Background: Ankle-brachial index (ABI) used for diagnosis of peripheral vascular disease is related to endothelial dysfunction. Previous studies showed the relationship between endothelial dysfunction and chronic kidney disease (CKD). Therefore, we aimed to investigate the association between ankle-brachial index and CKD progression in patients with hypertension. Methods: A total of 2,429 patients with hypertension were enrolled from the prospective observational cohort of CMERC-HI (Cardiovascular and Metabolic Disease Etiology Research Center-High Risk). Patients were classified into quartile based on ABI (A1: ABI &lt; 1.11, A2: ABI 1.11 to 1.17, A3: ABI 1.17 to 1.23, A4: ABI&gt; 1.23). Primary outcome was progression of CKD, which was composite of at least 50% decrease in estimated glomerular filtration rate (eGFR) from baseline or end stage kidney disease requiring dialysis, or incident CKD which was defined as eGFR &lt; 60 ml/min/1.73m2. Results: The mean age of study subjects was 60.1 ± 11.3 years and 1,346 (55.4%) were male. There were statistically significant differences in DM status (40.1%, 41.1%, 43.7%, 51.7% in A1, A2, A3, A4 group, respectively, P &lt; 0.001) among ABI quartile groups. During a median follow-up of 42.5 months, the primary outcome met the pre-specified CKD progression in 490 (20.2%). In multivariate Cox analysis, A1 and A3 group were associated with increased risk of CKD progression (HR, 2.28; 95% CI, 1.30–4.00, P = 0.004, HR, 2.22: 95% CI, 1.27–3.90, P = 0.005) compared to A2 group. Moreover, low ABI showed increased risk of CKD progression (HR, 1.57; 95% CI, 1.04–2.38; P = 0.03) after adjusting confounding factors. Conclusions: Ankle-brachial index may be an independent predictor of renal outcome in patients with hypertension.