Chronic Kidney Disease Cohort Research Articles

Characteristics, management and outcomes in patients with CKD in a healthcare region in Sweden: a population-based, observational study

ObjectivesTo describe chronic kidney disease (CKD) regarding treatment rates, comorbidities, usage of CKD International Classification of Diseases (ICD) diagnosis, mortality, hospitalisation, evaluate healthcare utilisation and screening for CKD in relation...

Associations between collagen X biomarker and linear growth velocity in a pediatric chronic kidney disease cohort.

Collagen X biomarker (CXM) is a novel biomarker of linear growth velocity. We investigated whether CXM correlated with measuredgrowth velocity in children with impaired kidney function. We used data from children aged 2 through 16years old enrolled in the Chronic Kidney Disease in Children (CKiD) study. We assessed the association between CXM level and growth velocity based on height measurements obtained at study visits using linear regression models constructed separately by sex, with and without adjustment for CKD covariates. Linear mixed-effects models were used to capture the between-individual and within-individual CXM changes over time associated with concomitant changes in growth velocity from baseline through follow-up. A total of 967 serum samples from 209 participants were assayed for CXM. CXM correlated more strongly in females compared to male participants. After adjustment for growth velocity and CKD covariates, only proteinuria in male participants affected CXM levels. Finally, we quantified the between- and within-participant associations between CXM level and growth velocity. A between-participant increase of 24% and 15% in CXM level in females and males, respectively, correlated with a 1cm/year higher growth velocity. Within an individual participant, on average, 28% and 13% increases in CXM values in females and males, respectively, correlated with a 1cm/year change in measured growth. CXM measurement is potentially a valuable aid for monitoring growth in pediatric CKD. However, future research, including studies of CXM metabolism, is needed to clarify whether CXM can be a surrogate of growth in children with CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Anaemia due to chronic kidney disease: A cross-sectional analysis from a tertiary referral centre in Sri Lanka

Introduction: Anaemia is a common complication of chronic kidney disease (CKD) that adversely affects cardiovascular health and quality of life. Data on anaemia in Sri Lankan CKD patients is scarce.Objectives: This study was conducted to assess the prevalence, associations, and treatment response of anaemia in a cohort of patients with CKD.Methodology: A descriptive cross-sectional study was conducted among consecutive, consenting adult patients with stable CKD attending clinics and wards of the University Medical Unit, Colombo North Teaching Hospital, Ragama.Results: Of 149 patients with CKD (males 57.7%), 70.5% had diabetes, 83.9% had hypertension and 37.6% had ischemic heart disease. Anaemia was present in 90.6% of females and 93% of males. The severity of anaemia was significantly (p=<.05) associated with female gender, advancing CKD stage, diabetes, chronic liver cell disease, being on dialysis, and increasing degree of proteinuria.Of 91 patients investigated for the cause of anaemia, 60.4% had iron deficiency with anaemia of chronic disease, while 27.5% had anaemia of chronic disease based on the blood picture. Of 88 patients with haemoglobin <10g/dl, only 45.4% were on erythropoietin and 56.8% had received blood transfusions. 76.1% of the anaemic patients had hemoglobin below 10g/dL at follow-up despite treatment.Conclusions: Anaemia was highly prevalent in the CKD cohort with a significant number requiring transfusions. Patients continued to have anaemia despite being treated with nutritional supplements and erythropoietin.

Evidence of increased vascular stiffness and left ventricular hypertrophy in children with cystic kidney disease.

Cardiovascular disease (CVD) is the most common cause of mortality in chronic kidney disease (CKD). Children with early-onset CKD arguably experience the greatest lifetime CVD burden. We utilized data from the Chronic Kidney Disease in Children Cohort Study (CKiD) to evaluate two pediatric CKD cohorts: congenital anomalies of the kidney and urinary tract (CAKUT) and cystic kidney disease for CVD risks and outcomes. CVD risk factors and outcomes including blood pressures, left ventricular hypertrophy (LVH), left ventricular mass index (LVMI), and ambulatory arterial stiffness index (AASI) scores were evaluated. Forty-one patients in the cystic kidney disease group were compared to 294 patients in the CAKUT group. Cystic kidney disease patients had higher cystatin-C levels, despite similar iGFR. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) indexes were higher in the CAKUT group, but a significantly higher proportion of cystic kidney disease patients was on anti-hypertensive medications. Cystic kidney disease patients had increased AASI scores and a higher incidence of LVH. This study provides a nuanced analysis of CVD risk factors and outcomes including AASI and LVH in two pediatric CKD cohorts. Cystic kidney disease patients had increased AASI scores, higher incidence of LVH, and higher rates of anti-hypertensive medication use which could imply a greater burden of CVD despite similar GFR. Our work suggests that additional mechanisms may contribute to vascular dysfunction in cystic kidney disease, and that these patients may need additional interventions to prevent the development of CVD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Development of an adaptive clinical web-based prediction tool for kidney replacement therapy in children with chronic kidney disease

Clinicians need improved prediction models to estimate time to kidney replacement therapy (KRT) for children with chronic kidney disease (CKD). Here, we aimed to develop and validate a prediction tool based on common clinical variables for time to KRT in children using statistical learning methods and design a corresponding online calculator for clinical use. Among 890 children with CKD in the Chronic Kidney Disease in Children (CKiD) study, 172 variables related to sociodemographics, kidney/cardiovascular health, and therapy use, including longitudinal changes over one year were evaluated as candidate predictors in a random survival forest for time to KRT. An elementary model was specified with diagnosis, estimated glomerular filtration rate and proteinuria as predictors and then random survival forest identified nine additional candidate predictors for further evaluation. Best subset selection using these nine additional candidate predictors yielded an enriched model additionally based on blood pressure, change in estimated glomerular filtration rate over one year, anemia, albumin, chloride and bicarbonate. Four additional partially enriched models were constructed for clinical situations with incomplete data. Models performed well in cross-validation, and the elementary model was then externally validated using data from a European pediatric CKD cohort. A corresponding user-friendly online tool was developed for clinicians. Thus, our clinical prediction tool for time to KRT in children was developed in a large, representative pediatric CKD cohort with an exhaustive evaluation of potential predictors and supervised statistical learning methods. While our models performed well internally and externally, further external validation of enriched models is needed.

Determinants of urgent start dialysis in a chronic kidney disease cohort followed by nephrologists

BackgroundThe French Renal Epidemiology and Information Network (REIN) registry collect dialysis initiation context for each patient starting dialysis with a flawed definition of urgent start dialysis (USD). The main objective of this study was to identify factors associated with USD in patients regularly followed-up by a nephrologist using a classification of USD considering the preparation to renal replacement therapy.MethodsThis retrospective cohort study included adult patients who started dialysis between 2012 and 2018 in the Franche-Comté region of France after a minimum of two nephrology consultations. We classified dialysis initiation context as follows: USD for patients with no dialysis access (DA) created or planned, unplanned non urgent start dialysis (UNUSD) for patients starting with a recent or non-functional DA and planned start dialysis (PSD) for those starting with a functional and mature DA.ResultsFour hundred and sixty-five patients met inclusion criteria. According to REIN registry, 94 (20.3%) patients were urgent starters (US) whereas with our classification 80 (17.2%) and 73 (15.7%) where respectively US and unplanned non urgent starters (UNUS). The factors independently associated with USD in our classification were: stroke (odds ratio(OR) = 2.76, 95% confidence interval (95%CI)=[1.41–5.43]), cardiac failure (OR = 1.78, 95%CI=[1.07–2.96]) and the number of nephrology consultations prior dialysis onset (OR = 0.73, 95%CI=[0.64–0.83]). Thirty-one patients died during the first year after dialysis start. According to our classification, we observed significantly different survival probabilities: 95.7%, 89.5% and 83.4% respectively for planned starters, UNUS and US (p = 0.001).ConclusionThe two factors independently associated with USD were cardiac failure and stroke.

#4522 PREVALENCE OF CHRONIC KIDNEY DISEASE IN PREGNANCY: A UK POPULATION STUDY

Abstract Background and Aims Women with chronic kidney disease (CKD) are at greater risk of adverse pregnancy outcomes. Historically CKD in has been proposed to affect 3% of all pregnancies (0.13% with ‘moderate to severe’ CKD) but is based on expert opinion and numbers affected are propose to rise due to the rise of maternal obesity and age and could impact on service planning. However, there are no accurate estimates of CKD prevalence in pregnancy. This study aimed to investigate how many pregnancies may be affected by CKD, according to disease severity, in a UK population cohort. Method Routinely collected pregnancy data from three NHS Trust hospitals in Kent (UK) between 2010 and 2020 were extracted with Research Ethics Committee approval (19/LO/1242 and 18/SC/0158). Local laboratory and health care records were linked and used to identify women between 18 and 50 years of age with a confirmed eGFR measurement (Chronic Kidney Disease Epidemiology Collaboration 2009 without ethnicity correction) within two years prior to conception, and no current pregnancy recorded at the time of sampling. Baseline characteristics and prevalence of CKD at different stages were described. Results A total of 76, 755 pregnancies were recorded between 2010 and 2020, including 14,257/76,755 (18.6%) pregnancies with preconception eGFR (median eGFR 115 ml/min/1.73 m2 (IQR 21)). There were 1,184/14,257 (8.3%) pregnancies with a preconception eGFR <90ml/min/1.73 m2, including eGFR between 60-89 ml/min/1.73 m2 (1170 /14,257, 8.2%). Only 12/14,257 (0.08%) of pregnancies had an eGFR 30-59 ml/min/1.73 m2 and two pregnancies (0.01%) had an eGFR between eGFR 15-29 ml/min/1.73 m2. There were no pregnancies in the cohort with an eGFR <15 ml/min/1.73 m2. The cohort was majority White ethnicity (12911/13790; 94%) with 6.4% (879/13790) from Black, Asian, Mixed and East Asian ethnicities. Women with pregnancies that were affected with CKD were significantly older at conception (27, SD 5.5, vs 30.8, SD 5.5, p <0.001) and had greater prevalence of chronic hypertension (8.6% vs 11.3%, p = 0.013). Considering the whole cohort, including those without kidney function testing, the proportion of pregnancies affected by CKD was low (1,185/76,755; 1.5%). Conclusion This is the largest cohort reporting the prevalence of CKD including severity in pregnancies in the UK. Overall the total number of pregnancies affected by CKD was lower than previous estimates, especially for those with advanced disease. This finding may represent reduced fertility in women with CKD, individual decisions not to conceive, negative advice from clinicians or obstetric management at different centres not captured in this cohort. However, only 1 in 5 women prior to pregnancy had an eGFR and gestational changes in creatinine may mask identification of CKD in pregnancy. A further limitation includes only eGFR measurement prior to pregnancy was used thus women with temporary eGFR reduction may have been incorrectly included in the CKD cohort. Finally there were few women from ethnic minority groups who are disproportionately affected by CKD. Further information regarding kidney function in women of reproductive age and at conception is needed to enable true estimated of CKD prevalence in obstetric care.

#3953 TOXIC MICROBIOME AND CHRONIC KIDNEY DISEASE: INSIGHTS FROM THE CKD-REIN COHORT STUDY

Abstract Background and Aims Many uremic toxins (UTs) originate from gut microbiome, and contribute to chronic kidney disease (CKD) progression and cardiovascular morbidity. In order to reduce uremic symptoms and CKD progression, patients have several dietary restrictions, which may influence gut microbiome composition, and impact UTs production. An altered microbiome may contribute to UTs increase in those patients. However, the role of key bacterial taxa in producing UTs and the impact of diet on UTs variance in non-dialyzed patients are not well known. The objectives of this study were, first, to compare microbial features between CKD patients and healthy controls, and, second, to investigate the relation of gut microbiome with uremic toxicity, as well as the potential impact of diet on such relationship. Method Characterization of gut metagenomes, 10 UTs and 3 precursors’ serum concentrations by LC-MS/MS, host characteristics and diet were obtained from 240 non-dialysis CKD patients from the CKD-REIN cohort (mean ± SD): age: 68 ± 11 years, 71% male, estimated glomerular filtration rate (eGFR): 33.2 ± 12.7 ml/min/1.73m². First, to identify microbial biomarkers characterizing the gut microbiome-related toxicity in CKD, we compared microbiome features between 78 CKD patients and 78 age-, sex-, and BMI-matched healthy controls from the Milieu Interieur (MI) cohort: age: 58 ± 10 years, 60% male, eGFR: 89 ± 13. Second, we performed a multiomics’ data integration analysis via a supervised modelling to investigate cross-sectionally the association between host characteristics, gut microbiome, UTs, and diet-related features according to CKD severity (eGFR<30, n = 110 vs eGFR ≥30 mL/min/1.73m², n = 130). Results Compared to healthy controls, CKD patients had a significant reduced gut microbiome health index. Several Metagenomic Species Pan-genomes (MSPs) were significantly contrasted between MI and CKD cohorts: 43 species were enriched in CKD patients vs 24 in controls. Species most enriched in CKD patients included several UTs producers such as Lachnospiraceae spp, Dysosmobacter – Oscillibacter spp, Butyricimonas faecihominis, Victivallis vadensis and Hungatella spp, some of which were positively correlated with the following UTs: 3-Carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), trimethylamine-N-oxide (TMAO), and indole-3-acetic acid (3-IAA). Moreover, species belonging to Enterocloster and Hungatella genera (both members of Lachnospiraceae family) were found to be negatively correlated with eGFR. Among species associated with CKD severity, species carrying genes for UTs production were observed such as Desuflovibiro fairfieldensis, Bacteroides clarus and Blautia obeum along with increasing alcohol and hot drinks consumption, CRP and several UTs (kynurenic acid, indoxyl sulfate and Phenylacetylglutamine) levels. In contrast, some taxa like Faecalibacterium prausnitzii and Dysosmobacter welbionis were associated with legume intake but not with UTs. Conclusion Our study highlights an alteration of gut microbiome in CKD patients compared to healthy controls, with increased abundance of UTs producer species. The results of the multidimensional data integration modelling suggest a strong interplay between food intake, gut microbiome modifications, UTs accumulation and clinical features. These findings might open to promising therapeutic strategies to reduce microbiome-related toxicity.

#4184 MALE CHRONIC KIDNEY DISEASE IS A STATE OF PREMATURE TESTICULAR AGING

Abstract Background and Aims Sex steroid levels have been reported to be decreased in male patients with chronic kidney disease (CKD), parallel to the severity of the kidney dysfunction. These studies, at large, used immuno-assays, a method that is inferior to gold standard chromatography measurements and, in addition, failed to give insights into the underlying pathophysiology as they lacked data on gonadotropin levels. The aim of this study was to comprehensively map the gonadal status in male CKD patients not yet on dialysis and age- and BMI-matched controls, using gold standard techniques. Method We performed a case-control study in 120 male CKD patients (age 65.0 y, BMI 26.8 kg/m2), matched (1:1) with non-CKD controls for age and BMI. We divided CKD patients into 3 categories based on KDIGO classification: CKD 1–2 (n = 24), CKD 3 (n = 42) and CKD 4–5 (n = 54). We measured total testosterone (T) and estradiol (E2) using liquid chromatography tandem mass-spectrometry. Sex hormone binding globulin (SHBG), prolactin, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured on the Roche Cobas 8000 platform. Free T levels were calculated via Vermeulen formula. Inhibin B (a readout for testicular Sertoli cell function) was measured by ELISA. Results CKD patients showed lower total T (426.0 ng/dL [297.5-516.5] vs. 541.0 ng/dL [452.0-647.8]; p<0.0001) and free T levels (7.4 ng/dL ±3.2 vs. 9.4 ng/dL +/-2.2; p<0.0001) as compared to non-CKD counterparts. SHBG and E2 levels, conversely, were comparable in cases and controls. Inhibin B levels were lower in CKD patients as well (112.7 pg/mL [38.1-189.0] vs. 181.1 [122.2-236.4]; p<0.0001). LH and FSH levels were higher in CKD patients (9.1 IU/L [5.4-16.2] vs. 5.4 IU/L [3.6-8.1]; p<0.0001 and 7.8 IU/L [5.0-20.2] vs. 5.6 IU/L [4.0-9.7]; p<0.0001 respectively). Consequently, the T/LH ratio and inhibin B/FSH ratio, respectively reflecting Leydig and Sertoli cell function, were markedly depressed in CKD (1.8 nmol/IU [0.7-3.0] vs. 4.0 nmol/IU [2.4-5.2]; p<0.0001 and 14.4 ng/IU [1.2-33.6] vs. 32.2 ng/IU [32.2 [16.3-56.7]; p<0.0001). In the CKD cohort, regression analysis identified eGFR and age as independent determinants of T/LH ratio (R2 0.29). According to the T/LH ratio a male CKD patient of 45y old has a testicular age of an 81y old control. Conclusion Male patients with CKD not yet on dialysis show low total and free T levels, confirming CKD as a risk factor for male hypogonadism. The low T/LH and inhibin B/FSH ratio point to testicular failure as the underlying pathophysiological mechanism.

#3841 ASSOCIATION BETWEEN BODY MASS INDEX, WAIST CIRCUMFERENCE AND CLINICAL OUTCOMES IN KOREAN ADVANCED CHRONIC KIDNEY DISEASE PATIENTS

Abstract Background and Aims This study analysed the association between body mass index (BMI) and waist circumference (WC) with all-cause death, 3-point major cardiovascular event (MACE), end-stage kidney disease (ESKD) and total composite events in nation-wide cohort of Korean advanced chronic kidney disease (CKD) patients. Method This nationwide cohort study, using the National Health Insurance Database, included adult health examinees who received two or more check-ups from 2009 to 2012. Among them, CKD patients (N = 325,657, stage G3a, G3b and 4) were identified. Patients were classified into three groups for BMI (<18.5, 18.5-25 [reference] and ≥25) and four groups for WC (female; <75 cm or male; <85 cm [WC1], female; 75 cm≤WC<85 cm or male; 85 cm≤WC<95 cm [reference], female; 85 cm≤WC<95 cm, male; 95 cm≤WC<105 cm [WC2] and female; ≥95 cm, male; ≥105 cm [WC3]). Risks were evaluated using Cox proportional hazard analysis. Results Patients (58.6±7.7 years) had mean eGFR of 54.32±5.83ml/min/1.73 m2. The underweight (BMI<18.5) group had increased risks of death [HR 1.757, 95% CI (1.573-1.964)] and total events [HR 1.244, (1.144-1.353)]. Overweight (BMI≥25) group showed lower risks of death [HR 0.888, (0.86-0.917)], ESKD [HR 0.855, (0.788-0.927)] and total events [HR 0.975, (0.956-0.995)]. However, the risk was increased for 3-point MACE [HR 1.056, (1.031-1.081)]. For the association between WC and clinical outcomes, the low WC group (WC1) had increased risk of death [HR 1.129, (1.089-1.17)] and reduced risk for 3-point MACE [HR 0.92, (0.894-0.947)]. In higher WC groups, increased risks were observed for death [WC2: HR 1.052, (1.008-1.098), WC3: HR 1.32, (1.213-1.437)], 3-point MACE [WC2: HR 1.071, (1.038-1.104), WC3: HR 1.104, (1.036-1.176)] and total events [WC2: HR 1.049, (1.022-1.077), WC3: HR 1.12, (1.062-1.181)]. Conclusion In CKD patients, both lower BMI and WC were risk factors for mortality and ESKD. However, compared to the reference group, higher BMI group exhibited better outcomes while higher WC groups exhibited poorer outcomes. As increased WC is more specifically related to central obesity, we need different approaches to interpreting clinical risks associated with different BMI and WC criteria.

#4778 THE NATURAL HISTORY OF IGA NEPHROPATHY IN THE GERMAN CHRONIC KIDNEY DISEASE (GCKD) COHORT

Abstract Background and Aims Primary IgA nephropathy (IgAN) is the most common form of glomerulonephritis and a major cause of kidney failure. Here we describe the natural history of individuals with IgAN in the German Chronic Kidney Disease (GCKD) cohort. Method From 2010 to 2012, 421 patients with biopsy-proven IgAN have been enrolled into the GCKD study, a prospective observational cohort study (N = 5217). Inclusion criteria were an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2 or overt proteinuria in the presence of an eGFR>60 mL/min/1.73 m2. The adjudicated composite renal endpoint (Major Adverse Kidney Events; MAKE) was defined as eGFR decline>40%, eGFR< 15 ml/min or initiation of kidney replacement therapy. The associations between the incidence of MAKE and baseline risk factors were analyzed using the Cox proportional hazards regression model. Data relating to baseline demographics, laboratory, comorbidity, and mortality were used. Results The mean age at baseline of IgAN patients was 51.6 years (±13.6) and 67% were male. Duration of disease at baseline was 5.9 ± 8.1 years. Baseline median UACR was 0.4 g/g (0.1-0.8) and mean eGFR was 52.5 ± 22.4 mL/min/1.73m2. Over a follow-up of 6.5 years, 53 (12.6%) initiated kidney replacement therapy, 64 (15.2%) experienced >40% eGFR decline and additional 3 (0.7%) reached eGFR< 15 ml/min, i.e. 28% of the patients experienced a MAKE. Albuminuria, with reference to < 0.1 g/g was most associated with MAKE. Hazard ratios at UACR 0.1-0.6 g/g, 0.6-1.4 g/g, 1.4-2.2 g/g and >2.2 g/g were 2.03 (1.02-4.05), 3.8 (1.92-7.5), 5.64 (2.58-12.33) and 5.02 (2.29-11-03), respectively. Relapse, defined as UACR >2.2g/g, after partial remission (defined as UACR ≥0.1 g/g to <0.6 g/g) or complete (defined as UACR < 0.1 g/g) remission developed in only 13 (3.1%) patients. Conclusion The GCKD study reflects a large cohort with long follow up allowing for a thorough analysis of the natural history of IgAN. More than every fourth patient experienced a MAKE event within 6.5 years. Our findings support the use of albuminuria as a surrogate for poor kidney outcomes.

#5142 THE NATURAL HISTORY OF FSGS IN THE GERMAN CHRONIC KIDNEY DISEASE (GCKD) COHORT

Abstract Background and Aims FSGS is a heterogenic glomerular disease and a common cause of kidney failure in adults. Here we describe the natural history of individuals with FSGS in the German Chronic Kidney Disease (GCKD) cohort. Method From 2010 to 2012, 159 patients with biopsy-proven FSGS have been enrolled into the GCKD study, a prospective observational cohort study (N = 5217). Inclusion criteria were an estimated glomerular filtration rate (eGFR) of 30–60 mL/min/1.73 m2 or overt proteinuria in the presence of an eGFR>60 mL/min/1.73 m2. Baseline date was defined as first study visit. Endpoints were the composite renal endpoint (MAKE); eGFR decline >40%, eGFR< 15ml/min/1.73 m2 or initiation of kidney replacement therapy. The associations between the incidence of MAKE and clinical parameters were analyzed using the Cox proportional hazards regression model. Data relating to baseline demographics, laboratory, comorbidity, and mortality were used. Results The mean age at baseline of patients with FSGS was 52.1 ± 13.6 years. Median proteinuria at baseline was 0.7 g/g (Q1 0.1; Q3 1.8), while mean eGFR was 55.8 ± 23 mL/min/1.73 m². Mean duration of the disease before enrollment was 4.7 ± 6.8 years. The majority (101;63.5%) were male; 69 (43.4%) were diagnosed as primary FSGS using clinical and pathological criteria, 55 (34.6%) as secondary FSGS and for 35 (22%) the etiology was uncertain. At baseline, 37 (23.3%) were under immunosuppressive treatment. Over a follow-up of 6.5 years, 44 reached MAKE, in detail 19 (12%) initiated kidney replacement therapy, an additional 25 (15.8%) experienced a >40% eGFR decline. Albuminuria >0.7 g/g was associated with MAKE, with a HR of 1.47 (95% CI: 1.27-1.7) compared to <0.7 g/g. Higher eGFR at baseline (per 10 ml/min) protected from MAKE with a HR of 0.8 (95% CI: 0.68-0.95). Conclusion The GCKD cohort represents a large study population with lengthy and adjudicated follow-up data. Lower eGFR and higher albuminuria are significant risk factors for progressive kidney disease and ESKD in patients with FSGS.

#4292 PATIENT-REPORTED MENTAL HEALTH PROBLEMS, SUICIDE IDEATION, AND CLINICAL OUTCOMES IN ADULTS WITH NON-DIALYSIS CKD: RESULTS OF THE KNOW-CKD STUDY

Abstract Background and Aims Mental health is important for health and well-being at every stage of life and disease. Mental health problems are common and bothersome in chronic kidney disease (CKD). Mental health problems of CKD are poorly understood and evaluated. To address the importance of mental health in CKD, we analyzed a prospective cohort database from prospective CKD cohort. Method We analyzed 1897 participants from the KNOW-CKD cohort. We evaluated 4 items as indicators of patient-reported mental health: sleep duration, perceived stress, depressive symptoms, and suicidal ideation. To facilitate interpretation of the mental health problems in CKD, we measure a scaled effect size (ES) for the Kidney Disease Quality of Life Short Form (KDQOL-SF) differences among the groups of mental health problems. We investigated the association between patient-reported mental health problems and clinical outcomes of incident end-stage kidney disease (ESKD) all-cause death in non-dialysis CKD. Results The mean age was 53 ± 12 years and 62% were male. The participants had mental health problems of inadequate sleep duration (17.4%), subject distress (27.3%), experience of depression (13.2%), and suicide ideation (16.8%), but had not well taken care (psychiatric counselling 1.9%, antidepressant therapy 2.8%). The 4 item indicators of mental health showed large effect size between-groups KDQOL mental component summary (ES = 1.67). In the fully adjusted Cox proportional model, poor mental health (≥2 mental health problems) was associated with high risk of ESKD [HR = 1.46; 95% CI (1.18∼1.08)] and death [HR = 1.55; 95% CI (1.04∼2.32)] compared to good mental health (no mental health problems). Among 4 item indicators of patient-reported mental health, suicide ideation was the most predictive indicator of clinical outcomes. Conclusion Mental health problem is common and undertreated in CKD. Poor mental health is associated with high risk of ESKD and death in non-dialysis CKD and the single question of suicide ideation is significantly associated with high risk of ESKD and death. It suggests that the evaluation and management of mental health problem is important to the clinical outcomes in CKD.

#5000 DIFFERENCES IN CIRCULATING IMMUNE CELLS PROFILE BETWEEN MALES WITH CARDIORENAL SYNDROME TYPE II AND CKD PATIENTS WITHOUT CARDIOVASCULAR DISEASE

Abstract Background and Aims Maladaptive activation of the immune system plays an important role in the pathogenesis of cardiovascular disease (CVD) and chronic kidney disease (CKD). The immune system components can act as mediators of organ cross-talk and may be involved in the reciprocal dysfunction that occurs in cardiorenal syndromes (CRS). The aim of our study was to investigate potential differences in blood levels of specific immune cells subsets between a cohort of type II CRS patients and CKD patients without established CVD. Method 40 stable male patients with CRS type II and 30 male CKD patients without CVD, matched for eGFR (CKD-EPI) were enrolled in this cross-sectional study. Exclusion criteria were history of malignancy, autoimmunity and active or chronic infections. The peripheral blood immune cell subsets CD14++CD16-, CD14++CD16+ and CD14+CD16++ absolute values and percentages out of total monocytes and NK cells (CD3+CD16+56+), CD3-CD19+ B lymphocytes, CD3+ CD4+ T cells, CD3+CD8+ T cells and Tregs (CD4+CD25+FoxP3+) absolute values and percentages out of total lymphocytes were measured by flow cytometry. Simultaneously, clinical, laboratory and echocardiographic data were assessed. Multiple regression analyses to assess independent relationships were performed by building separate models with each of the immune cells as the dependent variable and respective univariate correlates including patient group. Results Mean age of patients with CRS and CKD was 72±10 versus 66±10 years respectively (p = 0.01), mean eGFR was 37±14 and 33±16ml/min/1.73 m2 respectively (p = 0.28) and median urinary protein to creatine ratio (UPCR) was 0.19 (IQR, 0.10-0.52) versus 1.03 (IQR, 0.17-2.09) gr protein/gr creatinine (p = 0.02) respectively. CRS patients displayed increased levels of pro-inflammatory, intermediate CD14++CD16+ monocytes [41 (IQR, 24-78)/µL] compared to their CKD counterparts [35 (IQR, 18-43)/µL] (p = 0.04). A higher Tregs percentage was found in CRS patients [2.7% (IQR, 2.0%-3.9%)] compared to CKD patients [2.0% (IQR, 1.6%-2.6%)] (p = 0.03). Lower mean levels of lymphocytes were observed in CRS patients (1557±691/µL) compared to the CKD cohort (1920±545/µL) (p = 0.04). Finally, CRS patients displayed lower NK cell counts [148 (IQR, 103-258)/µL] compared to CKD patients [324 (IQR, 179-368)/µL] (p = 0.001). Age and UPCR did not correlate with immune cells subsets in the whole cohort, neither in the two groups separately. At multivariate regression analysis, the differences in immune cells between the two groups remained statistically significant. Specifically, in patients with CRS the intermediate CD14++CD16+ monocytes counts correlated positively with CRP (p = 0.002) and ESR (p = 0.02). A positive correlation was found between eGFR and total lymphocytes (p = 0.009), T cells (p = 0.005) and CD4+ T cells (p = 0.005) counts. The number and percentage of nonclassical CD14+CD16++ monocytes were higher in CRS patients with left ventricular ejection fraction (LVEF) less than 30% compared to patients with LVEF above 30% [33 (IQR, 18-37)/µL versus 13 (IQR, 10-29)/µL (p = 0.02) and 4.5% (IQR, 3.4%-7.2%) versus 2.7% (IQR, 1.9%-5.4%) (p = 0.03) respectively]. With regard to etiology, patients with dilated cardiomyopathy compared to patients with ischemic CVD displayed increased counts of intermediate CD14++CD16+ monocytes [75 (IQR, 41-104)/µL versus 36 (IQR, 22-61)/µL (p = 0.01)] and non-classical CD14+CD16++ monocytes [37 (IQR, 35-49)/µL versus 21 (IQR, 12-32)/µL (p = 0.02)]. Finally, NK cells and Tregs levels were lower in patients with atrial fibrillation compared to those without [133 (IQR, 79-173)/µL versus 260 (IQR, 151-314)/µL (p = 0.01)] and [32 (IQR, 21-43)/µL vs 47 (IQR, 34-85)/µL (p = 0.006)] respectively. Conclusion Patients with CRS type II exhibit alterations of the immune cells subsets profile in the peripheral blood compared to CKD patients of similar kidney function but without CVD. Our findings suggest that distinct immune mechanisms might be involved in the pathogenesis or the chronic course of CRS type II as compared to CKD. Future research is required to evaluate their pathophysiological or prognostic significance.

#2889 CAROTID PLAQUE THICKNESS PREDICTS CARDIOVASCULAR EVENTS AND DEATH IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Classical risk scoring systems highly underestimate the elevated risk of cardiovascular (CV) disease in chronic kidney disease (CKD) (1). Coronary artery calcification score (CACS) has improved prediction of CV events in patients with CKD (2). Recently, ultrasound examination of the carotid arteries with measurement of maximal carotid plaque thickness (cPTmax) has demonstrated similar predictive value as CACS in the general population (3). This is the first study to investigate whether cPTmax can predict CV events in patients with CKD. We also compared the predictive value of cPTmax and CACS. Method Two hundred patients with CKD stage 3 from the Copenhagen CKD Cohort underwent ultrasound scanning of the carotid arteries in 2016 to 2017. The assessment consisted of finding areas with plaque, if there were any, and measuring the thickest part of the plaque, cPTmax, defined as the radial distance from the media–adventitia interface to the intima–lumen interface towards the center of the arterial lumen. For the statistical analysis only the anatomical side with the highest cPTmax was used. The intra-observer coefficient of variation was 9%. Based on the distribution of cPTmax, the subjects were divided into 3 groups: No plaques, cPTmax 1.0-1.9 mm and cPTmax > 1.9 mm (the median cPTmax in the group was 1.9 mm). One hundred and seventy-five of the patients underwent a non-contrast CT scan of the coronary arteries, which was used to measure CACS. The patients were divided into the following categories: no calcification, CACS = 1-100, CACS = 101-400 and CACS > 400. The follow-up time was time elapsed from the ultrasound scan and until a predefined end-date or the time of first event, which was defined as a composite of major CV events or death of any cause (MACE). CV events included: myocardial infarction, percutaneous coronary intervention, coronary bypass surgery, ischemic stroke, carotid endarterectomy or stenting, non-traumatic lower limb amputation, lower limb artery bypass graft, percutaneous transluminal angioplasty of a lower limb. Results The average follow-up time was 5.4 years. Twenty patients (10%) experienced a CV event and 28 patients died (14%). In a crude absolute risk plot (Figure), patients with no plaque at baseline showed the lowest risk of MACE, whereas patients with cPTmax 1.0-1.9 mm showed an intermediate risk, and patients with cPTmax >1.9 mm the highest risk (log rank test, p<0.0001). When using the group of patients with no plaque as the reference in an unadjusted Cox-regression analysis, the hazard ratio (HR) of MACE was significantly increased in patients with cPTmax = 1.0-1.9 mm (HR = 3.8 (CI: 1.5 - 9.9), p<0.01) and in patients with cPTmax >1.9 mm (HR = 8.4 (CI: 3.4 – 20.8), p<0.0001). After adjustment for age, sex, diabetes, smoking, hypertension, and hypercholesterolemia, only patients with cPTmax >1.9 mm showed a significantly increased HR of MACE (HR 3.2, CI 1.1-9.3), p<0.05. We applied C-statistics to assess which imaging technique had the best predictive value of MACE in this cohort. The differences in C-statistics were similar for the two imaging methods: cPTmax (0.21, p < 0.0001) and CACS (0.21, p < 0.0001). Conclusion Our results indicate that measurement of cPTmax may be a useful method for prediction of MACE in CKD. In the present small study, cPTmax and CACS showed equal potential for predicting MACE Ultrasound imaging is more convenient, more widely available, and without radiation exposure. To further assess the value of cPTmax in predicting CV risk in CKD, a larger study of patients with all CKD stages is needed.

#3790 BASELINE BLOOD PRESSURE CONTROL IN THE NURTURE CKD COHORT STUDY

Abstract Background and Aims Blood pressure (BP) control is one of the most important therapeutic interventions in chronic kidney disease (CKD) and reduces cardiovascular morbidity, mortality and progression to end stage kidney disease. The optimal BP target for patients with CKD is debated, with several guidelines making different recommendations. This analysis of the UK multicentre NURTuRE CKD cohort study assessed achievement of BP targets and investigated associations with achieved BP. Method 2996 participants with CKD stages G3-4 or G1-2 plus albuminuria >30 mg/mmol were enrolled from 16 nephrology centres in the UK from 2017 to 2019. Medical history, demographic, biometric and laboratory samples were collected at baseline. BP was measured according to a standard operating procedure. Three measurements differing by <10% were recorded and the mean value used for analysis. BP control was assessed against the following guidelines: National Institute for Health and Clinical Excellence (NICE), Kidney Disease Improving Global Outcomes (KDIGO) 2012 and 2021 guidelines. Results 2992 participants had a baseline BP measurement and of these 59% were male, 53% were ≥65 years, 87% were of white ethnicity and 31% had diabetes. Median eGFR was 33.8 (24.0 to 46.6) ml/min/1.73m2. The mean systolic BP for the cohort was 139 ± 20 and diastolic 80 ± 12 mmHg. The characteristics of patients with a higher mean systolic BP included: ≥65 years, male sex, black ethnicity, diabetic, body mass index >30 kg/m2, a history of atherosclerotic cardiovascular disease, lower eGFR values and higher albuminuria category. Conversely, mean systolic BP was not associated with index of multiple deprivation quintiles, health literacy by the single-literacy item screener and smoking status. Achievement of BP targets is shown in Table 1. Of 2723 with centrally calculated urine albumin creatinine ratio (ACR) and BP data available, only 1036 participants (38.0%) met the NICE guideline recommended BP. For the KDIGO 2012 guideline, 794 participants (29.2%) achieved recommended BP control. For KDIGO 2021, only 420 participants (15.4%) met the standard of systolic BP <120mmHg. For those in the highest risk albuminuria category (A3) only 143 (18.6%) and 96 (12.5%) of participants met the KDIGO BP recommendations for 2012 and 2021, respectively. Conclusion BP control in the NUTuRE-CKD cohort at baseline was suboptimal when compared to all three major guidelines. Subgroups at highest risk of adverse outcomes demonstrated poorer BP control. Given the importance of BP control in people with CKD, further research into BP management approaches and barriers to achieving optimal control is required. Priority should be given to developing a patient-centred approach to reduce BP more effectively.

Impact of SGLT2-inhibitors on contrast-induced acute kidney injury in diabetic patients with acute myocardial infarction with and without chronic kidney disease: Insight from SGLT2-I AMI PROTECT registry

AimsTo analyze the association between chronic SGLT2-I treatment and development of contrast-induced acute kidney injury (CI-AKI) in diabetic patients with acute myocardial infarction (AMI) undergoing PCI. MethodsMulticenter international registry of consecutive patients with type 2 diabetes mellitus (T2DM) and AMI undergoing PCI between 2018 and 2021. The study population was stratified by the presence of chronic kidney disease (CKD) and anti-diabetic therapy at admission (SGLT2-I versus non-SGLT2-I users). ResultsThe study population consisted of 646 patients: 111 SGLT2-I users [28 (25.2%) with CKD] and 535 non-SGLT2-I users [221 (41.3%) with CKD]. The median age was 70 [61–79] years. SGLT2-I users exhibited significantly lower creatinine values at 72 h after PCI, both in the non-CKD and CKD stratum. The overall rate of CI-AKI was 76 (11.8%), significantly lower in SGLT2-I users compared to non-SGLT2-I patients (5.4% vs 13.1%, p = 0.022). This finding was also confirmed in patients without CKD (p = 0.040). In the CKD cohort, SGLT2-I users maintained significantly lower creatinine values at discharge. The use of SGLT2-I was an independent predictor of reduced rate of CI-AKI (OR 0.356; 95%CI 0.134–0.943, p = 0.038). ConclusionIn T2DM patients with AMI, the use of SGLT2-I was associated with a lower risk of CI-AKI, mostly in patients without CKD.

The association between changes in echocardiography and risk of heart failure hospitalizations and death in adults with chronic kidney disease

Adults with chronic kidney disease (CKD) are at increased risk for developing heart failure (HF). However, longitudinal cardiac remodeling in CKD has not been well-characterized and its association with HF outcomes remains unknown. We evaluated the association between change in echocardiographic parameters between baseline and year 4 with the subsequent risk of HF hospitalization and death using Cox proportional hazard models in a landmark analysis of a prospective multicenter CKD cohort. Among 2673 participants, mean ± SD age was 61 ± 11 years, with 45% women, and 56% non-white. A total of 472 hospitalizations for HF and 776 deaths occurred during a median (interquartile range) follow-up duration of 8.0 (6.3–9.1) years. Patients hospitalized for HF experienced larger preceding absolute increases in left ventricular (LV) volumes and decreases in LV ejection fraction. Adverse changes in LV ejection fraction, LV cavity volume, LV mass index, and LV geometry were independently associated with an increased risk of HF hospitalization and death. Among adults with CKD, deleterious cardiac remodeling occurs over a relatively short timeframe and adverse remodeling is associated with increased risk of HF-related morbidity and mortality.

In-Hospital outcome of acute coronary syndrome in patients with Diabetes Mellitus with and without chronic Kidney disease

Background: Chronic kidney disease (CKD) and Diabetes Mellitus (DM) are highly prevalent, morbid diseases in every population. They are even more common among patients presenting with acute coronary syndromes (ACS). Objective: The present study was, conducted to see the outcome of ACS patients with concurrent DM and CKD. Methods: The cohort study was carried out in the Department of Medicine, Dhaka Medical College & Hospital, Dhaka over a period six months from July 2017 to December 2017. All acute coronary syndrome patients having DM with or without CKD admitted in Medicine and Cardiology (CCU) Departments were the study population. ACS patients with concurrent DM with CKD formed the cohort group (n = 75) and DM without CKD were termed as control group (n = 75). Result: The study was concluded that the ACS patients with concomitant CKD and DM (cohort) are usually older and more often hypertensive than the ACS patients with CKD alone (control) (63.9 vs. 55.9 years, p < 0.001 and 92% vs. 64%, p < 0.001 respectively). The typical chest pain is less commonly observed (68% vs. 86.7%, p = 0.003) and dyspnoea is more often present in this cohort than those in the control (92% vs. 52%, p < 0.001). NSTEMI is significantly present in the cohort compared that in the control group (p < 0.001). Serum Troponin I, CKMB and eGFR were significantly higher in the former group than those in the latter group (p = 0.044, p = 0.050 and p < 0.001 respectively). Almost all the outcome parameters demonstrated their significance. Conclusion: The diabetic with CKD (cohort group) is less likely to have ST elevations but is significantly prevalent having NSTEMI. Typical angina is less and dyspnea is more in cohort group. Bangladesh Medical Res Counc Bull 2022; 48: 133-137

Ex vivo exposure to calcitonin or raloxifene improves mechanical properties of diseased bone through non-cell mediated mechanisms

Raloxifene (RAL) reduces clinical fracture risk despite modest effects on bone mass and density. This reduction in fracture risk may be due to improved material level-mechanical properties through a non-cell mediated increase in bone hydration. Synthetic salmon calcitonin (CAL) has also demonstrated efficacy in reducing fracture risk with only modest bone mass and density improvements. This study aimed to determine if CAL could modify healthy and diseased bone through cell-independent mechanisms that alter hydration similar to RAL.26-week-old male C57BL/6 mice induced with chronic kidney disease (CKD) beginning at 16 weeks of age via 0.2 % adenine-laced casein-based (0.9 % P, 0.6 % C) chow, and their non-CKD control littermates (Con), were utilized. Upon sacrifice, right femora were randomly assigned to the following ex vivo experimental groups: RAL (2 μM, n = 10 CKD, n = 10 Con), CAL (100 nM, n = 10 CKD, n = 10 Con), or Vehicle (VEH; n = 9 CKD, n = 9 Con). Bones were incubated in PBS + drug solution at 37 °C for 14 days using an established ex vivo soaking methodology. Cortical geometry (μCT) was used to confirm a CKD bone phenotype, including porosity and cortical thinning, at sacrifice. Femora were assessed for mechanical properties (3-point bending) and bone hydration (via solid state nuclear magnetic resonance spectroscopy with magic angle spinning (ssNMR)). Data were analyzed by two-tailed t-tests (μCT) or 2-way ANOVA for main effects of disease, treatment, and their interaction. Tukey's post hoc analyses followed a significant main effect of treatment to determine the source of the effect.Imaging confirmed a cortical phenotype reflective of CKD, including lower cortical thickness (p < 0.0001) and increased cortical porosity (p = 0.02) compared to Con. In addition, CKD resulted in weaker, less deformable bones. In CKD bones, ex vivo exposure to RAL or CAL improved total work (+120 % and +107 %, respectively; p < 0.05), post-yield work (+143 % and +133 %), total displacement (+197 % and +229 %), total strain (+225 % and +243 %), and toughness (+158 % and +119 %) vs. CKD VEH soaked bones. Ex vivo exposure to RAL or CAL did not impact any mechanical properties in Con bone. Matrix-bound water by ssNMR showed CAL treated bones had significantly higher bound water compared to VEH treated bones in both CKD and Con cohorts (p = 0.001 and p = 0.01, respectively). RAL positively modulated bound water in CKD bone compared to VEH (p = 0.002) but not in Con bone. There were no significant differences between bones soaked with CAL vs. RAL for any outcomes measured.RAL and CAL improve important post-yield properties and toughness in a non-cell mediated manner in CKD bone but not in Con bones. While RAL treated CKD bones had higher matrix-bound water content in line with previous reports, both Con and CKD bones exposed to CAL had higher matrix-bound water. Therapeutic modulation of water, specifically the bound water fraction, represents a novel approach to improving mechanical properties and potentially reducing fracture risk.