Incident CKD Research Articles

Abstract 13644: Management Patterns in Patients With Heart Failure: Insights From iCaReMe Global Registry

Introduction: Heart failure (HF) is an increasing major case of morbidity and mortality, including in low and middle income countries (LMIC) due to the rising incidence of HTN, T2D and CKD. Little information is available on the management of HF in LMIC. iCaReMe is a unique ongoing registry collecting data from contemporary routine clinical practice in patients with HF, T2D, HTN and/or CKD. Aims: Describe clinical characteristics, comorbidities and management of HF patients based on data from iCaReMe Registry. Methods: iCaReMe Global Registry (NCT03549754) is a multinational, prospective, observational study to assess the management and quality of care in patients with HF, T2D, HTN and/or CKD. We present baseline descriptive analysis of the HF cohort enrolled from February 2018 to December 2022. Results: A total of 3069 adults (mean age±SD 58.7±12.6 years, 59.2% males, 40.3% obese) with HF from 21 countries were evaluated in this initial report. Of the 2307 (75.2%) patients with available LVEF data; 63.4% had HFrEF, 14.3% HFmrEF, and 22.3% HFpEF. The median (IQR) LVEF was 36(30-47) % and 83% had NYHA class II-IV symptoms. Overall, 27.1% of patients reported history of hospitalization for HF. The comorbidities were common including T2D (60.4%), HTN (57.1%), CAD (45.4%), dyslipidemia (36.0%), and CKD (30.5%). In patients with available data, the mean UACR was 282.5 mg/g [reported in 666 (21.7%) patients] and mean eGFR was 70.3 ml/min/1.73m 2 [reported in 2325 (75.8%) patients]. The medications included ACEi or ARB in 66.6%, ARNI in 15.9%, b-blockers in 65%, MRA in 38.7%, and SGLT2i in 40.3%. Conclusions: iCaReMe Registry provides a unique perspective on the characteristics and management of patients with HF in low and middle income countries and demonstrates substantial burden of multimorbidity. The data highlight gaps between guidelines and routine care and the need to identify and address barriers to the implementation of optimal management and evidence-based therapies.

Incidence of CKD in Prediabetes

Incidence of CKD in Prediabetes

Risk of ESKD and Death Among Homeless Veterans with Incident CKD

Risk of ESKD and Death Among Homeless Veterans with Incident CKD

Racial and Ethnic Differences in Incident CKD in US Veterans

Racial and Ethnic Differences in Incident CKD in US Veterans

Hospital Health Care Costs Following Incident CKD in Japan, Sweden, and the United States

Hospital Health Care Costs Following Incident CKD in Japan, Sweden, and the United States

Uncovering the Added Benefits of Lowering Resting Heart Rate by Physical Activity in Reducing the Incidence and Mortality Risks of CKD and Proteinuria

Uncovering the Added Benefits of Lowering Resting Heart Rate by Physical Activity in Reducing the Incidence and Mortality Risks of CKD and Proteinuria

Association of Polygenic Risk Scores for Blood Pressure with Incidence of Hypertension and CKD

Association of Polygenic Risk Scores for Blood Pressure with Incidence of Hypertension and CKD

Hypothyroidism (HT) Rate and Testing Among Incident CKD Patients Who Transitioned to Dialysis Within Kaiser Permanente Southern California (KPSC)

Hypothyroidism (HT) Rate and Testing Among Incident CKD Patients Who Transitioned to Dialysis Within Kaiser Permanente Southern California (KPSC)

Mitochondrial DNA copy number is associated with incident chronic kidney disease and proteinuria in the AIDS linked to the intravenous experience cohort

We evaluated the prospective association of mitochondrial DNA copy number (mtDNA CN) with markers of kidney function among a cohort of persons who inject drugs (PWID). This is a Prospective cohort study nested in the AIDS linked to the intravenous experience cohort (community-based cohort of PWID in Baltimore, MD). mtDNA CN was measured at two time-points 5 years apart using a real-time polymerase chain reaction. Kidney function (estimated glomerular filtration rate [eGFR], serum creatinine, urine protein) was measured annually. We used linear mixed effects models to evaluate kidney function trajectories (N = 946) and Cox regression models to assess hazard of incident CKD (eGFR < 60 at two consecutive visits, N = 739) and proteinuria (urine protein:creatinine ratio > 200, N = 573) by level of mtDNA CN (Low [lowest quartile], vs high [other three quartiles]. Models were adjusted for demographic and behavioral characteristics, HIV and/or HCV infection, and comorbidity burden. Low mtDNA CN was independently associated with higher hazard of incident CKD (aHR: 2.33, 95% CI 1.42, 3.80) and proteinuria (aHR: 1.42, 95% CI 1.04, 1.96). Participants with low mtDNA CN had greater declines in eGFR and greater increases in serum creatinine over time. Low mtDNA CN is associated with more rapid kidney function decline and risk of incident CKD and proteinuria.

A Nomogram for Predicting the Risk of CKD Based on Cardiometabolic Risk Factors.

In China, the spectrum of causes for CKD has been changing in recent years, and the proportion of CKD caused by cardiometabolic diseases, such as diabetes and hypertension continues to increase. Thus, predicting CKD based on cardiometabolic risk factors can to a large extent help identify those at increased risk and facilitate the prevention of CKD. In this study, we aimed to develop a nomogram for predicting CKD risk based on cardiometabolic risk factors. We developed a nomogram for predicting CKD risk by using a subcohort population of the 4C study, which was located in central China. The prediction model was designed by using a logistic regression model, and a backwards procedure based on the Akaike information criterion was applied for variable selection. The performance of the model was evaluated by the concordance index (C-index), and Hosmer‒Lemeshow goodness-of-fit test. The bootstrapping method was applied for internal validation. During the 3-years follow-up, 167 cases of CKD developed. By using univariate and multivariate logistic regression models, the following factors were identified as predictors in the nomogram: age, sex, HbA1c, baseline eGFR, low HDL-C levels, high TC levels and SBP. The bootstrap-corrected C-index for the model was 0.84, which indicated good discrimination ability. The Hosmer‒Lemeshow goodness-of-fit tests yielded chi-square of 13.61 (P=0.192), and the calibration curves demonstrated good consistency between the predicted and observed probabilities, which indicated satisfactory calibration ability. We developed a convenient and practicable nomogram for the 3‑year risk of incident CKD among a population in central China, which may help to identify high-risk individuals for CKD and contribute to the prevention of CKD.

Role of haptoglobin 2-2 genotype on disease progression and mortality among South Indian chronic kidney disease patients.

Haptoglobin (HP), a plasma glycoprotein, binds to free hemoglobin and prevents the loss of iron and kidney damage. The variations of HP gene affect its enzyme activity, resulting in varied antioxidant, angiogenic and anti-inflammatory properties. HP 2-2 genotype showed 3.84 fold increased risk for the development of CKD in Taiwan population. With this background, the present work focused to conduct a prospective case-control study in South Indian population to evaluate whether the HP variants are associated to nondialysis (ND) (CKD stages 1-4) and ESRD (CKD stage 5) conditions. Totally 392 CKD patients (nondialysis, ND; n = 170, end-stage renal disease, ESRD; n = 222) and 202 healthy individuals were enrolled. The blood samples collected from the patients were used to determine biochemical parameters and HP genotyping. Gene frequency and biochemical parameters were statistically analyzed for disease association. Results showed that HP 2-2 genotypes were significantly associated with ND and ESRD disease development compared to controls. Higher HP2-2 genotype frequency showed an increased hazard ratio for overall disease progression among ND patients (hazard ratio = 3.86; 95% CI 1.88 to 7.93; P = 0.0002). Survival analysis also showed that non-HP2-2 patients have a statistically significantly decreased risk for mortality compared to patients with the HP2-2 genotype (ESRD patients hazard ratio = 4.05; P = 0.04). The present study confirms that HP2-2 polymorphism is statistically associated with the risk of CKD incidence, progression, and mortality among South Indians. Concluding our results, the HP2-2 genotype could be an independent predictor of all-cause mortality and disease progression in patients with CKD.

1314-P: Adherence to Life’s Essential 8 and Incident Chronic Kidney Disease—A Prospective Study of 142,567 UK Biobank Participants

Background: The American Heart Association (AHA) recently updated an improved method for evaluating cardiovascular health (CVH): Life’s essential 8 (LE8). We aimed to investigate the association between levels of CVH and the risk of CKD in UK biobank. Methods: A total of 142,567 participants free of CKD and CVD were included. LE8 score at baseline was created including DASH diet, physical activity, smoking, sleep, BMI, non-HDL cholesterol, HbA1c, and BP. CVH levels were categorized as low, moderate, and high. Cox proportional hazard model was used to investigate the association between LE8 and CKD. Results: During a median follow-up of 11.8 years, 4,914 CKD cases were documented. We observed a linear dose-response relationship. Compared to participants with a low CVH, those with a moderate CVH were associated with a 35% lower risk of developing CKD (HR=0.65, 95% CI: 0.59, 0.73). Participants with a high CVH had a 48% lower risk of CKD incidence (HR=0.52, 95% CI: 0.45, 0.60) after adjustment for covariates. Additionally, the HR (95% CI) for each SD increment in behavior subscale score was 0.46 (0.39, 0.53) for CKD, and the HR (95% CI) for each SD increment in biological subscale score was 0.86 (0.76, 0.98) for CKD. Conclusion: Participants with high CVH, defined by LE8, were significantly associated with a lower risk of CKD. The burden of CKD may be reduced by promoting adherence to optimal CVH levels. Disclosure R.Tang: None. X.Wang: None. X.Li: None. H.Ma: None. Y.Heianza: None. L.Qi: None.

#5772 ESTIMATING CKD PREVALENCE AND INCIDENCE USING CROSS-SECTIONAL GERMAN CLAIMS DATA IN PERSONS AGED 70+

Abstract Background and Aims Little is known about trends over time and anticipated improvements in CKD diagnosis after the implementation of the Kidney Disease – Improving Global Outcomes (KDIGO) guidelines in 2012. We investigated CKD prevalence and incidence over time using claims data in persons aged 70+. Method We assessed CKD prevalence and incidence biennially in cross-sectional claims data of the German health insurance fund “AOK Nordost” for persons aged 70+ between 2012 and 2018. Data are available for n = 62,200 persons per year and were sampled equally distributed for five age strata (70-74, 75–79, 80–84, 85–89, ≥90) and for sex. CKD prevalence and incidence were estimated in 2012, 2014, 2016, and 2018 using in- and outpatient ICD-10 diagnoses (N18.3, N18.4, N18.5, N18.8, N18.9, N19). Incidence was defined as prevalent cases without a diagnosis in the four quarters preceding their first CKD diagnosis over all persons at risk (i.e., who were not prevalent in the respective previous year). Results are shown in total (standardized by age and sex using nationwide demographic distributions for a respective year) as well as stratified by age and sex. Cochran-Armitage test was applied to test time trends for incidence and prevalence from 2012–2018. Results Claims data-based CKD prevalence showed a significant constant increase from 0.18 in 2012 to 0.26 in 2018 (p &amp;lt;0.001). This time trend in CKD prevalence was consistent among all age and sex strata (Figure 1). Over the same time period, CKD incidence increased from 0.06 to 0.08 (p &amp;lt;0.001), while the percentage of persons at risk decreased from 0.81 to 0.72 between 2012 and 2018 due to increasing prevalence (Table 1). Both prevalence and incidence estimates were higher in males compared to females in all age strata (Figure 1). Conclusion The present cross-sectional analysis in claims data allows novel insights of CKD prevalence and incidence among older adults in Germany. CKD prevalence increased constantly over time after the introduction of the KDIGO guidelines in 2012. For CKD incidence, we detected only a small increase over the observation period. The extent of time trends for CKD incidence might be underestimated due to increasing prevalence.

#3011 INCIDENT CHRONIC KIDNEY DISEASE IN NEWLY DIAGNOSED DIABETES MELLITUS

Abstract Background and Aims Singapore has the world's 3rd highest rate of incident end-stage kidney disease (ESKD) on dialysis. Diabetes mellitus (DM) was the cause of ESKD in 68% of patients initiating dialysis in 2020. We explored the rate of incident CKD in newly diagnosed DM, and risk factors associated with the development of incident CKD. Method This is a retrospective cohort of patients newly diagnosed with DM in 2014-2020, in primary care and specialist clinics across Singapore's largest health system. Patients were excluded if they had known CKD, were not screened for CKD, or were diagnosed with CKD at the first screening (which may reflect pre-existing CKD). CKD was defined as a CKD-EPI glomerular filtration rate (GFR) &amp;lt;60 ml/min/1.73 m2, and/or urine albumin-creatinine ratio (UACR) &amp;gt;3 mg/mmol. Two readings ≥3 months apart were required for diagnosis. Demographic and laboratory data was retrieved from electronic records, and analysed using Pearson's Chi-square, Wilcoxon rank-sum test, and Cox regression evaluating time to onset of incident CKD. Results Of 25714 patients with newly-diagnosed DM and no known CKD, 3963 (15.4%) were not screened for CKD, and 2019 (7.9%) were diagnosed with CKD at the first screening; both groups were excluded. The remainder 19732 patients (76.7%) formed the study cohort. This included 14175 Chinese (71.8%), 3085 Malay (15.6%), 1658 Indian (8.4%), and 814 patients of other ethnicities (4.1%). Baseline mean (SD) GFR was 90.7 (17.6) ml/min/1.73 m2. Over a mean follow up of 2.28 (1.98) years, 5929 patients (30.0%) developed incident CKD after a mean of 1.35 (1.09) years. Of patients who developed CKD, 869 (14.7%) met the GFR criteria, 4847 (81.8%) developed albuminuria, and 213 (3.6%) met both criteria. GFR declined more rapidly in patients who developed CKD (−2.8 (4.4) ml/min/1.73 m2/year), than in patients who did not (−1.7 (5.7) ml/min/1.73 m2/year, p&amp;lt;0.001). GFR decline began in the first year. Baseline characteristics associated with incident CKD on bivariate analysis (Table 1) included older age (61 (11) vs 59 (12) years, p&amp;lt;0.001), female gender (p&amp;lt;0.001), lower GFR (89 (19) vs 91 (17) ml/min/1.73 m2, p&amp;lt;0.001), higher systolic blood pressure (136 (17) vs 135 (17) mmHg, p&amp;lt;0.001), and ischemic heart disease (p&amp;lt;0.001). On multivariate Cox regression exploring characteristics associated with time to incident CKD, independent risk factors include female gender (HR 1.30, 95%CI 1.23-1.39), lower GFR (per 10ml/min/1.73 m2 lower GFR, HR 1.10, 95%CI 1.08-1.11), higher systolic blood pressure (per 10mmHg rise, HR 1.06, 95%CI 1.04-1.08), higher HbA1c (per 1% rise, HR 1.06, 95%CI 1.05-1.08), cerebrovascular accident (HR 1.16, 95%CI 1.02-1.31) and gout (HR 1.16, 95%CI 1.01-1.32). Despite a prevalence of hypertension of 85%, only 5440 (28%) of the cohort with incident CKD received an angiotensin converting enzyme inhibitor (ACE) or angiotensin receptor blocker (ARB) (as at 6 months after diagnosis of DM). 498 patients (2.5%) received a sodium-glucose cotransporter-2 inhibitor, which was not widely available during the period of this study. Conclusion Incident CKD was frequent in early DM; the risk factors above may identify higher-risk patients who benefit from enhanced screening. The relatively low rate of ACE/ARB prescription may require further review.

#4494 DRUG UTILIZATION FOLLOWING INCIDENT CHRONIC KIDNEY DISEASE: AN OBSERVATIONAL STUDY IN THE UNITED STATES AND JAPAN

Abstract Background and Aims Chronic kidney disease (CKD) affects &amp;gt;840 million individuals worldwide and is a leading cause of morbidity and mortality. Complications include cardiorenal outcomes (e.g. end stage kidney disease and heart failure (HF)) and premature death, which may be preventable with early identification and appropriate treatment of CKD. Treatment of CKD with renin-angiotensin-system inhibitors (RASi) has been the main recommendation of guidelines in the past 20 years, but prescribing rates remain low and discontinuation rates remain high, particularly after adverse events like hyperkalaemia episodes. This study aims to describe RASi utilization following incident CKD. Method Adult patients with incident CKD in the United States (US; OPTUM Market Clarity until 31 March 2022) and Japan (Medical Data Vision until 28 February 2022) from 1 January 2016 onwards were included. CKD was defined as any of the following: a UACR measure of ≥30 mg/g, two estimated glomerular filtration rate (eGFR) ≥90 days apart of which the second was ≤75 ml/min/1.73 m2, or a CKD diagnosis code. Patients were included if they had an eGFR ≤60 ml/min/1.73 m2. Patients with ongoing RASi treatment at index, a history of diabetes, heart failure or dialysis were excluded. Results A total of 66,375 incident CKD patients were identified in the US (n = 32,158) and Japan (n = 34,217). Mean age was 66 and 78 years in the US and Japan, respectively, and about half of the patients were female. Mean eGFR was 48 and 40 ml/min/1.73 m2 in the US and Japan, respectively. Approximately 30% of patients had cardiovascular disease, but only 13% (US) and less than 5% (Japan) were prescribed cardiovascular preventive drugs (e.g. statins and low dose aspirin). During a 1-year follow-up after the incident CKD index date, only 15% and 5% had been initiated on RASi in the US and Japan, respectively (Figure 1). Time to RASi initiation was shorter among those with a CKD diagnosis vs those without a diagnosis (US: 15 vs 19 months, Japan: 6 vs 11 months). Of those who initiated treatment, approximately 50% discontinued within one year (Figure 1). Results for initiation and discontinuation were similar across CKD stages in both countries. Conclusion In the US and Japan, initiation of RASi was remarkably low among newly identified CKD patients, and discontinuation of initiated treatment was substantial. Given that most patients with CKD benefit from multi-drug therapy (RASi + SGLT2i) for slowing CKD progression and reduction of adverse events, efforts to increase prescribing and adherence are needed.

#3383 ASSOCIATION BETWEEN MELAMINE AND PHTHALATES AND URINARY RENAL INJURY MARKERS AMONG CHILDREN AGED 4 YEARS

Abstract Background and Aims Chronic kidney disease (CKD) is a global public health issue and the prevalence and incidence of CKD and end-stage renal disease (ESRD) in Taiwan are among the highest in the world. The pathophysiology of renal function downhill is complex and multifactorial, and previous studies suggest that we should be concerned about the effects of low-dose environmental exposure to melamine and phthalate in increasing the risk of renal injury in susceptible populations such as children. However, the sex difference in renal injury related to environmental exposure among children is unknown. The aim of this study is to investigate the relationship between early renal injury biomarkers and melamine and phthalate exposure among boys and girls aged 4 years in Taiwan. Method In total, 1,676 pregnant women were enrolled in the original Taiwan Maternal and Infant Cohort Study (TMICS), a multicenter birth cohort study conducted at 9 hospitals in northern, central, southern, and eastern Taiwan from October 2012 to May 2015. Of those, 694 children aged 4 years participated in follow-up questionnaire interviews, received physical examinations and blood and urine tests from August 2016 to February 2020. After excluding 142 participants with missing data, the final statistical analysis of follow-up data included 552 children. One-spot overnight urine specimens were used to simultaneously measure melamine, 11 phthalate metabolites, and two markers of renal injury, microalbumin and N-acetyl-beta-D-glucosaminidas (NAG). Average daily intake (ADI) levels of melamine and six parental phthalates, including DEHP (di-2-ethylhexylphthalate), DiBP (Dibutyl phthalate), DnBP (Di-n-butyl phthalate), BBzP (Butyl benzyl phthalate), and DEP (Diethyl phthalate), were estimated using a creatinine excretion-based model from urine melamine and phthalate metabolites. We used a weighted quantile sum (WQS) regression model to select the most important exposure variables of ADI levels of phthalates and melamine associated with urine microalbumin to creatinine ratio (ACR) and NAG; Furthermore, to examine effects of those most important exposure variables on ACR and NAG in multivariable linear regression models. The significance was set as two-sided p &amp;lt; 0.05. Results Of them, 319 (57.8%) and 223(42.2%) were boys and girls, respectively, with a median age of 4.0±0.8 years old. Median ADI levels (µg/kg bw/day) were 5.73 for DEHP, 1.75 for DEP, 3.23 for DnBP, 0.07 for BBzP, 1.37 for DiBP, and 1.18 for melamine and there is not significantly different between boys and girls. Using the WQS regression model to examine the association between ADI levels of melamine and phthalates and urine ACR and NAG, we found that a significant and positive association between the WQS score and ACR (β1 = 0.083, p = 0.023). ADI levels of melamine had the highest weight (0.650). Furthermore, we found that the highest (quartile 4) of ADI levels of melamine had the significantly higher ACR in all children (adjusted β = 0.131, p = 0.036), compared to other quartiles (quartile 1, 2 and 3). In subgroup analysis, the significant association between melamine intake and urine ACR was found in boys (adjusted β = 0.249, p = 0.003), not in girls. Conclusion Environmental exposure to melamine may be associated with urine ACR among children aged 4 years in Taiwan, and boys may be easily affected by melamine exposure.

#5418 ASSOCIATION BETWEEN TRANSIENT AKI AND ALL-CAUSE MORTALITY IN PATIENTS WITH CRITICAL ILLNESS: AN INTERNATIONAL MULTICENTRE RETROSPECTIVE COHORT STUDY

Abstract Background and Aims Transient acute kidney injury (AKI) is common in critically ill patients. However, the effect of transient AKI on prognosis of patients remains controversial. We aimed to investigate the association of transit AKI with all-cause mortality and kidney outcomes in critically ill patients. Method We conducted a multicentre retrospective cohort study involving 40168 critically ill patients from CRDS and 8657 patients from MIMIC-IV databases. Among them, 10147 patients were diagnosed as AKI according to KDIGO criteria and classified into transient (duration ≤48 h) and persistent (duration &amp;gt;48 h). The study outcomes included mortality in hospital, by day 30 and up to 1 year, and risk of progress to CKD. We determined the effect of transit AKI on mortality by Cox regression model adjusting for confounding variables and analyzed CKD incidence by Fine-Gray model adjusted for difference in biologically plausible confounders. Results AKI occurred in 20.8% of 48825 critically ill patients, of which 36.4% was classified into transient and 63.6% persistent. Compared with those without AKI, Patients with transit AKI were older, more often received diuretic therapy and sedative therapy, and higher Charlson comorbidity index. After adjusting confounders including AKI severity, transient AKI was independently associated with increased risk of in hospital death (HR 1.97, 95% CI 1.68 to 2.31), 30-day mortality (HR 1.73, 95% CI 1.51 to 1.98) and 1- year mortality (HR 1.31, 95% CI 1.19 to 1.44). Meanwhile, the risk of all-cause mortality increased with the duration of AKI in those with persistent patients (P&amp;lt;0.05). Among survivors without history of CKD, compared with patients without AKI, transient AKI was also associated with increased risk of incident CKD after discharge (HR 1.61, 95% CI 1.33 to 1.96). Conclusion Transient AKI was associated with increased risk of all-cause mortality and incident CKD in critically ill patients. Raising of awareness about transient AKI was required to urge clinician monitor such patients closer.

#2789 HIGHER MORTALITY RISK WITH CHRONIC KIDNEY DISEASE IN TYPE 2 DIABETES IN YOUNGER AGES: A DANISH NATIONWIDE COHORT STUDY 2014-2018

Abstract Background and Aims Chronic kidney disease (CKD) is a frequent complication to diabetes. CKD is associated with significantly increased risk of morbidity and mortality among people with diabetes. It is well known that the incidence and progression of CKD differ between men and women. Women are more likely to get CKD, while men have a more rapid progression of the disease. However, previous studies were based on small populations. We aimed to investigate the mortality with and without CKD in men and women with type 2 diabetes (T2D). Method Secular and age trends in mortality rates and sex differences were investigated in a dynamic, nationwide cohort of people with T2D. CKD was defined based on hospital diagnosis, procedure codes and laboratory measurements. Mortality rates were modelled as an age-period-cohort model using Poisson models with log person time, smooth effects of current age, and calendar time (date of follow-up), separate for each sex and CKD status. Results The study included 304,956 persons (55,9% men) and 1,2 million person-years. 87,696 persons were recorded with CKD, of which 34,967 persons had a CKD event during follow-up. The overall mortality rate was 37.8 [37.4; 38.2] versus 31.1 [30.4; 31.7] per 1000 person-years for people with T2D, without and with CKD, respectively. The mortality rate for people with T2D and CKD is larger and more pronounced in the younger ages. For elderly people the mortality rate is larger for people with T2D and without CKD. In general, mortality for men is higher than mortality for women at all ages, observed for both people with and without CKD. The overall secular trend per year was increasing for persons without CKD 2.0 [1.8; 2.2] %/year. For those with CKD, a decrease −2.4 [−2.1; −2.6] %/year was observed, decreasing until start 2017 followed by an increase. The overall M/F mortality ratios were 1.23 [1.20; 1.25] and 1.91 [1.83; 2.00], respectively. Conclusion The observed larger and more pronounced mortality rate for people with T2D and CKD in the younger ages, suggests a potential for early preventive intervention among young adults. Supported by an unrestricted grant from Bayer.

#4018 CHARACTERISATION OF THE CLINICAL, HUMANISTIC AND ECONOMIC BURDEN OF ANAEMIA IN CHRONIC KIDNEY DISEASE: A SYSTEMATIC LITERATURE REVIEW

Abstract Background and Aims Chronic kidney disease (CKD) is defined as structural kidney damage and/or decreased kidney function (glomerular filtration rate &amp;lt;60mL/min/1.73 m2) persisting for ≥3 months [1]. Anaemia is a frequent CKD comorbidity associated with increased cardiovascular (CV) morbidity, mortality, reduced health-related quality of life (HRQoL) and greater healthcare resource utilisation (HRU) [2]. Our systematic literature review provided an overview of the clinical, humanistic and economic burden of anaemia of CKD. Method A search was performed in MEDLINE, EMBASE, MEDLINE IN-PROCESS, Cochrane Controlled Trials Register and the Cochrane Database of Systematic Reviews from database inception to 10 April 2022, using predefined criteria to identify cohort, cross-sectional, observational and cost studies, economic evaluations, conceptual model studies, systematic and literature reviews (complemented by grey literature and congress abstract searches and back-referencing relevant review papers [2016–2021]). Full-text selected citations were examined by two independent reviewers. Clinical burden parameters included CKD progression, differences in progression between patients with/without CKD anaemia, time to blood transfusion and association of CKD stage/progression with CV outcomes or mortality. Humanistic burden included HRQoL and caregiver burden. Economic burden was determined by HRU and direct/indirect costs. Results Data were extracted from 115 studies (12,109 database records, 79 supplementary items; Figure 1), including patients: pre- or non-dialysis (n = 61), on dialysis (n = 21), mixed non-/on dialysis (n = 19) and unknown dialysis status (n = 14). Incidence of advanced CKD was significantly higher in adult non-dialysis dependent (NDD) patients with anaemia of CKD vs those without (incidence per 1000 person-years: 15 to ∼85 vs 3 to ∼25). Patients with CKD anaemia had a higher risk of disease progression than those without anaemia (n = 21), e.g. non-dialysis stage 1–5 adults with CKD anaemia had ∼double the risk of developing end-stage CKD (hazard ratio [95% confidence interval [CI]] = 2.08 [1.50–2.89]). Median time to dialysis initiation was significantly lower in adult NDD stage 1–5 patients with anaemia of CKD vs those without anaemia (45.1 vs 68.3 months p&amp;lt;0.01). A higher proportion of stage 3 adult NDD patients with anaemia of CKD progressed to stage 4 or 5 over follow-up periods of 1, 2 and 3 years vs those without anaemia (40% vs 20%; 60% vs 25%; 75% vs 30%, respectively). Available data from the 43 studies reporting humanistic burden suggested significantly worse HRQoL in patients with vs without CKD anaemia; e.g. non-dialysis adults with CKD anaemia had worse 36-item kidney disease and QoL scores for symptoms/problems, effect- and burden-of CKD. Comparative caregiver burden data in patients with/without CKD anaemia were limited. Limited available evidence from an economic perspective suggested higher HRU in patients with anaemia of CKD vs those without. Patients with anaemia of CKD has ∼2 times greater risk of hospitalisation due to heart failure vs those without (crude incidence rate ratio [95% CI] = 1.9 [1.6–2.1]). Similarly, patients with anaemia of CKD has significantly higher risk of hospitalisations (adjusted relative risk [ARR] [95% CI] = 1.33 [1.31–1.34]) and emergency department visits (ARR [95% CI] = 1.14 [1.12–1.15]) in a multivariate logistic regressions model. No data were available on change in economic parameters over time or on inter-relationships between humanistic/economic burden parameters. There were no published disease models in CKD anaemia; Figure 2 illustrates identified relationships between clinical, humanistic and economic burden parameters. Conclusion Based on limited moderate-to-good quality data, we found that patients with CKD anaemia face greater clinical, humanistic and economic burdens than those without anaemia, with significantly worse HRQoL and greater HRU. CKD anaemia was also associated with a higher risk of CKD progression.

Validation of eGFR for Detecting Associations Between Serum Protein Biomarkers and Subsequent GFR Decline.

eGFR from creatinine, cystatin C, or both has been primarily used in search of biomarkers for GFR decline. Whether the relationships between biomarkers and eGFR decline are similar to associations with measured GFR (mGFR) decline has not been investigated. This study revealed that some biomarkers showed statistically significant different associations with eGFR decline compared with mGFR decline, particularly for eGFR from cystatin C. The findings indicate that non-GFR-related factors, such as age, sex, and body mass index, influence the relationship between biomarkers and eGFR decline. Therefore, the results of biomarker studies using eGFR, particularly eGFRcys, should be interpreted with caution and perhaps validated with mGFR. Several serum protein biomarkers have been proposed as risk factors for GFR decline using eGFR from creatinine or cystatin C. We investigated whether eGFR can be used as a surrogate end point for measured GFR (mGFR) when searching for biomarkers associated with GFR decline. In the Renal Iohexol Clearance Survey, GFR was measured with plasma iohexol clearance in 1627 individuals without diabetes, kidney, or cardiovascular disease at baseline. After 11 years of follow-up, 1409 participants had one or more follow-up GFR measurements. Using logistic regression and interval-censored Cox regression, we analyzed the association between baseline levels of 12 serum protein biomarkers with the risk of accelerated GFR decline and incident CKD for both mGFR and eGFR. Several biomarkers exhibited different associations with eGFR decline compared with their association with mGFR decline. More biomarkers showed different associations with eGFRcys decline than with eGFRcre decline. Most of the different associations of eGFR decline versus mGFR decline remained statistically significant after adjustment for age, sex, and body mass index, but several were attenuated and not significant after adjusting for the corresponding baseline mGFR or eGFR. In studies of some serum protein biomarkers, eGFR decline may not be an appropriate surrogate outcome for mGFR decline. Although the differences from mGFR decline are attenuated by adjustment for confounding factors in most cases, some persist. Therefore, proposed biomarkers from studies using eGFR should preferably be validated with mGFR.