Mortality In Kidney Disease Research Articles

PP105 Efficacy, Effectiveness And Safety Of Letermovir For Prophylaxis Of Cytomegalovirus Infection And Disease Post-Allogeneic Hematopoietic Stem Cell Transplantation

IntroductionClinically significant cytomegalovirus infection (CSI-CMV) is an important factor associated with mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). It is estimated that the incidence of CSI-CMV in the post-HSCT period is 30 percent to 70 percent in transplanted individuals. Therefore, CSI-CMV is considered a complication in allogeneic HSCT, which can trigger Cytomegalovirus disease (CMVD). Letermovir is an antiviral agent indicated especially for the prophylaxis of CMVD post-HSCT. The objective of this work was to evaluate the efficacy, effectiveness and safety of letermovir, comparing it with placebo or other existing prophylactic treatments.MethodsA systematic review was carried out according to PRISMA 2020. A strategy was developed for searching electronic bibliographic databases. Retrieved publications were selected by a pair of reviewers. The same pair performed the data extraction. A qualitative assessment of the efficacy, effectiveness and safety of letermovir was performed.ResultsEighteen studies were included, being experimental and observational. Overall, the pivotal RCT demonstrates the efficacy of letermovir in reducing the incidence of CSI-CMV. However, there was no statistically significant difference in all-cause mortality and letermovir-related overall survival, events of graft versus host disease, neutropenia, acute kidney disease and 48-week mortality. Observational studies, in general, present results similar to those found in the pivotal RCT. The main adverse events associated with letermovir were peripheral edema (14.5%), vomiting (18.5%), headache (13.9%), cough (14.2%), abdominal pain (11.8%) and fatigue (13.4%).ConclusionsThe prophylactic use of letermovir in CMV-R+ patients after allogeneic HSCT demonstrates beneficial results in the prevention of CSI-CMV. However, there were no identified improvements for other outcomes. As for safety, it was observed that there is still little information about adverse events related to the drug, and studies assessing this aspect are needed for better comprehension.

Association of renal resistive indices with kidney disease progression and mortality

BackgroundRenal resistive indices (RRI) have been shown to predict the progression of kidney disease. This study aims to evaluate the association of RRI with mortality and dialysis initiation after adjustment to therapeutic and life style interventions.MethodsThis is a retrospective study that included all chronic kidney disease patients followed for at least two years in three nephrology clinics between 2006 and 2019 and who had a RRI level in their files. Kaplan Meier and log rank test compared the survival of patients with normal versus high RRI. Cox regression analysis evaluated the association between RRI and death or dialysis initiation after adjustment to treatments and life style modifications.ResultsA total of 192 patients were analyzed: 68 had RRI < 0.7 and 124 had RRI ≥ 0.7. Their mean age was 66.5 ± 13.1 years at first visit, 78.1% were males. There was a negative correlation between baseline eGFR and RRI (p < 0.001; Spearman correlation coefficient = -0.521). The survival was significantly better in patients with RRI < 0.7 with a Log Rank test < 0.001. The univariate cox regression analysis showed a significant association between RRI and mortality (HR = 1.08; 95%CI: 1.04–1.11; p < 0.001) that remained significant after adjustment to cardiovascular risk factors and interventions such as salt reduction, blood pressure control, statins and RAAS inhibitors (HR = 1.04; 95%CI: 1.00–1.08; p = 0.036). Cox regression analysis showed a significant association between RRI and dialysis initiation (HR = 1.06; 95%CI 1.01–1.10; p = 0.011).ConclusionOur study revealed that patients with an elevated RRI ≥ 0.7 are at a higher risk of mortality after adjustment to medications and lifestyle modifications. RRI can, according to this study, be considered as an independent prognostic factor in CKD patients.

PRO-C3 as a Risk Marker for Kidney Disease Progression and Mortality in Type 1 Diabetes

PRO-C3 as a Risk Marker for Kidney Disease Progression and Mortality in Type 1 Diabetes

Data quality and patient characteristics in European ANCA-associated vasculitis registries: data retrieval by federated querying

ObjectivesThis study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil cytoplasmic antibody-associated vasculitis (AAV)...

Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort

Mineral and bone disorder (MBD) in chronic kidney disease (CKD) is tightly linked to cardiovascular disease (CVD). In this study, we aimed to compare the prognostic value of nine MBD biomarkers to determine those associated best with adverse cardiovascular (CV) outcomes and mortality. In 5 217 participants of the German CKD (GCKD) study enrolled with an estimated glomerular filtration rate (eGFR) between 30–60 mL·min−1 per 1.73 m2 or overt proteinuria, serum osteoprotegerin (OPG), C-terminal fibroblast growth factor-23 (FGF23), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), cross-linked C-telopeptide of type 1 collagen (CTX1), procollagen 1 intact N-terminal propeptide (P1NP), phosphate, calcium, and 25-OH vitamin D were measured at baseline. Participants with missing values among these parameters (n = 971) were excluded, leaving a total of 4 246 participants for analysis. During a median follow-up of 6.5 years, 387 non-CV deaths, 173 CV deaths, 645 nonfatal major adverse CV events (MACEs) and 368 hospitalizations for congestive heart failure (CHF) were observed. OPG and FGF23 were associated with all outcomes, with the highest hazard ratios (HRs) for OPG. In the final Cox regression model, adjusted for CV risk factors, including kidney function and all other investigated biomarkers, each standard deviation increase in OPG was associated with non-CV death (HR 1.76, 95% CI: 1.35–2.30), CV death (HR 2.18, 95% CI: 1.50–3.16), MACE (HR 1.38, 95% CI: 1.12–1.71) and hospitalization for CHF (HR 2.05, 95% CI: 1.56–2.69). Out of the nine biomarkers examined, stratification based on serum OPG best identified the CKD patients who were at the highest risk for any adverse CV outcome and mortality.

Serum uric acid is related to liver and kidney disease and 12-year mortality risk after myocardial infarction.

To study the associations of non-alcoholic fatty liver disease (NAFLD), chronic kidney disease (CKD), and serum uric acid (SUA) in patients with post-myocardial infarction (MI) patients, and the relationship of SUA with 12-year mortality risk. We included 3,396 patients (60-80 years old, 78% men) of the Alpha Omega Cohort. Multivariable prevalence ratios (PRs) were obtained for the association of NAFLD [fatty liver index (FLI), ≥77 (women) and ≥79 (men)] with CKD [estimated glomerular filtration rate (eGFR), <60 mL/min per 1.73 m2]. We calculated sensitivity and specificity of SUA to detect the (combined) presence and absence of NAFLD and CKD. Cause-specific mortality was monitored from enrolment (2002-2006) through December 2018. Hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality in SUA categories were obtained from multivariable Cox models. Median baseline FLI was 67 (men, 68; women, 64), and mean ± SD eGFR was 81 ± 20 mL/min per 1.73 m2 (17% with CKD). Sex-specific FLI was associated with higher CKD prevalence (PRtertile3 vs. tertile1, 1.94; 95% confidence interval: 1.57, 2.39). Baseline SUA was 0.36 ± 0.09 mmol/L. With increasing SUA concentrations, specificity for the presence of NAFLD, CKD, or both increased, and sensitivity decreased. During 12 (interquartile range, 9-14) years of follow-up, 1,592 patients died (713 from CVD). HRs ranged from 1.08 (0.88, 1.32) for SUA ≤0.25 mmol/L to 2.13 (1.75, 2.60) for SUA >0.50 mmol/L vs. SUA >0.30-0.35 mmol/L for all-cause mortality. For CVD mortality, HRs ranged from 1.05 (0.77, 1.44) to 2.43 (1.83, 3.25). NAFLD and CKD were strongly associated, which was reflected by higher SUA concentrations. SUA was a strong predictor of 12-year mortality risk after MI.

Heart rate variability at rest and in response to stress: Comparative study between hemodialysis and peritoneal dialysis patients.

Cardiac arrhythmias and sudden death are the leading causes of mortality in end-stage kidney disease (ESKD). Autonomic nervous system (ANS) dysfunction contributes to this arrhythmogenic background. This study compared heart rate variability (HRV) indices between hemodialysis (HD) and peritoneal dialysis (PD) patients, both at rest and in response to mental and physical stimulation maneuvers. Thirty-four HD and 34 PD patients matched for age, sex, and dialysis vintage, and 17 age- and sex-matched controls were studied. ANS function was examined by linear and non-linear HRV indices. Heart rate was recorded continuously (Finometer-PRO) at rest and during ANS maneuvers (orthostatic, mental-arithmetic, sit-to-stand, handgrip exercise tests). At rest, no significant differences between HD and PD were observed in HRV (root mean square of successive differences [RMSSD]: HD = 57.1 ± 81.1 vs PD = 69.6 ± 113.4 ms; P = 0.792), except for detrended fluctuation analysis (DFA-α1) (HD = 0.87 ± 0.40 vs PD = 0.70 ± 0.20; P = 0.047). DFA-α1 was significantly lower in PD than controls (1.00 ± 0.33; P < 0.05). All HRV indices during the mental-arithmetic test (RMSSD: HD = 128.2 ± 346.0 vs PD = 87.5 ± 150.0 ms; P = 0.893) and the physical stress tests were similar between HD and PD. The standard deviation along the line-of-identity (SD2)/the standard deviation perpendicular to the line-of-identity (SD1) ratio during mental-arithmetic was marginally lower in HD and significantly lower in PD than controls (PD = 1.31 ± 0.47 vs controls = 1.79 ± 0.64; P < 0.05). Both dialysis groups presented similar patterns in HRV responses during orthostatic and handgrip exercise tests. After the sit-to-stand, RMSSD, SD1, SD2, and DFA-α2 were higher compared to rest only in HD (RMSSD = 57.1 ± 81.1 vs 126.7 ± 185.7 ms; P = 0.028), suggesting a greater difficulty of HD patients in recovering normal ANS function in response to physical stress. In conclusion, HRV indices at rest and after mental and physical stimulation did not differ between HD and PD; however, the ANS responses following the sit-to-stand test were more impaired in HD. These findings suggest that ANS dysfunction is not largely affected by dialysis modality, but small differences in normal ANS recovery may exist.

Development and validation of the prediction model for mortality in patients with diabetic kidney disease in intensive care unit: a study based on medical information Mart for intensive care

We aimed to explore factors associated with mortality of diabetic kidney disease (DKD), and to establish a prediction model for predicting the mortality of DKD. This was a cohort study. In total, 1,357 DKD patients were identified from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, with 505 DKD patients being identified from the MIMIC-III as the testing set. The outcome of the study was 1-year mortality. COX proportional hazard models were applied to screen the predictive factors. The prediction model was conducted based on the predictive factors. A receiver operating characteristic (ROC) curve with the area under the curve (AUC) was calculated to evaluate the performance of the prediction model. The median follow-up time was 365.00 (54.50,365.00) days, and 586 patients (43.18%) died within 1 year. The predictive factors for 1-year mortality in DKD included age, weight, sepsis, heart rate, temperature, Charlson Comorbidity Index (CCI), Simplified Acute Physiology Score (SAPS) II, and Sequential Organ Failure Assessment (SOFA), lymphocytes, red cell distribution width (RDW), serum albumin, and metformin. The AUC of the prediction model for predicting 1-year mortality in the training set was 0.771 [95% confidence interval (CI): 0.746-0.795] and the AUC of the prediction model in the testing set was 0.795 (95% CI: 0.756-0.834). This study establishes a prediction model for predicting mortality of DKD, providing a basis for clinical intervention and decision-making in time.

Controlling nutritional status score is associated with renal progression, cardiovascular events, and all-cause mortality in biopsy-proved diabetic kidney disease.

Background: The Controlled Nutritional Status (CONUT) score, calculated from albumin, total cholesterol, and lymphocyte count, is a useful indicator for immune-nutritional assessment and is associated with the prognosis of various diseases. However, its relationship with renal outcomes, cardiovascular disease (CVD), and all-cause mortality in patients with diabetic kidney disease is unclear. Methods: This retrospective single-center study enrolled 336 patients with biopsy-confirmed diabetic kidney disease from August 2009 to December 2018. The outcomes were progression to end-stage renal disease (ESRD), CVD events, and death. Univariate and multivariate Cox regression analyses were performed to estimate the association between confounding factors and outcomes. The Kaplan-Meier curve was used to compare the outcomes of the patients according to the median CONUT score. The area under the curve (AUC) evaluated with time-dependent receiver operating characteristics was used to test discriminative power of COUNT score. Results: During a median follow-up period of 5.1years. The Kaplan-Meier analysis showed that patients in the high CONUT group (CONUT score > 3) had a significantly higher incidence of ESRD, CVD events, and all-cause mortality than those in the low CONUT group (CONUT score ≤ 3). The multivariate COX regression analysis indicated that, The CONUT score was an independent predictor of ESRD (hazards ration [HR] = 1.129, 95% confidence interval [CI] 1.037-1.228, p = 0.005), CVD events (HR = 1.159, 95% CI 1.057-1.271, p = 0.002), and all-cause mortality (HR = 1.299, 95% CI 1.143-1.478, p < 0.001). Conclusion: The CONUT score is an independent risk factor for ESRD, CVD events, and overall death in patients with diabetic kidney disease.

Taiwan renal data report system: Framework, function, and development.

The world healthcare system is actively seeking possible solutions for the rapid growth of kidney disease threats. The Taiwan Renal Data System (TWRDS) was central in assisting kidney health and care policymaking to reduce end-stage kidney disease incidence and mortality. This article summarizes the TWRDS framework, recent applications, and developments to provide new insights for some international researchers to promote planetary kidney health. The TWRDS originated in 1987 for the accreditation and quality monitoring of dialysis units and was connected with enriched health claim databases after the implementation of universal national health insurance in Taiwan in 1995. As a healthcare information centre, TWRDS has published annual reports forming indispensable instructions for renal care improvement since 2014. The TWRDS possesses three main functions: (1) kidney disease surveillance; (2) offering rich materials for research purposes; (3) achieving precision prevention and care through complex algorithms. In the new era, TWRDS can help build a more resilient society against communicable disease threats by integrating remote sensor techniques for developing future remote healthcare structures, as well as identifying kidney health inequity populations and promoting healthcare resources distributed equity. The global healthcare system is facing escalating burdens of non-communicable disease care due to the rapidly growing elderly population. Therefore, a considerable-scale data system is an essential decision-supportive tool in promoting an evidence-based, resilient, sustainable, equity care environment. Undoubtedly, TWRDS experience is a practical example of leveraging healthcare providers' decisions, care outcomes, and renovation.

Triiodothyronine and Protein Malnutrition Could Influence Pulse Wave Velocity in Pre-Dialysis Chronic Kidney Disease Patients.

Cardiovascular diseases (CVD) are the first cause of chronic kidney disease (CKD) mortality. For personalized improved medicine, detecting correctable markers of CVD can be considered a priority. The aim of this study was the evaluation of the impact of nutritional, hormonal and inflammatory markers on brachial-ankle Pulse Wave Velocity (PWV) in pre-dialysis CKD patients. A cross-sectional observational study was conducted on 68 pre-dialysis CKD patients (median age of 69 years, 41.2% with diabetes mellitus, 52.9% male). Laboratory data were collected, including levels of prolactin, triiodothyronine, TGF α, IL-6, and IL-1β. The high values of brachial-ankle PWV were associated with reduced muscle mass (p = 0.001, r = -0.44), low levels of total cholesterol (p = 0.04, r = -0.26), triglycerides (p = 0.03, r = -0.31), triiodothyronine (p = 0.04, r = -0.24), and prolactin (p = 0.02, r = -0.27). High PWV was associated with advanced age (p < 0.001, r = 0.19). In the multivariate analysis, reduced muscle mass (p = 0.018), low levels of triiodothyronine (p = 0.002), and triglycerides (p = 0.049) were significant predictors of PWV, but age (p < 0.001) remained an important factor. In conclusion, reduced triiodothyronine together with markers of malnutrition and age were associated with PWV in pre-dialysis CKD patients.

The NAFLD burden on mortality and morbidities in general population: A community-based longitudinal study (NASH-CO study).

The impact of non-alcoholic fatty liver disease (NAFLD) on morbidity and mortality has yet to be documented at the general population level. This study aimed to assess whether NAFLD was associated with morbidities and mortality and to estimate its impact on health status and mortality. The study population consisted of 137 206 participants from Constances cohort. Non-invasive diagnosis of NAFLD and advanced fibrosis was performed using the fatty liver index and Forns index, respectively. Constances data were linked to health care and hospitalization data to identify liver-related events, cardiovascular diseases (CVD), extrahepatic cancers (EHC), chronic kidney disease (CKD) and all-cause mortality. The prevalence of NAFLD was 18.3% in subjects without other chronic liver diseases, among whom 2.7% had fibrosis. NAFLD after IPTW-weighted remained associated with an increased risk of death (HR 1.26, 95% CI 1.01-1.57), hepatic-related complications (HR 2.48, 95% CI 1.99-3.29), CVD (HR 1.42, 95% CI 1.30-1.55), EHC (HR 1.11, 95% CI 1.01-1.28) and CKD (HR 1.81, 95% CI 1.53-2.07) compared to those without chronic liver diseases risk factors (Non-NAFLD). In the trend analysis over the study period of inclusion and compared to Non-NAFLD, NAFLD has shown a fastest growing cause of hepatic events (HR 1.38, 95% CI 1.07-1.76 per year), CVD (HR 1.08, 95% CI 1.03-1.12), CKD (HR 1.16, 95% CI 1.07-1.25), and death (HR 1.39, 95% CI 1.39-1.50). This large community-based cohort showed that NAFLD was associated with excess morbidity and mortality and demonstrated a fastest-growing trend.

Finerenone: A Novel Third-Generation Mineralocorticoid Receptor Antagonist.

Finerenone is a novel third-generation, selective nonsteroidal mineralocorticoid receptor antagonist (MRA) that was approved by the Food and Drug Administration in July of 2021 for its use in adults with chronic kidney disease and Type II diabetes mellitus. Randomized controlled trials The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease and Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease showed decreased adverse kidney and cardiovascular outcomes, respectively, in this population. The incidence of hyperkalemia, while higher in the study versus placebo group, was lower than older generations of MRAs (spironolactone and eplerenone) and proved to be an infrequent cause for drug discontinuation. The incidences of other adverse effects such as gynecomastia and acute kidney injury were similar in both the study and the placebo groups. This is the first third-generation MRA authorized to use to reduce the burden of cardiorenal disease.

Association of Primary Kidney Disease Type and Donor Relatedness With Live Donor Kidney Transplant Outcomes: An Analysis of ANZDATA

There is limited information about the association between primary kidney disease and donor relatedness with transplant outcomes. This study addresses this gap by evaluating clinical outcomes after kidney transplantation in recipients of living donor kidneys as a function of primary kidney disease type and donor relatedness in Australia and New Zealand. Retrospective observational study. Kidney transplant recipients who received allografts from living donors between January 1, 1998, and December 31, 2018, as recorded in the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). Primary kidney disease type categorized as majority monogenic, minority monogenic, or other primary kidney disease based on disease heritability as well as donor relatedness. Primary kidney disease recurrence, graft failure. Kaplan-Meier analysis and Cox proportion hazards regression to generate hazard ratios for primary kidney disease recurrence, allograft failure, and mortality. Partial likelihood ratio test was used to examine possible interactions between primary kidney disease type and donor relatedness for both study outcomes. Among 5,500 live donor kidney transplant recipients, majority monogenic (adjusted HR, 0.58, P<0.001) and minority monogenic primary kidney diseases (adjusted HR, 0.64, P<0.001) were associated with reduced primary kidney disease recurrence compared with other primary kidney diseases. Majority monogenic primary kidney disease was also associated with reduced allograft failure (adjusted HR, 0.86, P=0.04) compared with other primary kidney diseases. Donor relatedness was not associated with primary kidney disease recurrence nor graft failure. No interaction was detected between primary kidney disease type and donor relatedness for either study outcome. Potential misclassification of primary kidney disease type, incomplete ascertainment of primary kidney disease recurrence, unmeasured confounding. Monogenic primary kidney disease is associated with lower rates of primary kidney disease recurrence and allograft failure. Donor relatedness was not associated with allograft outcomes. These results may inform pretransplant counseling and live donor selection. There are theoretical concerns that live-donor kidney transplants may be associated with increased risks of kidney disease recurrence and transplant failure due to unmeasurable shared genetic factors between the donor and the recipient. This study analyzed data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry and showed that, although disease type was associated with the risk of disease recurrence and transplant failure, donor relatedness did not impact transplant outcomes. These findings may inform pretransplant counseling and live donor selection.

PATIENTS WITH END-STAGE RENAL DISEASE ADMITTED TO THE INTENSIVE CARE UNIT: SYSTEMATIC REVIEW

Background: The prevalence and incidence of Chronic Kidney Disease (CKD), especially End-Stage Renal Disease (ESRD), are rising globally, primarily due to aging populations, hypertension, diabetes, and obesity. The prevalence of chronic kidney disease (CKD) in critically ill patients is incompletely documented.&#x0D; &#x0D; Aim: This study aims to determine the frequency of critical care unit visits among individuals with end-stage renal disease.&#x0D; &#x0D; Methods: This study demonstrated compliance with all requirements of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 standards through self-comparison. The experts ensured the study's maximum contemporaneity. The search strategy involved examining publications published from 2013 to 2023. This was accomplished using various online reference databases, including Pubmed and SagePub. Only completed papers and publications were considered, while incomplete pieces and previously published works were excluded.&#x0D; &#x0D; Result: 1,662 and 1,212 articles were retrieved from PubMed and SagePub, respectively. In 2013, we collated 16 papers, including 11 from PubMed and 5 from SagePub, 4 of which met the research criteria.&#x0D; &#x0D; Conclusion: ICU patients frequently exhibit advanced kidney disease and elevated mortality rates.

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study

BackgroundSevere secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery.MethodsWe aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months. Inclusion criteria were age older than 18 years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of 418 patients treated in the same centers, who did not undergo parathyroidectomy was selected after matching for age, sex, and dialysis vintage.ResultsFrom 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients who underwent parathyroidectomy (age 58.2 ± 12.8 years; M/F: 44%/56%, dialysis vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age 60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group that underwent parathyroidectomy (Kaplan–Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387–0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465–0.970, p = 0.034), identified parathyroidectomy as a protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients who underwent parathyroidectomy compared to controls (PTX vs non-PTX: PTH < 150 pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH > 300 pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%, p = 0.002).ConclusionsOur data suggest that parathyroidectomy is associated with survival rate at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term.Graphical abstract

686-P: Risk Associations between Patient Reported Depression, Cardiovascular-Renal Events, All-Cause Mortality, and Potential Single-Item Patient Health Questionnaire (PHQ) Screening for All-Cause Mortality in Asians—Six-Year Prospective Analysis of the Hong Kong Diabetes Register

Background: Asians are at higher risk of diabetes, though risk associations of depression and diabetes complications were reported mainly in the Western population. This is the first prospective study reporting association between depression and clinical outcomes in Asian patients with type 2 diabetes (T2D), adjusted for patient report outcomes (PRO) including lifestyle behaviours, self-care and health-related quality of life (HRQoL). Methods: We performed a retrospective analysis of 4525 Chinese patients with T2D utilizing the Hong Kong Diabetes Register medical records and PRO data collected between 2013 and 2019. Hazard ratios (HR) of depression for the following diabetes complications were estimated: cardiovascular disease (CVD) including ischemic heart disease (IHD), stroke, chronic kidney disease (CKD) and all-cause mortality adjusted for PRO with Cox regression models. Results: At baseline, 537 patients reported depressive symptoms with a PHQ-9 score≥7. Depression was significantly associated with CVD (HR 1.90 [1.20-3.01]) particularly for IHD (HR 2.21 [1.21-4.02]) after adjusting for conventional risk factors and PRO. Depression was significantly associated with all-cause mortality (HR 1.87 [1.16-3.03]) before adjusting for HRQoL. Patient Health Questionnaire (PHQ-9) Q4 (feeling tired or having little energy) was significantly associated with all-cause mortality (HR 1.76 [1.38-2.24]), indicating a potential single screening item for all-cause mortality in Asian patients with T2D. Conclusion: Depression is reported to have significant associations with diabetes complications considering PRO. PHQ-9 Q4 can be used as a single item tool in identifying patients with T2D who are at high risk of all-cause mortality, for early counselling and behaviour modifications. Disclosure J.N.M.Lui: None. H.Yeung: None. K.Loo: None. R.Ozaki: None. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer Inc., Celltrion, Boehringer Ingelheim and Eli Lilly Alliance, Sanofi, Research Support; AstraZeneca, Servier Laboratories, Viatris Inc., Hua Medicine, Merck KGaA, Applied Therapeutics Inc., Lee Powder, Pfizer Inc., Speaker's Bureau; Novartis, Stock/Shareholder; GemVCare Ltd. E.S.H.Lau: None. Y.Yeung: None. K.Lee: None. T.Yung: None. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Speaker's Bureau; Abbott, AstraZeneca, Lilly, Bayer Inc., Boehringer Ingelheim Inc. A.Luk: Research Support; Novo Nordisk, Boehringer-Ingelheim, Bayer Inc., Speaker's Bureau; Eli Lilly and Company. E.Chow: Research Support; Medtronic, Merck KGaA, Speaker's Bureau; Novartis, Bayer Inc., Sanofi. R.C.Ma: Advisory Panel; AstraZeneca, Merck &amp; Co., Inc., Other Relationship; Bayer Inc., Boehringer-Ingelheim, Research Support; Tricida, Inc., Roche Diagnostics, Novo Nordisk.

A nationwide cohort study comparing the effectiveness of diuretics and calcium channel blockers on top of renin-angiotensin system inhibitors on chronic kidney disease progression and mortality

It is unknown whether initiating diuretics on top of renin-angiotensin system inhibitors (RASi) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs) in patients with chronic kidney disease (CKD). For this purpose, we emulated a target trial in the Swedish Renal Registry 2007-2022 that included nephrologist-referred patients with moderate-advanced CKD and treated with RASi, who initiated diuretics or CCB. Using propensity score-weighted cause-specific Cox regression, we compared risks of major adverse kidney events (MAKE; composite of kidney replacement therapy [KRT], experiencing over a 40% eGFR decline from baseline, or an eGFR under 15 ml/min per 1.73m2), major cardiovascular events (MACE; composite of cardiovascular death, myocardial infarction or stroke), and all-cause mortality. We identified 5875 patients (median age 71 years, 64% men, median eGFR 26 ml/min per 1.73m2), of whom 3165 started a diuretic and 2710 a CCB. After a median follow-up of 6.3 years, 2558 MAKE, 1178 MACE and 2299 deaths occurred. Compared to CCB, diuretic use was associated with a lower risk of MAKE (weighted hazard ratio 0.87 [95% confidence interval: 0.77-0.97]), consistent across single components (KRT: 0.77 [0.66-0.88], over 40% eGFR decline: 0.80 [0.71-0.91] and eGFR under 15ml/min/1.73m2: 0.84 [0.74-0.96]). The risks of MACE (1.14 [0.96-1.36]) and all-cause mortality (1.07 [0.94-1.23]) did not differ between therapies. Results were consistent when modeling the total time drug exposure, across sub-groups and a broad range of sensitivity analyses. Thus, our observational study suggests that in patients with advanced CKD, using a diuretic rather than a CCB on top of RASi may improve kidney outcomes without compromising cardioprotection.

#4185 EPISODES OF AKI FOLLOWING HOSPITALISATION AND ASSOCIATION WITH ADVERSE OUTCOMES: ANALYSIS FROM A PROSPECTIVE COHORT STUDY

Abstract Background and Aims AKI is associated with adverse long-term outcomes, including mortality, cardiovascular events and CKD development and progression. Individuals who have sustained AKI are at increased risk of developing further AKI. This analysis presents the association of long-term risk related to recent and further episodes of AKI in a prospective cohort of recently hospitalised individuals. Method Two matched cohorts of hospitalised individuals who had survived to at least 90 days after hospital discharge were recruited. The cohorts consisted of people who had sustained AKI during hospital admission (exposed group), and those who had not (non-exposed group), and were matched 1:1 for age, baseline eGFR stage and diabetes. Renal function, albuminuria and new AKI episodes were measured at 3 months, one, three and five years after index hospitalisation. Mortality, further AKI episodes and episodes of heart failure were recorded. Kidney disease progression was defined as decrease in eGFR of ≥25% associated with a decline in eGFR stage. Multivariable analysis was performed with binary logistic regression to assess the associations between repeated AKI episodes and outcomes. Results 866 exposed and non-exposed participants were recruited and successfully matched. Over the 5-year follow-up period, 138 (34%) participants in the exposed group had ≥1 further AKI compared with 67 (16%) in the non-exposed group (OR 2.71 [95% CI 1.94 to 3.77]; p&amp;lt;0.001). Independent associations with developing AKI during the follow-up period were AKI during index admission, baseline eGFR, albuminuria at 3 months and smoking status. Binary logistic regression, including all matched participants, showed that AKI during follow-up was independently associated with 5-year kidney disease progression (adjusted OR 2.49, 95% CI 1.42-4.37, p = 0.002), mortality (adjusted OR 3.076 95% CI 2.039-4.639 p&amp;lt;0.001) and episodes of heart failure (adjusted OR 5.234 95% CI 3.355-8.164, p&amp;lt;0.001). There was an additive effect, with the frequency of adverse outcomes increasing as number of AKI exposures increased (Table 1). Exposure to AKI during index admission or follow-up episodes conferred similar risk of kidney disease progression. AKI during the follow-up period had a stronger association with mortality and heart failure episodes than AKI during the index admission in this survivor cohort. Conclusion Previous AKI episodes were associated with increased frequency of future AKI episodes. AKI episodes during follow up period were independently associated with adverse outcomes regardless of AKI exposure during index hospitalisation. Increasing number of exposures to AKI had an additive effect on the proportion of individuals showing kidney disease progression, mortality and heart failure episodes. In this cohort of AKI survivors, AKI during the follow-up period had a stronger association with these outcomes than exposure to AKI during the index admission. A strategy for improving long-term outcomes in AKI survivors may be improving the identification of those at greatest risk of future AKI and strategies to prevent or optimise early detection and management.

#3367 NON-INVASIVE OPTICAL ESTIMATION OF INTRADIALYTIC CONCENTRATIONS OF UREMIC TOXINS IN BLOOD OF HEMODIALYSIS PATIENTS

Abstract Background and Aims Hemodialysis (HD) adequacy is generally estimated by the dialysis adequacy marker Kt/V urea that poorly describes removal of uremic toxins with different removal kinetics, such as protein bound or middle molecule uremic toxins, which have direct effect on morbidity and mortality of end stage kidney disease (ESKD) patients. We have recently shown the feasibility of estimating an alternative dialysis adequacy marker that can be applied to dialysis sessions with varying settings and different uremic toxins, intradialytic time average concentration (TAC) of uremic toxins, such as urea, uric acid (UA), indoxyl sulfate (IS) and beta-2-microglobulin in blood of ESKD patients, from spent dialysate concentrations determined by laboratory methods [1]. The aim of this retrospective observational study was to estimate intradialytic TAC of uremic toxins UA and IS non-invasively from spent dialysate concentrations determined by optical methods. Method Twenty-two ESKD patients on chronic HD were enrolled into the study. For each patient 4 midweek dialysis sessions with different treatment settings were included (1 HD: Qb = 200 mL/min, Qd = 300 mL/min, dialyzer 1,5m2; 3 HDF: median (interquartile range) Qb = 298 (296-356) mL/min, Qd = 795 (500–800) mL/min, Vsubst = 21.8 (15–24.5) L, dialyzers 1,8 m2 and 2,2 m2). During each dialysis session, blood samples were taken at 0 min (start) and 240 min after the start from the arterial blood line and dialysate samples were taken at 7 min and 240 min after the start from the outlet of the dialysis machine. Concentrations of UA and IS in serum and spent dialysate samples were determined with HPLC. In addition, UV absorbance and fluorescence of the spent dialysate samples were measured with spectrophotometer UV-3600 and spectrofluorometer RF-6000 (both from Shimadzu Corp., Japan), after which concentrations of UA and IS in spent dialysate samples were determined based on the optical properties of samples. Stability of HD treatment settings were monitored online and dialysis sessions with unstable blood and dialysate flow rates were excluded. TAC of UA and IS were calculated from serum concentrations and evaluated from laboratory and optically estimated logarithmic mean concentrations (Mln D) of spent dialysate. Results Mean intradialytic serum TAC values of UA and IS were 198.4±44.0 μmol/L and 69.5 ± 37.8 μmol/L and strongly correlated to those estimated from optically determined Mln D 198.0±38.9 μmol/L (R2 = 0.75) and 69.5 ± 37.8 μmol/L (R2 = 0.81), respectively. Mln D of UA and IS in spent dialysate based on laboratory methods were 102.2 ± 22.8 μmol/L and 5.9 ± 3.5 μmol/L and strongly correlated with the optically determined concentrations of 102.7 ± 23.1 μmol/L (R2 = 0.97) and 6.1 ± 3.4 μmol/L (R2 = 0.97), respectively. Conclusion Intradialytic serum TAC of UA and IS can be estimated non-invasively with optical methods from their concentration in spent dialysate independent of treatment modality. Optical online monitoring of spent dialysate in real-time could therefore provide additional information about treatment adequacy regarding the removal of uremic toxins’ other than urea. In future, TAC estimation models should be optimized for each uremic toxin to establish higher accuracy, considering real-time treatment settings, recirculation etc.