Lower Renal Function Research Articles

#4353 HEALTH-RELATED QUALITY OF LIFE IN ADULTS WITH PRIMARY GLOMERULAR DISEASES IN INDIA

Abstract Background and Aims Glomerular diseases pose a substantial burden on the healthcare system. While the medical and economic burden of glomerular diseases is well established, the data on the health-related quality of life impact is scant. Method We used the PROMIS 29 v2.1 (Patient-Reported Outcomes Measurement Information System) tool to assess HRQOL impact of primary glomerular diseases in adult Indian patients [1], under the domains: physical function, anxiety, fatigue, depression, sleep disturbance, ability to participate in social roles and activities and pain interference in daily activities. The questionnaire was administered in English and Hindi. Patient responses were then used to calculate T-scores with a mean of 50 and an SD of 10 with the score having positive correlation with the quantum of the outcome measured. Results 141 adult patients were recruited (39 minimal change disease/ focal segmental glomerulosclerosis, 36 membranous nephropathy, 56 IgA nephropathy, 9 membrano-proliferative glomerulonephritis). Mean T-scores across domains were as follows: physical function- 48.2 (46.8-49.6), fatigue- 49.2 (47.5-51), anxiety- 52.3 (50.6-53.9), sleep impairment- 43.5 (41.9-45.1), depression- 50.7 (49-52.4), ability to participate in social roles and activities- 55 (53.3-56.7), hindrance in daily activities due to pain 51.2 (49.7-52.8). Better physical function was associated with higher eGFR (T-score of 44 at eGFR<45 ml/min/1.73m2 and 49.8 at eGFR>45 ml/min/1.73m2, p<0.001), lower BMI (42.4 in obese vs 48.6 in non-obese, p = 0.02), and male sex (50.2 vs 44.5 in females, p<0.001). Fatigue was associated with eGFR<45 ml/min/1.73m2 (52.2 vs 48.1 at eGFR>45 ml/min/1.73m2, p = 0.04), and female sex (53.2 vs 47.1 in males, p<0.001). Worse anxiety was seen in females (55.8 vs 50.4 in males, p = 0.002) and patients with eGFR<45 ml/min/1.73m2 (55.4 vs 51.1 at eGFR>45 ml/min/1.73m2, p = 0.02). Sleep impairment was seen in patients having a history of steroid usage in the last 2 months (45.8 vs 42.1, p = 0.02), females (45.8 vs 42.3, p = 0.04), and patients with eGFR<45 ml/min/1.73m2 (46.2 vs 42.5 at eGFR>45 ml/min/1.73m2, p = 0.04). Pain interference was higher in females (55.9 vs 48.8 in males, p<0.001) and patients with eGFR<45 ml/min/1.73m2 (54 vs 50.2 at eGFR>45 ml/min/1.73m2, p = 0.03). eGFR>45 ml/min/1.73m2 (56.4 vs 51.4 at eGFR<45 ml/min/1.73m2, p = 0.008) was associated with better involvement in social roles. Depression was associated with female sex (54.2 vs 48.9 in males, p = 0.003). Degree of proteinuria, serum albumin, duration of disease, immunosuppressive drug use, age, patient-reported edema, and socio-economic status were not associated with a significant decrease in HRQOL. Multivariable linear regression models were evaluated for all domains. Physical function was negatively associated with eGFR<45ml/min/1.73m2 (β = -5.46), female sex (β = -5.16), and obesity (β = -6.36). Fatigue was associated with eGFR<45ml/min/1.73m2 (β = 3.89), female sex (β = 5.76), and obesity (β = 9.62). Worse anxiety was associated with eGFR<45ml/min/1.73m2 (β = 3.82) and female sex (β = 4.97). Sleep impairment was associated with eGFR<45ml/min/1.73m2 (β = 3.46) and female sex (β = 3.24). Pain interference was associated with eGFR<45ml/min/1.73m2 (β = 3.39) and female sex (β = 7.19) Ability to participate in social roles and activities was negatively associated with eGFR<45ml/min/1.73m2 (β = -4.86) and female sex (β = −3). Depression was associated with obesity (β = 6.16) and female sex (β = 5.22). Conclusion Glomerular diseases adversely impact the quality of life. Female sex, lower renal function (eGFR), higher BMI and history of recent steroid use correlated with higher morbidity.

#4072 HEART OF STONE: THE IMPACT OF CARDIOVASCULAR RISK ON NEPHROLITHIASIS: AN OBSERVATIONAL STUDY

Abstract Background and Aims The incidence of nephrolithiasis has risen in recent years, largely due to changes in diet and lifestyle. An association between nephrolithiasis and risk of cardiovascular disease has been described, including atherosclerosis. The underlying mechanisms linking the two conditions are not well understood, making it important to study the role of exercise and nutritional habits. This study aims to examine the incidence of cardiovascular comorbidities in patients with nephrolithiasis, considering demographic information and the timeline of disease diagnosis and follow-up. Conditions such as dyslipidemia, myocardial infarction, stroke, and metabolic syndrome are of particular interest in this population. Method We retrospectively analysed consecutive patients that were referred to our tertiary medical center nephrolithiasis clinic between 2021 and 2023. The demographic information collected included gender, age at first nephrolithiasis diagnosis, current age, and family history. The cardiovascular conditions analysed included metabolic syndrome, hypertension, diabetes, gout, smoking, stroke, and dyslipidemia. Additionally, renal function (GFR-EPI) was also taken into account. Appropriate tests for continuous and categorical variables were applied, recurring to SPSS v21.0. Results A total of 84 patients were included in the study. Of these, 51.2% (n=43) were women with a median age of 52 years (IQR: 13-83) and a median age of first nephrolithiasis diagnosis of 34 years (IQR: 9-75). The analysed comorbidities showed a high incidence of hypertension (n=35, 41.7%), obesity (n=33, 40.7%), dyslipidemia (n=50, 61%), and metabolic syndrome (n=20, 23.8%). Family history was identified in 37.3% (n=31) of patients, with a significant difference for men, where 64.5% (n=20) had a positive family history (p-value 0.033). The results showed a relationship between increased body mass index and younger age of first nephrolithiasis diagnosis (p-value 0.012) and lower renal function at diagnosis (p-value 0.005). Conclusion The diagnosis of nephrolithiasis requires a change in the patient's diet and lifestyle, not only because of the risk of recurrence, but also because these patients are at a higher risk of developing serious cardiovascular events. This study highlights the high incidence of these comorbidities and underscores the importance of both the patient and the nephrologist being diligent in addressing these issues to achieve better kidney and overall health outcomes.

#4343 COMPARISONS OF CLINICAL OUTCOMES BETWEEN HYPERTENSIVE AND NORMOTENSIVE LIVING KIDNEY DONORS: A NATIONWIDE PROSPECTIVE COHORT STUDY

Abstract Background and Aims Living kidney donors with hypertension is potential candidates to solve the imbalance between supply and demand for renal transplantation. However, the safety of hypertensive donor is not sufficiently ensured after donor nephrectomy and there are limited studies, which compare the clinical outcomes between hypertensive and normotensive donors. Method All data from this study were obtained from the Korean Organ Transplantation Registry (KOTRY). A total 672 hypertensive donors and 5,134 normotensive living kidney donors were included from May 2014 to December 2020. Primary outcome was the occurrence of proteinuria and the development of lower renal function, defined as an estimated glomerular filtration rate (eGFR) less than 60 or 45 ml/min/1.73 m2. Results Compared to normotensive donors, hypertensive donors had lower eGFR before nephrectomy and remained lower after kidney transplantation. However, the risk of eGFR below 60 ml/min/1.73 m2 (adjusted HR, 0.87; 95% CI 0.70-1.09; P = 0.226) or below 45 ml/min/1.73 m2 (adjusted HR, 1.49; 95% CI 0.77-2.86; P = 0.234) was not significantly increased in hypertensive donors after multiple adjustment. When comparing the rate of eGFR decline between the hypertensive and normotensive donors, there was no significant difference (adjusted unstandardized β, −0.19; −1.15 – 0.76, P = 0.691). The incidence of proteinuria occurrence in hypertensive donor was increased, and it tended to increase even after 4-5 years. Hypertensive donors were found to have significantly more proteinuria than normotensive donors (adjusted HR, 1.83; 95% CI 1.13-2.96; P = 0.014). Conclusion Our study indicated that the risk of proteinuria after donation was increased in hypertensive donor, while it was not translated into significant decline in renal function. The continuous and careful monitoring for proteinuria should be required in hypertensive donor after nephrectomy.

Abstract 296: Role Of Endothelial Cell-specific Knockout Of The Aryl Hydrocarbon Receptor In Ischemic Limb Myopathy In Mice Subjected To Hind Limb Ischemia

Introduction: Chronic kidney disease (CKD) is a risk factor for peripheral arterial disease (PAD) that accelerates disease evolution and worsens limb outcomes, however the molecular mechanisms linking the pathobiologies are ill-defined. The aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, has been previously shown to regulate angiogenesis. Notably, CKD results in the accumulation of tryptophan-derived metabolites that are endogenous ligands for the AHR. On this basis, we tested the hypothesis that endothelial cell-specific knockout of the AHR would enhance limb perfusion recovery and capillarity in mice with CKD subjected to hindlimb ischemia. Methods: Twelve-week-old conditional AHR knockout mice (AHR fl/fl , Cre-negative) and endothelium-specific AHR knockout mice (AHR ecKO ) were fed 0.2% adenine to induce CKD or casein control diet (n=10/group/sex). Femoral artery ligation (FAL) was performed on the left limb using the right limb as a non-ischemic control. Limb perfusion was measured using laser Doppler flowmetry. Skeletal muscle function was measured using nerve stimulus. Gastrocnemius mitochondrial respiratory function and H 2 O 2 production were assessed. Results: Regardless of genotype, mice with CKD had significantly lower renal function. Interestingly, male AHR ecKO mice with CKD displayed a significant increase in percentage of perfused capillaries within the ischemic tibialis anterior muscle (AHR ecKO 73.41% ± 4.80% vs AHR fl/fl 64.75% ± 8.325%; p= 0.0074 ) and improved laser Doppler perfusion recovery in the paw and gastrocnemius muscle compared to male AHR fl/fl mice with CKD. AHR ecKO mice had a larger mean myofiber size ( p=0.0258 ), although muscle weight and contractile function were not different. Mitochondrial respiratory capacity was significantly higher (p=0.0085) in AHR ecKO than AHR fl/fl mice. Conclusion: In mice with CKD, endothelium-specific deletion of the AHR improved blood perfusion and increased myofiber size in the ischemic limb muscle. These changes conferred improvement in muscle mitochondrial function, but not muscle strength. Interestingly, these changes were observed in male, but not female, mice.

Prognostic value of proteinuria monitoring in anti-neutrophil cytoplasmic antibody-associated vasculitis.

To determine the prognostic significance of proteinuria monitoring in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). We retrospectively analyzed the data of kidney biopsy-confirmed patients with AAV. Proteinuria was evaluated by a urine dipstick test. Poor renal outcome was defined as stage 4/5 chronic kidney disease (CKD) (estimated glomerular filtration rate < 30mL/min/1.73 m2). We enrolled 77 patients with a median follow-up duration of 36months (interquartile range, 18-79) in this study. Excluding 8 patients on dialysis at 6months, 59/69 (85.5%) achieved remission after induction therapy. Patients were then divided into two groups according to the presence of proteinuria at 6months after induction therapy (n = 29 with proteinuria, 40 without proteinuria). There was no significant difference in the rate of relapse or death according to the presence of proteinuria (p = 0.304 relapse, 0.401 death). In contrast, patients with proteinuria had significantly lower kidney function than those without proteinuria (41 vs. 53.5mL/min/1.73 m2, p = 0.003). Multivariate analysis revealed that eGFR values at 6months (hazard ratio [HR] 0.925; 95% CI 0.875-0.978, p = 0.006) and proteinuria at 6months (HR 4.613; 95% CI 1.230-17.298, p = 0.023) were significantly associated with stage 4/5 CKD. The presence of proteinuria at 6months after induction therapy and low renal function was significantly associated with a higher risk of stage 4/5 CKD in patients with AAV. Monitoring for proteinuria after induction therapy may help predict poor renal outcomes in patients with AAV.

A253 PRIMARY PROPHYLAXIS FOR SPONTANEOUS BACTERIAL PERITONITIS IN HOSPITALIZED CIRRHOTIC PATIENTS WITH LOW PROTEIN ASCITES AND RENAL DYSFUNCTION OR LIVER FAILURE: A RETROSPECTIVE REVIEW FROM A TERTIARY CENTRE IN BRITISH COLUMBIA

Abstract Background Spontaneous bacterial peritonitis (SBP) is a severe and often fatal infection that can occur in patients with cirrhosis and ascites. The benefits of primary prophylaxis with antibiotics for SBP have been demonstrated in patients with cirrhosis presenting with gastrointestinal (GI) bleeding; patients hospitalized for other reasons with an ascitic protein less than 10 g/L; and patients with ascitic protein less than 15 g/L with either impaired renal function (serum creatinine greater than 106 µmol/L, BUN greater than 8.9 mmol/L, or serum sodium less than or equal to 130 mEq/L) or liver failure (Child-Pugh score greater than or equal to 9 or bilirubin greater than 50 umol/L). Purpose To evaluate the rate of primary prophylaxis in patients discharged from a tertiary care hospital with low protein ascites and impaired renal function or liver failure, and subsequent episodes of SBP, hospitalizations, or deaths. Method A retrospective chart review at St. Paul’s Hospital in Vancouver, British Columbia, from November 2019 to August 2021 was conducted. Hospitalized patients with cirrhosis who had an ascitic protein less than 15 g/L and met criteria for either renal dysfunction or liver failure were included in the study. The rate of primary prophylaxis prescribed in eligible patients as well as the subsequent incidence of SBP, hospitalizations, or all-cause mortality were evaluated. Patients were followed up to 12 months after the index paracentesis. Result(s) A total of 279 patients with cirrhosis were hospitalized during the study period. 69 patients underwent a diagnostic paracentesis and 41 patients met the inclusion criteria for primary SBP prophylaxis. 28 patients were excluded with most common reasons being ascitic protein above 15 g/L (n=12), no documented ascitic protein concentration (n=9), or index paracentesis met the criteria for the diagnosis of SBP (n=5). Of the patients included, 37 (90.2%) did not receive primary prophylaxis. 8 of these patients (21.6%) developed subsequent SBP. 30 patients (81.1%) were hospitalized at least once in the following 12 months. 18 (48.6%) died during the follow-up period with 1 death attributed to SBP. 4 patients (9.76%) received primary prophylaxis and were prescribed either ciprofloxacin or trimethoprim/sulfamethoxazole. None of these patients developed SBP, however, 3 (75%) were hospitalized and died from other causes. Conclusion(s) The rate of primary prophylaxis for SBP in hospitalized patients with low protein ascites and impaired renal function or liver failure at our institution is low. The guarded prognosis in this subset of patients is also demonstrated. Further studies are needed to assess the root causes for the lack of primary prophylaxis given. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Impact of different automated peritoneal dialysis modalities on the inflammatory profile of elderly patients with chronic kidney disease.

Chronic kidney disease, more prevalent in the elderly, is considered a public health issue worldwide. To evaluate the impact of automated, peritoneal dialysis modalities, intermittent and continuous, on the inflammatory profile of elderly people with chronic kidney disease. Prospective, cross-sectional and analytical study carried out in a dialysis clinic in Brasília - Brazil, with 74 elderly people aged 60 years or older. The patients underwent rapid Peritoneal Equilibration Test, clinical assessment, blood collection for biochemical and cytokine assessments, interleukin 6 and transforming growth factor beta 1, and answered a quality-of-life questionnaire (KDQOL-SF36). We used a 5% significance level for data analysis, associations and correlations. Patients in the continuous modality had higher serum values of transforming growth factor beta 1 than those in the intermittent modality, which had higher peritoneal transforming growth factor beta 1, age and residual renal function than those in continuous mode. Interleukin 6 dosage in the peritoneum was associated with age, while serum IL-6 was associated with IL-6 in the peritoneum, time on dialysis and age. There was no association between the modality and the presence of diabetes, blood volume or nutritional status. Both modalities enable good adaptation to the dialysis treatment. Inflammation in automated peritoneal dialysis is mainly associated with low residual renal function, advanced age and longer time on therapy, and not to the type of dialysis performed.

A Retrospective Analysis of Risk Factors and Impact of Acute Kidney Injury in Critically Ill Children.

Acute kidney injury (AKI) is a serious clinical condition in critically ill children and is associated with worse outcomes. A few pediatric studies focused on the risk factors of AKI. We aimed to identify the incidence, risk factors, and outcomes of AKI in the pediatric intensive care unit (PICU). All the patients admitted to PICU over a period of 20 months were included. We compared both groups the risk factors between AKI and non-AKI. A total of 63 patients (17.5%) of the 360 patients developed AKI during PICU stay. The presence of comorbidity, diagnosis of sepsis, increased PRISM III score, and positive renal angina index were found to be risk factors for AKI on admission. Thrombocytopenia, multiple organ failure syndrome, the requirement of mechanical ventilation, use of inotropic drugs, intravenous iodinated contrast media, and exposure to an increased number of nephrotoxic drugs were independent risk factors during the hospital stay. The patients with AKI had a lower renal function on discharge and had worse overall survival. AKI is prevalent and multifactorial in critically sick children. The risk factors of AKI may be present on admission and during the hospital stay. AKI is related to prolonged mechanical ventilation days, longer PICU stays, and a higher mortality rate. Based on the presented results early prediction of AKI and consequent modification of nephrotoxic medication may generate positive effects on the outcome of critically ill children.

Relationship between Cytomegalovirus Viremia and Long-Term Outcomes in Kidney Transplant Recipients with Different Donor Ages.

To explore the Cytomegalovirus (CMV) burden on the long-term post-transplant course in different donor ages, we evaluated the incidence and risk factors for CMV in our kidney-transplanted patients (KTs) with extensive adoption of expanded-criteria donors (ECDs). Retrospective evaluation of 929 consecutive first KTs (49.5% receiving an organ from a donor ≥ 60 years) performed between 01-2003 and 12-2013. Overall survival was estimated using Kaplan-Meier curves; cumulative incidence function was additionally analyzed to consider the potential role of death with a functioning graft as a competitive event with graft dysfunction and to avoid overestimation. Apart from regular DNAemia monitoring in all patients, prophylaxis was adopted in high-risk groups (D+/R- or recipients of anti-thymocyte globulin induction), with pre-emptive therapy in the remaining groups. CMV incidence was 19.5% (4-34.9% according to serostatus combination: D-/R-, D-/R+, D+/R+, D+/R-). Donor and recipient age, recipient pre-transplant hypertension, DR antigen compatibility, cold ischemia time, and post-transplant early complications, including rejection, urologic and renal artery stenosis, and lower renal function and proteinuria ≥ 0.5 g/day at one year after KT were associated with CMV. CMV determined lower death-censored graft survival (DCGS) (p < 0.01), with a prominent effect in R+ (p < 0.01) and without impact in R- (p = 0.32 in D-/R- and p = 0.006 in D+/R-). Interestingly, CMV occurrence influenced DCGS only in KTs who received grafts from donors < 50 or 50-69 years old (p < 0.01), while it was not significant with older donors (p = 0.07). The analysis of the cumulative incidence of graft loss accounting for death as a competing risk confirmed all these findings. In multivariate analysis, CMV replication/disease in the first year was an independent predictor for DCGS (HR 1.73 [1.3-2.3]). In a large population with extensive ECD adoption, CMV viremia in the first year demonstrates its harmful effect with an independent role for graft loss and significant impact among R+ recipients and KTs with donors < 70 years.

Association between Bone Mineral Density and Oral Frailty on Renal Function: Findings from the Shika Study.

The association between oral frailty (OFr) and body action has been investigated, but its association with systemic function remains unclear. Therefore, this cross-sectional study examined the association between OFr with decreased bone mineral density (BMD) and renal function in residents of Shika town, Ishikawa Prefecture, Japan aged ≥40 years. This study included 400 inhabitants. The OFr total score was assessed using three oral domains in the Kihon Checklist (a self-reported comprehensive health checklist), the number of teeth, and brushing frequency per day. Measurements were the estimated glomerular filtration rate (eGFR) and the osteo-sono assessment index (OSI). Using a two-way analysis of covariance (p = 0.002), significantly lower OSI was indicated in the eGFR < 60 and OFr group than in the eGFR of < 60 and non-OFr group after adjusting for age, body mass index, and drinking and smoking status as confounding factors. Multiple logistic regression analysis confirmed this relationship (p = 0.006). Therefore, lower BMD seems to be associated with lower renal function only when accompanied by OFr. Further longitudinal studies are needed to confirm these results.

High Mean Platelet Volume Is Associated with Cerebral White Matter Hyperintensities in Non-Stroke Individuals

The mean platelet volume (MPV) is regarded as a marker for thrombosis, atherosclerosis, and inflammation in various vascular diseases. However, it still remains unclear whether plasma MPV is associated with cerebral white matter hyperintensities (WMH) and cerebral microvascular pathology in the elderly population. We examined whether MPV level is associated with the presence of cerebral WMH on brain magnetic resonance imaging from 870 non-stroke outpatient subjects. The subjects were divided into three groups according to the consecutive level of MPV (low T1, middle T2, and high T3 MPV tertile groups). To determine the association of MPV levels with the WMH, logistic regression and receiver operating characteristic curve analyses were conducted. Subjects with higher MPV level were older and more likely to have hypertension, diabetes mellitus, and low renal function. Cerebral WMH were more prevalent in subjects with higher MPV level. After adjusting for confounding factors, moderate to severe cerebral WMH were significantly associated with high MPV tertile level. This association remained significant after adjusting for other cerebral vascular pathologies. T2 [odds ratio (OR): 1.49, 95% confidence interval (CI): 1.03-2.15] and T3 MPV tertile groups (OR: 1.51, 95%CI: 1.04-2.20) had more cerebral WMH lesions compared to T1 MPV tertile group. In addition, the subjects with higher Fazekas scores showed higher MPV level (p=0.020). We found that high MPV level is independently associated with cerebral WMH. This result suggests that platelet activation plays a role in the development of cerebral WMH.

Investigation of Prescription Status and Exploration of Risk Factors Related to Denosumab-Induced Hypocalcemia in Combination Therapy with 1α,25-Dihydroxy-vitamin D3.

To prevent denosumab-induced hypocalcemia in patients with renal dysfunction, combination therapy with 1α,25-dihydroxy-vitamin D3 (active vitamin D) is recommended. We previously developed a risk prediction model for hypocalcemia in patients with cholecalciferol/calcium (natural vitamin D). However, the prescription status and the risk factors of patients with active vitamin D have not been identified, so we designed this retrospective observational study using a large practice database covering June 2013 to May 2020 to analyze prescription status and risk factors. Patients were classified according to vitamin D type. After that, factors associated with development of hypocalcemia in patients with active vitamin D were explored. Univariate analysis was conducted to compare patient backgrounds between the hypocalcemia and non-hypocalcemia groups. Receiver operating characteristic analysis was conducted to evaluate the predictive potential of the extracted factors. Of the 33442 patients who received denosumab, 22347 and 3560 patients were co-administered natural and active vitamin D, respectively. Patients with active vitamin D had significantly lower renal function (estimated glomerular filtration rate (eGFR) median: 74.0 vs. 69.7 mL/min/1.73 m2), but some patients (23.6%) with sufficient renal function (eGFR ≥90) were also receiving active vitamin D. Of the 3560 patients with active vitamin D, non-hypocalcemia (n = 166) and hypocalcemia (n = 17) groups who met the study criteria were analyzed. Renal function was lower in the hypocalcemia group, and alkaline phosphatase gave the best discrimination. High aspartate aminotransferase (AST), renal dysfunction, high alkaline phosphatase (ALP), and low hemoglobin may be significant factors in risk prediction for hypocalcemia in patients with active vitamin D.

Elevated serum leptin levels are associated with lower renal function among middle-aged and elderly adults in Taiwan, a community-based, cross-sectional study.

Plasma leptin is considered a risk factor for obesity and cardio-metabolic disease, but the link between serum leptin and renal function is still under evaluation. In our study, we focused on the relationship between serum leptin and renal function, and we investigated the relationship in more detail. The 396 middle-aged and elderly Taiwanese adults recruited for our health survey were the subject of our research. All participants agreed to participate and signed a consent form before they joined and completed our study. We divided the participants into three groups according to eGFR tertiles and analyzed the parameters between each group. Then, we used Pearson's correlation test to investigate the relationship between eGFR levels and cardio-metabolic risk factors with adjustment for age. The scatter plot indicates the trend between serum leptin levels and eGFR levels. Participants were reclassified into three subgroups according to their leptin levels and the bar chart reveals the prevalence of chronic kidney disease (CKD) in each group. Finally, we used multivariate linear regression to evaluate the relationship between serum leptin and eGFR levels with adjustment for age, sex, smoking status, drinking status, body mass index (BMI), uric acid levels, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia. In our study, we analyzed the data from 396 eligible participants. A total of 41.4% of the participants were male, and the average age of all participants was 64.81 years ( ± 8.78). The participants in the high eGFR group were more likely to have lower serum leptin levels. Furthermore, eGFR values were negatively correlated with serum leptin levels even after adjustment for age. The prevalence of CKD in the high serum leptin group was higher than that in the low serum leptin group. Serum leptin levels showed significant negative correlations with eGFR levels (β=-0.14, p<0.01) in the multivariate linear regression after adjusting for age, sex, smoking status, drinking status, BMI, uric acid levels, HTN, DM, and dyslipidemia. According to our study, serum leptin levels show a negative relationship with eGFR levels in middle-aged and elderly people in Taiwan. In addition, high serum leptin levels could be an novel marker to survey kidney failure in clinical practices.

The Prognostic Value of B-Type Natriuretic Peptide in Patients With Cardiac Sarcoidosis Without Heart Failure: Insights From ILLUMINATE-CS.

Background The prognostic role of BNP (B-type natriuretic peptide) in patients with cardiac sarcoidosis without evident heart failure is unknown. Methods and Results This is a post hoc analysis of ILLUMINATE-CS (Illustration of the Management and Prognosis of Japanese Patients With Cardiac Sarcoidosis), a multicenter, retrospective, and observational study that evaluated the clinical characteristics and prognosis of cardiac sarcoidosis. We analyzed patients with cardiac sarcoidosis without evident heart failure at the time of diagnosis. The association between baseline BNP levels and prognosis was investigated. The primary end point was the combined end point of all-cause death, heart failure hospitalization, and fatal ventricular arrhythmia. In total, 238 patients (61.0±11.1 years, 37% men) were analyzed, and 61 primary end points were observed during a median follow-up period of 3.0 (interquartile range, 1.7-5.8) years. Patients with high BNP (BNP above the median value of BNP) were older and had a lower renal function and left ventricular ejection fraction than those with low BNP values. Kaplan-Meier curve analysis indicated that high BNP levels were significantly associated with a high incidence of primary end points (log-rank P=0.004), and this association was retained even in multivariable Cox regression (hazard ratio, 2.06 [95% CI, 1.19-3.55]; P=0.010). Log-transformed BNP as a continuous variable was associated with the primary end point (hazard ratio, 2.12 [95% CI, 1.31-3.43]; P=0.002). Conclusions High baseline BNP level was an independent predictor of future adverse events in patients with cardiac sarcoidosis without heart failure at the time of diagnosis. Registration URL: https://www.umin.ac.jp/english/; Unique Identifier: UMIN-CTR: UMIN000034974.

Severe hypercholesterolemia in a patient with very low albumin and normal renal function

A 20-year-old male presented with severe elevation in low-density lipoprotein cholesterol (LDL-C). Initial genetic testing for familial hypercholesterolemia was negative. Patient also had low albumin, and further genetic testing showed homozygous variants in the ALB gene, suggesting congenital analbuminemia (CAA) causing severe hyperlipidemia. CAA is an autosomal recessive disorder with incidence of about 1:1,000,000. The gene for albumin is a single autosomal gene, and pathological variants that affect splicing lead to premature stop, nonsense variants, and deletions that result in a defect in albumin synthesis with CAA. CAA can be fatal in the prenatal period and cause infections in early childhood. CAA is tolerated better in adulthood because of compensatory increase in other plasma proteins. Plasma lipoproteins also increase, and CAA can cause gross hyperlipidemia with severe elevations in LDL-C and hypercholesterolemia. Genetic examination of ALB is mandatory to establish the diagnosis. Early diagnosis may be important to initiate lipid-lowering treatments to avoid premature coronary artery disease.

Abstract 11642: Biologic Associations of the Senescence-Associated Secretory Phenotype (SASP) in Heart Failure (HF): Insights From Plasma Proteomics

Background: Cell senescence is involved in various age-related pathologies, including HF. The SASP is a characteristic secretory phenotype from senescent cells. We assessed biologic pathways associated with the SASP in human HF using a plasma proteomics approach. Methods: We measured 25 known SASP proteins among 2248 Penn HF Study (PHFS) participants using the SomaScan V4 assay. Factor analysis was used to extract the common variance among these proteins. Linear regression was used to assess the relationship of each factor to 4,746 other proteins, correcting for multiple comparisons, followed by pathway analyses. Results: Two underlying SASP factors were identified: Factor 1 was mainly represented by with matrix metallopeptidase 2, Tissue inhibitor of metalloproteinase 2 and Insulin Like Growth Factor Binding Protein 7. Factor 2 was correlated with cystatin C, Growth/differentiation factor-15 and Insulin-like Growth Factor Binding Protein-2. Both factors were associated with older age, male sex, lower BMI, higher prevalence of diabetes, higher prevalence of atrial fibrillation, lower estimated glomerular filtration rate and more advanced NYHA class. There was a lower prevalence of HF with recovered EF (as opposed to HF with reduced EF) among participants with higher levels of factor 1, but the prevalence of HF with preserved EF did not differ accordingly to levels of either factor. Factors 1 and 2 were associated with 1245 and 1509 proteins respectively. Both factors were associated with the coagulation system, complement system, acute phase response signaling, and retinoid X receptor (RXR) pathways that regulate cell metabolism ( Figure ). Conclusion: Higher levels of SASP are associated with older age, lower renal function and metabolic abnormalities in HF. Lower levels of SASP are associated with the presence of a recovered EF but not a preserved EF. Biologic pathways associated with SASP are predominantly related to inflammation and metabolic regulation.

Early Invasive Strategy and Outcome ofNon-ST-Segment Elevation MyocardialInfarction Patients WithChronicKidney Disease.

Current guidelines suggest that an early invasive strategy should be considered for the treatment of non-ST-segment elevation myocardial infarction (NSTEMI). Although chronic kidney disease (CKD) is common among NSTEMI patients, these patients are under-represented in clinical trials, and data regarding their management are limited. The authors sought to evaluate the association between early invasive strategy and long-term survival among patients with NSTEMI and CKD. This was a retrospective analysis of 7,107 consecutive NSTEMI patients between 2008 and 2021. Patients were dichotomized into early (≤24 hours) and delayed invasive groups and stratified by kidney function. Inverse probability treatment weighting was used to adjust for differences in baseline characteristics. The primary outcome wasall-cause mortality. The final study population comprised 3,529 invasively treated patients with a median age of 66 years (IQR:58-74 years), 1,837 (52%) of whom were treated early. There were 483 (14%) patients with at least moderate CKD(estimated glomerular filtration rate [eGFR]<45mL/min/1.73m2). During a median follow-up of 4 years (IQR: 2-6years), 527 (15%) patients died. After inverse probability treatment weighting, an early invasive strategy was associated with a significant 30% lower mortality compared with a delayed strategy (HR: 0.7; 95%CI: 0.56-0.85). The association between early invasive strategy and mortality was modified by eGFR (Pinteraction< 0.001) and declined with lower renal function, with no difference in mortality among patients with eGFR<45 mL/min/1.73m2 (HR: 0.89; 95%CI: 0.64-1.24). Among NSTEMI patients, the association of early invasive strategy with long-term survival is modified by CKD and was not observed in patients with eGFR<45mL/min/1.73m2.

Efficacy of Yishen Huashi Granules Combined with Linagliptin Tablets on Blood Glucose and Renal Function in Patients with Type 2 Diabetic Nephropathy

Objective To probe into the efficacy of Yishen Huashi granules combined with linagliptin tablets in the treatment of type 2 diabetic nephropathy (DN) and its effect on blood glucose and renal function in patients. Methods 70 patients with type 2 DN at our hospital between May 2020 and May 2022 were chosen as the research objects and separated into the control group and the research group based on their treatments. With 35 cases in each group, the patients treated with initial therapy and linagliptin tablets were enrolled in the control group, and those who received the above treatments and also Yishen Huashi granules were included in the research group. Their clinical indexes such as blood glucose and renal function were compared with both groups after treatment. Results After treatment, the research group had remarkably lower fasting blood glucose (FPG), 2 h-postprandial blood glucose (2 h-PBG), and glycosylated hemoglobin A1c (HbA1c) levels than those in the control group (P < 0.05). After treatment, the research group had remarkably lower levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) (P < 0.05) and higher high-density lipoprotein (HDL) levels (P < 0.05) than those in the control group. After treatment, the urinary microalbumin (u-mALB) level was remarkably lower in both groups (P < 0.05) and was distinctly lower in the research group than in the control group (P < 0.05). After treatment, the research group had remarkably lower renal function indexes such as serum creatinine (SCr), blood urea nitrogen (BUN), urinary protein (UPro), and urinary albumin excretion rate (UAER) (P < 0.05) and a higher estimated glomerular filtration rate (eGFR) level (P < 0.05) than those in the control group. The efficacy was evaluated by the traditional Chinese medicine (TCM) syndrome score after treatment. There were no patients in complete remission between both the groups, where slight differences were found in the proportion of significant remission (P > 0.05), with the total effective rate of the research group remarkably higher than that of the control group (P < 0.05). Conclusion The combination of Yishen Huashi granules and linagliptin tablets can reduce the blood glucose and blood lipid levels in patients with type 2 DN and lower UPro and protect renal function at the same time, which provides a new idea and a method for clinical treatment of type 2 DN with integrated traditional Chinese and Western medicine.

313.2: Higher Tomographic Abdominal Fat Volume Is Associated With Lower Renal Function Before and Long-term After Living Kidney Donation

313.2: Higher Tomographic Abdominal Fat Volume Is Associated With Lower Renal Function Before and Long-term After Living Kidney Donation

Appropriateness of Non-vitamin K Antagonist Oral Anticoagulants Dosing According to Different Prescription Guides Used in Belgian Ambulatory Care.

BackgroundNon-vitamin K antagonist oral anticoagulants (NOACs) are the preferred choice of anticoagulants to prevent stroke in most patients with atrial fibrillation (AF). NOAC's dosing algorithms are defined in the respective Summary of Product Characteristics (SmPC) but the European Heart Rhythm Association (EHRA) Practical Guide can also be used as it considers more complex clinical scenarios. Nevertheless, suboptimal dosing of NOACs compromises the efficacy and safety of this commonly prescribed therapy in the AF population. Clearer objectification of inappropriate dosing and its influencing factors is needed to optimise management of AF patients.ObjectivesThe primary aim of this study was to investigate whether there is a difference in the perceived appropriateness of NOAC dosing with respect to the SmPC or the 2018 EHRA Practical Guide in AF patients criteria and influencing factors. The secondary aim was to explore if there were differences in appropriateness of NOAC dosing between primary care and specialist care, and when using different renal function formulas.MethodsThis retrospective study included AF patients treated with a NOAC in primary or in ambulatory specialist care in Antwerp (Belgium). Appropriateness of the NOAC dose was assessed according to the SmPC and 2018 EHRA recommendations. Univariate/multivariate analyses were performed to explore influencing factors for under- and overdosing of NOACs.ResultsOf the included 294 AF patients, 19.4% and 15.6% received an inappropriate dose according to the SmPC and the 2018 EHRA Practical Guide respectively (p = 0.003). Perceived frailty and higher weight were associated with underdosing relative to the SmPC, while a higher body mass index and the use of drugs/alcohol were associated with underdosing relative to the EHRA 2018 recommendations. Lower renal function and treatment with other NOACs than apixaban were associated with relative overdosing compared to both standards.ConclusionsInappropriate NOAC dosing is present in almost twenty percent of AF patients according to the SmPC and requires further education of health care professionals and frequent reassessment of NOAC dosing. However, a significant lower prevalence of underdosing was present when judged by the 2018 EHRA criteria, likely reflecting decision making in complex AF patients. Perceived frailty, weight, renal function and type of NOAC are the main determinants of deviated dosing.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40261-022-01190-2.