Independent Risk Factor For Decline Research Articles

#2293 Cardiac autonomic neuropathy: an independent risk factor for renal decline in diabetic kidney disease

Abstract Background and Aims Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and end stage kidney disease (ESKD) in the UK and worldwide. Due to its unpredictability and incurable nature, novel risk factors associated with incidence and progression of DKD need to be identified. One such factor is cardiac autonomic neuropathy (CAN). Many studies over last 30 years had demonstrated a significant relationship between CAN and incidence and progression of DKD using estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR) as end points. However, no prospective studies have looked into relationship between CAN diagnosed by gold standard cardiac autonomic reflex tests (CARTs) and DKD with different prognostic risks as per KDIGO classification. The aim of the study is to examine this relationship further. Method Data from 91 participants (type 1 and type 2 DM) with eGFR >30 ml/min/1.73 m2 who underwent assessment for CAN using CARTs as per O'Brien's and Ewing's criteria during baseline visits performed between 2007 and 2010 were collected. Additional participants (n = 113) were also recruited in 2021 as part of iBEAt study which is an EU-funded, multi-centre renal imaging study to identify novel biomarkers for DKD. Data analysis for 204 participants in total was performed for this study. CAN was defined as 2 or more abnormal CARTs out of 5 (Table 1). The level of prognostic risk was calculated based on eGFR (G1-G5) and UACR (A1-A3), following KDIGO risk table from 2012 CKD guidelines. eGFR was calculated by chronic kidney disease epidemiology collaboration (CKD-EPI) equation and UACR was assessed by early morning urine sample. Participants were categorised as follow: low risk, moderate risk and high risk. Due to limited numbers of participants with G3 in eGFR, we have combined ‘high risk’ and ‘very high risk’ into one group. CAN was divided into 2 groups—with and without CAN. Differences in proportions were examined using chi-square test. The association between baseline CAN and risk of renal decline was assessed using multinominal logistic regression adjusted for baseline age, HbA1c, ACEi/ARBs use, retinopathy status, total cholesterol and triglyceride. If significant differences were found, individual groups were compared by Bonferroni post hoc test. All analyses were performed in SPSS (version 29.0) and correlations were considered significant if p < 0.05. Results We analysed data of 204 participants (130 T1DM, 74 T2DM), 44.6% (n = 91) of them were women, mean (SD) age at baseline visit was 51 (15.7) years, eGFR 82.6 (13) ml/min/1.73 m2, UACR 5.2 (21.8) mg/mmol, duration of diabetes at baseline 19.7 (12.3) years and 36.8% had hypertension. Baseline eGFR and UACR were available for 198 and 193 participants respectively. Of these, 42.9% (85/198) had G1, 47.5 (94/198) had G2 and 9.6 (19/198) had G3. For UACR, 80.8% (156/193) had A1, 15.5% (30/193) had A2 and 3.6% (7/193) had A3. 53.4% (103/204) of participants had CAN and 46.6% (101/204) had no CAN. A higher proportion of participants was in low prognostic risk category 77.8% (154/198), followed by 13.1% (26/198) with moderate risk and 9.8% (18/198) with high risk for CKD progression. The risk of DKD progression was significantly associated with presence of CAN in multinominal logistic regression analysis (p = 0.020). The presence of CAN was closely related to low risk (95% CI: 1.44 to 22.04, p = 0.013) and moderately increased risk (95% CI: 1.03 to 24.7, p = 0.04). The participants with moderate and high risk had lower eGFR (p < 0.001) and higher UACR with increased risk (p < 0.001) (Table 2). This finding was independent of baseline age, HbA1C, retinopathy, ACEI/ARB use, type of diabetes, cholesterol and triglyceride levels at baseline as measured by logistic regression. Conclusion To our knowledge, this is one of the first studies to examine the relationship between presence of CAN in three stages of prognostic risk in DKD. We demonstrated that presence of CAN was an independent risk factor for decline in renal function in DKD. Further large prospective studies are required to confirm the findings of this study and examine the underlying mechanisms how CAN leads to greater risk of DKD.

Executive Summary of Evidence and Consensus-Based Clinical Practice Guidelines for Management of Obesity and Overweight in Midlife Women: An AIIMS-DST Initiative.

Weight gain is an independent risk factor for decline in cardiometabolic and overall health-related quality of life in midlife women. The AIIMS-DST initiative aims to develop and validate stepwise recommendations specific for weight management in midlife women. The key clinical questions specific to weight management in midlife women were finalized with the help of a multidisciplinary team of experts in the guideline development group. Phase I including a systematic and/or narrative review, grading of evidence, and expert opinion was sought to develop clinical practice recommendations for each clinical question. Phase II focused on validation of clinical practice recommendations using the peer-review, Delphi method, and GRADE approach. The guidelines provide clinical practice points to address challenges encountered by midlife women in their attempts to manage obesity via lifestyle modification techniques. The initiation of discussion would help the health-care provider to identify the weight management needs of the women, educate women on different modalities of weight management, and empower them to incorporate corrective lifestyle behaviors. Before initiating the management, a comprehensive assessment of clinical and lifestyle-related parameters should be completed. A personalized behavioral lifestyle modification program addressing the midlife-specific barriers for optimal metabolic, musculoskeletal, and mental health should be planned. A consistent follow-up is required for maintenance of corrective eating and activity habits by addressing midlife-specific barriers for sustenance of healthy weight. These recommendations will be useful in opportunistic screening and management of obesity in midlife women across health-care settings.

Red blood cell distribution width predicts residual renal function decline in patients undergoing continuous ambulatory peritoneal dialysis.

To investigate the relationship between red blood cell distribution width (RDW) and residual renal function (RRF) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Seventy-seven CAPD patients were enrolled in this study. According to receiver operator characteristic (ROC) curve analysis, patients were divided into high RDW (RDW > 14.95%) and low RDW (RDW ≤ 14.95%) groups. The data of baseline clinical, biochemical parameters, comorbidities, medication status, peritoneal function, and dialysis adequacy were compared. Survival curves were calculated using Kaplan-Meier method. Cox regression model was employed to analyze risk factors of decline in RRF. The overall median survival time was 24 months, the median survival time of high RDW group (46 patients) and low RDW group (31 patients) were 24 and 12 months, respectively. Compared with the low RDW group, patients in the high RDW group were older, higher rate of decline RRF and white blood cells count as well as lower total Kt/V (all p < 0.05). Kaplan-Meier survival curves showed that the low RDW group had higher survival of RRF compared with the high RDW group (p < 0.001). Multivariate Cox regression analysis showed that high RDW was independent risk factor for decline of RRF(hazard ratio=1.441, 95% confidence interval: 1.089-1.905, p=0.01). Increased baseline RDW is associated with decline of RRF in CAPD patients and RDW can be stratified as a valuable indicator for the risk of RRF decline.

Atrial Fibrillation and Longitudinal Change in Cognitive Function in CKD

BackgroundStudies in the general population suggest that atrial fibrillation (AF) is an independent risk factor for decline in cognitive function, but this relationship has not been examined in adults with chronic kidney disease (CKD). We investigated the association between incident AF and changes in cognitive function over time in this population.Methods and ResultsWe studied a subgroup of 3254 adults participating in the Chronic Renal Insufficiency Cohort Study. Incident AF was ascertained by 12-lead electrocardiogram (ECG) obtained at a study visit and/or identification of a hospitalization with AF during follow-up. Cognitive function was assessed biennially using the Modified Mini-Mental State Exam. Linear mixed effects regression was used to evaluate the association between incident AF and longitudinal change in cognitive function. Compared with individuals without incident AF (n = 3158), those with incident AF (n = 96) were older, had a higher prevalence of cardiovascular disease and hypertension, and lower estimated glomerular filtration rate. After median follow-up of 6.8 years, we observed no significant multivariable association between incident AF and change in cognitive function test score.ConclusionIn this cohort of adults with CKD, incident AF was not associated with a decline in cognitive function.

Uric Acid Is an Independent Risk Factor for Decline in Kidney Function, Cardiovascular Events, and Mortality in Patients With Type 1 Diabetes.

Previous studies have provided inconclusive results on the role of uric acid (UA) in risk prediction. Here we aimed to improve the power and precision of the predictive value of UA for the risk of decline in kidney function, cardiovascular events (CVEs), and mortality in patients with type 1 diabetes (T1D). Plasma UA was measured in 670 patients with T1D and various degrees of albuminuria, ranging from normoalbuminuria to macroalbuminuria. Associations of UA with an estimated glomerular filtration rate (eGFR) decline of ≥30%, CVEs, and mortality were analyzed. The median follow-up time was 5.3 years [interquartile range (IQR) 2.7-6.2 years] for a decline in eGFR of ≥30%, 5.8 years (2.5-6.4 years) for progression in albuminuria status, 5.1 years (4.7-5.6 years) for CVE, and 6.2 years (5.8-6.7 years) for mortality. Both univariable and multivariable associations of UA with relevant outcomes and variables were reported. Hazard ratios (HRs) were calculated per doubling of the UA level. A doubling in UA level was associated with a higher risk of decline in eGFR of ≥30% (n = 89) (HR 3.18 [IQR 1.71-5.93]; P < 0.001), CVE (n = 94) (HR 2.25 [IQR 1.20-4.21]; P = 0.011), and mortality (n = 58) (HR 2.58 [IQR 1.12-5.90]; P = 0.025) in adjusted analyses. Adding UA to the adjusted model including conventional risk factors improved the relative integrated discrimination index by 12.6% for a decline in eGFR of ≥30% (P < 0.001), 6.5% for CVE (P = 0.010), and 11.8% (P = 0.003) for mortality. A doubling in UA level was also associated with a steeper decline in eGFR (P < 0.0026) and a steeper increase in urine albumin-to-creatinine ratio (P < 0.0027) in adjusted analysis. In individuals with T1D, a higher UA level is associated with a higher risk of decline in kidney function, CVE, and mortality, independently of other risk factors. Our results suggest that UA has a promising role in risk stratification among individuals with T1D.

Urinary tubular biomarkers as predictors of kidney function decline, cardiovascular events and mortality in microalbuminuric type 2 diabetic patients.

Urinary levels of kidney injury molecule 1 (u-KIM-1) and neutrophil gelatinase-associated lipocalin (u-NGAL) reflect proximal tubular pathophysiology and have been proposed as risk markers for development of complications in patients with type 2 diabetes (T2D). We clarify the predictive value of u-KIM-1 and u-NGAL for decline in eGFR, cardiovascular events (CVE) and all-cause mortality in patients with T2D and persistent microalbuminuria without clinical cardiovascular disease. This is a prospective study that included 200 patients. u-KIM-1 and u-NGAL were measured at baseline and were available in 192 patients. Endpoints comprised: decline in eGFR > 30%, a composite of fatal and nonfatal CVE consisting of: cardiovascular mortality, myocardial infarction, stroke, ischemic heart disease and heart failure based on national hospital discharge registries, and all-cause mortality. Adjusted Cox models included traditional risk factors, including eGFR. Hazard ratios (HR) are provided per 1 standard deviation (SD) increment of log2-transformed values. Relative integrated discrimination improvement (rIDI) was calculated. During the 6.1years' follow-up, higher u-KIM-1 was a predictor of eGFR decline (n = 29), CVE (n = 34) and all-cause mortality (n = 29) in adjusted models: HR (95% CI) 1.68 (1.04-2.71), p = 0.034; 2.26 (1.24-4.15), p = 0.008; and 1.52 (1.00-2.31), p = 0.049. u-KIM-1 contributed significantly to risk prediction for all-cause mortality evaluated by rIDI (63.1%, p = 0.001). u-NGAL was not a predictor of any of the outcomes after adjustment. In patients with T2D and persistent microalbuminuria, u-KIM-1, but not u-NGAL, was an independent risk factor for decline in eGFR, CVE and all-cause mortality, and contributed significant discrimination for all-cause mortality, beyond traditional risk factors.

Retrospective study of long-term outcomes of enzyme replacement therapy in Fabry disease: Analysis of prognostic factors.

Despite enzyme replacement therapy, disease progression is observed in patients with Fabry disease. Identification of factors that predict disease progression is needed to refine guidelines on initiation and cessation of enzyme replacement therapy. To study the association of potential biochemical and clinical prognostic factors with the disease course (clinical events, progression of cardiac and renal disease) we retrospectively evaluated 293 treated patients from three international centers of excellence. As expected, age, sex and phenotype were important predictors of event rate. Clinical events before enzyme replacement therapy, cardiac mass and eGFR at baseline predicted an increased event rate. eGFR was the most important predictor: hazard ratios increased from 2 at eGFR <90 ml/min/1.73m2 to 4 at eGFR <30, compared to patients with an eGFR >90. In addition, men with classical disease and a baseline eGFR <60 ml/min/1.73m2 had a faster yearly decline (-2.0 ml/min/1.73m2) than those with a baseline eGFR of >60. Proteinuria was a further independent risk factor for decline in eGFR. Increased cardiac mass at baseline was associated with the most robust decrease in cardiac mass during treatment, while presence of cardiac fibrosis predicted a stronger increase in cardiac mass (3.36 gram/m2/year). Of other cardiovascular risk factors, hypertension significantly predicted the risk for clinical events. In conclusion, besides increasing age, male sex and classical phenotype, faster disease progression while on enzyme replacement therapy is predicted by renal function, proteinuria and to a lesser extent cardiac fibrosis and hypertension.

Influence of Studies Published by the Journal of the American Geriatrics Society: Top 20 Articles from 2000-2015.

Influence of Studies Published by the Journal of the American Geriatrics Society: Top 20 Articles from 2000-2015.

Severity of coronary artery disease is an independent risk factor for decline in kidney function

Background and aimChronic kidney disease (CKD) and cardiovascular disease are closely interrelated and the presence of one condition synergistically affects the prognosis of the other, in a negative manner. There are surprisingly very few data on the relationship between baseline coronary artery disease (CAD) severity and subsequent decline in kidney function. We aimed to evaluate for the first time whether baseline coronary artery lesion severity predicts the decline in kidney function. Materials and methodsThe study population was derived from a series of consecutive patients presenting with stable angina pectoris or angina equivalents, who underwent coronary angiography. SYNTAX score for each patient was calculated to define severity of CAD. Change in kidney function was defined by calculating the rates of change in eGFR. ResultsAmong the 823 patients included in our study, the mean age was 59.2±10.7years, 78.4% were males, and 32% had diabetes. The mean baseline eGFR was 87.3±24.9ml/min/1.73m2 and the median Syntax score was 14 (IQR=10–20). The median length of follow-up was 2.75years (IQR=2.42–3.50). The mean yearly change for eGFR in the entire study population was 4.06 (95% CI: 3.59–4.51)ml/min/1.73m2. A higher Syntax score was associated with a significantly faster decline in eGFR in all (unadjusted and adjusted) models. During the follow-up, 103 patients developed CKD. A higher Syntax score, analyzed both as continuous and categorical variable, was associated with incident CKD in all models. ConclusionWe have demonstrated for the first time that severity of CAD is an independent risk factor for the decline in kidney function. Studies are needed to highlight the potential mechanisms regarding the association between severity of CAD and decline in kidney function.

Male Sexual Function Outcome After Three Laser Prostate Surgical Techniques: A Single Center Perspective

To assess the change and predictors of sexual-related outcomes after laser prostate surgery. This is a longitudinal study of 216 sexually active men who underwent laser prostatectomy between 2005 and 2010. The International Index of Erectile Function-15 questionnaire was used both preoperatively and during the first year of follow-up. Cases with unreliable answers or patients without interested partners were excluded. All relevant data of both groups were depicted and statistically analyzed. We identified 191 patients that met the inclusion criteria, 99 holmium laser enucleation of the prostate, 34 holmium laser ablation, and 58 photoselective vaporization of the prostate (GreenLight-532-mm laser photoselective vaporization of the prostate). There were significant differences among the 3 groups regarding the International Index of Erectile Function-15 direction of change at 1 year, being unchanged in (22.2%, 24.4%, and 29.3%), improved in (60.6%, 29.4%, and 41.4), and declined in (17.2%, 41.2%, and 29.3%) in the 3 groups, respectively (P < .05). After adjusting for clinical and perioperative variables, the independent risk factors for decline in the International Index of Erectile Function score were basal International Index of Erectile Function ≥ 55 and energy to prostate ratio. In holmium laser enucleation of the prostate group, there was significant improvement of the mean overall score, erectile function, desire, and intercourse satisfaction domains (P < .05). In holmium laser ablation and photoselective vaporization of the prostate groups, there were no significant changes between mean preopeative and postoperative scores (P > .05). The incidence of new onset retrograde ejaculation in the holmium laser enucleation of the prostate group was (77.3%) significantly different compared to (31.1%) in the holmium laser ablation group and (33.2%) in photoselective vaporization of the prostate group (P < .05). Laser prostate surgery using more size-related laser energy might have possible negative influence on sexual function. Patients with normal preoperative sexuality are more at risk.

P02-253 - Hippocampal cavities in elderly subjects - prevalence, evolution and impact on cognition

Hippocampal cavities (HcC) are frequent findings in brain MRIs of elderly subjects. The prevalence, evolution and impact on cognitive performance of these cavities are unclear. Our study therefore aims at providing data on prevalence, morphological evolution and clinical significance of HcC. We used a population-based sample of nondemented elderly subjects aged 75–85 and a comparison group with Alzheimer's disease for cross-sectional analysis. All nondemented subjects were included in a prospective study (mean follow-up 3.2 years). HcC numbers and volume were recorded from volumetric T1w MRI scans. Serial MRIs were performed for a subgroup of subjects. Cognitive functions were assessed by SIDAM and CDR. Hippocampal and brain volume, medial temporal lobe atrophy, white matter lesions, ApoE genotype and vascular risk factors were considered as confounders. The prevalence of HcC in our sample was approx. 60% with no differences between cognitive groups. HcC volume was found to be a predictor of short-term episodic memory performance. The effect of HcC volume was non-linear with the highest risk for decrease in short-term memory associated with the smallest HcC volumes. Mean HcC number and volume remained stable during follow-up. However, we provide anectodal evidence for both cases with increase and decrease of HcC volume over time. In conclusion, small HcC may be an independent risk factor for decline in short term episodic memory performance in elderly subjects.

Risk Factors For Rate of Decline in Forced Expiratory Volume in One Second in Children and Adolescents with Cystic Fibrosis

To characterize the rate of decline of forced expiratory volume in 1 second (FEV(1)) in children and adolescents with cystic fibrosis and to identify and compare risk factors associated with FEV(1) decline. The rate of decline in FEV(1)% predicted over 3 to 6 years in 3 different age groups was determined. Risk factors for decline were identified and compared among and within age groups as a function of disease severity with repeated-measures, mixed-model regression. Mean (+/-SD) baseline FEV(1)% predicted was 88.4% +/- 20.5% for 6- to 8-year-olds (n = 1811), 85.3% +/- 20.8% for 9- to 12-year-olds (n = 1696), and 78.4% +/- 22.0% for 13- to 17-year-olds (n = 1359). Decline in FEV(1)% predicted/year was -1.12, -2.39, and -2.34, respectively. High baseline FEV(1) and persistent crackles were significant independent risk factors for decline across all age groups. Female sex, Pseudomonas aeruginosa infection, low weight-for-age, sputum, wheezing, sinusitis, pulmonary exacerbations treated with intravenous antibiotics, elevated liver test results, and pancreatic insufficiency were also identified as independent risk factors in some age groups. This study identifies risk factors for FEV(1) decline in children and adolescents with cystic fibrosis. Clinicians should not be reassured by high lung function, particularly in young children, because this factor, among others, is independently associated with steeper decline in FEV(1).

Anemia and decline in physical performance among older persons

Purpose Anemia is prevalent in old age and is potentially modifiable, but its effects on physical function have not been determined. We examined whether anemia in older persons increases the risk of subsequent decline in physical function, as measured by objective performance-based tests. Methods Participants in this 4-year prospective cohort study included 1146 participants, aged 71 years or older, living in Iowa and Washington counties, Iowa. Anemia was defined according to World Health Organization (WHO) criteria as a hemoglobin concentration below 12 g/dL in women and below 13 g/dL in men. An assessment of standing balance, a timed 2.4-m walk, and a timed test of five chair rises were used to assess physical performance; these were combined into a 0 (poor) to 12 (excellent) summary scale. Results After adjustment for baseline performance score, health status, and demographic characteristics, anemia was associated with greater mean decline in physical performance over 4 years; the adjusted mean decline was 2.3 (95% confidence interval [CI]: 1.7 to 2.8) in subjects with anemia and 1.4 (95% CI: 1.2 to 1.5) in those without anemia ( P = 0.003). The association between anemia and greater physical decline was also present in participants who were free of diseases associated with anemia (cancer, infectious disease, and renal failure), and after adjustment for serum cholesterol, iron, and albumin levels. Persons with borderline anemia, a hemoglobin concentration within 1 g/dL above the WHO criteria, also showed greater mean physical decline (1.8; 95% CI: 1.5 to 2.2) than did those with higher hemoglobin concentrations ( P = 0.02). Conclusion This study suggests that anemia in old age is an independent risk factor for decline in physical performance.