Effects of Hemodialysis Therapy on Sit-to-Walk Characteristics in End Stage Renal Disease Patients

Patients with end stage renal diseases (ESRD) undergoing hemodialysis (HD) have high morbidity and mortality due to multiple causes; one of which is dramatically higher fall rates than the general population. In spite of the multiple efforts aiming to decrease the high mortality and improve quality of life in ESRD patients, limited success has been achieved. If adequate interventions for fall prevention are to be achieved, the functional and mobility mechanisms consistent with falls in this population must be understood. Human movements such as sit-to-walk (STW) tasks are clinically significant, and analysis of these movements provides a meaningful evaluation of postural and locomotor performance in elderly patients with functional limitations indicative of fall risks. In order to assess the effects of HD therapy on fall risks, 22 sessions of both pre- and post-HD measurements were obtained in six ESRD patients utilizing customized inertial measurement units (IMU). IMU signals were denoised using ensemble empirical mode decomposition and Savistky-Golay filtering methods to detect relevant events for identification of STW phases. The results indicated that patients were slower to get out of the chair (as measured by trunk flexion angular accelerations, time to peak trunk flexion, and overall STW completion time) following the dialysis therapy session. STW is a frequent movement in activities of daily living, and HD therapy may influence the postural and locomotor control of these movements. The analysis of STW movement may assist in not only assessing a patient’s physical status, but in identifying HD-related fall risk as well. This preliminary study presents a non-invasive method of kinematic measurement for early detection of increased fall risk in ESRD patients using portable inertial sensors for out-patient monitoring. This can be helpful in understanding the pathogenesis better, and improve awareness in health care providers in targeting interventions to identify individuals at risk for fall

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Regulation of renal 12(S)-hydroxyeicosatetraenoic acid in diabetes by angiotensin AT1 and AT2 receptors

Diabetes is associated with increased production of 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE]. The mechanisms involved in this process remain unclear. We hypothesized that hyperglycemia and angiotensin II (ANG II) regulate renal 12(S)-HETE production via a balance between angiotensin AT1 and AT2 receptors activities. Using a microdialysis technique, renal interstitial fluid (RIF) levels of ANG II and 12(S)-HETE were monitored in normal control and streptozotocin-induced diabetic rats at baseline and then weekly thereafter for 12 wk. In a second group of normal and diabetic rats, 3 wk after development of diabetes, we monitored RIF 12(S)-HETE levels in response to acute AT1 receptor blockade with valsartan or AT2 receptor blockade with PD123319 individually or combined. Two weeks after induction of diabetes there was a 404% increase in ANG II (P < 0.05), a 149% increase in 12S-HETE (P < 0.05), and a 649% increase in urinary albumin excretion (P < 0.05). These levels remained elevated throughout the study. PD123319 given alone had no effect on 12(S)-HETE. Valsartan decreased 12(S)-HETE by 61.6% (P < 0.0001), a response that was abrogated when PD123319 was given with valsartan. These data demonstrate that hyperglycemia increases renal ANG II and 12(S)-HETE levels. The increase in 12(S)-HETE is mediated via AT1 receptor. The attenuation of the effects of AT1 receptor blockade by PD123319 suggests that AT2 receptor contributes to the downregulation of renal 12(S)-HETE production

Acute Kidney Injury: Medical Causes and Pathogenesis

Acute kidney injury (AKI) is a common clinical syndrome characterized by a sudden decline in or loss of kidney function. AKI is not only associated with substantial morbidity and mortality but also with increased risk of chronic kidney disease (CKD). AKI is classically defined and staged based on serum creatinine concentration and urine output rates. The etiology of AKI is conceptually classified into three general categories: prerenal, intrarenal, and postrenal. Although this classification may be useful for establishing a differential diagnosis, AKI has mostly multifactorial, and pathophysiologic features that can be divided into different categories. Acute tubular necrosis, caused by either ischemia or nephrotoxicity, is common in the setting of AKI. The timely and accurate identification of AKI and a better understanding of the pathophysiological mechanisms that cause kidney dysfunction are essential. In this review, we consider various medical causes of AKI and summarize the most recent updates in the pathogenesis of AKI

Optimum Post-Discharge Care of Acute Kidney Injury (AKI) Survivors

Acute kidney injury (AKI) is a serious problem, affecting multiple organs, and is associated with a high mortality. The severe consequences of AKI extend beyond hospital discharge to the outpatient setting. While a plethora of literature exists guiding the management of AKI in the hospital setting, currently, there are no guidelines for the best care of AKI patients post-hospital discharge. In this review, we address the burden of AKI on patients and the importance of optimal coordinated care of these patients post-hospital discharge. We review the care of patients with or without dialysis requirements at the time of discharge and thereafter

Sodium-Glucose Co-Transporter 2 Inhibitors: Mechanism of Action and Efficacy in Non-Diabetic Kidney Disease from Bench to Bed-Side

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are currently available for the management of type 2 diabetes mellitus. SGLT2i acts by inhibiting renal SGLT2, thereby increasing glucosuria and lowering serum glucose. Recent trials are emerging supporting a role for SGLT2i irrespective of the diabetic status pointing towards that SGLT2i have other mechanisms of actions beyond blood sugar control. In this review, we will shed light on the role of this group of medications that act as SGLT2i in non-diabetics focusing on pre-clinical and clinical data highlighting the mechanism of renoprotection and effects of SGLT2i in the non-diabetic kidneys

Association of Intradialytic Hypotension and Ultrafiltration with AKI-D Outcomes in the Outpatient Dialysis Setting

Identifying modifiable predictors of outcomes for cases of acute kidney injury requiring hemodialysis (AKI-D) will allow better care of patients with AKI-D. All patients with AKI-D discharged to University of Virginia (UVA) outpatient HD units between 1 January 2017 to 31 December 2019 (n = 273) were followed- for up to six months. Dialysis-related parameters were measured during the first 4 weeks of outpatient HD to test the hypothesis that modifiable factors during dialysis are associated with AKI-D outcomes of recovery, End Stage Kidney Disease (ESKD), or death. Patients were 42% female, 67% Caucasian, with mean age 62.8 &plusmn; 15.4 years. Median number of dialysis sessions was 11 (6&ndash;15), lasting 3.6 &plusmn; 0.6 h. At 90 days after starting outpatient HD, 45% recovered, 45% were declared ESKD and 9.9% died, with no significant changes noted between three and six months. Patients who recovered, died or were declared ESKD experienced an average of 9, 10 and 16 intradialytic hypotensive (IDH) episodes, respectively. More frequent IDH episodes were associated with increased risk of ESKD (p = 0.01). A one liter increment in net ultrafiltration was associated with 54% increased ratio of ESKD (p = 0.048). Optimizing dialysis prescription to decrease frequency of IDH episodes and minimize UF, and close monitoring of outpatient dialysis for patients with AKI-D, are crucial and may improve outcomes for these patients

SGLT2 inhibitors: Beyond glycemic control

Multiple randomized controlled trials have extensively examined the therapeutic effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors, ushering in a transformative approach to treating individuals with type 2 diabetes mellitus (DM). Notably, emerging reports have drawn attention to the potential positive impacts of SGLT2 inhibitors in nondiabetic patients. In an effort to delve into this phenomenon, a comprehensive systematic literature review spanning PubMed (NLM), Medline (Ovid), and Cochrane Library, covering publications from 2000 to 2024 was undertaken. This systematic review encompassed twenty-six randomized control trials (RCTs) involving 35,317 participants. The findings unveiled a multifaceted role for SGLT2 inhibitors, showcasing their ability to enhance metabolic control and yield cardioprotective effects through a reduction in cardiovascular death (CVD) and hospitalization related to heart failure (HF). Additionally, a renalprotective effect was observed, evidenced by a slowdown in chronic kidney disease (CKD) progression and a decrease in albuminuria. Importantly, these benefits were coupled with an acceptable safety profile. The literature also points to various biological plausibility and underlying mechanistic pathways, offering insights into the association between SGLT2 inhibitors and these positive outcomes in nondiabetic individuals. Current research trends indicate a continual exploration of additional role for SGLT2 inhibitors in. Nevertheless, further research is imperative to fully elucidate the mechanisms and long-term outcomes associated with the nondiabetic use of SGLT2 inhibitors

Association of depression and antidepressant use with mortality in a large cohort of patients with nondialysis-dependent CKD.

Background and objectivesDepression is common and is associated with higher mortality in patients with ESRD or CKD (stage 5). Less information is available on earlier stages of CKD. This study aimed to determine the prevalence of depression and any association with all-cause mortality in patients with varying severity of nondialysis-dependent CKD.Design, setting, participants, &amp; measurementsThis is a retrospective study of a national cohort of 598,153 US veterans with nondialysis-dependent CKD stages 1-5 followed for a median of 4.7 years in the US Department of Veterans Affairs Health System. Diagnosis of depression was established as a result of systematic screening and administration of antidepressants. Association of depression with all-cause mortality overall and stratified by CKD stages were examined with the Kaplan-Meier method and in Cox models.ResultsThere were 179,441 patients (30%) with a diagnosis of depression. Over median follow-up of 4.7 years, depression was associated with significantly higher age-adjusted mortality overall (hazard ratio, 1.55; 95% confidence interval, 1.54-1.57; P&lt;0.001). Sequential adjustments for sociodemographic characteristics and especially for comorbid conditions attenuated this association, which nevertheless remained significant (hazard ratio, 1.25; 95% confidence interval, 1.23-1.26).ConclusionsIn this large cohort of predominantly elderly male patients with CKD, prevalence of depression and antidepressant use is high (30%) and is associated with significantly higher all-cause mortality independent of comorbid conditions