Comparative effectiveness of an individualized model of hemodialysis vs conventional hemodialysis: a study protocol for a multicenter randomized controlled trial (the TwoPlus trial).

BACKGROUND: Most patients starting chronic in-center hemodialysis (HD) receive conventional hemodialysis (CHD) with three sessions per week targeting specific biochemical clearance. Observational studies suggest that patients with residual kidney function can safely be treated with incremental prescriptions of HD, starting with less frequent sessions and later adjusting to thrice-weekly HD. This trial aims to show objectively that clinically matched incremental HD (CMIHD) is non-inferior to CHD in eligible patients. METHODS: An unblinded, parallel-group, randomized controlled trial will be conducted across diverse healthcare systems and dialysis organizations in the USA. Adult patients initiating chronic hemodialysis (HD) at participating centers will be screened. Eligibility criteria include receipt of fewer than 18 treatments of HD and residual kidney function defined as kidney urea clearance ≥3.5 mL/min/1.73 m2 and urine output ≥500 mL/24 h. The 1:1 randomization, stratified by site and dialysis vascular access type, assigns patients to either CMIHD (intervention group) or CHD (control group). The CMIHD group will be treated with twice-weekly HD and adjuvant pharmacologic therapy (i.e., oral loop diuretics, sodium bicarbonate, and potassium binders). The CHD group will receive thrice-weekly HD according to usual care. Throughout the study, patients undergo timed urine collection and fill out questionnaires. CMIHD will progress to thrice-weekly HD based on clinical manifestations or changes in residual kidney function. Caregivers of enrolled patients are invited to complete semi-annual questionnaires. The primary outcome is a composite of patients' all-cause death, hospitalizations, or emergency department visits at 2 years. Secondary outcomes include patient- and caregiver-reported outcomes. We aim to enroll 350 patients, which provides ≥85% power to detect an incidence rate ratio (IRR) of 0.9 between CMIHD and CHD with an IRR non-inferiority of 1.20 (α = 0.025, one-tailed test, 20% dropout rate, average of 2.06 years of HD per patient participant), and 150 caregiver participants (of enrolled patients). DISCUSSION: Our proposal challenges the status quo of HD care delivery. Our overarching hypothesis posits that CMIHD is non-inferior to CHD. If successful, the results will positively impact one of the highest-burdened patient populations and their caregivers. TRIAL REGISTRATION: Clinicaltrials.gov NCT05828823. Registered on 25 April 2023.

Management of Double-Seropositive Anti-Glomerular Basement Membrane and Anti-Neutrophil Cytoplasmic Antibodies with 100% Crescentic Glomerulonephritis and Nephrotic Range Proteinuria in a Young Female.

Nephrotic range proteinuria in the setting of dual-positive anti-glomerular basement membrane (AGBM) and anti-neutrophil cytoplasmic antibodies (ANCAs) is rare. Furthermore, using rituximab as a primary immunosuppressant along with steroids and plasmapheresis has not been widely studied. We present a case of dual AGBM and ANCA with nephrotic range proteinuria in a young female, where rituximab was used as a primary immunosuppressant with partial recovery.

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.

Prevalence of Cognitive Impairment and Relationships with Other Factors in Patients with End Stage Kidney Disease Receiving Hemodialysis.

Despite recommendations, cognitive screening in patients with end stage kidney disease (ESKD) rarely happens, leading to underestimates of cognitive impairment (CI) prevalence and missed opportunities for intervention. We aimed to describe CI prevalence and associated factors in 100 patients receiving in-center hemodialysis aged 50 years and older. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA). Descriptive analysis techniques characterized the sample and estimated mean scores. Non-parametric and parametric tests explored relationships among MoCA scores and other patient factors. Of the 100 patients, 32% had normal cognitive function, 56% mild CI, and 12% moderate CI. Age, income, and education level significantly corelated with cognitive function in our sample. Identifying clinical factors and appropriate follow up for abnormal screening are crucial next steps in managing cognitive impairment in patients with ESKD receiving in-center hemodialysis.

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.

Effectiveness of an Advance Care Planning Intervention in Adults Receiving Dialysis and Their Families: A Cluster Randomized Clinical Trial.

Importance: Evidence of effectiveness of advance care planning (ACP) strategies for patients receiving dialysis and their families is needed. Objectives: To test the effectiveness of an ACP intervention to prepare patients and their surrogates for end-of-life (EOL) decision-making and to improve surrogate bereavement outcomes. Design, Setting, and Participants: This cluster randomized clinical trial, An Effectiveness-Implementation Trial of SPIRIT (Sharing Patients' Illness Representations to Increase Trust) in ESRD, was conducted from December 2017 to March 2023 and included 42 dialysis clinics in 5 US states (Georgia, New Mexico, North Carolina, Pennsylvania, and Virginia) randomized to provide intervention or usual care. Recruitment was from February 15, 2018, to January 31, 2022, and patient-surrogate dyads were followed up for 21 months (until January 17, 2023) or until patient death. Intervention: Each clinic selected 1 or 2 health care workers (eg, nurse practitioner, registered nurse, or social worker) to conduct 45- to 60-minute ACP discussions with dyads in the clinic or remotely. After March 13, 2020 (commencement of the COVID-19 emergency declaration), all discussions were conducted remotely. An ACP summary was placed in patients' medical records. Main Outcomes and Measures: The primary, 2-week preparedness outcomes were dyad congruence on EOL goals of care, patient decisional conflict, surrogate decision-making confidence, and a composite of dyad congruence and surrogate decision-making confidence. Secondary bereavement outcomes were anxiety, depression, and posttraumatic distress 3 months after patient death. To adjust for COVID-19 pandemic effects on bereavement outcomes, a variable to indicate the timing of baseline and 3-month assessment relative to the COVID-19 emergency declaration was created. Results: Of the 426 dyads enrolled, 231 were in the intervention clinics, and 195 were in the control clinics. Among all dyads, the mean (SD) patient age was 61.9 (12.7) years, and the mean (SD) surrogate age was 53.7 (15.4) years. At 2 weeks, after adjusting for baseline values, dyad congruence (odds ratio [OR], 1.61; 95% CI, 1.12-2.31; P = .001), decisional conflict scores (ß, -0.10; 95% CI, -0.13 to -0.07; P < .001), and the composite (OR, 1.57; 95% CI, 1.06-2.34; P = .03) were higher in the intervention group than in the control group. Surrogate decision-making confidence was similar between groups (ß, 0.06; 95% CI, -0.01 to 0.13; P = .12). Among 77 bereaved surrogates, after adjusting for baseline values and assessment timing, intervention group anxiety was lower than control group anxiety (ß, -1.55; 95% CI, -3.08 to -0.01; P = .05); however, depression (ß, -0.18; 95% CI, -2.09 to 1.73; P = .84) and posttraumatic distress (ß, -0.96; 95% CI, -7.39 to 5.46; P = .75) were similar. Conclusions and Relevance: In this randomized clinical trial, the ACP intervention implemented by health care workers at dialysis centers improved preparation for EOL decision-making but showed mixed effectiveness on bereavement outcomes. The ACP intervention implemented in dialysis centers may be an effective strategy to the dyad preparation for end-of-life care as opposed to the current focus on advance directives. Trial Registration: ClinicalTrials.gov Identifier: NCT03138564.

Challenges in the Care of Patients with AKI Receiving Outpatient Dialysis: AKINow Recovery Workgroup Report.

BACKGROUND: Up to one third of survivors of AKI that required dialysis (AKI-D) during hospitalization remain dialysis dependent at hospital discharge. Of these, 20%-60%, depending on the clinical setting, eventually recover enough kidney function to stop dialysis, and the remainder progress to ESKD. METHODS: To describe the challenges facing those still receiving dialysis on discharge, the AKINow Committee conducted a group discussion comprising 59 participants, including physicians, advanced practitioners, nurses, pharmacists, and patients. The discussion was framed by a patient who described gaps in care delivery at different transition points and miscommunication between care team members and the patient. RESULTS: Group discussions collected patient perspectives of ( 1 ) being often scared and uncertain about what is happening to and around them and ( 2 ) the importance of effective and timely communication, a comfortable physical setting, and attentive and caring health care providers for a quality health care experience. Provider perspectives included ( 1 ) the recognition of the lack of evidence-based practices and quality indicators, the significant variability in current care models, and the uncertain reimbursement incentives focused on kidney recovery and ( 2 ) the urgency to address communication barriers among hospital providers and outpatient facilities. CONCLUSIONS: The workgroup identified key areas for future research and policy change to ( 1 ) improve communication among hospital providers, dialysis units, and patients/care partners; ( 2 ) develop tools for risk classification, subphenotyping, and augmented clinical decision support; ( 3 ) improve education to providers, staff, and patients/care partners; ( 4 ) identify best practices to improve relevant outcomes; ( 5 ) validate quality indicators; and ( 6 ) assess the effect of social determinants of health on outcomes. We urge all stakeholders involved in the process of AKI-D care to align goals and work together to fill knowledge gaps and optimize the care to this highly vulnerable patient population.

Optimum Care of AKI Survivors Not Requiring Dialysis after Discharge: An AKINow Recovery Workgroup Report.

AKI survivors experience gaps in care that contribute to worse outcomes, experience, and cost.Challenges to optimal care include issues with information transfer, education, collaborative care, and use of digital health tools.Research is needed to study these challenges and inform optimal use of diagnostic and therapeutic interventions to promote recovery AKI affects one in five hospitalized patients and is associated with poor short-term and long-term clinical and patient-centered outcomes. Among those who survive to discharge, significant gaps in documentation, education, communication, and follow-up have been observed. The American Society of Nephrology established the AKINow taskforce to address these gaps and improve AKI care. The AKINow Recovery workgroup convened two focus groups, one each focused on dialysis-independent and dialysis-requiring AKI, to summarize the key considerations, challenges, and opportunities in the care of AKI survivors. This article highlights the discussion surrounding care of AKI survivors discharged without the need for dialysis. On May 3, 2022, 48 patients and multidisciplinary clinicians from diverse settings were gathered virtually. The agenda included a patient testimonial, plenary sessions, facilitated small group discussions, and debriefing. Core challenges and opportunities for AKI care identified were in the domains of transitions of care, education, collaborative care delivery, diagnostic and therapeutic interventions, and digital health applications. Integrated multispecialty care delivery was identified as one of the greatest challenges to AKI survivor care. Adequate templates for communication and documentation; education of patients, care partners, and clinicians about AKI; and a well-coordinated multidisciplinary posthospital follow-up plan form the basis for a successful care transition at hospital discharge. The AKINow Recovery workgroup concluded that advancements in evidence-based, patient-centered care of AKI survivors are needed to improve health outcomes, care quality, and patient and provider experience. Tools are being developed by the AKINow Recovery workgroup for use at the hospital discharge to facilitate care continuity.

Nonsteroidal Mineralocorticoid Receptor Antagonist (Finerenone) in Cardiorenal Disease.

Nonsteroidal mineralocorticoid receptor antagonists (MRAs) present a promising therapeutic option in cardiorenal diseases, mitigating the limitations of steroidal MRAs. Finerenone, a third-generation nonsteroidal MRA, has demonstrated beneficial effects in heart failure (HF) and chronic kidney disease (CKD). Clinical trials, including FIDELIO-DKD and FIGARO-DKD, revealed finerenone's efficacy in improving kidney and cardiovascular (CV) outcomes. Patients with CKD and type 2 diabetes (T2DM) on finerenone experienced reduced rates of cardiovascular events, including hospitalization for HF. However, these trials excluded symptomatic HF patients, focusing on asymptomatic or early-stage HF. The ongoing FINEARTS-HF trial evaluates finerenone in HF with preserved ejection fraction (HFpEF). Additionally, studies exploring finerenone and sodium-glucose cotransporter 2 (SGLT2) inhibitors' (Empagliflozin) combination effects in CKD and T2DM (CONFIDENCE) and the selective MR modulator AZD9977 with another SGLT2 inhibitor (dapagliflozin) in HF and CKD (MIRACLE) aim to expand treatment options. While SGLT-2 inhibitors were shown to reduce hyperkalemia risk in FIDELIO-DKD and potentially lower new-onset HF incidence in FIGARO-DKD, further research is essential. So far, the evidence for the beneficial effect of finerenone in the spectrum of cardiorenal diseases is based only on the results of studies conducted in patients with T2DM, and clinical trials of finerenone in patients with nondiabetic kidney disease are ongoing. Nonsteroidal MRAs hold significant potential as pivotal treatment targets across the cardiorenal disease spectrum. This review will focus on the effects of finerenone on cardiorenal disease.

Clinical Advances in Kidney Failure: AKI.

Kidney failure poses an enormous burden on patients, caregivers, healthcare providers, and society as a whole [...].

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.

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 ± 15.4 years. Median number of dialysis sessions was 11 (6-15), lasting 3.6 ± 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.

Recovery after Critical Illness and Acute Kidney Injury.

AKI is a common complication in hospitalized and critically ill patients. Its incidence has steadily increased over the past decade. Whether transient or prolonged, AKI is an independent risk factor associated with poor short- and long-term outcomes, even if patients do not require KRT. Most patients with early AKI improve with conservative management; however, some will require dialysis for a few days, a few weeks, or even months. Approximately 10%-30% of AKI survivors may still need dialysis after hospital discharge. These patients have a higher associated risk of death, rehospitalization, recurrent AKI, and CKD, and a lower quality of life. Survivors of critical illness may also suffer from cognitive dysfunction, muscle weakness, prolonged ventilator dependence, malnutrition, infections, chronic pain, and poor wound healing. Collaboration and communication among nephrologists, primary care physicians, rehabilitation providers, physical therapists, nutritionists, nurses, pharmacists, and other members of the health care team are essential to create a holistic and patient-centric care plan for overall recovery. Integration of the patient and family members in health care decisions, and ongoing education throughout the process, are vital to improve patient well-being. From the nephrologist standpoint, assessing and promoting recovery of kidney function, and providing appropriate short- and long-term follow-up, are crucial to prevent rehospitalizations and to reduce complications. Return to baseline functional status is the ultimate goal for most patients, and dialysis independence is an important part of that goal. In this review, we seek to highlight the varying aspects and stages of recovery from AKI complicating critical illness, and propose viable strategies to promote recovery of kidney function and dialysis independence. We also emphasize the need for ongoing research and multidisciplinary collaboration to improve outcomes in this vulnerable population.

Determinants of Outcomes of Acute Kidney Injury: Clinical Predictors and Beyond.

Acute kidney injury (AKI) is a common clinical syndrome characterized by rapid impairment of kidney function. The incidence of AKI and its severe form AKI requiring dialysis (AKI-D) has been increasing over the years. AKI etiology may be multifactorial and is substantially associated with increased morbidity and mortality. The outcome of AKI-D can vary from partial or complete recovery to transitioning to chronic kidney disease, end stage kidney disease, or even death. Predicting outcomes of patients with AKI is crucial as it may allow clinicians to guide policy regarding adequate management of this problem and offer the best long-term options to their patients in advance. In this manuscript, we will review the current evidence regarding the determinants of AKI outcomes, focusing on AKI-D.

A Narrative Review of Management Strategies for Common Symptoms in Advanced CKD.

Patients with advanced chronic kidney disease (CKD) experience multiple bothersome symptoms, undermining their quality of life (QOL). With growing attention to the importance of symptom management in advanced CKD, the evidence regarding symptoms is increasing. In this review, we briefly summarize the current evidence of effective pharmacologic and nonpharmacologic interventions to improve symptoms and QOL in patients with advanced CKD, including those on dialysis. We focused on symptoms that are commonly experienced by patients, such as pain, fatigue, sleep disturbances, itching, nausea and vomiting, cognitive impairment, and anxiety and depression. We noted that research in symptom science focused on improving symptom management in CKD is still very limited. In addition to the lack of clinical practice guidelines to address those common symptoms, the major gaps in the current literature include the evidence regarding mechanistic pathways to inform the development of effective symptom management for CKD populations, the evidence to confirm effective pharmacologic interventions in other populations for CKD populations, and research on how to incorporate effective symptom management approaches into clinical care. Although improving mortality remains as an important area in the kidney community, there is an urgent need to focus on improving symptom management to improve QOL in advanced CKD.

Association of Race with In-Hospital and Post-Hospitalization Mortality in Patients with Acute Kidney Injury.

INTRODUCTION: Acute kidney injury (AKI) is known to be associated with increased mortality, and racial differences in hospital mortality exist in patients with AKI. However, it remains to be seen whether racial differences exist in post-hospitalization mortality among AKI patients. METHODS: We analyzed data of adult AKI patients admitted to the University of Virginia Medical Center between January 1, 2001, and December 31, 2015, to compare in-hospital and post-hospitalization mortality among hospitalized black and white patients with AKI. Multivariable logistic regression analysis was used to analyze the association between race and in-hospital mortality, and 90-day post-hospitalization mortality among AKI patients that were discharged. Kaplan-Meier survival curve was used to evaluate long-term survival between black and white patients. RESULTS: Black patients had lower in-hospital mortality than white patients after adjusting for age, sex, estimated glomerular filtration rate, hospital length of stay, severity of AKI, comorbidities, and the need for dialysis and mechanical ventilation (odds ratio: 0.82; 95% confidence interval, 0.70-0.96, p = 0.0015). Similarly, at 90-day post-hospitalization, black patients had significantly lower adjusted odds of death than white patients (odds ratio: 0.64; 95% confidence interval, 0.46-0.93; p = 0.008). The median length of follow-up was 11.9 months (0.6-46.7 months). Kaplan-Meier survival curve showed that long-term survival was significantly better in black patients compared to white patients (median duration of survival; 39.7 vs. 24.8 months; p ≤ 0.001). CONCLUSIONS: Black patients with AKI had lower in-hospital mortality, 90-day post-hospitalization mortality, and better long-term survival rates compared to white patients with AKI.

Association between Palliative Care Consultation and Advance Palliative Care Rates: A Descriptive Cohort Study in Patients at Various Stages in the Continuum of Chronic Kidney Disease.

Background: Despite evidence that advance care planning (ACP) benefits patients with serious illnesses, there is a dearth of information about "who" is referred for palliative care (PC) consultation, the rate of PC consultation, and the outcomes of referrals in patients with advanced chronic kidney disease/end-stage kidney disease (aCKD/ESKD). Objectives: (1) To describe patient characteristics associated with PC consultations and (2) to determine the frequency and outcome of PC consultation on documented ACP discussions for patients with aCKD/ESKD. Methodology/Design: This is retrospective observational electronic health record cohort review. Settings: University of Virginia (UVA) hospital, clinics, and dialysis units. Participants: Patients were studied along two time intervals. Time period January 1, 2015 to June 30, 2017 included all patients admitted to UVA during that time period with estimated glomerular filtration rate (eGFR) <60 mL/minute. Time period January 1, 2018 to March 31, 2019 included two cohorts: patients with eGFR <15 mL/minute who had died during study period excluding those who withdrew from dialysis and those who were dialysis dependent and withdrew from dialysis. Results: Aside from higher rates of PC consultation in patients with heart failure, none of the demographic and comorbidity data studied affected whether or not a patient is referred to PC in patients with aCKD/ESKD. PC consultation rates were low among all patients studied: 14.7% in patients with eGFR <60 mL/minute, 28.9% in dialysis patients withdrawing from dialysis, and 57.1% in terminally ill patients with eGFR <15 mL/minute. In all cohorts, PC consultations were associated with improved ACP. Conclusion: PC consultation is significantly associated with better end-of-life outcomes with more completion of ACP and hospice referral in patients with aCKD/ESKD. PC consultation rates remain low. Even in terminally ill patients with more aCKD, >40% were never seen by PC. Until policies and curricula better prepare nephrologists to independently address ACP, collaboration between nephrologists and PC specialists is recommended.