Severe refeeding syndrome after starvation ketoacidosis requiring stopping feeds.

INTRODUCTION: Starvation ketoacidosis (SKA) is a rare cause of ketoacidosis in the general population but can be seen with malignancy. Patients often respond well to treatment, but some rarely develop refeeding syndrome (RFS) as their electrolytes drop to dangerous levels causing organ failure. Typically, RFS can be managed with low-calorie feeds, but sometimes patients require a halt in feeds until their electrolyte imbalances are managed. CASE REPORT: We discuss a woman with synovial sarcoma on chemotherapy who was diagnosed with SKA and then developed severe RFS after treatment with intravenous dextrose. Phosphorus, potassium, and magnesium levels dropped precipitously and remained fluctuant for 6 days. She also developed normal sinus ventricular tachycardia, premature ventricular beats, and bigeminy. She could not tolerate calorie supplementation at that time. She was managed with electrolyte repletions until clinically stable and then progressed to a liquid diet. DISCUSSION: We present a unique case of severe SKA that resulted in RFS requiring nihil per orem (NPO) treatment for 6 days. There are no specific guidelines for SKA or RFS management. Patients with pH < 7.3 may benefit from baseline serum phosphorus, potassium, and magnesium levels. Clinical trials are needed to further study which patients may benefit from starting at a low-calorie intake versus those that require holding nutrition until clinically stable. CONCLUSION: Completely stopping caloric intake until a patient's electrolyte imbalance improves is an important management aspect of RFS to underscore and study, as grave complications can occur even with cautious refeeding regimens.

Improving quality of life and self-care for patients on hemodialysis using cognitive behavioral strategies: A randomized controlled pilot trial.

INTRODUCTION: Behavioral-education interventions have the potential to improve quality of life and self-care for patients on hemodialysis (HD) but have not been incorporated into routine clinical practice. The purpose of this pilot study was to determine the feasibility of delivering a simple behavioral-education intervention using cognitive behavioral strategies in patients receiving HD with poor quality of life. METHODS: In this mixed methods study, HD patients were randomly assigned to the study intervention (8 behavioral-education sessions delivered over 12 weeks) or a control group of dialysis education alone. Kidney disease quality of life (KDQOL)-36 scores, depressive symptoms and self-care behaviors were measured at weeks 0, 8, and 16. Following study completion, participants, social workers, and physicians provided their perspectives about the intervention via qualitative interviews. FINDINGS: Forty-five participants were randomized. Due, in part, to social worker attrition from the intervention arm, 34 participants (76%) completed at least 1 study session and were included in the analysis. The intervention led to modest, but non-significant, increase in KDQOL-physical component summary scores (+3.1±1.2 points) from week 0 to week 16. There were small, non-significant decreases in interdialytic weight gain and pre-dialysis phosphorus levels in the intervention group. Participants felt that chair-side delivery was practical and efficient, and that content related to the impact of dialysis on daily life was unique and important. Suggestions for adapting the intervention included narrowing its content and its delivery by additional providers that are not necessarily therapy trained. DISCUSSION: In this pilot study, we were able to deliver a simple behavioral-education intervention to improve both quality of life and self-care. Participants had a positive impression of the intervention, but we did not find significant improvements in quality of life or self-care. We will now adapt our intervention by narrowing its content and by using other providers that are focused solely on delivering the intervention.

Cancer Screening in End-Stage Kidney Disease.

The incidence of cancer is higher in patients with end-stage kidney disease (ESKD) than among the general population. Despite this, screening for cancer is generally not cost-effective and may worsen quality of life in these patients. This is due to high mortality rates (patients are not living long enough to reap the benefits of screening), the inaccuracy of cancer screening tests, and the increased risks associated with therapy in patients with ESKD. Specific groups of patients with ESKD who have a longer-than-expected life expectancy or higher-than-expected cancer risk may benefit from screening. These groups include patients on peritoneal dialysis, patients on home hemodialysis, Black and Asian-American patients, transplant-eligible patients, and those at higher risk of cancer including patients with acquired cystic kidney disease, those who have been previously exposed to cytotoxic agents or aristolochic acid, and patients with a genetic predisposition to cancer. In this narrative review, we will examine the prevalence of and risk factors for cancer in patients with ESKD and the effectiveness of cancer screening, and discuss specific situations in which cancer screening may be effective.

A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant.

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.

High rate of renal recovery in survivors of COVID-19 associated acute renal failure requiring renal replacement therapy.

INTRODUCTION: A large proportion of patients with COVID-19 develop acute kidney injury (AKI). While the most severe of these cases require renal replacement therapy (RRT), little is known about their clinical course. METHODS: We describe the clinical characteristics of COVID-19 patients in the ICU with AKI requiring RRT at an academic medical center in New York City and followed patients for outcomes of death and renal recovery using time-to-event analyses. RESULTS: Our cohort of 115 patients represented 23% of all ICU admissions at our center, with a peak prevalence of 29%. Patients were followed for a median of 29 days (2542 total patient-RRT-days; median 54 days for survivors). Mechanical ventilation and vasopressor use were common (99% and 84%, respectively), and the median Sequential Organ Function Assessment (SOFA) score was 14. By the end of follow-up 51% died, 41% recovered kidney function (84% of survivors), and 8% still needed RRT (survival probability at 60 days: 0.46 [95% CI: 0.36-0.56])). In an adjusted Cox model, coronary artery disease and chronic obstructive pulmonary disease were associated with increased mortality (HRs: 3.99 [95% CI 1.46-10.90] and 3.10 [95% CI 1.25-7.66]) as were angiotensin-converting-enzyme inhibitors (HR 2.33 [95% CI 1.21-4.47]) and a SOFA score >15 (HR 3.46 [95% CI 1.65-7.25). CONCLUSIONS AND RELEVANCE: Our analysis demonstrates the high prevalence of AKI requiring RRT among critically ill patients with COVID-19 and is associated with a high mortality, however, the rate of renal recovery is high among survivors and should inform shared-decision making.

CKD-Associated Pruritus: New Insights Into Diagnosis, Pathogenesis, and Management.

Chronic kidney disease-associated pruritus (CKD-aP) is a common, troubling and in some cases debilitating problem for patients with CKD and end-stage renal disease. Despite a prevalence rate of approximately 20% in CKD and 40% in end-stage renal disease, and a clear association with poorer psychosocial and medical outcomes, this condition is often underreported by patients and overlooked by health care providers. This is likely due, in part, to uncertainty regarding its pathogenesis and treatment. Most commonly, CKD-aP is attributed to toxin build-up, peripheral neuropathy, immune system dysregulation, or opioid dysregulation. Prior treatment studies of CKD-aP have targeted these potential etiologies but have been limited by noncontrolled design, small sample size, and non-uniform definitions of CKD-aP. Recently, several large, randomized controlled trials targeting opioid dysregulation have yielded promising results. These trials have spurred new hope for understanding and treating this condition.

Randomized Controlled Trial of Difelikefalin for Chronic Pruritus in Hemodialysis Patients.

INTRODUCTION: There is an unmet medical need for pruritus associated with chronic kidney disease, a distressing complication characterized by generalized and persistent itch affecting 20% to 40% of patients undergoing hemodialysis. Here we report the results of a phase 2 trial evaluating the efficacy and safety of a novel peripherally restricted kappa opioid receptor agonist, difelikefalin, in adult patients undergoing hemodialysis with pruritus. METHODS: In this study, 174 hemodialysis patients with moderate-to-severe pruritus were randomly assigned to receive difelikefalin (0.5, 1.0, or 1.5 µg/kg) or placebo intravenously thrice weekly after each hemodialysis session for 8 weeks in a double-blind, controlled trial. The primary endpoint was the change from baseline at week 8 in the weekly mean of the 24-hour Worst Itching Intensity Numerical Rating Scale score. The secondary efficacy endpoint was the change in itch-related quality of life measured by the Skindex-10 questionnaire. Other endpoints included safety, sleep quality, and additional measures including the 5-D itch scale. RESULTS: A significant reduction from baseline in itch intensity scores at week 8 favored all difelikefalin doses combined versus placebo (P = 0.002). Difelikefalin also showed improvement over placebo in Skindex-10, 5-D itch, and sleep disturbance scores (P ≤ 0.005). Overall, 78% of patients receiving difelikefalin reported treatment-emergent adverse events versus 42% of patients given placebo, with diarrhea, dizziness, nausea, somnolence, and fall being the most frequent (≥5%). CONCLUSION: In this trial, difelikefalin effectively reduced itching intensity and improved sleep and itch-related quality of life.

Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.

BACKGROUND: Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse. METHODS: We conducted a multicenter study of 138 patients with immune checkpoint inhibitor-associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI. RESULTS: Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor-associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI. CONCLUSIONS: This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.

A protocol for a pilot randomized controlled trial to assess the feasibility and effect of a cognitive behavioral intervention on quality of life for patients on hemodialysis.

INTRODUCTION: Poor health-related quality of life (HrQOL) is highly prevalent in patients on hemodialysis (HD), and is associated with increased hospitalizations and mortality. Cognitive behavioral (CB) techniques have improved HrQOL in HD patients but have not been routinely translated into clinical practice. The investigators present the rationale, study design and protocol of a randomized controlled trial to pilot the feasibility and effect of a translatable, behavioral-education intervention using CB techniques to improve poor HrQOL and self-management in hemodialysis patients. METHODS: Forty-eight HD patients will be randomly assigned to either the study intervention which includes 8-12 behavioral-education sessions with incorporated CB techniques delivered over 12 weeks or a control group of dialysis education without incorporated CB techniques. Subjects will be followed for 16 weeks and the primary outcome, change in kidney disease quality of life (KDQOL)-36 scores, will be measured at 0, 8, and 16 weeks. The study will have 85% power to detect an 8-point change in KDQOL-36 scores. At the end of the study, qualitative data will be gathered through end-of-study focus groups, and semi-structured interviews. These data will be used to refine the intervention and help translate it into clinical practice. DISCUSSION: There is promising evidence in support of CB-based interventions to improve HrQOL for patients on HD. Despite this, these interventions have not been routinely incorporated into clinical practice. The proposed intervention has the potential to improve both HrQOL and self-management, while also being easily translatable to other HD units.

Design of the Magnetic Resonance Imaging Evaluation of Mineralocorticoid Receptor Antagonism in Diabetic Atherosclerosis (MAGMA) Trial.

Mineralocorticoid receptor (MR) activation plays an essential role in promoting inflammation, fibrosis, and target organ damage. Currently, no studies are investigating MR antagonism in patients with type 2 diabetes mellitus (T2DM) with chronic kidney disease, at high risk for cardiovascular complications, who are otherwise not candidates for MR antagonism by virtue of heart failure. Further, there is limited information on candidate therapies that may demonstrate differential benefit from this therapy. We hypothesized that MR antagonism may provide additional protection from atherosclerosis progression in higher-risk patients who otherwise may not be candidates for such a therapeutic approach. In this double-blind, randomized, placebo-controlled trial, subjects with T2DM with chronic kidney disease (≥ stage 3) will be randomized in a 1:1 manner to placebo or spironolactone (12.5 mg with eventual escalation to 25 mg daily over a 4-week period). The co-primary efficacy endpoint will be percentage change in total atheroma volume in thoracic aorta and left ventricular mass at 52 weeks in patients treated with spironolactone vs placebo. Secondary outcomes include 24-hour mean systolic blood pressure, central aortic blood pressure, and insulin resistance (HOMA-IR) at 6 weeks. A novel measure in the study will be changes in candidate miRNAs that regulate expression of NR3C2 (MR gene) as well as measuring monocyte/macrophage polarization in response to therapy with spironolactone. We envision that our strategy of simultaneously probing the effects of a drug combined with analysis of mechanisms of action and predictive response will likely provide key information with which to design event-based trials.

Chronic kidney disease-associated pruritus: impact on quality of life and current management challenges.

Chronic kidney disease-associated pruritus (CKD-aP) is a distressing, often overlooked condition in patients with CKD and end-stage renal disease. It affects ~40% of patients with end-stage renal disease and has been associated with poor quality of life, poor sleep, depression, and mortality. Prevalence estimates vary based on the instruments used to diagnose CKD-aP, and standardized diagnostic instruments are sorely needed. Treatment studies have often yielded conflicting results. This is likely related to studies that are limited by small sample size, flawed designs, and nonstandardized diagnostic instruments. Several large well-designed treatment trials have recently been completed and may soon influence CKD-aP management.

Depression in Chronic Kidney Disease and End-Stage Renal Disease: Similarities and Differences in Diagnosis, Epidemiology, and Management.

Depression is highly prevalent and is associated with poor quality of life and increased mortality among adults with chronic kidney disease (CKD), including those with end-stage renal disease (ESRD). However, there are several important differences in the diagnosis, epidemiology, and management of depression between patients with non-dialysis-dependent CKD and ESRD. Understanding these differences may lead to a better understanding of depression in these 2 distinct populations. First, diagnosing depression using self-reported questionnaires may be less accurate in patients with ESRD compared with CKD. Second, although the prevalence of interview-based depression is approximately 20% in both groups, the risk factors for depression may vary. Third, potential mechanisms of depression might also differ in CKD versus ESRD. Finally, considerations regarding the type and dose of antidepressant medications vary between CKD and ESRD. Future studies should further examine the mechanisms of depression in both groups, and test interventions to prevent and treat depression in these populations.