Emerging Treatments for Insomnia, Sleep Apnea, and Restless Leg Syndrome Among Dialysis Patients.

Sleep disturbances are highly prevalent in patients with predialysis chronic kidney disease, end-stage kidney disease, and after a kidney transplant. They contribute to impairment in daily function and are associated with a high burden of physical and psychiatric symptoms, decreased quality of life, and increased morbidity and mortality. Sleep disturbances also may precipitate and accelerate kidney disease progression. They often evolve across the spectrum of kidney dysfunction and may persist or re-emerge in kidney transplant recipients. Investigation into the multifaceted and dynamic relationships between sleep disturbance and chronic kidney disease requires consideration of myriad contributors including the progression of kidney disease itself, the role of treatment via dialysis and kidney transplant, psychosocial factors, and underlying sleep disorders. Despite sleep disturbance being identified as a priority to address by patients and caregivers, sleep disorders including insomnia, sleep apnea, and restless leg syndrome remain under-recognized and undertreated, and innovation in their management remains modest. In this article, we review the relationships between sleep disturbance and kidney disease, the impact of sleep disturbance and sleep disorders on symptom burden and mental health, and treatment opportunities that may address overlapping symptoms across the spectrum of kidney disease and that could improve patient-related and clinical outcomes.

Sleep-HD trial: short and long-term effectiveness of existing insomnia therapies for patients undergoing hemodialysis.

BACKGROUND: Patients with end-stage kidney disease (ESKD) treated with hemodialysis (HD) experience many distressing symptoms. One frequently reported symptom is insomnia. There are unique issues about HD treatments and schedules that disrupt regular sleep/wake routines and possibly contribute to the high severity of insomnia. Despite evidence for broad-ranging health effects of insomnia, very few clinical trials have tested the efficacy of treatments for HD patients. Cognitive-behavioral therapy for insomnia (CBT-I) is a recommended first-line therapy but largely inaccessible to HD patients in the United States, partly because they commit considerable amounts of time to thrice-weekly dialysis treatments. Another important reason could be the logistical and reimbursement challenges associated with providing behavioral health care at the dialysis center. CBT-I delivered by telehealth can overcome barriers to access, but its efficacy has never been rigorously tested for these patients. Pharmacotherapy is the most widely used treatment for insomnia; however, some drugs presently used are unsafe as they are associated with a higher risk for death for HD patients (benzodiazepines and zolpidem-like drugs). The efficacy and safety of other medications (trazodone) for the treatment of insomnia has never been tested for patients treated with HD. METHODS: This trial tests the short- and long-term comparative effectiveness of 6-week treatment with telehealth CBT-I, trazodone, or medication placebo. This will be accomplished with a randomized controlled trial (RCT) in which 126 participants treated with HD in community-based dialysis facilities with chronic insomnia will be assigned 1:1:1 to telehealth CBT-I, trazodone, or medication placebo, respectively; short-term effectiveness of each treatment arm will be determined at the end of 6-weeks of treatment and long-term effectiveness at 25-weeks. The primary and secondary patient-reported outcomes will be assessed with computer-based telephone interviewing by research scientists blinded to treatment assignment; additional secondary outcomes will be assessed by participant interview and actigraphy. DISCUSSION: This clinical RCT will provide the first evidence for the comparative effectiveness of two distinct approaches for treating chronic insomnia and other patient-reported outcomes for patients receiving maintenance HD. TRIAL REGISTRATION: NCT03534284 May 23, 2018. SLEEP-HD Protocol Version: 1.3.4 (7/22/2020).

A Unique Case of Metformin-associated Severe Lactic Acidosis Without Preexisting Renal Disease: Perspectives on Prolonged Dialysis and Education for Prevention.

Metabolic acidosis is a common disorder defined by an imbalance in the body's acid-base balance. Identifying the cause of acidosis is critical for its management. We describe a case of acute renal failure with lactic acidosis in a 69-year-old man who was taking metformin for type 2 diabetes. The patient presented with decreased urine output after two weeks of intermittent nausea and vomiting. During this time, the patient had continued to take limited fluids and medication, including lisinopril and metformin. Physical exam on initial evaluation was remarkable only for hypertension and minimal abdominal tenderness. However, laboratory tests revealed a severe lactic acidosis and renal failure with hyperkalemia. The patient had normal renal function and a normal urine albumin level three weeks prior. Broad-spectrum antibiotics and sodium bicarbonate were administered, followed by hemodialysis. During hemodialysis, the patient became hemodynamically unstable, requiring vasopressors. Post-dialysis, the lactic acidosis worsened, prompting the initiation of additional prolonged dialysis during the first hospital day. After the second lengthy dialysis, the patient's condition improved significantly and he was discharged on hospital day 12, with the diagnosis of metformin-associated lactic acidosis (MALA) in the setting of acute tubular necrosis from gastrointestinal fluid loss accompanied by the continued use of an angiotensin-converting enzyme inhibitor. After discharge, his renal function returned to normal. Severe lactic acidosis from metformin is relatively rare. Metformin has a large volume of distribution and accumulates in erythrocytes and intestinal cells, resulting in less efficient removal with dialysis and rebound lactic acidosis. Prolonged dialysis may be necessary for MALA to improve outcomes. Identifying metformin levels may help in diagnosis and management. However, the means to Identify metformin levels are not widely available. Patients receiving metformin should be counseled to stop metformin and seek medical care in the setting of illnesses. This is particularly important given the frequency of metformin prescription and the common use of renin-angiotensin system blockade in patients with type 2 diabetes, which increases the risk of kidney dysfunction.