Use of Urea for the Syndrome of Inappropriate Secretion of Antidiuretic Hormone: A Systematic Review.

Importance: Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and safety of oral urea for SIADH are still debated. Objective: To evaluate the efficacy and safety of urea for the treatment of SIADH. Evidence Review: A systematic search of Medline and Embase was conducted for controlled and uncontrolled studies of urea for SIADH in adult patients. The primary outcome was serum sodium concentration after treatment. Secondary outcomes included the proportion of patients with osmotic demyelination syndrome (ODS), intracranial pressure, and resource use such as length of stay. Findings: Twenty-three studies involving 537 patients with SIADH were included, of which 462 were treated with urea. The pooled mean baseline serum sodium was 125.0 mmol/L (95% CI, 122.6-127.5 mmol/L). The median treatment duration with oral urea was 5 days. Urea increased serum sodium concentration by a mean of 9.6 mmol/L (95% CI, 7.5-11.7 mmol/L). The mean increase in serum sodium after 24 hours was 4.9 mmol/L (95% CI, 0.5-9.3 mmol/L). Adverse events were few, mainly consisting of distaste or dysgeusia, and no case of ODS was reported. Resource use was too infrequently reported to be synthesized. Conclusions and Relevance: In this systematic review of the use of urea in SIADH and despite the lack of randomized clinical trials, lower-quality evidence was identified that suggests that urea may be an effective, safe, and inexpensive treatment modality that warrants further exploration.

Spontaneous haematomas and haematochezia due to vitamin C deficiency in a haemodialysis patient.

A man in his 50s with dialysis-dependent end-stage renal disease, several weeks history of progressive skin bruising and acute-onset gastrointestinal bleeding presented to the emergency department following a syncopal event during routine haemodialysis owing to profound hypotension. He was found to have a severe normocytic, normochromic anaemia requiring several blood transfusions. He followed a diet lacking fruits and vegetables and stopped taking renal multivitamins. All parameters of coagulation were unremarkable, but serum vitamin C level was undetectable, supporting a diagnosis of scurvy. Although typically associated with individuals who are at risk of malnourishment, such as those with alcohol use disorder, malabsorption, and those who experience homelessness, scurvy should be considered in patients receiving renal replacement therapy as vitamin C is removed during haemodialysis.

Severe babesiosis with associated splenic infarcts and asplenia.

We describe two patients who presented with severe autoimmune hemolytic anemia in the setting of babesiosis. Notably, one patient was immunocompetent but was found to have splenic infarcts of uncertain duration, while the other patient developed disease in the context of asplenia secondary to prior surgical removal of the spleen. Both patients received antibiotics and transfusion support and eventually made a full recovery. While the patient in case 1 had parasitemia >10%, neither patient ultimately required therapeutic red blood cell exchange transfusion during the course of their respective hospitalizations. Our two cases emphasize the importance of recognizing the hemolytic anemia component of this potentially life-threatening infection, and the importance of rapidly initiating treatment in these complex clinical situations.

Approach to Patients With High Anion Gap Metabolic Acidosis: Core Curriculum 2021.

The anion gap (AG) is a mathematical construct that compares the blood sodium concentration with the sum of the chloride and bicarbonate concentrations. It is a helpful calculation that divides the metabolic acidoses into 2 categories: high AG metabolic acidosis (HAGMA) and hyperchloremic metabolic acidosis-and thereby delimits the potential etiologies of the disorder. When the [AG] is compared with changes in the bicarbonate concentration, other occult acid-base disorders can be identified. Furthermore, finding that the AG is very small or negative can suggest several occult clinical disorders or raise the possibility of electrolyte measurement artifacts. In this installment of AJKD's Core Curriculum in Nephrology, we discuss cases that represent several very common and several rare causes of HAGMA. These case scenarios highlight how the AG can provide vital clues that direct the clinician toward the correct diagnosis. We also show how to calculate and, if necessary, correct the AG for hypoalbuminemia and severe hyperglycemia. Plasma osmolality and osmolal gap calculations are described and when used together with the AG guide appropriate clinical decision making.

Seronegative necrotizing autoimmune myopathy with favorable response to intravenous immunoglobulin.

We describe a 68-year-old man who presented with progressive weakness in proximal muscles of all four limbs and was found to have autoantibody-negative necrotizing autoimmune myopathy (NAM). His myopathy was refractory to corticosteroids and methotrexate, but subsequently demonstrated successful response to intravenous immunoglobulin (IVIG). The patient also received rituximab, but the timing of his recovery favored IVIG as the more important factor in terms of efficacy. Treatment guidelines for seronegative necrotizing myopathies are lacking. This case suggests a potential efficacious treatment option for the seronegative subset of NAM.

Utility of Hypertonic Saline and Diazepam in COVID-19-Related Hydroxychloroquine Toxicity.

BACKGROUND: Hydroxychloroquine (HCQ) poisoning is a life-threatening but treatable toxic ingestion. The scale of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) and the controversial suggestion that HCQ is a treatment option have led to a significant increase in HCQ use. HCQ poisoning should be at the top-of-mind for emergency providers in cases of toxic ingestion. Treatment for HCQ poisoning includes sodium bicarbonate, epinephrine, and aggressive electrolyte repletion. We highlight the use of hypertonic saline and diazepam. CASE REPORT: We describe the case of a 37-year-old man who presented to the emergency department after the ingestion of approximately 16 g of HCQ tablets (initial serum concentration 4270 ng/mL). He was treated with an epinephrine infusion, hypertonic sodium chloride, high-dose diazepam, sodium bicarbonate, and aggressive potassium repletion. Persistent altered mental status necessitated intubation, and he was managed in the medical intensive care unit until his QRS widening and QTc prolongation resolved. After his mental status improved and it was confirmed that his ingestion was not with the intent to self-harm, he was discharged home with outpatient follow-up. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: For patients presenting with HCQ overdose and an unknown initial serum potassium level, high-dose diazepam and hypertonic sodium chloride should be started immediately for the patient with widened QRS. The choice of hypertonic sodium chloride instead of sodium bicarbonate is to avoid exacerbating underlying hypokalemia which may in turn potentiate unstable dysrhythmia. In addition, early intubation should be a priority in vomiting patients because both HCQ toxicity and high-dose diazepam cause profound sedation.

Evaluation of the use of erythropoietin-stimulating agents in a hospital setting to assess the necessity of a protocol-driven anemia management service.

Erythropoietin-stimulating agents (ESA) have revolutionized the management of anemia. However, these agents are not always utilized with proper monitoring parameters, which can present significant safety concerns, unwarranted drug expenditures, and decreased ESA efficacy. This retrospective study assessed the utilization of all ESAs in non-intensive care unit hospitalized patients at a large academic medical center from August 18, 2018, to August 31, 2018, using established guideline-based assessment criteria. Among the 167 doses of ESA evaluated, 86% (n = 144) were utilized in accordance with guideline-based assessment criteria regarding laboratory monitoring of iron studies. However, 24% (n = 40) of ESA doses were administered to patients with active, untreated iron deficiency at the time of administration. Although most ESA doses were utilized in accordance with the guideline-based criteria, interventions can be implemented to further improve anemia treatment. Implementing a protocol-driven anemia management service is one strategy that can improve patient care, advance patient safety, and be cost-beneficial.

Beta-2 Microglobulin Amyloidosis: Past, Present, and Future.

Almost half a century has elapsed since the first description of dialysis-related amyloidosis (DRA), a disorder caused by excessive accumulation of ß-2 microglobulin (B2M). Within that period, substantial advances in RRT occurred. These improvements have led to a decrease in the incidence of DRA. In many countries, DRA is considered a "disappearing act" or complication. Although the prevalence of patients living with RRT increases, not all will have access to kidney transplantation. Consequently, the number of patients requiring interventions for treatment of DRA is postulated to increase. This postulate has been borne out in Japan, where the number of patients with ESKD requiring surgery for carpal tunnel continues to increase. Clinicians treating patients with ESKD have treatment options to improve B2M clearance; however, there is a need to identify ways to translate improved B2M clearance into improved quality of life for patients undergoing long-term dialysis.

Pathophysiology and Management of Hyperammonemia in Organ Transplant Patients.

Neurologic complications are common after solid-organ transplantation, occurring in one-third of patients. Immunosuppression-related neurotoxicity (involving calcineurin inhibitors and corticosteroids), opportunistic central nervous system infections, seizures, and delirium are some of the causes of neurologic symptoms following solid-organ transplantation. An uncommon often missed complication posttransplantation involves buildup of ammonia levels that can lead to rapid clinical deterioration even when treated. Ammonia levels are not routinely checked due to the myriad of other explanations for encephalopathy in a transplant recipient. A treatment of choice for severe hyperammonemia involves renal replacement therapy (RRT), but there are no guidelines on the mode or parameters of RRT for reducing ammonia levels. Hyperammonemia in a transplant recipient poses specific challenges beyond the actual condition because the treatment (RRT) involves significant hemodynamic fluctuations that may affect the graft. In this review, we describe a patient with posttransplantation hyperammonemia and discuss the pathways of ammonia metabolism, potential factors underlying the development of hyperammonemia posttransplantation, and choice of appropriate therapeutic options in these patients.

Spontaneous bleeding in a patient on enoxaparin with poor renal function.

Creatinine-based equations are used as standard ways to estimate glomerular filtration rate and kidney function. Unfortunately, serum creatinine varies based on factors such as age, gender, and muscle mass. Overestimation of renal function by creatinine-based equations can be dangerous for renally dosed medications, such as enoxaparin. We present a patient who developed spontaneous bleeding on enoxaparin where kidney function was significantly overestimated by creatinine-based equations. The use of cystatin C levels, which are creatinine independent, can provide a better prediction of renal function.

Uremic Pericarditis: Distinguishing Features in a Now-Uncommon Clinical Syndrome.

We present the case of a 47-year-old man with a history of diabetes mellitus and diabetic nephropathy who was admitted to our hospital with acute uremic myopericarditis. Echocardiography demonstrated a fibrinous pericardial effusion. The patient was initiated on hemodialysis for hyperkalemia, metabolic acidosis, and uremia. He subsequently developed shock from cardiac tamponade, which required emergent pericardiocentesis. He was notably without tachycardia while he was hypotensive, and his admission electrocardiogram did not show typical ST- or PR-segment changes typically associated with acute pericarditis. This case highlights important differences between uremic pericarditis and other prevalent types of acute pericarditis, including the lack of tachycardia during tamponade and normal electrocardiography. Uremic pericarditis is now a less common diagnosis. It is often seen in the setting of previously undiagnosed advanced kidney disease or when patients are ineffectively dialyzed. Given its atypical features, low incidence, and adverse attendant complications, internists must maintain a high degree of suspicion to correctly diagnose acute uremic pericarditis.