It is not common knowledge that, besides venous thrombosis, arterial thrombotic events may also be associated with the nephrotic syndrome. Two patients are reported who were admitted because of thrombotic occlusions in the peripheral arteries and developed nephrotic syndrome due to membranous glomerulonephritis after various lapses of time. These two cases and the literature support the hypothesis that an identical pathogenetic mechanism may be responsible for the arterial thrombosis as well as the glomerular lesions.

Arterial thrombosis in the nephrotic syndrome

Thromboembolism is a life-threatening, limb-threatening or organ-threatening complication that occurs in patients with primary nephrotic syndrome (NS). There are few studies on the spectrum, complications and outcomes of thrombosis in children with NS. This study aimed to determine the spectrum of thrombosis and its relationship with the nephrotic state, treatment and outcomes in children and adolescents with primary NS. The medical records of subjects aged 1–18 years with NS complicated with thromboembolism treated at our centre within the last 26 years were retrieved. Data on the status of NS, site, symptoms and signs, laboratory investigations, diagnosis, treatment, complications and outcomes of thrombosis were collected and reviewed retrospectively. A severe complication was defined as a condition associated with thrombosis requiring a special diagnostic modality to confirm or a specific treatment such as surgical intervention. The outcome of thrombosis was defined as the status of thrombosis, as determined by imaging methods and the functional status with respect to the anatomic sites of thrombosis at the last follow-up. The permanent dysfunction of an organ or limb related to thrombosis was defined as a sequela. We observed thrombosis in 1.4% (27/1995) of subjects with NS during the study period. There were 27 subjects with thrombosis, including 21 males and 6 females. Thrombosis was observed in 51.9% (14/27) of the study participants with steroid resistant NS. Most episodes of thrombosis occurred during the active stage of NS; however, 7.4% of thrombosis cases occurred during the remission of proteinuria. Renal vein thrombosis (33.3%) and pulmonary embolism (25.9%) were the most common types of thrombosis. Among the 17 subjects biopsied, minimal change disease and membranous nephropathy were the two most common findings. Six (22.2%) subjects experienced severe complications or sequelae; 1 had persistent intracranial hypertension, 1 had intestinal perforation, 1 had hypoxemia and pulmonary hypertension, 1 had lameness, 1 had epilepsy, and 1 had an askew mouth due to facial paralysis. In 19 (70.4%) subjects, the symptoms resolved completely or improved without severe complications or sequelae. Thrombosis mostly occurred in males of school age during the active stage of NS. Renal vein thrombosis and pulmonary embolism were the most common types of thrombosis. In most patients with thrombosis, the symptoms improved completely without complications with standard anticoagulation therapy. However, 22.2% had severe complications or sequelae requiring an advanced diagnostic modality and aggressive treatment.

/pdf/spectrum-of-thrombotic-complications-and-their-outcomes-in-17ecig146k.pdf

Spectrum of thrombotic complications and their outcomes in Chinese children with primary nephrotic syndrome.

Background Loperamide, commonly sold under the brand name Imodium® (Johnson & Johnson, Fort Washington, PA), is a widely available, over-the-counter antidiarrheal medication that possesses µ-opioid agonist properties and can have catastrophic cardiac events when misused or abused. Since the start of the opioid epidemic in the United States, there has been an increasing number of case reports and deaths linking loperamide abuse with cardiac events such as torsades de pointes (TdP) and Brugada syndrome. Case Report This case report presents a 22-year-old man who presented in cardiac arrest from polymorphic ventricular tachycardia consistent with TdP and a Type 1 Brugada pattern after intentional loperamide abuse. We discuss this patient's management and the proposed pathophysiology of these two cardiotoxicities, of which, to our knowledge, no previously published case report has displayed both in the same patient after a supratherapeutic loperamide ingestion. Why Should an Emergency Physician Be Aware of This? As the prevalence of opioid dependency and misuse has increased, so, too, has the misuse of un-scheduled medications such as loperamide to achieve central nervous system opioid effects. It is important for the emergency physician to know about and understand loperamide-associated cardiotoxicities such as prolongation of the QRS, unmasking of Brugada patterns, QT prolongation, or ventricular dysrhythmias such as TdP to be able to recognize and treat it.

A Case Report of Torsade de Pointes and Brugada Pattern Associated with Loperamide Misuse and Supratherapeutic Loperamide Concentrations

Loperamide is a synthetic opioid commonly used as an antidiarrheal due to its activation of u-opioid receptors in the myenteric plexus. In therapeutic doses, it inhibits peristalsis and has anti-secretory and anti-motility effects, until metabolized by intestinal and hepatic CYP3A4 and CYP2C8 into inactive metabolites. Furthermore, loperamide also inhibits L-type voltage-gated calcium (Ca2+) channels, increases action potential duration, and can induce arrhythmias and even cardiotoxicity, particularly when taken in extremely high doses. Thus, the aim of this study was to perform an integrative review of the available evidence in the recent literature on the cardiac risks of acute and chronic use of loperamide. In electrocardiogram (ECG) analysis, the most common finding was QTc prolongation in 27 cases, followed by QRS prolongation, first-degree atrioventricular (AV) block, torsades de pointes, ventricular tachycardia, and right bundle branch block. As for the symptoms encountered, syncope, weakness, palpitations, lightheadedness, shortness of breath, nausea, vomiting, bradycardia, and cardiac arrest were the most common. Loperamide can inhibit hERG voltage-gated potassium (K+) channels (Kv11.1), leading to the prolongation of repolarization, QTc interval prolongation, and increased risk of torsades de pointes. In addition, loperamide can inhibit voltage-gated sodium (Na+) channels (Nav1.5), impairing electrical cardiac conduction and potentiating QRS interval widening. Therefore, QTc prolongation, torsades de pointes, and other ECG alterations are of particular concern regarding loperamide toxicity, particularly when overdosed.

/pdf/risk-of-cardiac-lesion-with-chronic-and-acute-use-of-1rqdtrsb.pdf

Risk of Cardiac Lesion with Chronic and Acute Use of Loperamide—An Integrative Review

Minimal change nephrotic syndrome (MCNS) cases achieving spontaneous remission without external factors are rarely reported. We report a case of MCNS that achieved spontaneous remission without external factors that triggered its onset. An 82-year-old male patient was admitted to the hospital for close examination of nephrotic syndrome. Renal biopsy was performed and MCNS was diagnosed. Owing to the patient's age and history of foot and microvascular arteriovenous thrombosis, we did not start immunosuppressive drugs, including steroids, and opted for conservative management. After conservative treatment, proteinuria gradually decreased, and the patient achieved complete remission. Given that the patient had a history of urinary protein and thrombosis, recurrence of MCNS was considered again this time. In addition, the involvement of external factors that trigger the onset of MCNS was not found. In conclusion, in elderly-onset MCNS, clinicians generally hesitate to initiate treatment with an immunosuppressive drug, containing steroids, because of its many complications. Thus, our data provide valuable insight into MCNS.

Spontaneous remission of minimal change nephrotic syndrome in an elderly man

The column in this issue is supplied by Whitney Sharp, D.O., and Juan Jose Olivero, M.D. Dr. Sharp is chief medical resident in internal medicine at Houston Methodist Hospital and earned her Doctor of Osteopathic Medicine degree at Nova Southeastern University in Fort Lauderdale, Florida. Dr. Olivero is a nephrologist at Houston Methodist Hospital and a member of the hospital's Nephrology Training Program. He obtained his medical degree from the University of San Carlos School of Medicine in Guatemala, Central America, and completed his residency and nephrology fellowship at Baylor College of Medicine in Houston, Texas.

/pdf/venous-thrombosis-in-nephrotic-syndrome-1l8mgwvelr.pdf

Venous Thrombosis in Nephrotic Syndrome

Brugada syndrome is an inherited arrhythmia that increases a patient's risk of sudden cardiac death. Certain pharmacologic agents may induce a transient Brugada pattern on surface electrocardiogram (EKG). One of these is loperamide, an over-the-counter agent commonly used to manage diarrhea. We report the case of a patient who experienced EKG changes that mimicked Brugada pattern after excessive intake of loperamide.

/pdf/loperamide-mimicking-brugada-pattern-nr67mzgn19.pdf

Loperamide Mimicking Brugada Pattern

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Venous Thrombosis in Nephrotic Syndrome

Loperamide Mimicking Brugada Pattern