Canagliflozin-associated severe hyponatremia: a rare and potentially adverse effect?

Summary: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce osmotic diuresis by inhibiting the proximal renal tubular reabsorption of the filtered glucose load, which in turn can occasionally lead to severe dehydration and hypotension amidst other adverse effects. We present a case of a 49-year-old man with type 2 diabetes mellitus (T2D) on canagliflozin, a SGLT2i. The patient was brought to the emergency room following a motor vehicle accident. He was confused and had an altered mental status. His blood alcohol and urine toxicology screens were negative. Initial investigations revealed that he had severe hyponatremia with euglycemic ketoacidosis. The adverse condition was reversed with close monitoring and timely management, and the patient was eventually discharged. This is the first report to suggest hyponatremia as a potentially serious adverse effect following SGLT2i therapy. Its impact on the renal tubule handling of sodium and water is not yet well characterized. While further studies are warranted to understand better the pathophysiological mechanisms associated with SGLT2i-induced adverse effects, timely dose reduction or perhaps even its temporary discontinuation may be recommended to prevent complications. Learning points: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are usually well-tolerated, but some serious adverse effects have been documented. Our case report suggests hyponatremia as a potential, rare side effect of SGLT2i and makes physicians aware of the occurrence of such life-threatening but preventable complications. Timely and close monitoring of the patient, with temporary discontinuation of this drug, may be recommended towards effective management. Studies demonstrating a comprehensive understanding of SGLT2i-related electrolyte derangements are warranted.

Sepsis-induced cardiomyopathy is associated with higher mortality rates in patients with sepsis.

BACKGROUND: Patients with sepsis are at risk for developing sepsis-induced cardiomyopathy (SIC). Previous studies offer inconsistent results regarding the association of SIC and mortality. This study sought to assess whether SIC is linked to mortality in patients with sepsis and to evaluate predictors of the development of SIC. METHODS: In this retrospective study, patients admitted to the medical intensive care unit with a diagnosis of sepsis in the absence of acute coronary syndrome were included. SIC was identified using transthoracic echo and was defined by a new onset decline in left ventricular ejection fraction (LVEF) ≤50%, or ≥10% decline in LVEF compared to baseline in patients with a history of heart failure with reduced ejection fraction. Multivariable logistic regression analysis was performed using the R software program. RESULTS: Of the 359 patients in the final analysis, 19 (5.3%) had SIC. Eight (42.1%) of the 19 patients in the SIC group and 60 (17.6%) of the 340 patients in the non-SIC group died during hospitalization. SIC was associated with an increased risk for all-cause in-hospital mortality (odds ratio [OR], 4.46; 95% confidence interval [CI], 1.15-18.69; P=0.03). Independent predictors for the development of SIC were albumin level (OR, 0.47; 95% CI, 0.23-0.93; P=0.03) and culture positivity (OR, 8.47; 95% CI, 2.24-55.61; P=0.006). Concomitant right ventricular hypokinesis was noted in 13 (68.4%) of the 19 SIC patients. CONCLUSIONS: SIC was associated with an increased risk for all-cause in-hospital mortality. Low albumin level and culture positivity were independent predictors of SIC.

A hypothesis for mechanism for brain oedema due to glycine.

Death following the use the glycine distension solution in transurethral prostatectomy (TURP) or hysteroscopic surgery has been attributed to the toxic effect of glycine on the brain through the glycine receptors and hyperammonemia, contending that glycine-associated hyponatremia is isosmotic and therefore would not cause brain oedema. Here we propose a hypothesis that the mechanism of brain oedema and death is actually osmotic brain oedema caused by selective diffusion of glycine into the brain while sodium cannot diffuse out of the brain despite favourable concentration gradient because of the absence of sodium transporter on the cerebral capillaries needed for the exit of sodium from the brain. The mechanism for unidirectional diffusion of solutes into the brain in glycine-associated hyponatremia is explained.

Alport's Syndrome in Pregnancy.

Background. Alport's syndrome is an X-linked hereditary disorder affecting the glomerular basement membrane associated with ocular and hearing defects. In women, the disease is much less severe compared to that in men. However, women with Alport's syndrome can have an accelerated form of their disease during pregnancy with worsening of kidney function and can also develop preeclampsia. There are only four described cases of Alport's syndrome in pregnancy. Case Presentation. 20-year-old woman with a history of Alport's syndrome, which during pregnancy worsened resulting in hypertension, proteinuria, and acute kidney injury. Fortunately, there was complete resolution of the proteinuria and kidney injury with delivery, and the patient did not require any renal replacement therapy. Conclusion. One of the four reported cases had an accelerated form of the disease during pregnancy with rapid progression of kidney injury and end-stage renal disease. There are no definite guidelines to monitor these patients during pregnancy. Further studies are required to understand the exact pathophysiology of kidney damage that occurs in pregnant women with Alport's syndrome. This may give us some insight into the prognostic predictors, so that we can monitor these women more thoroughly and prevent adverse outcomes.

Diabetes insipidus: a challenging diagnosis with new drug therapies.

Diabetes Insipidus (DI) is either due to deficient secretion of arginine vasopressin (central) or to tubular unresponsiveness (nephrogenic). Drug induced DI is a well-known entity with an extensive list of medications. Polyuria is generally defined as urine output exceeding 3 liters per day in adults. It is crucial to identify the cause of diabetes insipidus and to implement therapy as early as possible to prevent the electrolyte disturbances and the associated mortality and morbidity. It is very rare to have an idiosyncratic effect after a short use of a medication, and physicians should be aware of such a complication to avoid volume depletion. The diagnosis of diabetes insipidus is very challenging because it relies on laboratory values, urine output, and the physical examination of the patient. A high clinical suspicion of diabetes insipidus should be enough to initiate treatment. The complications related to DI are mostly related to the electrolyte imbalance that can affect the normal physiology of different organ systems.

Use of continuous venovenous hemofiltration for acute renal failure due to multiple myeloma cast nephropathy.

Renal insufficiency is associated with high morbidity and mortality in multiple myeloma. One of the common causes for acute renal failure in multiple myeloma is cast nephropathy. It is important to reduce the levels of light chains to improve renal failure and also the overall outcome. Plasmapheresis has failed to show any significant improvement in renal failure due to cast nephropathy as demonstrated in a recent randomized control trial. Here, we present a case series of three patients who were treated with continuous venovenous hemofiltration as a modality to remove these free light chains. There was improvement in renal failure in these patients with decrease in the levels of free light chains. These patients remained off hemodialysis on follow-up and two of them were able to undergo hematopoietic stem cell transplantation.