Intractable hyponatremia complicated by a reset osmostat: a case report.

BACKGROUND: Hyponatremia associated with a low serum osmolality is a common and confounding electrolyte disorder. Correcting hyponatremia is also complicated, especially in the setting of chronic hyponatremia. Here, we provide a rational approach to accurately detecting and safely treating acute on chronic euvolemic hyponatremia in the setting of acute polydipsia with a chronic reset osmostat. CASE PRESENTATION: A 71-year-old hispanic gentleman with chronic hyponatremia presented with hiccups, polydipsia, and a serum sodium concentration of 120 mEq/L associated with diffuse weakness, inattentiveness, and suicidal ideation. Symptomatic euvolemic hyponatremia warranted hypertonic saline treatment in the acute phase and water restriction in the chronic phase. Both interventions resulted in improvement in symptoms and/or the serum sodium concentration, but to a serum sodium level that persistently remained below the normal range. Remarkably, the urine osmolality appropriately fell when the serum sodium concentration fell below 126 mEq/L. Also remarkable was the appropriate increase in urine osmolality when the serum sodium concentration exceeded 126 mEq/L. The preservation of both concentration and dilution, albeit at a lower-than-normal serum osmolality, shows that the osmostat regulating antidiuretic hormone release had been "reset." Both physiologic and pharmacologic resetting of the osmostat are discussed. CONCLUSIONS: Preservation of urinary concentrating and diluting ability at a lower-than-normal serum sodium concentration, especially in the setting of chronic hyponatremia, is diagnostic of a reset osmostat. The presence of a reset osmostat often confounds the treatment of concomitant acute hyponatremia. Early recognition of a reset osmostat avoids the need to normalize serum sodium concentration, expedites hospital discharge, and limits potential harm from overcorrecting acute hyponatremia.

The Complement System in the Modern Era of Kidney Transplantation: Mechanisms of Injury and Targeted Therapies.

Kidney transplantation remains the treatment of choice for patients with end-stage kidney disease. Significant progress has been made over the course of many years to improve both patient and graft outcomes after transplant. Modern immunosuppressive therapy has reduced the rate of acute rejection and resulted in excellent short- and long-term graft survival. Over the past decade or so, we have become more cognizant of the role of the complement in many events related to the transplant process. A myriad of events that include the cause of death in deceased donors, organ procurement and preservation events, cold ischemia time, time to kidney anastomosis, ischemia-reperfusion injury, recipient immunologic response during and after transplantation, immunosuppressive drug toxicity, and recurrence of original disease all have been shown to affect graft survival. The involvement of the complement system and its activation around the time of kidney transplantation increasingly is recognized as a key player affecting long-term graft survival. In this review, we highlight the important role of the complement system at every stage of the kidney transplantation process. We review potential triggers of complement activation in kidney transplant patients and discuss novel therapeutic agents that can inhibit the complement system.

End-stage kidney disease and COVID-19 in an urban safety-net hospital in Boston, Massachusetts.

INTRODUCTION: End-stage kidney disease (ESKD) patients are at a high risk for Coronavirus Disease 2019 (COVID-19). In this study, we compared characteristics and outcomes of ESKD and non-ESKD patients admitted with COVID-19 to a large safety-net hospital. METHODS: We evaluated 759 adults (45 with ESKD) hospitalized with COVID-19 in Spring of 2020. We examined clinical characteristics, laboratory measures and clinical outcomes. Logistic regression analyses were performed to investigate the associations between ESKD status and outcomes. RESULTS: 73% of ESKD and 47% of non-ESKD patients identified as Black (p = 0.002). ESKD patients were older and had higher rates of comorbidities. Admission ferritin was approximately 6-fold higher in ESKD patients. During hospitalization, the rise in white blood cell count, lactate dehydrogenase, ferritin and C-reactive protein, and the decrease in platelet count and serum albumin were all significantly greater in ESKD patients. The in-hospital mortality was higher for ESKD [18% vs. 10%; multivariable adjusted odds ratio 1.5 (95% CI, 0.48-4.70)], but this did not reach statistical significance. CONCLUSIONS: Among hospitalized COVID-19 patients, ESKD patients had more co-morbidities and more robust inflammatory response than non-ESKD patients. The odds ratio point estimate for death was higher in ESKD patients, but the difference did not reach statistical significance.

Uraemic solutes as therapeutic targets in CKD-associated cardiovascular disease.

Chronic kidney disease (CKD) is characterized by the retention of a myriad of solutes termed uraemic (or uremic) toxins, which inflict damage to several organs, including the cardiovascular system. Uraemic toxins can induce hallmarks of cardiovascular disease (CVD), such as atherothrombosis, heart failure, dysrhythmias, vessel calcification and dysregulated angiogenesis. CVD is an important driver of mortality in patients with CKD; however, reliance on conventional approaches to managing CVD risk is insufficient in these patients, underscoring a need to target risk factors that are specific to CKD. Mounting evidence suggests that targeting uraemic toxins and/or pathways induced by uraemic toxins, including tryptophan metabolites and trimethylamine N-oxide (TMAO), can lower the risk of CVD in patients with CKD. Although tangible therapies resulting from our growing knowledge of uraemic toxicity are yet to materialize, a number of pharmacological and non-pharmacological approaches have the potential to abrogate the effects of uraemic toxins, for example, by decreasing the production of uraemic toxins, by modifying metabolic pathways induced by uraemic toxins such as those controlled by aryl hydrocarbon receptor signalling and by augmenting the clearance of uraemic toxins.

Hyperthrombotic Milieu in COVID-19 Patients.

COVID-19 infection has protean systemic manifestations. Experience from previous coronavirus outbreaks, including the current SARS-CoV-2, has shown an augmented risk of thrombosis of both macrovasculature and microvasculature. The former involves both arterial and venous beds manifesting as stroke, acute coronary syndrome and venous thromboembolic events. The microvascular thrombosis is an underappreciated complication of SARS-CoV-2 infection with profound implications on the development of multisystem organ failure. The telltale signs of perpetual on-going coagulation and fibrinolytic cascades underscore the presence of diffuse endothelial damage in the patients with COVID-19. These parameters serve as strong predictors of mortality. While summarizing the alterations of various components of thrombosis in patients with COVID-19, this review points to the emerging evidence that implicates the prominent role of the extrinsic coagulation cascade in COVID-19-related coagulopathy. These mechanisms are triggered by widespread endothelial cell damage (endotheliopathy), the dominant driver of macro- and micro-vascular thrombosis in these patients. We also summarize other mediators of thrombosis, clinically relevant nuances such as the occurrence of thromboembolic events despite thromboprophylaxis (breakthrough thrombosis), current understanding of systemic anticoagulation therapy and its risk-benefit ratio. We conclude by emphasizing a need to probe COVID-19-specific mechanisms of thrombosis to develop better risk markers and safer therapeutic targets.