Acute kidney injury among salicylate intoxication hospitalisations in the United States.

BACKGROUND: This study aimed to evaluate the risk factors and the association of acute kidney injury (AKI) with outcomes, and resource utilisation in patients hospitalised because of salicylate intoxication in the United States. METHODS: Hospitalised patients with a primary diagnosis of salicylate intoxication from 2003 to 2014 were identified in the National Inpatient Sample (NIS) database. End-stage kidney disease patients were excluded. The occurrence of AKI was identified using hospital diagnosis code. Clinical characteristics, in-hospital treatment, outcomes and resource utilisation were compared between patients with and without AKI. RESULTS: A total of 13 787 eligible hospital admissions were included in the analysis. AKI occurred in 1279 (9.3%) admissions. Older age, male sex, more recent year of hospitalisation, anaemia, hypertension, congestive heart failure, chronic kidney disease, volume depletion, sepsis and ventricular arrhythmia/cardiac arrest were significantly associated with increased risk of AKI, whereas Hispanic race was associated with decreased risk. AKI was significantly associated with increased risk of organ failure, and in-hospital mortality. In addition, the need for ventilation support, blood component transfusion, renal replacement therapy, length of hospital stay and hospitalisation cost were higher in AKI patients. CONCLUSION: Approximately one tenth of salicylate intoxication patients developed AKI during hospitalisation. AKI was associated with higher morbidity, mortality and resource utilisations.

Thrombotic Microangiopathy among Hospitalized Patients with Systemic Lupus Erythematosus in the United States.

BACKGROUND: This study aimed to evaluate thrombotic microangiopathy's (TMA) incidence, risk factors, and impact on outcomes and resource use in hospitalized patients with systemic lupus erythematosus (SLE). METHODS: We used the National Inpatient Sample to construct a cohort of hospitalized patients with SLE from 2003-2014. We compared clinical characteristics, in-hospital treatments, outcomes, and resource use between SLE patients with and without TMA. RESULTS: Of 35,745 hospital admissions for SLE, TMA concurrently presented or developed in 188 (0.5%) admissions. Multivariable analysis showed that age ≥ 40 years and Hispanics were significantly associated with decreased risk of TMA, whereas Asian/Pacific Islanders and history of chronic kidney disease were significantly associated with increased risk of TMA. TMA patients required more kidney biopsy, plasmapheresis, mechanical ventilation, and renal replacement therapy. TMA was significantly associated with increased risk of in-hospital mortality and acute conditions including hemoptysis, glomerulonephritis, encephalitis/myelitis/encephalopathy, hemolytic anemia, pneumonia, urinary tract infection, sepsis, ischemic stroke, seizure, and acute kidney injury. The length of hospital stays and hospitalization cost was also significantly higher in SLE with TMA patients. CONCLUSION: TMA infrequently occurred in less than 1% of patients admitted for SLE, but it was significantly associated with higher morbidity, mortality, and resource use.

Salt and water balance after sweat loss: A study of Bikram yoga.

Bikram yoga is practiced in a room heated to 105°F with 40% humidity for 90 min. During the class a large volume of water and electrolytes are lost in the sweat, specifically, sodium is lost, the main cation of the extracellular fluid. There is little known about the volume of sweat and the amount of sodium lost in sweat during Bikram yoga or the optimum quantity of fluid required to replace these losses. The participants who took part in this small feasibility study were five females with a mean age of 47.4 ± 4.7 years and 2.6 ± 1.6 years of experience at Bikram yoga. The total body weight, water consumed, serum sodium concentration, serum osmolality, and serum aldosterone levels were all measured before and after a Bikram yoga practice. Sweat sodium chloride concentration and osmolality were measured at the end of the practice. The mean estimated sweat loss was 1.54 ± 0.65 L, while the amount of water consumed during Bikram yoga was 0.38 ± 0.22 L. Even though only 25% of the sweat loss was replenished with water intake during the Bikram yoga class, we did not observe a change in serum sodium levels or serum osmolality. The sweat contained 82 ± 16 mmol/L of sodium chloride for an estimated total of 6.8 ± 2.1 g of sodium chloride lost in the sweat. The serum aldosterone increased 3.5-fold from before to after Bikram yoga. There was a decrease in the extracellular body fluid compartment of 9.7%. Sweat loss in Bikram yoga predominately produced a volume depletion rather than the dehydration of body fluids. The sweating-stimulated rise in serum aldosterone levels will lead to increased sodium reabsorption from the kidney tubules and restore the extracellular fluid volume over the next 24 hr.

Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients: A Systematic Review.

BACKGROUND: C3 glomerulopathy (C3G), a rare glomerular disease mediated by alternative complement pathway dysregulation, is associated with a high rate of recurrence and graft loss after kidney transplantation (KTx). We aimed to assess the efficacy of different treatments for C3G recurrence after KTx. METHODS: Databases (MEDLINE, EMBASE, and Cochrane Database) were searched from inception through 3 May, 2019. Studies were included that reported outcomes of adult KTx recipients with C3G. Effect estimates from individual studies were combined using the random-effects, generic inverse variance method of DerSimonian and Laird., The protocol for this meta-analysis is registered with PROSPERO (no. CRD42019125718). RESULTS: Twelve studies (7 cohort studies and 5 case series) consisting of 122 KTx patients with C3G (73 C3 glomerulonephritis (C3GN) and 49 dense deposit disease (DDD)) were included. The pooled estimated rates of allograft loss among KTx patients with C3G were 33% (95% CI: 12-57%) after eculizumab, 42% (95% CI: 2-89%) after therapeutic plasma exchange (TPE), and 81% (95% CI: 50-100%) after rituximab. Subgroup analysis based on type of C3G was performed. Pooled estimated rates of allograft loss in C3GN KTx patients were 22% (95% CI: 5-46%) after eculizumab, 56% (95% CI: 6-100%) after TPE, and 70% (95% CI: 24-100%) after rituximab. Pooled estimated rates of allograft loss in DDD KTx patients were 53% (95% CI: 0-100%) after eculizumab. Data on allograft loss in DDD after TPE (1 case series, 0/2 (0%) allograft loss at 6 months) and rituximab (1 cohort, 3/3 (100%) allograft loss) were limited. Among 66 patients (38 C3GN, 28 DDD) who received no treatment (due to stable allograft function at presentation and/or clinical judgment of physicians), pooled estimated rates of allograft loss were 32% (95% CI: 7-64%) and 53% (95% CI: 28-77%) for C3GN and DDD, respectively. Among treated C3G patients, data on soluble membrane attack complex of complement (sMAC) were limited to patients treated with eculizumab (N = 7). 80% of patients with elevated sMAC before eculizumab responded to treatment. In addition, all patients who responded to eculizumab had normal sMAC levels after post-eculizumab. CONCLUSIONS: Our study suggests that the lowest incidence of allograft loss (33%) among KTX patients with C3G are those treated with eculizumab. Among those who received no treatment for C3G due to stable allograft function, there is a high incidence of allograft loss of 32% in C3GN and 53% in DDD. sMAC level may help to select good responders to eculizumab.

Hospitalizations for Acute Salicylate Intoxication in the United States.

BACKGROUND: The objective of this study was to describe inpatient prevalence, characteristics, outcomes, and resource use for acute salicylate intoxication hospitalizations in the United States. METHODS: A total of 13,805 admissions with a primary diagnosis of salicylate intoxication from 2003 to 2014 in the National Inpatient Sample database were analyzed. Prognostic factors for in-hospital mortality were determined using multivariable logistic regression. RESULTS: The overall inpatient prevalence of salicylate intoxication among hospitalized patients was 147.8 cases per 1,000,000 admissions in the United States. The average age was 34 ± 19 years. Of these, 35.0% were male and 65.4% used salicylate for suicidal attempts. Overall, 6% required renal replacement therapy. The most common complications of salicylate intoxication were electrolyte and acid-base disorders, including hypokalemia (25.4%), acidosis (19.1%), and alkalosis (11.1%). Kidney failure (9.3%) was the most common observed organ dysfunction. In-hospital mortality was 1.0%. Increased in-hospital mortality was associated with age ≥30, Asian/Pacific Islander race, diabetes mellitus, hyponatremia, ventricular arrhythmia, kidney failure, respiratory failure, and neurological failure, while decreased in-hospital mortality was associated with African American and Hispanic race. CONCLUSION: hospitalization for salicylate intoxication occurred in 148 per 1,000,000 admissions in the United States. Several factors were associated with in-hospital mortality.

SGLT2 Inhibitors and Kidney Outcomes in Patients with Chronic Kidney Disease.

Globally, diabetes mellitus is a leading cause of kidney disease, with a critical percent of patients approaching end-stage kidney disease. In the current era, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as phenomenal agents in halting the progression of kidney disease. Positive effects of SGLT2i are centered on multiple mechanisms, including glycosuric effects, tubule-glomerular feedback, antioxidant, anti-fibrotic, natriuretic, and reduction in cortical hypoxia, alteration in energy metabolism. Concurrently, multiple kidney and cardiovascular outcome studies have reported remarkable advantages of SGLT2i including mortality benefits. Additionally, the superiority of combination therapies (SGLT2I along with metformin/DDP-4 Inhibitors) in treatment-naïve diabetic patients is further looked into with potential signal towards glycemic and blood pressure control. Reported promising results initiate a gateway for future research targeting kidney outcomes with combination therapies as an initial approach. In the current paper, we summarize leading cardiovascular and kidney outcome trials in patients with type 2 diabetes, the role of SGLT2i in non-diabetic proteinuric kidney disease, and the potential mechanisms of action of SGLT2i with special focus on combination therapy as an initial therapeutic approach in treatment-naïve diabetic patients.

Calcium loss in sweat does not stimulate PTH release: A study of Bikram hot yoga.

It has been hypothesized that sweat loss during exercise causes a disruption in calcium homeostasis that activates bone resorption and over time leads to low bone mineral density. The purpose of this small pilot study was to determine whether dermal calcium loss from a bout of excessive sweating during light intensity physical activity triggers an increase in biomarkers of bone resorption. Biochemical markers related to bone homeostasis were measured before and after a 90 min Bikram hot yoga practice performed in a room heated to 105 °F with 40 % humidity. Participants were five females with a mean age of 47.4 ± 4.7 years. Nude body weight, serum total calcium (Ca2+), free ionized calcium, albumin, parathyroid hormone (PTH) and CTX-I were measured before and after a Bikram hot yoga practice. Mean estimated sweat loss was 1.54 ± 0.65 L, which elicited a 1.9 ± 0.9 % decrease in participant's body weight. Mean Ca2+ concentration in sweat was 2.9 ± 1.7 mg/dl and the estimated mean total calcium lost was 41.3 ± 16.4 mg. Serum ionized Ca2+ increased from 4.76 ± 0.29 mg/dl to 5.35 ± 0.36 mg/dl after the Bikram hot yoga practice (p = 0.0118). Serum PTH decreased from pre- 33.9 ± 3.3 pg/ml to post- 29.9 ± 2.1 pg/ml yoga practice (p = 0.0015) when adjusted for hemoconcentration (PTHADJ), implying a decrease in PTH secretion. We conclude that calcium loss in sweat during 90 min of Bikram hot yoga did not trigger an increase in PTH secretion and did not initiate bone resorption.

Sporadic Medullary Thyroid Carcinoma with Paraneoplastic Cushing Syndrome.

Medullary thyroid cancer (MTC) is a rare form of neoplasm affecting the thyroid gland. This neuroendocrine tumor is capable of releasing active substances causing systemic manifestation in the form of flushing, diarrhea, and uncommonly, Ectopic Cushing's syndrome (ECS). MTC can be hereditary as a part of multiple endocrine neoplasm type 2 syndrome (MEN2) or arise sporadically. We report a case of a 74-year-old female presenting with chronic diarrhea, in whom diagnosis of sporadic MTC was delayed due to previous history of gastrointestinal (GI) disturbances. The patient developed liver metastases yielding ACTH dependent Cushing's Syndrome leading to abnormal clinical presentation and laboratory values driven by elevated cortisol level. Metastatic MTC should be considered in patients presenting with chronic diarrhea and weakness unexplained by other GI related causes.

Glucose-dependent growth arrest of leukemia cells by MCT1 inhibition: Feeding Warburg's sweet tooth and blocking acid export as an anticancer strategy.

This study aims to investigate the utilization of The Warburg Effect, cancer's "sweet tooth" and natural greed for glucose to enhance the effect of monocarboxylate transporter inhibition on cellular acidification. By simulating hyperglycemia with high glucose we may increase the effectiveness of inhibition of lactate and proton export on the dysregulation of cell pH homeostasis causing cell death or disruption of growth in cancer cells. MCT1 and MCT4 expression was determined in MCF7 and K562 cell lines using RT-PCR. Cell viability, growth, intracellular pH and cell cycle analysis was measured in the cell lines grown in 5 mM and 25 mM glucose containing media in the presence and absence of the MCT1 inhibitor AR-C155858 (1 µM) and the NHE1 inhibitor cariporide (10 µM). The MCT1 inhibitor, AR-C155858 had minimal effect on the viability, growth and intracellular pH of MCT4 expressing MCF7 cells. AR-C155858 had no effect on the viability of the MCT1 expressing K562 cells, but decreased intracellular pH and cell proliferation, by a glucose-dependent mechanism. Inhibition of NHE1 on its own had a no effect on cell growth, but together with AR-C155858 showed an additive effect on inhibition of cell growth. In cancer cells that only express MCT1, increased glucose concentrations in the presence of an MCT1 inhibitor decreased intracellular pH and reduced cell growth by G1 phase cell-cycle arrest. Thus we propose a transient hyperglycemic-clamp in combination with proton export inhibitors be evaluated as an adjunct to cancer treatment in clinical studies.