Journal of the American Society of Nephrology : JASN
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J. Am. Soc. Nephrol. · Dec 2015
P2Y12 Receptor Localizes in the Renal Collecting Duct and Its Blockade Augments Arginine Vasopressin Action and Alleviates Nephrogenic Diabetes Insipidus.
P2Y12 receptor (P2Y12-R) signaling is mediated through Gi, ultimately reducing cellular cAMP levels. Because cAMP is a central modulator of arginine vasopressin (AVP)-induced water transport in the renal collecting duct (CD), we hypothesized that if expressed in the CD, P2Y12-R may play a role in renal handling of water in health and in nephrogenic diabetes insipidus. We found P2Y12-R mRNA expression in rat kidney, and immunolocalized its protein and aquaporin-2 (AQP2) in CD principal cells. ⋯ Furthermore, selective blockade of P2Y12-R by the reversible antagonist PSB-0739 in primary cultures of rat inner medullary CD cells potentiated the expression of AQP2 and AQP3 mRNA, and cAMP production induced by dDAVP (desmopressin). In conclusion, pharmacologic blockade of renal P2Y12-R increases urinary concentrating ability by augmenting the effect of AVP on the kidney and ameliorates lithium-induced NDI by potentiating the action of AVP on the CD. This strategy may offer a novel and effective therapy for lithium-induced NDI.
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J. Am. Soc. Nephrol. · Dec 2015
Randomized Controlled TrialIntraoperative High-Dose Dexamethasone and Severe AKI after Cardiac Surgery.
Administration of prophylactic glucocorticoids has been suggested as a strategy to reduce postoperative AKI and other adverse events after cardiac surgery requiring cardiopulmonary bypass. In this post hoc analysis of a large placebo-controlled randomized trial of dexamethasone in 4465 adult patients undergoing cardiac surgery, we examined severe AKI, defined as use of RRT, as a primary outcome. ⋯ In stratified analyses, the strongest signal for potential benefit of dexamethasone was in patients with an eGFR<15 ml/min per 1.73 m(2). In conclusion, compared with placebo, intraoperative dexamethasone appeared to reduce the incidence of severe AKI after cardiac surgery in those with advanced CKD.
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J. Am. Soc. Nephrol. · Dec 2015
Multicenter StudyPlasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery.
Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n = 960). ⋯ Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P = 0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes.
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J. Am. Soc. Nephrol. · Dec 2015
Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of Hypercalciuria.
Potassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. ⋯ Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation.
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J. Am. Soc. Nephrol. · Dec 2015
Rehospitalizations and Emergency Department Visits after Hospital Discharge in Patients Receiving Maintenance Hemodialysis.
Clinical outcomes after a hospital discharge are poorly defined for patients receiving maintenance in-center (outpatient) hemodialysis. To describe the proportion and characteristics of these patients who are rehospitalized, visit an emergency department, or die within 30 days after discharge from an acute hospitalization, we conducted a population-based study of all adult patients receiving maintenance in-center hemodialysis who were discharged between January 1, 2003, and December 31, 2011, from 157 acute care hospitals in Ontario, Canada. For patients with more than one hospitalization, we randomly selected a single hospitalization as the index hospitalization. ⋯ In multivariable analysis using a cause-specific Cox proportional hazards model, the following characteristics were associated with 30-day rehospitalization: older age, the number of hospital admissions in the preceding 6 months, the number of emergency department visits in the preceding 6 months, higher Charlson comorbidity index score, and the receipt of mechanical ventilation during the index hospitalization. Thus, a large proportion of patients receiving maintenance in-center hemodialysis will be readmitted or visit an emergency room within 30 days of an acute hospitalization. A focus on improving care transitions from the inpatient setting to the outpatient dialysis unit may improve outcomes and reduce healthcare costs.