Gastrointestinal Hemorrhage in Acute Kidney Injury Patients on Hemodialysis.

Background Gastrointestinal bleeding (GIB) has been reported to be more common in patients with chronic renal failure and end-stage renal disease requiring hemodialysis with higher mortality than in the general population. Limited epidemiological data exist on the annual number of hospitalizations, demographic variation, cost of care, and outcomes for GIB in patients with acute kidney injury (AKI) requiring and not requiring hemodialysis (HD). The main objective of this study was to analyze the trends of GIB in patients with AKI requiring HD and those not requiring HD during hospitalization. Methods and Results We analyzed the National (Nationwide) Inpatient Sample (NIS) database for all subjects with a discharge diagnosis of AKI as the primary or secondary diagnosis during the period from 2001 to 2011. Subjects with a discharge diagnosis of hemodialysis and GIB were then identified from the pool and trends were analyzed. A significant rise in the annual number of hospitalizations with AKI was found with a greater proportion being discharged without HD. From 2001 to 2011, there were 19,393,811 hospitalizations with a discharge diagnosis of AKI of which 1,424,692 (7.3%) received HD (HD group), whereas 17,969,119 (92.7%) did not receive HD (non-HD group) (p < 0.0001). The male gender was more commonly affected by GIB than the female gender in both groups (p < 0.0001). The cost of care per hospitalization for GIB patients in the HD group increased over the study period with average found to be $61,463 (adjusted for inflation, p < 0.0001), whereas for GIB patients in the non-HD group, it showed a slight decrease in trend with the average found to be $28,419 (p < 0.0001). All-cause mortality was higher for GIB patients in the HD group (38.1%) than in the non-HD group (25.1%) (p < 0.0001). Conclusions GIB is more common and associated with higher all-cause inpatient mortality in patients receiving HD in comparison to non-HD patients.

Type B Lactic Acidosis Associated With Venlafaxine Overdose.

Lactic acidosis that is not secondary to tissue hypoperfusion or hypoxemia (type B lactic acidosis) is a rare but potentially fatal condition that has been associated with drugs like metformin, linezolid, and nucleoside reverse-transcriptase inhibitors in patients with HIV. We report the first case of type B lactic acidosis caused by overdose of the serotonin-norepinephrine reuptake inhibitor, venlafaxine. A 55-year-old man with no significant medical history was brought to the emergency department after intentional ingestion of around 80 capsules of venlafaxine (a total dose of over 6000 mg) in an attempt to commit suicide. Complete blood count and comprehensive metabolic panel were unremarkable except for a bicarbonate level of 13 mEq/L and an anion gap of 22 mEq/L. An arterial blood gas revealed a pH of 7.39, partial pressure of CO2 of 19 mm Hg, calculated bicarbonate of 11.5 mEq/L, and a lactate level of 8.6 mmol/L. The patient was started on aggressive intravenous hydration with normal saline along with oral activated charcoal with sorbitol. Repeat laboratory work after 4 hours showed an improvement in anion gap (15 mEq/L) and serum lactate (5.6 mmol/L). The patient remained stable throughout the hospital stay and lactic acidosis resolved in 24 hours. In the absence of hypotension, hypoxemia, kidney or liver dysfunction, myopathy, malignancy, or use of other medications, venlafaxine was the most likely cause of lactic acidosis in our case. Rapid improvement of acidosis was probably related to clearance of the drug.

The Secretome of Hydrogel-Coembedded Endothelial Progenitor Cells and Mesenchymal Stem Cells Instructs Macrophage Polarization in Endotoxemia.

UNLABELLED: : We previously reported the delivery of endothelial progenitor cells (EPCs) embedded in hyaluronic acid-based (HA)-hydrogels protects renal function during acute kidney injury (AKI) and promotes angiogenesis. We attempted to further ameliorate renal dysfunction by coembedding EPCs with renal mesenchymal stem cells (MSCs), while examining their paracrine influence on cytokine/chemokine release and proinflammatory macrophages. A live/dead assay determined whether EPC-MSC coculturing improved viability during lipopolysaccharide (LPS) treatment, and HA-hydrogel-embedded delivery of cells to LPS-induced AKI mice was assessed for effects on mean arterial pressure (MAP), renal blood flow (RBF), circulating cytokines/chemokines, serum creatinine, proteinuria, and angiogenesis (femoral ligation). Cytokine/chemokine release from embedded stem cells was examined, including effects on macrophage polarization and release of proinflammatory molecules. EPC-MSC coculturing improved stem cell viability during LPS exposure, an effect augmented by MSC hypoxic preconditioning. The delivery of coembedded EPCs with hypoxic preconditioned MSCs to AKI mice demonstrated additive improvement (compared with EPC delivery alone) in medullary RBF and proteinuria, with comparable effects on serum creatinine, MAP, and angiogenesis. Exposure of proinflammatory M1 macrophages to EPC-MSC conditioned medium changed their polarization to anti-inflammatory M2. Incubation of coembedded EPCs-MSCs with macrophages altered their release of cytokines/chemokines, including enhanced release of anti-inflammatory interleukin (IL)-4 and IL-10. EPC-MSC delivery to endotoxemic mice elevated the levels of circulating M2 macrophages and reduced the circulating cytokines/chemokines. In conclusion, coembedding EPCs-MSCs improved their resistance to stress, impelled macrophage polarization from M1 to M2 while altering their cytokine/chemokines release, reduced circulating cytokines/chemokines, and improved renal and vascular function when MSCs were hypoxically preconditioned. SIGNIFICANCE: This report provides insight into a new therapeutic approach for treatment of sepsis and provides a new and improved strategy using hydrogels for the delivery of stem cells to treat sepsis and, potentially, other injuries and/or diseases. The delivery of two different stem cell lines (endothelial progenitor cells and mesenchymal stem cells; delivered alone and together) embedded in a protective bioengineered scaffolding (hydrogel) offers many therapeutic benefits for the treatment of sepsis. This study shows how hydrogel-delivered stem cells elicit their effects and how hydrogel embedding enhances the therapeutic efficacy of delivered stem cells. Hydrogel-delivered stem cells influence the components of the overactive immune system during sepsis and work to counterbalance the release of many proinflammatory and prodamage substances from immune cells, thereby improving the associated vascular and kidney damage.

Trends in acute kidney injury and outcomes after early percutaneous coronary intervention in patients ≥75 years of age with acute myocardial infarction.

We analyzed the Nationwide Inpatient Sample database from 2002 to 2010 to examine the temporal trends in incidence of acute kidney injury (AKI), AKI requiring dialysis, and associated in-hospital mortality in patients ≥75 years of age hospitalized with acute myocardial infarction and undergoing early (within 24 hours) percutaneous coronary intervention. Of 2,225,707 patients ≥75 years of age with acute myocardial infarction, 233,508 (10.5%) underwent early percutaneous coronary intervention, of which 21,961 (9.4%) developed AKI and 1,257 (0.54%) developed AKI requiring dialysis. From 2002 to 2010, the incidence of AKI increased from 5.6% to 14.2% (p for trend <0.001) and that for AKI requiring dialysis decreased (0.6% to 0.4%; p for trend 0.018). Compared with 2002, multivariable-adjusted odds ratios and 95% confidence intervals for AKI, AKI requiring dialysis, and in-hospital mortality in 2010 were 1.87 (1.71 to 2.05), 0.20 (0.15 to 0.27) and 0.74 (0.60 to 0.90), respectively. In conclusion, among hospitalized adults ≥75 years of age, from 2002 to 2010, there was an increase in AKI, but there was paradoxical decrease in AKI requiring dialysis and in-hospital mortality, potentially reflecting increased health-care provider awareness resulting in early recognition and implementation of renal-protective strategies and diagnosis-related group creep.

Risk factors for hemodialysis and mortality in patients with contrast-induced nephropathy.

The purpose of this study was to identify risk factors for renal failure requiring hemodialysis and mortality in patients who developed contrast-induced nephropathy (CIN) after cardiac catheterization. Out of 13,742 patients who received cardiac catheterization at Westchester Medical Center/New York Medical College from 2005 to 2008, 268 patients (2%) with a discharge diagnosis of renal failure were screened for CIN. CIN was defined as either a >25% increase of the serum creatinine or an absolute increase in serum creatinine of 0.5 mg/dL within the first 48 hours of the procedure. Chart reviews were performed on 80 patients (1%) who met the criteria for CIN. The 80 patients in the study included 46 men and 34 women, mean age 69 ± 14 years. Of the 80 patients, 18 patients (23%) died, and 22 patients (28%) developed renal failure requiring hemodialysis. Stepwise logistic regression analysis showed that independent risk factors for mortality were the use of calcium channel blockers [odds ratio = 0.0025, 95% confidence interval (CI), 0.0001-0.1210, P < 0.01], catecholamine use (odds ratio = 71.2177, 95% CI, 4.2153-1203, P < 0.01), circulatory failure with lactic acidosis (odds ratio = 32.1405, 95% CI, 2.6331-392, P < 0.01), and renal failure requiring hemodialysis (odds ratio = 17.0376, 95% CI, 1.2344-235, P < 0.05). Significant independent risk factors for renal failure requiring hemodialysis were smoking (odds ratio = 0.06, 95% CI, 0.0045-0.8080, P < 0.05), N-acetylcysteine use (odds ratio = 0.08, 95% CI, 0.0148-0.4179, P < 0.01), anemia (odds ratio = 11.32, 95% CI, 2.57-50, P < 0.01), and circulatory failure with lactic acidosis (odds ratio = 9.76, 95% CI, 2.37-40, P < 0.01). Our data showed that risk factors for mortality in patients with CIN were catecholamine use, circulatory failure with lactic acidosis, and renal failure requiring hemodialysis. Risk factor for reducing mortality in patients with CIN was calcium channel blocker use. Significant risk factors for renal failure requiring hemodialysis were anemia, and circulatory failure with lactic acidosis. Risk factors for reducing renal failure requiring hemodialysis were N-acetylcysteine use and smoking.