Outcomes and Predictors of In-hospital Mortality in Critically Ill Acute Kidney Injury Patients: A Tertiary Care Center Experience.

Acute kidney injury (AKI) is associated with high mortality and morbidity risk. Factors predictive of mortality can guide in early identification of high-risk patients and escalation of therapy to improve outcomes. There is a paucity of data on AKI in Pakistan, and this study was done to determine in-hospital AKI mortality and the associated predictors of mortality. This was a prospective observational study conducted in the Acute Medical Unit and High Dependency Unit of Pak Emirates Military Hospital, Rawalpindi, from June to December 2018. Based on the Kidney Disease Improving Global Outcomes (KDIGO) AKI definition, 130 critically ill patients were included, while patients with chronic kidney disease were excluded. Data were collected on demographic profile-morbid conditions, etiology, laboratory values, and outcomes. The overall mortality was 45.4% (59/130) and varied with the stage of AKI, as it was 21.6%, 36.0%, and 61.8% in KDIGO stages 1, 2, and 3, respectively (P <0.05). There was a significant association (P <0.001) between sepsis, age >65 years, and mortality. Patients with inhospital mortality had higher median serum creatinine and mean potassium levels (P <0.01), with lower mean sodium levels and bicarbonate levels <10 mmol/L. However, on multivariate analysis using variables age >65 years, AKI stage 3, oliguria, bicarbonate <10 mmol/L, and sodium levels <130 mmol/L, only age [odds ratio (OR): 3.16, confidence interval (CI) 95%: 1.40-7.15), AKI stage 3 (OR: 3.12, CI 95%: 1.32-7.38], and low sodium levels <130 mmol/L (OR: 4.52, CI 95%: 1.40-14.61) were found to be independent predictors of mortality. Diabetes mellitus need for vasopressors, oliguria, hemodialysis requirement, and mean leukocyte counts had no significant association with mortality. AKI was associated with high in-hospital mortality in critically ill patients. Sepsis, hypertension, older age, Stage 3 AKI, higher mean creatinine, and potassium were predictive of increased mortality risk.

A cluster of metabolic defects caused by mutation in a mitochondrial tRNA.

Hypertension and dyslipidemia are risk factors for atherosclerosis and occur together more often than expected by chance. Although this clustering suggests shared causation, unifying factors remain unknown. We describe a large kindred with a syndrome including hypertension, hypercholesterolemia, and hypomagnesemia. Each phenotype is transmitted on the maternal lineage with a pattern indicating mitochondrial inheritance. Analysis of the mitochondrial genome of the maternal lineage identified a homoplasmic mutation substituting cytidine for uridine immediately 5' to the mitochondrial transfer RNA(Ile) anticodon. Uridine at this position is nearly invariate among transfer RNAs because of its role in stabilizing the anticodon loop. Given the known loss of mitochondrial function with aging, these findings may have implications for the common clustering of these metabolic disorders.

Evidence for genetic heterogeneity in Dent's disease.

BACKGROUND: Dent's disease (X-linked nephrolithiasis) is a proximal tubulopathy that has been consistently associated with inactivating mutations in the CLCN5 gene encoding the ClC-5 chloride channel expressed in tubular epithelial cells. METHODS: We performed mutation analysis of the coding region of CLCN5 by DNA sequencing in 32 unrelated males, all of whom met the following three clinical criteria for the diagnosis of Dent's disease: (1) low-molecular-weight (LMW) proteinuria; (2) hypercalciuria; and (3) at least one of the following: nephrocalcinosis, kidney stones, renal insufficiency, hypophosphatemia, or hematuria. RESULTS: Sixteen mutations (ten missense, four nonsense, two frameshift) were found in 19 patients. Mutations were confirmed by restriction analysis or allele-specific polymerase chain reaction (PCR), segregated with disease in the families, and were not polymorphisms. In the other 13 patients with Dent's disease, the coding sequence of CLCN5 was normal. In these 13 patients, we also sequenced two regions of the CLCN5 promoter (626 and 586 bp, respectively, 2.1 and 1 kb upstream of exon 2) containing regulatory sites [activating protein-1 (AP-1)-like, AP-4, and cyclic adenosine monophosphate (cAMP)-receptor element binding protein (CREB)] and primary and secondary transcription start sites. We found no mutations in these promoter sequences in any of the 13 patients. In one three-generation family, the absence of mutation was confirmed by sequencing in two additional affected family members, and in this family haplotype analysis excluded linkage to the region of the CLCN5 gene. There were no differences between the 19 patients with CLCN5 mutations and the 13 without mutations with regard to any clinical features of Dent's disease. CONCLUSION: These findings suggest that mutation in other gene(s) may be responsible for the phenotype of Dent's disease in some patients.