BACKGROUND Intraindividual blood pressure (BP) fluctuates dynamically over time. Previous studies suggested an adverse link between greater visit-to-visit variability (VVV) in systolic blood pressure (SBP) and various outcomes. However, these studies have significant limitations, such as a small size, inclusion of selected populations, and restricted outcomes. OBJECTIVES We investigated the association of increased VVV and all-cause mortality, cardiovascular events, and end-stage renal disease (ESRD) in a large cohort of U.S. veterans. METHODS From among 3,285,684 U.S. veterans with and without hypertension and normal estimated glomerular filtration rates (eGFR) during 2005 and 2006, we identified 2,865,157 patients who had 8 or more outpatient BP measurements. SBP variability (SBPV) was measured using the SD of all SBP values (normally distributed) in 1 individual. Associations of SD quartiles (<10.3, 10.3 to 12.7, 12.7 to 15.6, and ≥15.6 mm Hg) with all-cause mortality, incident coronary heart disease (CHD), stroke, and ESRD was examined using Cox models adjusted for sociodemographic characteristics, baseline eGFR, comorbidities, body mass index, SBP, diastolic BP, and antihypertensive medication use. RESULTS Several sociodemographic variables (older age, male sex, African-American race, divorced or widowed status) and clinical characteristics (lower baseline eGFR, higher SBP and DBP), and comorbidities (presence of diabetes, hypertension, cardiovascular disease, and lung disease) were all associated with higher intraindividual SBPV. The multivariable adjusted hazard ratios and 95% confidence intervals for SD quartiles 2 through 4 (compared to the first quartile) associated with all-cause mortality, CHD, stroke, and ESRD were incrementally higher. CONCLUSIONS Higher SBPV in individuals with and without hypertension was associated with increased risks of all-cause mortality, CHD, stroke, and ESRD. Further studies are needed to determine interventions that can lower SBPV and their impact on adverse health outcomes.

Diabetic ketoacidosis (DKA) is a rare yet potentially fatal hyperglycemic crisis that can occur in patients with both type 1 and 2 diabetes mellitus. Due to its increasing incidence and economic impact related to the treatment and associated morbidity, effective management and prevention is key. Elements of management include making the appropriate diagnosis using current laboratory tools and clinical criteria and coordinating fluid resuscitation, insulin therapy, and electrolyte replacement through feedback obtained from timely patient monitoring and knowledge of resolution criteria. In addition, awareness of special populations such as patients with renal disease presenting with DKA is important. During the DKA therapy, complications may arise and appropriate strategies to prevent these complications are required. DKA prevention strategies including patient and provider education are important. This review aims to provide a brief overview of DKA from its pathophysiology to clinical presentation with in depth focus on up-to-date therapeutic management.

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. LPA protects intestinal epithelial cells from apoptosis by inhibiting the mitochondrial pathway. Am J Physiol Gastrointest Liver Physiol 284: G821-G829, 2003; 10.1152/ajpgi.00406.2002.-We previously showed (Gastroenterology 123: 206-216, 2002) that lysophosphatidic acid (LPA) protects and rescues rat intestinal epithelial cells (IEC-6) from apoptosis. Here, we provide evidence for the LPA-elicited inhibition of the mitochondrial apoptotic pathway leading to attenuation of caspase-3 activation. Pretreatment of IEC-6 cells with LPA inhibited campothecin-induced caspase-9 and caspase-3 activation and DNA fragmentation. A caspase-9 inhibitor peptide mimicked the LPA-elicited antiapoptotic activity. LPA elicited ERK1/ ERK2 and PKB/Akt phosphorylation. The LPA-elicited antiapoptotic activity and inhibition of caspase-9 activity were abrogated by pertussis toxin, PD 98059, wortmannin, and LY 294002. LPA reduced cytochrome c release from mitochondria and prevented activation of caspase-9. LPA prevented translocation of Bax from cytosol to mitochondria and increased the expression of the antiapoptotic Bcl-2 mRNA and protein. LPA had no effect on Bcl-xl, Bad, and Bak mRNA or protein expression. These data indicate that LPA protects IEC-6 cells from camptothecin-induced apoptosis through Gi-coupled inhibition of caspase-3 activation mediated by the attenuation of caspase-9 activation due to diminished cytochrome c release, involving upregulation of Bcl-2 protein expression and prevention of Bax translocation. lysophosphatidic acid; camptothecin; cytochrome c; Bcl-2 protein; caspase-9; caspase-3/cpp32

Background Medication non-adherence is a known risk factor for adverse outcomes in the general population. However, little is known about the association of pre-dialysis medication adherence among patients with advanced chronic kidney disease with mortality following their transition to dialysis. Study Design Observational study. Setting & Participants 32,348 US veterans who transitioned to dialysis during 2007–2011. Predictors Adherence to treatment with cardiovascular drugs, ascertained from pharmacy database records using proportion of days covered (PDC) and persistence during the pre-dialysis year. Outcomes Post-dialysis initiation all-cause and cardiovascular mortality, using Cox models with adjustment for confounders. Results The mean age of the cohort was 72±11 (SD) years, among whom 96% were male, 74% were white, 23% were African American, and 69% were diabetic. During median follow-up of 23 (IQR, 9–36) months, 18,608 patients died. Among patients with PDC >80%, there were 14,006 deaths (mortality rate, 283 [95% CI, 278–288]/1000 patient-years [PY]); among patients with PDC >60%–80%, there were 3,882 deaths (mortality rate, 294 [95% CI, 285–304]/1000 PY); among patients with PDC ≤60%, there were 720 deaths (mortality rate, 291 [95% CI, 271–313]/1000 PY). Compared to patients with PDC >80%, adjusted HR for post-dialysis initiation all-cause mortality for patients with PDC >60%–80% was 1.12 (95% CI, 1.08–1.16) and for patients with PDC ≤60% was 1.21 (95% CI, 1.11–1.30). In addition, compared to patients showing medication persistence, adjusted HR risk for post-dialysis initiation all-cause mortality for patients with non-persistence was 1.11 (95% CI, 1.05–1.16). A similar trend was detected for cardiovascular mortality and in subgroup analyses. Limitations Large number of missing values; the results may not be generalizable to women or the general US population. Conclusions Pre-dialysis cardiovascular medication non-adherence is an independent risk factor for post-dialysis mortality among advanced chronic kidney disease patients transitioning to dialysis. Further studies are needed to assess whether interventions targeting adherence improve survival after dialysis initiation.

Background and objectives Hypertension is the most important treatable risk factor for cardiovascular outcomes. Many patients with CKD are elderly, but the ideal BP in these individuals is unknown.Design, setting, participants, & measurements From among 339,887 patients with incident eGFR,60 ml/min per 1.73 m 2 , we examined associations of systolic BP (SBP) and diastolic BP (DBP) with all-cause mortality, incident coronary heart disease (CHD), ischemic strokes, and ESRD from the time of developing CKD until the end of follow-up (July 26, 2013, for mortality, CHD, and stroke, and December 31, 2011, for ESRD) in multivariableadjusted survival models categorized by patients' age.Results Of the total cohort, 300,424 (88%) had complete data for multivariable analysis. Both SBP and DBP showed a U-shaped association with mortality. SBP displayed a linear association with CHD, stroke, and ESRD, whereas DBP showed no consistent association with either. SBP.140 mmHg was associated with higher incidence of all examined outcomes, but with an incremental attenuation of the observed risk in older compared with younger patients (P,0.05 for interaction) The adjusted hazard ratios and 95% confidence intervals associated with SBP$170 mmHg (compared with 130-139 mmHg) in patients ,50, 50-59, 60-69, 70-79, and $80 years were 1.95 (1.34 to 2.84), 2.01 (1.75 to 2.30), 1.68 (1.49 to 1.89), 1.39 (1.25 to 1.54), and 1.30 (1.17 to 1.44), respectively. The risk of incident CHD, stroke, and ESRD was incrementally higher with higher SBP in patients aged ,80 years but showed no consistent association in those aged $80 years (P,0.05 for interaction for all outcomes). ConclusionsIn veterans with incident CKD, SBP showed different associations in older versus younger patients. The association of higher SBP with adverse outcomes was present but markedly reduced in older individuals, especially in those aged $80 years. Elevated DBP showed no consistent association with vascular outcomes in patients with incident CKD.

Chronic kidney disease is common in patients with SCD and its prevalence increases with age. Several baseline modifiable and nonmodifiable factors were associated with the development and progression of CKD in patients with SCD. Strategies targeting BP control and proteinuria may be beneficial for individuals with SCD.

Significant progress has been made in the management of hypertension (HTN) in the last 60 years. A large number of antihypertensive drugs (AHD) is available for effective control of elevated blood pressure (BP) that were also shown to be beneficial in improving all-cause mortality and cardiovascular morbidity in hypertensive individuals. Despite these successes, rates of BP control and outcomes in hypertensive patients remain suboptimal. Therefore, the availability of effective drug therapy itself appears to be insufficient to guarantee desirable results. Adherence to antihypertensive medications is a crucial mediator of favorable outcomes in treating HTN, and non-adherence, in turn, halts BP control. In this review, we will summarize the available evidence on health-related impacts of adherence to AHD, methods for the evaluation of adherence and potential interventions aimed to improve adherence in hypertensive individuals.