Elvira O. Gosmanova

Management of adult diabetic ketoacidosis.

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.

Association of Medical Treatment Nonadherence With All-Cause Mortality in Newly Treated Hypertensive US Veterans

Nonadherence to antihypertensive drugs is associated with adverse outcomes; however, mediators of this relationship are poorly understood. We examined the association between the International Classification of Diseases-Ninth Revision code for medical treatment nonadherence (V15.81) assigned before initiation of antihypertensive drug therapy and all-cause mortality in a large cohort of incident hypertensive US veterans. A propensity score–matched cohort of 18 822 patients (9411 patients with and without a V15.81 code) was generated based on variables predictive of the presence of the V15.81 code to assess its independent association with all-cause mortality during 3.8 years of follow-up. We used Cox models before and after adjustment for antihypertensive drug adherence (measured as the proportion of days covered) and for measures of blood pressure to determine whether the association of nonadherence with mortality was mediated through consequences of not following prescribed antihypertensive drugs. At baseline, the mean age of patients was 50.0 years, 91.4% were men, and 33.2% were blacks. The V15.81 code presence was associated with higher all-cause mortality (hazard ratio, 1.38, 95% confidence interval, 1.26–1.52; P<0.001). Adjustment for medication adherence, blood pressure levels, and blood pressure variability during follow-up did not alter the association between the V15.81 code and all-cause mortality (hazard ratio, 1.35; 95% confidence interval, 1.20–1.52; P<0.001). In conclusion, assignment of a V15.81 code before antihypertensive drug therapy was associated with higher all-cause mortality in incident hypertensive US veterans and can be useful to identify high-risk patients in administrative databases. This association was not mediated by worse adherence to antihypertensive drugs or differences in follow-up blood pressure.

Prevalence and Progression of Chronic Kidney Disease in Adult Patients With Sickle Cell Disease

Aim We evaluated the prevalence and progression of chronic kidney disease (CKD) during the 5-year period in a cohort of patients with sickle cell disease (SCD) aged 18 years and older. Methods We studied 98 patients with SCD. Chronic kidney disease stages I through V were defined based on estimated glomerular filtration rate (eGFR), and albuminuria grades were defined based on spot urine protein-to-creatinine ratio according to the 2012 Kidney Disease Improving Global Outcomes recommendations. In patients with eGFR of greater than 60 mL/min per 1.73 m2, CKD was diagnosed if grade A2 or A3 albuminuria was present. Chronic kidney disease progression was defined as an increase in CKD stage with an additional eGFR reduction of more than 25% from baseline. Results At baseline, 28.6% of patients had CKD. After a mean follow-up of 5.0 (SD, 0.9) years, 17 patients developed new CKD and the overall CKD prevalence increased to 41.8%. In addition, 8 patients experienced CKD progression. The following baseline variables were associated with the development and progression of CKD in univariate analysis: older age (P = 0.003), higher systolic blood pressure (BP; P = 0.003), lower eGFR (P = 0.001), higher serum creatinine (P = 0.001), and A3 albuminuria (P = 0.008). In multivariate analysis, baseline A3 albuminuria (adjusted odds ratio, 5.0; 95% confidence interval, 1.1-24.3; P = 0.048) and each 1-mm Hg increase in systolic BP (adjusted odds ratio, 1.04; 95% confidence interval, 1.0-1.07; P = 0.039) predicted CKD development and progression. Conclusions 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.

Diagnosis and treatment of diabetic kidney disease.

Abstract:Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease in the United States. In the last several years, there have been several new developments in the field of the DKD. In 2007, the National Kidney Foundation and Kidney Disease Outcomes Quality Initiative released clinical practice guidelines that included new definitions and summarized diagnostic and therapeutic approaches for DKD. The results of several recent randomized controlled trials provided novel insights regarding effects of glycemic and lipid control on vascular and renal outcomes in patients with diabetes. Additionally, the findings of the Action to Control Cardiovascular Risk in Diabetes—Blood Pressure trial played a critical role in the revision of blood pressure target guidelines in patients with diabetes. The goal of this review article is to summarize recent updates and recommendations for the diagnosis and treatment of DKD.

Effect of Metformin-Containing Antidiabetic Regimens on All-cause Mortality in Veterans With Type 2 Diabetes Mellitus

Objective:There are conflicting reports concerning metformin use and mortality rates in patients with type 2 diabetes (T2DM). The aim of this study was to examine the relationship between metformin use and all-cause mortality in veterans with T2DM. Research design and methods:An observational cohort study involving 2206 patients with T2DM was performed using computerized database from the Veterans Affairs Medical Center, Memphis, TN. All-cause mortality was compared among cohorts of metformin and nonmetformin users. Univariate and multivariate Cox regression models were used to estimate hazard ratios (HR) for all-cause mortality after adjusting for age, race, baseline estimated glomerular filtration rate, glycosylated hemoglobin, use of insulin, use of ACE inhibitors or angiotensin II receptor blockers or statins. Results:The average length of follow-up in metformin and nonmetformin users was 62 ± 17 and 61 ± 18 months, respectively. The mean age was 63 ± 11 years. Crude mortality rates were similar in both groups: 266 (22%) metformin users and 253 (25.3%) nonmetformin users died. There was a trend for improved survival with metformin use (unadjusted HR 0.85, P = 0.07). After multivariate adjustment, metformin users had significantly decreased HR for time to all-cause mortality compared with nonmetformin users (adjusted HR 0.77, P < 0.01). Insulin use was an independent predictor of worsened survival in both univariate and multivariate analyses. In subgroup analysis of patients exposed to insulin, all-cause mortality remained decreased in metformin users (adjusted HR 0.62, P < 0.04). Conclusion:Treatment of T2DM with regimens containing metformin alone or in combination with other hypoglycemic agents was associated with reduced all-cause mortality compared with regimens without metformin.

Evaluation and management of diabetic and non-diabetic hypoglycemia in end-stage renal disease

Patients with end-stage renal disease (ESRD) regardless of diabetes status are at increased risk of hypoglycemia with a resultant array of adverse clinical outcomes. Therefore, hypoglycemia should be thoroughly evaluated in ESRD patients. In diabetic dialysis patients, hypoglycemic agents and nutritional alterations can trigger hypoglycemia in the background of diminished gluconeogenesis, reduced insulin clearance by the kidney and improved insulin sensitivity following initiation of renal replacement therapy. Detailed evaluation of antidiabetic regimen and nutritional patterns, patient education on self-monitoring of blood glucose and/or referral to a diabetes specialist may reduce risk of subsequent hypoglycemia. In certain situations, it is important to recognize the possibility of non-diabetic causes of hypoglycemia in patients with diabetes and to avoid treating pseudo-hyperglycemia caused by glucose- non-specific glucometers in patients utilizing icodextrin-based solutions for peritoneal dialysis. Adrenal insufficiency, certain medications, malnutrition and/or infection are among the most common causes of hypoglycemia in non-diabetic ESRD patients, and they should be suspected after exclusion of inadvertent use of hypoglycemic agents. The goal of this review article is to summarize approaches and recommendations for the work up and treatment of hypoglycemia in ESRD.

Adherence to antihypertensive medications: is prescribing the right pill enough?

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.

Impact of Non-Adherence on Renal and Cardiovascular Outcomes in US Veterans

Background: Adherence is paramount in treating hypertension; however, no gold standard method is available for non-adherence screening, delineating high-risk patients. An International Classification of Diseases 9th Edition non-adherence diagnostic code (V15.81) has been available for decades; but, its utility is poorly studied. We examined the association between the V15.81 code assigned prior to the initiation of anti-hypertensive drugs (AHDs) and renal and cardiovascular outcomes. Methods: This was a historical prospective cohort study involving 312,489 newly treated hypertensive individuals (mean age 53.8 years, 90.9% males, 20.3% black, median follow-up 8.0 years). We used crude and Cox models adjusted for baseline socio-demographic characteristics, estimated glomerular filtration rate (eGFR), body mass index, blood pressure, comorbidities, and prospective AHD adherence (measured as proportion of days covered, PDC). Results: In the unadjusted analysis, the V15.81 code was associated with higher risks for faster eGFR decline (hazard ratio, HR 1.22, 95% CI 1.11-1.33), incident CKD (HR 1.17, 95% CI 1.09-1.27), end-stage renal disease (ESRD) (HR 2.53, 95% CI 1.72-3.72), incident coronary artery disease (CAD) (HR 1.26, 95% CI 1.15-1.38), and stroke (HR 1.55, 95% CI 1.38-1.73). In the adjusted model, the V15.81 code remained predictive of increased risk of CKD (HR 1.33, 95% CI 1.22-1.45), ESRD (HR 1.81, 95% CI 1.18-2.78), incident CAD (HR 1.26, 95% CI 1.14-1.40), and stroke (HR 1.46, 95% CI 1.29-1.65). Additional adjustment for PDC did not alter adverse associations between V15.81 code and studied outcomes. Conclusions: Assignment of V15.81 code prior to AHD therapy was associated with higher risks of renal and cardiovascular outcomes in incident hypertensive US veterans. Previous history of non-adherence is a poor prognostic marker in hypertensive individuals; therefore, patients with V15.81 code may require close monitoring. The observational nature of this study limits our ability to make firm recommendations for clinical practice.

Hyperglycemic Crises: Diabetic Ketoacidosis (DKA), And Hyperglycemic Hyperosmolar State (HHS)

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are acute metabolic complications of diabetes mellitus that can occur in patients with both type 1 and 2 diabetes mellitus. Timely diagnosis, comprehensive clinical and biochemical evaluation, and effective management is key to the successful resolution of DKA and HHS. Critical components of the hyperglycemic crises management include coordinating fluid resuscitation, insulin therapy, and electrolyte replacement along with the continuous patient monitoring using available laboratory tools to predict the resolution of the hyperglycemic crisis. Understanding and prompt awareness of potential of special situations such as DKA or HHS presentation in comatose state, possibility of mixed acid-base disorders obscuring the diagnosis of DKA, and risk of brain edema during the therapy are important to reduce the risks of complications without affecting recovery from hyperglycemic crisis. Identification of factors that precipitated DKA or HHS during the index hospitalization should help prevent subsequent episode of hyperglycemic crisis. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

Treatment of Proliferative and Membranous Lupus Nephritis: Review of Key Clinical Trials

Abstract:Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE), which is associated with significant morbidity and mortality. Renal involvement in SLE is heterogeneous; therefore, the treatment of LN is determined by the pathological type of LN and ranges from nonspecific measures such as maintenance of adequate blood pressure control and blockade of renin-angiotensin-aldosterone system to the use of immunosuppressive medications. Cyclophosphamide in combination with prednisone has been the standard of care for the treatment of proliferative forms of LN. However, the high rates of progression to end-stage renal disease coupled with adverse side effects from cyclophosphamide and prednisone administration have lead to an intensive search for more effective and less toxic therapies for LN. The authors review available treatment options for proliferative and membranous LN and summarize the results of recently published clinical trials that add new perspectives to the management of kidney disease in SLE.