Rajesh Mohandas

Uric Acid Levels Increase Risk for New-Onset Kidney Disease

Despite our best efforts, the past decade has seen little progress in the treatment of chronic kidney disease (CKD). The mainstay of therapy continues to be controlling BP, blocking the renin-angiotensin system, and, for the patient with diabetes, tight control of blood sugar. Even with optimal

Are diuretics harmful in the management of acute kidney injury

Purpose of reviewTo assess the role of diuretics in acute kidney injury (AKI) and their effectiveness in preventing AKI, achieving fluid balance, and decreasing progression to chronic kidney disease (CKD). Recent findingsDiuretics are associated with increased risk for AKI. The theoretical advantage of diuretic-induced preservation of renal medullary oxygenation to prevent AKI has not been proven. A higher cumulative diuretic dose during the dialysis period can cause hypotension and increase mortality in a dose-dependent manner. Data on the use of forced euvolemic diuresis to prevent AKI remains controversial. Positive fluid balance has emerged as an independent predictor of adverse outcomes. Post-AKI furosemide dose had a favorable effect on mortality due in part to the reduction of positive fluid balance. There are exciting experimental data suggesting that spironolactone may prevent AKI once an ischemic insult has occurred and thus prevent the progression to CKD. SummaryDiuretics are ineffective and even detrimental in the prevention and treatment of AKI, and neither shorten the duration of AKI, nor reduce the need for renal replacement therapy. Diuretics have an important role in volume management in AKI, but they are not recommended for the prevention of AKI. There is increased emphasis on the prevention of progression of AKI to CKD.

Endothelial Progenitor Cells and Endothelial Vesicles – What Is the Significance for Patients with Chronic Kidney Disease?

Endothelial progenitor cells are cells derived from the bone marrow that circulate in the bloodstream and can exhibit phenotypic characteristics of endothelial cells. They are thought to be involved in postnatal vasculogenesis and to potentially help repair injured endothelium. Circulating endothelial cells are mature endothelial cells in the circulation, and endothelial vesicles or microparticles are thought to be derived from the membranes of endothelial cells as a result of injury or activation. Recent research has focused on using these markers of endothelial injury and repair to assess the state of endothelial health. These efforts have been hampered by lack of uniformity in methodology and terminology. Recent developments in flow cytometry techniques have allowed better characterization and definition of these cells. We review the common techniques used to identify and isolate these cells, clinical studies in patients with chronic kidney disease (CKD) where they serve as markers of endothelial health and predictors of outcome, and possible mechanisms of progenitor cell dysfunction in CKD.

A Physiologic-Based Approach to the Treatment of a Patient With Hypokalemia

Hypokalemia is common and can be associated with serious adverse consequences, including paralysis, ileus, cardiac arrhythmias, and death. As a result, the body maintains serum potassium concentration within very narrow limits by tightly regulated feedback and feed-forward systems. Whereas the consequences of symptomatic hypokalemia and severe potassium depletion are well appreciated, chronic mild hypokalemia can accelerate the progression of chronic kidney disease, exacerbate systemic hypertension, and increase mortality. Persistent hypokalemia may reflect total-body potassium depletion or increased renal potassium clearance. In a patient with simple potassium depletion, potassium replacement therapy should correct serum potassium concentration, but may have little effect when renal potassium clearance is abnormally increased from potassium wasting. In such cases, the addition of potassium-sparing diuretics might be helpful. Serum potassium concentration is an inaccurate marker of total-body potassium deficit. Mild hypokalemia may be associated with significant total-body potassium deficits and conversely, total-body potassium stores can be normal in patients with hypokalemia due to redistribution. The speed and extent of potassium replacement should be dictated by the clinical picture and guided by frequent reassessment of serum potassium concentration(.) The goals of therapy should be to correct a potassium deficit, if present, without provoking hyperkalemia. Oral replacement is preferred except when there is no functioning bowel or in the setting of electrocardiogram changes, neurologic symptoms, cardiac ischemia, or digitalis therapy.

Mild renal dysfunction and long-term adverse outcomes in women with chest pain: Results from the National Heart, Lung, and Blood Institute–sponsored Women’s Ischemia Syndrome Evaluation (WISE)

BACKGROUND Chronic kidney disease (CKD) is associated with accelerated atherosclerosis and adverse cardiovascular outcomes, but mechanisms are unclear. We hypothesized that mild CKD independently predicts adverse outcomes in women with symptoms and signs of ischemia. METHODS We categorized 876 women from the Womens Ischemia Syndrome Evaluation cohort according to estimated glomerular filtration rate (eGFR) (eGFR ≥90 mL/min per 1.73 m(2) [normal], 60-89 mL/min per 1.73 m(2) [mild CKD], ≤59 mL/min per 1.73 m(2) [severe CKD]). Time to death from all-cause and cardiovascular causes and major adverse outcomes were assessed by multivariate regression adjusted for baseline covariates. RESULTS Obstructive coronary artery disease (CAD) was present only in few patients (39%). Even after adjusting for CAD severity, renal function remained a strong independent predictor of all-cause and cardiac mortality (P < .001). Every 10-unit decrease in eGFR was associated with a 14% increased risk of all-cause mortality (adjusted hazard ratio [AHR] 1.14 [1.08-1.20], P < .0001), 16% increased risk of cardiovascular mortality (AHR 1.16 [1.09-1.23], P < .0001), and 9% increased risk of adverse cardiovascular events (AHR 1.09 [1.03-1.15], P = .002). CONCLUSIONS Even mild CKD is a strong independent predictor of all-cause and cardiac mortality in women with symptoms/signs of ischemia, regardless of underlying obstructive CAD severity, underscoring the need to better understand the interactions between ischemic heart disease and CKD.

Calciphylaxis of the breast: a rare metabolic complication of kidney disease.

Calcific uraemic arteriolopathy (CUA) or calciphylaxis affects 1–4% of the population with end stage renal disease (ESRD) and associated with high mortality. Most lesions (90%) occur on the lower extremities1 followed by the lower abdomen. We report a severe case of CUA in an uncommon location—the breasts. A 54-year-old Caucasian woman with end stage kidney disease secondary to diabetic nephropathy, on maintenance haemodialysis for a year, was admitted with painful, open wound of the right breast. The initial lesion was …

Uric acid and the prediction models of tumor lysis syndrome in AML.

We investigated the ability of serum uric acid (SUA) to predict laboratory tumor lysis syndrome (LTLS) and compared it to common laboratory variables, cytogenetic profiles, tumor markers and prediction models in acute myeloid leukemia patients. In this retrospective study patients were risk-stratified for LTLS based on SUA cut-off values and the discrimination ability was compared to current prediction models. The incidences of LTLS were 17.8%, 21% and 62.5% in the low, intermediate and high-risk groups, respectively. SUA was an independent predictor of LTLS (adjusted OR 1.12, CI95% 1.0–1.3, p = 0.048). The discriminatory ability of SUA, per ROC curves, to predict LTLS was superior to LDH, cytogenetic profile, tumor markers and the combined model but not to WBC (AUCWBC 0.679). However, in comparisons between high-risk SUA and high-risk WBC, SUA had superior discriminatory capability than WBC (AUCSUA 0.664 vs. AUCWBC 0.520; p <0.001). SUA also demonstrated better performance than the prediction models (high-risk SUAAUC 0.695, p<0.001). In direct comparison of high-risk groups, SUA again demonstrated superior performance than the prediction models (high-risk SUAAUC 0.668, p = 0.001) in predicting LTLS, approaching that of the combined model (AUC 0.685, p<0.001). In conclusion, SUA alone is comparable and highly predictive for LTLS than other prediction models.

Renal function and coronary microvascular dysfunction in women with symptoms/signs of ischemia.

Objectives Chronic kidney disease (CKD) is more prevalent among women and is associated with adverse cardiovascular events. Among women with symptoms and signs of ischemia enrolled in the Women’s Ischemia Syndrome Evaluation (WISE), a relatively high mortality rate was observed in those with no obstructive coronary artery disease. Coronary microvascular dysfunction or reduced coronary flow reserve (CFR) was a strong and independent predictor of adverse outcomes. The objective of this analysis was to determine if renal function was associated with coronary microvascular dysfunction in women with signs and symptoms of ischemia. Methods The WISE was a multicenter, prospective, cohort study of women undergoing coronary angiography for suspected ischemia. Among 198 women with additional measurements of CFR, we determined the estimated glomerular filtration rate (eGFR) with the CKD-EPI equation. We tested the association between eGFR and CFR with regression analysis. Results The median eGFR was 89 ml/min. The eGFR correlated with CFR (r = 0.22; P = 0.002). This association persisted even after covariate adjustment. Each 10-unit decrease in eGFR was associated with a 0.04-unit decrease in CFR (P = 0.04).There was a strong interaction between eGFR and age (P = 0.006): in those ≥60 years old, GFR was strongly correlated with CFR (r = 0.55; P<0.0001). No significant correlation was noted in those <60 years old. Conclusions Reduced renal function was significantly associated with lower CFR in women with symptoms and signs of ischemia. Coronary microvascular dysfunction warrants additional study as a mechanism contributing to increased risk of cardiovascular events in CKD.

Racial and Socioeconomic Disparities in the Allocation of Expanded Criteria Donor Kidneys

BACKGROUND AND OBJECTIVES In carefully selected individuals, receiving expanded criteria donor (ECD) kidneys confer a survival advantage over remaining on dialysis. However, wait lists for ECD kidneys often include a significant proportion of young patients, who have no predictable survival benefit from ECD kidneys. This study hypothesized that educational and socioeconomic factors might influence a younger patients decision to accept an ECD kidney. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study was a retrospective analysis of all first single-kidney transplants in the Scientific Registry of Transplant Recipients database from 2000 to 2009 in patients aged 18-40 years and waitlisted <3 years. The primary outcome measured was the odds of receiving an ECD kidney compared with an standard criteria donor kidney in different demographic subgroups. Race, income, and education were analyzed in main-effect and two-way interaction models, corrected for candidate panel reactive antibodies and sex. RESULTS Of 13,615 ECD transplants, 591 kidneys (4.3%) went to recipients aged between 18 and 40 years who were waitlisted <3 years. African Americans (odds ratio, 1.71; 95% confidence interval, 1.26 to 2.33) or those with low education (odds ratio, 2.32; 95% confidence interval, 1.38 to 3.89) were more likely to receive an ECD kidney than Caucasians or those with a college degree, respectively. However, African Americans with higher education levels did not have significantly higher odds of receiving an ECD kidney than Caucasians with a college degree. CONCLUSIONS In patients aged <40 years and waitlisted <3 years, African Americans and those with lower educational status and low income are more likely to receive an ECD kidney than Caucasians or those with higher education. It is important that health care providers and patients understand such disparities to facilitate a more rational use of ECD kidneys.

Effects of Long-Term Type I Interferon on the Arterial Wall and Smooth Muscle Progenitor Cells Differentiation

Objective— Patients with systemic lupus erythematosis are at risk for premature atherosclerosis and half of the patients with systemic lupus erythematosis have elevated type I interferon (IFN-I) levels. We hypothesized that IFN-I would induce premature atherosclerosis by increasing the number of smooth muscle progenitor cells (SMPC) in the bloodstream and promoting atherosclerotic lesions within the vasculature. Approach and Results— SMPC isolated from wild-type and IFN receptor knockout animals were cultured in medium±IFN-I. In vivo, we used electroporation to generate stable IFN-I expression for as long as 4 months. The number of SMPC was determined in mice that expressed IFN-I and in control mice and sections from the bifurcation of the abdominal aorta were analyzed 3 months after electroporation of an IFN-I expression plasmid or a control plasmid. Adding IFN-I to the media increased the number of cultured wild-type SMPC and increased mRNA for SM22, but had no effect on SMPC isolated from IFN receptor knockout mice. Our in vivo results demonstrated a positive relationship between the preatherosclerotic-like lesions and endothelial damage. Although, there were no significant differences in smooth muscle cell density or thickness of the medial layer between groups, the IFN-I–expressing mice had a significant increase in preatherosclerotic-like lesions and immature smooth muscle cells, cells that expressed CD34 and smooth muscle &agr;-actin; but lacked smooth muscle myosin heavy chain. Conclusions— IFN-I seems to enhance SMPC number in vitro. In vivo IFN-I expression may maintain SMPC in an immature state. These immature smooth muscle cells could give rise to macrophages and eventually foam cells.