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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2008.09.039 Byline: Michel Chonchol (a), Rita Dale (b), Robert W. Schrier (a), Raymond Estacio (c)(d) Keywords: Calcium; Calcium-phosphorus product; Cardiovascular disease; Cardiovascular mortality; Phosphorus; Type 2 diabetes Abstract: Although serum phosphorus, calcium, and calcium-phosphorus product levels have been associated with cardiovascular events and mortality in patients with normal kidney function, most studies have not examined the association of these minerals with outcomes when collected repeatedly over time. Author Affiliation: (a) Division of Renal Diseases and Hypertension, University of Colorado at Denver, Health Sciences Center, Denver, Colo (b) Colorado Prevention Center, Denver, Colo (c) University of Colorado at Denver, Health Sciences Center, Denver, Colo (d) Department of Internal Medicine, Denver Health, Denver, Colo Article Note: (footnote) Funding: Clinical revenues., Conflict of Interest: None., Authorship: All authors participated in the conception and design of the study, the interpretation of data, drafting and critical revision of the manuscript, and have read and approved the manuscript.

Background: Acute tubular necrosis (ATN) is common in hospitalized patients, particularly in the intensive care unit. Over the past four decades, the mortality rate from ATN has remained at 50% to 80%. Purpose: To review recent studies of diagnosis and treatment strategies for ATN. Data Sources: MEDLINE search for all clinical studies of therapies for ATN, supplemented by a review of the references of the identified articles. Study Selection: Prospective studies and major retrospective studies evaluating therapies for ATN. Data Extraction: Data on the study sample, interventions performed, results, side effects, and duration of follow-up. Data Synthesis: Early diagnosis of ATN by exclusion of prerenal and postrenal causes of acute renal failure, examination of urinary sediment, and analysis of urine measures (for example, fractional excretion of sodium in the absence of diuretics) can allow the early involvement of nephrologists and improve survival. Enteral rather than parenteral hyperalimentation in severely malnourished patients may improve survival. Sepsis causes 30% to 70% of deaths in patients with ATN; therefore, avoidance of intravenous lines, bladder catheters, and respirators is recommended. Because septic patients are vasodilated, large volumes of administered fluid accumulate in the lung interstitium of these patients. This condition necessitates ventilatory support, which when prolonged leads to acute respiratory distress syndrome, multiorgan failure, and increased mortality. More aggressive dialysis (for example, given daily) with biocompatible membranes may improve survival in some patients with acute renal failure. Conclusions: New information about the importance of early diagnosis and supportive care for patients with ATN has emerged. However, randomized trials of these interventions are needed to test their effect on the morbidity and mortality of ATN.

Exercise capacity has been used as a noninvasive parameter for predicting cardiovascular events. It is known that diabetic patients have an impaired exercise capacity when compared with nondiabetic age-matched control subjects, but the risk factors associated with this impairment have not been thoroughly analyzed. A total of 453 male and female NIDDM patients who underwent graded exercise testing with expired gas analysis were studied to determine the possible influences of demographic and cardiac risk factors on exercise capacity. Univariate and multiple linear regression analyses were performed on baseline patient characteristics with respect to peak oxygen consumption ([VO.sub.2]). In the regression analyses, African-American race was strongly associated with a decrease in peak [VO.sub.2]; the difference in means between African-Americans and other subjects for men was -2.50 ml [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1] (-4.28, -0.07, 95% CI) (P < 0.006) and for women was -2.96 ml [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1] (-4.45, -1.47) (P < 0.0002). Univariate analyses revealed that African-American subjects had increased prevalence, longer duration, and higher systolic and diastolic hypertension than the non-Hispanic and Hispanic whites. Other independent predictors of peak [VO.sub.2] (reported as change in peak [VO.sub.2] in milliliters per kilogram per minute) were BMI (men: -0.39 kg/[m.sup.2] [-0.52, -0.29], P < 0.0001; women: -0.39 kg/[m.sup.2] [-0.48, -0.311, P < 0.0001), age (men: -0.16/year [-0.23, -0.091, P < 0.0001; women: -0.17/ year [-0.24, -0.11], P < 0.0001), baseline resting systolic blood pressure (men: -0.03/mmHg [-0.06, -0.011, P < 0.05; women: -0.03/mmHg (-0.06, -0.01], P < 0.05), and pack-years smoking (men: -0.0/(pack-years [-0.04, -0.01], P < 0.01; women: -0.04/pack-years [-0.07, -0.011, P < 0.0001). Thus, in this large NIDDM study, weight loss, smoking cessation, and aggressive blood pressure control, particularly in African-Americans with NIDDM, would appear to be important in improving exercise capacity and potentially improving the increased cardiovascular mortality associated with an impaired exercise capacity. Diabetes 45:79-85, 1996, Cardiovascular disease accounts for 40% of the overall mortality in this country (1) and is the leading cause of mortality in the NIDDM population (2,3). Moreover, NIDDM accounts for ~90% [...]

The body's normal homeostasis is maintained by the integrity of the excretory capacity of the kidneys. in advanced cardiac failure, however, the avidity of the renal sodium and water retention contributes to the occurrence of pulmonary congestion and peripheral edema. in patients with advanced cirrhosis, the kidneys again fail to excrete the amounts of sodium and water ingested, thus leading to ascites and peripheral edema. The signals for this renal retention of sodium and water in a patient with cirrhosis must be extrarenal because when the same kidneys are transplanted into persons with normal liver function, renal sodium and water retention no longer occurs; rather, the kidneys maintain normal fluid and electrolyte balance. Excessive sodium and water retention by the kidneys also occurs during pregnancy despite a 30% to 50% increase in plasma volume, cardiac output, and glomerular filtration rate. What are the afferent and efferent signals whereby normal kidneys retain sodium and water so that total extracellular, interstitial, and intravascular volumes expand far beyond those limits observed in normal subjects? These dilemmas are the subject of this review, in which a 'unifying hypothesis of body fluid volume regulation' is presented. (Schrier RW, Niederberger M: Paradoxes of body fluid volume regulation in health and disease - A unifying hypothesis. West J Med 1994; 161:393-408), The regulation of body fluid volume is important in almost every area of medicine and has been the focus of myriad investigations during this century. When most of life was [...]

The VSMC is an important target for the injurious effects of hyperglycemia in vivo. PKC plays a key role in the regulation of VSMC contraction and growth. This study examines [...]

Autosomal-dominant polycystic kidney disease (ADPKD) is an inherited disease of the kidney in which hypertension (high blood pressure) precedes the characteristic loss of kidney function in between 50 and 75 percent of the patients diagnosed with the condition. Evidence suggests that impaired blood flow to the kidney caused by cyst growth causes activation of the renin-angiotensin system (a kidney hormone system involved with the maintenance of fluid balance and blood pressure), resulting in increased blood pressure. Hence, angiotensin-converting enzyme (ACE) inhibitors, a widely used class of antihypertensive medication, have been reported to be extremely effective in the treatment of ADPKD-related hypertension. In patients with massive cyst infiltration of the kidney, ACE-inhibitor treatment may adversely affect kidney function. Eight instances are reported of reversible acute kidney deterioration in five patients with ADPKD, massive kidney involvement, and chronic renal (kidney) insufficiency during ACE-inhibitor treatment for hypertension. Patients were both men and women, ranging in age from 32 to 78 years; in all cases ACE-inhibitor therapy either predisposed the patient to or precipitated the acute event. Two of the patients who experienced renal failure during ACE-inhibitor treatment experienced a recurrence of the failure when an attempt was made to reintroduce treatment with the same drugs. Hence, patients with ADPKD-related hypertension who have compromised kidney function or extensive cystic involvement of the kidney are at risk for adverse effects of ACE inhibitor treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

A study investigates whether heart rate recovery (HRR) predicts all-cause mortality, cardiovascular (CV) mortality and CV events in patients with type 2 diabetes mellitus (T2DM). Results indicate that HRR provides information on key CV risk factors in asymptomatic patients with T2DM.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2006.09.012 Byline: Horng H. Chen (a), Robert W. Schrier (b) Keywords: Atrial natriuretic peptide; B-type natriuretic peptide; Neurohormones; Pulmonary capillary wedge pressure; Renin-angiotensin-aldosterone system Abstract: The inability to effectively regulate volume status is a major consequence of acute heart failure syndromes (AHFS). A variety of pathophysiologic processes contribute to this impairment, most notably neurohormonal activation of the renin-angiotensin-aldosterone system, arginine vasopressin, and the sympathetic nervous system. As a result, addressing volume overload is one of the most challenging aspects of AHFS management. Neurohormonal activation leads to substantial changes in hemodynamics and myocardial remodeling, which further contribute to the severity of heart failure (HF) disease and thereby cyclically increase the risk of further neurohormonal activation. Pulmonary capillary wedge pressure is a dependable reflection of volume status and has been used as a surrogate marker in recent studies to assess disease progression in response to innovative HF treatment strategies. Future approaches to HF treatment should focus on the more accurate assessment and management of volume status in an effort to improve patient care. Author Affiliation: (a) Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA (b) Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, Denver, Colorado, USA

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2006.05.007 Byline: Robert W. Schrier Keywords: Cardiac failure; Cirrhosis; Pregnancy; Vasopressin Abstract: This article discusses the pathophysiology of sodium and water retention in edematous disorders with a particular focus on cardiac failure, cirrhosis, and pregnancy. The body fluid volume hypothesis, which emphasizes the dominant role of arterial baroreceptors in renal sodium and water excretion, is reviewed. With arterial underfilling, either due to a decrease in cardiac output or peripheral arterial vasodilation, the normal central inhibition of the sympathetic nervous system activity and baroreceptor-mediated, nonosmotic arginine vasopressin (AVP) release is attenuated. The resultant increase in renal adrenergic activity stimulates the renin-angiotensin-aldosterone system. Although the resultant increase in systemic vascular resistance compensates for the primary arterial underfilling, this activation of the neurohumoral axis results in diminished sodium and water delivery to the renal collecting duct sites of aldosterone, AVP, and natriuretic peptide action. This diminished distal sodium and water delivery will be discussed as an important factor in the failure to escape from the sodium-retaining effects of aldosterone, the resistance to the natriuretic and diuretic effects of natriuretic peptides, and the diminished maximal solute-free water excretion in patients with edema. The role of the nonosmotic AVP release in water retention and hypo-osmolality/hyponatremia has been demonstrated in patients and experimental animals by administering nonpeptide, orally active vasopressin V.sub.2 receptor antagonists. These agents have been found to increase solute-free water excretion in patients with water-retaining, hyponatremic edema as well as in experimental animals. Author Affiliation: Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado School of Medicine, Denver, Colorado, USA Article Note: (footnote) This work was supported by Grant No. P01 DK19928 from the National Institute of Diabetes, Digestive, and Kidney Diseases.

The renin angiotensin system, a major regulator of vascular tone, has been implicated in the development of diabetic micro - and macroangiopathy. The D allele of the insertion/deletion (I/D) polymorphism [...]

OBJECTIVE -- The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective randomized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on [...]

ACE inhibitors may be beneficial in patients with end-stage kidney disease even if they don't have diabetes. ACE inhibitors can slow the progression of kidney disease in diabetics, but this is the first time they have been evaluated in non-diabetics with kidney disease.