Effect of age and dialysis vintage on obesity paradox in long-term hemodialysis patients.

BACKGROUND: In contrast to the general population, higher body mass index (BMI) is associated with greater survival in patients receiving hemodialysis (HD; "obesity paradox"). We hypothesized that this paradoxical association between BMI and death may be modified by age and dialysis vintage. STUDY DESIGN: Retrospective observational study using a large HD patient cohort. SETTING & PARTICIPANTS: 123,383 maintenance HD patients treated in DaVita dialysis clinics between July 1, 2001, and June 30, 2006, with follow-up through September 30, 2009. PREDICTORS: Age, dialysis vintage, and time-averaged BMI. Time-averaged BMI was divided into 6 subgroups; <18.5, 18.5-<23.0, 23.0-<25.0, 25.0-<30.0, 30.0-<35.0, and ≥35.0kg/m(2). BMI category of 23-<25kg/m(2) was used as the reference category. OUTCOMES: All-cause, cardiovascular, and infection-related mortality. RESULTS: Mean BMI of study participants was 27±7kg/m(2). Time-averaged BMI was <18.5 and ≥35kg/m(2) in 5% and 11% of patients, respectively. With progressively higher time-averaged BMI, there was progressively lower all-cause, cardiovascular, and infection-related mortality in patients younger than 65 years. In those 65 years or older, even though overweight/obese patients had lower mortality compared with underweight/normal-weight patients, sequential increases in time-averaged BMI > 25kg/m(2) added no additional benefit. Based on dialysis vintage, incident HD patients had greater all-cause and cardiovascular survival benefit with a higher time-averaged BMI compared with the longer term HD patients. LIMITATIONS: Causality cannot be determined, and residual confounding cannot be excluded given the observational study design. CONCLUSIONS: Higher BMI is associated with lower death risk across all age and dialysis vintage groups. This benefit is more pronounced in incident HD patients and those younger than 65 years. Given the robustness of the survival advantage of higher BMI, examining interventions to maintain or even increase dry weight in HD patients irrespective of age and vintage are warranted.

Causes and prevention of protein-energy wasting in chronic kidney failure.

Protein-energy wasting (PEW), defined as reduced somatic and/or circulating body protein mass, decreased fat mass, and usually reduced protein and energy intake, has a prevalence that is variously estimated to be 18% to 75% in maintenance hemodialysis and chronic peritoneal dialysis patients. PEW is associated with increased morbidity and mortality and often is preventable or treatable. Thus, it has been argued that maintenance hemodialysis and chronic peritoneal dialysis patients should be monitored routinely for PEW and treated for this condition, when it occurs. A trend toward PEW can emerge in early stage 3 chronic kidney disease with an increasing risk toward the development and worsening of PEW as chronic kidney disease progresses. A main cause of PEW is inflammation, which may occur with or without clinically evident illness and can be associated with the most severe forms of PEW. Another major cause of PEW is decreased nutrient intake relative to the patient's nutritional needs, and may be caused by anorexia, which may be engendered by uremic toxicity, emotional depression, medications, or inflammatory disorders. Nonanorexic causes of reduced nutrient intake include inadequate finances to purchase or prepare foods; medical or surgical illnesses that impair the person's ability to ingest, digest, assimilate, or process the nutrients; impaired cognitive function; other mental or physical disabilities; and loss of dentures. Losses of nutrients during dialysis treatments or in urine (eg, the nephrotic syndrome), acidemia, and hormonal disorders can contribute to the development of PEW. Early initiation and adequate doses of renal replacement therapy, rapid treatment of reversible inflammatory processes, ensuring an adequate nutrient intake, and prevention of acidemia may be used to prevent and treat PEW.

Acute kidney injury caused by intravascular hemolysis after mechanical thrombectomy.

BACKGROUND: A 43-year-old African-American female (gravida 5 para 0) with an 8-week intrauterine pregnancy presented to the emergency room with crampy abdominal pain, shortness of breath, and shoulder pain. She had normal renal function on admission. CT angiography of the chest revealed bilateral pulmonary emboli; therefore, the AngioJet (Possis Medical, Inc., Minneapolis, MN) device was used to perform mechanical thrombolysis. The patient subsequently developed hyperkalemia, red urine and anuria. INVESTIGATIONS: Physical examination, measurement of serum creatinine level and electrolytes, dipstick urinalysis and centrifugation of urine and blood. DIAGNOSIS: Acute kidney injury due to hemoglobinuria as a result of non-immune-mediated intravascular hemolysis following the use of a percutaneous mechanical thrombectomy device (AngioJet). MANAGEMENT: Hydration, alkalinization of urine and initiation of hemodialysis (temporarily switched to continuous venovenous hemodiafiltration). Urine output improved after the 20th day of hospitalization, at which point dialysis was discontinued. The patient's renal function completely recovered by day 25.

Cardiovascular implications of chronic kidney disease in older adults.

Because serum creatinine is an imprecise indicator of glomerular filtration rate (GFR), estimating equations derived from the Modification of Diet in Renal Diseases study are increasingly being used to estimate GFR. The notion that GFR declines with aging is based largely on the results of cross-sectional studies that have generally not differentiated the effects of senescence from those of co-existing conditions such as hypertension. Nevertheless, GFR probably declines in many, if not all, aging individuals. The introduction of automated reporting of estimated GFR may result in an over-diagnosis of chronic kidney disease (CKD). There is a large body of evidence to suggest that a decrease in GFR and/or albuminuria is associated with an increased risk of death, particularly from cardiovascular causes, and that this risk extends to the elderly. Although the data are not consistent with regard to the level of GFR at which the increase in cardiovascular risk becomes apparent, small amounts of urine albumin excretion (levels that do not meet the definition of microalbuminuria) are associated with a higher risk of death, even among the elderly. There is currently no evidence that aggressive control of blood pressure and/or use of medications that reduce proteinuria, such as those that block the renin-angiotensin-aldosterone system, reduce the risk of cardiovascular events or death among individuals with CKD. On the other hand, secondary analyses of at least two studies have documented the benefit of lipid lowering in CKD patients. Paradoxically, a recent study has raised concern that normalizing haemoglobin may enhance the cardiovascular risk associated with CKD. To conclude, the available evidence indicates that early identification of CKD may allow physicians to aggressively modify cardiovascular risk, which, in turn, has the potential to improve patient outcomes.

Structural characterization, tissue distribution, and functional expression of murine aminoacylase III.

Many xenobiotics are detoxified through the mercapturate metabolic pathway. The final product of the pathway, mercapturic acids (N-acetylcysteine S-conjugates), are secreted predominantly by renal proximal tubules. Mercapturic acids may undergo a transformation mediated by aminoacylases and cysteine S-conjugate beta-lyases that leads to nephrotoxic reactive thiol formation. The deacetylation of cysteine S-conjugates of N-acyl aromatic amino acids is thought to be mediated by an aminoacylase whose molecular identity has not been determined. In the present study, we cloned aminoacylase III, which likely mediates this process in vivo, and characterized its function and structure. The enzyme consists of 318 amino acids and has a molecular mass (determined by SDS-PAGE) of approximately 35 kDa. Under nondenaturing conditions, the molecular mass of the enzyme is approximately 140 kDa as determined by size-exclusion chromatography, which suggests that it is a tetramer. In agreement with this hypothesis, transmission electron microscopy and image analysis of aminoacylase III showed that the monomers of the enzyme are arranged with a fourfold rotational symmetry. Northern analysis demonstrated an approximately 1.4-kb transcript that was expressed predominantly in kidney and showed less expression in liver, heart, small intestine, brain, lung, testis, and stomach. In kidney, aminoacylase III was immunolocalized predominantly to the apical domain of S1 proximal tubules and the cytoplasm of S2 and S3 proximal tubules. The data suggest that in kidney proximal tubules, aminoacylase III plays an important role in deacetylating mercapturic acids. The predominant cytoplasmic localization of aminoacylase III may explain the greater sensitivity of the proximal straight tubule to the nephrotoxicity of mercapturic acids.