B-type Natriuretic Peptides Strongly Predict Mortality in Patients Who Are Treated with Long-Term Dialysis

Background and objectives: Left ventricular abnormalities contribute to cardiovascular disease in patients with chronic kidney disease and may be detected by measurement of B-type natriuretic peptide in serum.Design, setting, participants, & measurements: In a prospective cohort study of predialysis patients, patients who were on dialysis, and kidney transplant recipients, serum was collected and assayed for both B-type natriuretic peptide and its N-terminal fragment. Median levels were compared using nonparametric tests, and predictors of B-type natriuretic peptide were determined by linear regression. Survival analysis and Cox regression were performed to examine the association of levels of B-type natriuretic peptide with cardiovascular events and death.Results: Levels of B-type natriuretic peptide were highest in patients who were on dialysis. Patients who were receiving dialysis and had known cardiovascular disease, were not on the waiting list for kidney transplantation, or had left ventricular systolic dysfunction on echocardiography had significantly higher levels of B-type natriuretic peptide than patients without these characteristics. Glomerular filtration rate was an important predictor of B-type natriuretic peptide levels for patients who were not on dialysis (predialysis and renal transplant recipients). Left ventricular systolic dysfunction predicted B-type natriuretic peptide levels in patients who were on dialysis. Both forms of B-type natriuretic peptide were associated with a two- to three-fold increased risk for death in patients who were on dialysis.Conclusions: Levels of B-type natriuretic peptide are greatest in patients who are on dialysis and have cardiovascular comorbidities and are strong predictors of death.Patients with chronic kidney disease (CKD) have an increased prevalence of structural abnormalities of the left ventricle, such as left ventricular hypertrophy (LVH) and congestive heart failure (1). A biochemical marker that potentially allows for the early detection, intervention, and ongoing surveillance of myocardium at risk for developing these abnormalities is B-type natriuretic peptide (BNP). This peptide hormone is released from the left ventricular myocardium in response to increased wall tension (2). After being released, the prohormone is cleaved to the active hormone BNP-32 and the inactive N-terminal fragment NT-BNP-76 (3), both of which can be measured in serum. In people without CKD, BNP is most useful in ruling out a diagnosis of cardiac failure in the clinical setting of a presentation with dyspnea (4) but has also been validated in both the detection and prognostication of other cardiac (5) and respiratory conditions (6).In patients with CKD, BNP has yet to find its place in the management of cardiovascular disease (CVD), despite its potential for identification of left ventricular abnormalities in the general population. Both BNP-32 (7,8) and NT-BNP-76 (9) correlate positively with left ventricular mass index and negatively with left ventricular ejection fraction in patients who are on dialysis. The influence of reduction in GFR on levels of BNP is an important reason that its role is not established in CKD. Both forms of BNP are influenced by GFR (10,11), and patients who are on dialysis have the highest levels of BNP compared with other CKD populations (12); however, there is no established level of BNP that identifies patients who are on dialysis and have cardiac disease. We tested the hypotheses that patients who are on dialysis have higher levels of BNP than predialysis patients and kidney transplant recipients, that levels of BNP will differ in patients who are on dialysis by the level of existing cardiovascular comorbidities, and that elevated levels of BNP predict cardiovascular events and mortality.     

Mitochondrial DNA deletions cause the biochemical defect observed in Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia, increasing in prevalence with age. Most patients who develop AD have an unknown cause, but characteristic neuropathological features include the deposition of extracellular amyloid beta and of intraneuronal hyperphosphorylated tau protein. Researchers have previously implicated mitochondrial dysfunction in AD. We previously showed an increase in neurons displaying a mitochondrial biochemical defect-cytochrome-c oxidase (COX) deficiency-in the hippocampus in patients with sporadic AD compared with age-matched controls. COX deficiency is well described as a marker of mitochondrial (mt) DNA dysfunction. This present study analyzed the mtDNA in single neurons from both COX normal and COX-deficient cells. Analysis of the mtDNA revealed that COX deficiency is caused by high levels of mtDNA deletions which accumulate with age. Future research is needed to clarify the role mtDNA deletions have in normal aging and investigate the relationship between mtDNA deletions and the pathogenesis of sporadic AD.     

Apoenzyme of aspartate aminotransferase in serum in health and disease

Aspartate aminotransferase activity has been measured in the sera of normal subjects and in patients with various diseases both with and without addition of pyridoxal phosphate to the assay medium. Considerable quantities of apoaminotransferase were present in almost all samples. In normal subjects this potentially-active enzyme corresponds on average to about half the holoenzyme present before reactivation with pyridoxal phosphate. However, considerable variations between individuals were found in the amounts of apoaminotransferase present in serum, and also between groups of patients with various diseases.     

Erythrocyte ammonia in liver disease

This study reports the relevance of plasma and erythrocyte ammonia concentrations in patients with liver disease. Three groups of subjects were studied: group 1, 47 normal subjects; group 2, 73 patients with liver disease; and group 3, 14 patients with portal-systemic encephalopathy (PSE). The difference in plasma ammonia concentrations between groups 1 and 2 was not significant, but for erythrocyte ammonia this was significant (p less than 0.05). Group 3 subjects had significantly elevated plasma (p less than 0.001) and erythrocyte ammonia (p less than 0.001) compared with the other two groups (Mann-Whitney U-test). In group 3, two patients had plasma ammonia values within the reference range, whereas six patients had values within the range of group 2 subjects. However, none of group 3 subjects had erythrocyte ammonia concentrations within the range of either group 1 or 2. A cut-off level of 65 mumol/l was assigned to differentiate group 3 from group 2 subjects. We conclude that erythrocyte ammonia measurement is a better biochemical index of PSE than plasma ammonia.     

PLASMA FERRITIN LEVELS AS A GUIDE TO THE TREATMENT OF PORPHYRIA CUTANEA TARDA BY VENESECTION

We have examined prospectively the plasma ferritin levels during management often patients with porphyria cutanea tarda (PCT) who were being treated by venesection. We compared plasma ferritin levels with clinical features as well as with plasma, urine and faecal porphyrin levels.
Plasma ferritin and porphyrin levels were found to be variable during the initial period of treatment, and then decreased in parallel with the clinical improvement. Clinical remission and a fall in porphyrin levels lagged several weeks behind the near exhaustion of body iron stores as indicated by plasma ferritin levels. This lag period and the initial variable porphyrin levels are best explained, we believe, by the presence of a large accumulation of porphryin in the liver of patients with PCT. We suggest that venesection be stopped when plasma ferritin falls to the lower end of the reference range.