Cardiac structural and functional abnormalities in end stage renal disease patients with elevated cardiac troponin T.

OBJECTIVES: To identify in a prospective observational study the cardiac structural and functional abnormalities and mortality in patients with end stage renal disease (ESRD) with a raised cardiac troponin T (cTnT) concentration. METHODS: 126 renal transplant candidates were studied over a two year period. Clinical, biochemical, echocardiographic, coronary angiographic, and dobutamine stress echocardiographic (DSE) data were examined in comparison with cTnT concentrations dichotomised at cut off concentrations of < 0.04 microg/l and < 0.10 microg/l. RESULTS: Left ventricular (LV) size and filling pressure were significantly raised and LV systolic and diastolic function parameters significantly impaired in patients with raised cTnT, irrespective of the cut off concentration. The proportions of patients with diabetes and on dialysis were higher in both groups with raised cTnT. With a cut off cTnT concentration of 0.04 microg/l but not 0.10 microg/l, significantly more patients had severe coronary artery disease and a positive DSE result. The total ischaemic burden during DSE was similar in cTnT positive and negative patients, irrespective of the cut off concentration used. LV end systolic diameter index and E:Ea ratio were independent predictors of cTnT rises > or = 0.04 microg/l and > or = 0.10 microg/l, respectively. Diabetes was independently associated with cTnT at both cut off concentrations. Mortality was higher in all patients with raised cTnT. CONCLUSIONS: Patients with ESRD with raised cTnT concentrations have increased mortality. Raised concentrations are strongly associated with diabetes, LV dilatation, and impaired LV systolic and diastolic function, but not with severe coronary artery disease.

Dobutamine stress echocardiography and cardiac troponin T for the detection of significant coronary artery disease and predicting outcome in renal transplant candidates.

AIMS: Ischaemic heart disease is the leading cause of mortality and morbidity in patients with end-stage renal disease (ESRD) and after renal transplantation. However, the optimal non-invasive test for coronary artery disease (CAD) diagnosis in this population has yet to be established. The aim of this study was to assess the diagnostic accuracy of dobutamine stress echocardiography (DSE) and baseline plasma cardiac troponin T (cTnT) for detecting significant CAD and predicting adverse cardiac events in patients referred for renal transplantation. METHODS: Coronary angiography, DSE, and baseline cTnT measurements were performed in 118 consecutive patients (mean age 52+/-12 years, 75 male) with ESRD (mean creatinine 608+/-272 micromol/L) referred for renal transplantation. The mean follow-up period was 1.32+/-0.48 years. Significant CAD was defined as a reduction in luminal diameter >70% by visual estimation in at least one major epicardial vessel. An abnormal DSE result defined as the development of a new regional wall motion abnormality in one or more normal resting segments or a deterioration of wall motion in one or more resting hypokinetic segments. A baseline cTnT>0.1 microg/L was taken as positive. RESULTS: Significant CAD in at least one vessel was present in 35 patients (30%). The number of patients with significant 3 vessel and 2 vessel disease was 6 and 7, respectively. An abnormal DSE result was present in 36 (31%) patients. Thirty-one (26%) had cTnT>0.1 microg/L. Sixty-four (54%) patients were on dialysis and 46 (39%) were diabetic. The sensitivity, specificity, positive and negative predictive values for DSE in detecting significant coronary artery disease were 88%, 94%, 86% and 95%, respectively. The same values for a raised cTnT were 54%, 62%, 40% and 74%, respectively. The combination of an abnormal DSE result and raised cTnT gave values of 61%, 91%, 76%, and 80%, respectively. Over the follow-up period, mortality was significantly higher in those with a raised baseline cTnT but not those with an abnormal DSE result or significant CAD. CONCLUSION: DSE is an accurate technique for the detection of significant CAD in renal transplant candidates. An elevated cTnT does not predict significant CAD in this population and when used in conjunction with DSE, reduces the sensitivity of the combined tests. cTnT is an important marker of prognosis in renal transplant candidates.

Incubation of porcine high-density lipoprotein with the apical surface of LLC-PK1 renal tubular cells sustains the properties of orientated monolayers.

BACKGROUND: HDL is present in the urine of patients with the nephrotic syndrome. The amount of HDL is directly related to the protein selectivity and therefore to the renal prognosis. Urinary HDL may therefore be involved in the pathogenesis of progressive renal impairment in proteinuric renal disease. METHODS: LLC-PK1 cells were grown as orientated monolayers on filters. Uptake of HDL and permeability to inulin were measured. The influence of HDL in the growth medium on monolayer resistance, protein content, and sodium dependent glucose transport was studied. The effects of tetranitromethane (TNM) nitrosylation of HDL and of albumin, mevalonate, or simvastatin were investigated. RESULTS: Confluent LLC-PK1 monolayers took up fluorescently labelled HDL from either epithelial surface and formed a significant diffusion barrier to inulin. Monolayers incubated in 300 micrograms/ml HDL achieved a protein content and plateau of resistance equal to those in 10% fetal calf serum (FCS); 30-1000 micrograms/ml HDL applied to the apical surface of confluent monolayers maintained a plateau of resistance as well as 10% FCS and significantly better than serum-free medium. Sodium-dependent glucose transport was preserved in monolayers exposed to HDL. Simvastatin completely, and nitrosylation partially, removed the stimulatory properties of HDL. These were partly reproduced by albumin or mevalonate. CONCLUSIONS: HDL can enter renal epithelial cells from the apical surface. HDL added to this surface at confluence, reproducing the conditions found in the nephrotic syndrome, had a measurable positive effect on monolayer resistance. Results with nitrosylated HDL and HMG-CoA blockade suggest that these effects may be mediated via receptors and this enzyme system.

Gastric emptying in patients with chronic renal failure on continuous ambulatory peritoneal dialysis.

Radionuclide gastric emptying studies were carried out on 20 patients with end-stage renal failure (ESRF) undergoing continuous ambulatory peritoneal dialysis (CAPD). Nine of the patients had diabetes mellitus. Eight normal volunteers were also studied to establish normal ranges. Solid and liquid emptying patterns were investigated simultaneously using a meal made up of a solid phase labelled with 99mTechnetium and a liquid phase labelled with 111Indium. The solid emptying fitted a model with a lag phase followed by a linear emptying phase and the liquid emptying fitted a single exponential. Nine of the 20 patients (four diabetic, five non-diabetic) were found to have delayed solid emptying, and four of these (two diabetic, two non-diabetic) also had delayed liquid emptying. No correlation was found between any of the parameters studied and the clinical symptoms of the patients. It is concluded that almost half of the patients studied had abnormal gastric emptying, but that many of these did not suffer from severe symptoms.

Lipiduria in renal disease.

This article reviews the published data on lipiduria in both health and disease. Small amounts of lipid appear in the urine under normal circumstances but, in the nephrotic syndrome in humans, there is also a considerable amount of high-density lipoprotein in the urine as well as smaller amounts of other lipoproteins. Potential tubular re-uptake mechanisms for lipoproteins have been demonstrated in both animal and cell-culture models. In humans, there is no direct evidence for these specific re-uptake mechanisms--it is only through specific staining of renal biopsies for apolipoproteins that the presence of such mechanisms in intracellular vesicular structures is suggested. It is possible that lipoprotein filtration and re-uptake by the tubule are important mechanisms in tubular injury.