Predicting hospital cost in CKD patients through blood chemistry values

<p>Abstract</p> <p>Background</p> <p>Controversy exists in predicting costly hospitalization in patients with chronic kidney disease and co-morbid conditions. We therefore tested associations between serum chemistry values and the occurrence of in-patient hospital costs over a thirteen month study period. Secondarily, we derived a linear combination of variables to estimate probability of such occurrences in any patient.</p> <p>Method</p> <p>We calculated parsimonious values for select variables associated with in-patient hospitalization and compared sensitivity and specificity of these models to ordinal staging of renal disease.</p> <p>Data from 1104 de-identified patients which included 18 blood chemistry observations along with complete claims data for all medical expenses.</p> <p>We employed multivariable logistic regression for serum chemistry values significantly associated with in-patient hospital costs exceeding $3,000 in any single month and contrasted those results to other models by ROC area curves.</p> <p>Results</p> <p>The linear combination of weighted Z scores for parathyroid hormone, phosphorus, and albumin correlated with in-patient hospital care at p < 0.005. ROC curves derived from weighted variables of age, eGFR, hemoglobin, albumin, creatinine, and alanine aminotransferase demonstrated significance over models based on non-weighted Z scores for those same variables or CKD stage alone. In contrast, the linear combination of weighted PTH, PO4 and albumin demonstrated better prediction, but not significance over non-weighted Z scores for PTH alone.</p> <p>Conclusion</p> <p>Further study is justified to explore indices that predict costly hospitalization. Such metrics could assist Accountable Care Organizations in evaluating risk adjusted compensation for providers.</p

Effects of verapamil on the abnormalities in fatty acid oxidation of myocardium

The oxidation of long (LCFA) and short chain fatty acids (SCFA) by myocardial mitochondria is impaired in CRF due to reduced activity of carnitine palmitoyl transferase (CPT) and of enzymes in the β-oxidation sequence in mitochondrial matrix. It was proposed that PTH, through its ability to augment entry of calcium into cells, enhances calcium uptake by the myocardium leading to calcium accumulation which in turn affects mitochondrial function. A calcium channel blocker may therefore correct these derangements. The present study examined the effects of verapamil on LCFA and SCFA oxidation and on CPT activity of myocardial mitochondria and on 45Ca uptake by, and clacium content of, myocardium obtained from CRF rats and rats treated with PTH, with and without administration of verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P < 0.01) reduction in the oxidation of LCFA and SCFA by and of CPT activity of myocardial mitochondria and a significant increase in 45Ca uptake by, and content of, the myocardium. Simultaneous administration of verapamil reversed all these derangements. Administration of verapamil alone to normal rats for 4 or 21 days did not cause significant changes in these parameters. The results of our studies are consistent with the notion that the alterations in myocardial oxidation of LCFA and SCFA in CRF or after PTH treatment are related to PTH-induced calcium accumulation in the heart, and could be reversed by a calcium channel blocker. The data could provide a rational therapeutic approach for the management of uremic myocardiopathy

Effects of verapamil on the abnormalities in fatty acid oxidation of myocardium

The oxidation of long (LCFA) and short chain fatty acids (SCFA) by myocardial mitochondria is impaired in CRF due to reduced activity of carnitine palmitoyl transferase (CPT) and of enzymes in the β-oxidation sequence in mitochondrial matrix. It was proposed that PTH, through its ability to augment entry of calcium into cells, enhances calcium uptake by the myocardium leading to calcium accumulation which in turn affects mitochondrial function. A calcium channel blocker may therefore correct these derangements. The present study examined the effects of verapamil on LCFA and SCFA oxidation and on CPT activity of myocardial mitochondria and on 45Ca uptake by, and clacium content of, myocardium obtained from CRF rats and rats treated with PTH, with and without administration of verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P < 0.01) reduction in the oxidation of LCFA and SCFA by and of CPT activity of myocardial mitochondria and a significant increase in 45Ca uptake by, and content of, the myocardium. Simultaneous administration of verapamil reversed all these derangements. Administration of verapamil alone to normal rats for 4 or 21 days did not cause significant changes in these parameters. The results of our studies are consistent with the notion that the alterations in myocardial oxidation of LCFA and SCFA in CRF or after PTH treatment are related to PTH-induced calcium accumulation in the heart, and could be reversed by a calcium channel blocker. The data could provide a rational therapeutic approach for the management of uremic myocardiopathy

Verapamil reverses PTH- or CRF-induced abnormal fatty acid oxidation in muscle

Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and 45Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P < 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P < 0.01) increment in 45Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker

Fatty acid oxidation in the myocardium: Effects of parathyroid hormone and CRF

Fatty acids constitute an important substrate utilized by the myocardium as a major fuel for energy production; certain data suggest that oxidation of long chain fatty acids (LCFA) may be impaired in uremia, and such a derangement could, in part, contribute to the myocardiopathy of uremia. The latter is associated with secondary hyperparathyroidism and PTH has been shown to affect myocardial metabolism. The present study evaluated in rats the effects of four days administration of PTH and 21 days of chronic renal failure (CRF) with and without excess PTH on oxidation of α-ketoglutarate, β-hydroxybutyric acid, LCFA and short chain fatty acids (SCFA). PTH impaired oxidation of α-ketoglutarate, LCFA, SCFA, but not of β-hydroxybutyric acid and reduced the activity of carnitine palmitoyl transferase (CPT). Inactivation of the PTH abolished its effects. CRF rats with intact parathyroid glands also had impaired oxidation of LCFA and CTP activity. Carnitine contents of myocardium were not altered. The data show that PTH excess in normal rats is associated with impaired oxidation of LCFA and SCFA, and secondary hyperparathyroidism in CRF animals impairs oxidation of LCFA. This effect is due to: 1) reduction in the activity of CPT, a key enzyme for the transport of LCFA to mitochondrial matrix for β-oxidation; and 2) impairment in β-oxidation. The data provide for new and additional pathway through which excess PTH and CRF can affect myocardial metabolism

MECHANISM OF ORGAN DYSFUNCTION IN PHOSPHATE-DEPLETION - A CRITICAL ROLE FOR A RISE IN CYTOSOLIC CALCIUM

Phosphate depletion (PD) is associated with multiorgan dysfunction. it has been proposed that this phenomenon is due to two metabolic derangements: (a) there is a reduction in ATP content of cells and hence reduced availability of energy-rich phosphate compounds, and (b) there is a decrease in 2,3-diphosphoglycerate in red blood cells, a change that would increase the affinity of hemoglobin to oxygen resulting in tissue hypoxia. Recent studies have demonstrated that PD is associated with a significant elevation in basal levels of cytosolic calcium [Ca2+]i in many cells. This is due to an increased entry into and decreased extrusion of calcium out of cells. This rise in [Ca2+]i plays a major role in organ dysfunction in PD and in the genesis of decreased ATP content of cells