The HALOS-ND model: a step in the journey of predicting hospital length of stay after liver transplantation.

Hospital length of stay (LOS) after liver transplantation has been determined to correlate with liver disease severity, post-transplant survival rates, and transplant-associated costs. A patient's model for end-stage liver disease (MELD) score and an organ's Donor risk index (DRI) have both been found to be significant predictors of LOS, but these two factors alone are insufficient to form an accurate prediction. Previous studies have identified other factors predictive of LOS, which can be incorporated with MELD and DRI to create more specific results. The objective of this study was to create an algorithm, or models, based on the most significant LOS predictors as identified from national data at different stages of the transplant process. Four models were developed predicting LOS using recipient factors, payment factors, donor factors, and postoperative factors. A medical care team member can enter a patient's data into the model and receive a reasonably accurate prediction of LOS for each phase of the liver transplant process, specifying the impact of each factor. These predictions would help predict the factors most likely to prolong LOS, inform resource allocation, and provide patients with more specific predictions of their LOS following transplantation.

Clinical factors predicting readmission after orthotopic liver transplantation.

Hospitals with the highest readmission rates for high-cost conditions may be targeted for payment penalties. The primary aim of this study was to determine clinical predictors of 30-day readmission after discharge for patients undergoing orthotopic liver transplantation (OLT) at the University of Washington from January 2003 to October 2010. Secondary aims included the determination of predictors of institutional care after OLT and differences in survival between patients requiring 30-day readmission and patients not requiring 30-day readmission. Sixty-five of 766 discharged OLT patients (8.6%) required institutional care on discharge; 318 of the 701 remaining patients (45%) were readmitted within 30 days. The predictors of readmission included hospitalization within the 90 days before OLT [29.6% versus 18.4%, relative risk (RR) = 1.33, P = 0.04], pre-OLT portal vein thrombosis (7.9% versus 4.4%, RR = 1.76, P = 0.01), a creatinine level > 1.9 mg/dL (23.9% versus 11.5%, RR = 2.1, P ≤ 0.01), an albumin level < 2.6 mg/dL (51.9% versus 37.6%, RR = 1.57, P < 0.01), postoperative complications (38.7% versus 30.2%, RR = 1.31, P = 0.04), and a high school education or less (14.5% versus 10%, RR = 1.41, P = 0.04). One year after OLT, decreased survival was found for patients requiring 30-day readmission versus patients not requiring readmission (88.2% versus 95.6%, P < 0.05). In conclusion, this study has identified patients at high risk of readmission who may benefit from medical optimization.

New and experimental therapies for HCV.

Despite improvements to treatments for HCV infection, almost half of patients cannot be cured with standard combination therapy (pegylated interferon alpha and ribavirin). The HCV life cycle offers a number of potential targets for molecular therapy, and several specifically targeted antiviral therapies for HCV (STAT-Cs) are in preclinical and clinical stages of development. Evidence to date suggests that monotherapy with any antiviral drug is unlikely to eradicate HCV infection. Combination therapy with interferon and ribavirin is necessary for the augmentation of antiviral drug activity and/or prevention of drug resistance. Results from clinical trials carried out in the past few years on STAT-C agents in combination with standard therapy with peginterferon and ribavirin provide great promise of higher rates of sustained virological response and, potentially, shorter duration of therapy than standard therapy alone achieves. Although pegylated interferon and ribavirin are likely to remain a cornerstone of therapeutic regimens in the short term, combinations of antiviral drugs of different classes, possibly along with novel agents that target host factors and modulate viral replication or augment antiviral defenses, offer the eventual possibility of interferon-free regimens.

Subcortical cognitive impairment in dialysis patients.

Given the high burden of atherosclerotic cardiovascular disease in dialysis patients, we hypothesized that cognitive testing would reveal subtle abnormalities in subcortical brain function, a measure frequently associated with cerebrovascular disease. Detailed neurocognitive testing was performed in 25 hemodialysis patients. All patients had Mini-Mental State Examination (MMSE) scores >24 and had no history of cerebrovascular disease. Where appropriate, scores were normalized for age, gender, and education. One-sample t tests were used to compare differences in cognitive function between dialysis patients and normative data. The mean age was 57 years, and the mean MMSE was 27.5. Fourteen subjects (56%) were females, and 15 white (60%). Results of the North American Adult Reading Test, a measure of verbal intelligence, were comparable with the general population. Similarly, measures of cortical function, namely retention and recognition scores from the Word List Learning subtest of the Wechsler Memory Scale-III, were preserved when compared with normative data where reference = 10. Significant deficits were seen on tests assessing subcortical function: scores (mean+/-standard deviation) for block design, and symbol coding subtests of the Wechsler Adult Intelligence Scale-III were 7.0+/-1.7 and 7.7+/-3.1, respectively (p<0.001 for both comparisons with normative data). Similarly, adjusted scores on the trails A and B tests were 40.5+/-8.3 and 41.8+/-11.3, respectively (p<0.001 for both comparisons with normative data where reference= 50). These results suggest that, despite relatively normal MMSE scores, mild cognitive impairment may be prevalent in hemodialysis patients. The pattern of cognitive dysfunction is primarily subcortical in nature.

Adiponectin and mortality in patients with chronic kidney disease.

Adiponectin is presumed to possess antiatherogenic and cardioprotective properties. Limited data exist on the relationship between adiponectin and mortality in the earlier stages of chronic kidney disease. The Modification of Diet in Renal Disease study was a randomized, controlled trial that was conducted between 1989 and 1993. Adiponectin was measured in frozen samples that were obtained at baseline (N = 820). Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of adiponectin with all-cause and cardiovascular mortality. Mean +/- SD age was 52 +/- 12 yr, and mean +/- SD glomerular filtration rate (GFR) rate was 33 +/- 12 ml/min per 1.73 m2. Eighty-five percent of participants were white, and 60% were male. Mean +/- SD adiponectin was 12.8 +/- 8.0 mug/ml. Triglycerides, insulin resistance, glucose, body mass index, GFR, C-reactive protein, and albumin were inversely related and proteinuria and HDL cholesterol were directly related to adiponectin. During the 10-year follow-up period, 201 (25%) participants died of any cause, and 122 (15%) from cardiovascular disease. In multivariable adjusted Cox models, a 1-mug/ml increase in adiponectin was associated with a 3% (hazard ratio 1.03; 95% confidence interval 1.01 to 1.05; P = 0.02) increased risk for all-cause and 6% (hazard ratio 1.06; 95% confidence interval 1.03 to 1.09; P < 0.001) increased risk for cardiovascular mortality. High, rather than low, adiponectin is associated with increased mortality in this cohort of patients with chronic kidney disease stages 3 to 4. Further studies are necessary to confirm this association and to elucidate the underlying mechanisms.

Relationship between homocysteine and mortality in chronic kidney disease.

BACKGROUND: The relationship between total homocysteine (tHcy) and outcomes has not been investigated in patients with chronic kidney disease stages 3 to 4. METHODS AND RESULTS: The Modification of Diet in Renal Disease Study was a randomized, controlled trial of 840 patients. Serum tHcy was measured in frozen samples collected at baseline (n=804). Survival status and cause of death were obtained from the National Death Index. To evaluate its association with all-cause and cardiovascular disease (CVD) mortality, tHcy was evaluated both as tertiles (<14.7, 14.7 to 19.5, > or =19.6 micromol/L) and as a continuous variable (per 10/micromol/L). Participants had a mean age of 52+/-12 years and glomerular filtration rate (GFR) of 33+/-12 mL/min per 1.73 m2; 60% were male, and 85% were white. During a median follow-up of 10 years, 195 (24%) died from any cause, and 118 (15%) from CVD. The level of GFR was lower and proteinuria higher in the highest tHcy tertile. There was no association between the highest tertile of tHcy and all-cause (hazard ratio [HR]; 95% confidence interval [CI[, 1.32, 0.94 to 1.85) or CVD (HR; 95% CI, 1.50, 0.96 to 2.34) mortality in univariate analyses; this association was further attenuated by adjustment for GFR (HR; 95% CI all-cause, 1.04, 0.72 to 1.51; CVD, 1.20, 0.73 to 1.95). There was no association between tHcy as a continuous variable and all-cause (0.98, 0.83 to 1.16) or CVD (1.04, 0.85 to 1.27) mortality. CONCLUSIONS: Hyperhomocystinemia does not appear to be a risk factor for all-cause or CVD mortality in the Modification of Diet in Renal Disease Study. Prior studies demonstrating an association between tHcy and CVD risk may have inadequately adjusted for the confounding effects of kidney function.

Glycosylated hemoglobin and mortality in patients with nondiabetic chronic kidney disease.

In the general population, hyperglycemia in the absence of diabetes may be associated with increased risk for mortality. Hyperglycemia is prevalent in chronic kidney disease; however, the relationship between glycosylated hemoglobin (HbA(1c)) as a marker of chronic hyperglycemia and outcomes has not been studied in nondiabetic chronic kidney disease. HbA(1c) was measured at baseline in the randomized cohort of the Modification of Diet in Renal Disease Study (n = 840). Participants with diabetes (n = 43), fasting glucose levels >126 mg/dl (n = 20), or missing HbA(1c) levels (n = 9) were excluded. Survival status until December 2000 was obtained from the National Death Index. Death was classified as cardiovascular (CVD) when the primary cause was International Classification of Disease, Ninth Revision codes 390 to 459. Cox models were performed to assess the relationship of HbA(1c) with all-cause and CVD mortality. Mean (SD) age was 52 (12) years, and mean (SD) GFR was 32 (12) ml/min per 1.73 m(2). Eighty-six percent of participants were white, and 61% were male. Mean (SD) HbA(1c) was 5.6% (0.5). A total of 169 (22%) patients died, 96 (13%) from CVD. After adjustment for randomization assignments and demographic, CVD, and kidney disease factors, HbA(1c) was a predictor of all-cause mortality (hazard ratio per 1% increase 1.73; 95% confidence interval 1.24 to 2.41; P = 0.001). There was a trend toward statistical significance in the relationship between HbA(1c) and CVD mortality (hazard ratio per 1% increase 1.53; 95% confidence interval 0.96 to 2.43; P = 0.07). HbA(1c) is associated with increased mortality in nondiabetic kidney disease. Hyperglycemia may be a potential therapeutic target and HbA(1c) may be important as a risk stratification tool in this high-risk population.

Relationship of phosphorus and calcium-phosphorus product with mortality in CKD.

BACKGROUND: Abnormalities of mineral metabolism are prevalent in patients with kidney failure and are associated with increased risk for cardiovascular events. There are limited data investigating relationships of phosphorus and calcium-phosphorus product with outcomes in patients with chronic kidney disease (CKD) stages 3 to 4. METHODS: Serum phosphorus and calcium were measured at baseline in 840 participants from the randomized cohort of the Modification of Diet in Renal Disease Study. Survival status until December 31, 2000, was obtained from the National Death Index. Cox models were performed to assess the relationship of serum phosphorus level and calcium-phosphorus product with all-cause and cardiovascular disease (CVD) mortality. RESULTS: Mean serum phosphorus level was 3.8 +/- 0.7 mg/dL (1.23 +/- 0.23 mmol/L), calcium-phosphorus product was 34.7 +/- 6.3 mg2/dL2, and glomerular filtration rate (GFR) was 33 +/- 12 mL/min/1.73 m2 (0.55 +/- 0.20 mL/s/1.73 m2). All-cause and CVD mortality rates were 25% and 15%. Serum phosphorus level was not related to all-cause mortality in multivariable models (P = 0.46). In unadjusted analysis, serum phosphorus level was associated with (hazard ratio [HR] per 1 mg/dL increase, 1.34; 95% confidence interval [CI], 1.05 to 1.71; P = 0.02) increased risk for CVD mortality, but this association was partly attenuated and not statistically significant after adjustment for GFR and other confounders (HR, 1.27; 95% CI, 0.94 to 1.73; P = 0.12). Calcium-phosphorus product was not associated with all-cause mortality in unadjusted (P = 0.23) or multivariate analysis (P = 0.35). Calcium-phosphorus product was related to CVD mortality in unadjusted (HR per 10 mg2/dL2 increase, 1.30; 95% CI, 1.01 to 1.69; P = 0.04) analysis, but this association was not statistically significant after adjustment for GFR and other confounders (HR, 1.22; 95% CI, 0.89 to 1.66; P = 0.23). CONCLUSION: In the Modification of Diet in Renal Disease Study cohort, serum phosphorus level and calcium-phosphorus product were not statistically associated with all-cause or CVD mortality after adjustment for GFR; however larger studies with additional statistical power are needed to evaluate these relationships, especially in the context of current practice patterns in patients with CKD.

C-reactive protein and albumin as predictors of all-cause and cardiovascular mortality in chronic kidney disease.

BACKGROUND: High C-reactive protein (CRP) and hypoalbuminemia are associated with increased risk of mortality in patients with kidney failure. There are limited data evaluating the relationships between CRP, albumin, and outcomes in chronic kidney disease (CKD) stages 3 and 4. METHODS: The Modification of Diet in Renal Disease (MDRD) Study was a randomized controlled trial conducted between 1989 and 1993. CRP was measured in frozen samples taken at baseline. Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of CRP [stratified into high CRP > or =3.0 mg/L (N= 414) versus low CRP<3.0 mg/L (N= 283)], and serum albumin, with all-cause and cardiovascular mortality. RESULTS: Median follow-up time was 125 months, all-cause mortality was 20% (N= 138) and cardiovascular mortality was 10% (N= 71). In multivariable analyses adjusting for demographic, cardiovascular and kidney disease factors, both high CRP (HR, 95% CI = 1.56, 1.07-2.29) and serum albumin (HR = 0.94 per 0.1 g/dL increase, 95% CI = 0.89-0.99) were independent predictors of all-cause mortality. High CRP (HR 1.94, 95% CI 1.13-3.31), but not serum albumin (HR 0.94, 95% CI 0.87-1.02), was an independent predictor of cardiovascular mortality. CONCLUSION: Both high CRP and low albumin, measured in CKD stages 3 and 4, are independent risk factors for all-cause mortality. High CRP, but not serum albumin, is a risk factor for cardiovascular mortality. These results suggest that high CRP and hypoalbuminemia provide prognostic information independent of each other in CKD.

Cognitive function in dialysis patients.

There are few detailed studies of cognitive function in dialysis patients. However, appreciating the prevalence and risk factors for cognitive impairment is important because cognitive impairment may decrease an individual's quality of life, increase resource utilization, and result in suboptimal medical care because of difficulty following caregiver recommendations. Cognitive impairment also is likely to become more of a problem as the dialysis population ages. In this review, we argue that cerebrovascular disease is an important cause of cognitive impairment in dialysis patients and discuss risk factors specific for vascular disease, as well as other factors that may influence cognitive function. We describe the structural brain abnormalities frequently seen in dialysis patients and the specific neurocognitive changes noted in prior studies. We explore potential measures to reduce cognitive impairment in this population. We conclude that additional research is needed in this area.

Anemia as a risk factor for cardiovascular disease.

In the present review we examine the physiologic response to chronic anemia and describe potential adverse effects of anemia on myocardial and large arterial remodeling. We present observational data demonstrating that anemia is a risk factor for cardiovascular disease (CVD) outcomes in patients with chronic kidney disease and patients with heart failure. We also present data that have evaluated the relationship of level of hematocrit to CVD outcomes in patients with ischemic heart disease and in patients in the general population. The results from the latter studies have been inconclusive and have been limited by lack of knowledge of the cause of anemia. This is potentially important because iron deficiency anemia may, in fact, improve endothelial function. We conclude that additional randomized controlled trials of treatment of anemia are needed in chronic kidney disease and patients with heart failure; however, further exploration of the cause of anemia and the effect of different types of anemia on various CVD outcomes are needed in patients with ischemic heart disease and patients in the general population.