Lung transplantation following coronary artery bypass surgery-improved outcomes following single-lung transplant.

BACKGROUND: Prior coronary artery bypass grafting (CABG) has been a contraindication to lung transplantation (LTx) because of disease severity and technical considerations. Although patients increasingly are being referred for and receiving LTx, whether it should remain a contraindication is unknown. We sought to define the prevalence of LTx after CABG and determine the effect on outcomes. METHODS: The United Network for Organ Sharing Standard Transplant Analysis and Research data set was queried during the period 2004-2013 for adult LTx patients, as prior CABG became a mandatory reporting field in 2004. The primary end-points were 30-day and 1-, 3-, and 5-year survivals. RESULTS: The study cohort included 14,791 patients, of whom 292 patients had previously undergone CABG (single left, n = 68; single right, n = 181; bilateral, n = 43), representing 2% of all transplants. For the entire cohort, 30-day survival was 97%, and survival at 1, 3, and 5 years was 88%, 79%, and 74%. CABG was a predictor of mortality at all time points, with hazard ratios ranging from 1.97 (confidence interval, 1.23-3.16; p < 0.01) at 30 days to 1.38 (confidence interval, 1.12-1.69; p < 0.01) at 5 years. When stratified by type of transplant, CABG strongly predicted mortality at all time points for patients receiving bilateral, but not single, transplants. CONCLUSIONS: Although LTx after CABG is uncommon, it is increasingly performed in the current era. Single right LTx is the most common procedure performed in patients with prior CABG. CABG before LTx is an independent predictor of mortality at all time points and is driven by increased mortality in patients receiving bilateral LTx.

Ventricular assist devices or inotropic agents in status 1A patients? Survival analysis of the United Network of Organ Sharing database.

BACKGROUND: Improved outcomes as well as lack of donor hearts have increased the use of ventricular assist devices (VADs), rather than inotropic support, for bridging to transplantation. Recognizing that organ allocation in the highest status patients remains controversial, we sought to compare outcomes of patients with VADs and those receiving advanced medical therapy. METHODS: The United Network of Organ Sharing (UNOS) database was used to compare survival on the waiting list and posttransplantation survival in status 1A heart transplantation patients receiving VADs or high-dose/dual inotropic therapy or an intraaortic balloon pump( IABP), or both. Adjusted survival was calculated using Cox's proportional hazard model. RESULTS: Adjusted 1-year posttransplantation mortality was higher among patients with VADs compared with patients receiving inotropic agents alone (hazard ratio [HR], 1.48; p<0.05). Survival remained better for patients receiving inotropic agents alone in the post-2008 era (HR, 1.36; p=0.03) and among those with isolated left-sided support (HR, 1.33; p=0.008). When patients who received IABPs were added and analyzed after 2008, the left ventricular assist device (LVAD) group had similar survival (HR, 1.2; p=0.3). Survival on the waiting list, however, was superior among patients with LVADs (HR, 0.56; p<0.05). In a therapy transition analysis, failure of inotropic agents and the need for LVAD support was a consistent marker for significantly worse mortality (HR, 1.7; p<0.05). CONCLUSIONS: Although posttransplantation survival is better for patients who are bridged to transplantation with inotropic treatment only, the cost of failure of inotropic agents is significant, with a nearly doubled mortality for those who later require VAD support. Survival on the waiting list appears to be improved among patients receiving VAD support. Careful selection of the appropriate bridging strategy continues to be a significant clinical challenge.

Associations of serum skeletal alkaline phosphatase with elevated C-reactive protein and mortality.

BACKGROUND AND OBJECTIVES: Higher serum total alkaline phosphatase (AP) levels are associated with increased serum C-reactive protein (CRP) levels and mortality in the general and CKD populations. It is unclear to what extent these associations are related to bone disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a nationally representative sample of 10,707 adult participants from the 1999-2004 National Health and Nutrition Examination Survey, serum nonskeletal AP levels were estimated from the measured serum skeletal and total AP levels. The associations of serum skeletal AP and nonskeletal AP levels with elevated serum CRP concentrations (>3 mg/L) and mortality were examined in multivariable models. RESULTS: Skeletal AP was not associated with elevated CRP (for each doubling in non-CKD: odds ratio [OR], 1.00; 95% confidence interval [95% CI], 0.90-1.11; in CKD: OR, 1.19; 95% CI, 0.83-1.70) or mortality (for each doubling in non-CKD: hazard ratio [HR], 1.10; 95% CI, 0.94-1.29; in CKD: HR, 0.98; 95% CI, 0.75-1.28). In contrast, nonskeletal AP was associated with elevated CRP (for each doubling in non-CKD: OR, 4.51; 95% CI, 3.80-5.35; in CKD: OR, 5.98; 95% CI, 3.40-10.51). Nonskeletal AP was associated with mortality in non-CKD (for each doubling: HR, 1.96; 95% CI, 1.37-2.80) but not in CKD (for each doubling: HR, 0.92; 95% CI, 0.51-1.67) (interaction P=0.03). CONCLUSIONS: Bone disease is unlikely to account for the known associations of serum total AP with increased inflammation and mortality.

Impact of ventricular assist device complications on posttransplant survival: an analysis of the United network of organ sharing database.

BACKGROUND: Although current left ventricular assist device (LVAD) technology has proven more durable than first-generation devices, all mechanical devices are prone to complications that can elevate patient acuity before transplantation. LVAD patients with complications intuitively carry a higher risk profile than other status 1A LVAD patients who are generally stable and use their 30 days of clinically stable status 1A time. We sought to determine if the presence or absence of complications in status 1A LVAD patients at the time of transplant influenced survival after transplant. METHODS: The United Network of Organ Sharing database was retrospectively analyzed for 15,253 patients who were listed status 1A from 1998 to 2008. Survival after transplant survival was compared between patients who were and were not listed for LVAD-related complications. Standard statistical analysis was applied. RESULTS: No survival difference was identified at 1 and 10 years after transplant in patients who had device complications compared with those without complications. Of the five complication entries (thromboembolism, infection, malfunction, malignant arrhythmia, and other), only device infection increased mortality risk compared with noncomplicated patients (39% at 1 year, 30% at 10 years, p < 0.01). CONCLUSIONS: Long-term outcomes are generally not affected by the status 1A listing criteria for patients bridged to transplant with LVADs. However, the subset of patients with device infection had worse 1-year and 10-year posttransplant survival. Bridge to transplant patients, despite serious device-related complications, still have excellent transplant outcomes.

Effect of donor kidney volume on recipient outcome: does the "dose" matter?

BACKGROUND: The effect of donor kidney volume on recipient kidney function has not been fully evaluated. METHODS: We performed a prospective analysis of 125 consecutive living kidney donor/recipient pairs. Donor kidney volume was calculated from pretransplantation computed tomography angiograms using a three-dimensional computerized volume method. Cortical volume was calculated from arterial phase and total volume from delayed phase. Because weight is a surrogate marker for metabolic demands, we looked at the "volume dose" by calculating the ratio of donor kidney volume to recipient weight. Recipient kidney function was assessed by calculating the estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration formula. Logistic regression models were used to evaluate odds of developing eGFR of <60 mL/min per 1.73m(2) (eGFR<60) at 12 months. RESULTS: Because cortical and total volumes were correlated (R=0.734, P<0.001), we used total kidney volume to evaluate the dose effect. The mean donated volume dose (SD) was 2.13 (0.62) mL/kg. The mean recipient eGFR at 12 months was 63.6 (17.3) mL/min per 1.73 m, and it correlated with volume dose (r=0.341, P<0.001). Compared with the lowest tertile, those in the highest tertile of donor kidney volume to recipient weight had lower odds ratio of developing eGFR of less than 60 mL/min per 1.73 m(2) (odds ratio, 0.23; 95% confidence interval, 0.07-0.81) in a multivariate logistic regression model. Spline regression suggested that a volume dose greater than 2.5 mL/kg was associated with lowest risk of eGFR of less than 60 mL/min per 1.73 m(2) at 12 months. CONCLUSIONS: Donor kidney volume dosing is an important determinant of recipient graft outcomes and may predict recipient kidney function in kidney transplantation.

Education is associated with reduction in racial disparities in kidney transplant outcome.

In this study, we hypothesized that higher level of education might be associated with reduced racial disparities in renal transplantation outcomes. We used data from the United States Renal Data System (September 1, 1990-September 1, 2007) (n=79,223) and analyzed two outcomes, graft loss and recipient mortality, using Cox models. Compared with whites, African Americans had increased risk of graft failure (HR, 1.48; p<0.001) and recipient mortality (HR, 1.06; p=0.004). Compared with recipients who graduated from college, all other education groups had inferior graft survival. Specifically, compared with college-graduated individuals, African Americans who never finished high school had the highest risk of graft failure (HR, 1.45; p<0.001), followed by high school graduates (HR, 1.27; p<0.001) and those with some college education (HR, 1.18; p<0.001). A similar trend was observed in whites. In African Americans (compared with whites), the highest risk of graft failure was associated with individuals who did not complete high school (HR, 1.96; p<0.001) followed by high school graduates (HR, 1.47; p<0.001), individuals with some college education (HR, 1.45; p<0.001), and college graduates (HR, 1.39; p<0.001). A similar trend was observed with recipient mortality. In sum, higher education was associated with reduced racial disparities in graft and recipient survival.

Effect of education on racial disparities in access to kidney transplantation.

Higher education level might result in reduced disparities in access to renal transplantation. We analyzed two outcomes: (i) being placed on the waiting list or transplanted without listing and (ii) transplantation in patients who were placed on the waiting list. We identified 3224 adult patients with end-stage renal disease (ESRD) in United States Renal Data System with education information available (mean age of ESRD onset of 57.1 ± 16.2 yr old, 54.3% men, 64.2% white, and 50.4% diabetics). Compared to whites, fewer African Americans graduated from college (10% vs. 16.7%) and a higher percentage never graduated from the high school (38.6% vs. 30.8%). African American race was associated with reduced access to transplantation (hazard ratio [HR] 0.70, p < 0.001 for wait-listing/transplantation without listing; HR 0.58, p < 0.001 for transplantation after listing). African American patients were less likely to be wait-listed/transplanted in the three less-educated groups: HR 0.67 (p = 0.005) for those never completed high school, HR 0.76 (p = 0.02) for high school graduates, and HR 0.65 (p = 0.003) for those with partial college education. However, the difference lost statistical significance in those who completed college education (HR 0.75, p = 0.1). In conclusion, in comparing white and African American candidates, racial disparities in access to kidney transplantation do exist. However, they might be alleviated in highly educated individuals.

High dietary fiber intake is associated with decreased inflammation and all-cause mortality in patients with chronic kidney disease.

Chronic kidney disease is considered an inflammatory state and a high fiber intake is associated with decreased inflammation in the general population. Here, we determined whether fiber intake is associated with decreased inflammation and mortality in chronic kidney disease, and whether kidney disease modifies the associations of fiber intake with inflammation and mortality. To do this, we analyzed data from 14,543 participants in the National Health and Nutrition Examination Survey III. The prevalence of chronic kidney disease (estimated glomerular filtration rate less than 60 ml/min per 1.73 m(2)) was 5.8%. For each 10-g/day increase in total fiber intake, the odds of elevated serum C-reactive protein levels were decreased by 11% and 38% in those without and with kidney disease, respectively. Dietary total fiber intake was not significantly associated with mortality in those without but was inversely related to mortality in those with kidney disease. The relationship of total fiber with inflammation and mortality differed significantly in those with and without kidney disease. Thus, high dietary total fiber intake is associated with lower risk of inflammation and mortality in kidney disease and these associations are stronger in magnitude in those with kidney disease. Interventional trials are needed to establish the effects of fiber intake on inflammation and mortality in kidney disease.

Improved survival in heart transplant patients living at high altitude.

OBJECTIVE: Higher altitudes are associated with chronic hypoxia and elevated pulmonary vascular resistance, both potentially detrimental to patients requiring heart transplantation. The purpose of the present study was to determine whether altitude negatively affects survival among patients undergoing heart transplantation. METHODS: The United Network of Organ Sharing database for adult patients undergoing heart transplantation from 1990 to 2008 (n = 36,529) was analyzed, and each patient was assigned an altitude according to their home ZIP code. Survival was compared between patients at less than 2000 ft, 2000 or more to less than 4000 ft, and 4000 ft or more. Adjusted survival was calculated using Cox proportional hazards analysis with propensity-matched stratification. RESULTS: Patients living at above 2000 ft had a 16% reduction in the risk of death at 1 year after transplant (P = .006) compared with those at lower altitudes. At 5 and 10 years, the risk reduction was 6% (P = .21) and 6% (P = .114), respectively. Among patients living above 4000 ft, the 1-, 5-, and 10-year reduction in the risk of death was 20% (P = .022), 12% (P = .057), and 15% (P = .0052) compared with those living below 2000 ft, respectively. Patients at high altitude had a lower incidence of diabetes, used tobacco less often, and accounted for the greatest proportion of status 2 heart transplants. Comparing the factors predicting survival at high and low altitudes, patients with a status 1A listing had improved outcomes at higher altitudes. CONCLUSIONS: Patients living above 2000 ft have improved survival after heart transplantation, an advantage even more pronounced at 4000 ft. Although the mechanism of protection remains unclear, the findings might reflect differences in pre-2006 organ allocation.

Dietary phosphorus intake and mortality in moderate chronic kidney disease: NHANES III.

BACKGROUND: Dietary phosphorus intake is usually restricted in dialysis patients but the associations of dietary phosphorus intake with mortality in moderate chronic kidney disease (CKD) are unknown. Therefore, we examined these associations in National Health and Nutrition Examination Survey III. METHODS: Dietary phosphorus intake was estimated from 24-h dietary recalls administered by trained personnel. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2). Time to mortality was examined by Cox regression models taking into account the complex survey design. RESULTS: 1105 adults with CKD were studied. Phosphorus intake was 1033 ± 482 mg/day (mean ± SD), eGFR was 49.3 ± 9.5 mL/min/1.73 m(2) and serum phosphorus was 3.5 ± 0.5 mg/dL. Compared to those in the lowest tertile of phosphorus intake (mean 532 ± 161 mg/day), those in the highest third (1478 ± 378 mg/day) had similar serum phosphorus levels (3.6 ± 0.5 versus 3.5 ± 0.6 mg/dL, P = 0.113) and modestly higher eGFR (50.0 ± 8.1 versus 47.5 ± 12.0 mL/min/1.73 m(2), P = 0.014). After adjustment for demographics, comorbidity, eGFR, physical activity, energy intake and nutritional variables, phosphorus intake was not associated with mortality [hazard ratio (HR) 0.98 per 100 mg/dL increase, 0.93-1.03]. CONCLUSIONS: High dietary phosphorus intake is not associated with increased mortality in moderate CKD, presumably because serum phosphorus levels are maintained in the normal range at this level of GFR. Interventional trials are needed to define optimal phosphorus intake in moderate CKD.

Cognitive function and the risk of death in chronic kidney disease.

BACKGROUND AND AIMS: Cognitive impairment is a risk factor for death in dialysis patients and the general population. We sought to determine if cognitive impairment is associated with death in people with non-dialysis-dependent chronic kidney disease (CKD), and if so, whether this relationship is greater in the CKD population compared to the general population. METHODS: National Health and Nutrition Examination Survey-III participants older than 60 years were asked to subtract 3 from 20 five times and to perform immediate and delayed recall of three items. A cognitive score of 0-11 was assigned based on the number of correct responses. Participants were categorized according to cognitive score (11, 9-10, 6-9, and 0-5) and CKD status. Survival analyses were conducted using Cox models. RESULTS: Within the CKD subpopulation, those in the lowest cognitive score group had a twofold increased hazard of death compared to those with maximum score. Within the non-CKD subpopulation, those in the lowest cognitive score group had a 46% increased hazard of death compared to those with maximum score. However, the difference in the hazards of death in the CKD and non-CKD subpopulations with the lowest cognitive score was not significant (p = 0.99). CONCLUSIONS: Low cognitive score is associated with an increased risk of death in elderly individuals with and without CKD; however, there was no interaction of CKD and low cognitive score in this analysis.

Social adaptability index predicts kidney transplant outcome: a single-center retrospective analysis.

BACKGROUND: Social adaptability index (SAI) is the composite index of socioeconomic status based upon employment status, education level, marital status, substance abuse and income. It has been used in the past to define populations at higher risk for inferior clinical outcomes. The objective of this retrospective study was to evaluate the association of the SAI with renal transplant outcome. METHODS: We used data from the clinical database at the Beth Israel Deaconess Medical Center Transplant Institute, supplemented with data from United Network for Organ Sharing for the years 2001-09. The association between SAI and graft loss and recipient mortality in renal transplant recipients was studied using Cox model in the entire study population as well as in the subgroups based on age, race, sex and diabetes status. RESULTS: We analyzed 533 end-stage renal disease patients (mean age at transplant 50.8 ± 11.8 years, 52.2% diabetics, 58.9% males, 71.1% White). Higher SAI on a continuous scale was associated with decreased risk of graft loss [hazard ratio (HR) 0.89, P < 0.05, per 1 point increment in the SAI] and decreased risk of recipient mortality (HR 0.84, P < 0.01, per 1 point increment in the SAI). Higher SAI was also significantly associated with decreased risk for graft loss/recipient mortality in some study subgroups (age 41-65 years, males, non-diabetics). CONCLUSIONS: SAI has an association with graft and recipient survival in renal transplant recipients. It can be helpful in identifying patients at higher risk for inferior transplant outcome as a target population for potential intervention.

Predicting three-year kidney graft survival in recipients with systemic lupus erythematosus.

Predicting the outcome of kidney transplantation is important in optimizing transplantation parameters and modifying factors related to the recipient, donor, and transplant procedure. As patients with end-stage renal disease (ESRD) secondary to lupus nephropathy are generally younger than the typical ESRD patients and also seem to have inferior transplant outcome, developing an outcome prediction model in this patient category has high clinical relevance. The goal of this study was to compare methods of building prediction models of kidney transplant outcome that potentially can be useful for clinical decision support. We applied three well-known data mining methods (classification trees, logistic regression, and artificial neural networks) to the data describing recipients with systemic lupus erythematosus (SLE) in the US Renal Data System (USRDS) database. The 95% confidence interval (CI) of the area under the receiver-operator characteristic curves (AUC) was used to measure the discrimination ability of the prediction models. Two groups of predictors were selected to build the prediction models. Using input variables based on Weka (a open source machine learning software) supplemented with additional variables of known clinical relevance (38 total predictors), the logistic regression performed the best overall (AUC: 0.74, 95% CI: 0.72-0.77)-significantly better (p < 0.05) than the classification trees (AUC: 0.70, 95% CI: 0.67-0.72) but not significantly better (p = 0.218) than the artificial neural networks (AUC: 0.71, 95% CI: 0.69-0.73). The performance of the artificial neural networks was not significantly better than that of the classification trees (p = 0.693). Using the more parsimonious subset of variables (six variables), the logistic regression (AUC: 0.73, 95% CI: 0.71-0.75) did not perform significantly better than either the classification tree (AUC: 0.70, 95% CI: 0.68-0.73) or the artificial neural network (AUC: 0.73, 95% CI: 0.70-0.75) models. We generated several models predicting 3-year allograft survival in kidney transplant recipients with SLE that potentially can be used in practice. The performance of logistic regression and classification tree was not inferior to more complex artificial neural network. Prediction models may be used in clinical practice to identify patients at risk.

Associations of serum alkaline phosphatase with metabolic syndrome and mortality.

BACKGROUND: Recent data suggest that elevated serum alkaline phosphatase levels are associated with increased mortality, but the mechanisms for this association are unknown. As metabolic syndrome is associated with higher serum alkaline phosphatase levels, we examined the joint association of mortality with metabolic syndrome and serum alkaline phosphatase levels in the US general population. METHODS: Retrospective observational study of 15,234 adult participants in the National Health and Nutrition Examination Survey III. Multivariable Cox regression analyses were used to jointly relate mortality risk to serum alkaline phosphatase and indicators of metabolic syndrome. RESULTS: Prevalence of metabolic syndrome was 14% to 41% among patients in lowest and higher quartiles, respectively, for baseline serum alkaline phosphatase. The mortality hazard ratio for each doubling of serum alkaline phosphatase was 1.52 (95% confidence interval [CI], 1.35-1.72) adjusting only for demographic factors, and 1.37 (95% CI, 1.21-1.56) adjusting for both demographic and metabolic syndrome factors in the full cohort, and was 1.83 (95% CI, 1.36-2.46) adjusting for demographic factors in the subgroup without any of the component conditions of metabolic syndrome. CONCLUSIONS: In the US general population, higher levels of serum alkaline phosphatase is a predictor of mortality independent of the baseline prevalence of metabolic syndrome. Further studies are warranted to unravel the mechanisms of this association.

Validating prediction models of kidney transplant outcome using single center data.

Prediction of kidney transplant outcome represents an important and clinically relevant problem. Although several prediction models have been proposed based on large, national collections of data, their utility at the local level (where local data distributions may differ from national data) remains unclear. We conducted a comparative analysis that modeled the outcome data of transplant recipients in the national US Renal Data System (USRDS) against a representative local transplant dataset at the University of Utah Health Sciences Center, a regional transplant center. The performance of an identical set of prediction models was evaluated on both national and local data to assess how well national models reflect local outcomes. Compared with the USRDS dataset, several key characteristics of the local dataset differed significantly (e.g., a much higher local graft survival rate; a much higher local percentage of white donors and recipients; and a much higher proportion of living donors). This was reflected in statistically significant differences in model performance. The area under the receiver operating characteristic curve values of the models predicting 1, 3, 5, 7, and 10-year graft survival on the USRDS data were 0.59, 0.63, 0.76, 0.91, and 0.97, respectively. In contrast, in the local dataset, these values were 0.54, 0.58, 0.58, 0.61, and 0.70, respectively. Prediction models trained on a national set of data from the USRDS performed better in the national dataset than in the local data. This might be due to the differences in the data characteristics between the two datasets, suggesting that the wholesale adoption of a prediction model developed on a large national dataset to guide local clinical practice should be done with caution.

Social Adaptability Index predicts access to kidney transplantation.

Identifying the group of subjects prone to disparities in access to kidney transplantation is important for developing potential interventions. Data from the United States Renal Data System (January 1, 1990-September 1, 2007; n = 3407) were used to study association between the Social Adaptability Index (SAI; based upon employment, marital status, education, income, and substance abuse) and outcomes (time to being placed on the waiting list and time to being transplanted once listed). Patients were 56.9 ± 16.1 yr old, 54.2% men, 64.2% white, and 50.4% had diabetes. SAI was higher in whites (7.4 ± 2.4) than African Americans (6.5 ± 2.6) [ANOVA, p < 0.001] and greater in men (7.4 ± 2.4) than in women (6.7 ± 2.5) [T-test, p < 0.001]. In multivariate model, greater SAI (range 0-12) was associated with increased likelihood of being placed on the waiting list (hazard ratio [HR] 1.19 [95% CI 1.15-1.23] per each point of increase in SAI, p < 0.001) and greater likelihood of receiving a transplant once listed (HR of 1.06 [95% CI 1.03-1.09] per point of increase in SAI, p < 0.001). Similar trends were observed in most of the subgroups (based upon race, sex, diabetic status, age, comorbidities, and donor type). SAI is associated with access to renal transplantation in patients with end-stage renal disease; it may be used to indentify individuals at risk of healthcare disparities.

Social Adaptability Index: application and outcomes in a dialysis population.

BACKGROUND: Patient groups associated with disparities in health care are usually defined on the basis of race, gender or geographic location. Social Adaptability Index (SAI), calculated based on education, marital status, income, employment and substance abuse, has been strongly associated with clinical outcome in other patient populations and may be used to identify individuals at risk. We used data from the United States Renal Data System to evaluate the role of SAI in survival of patients on dialysis. METHODS: We used Cox model analyses to study the association between SAI and patient survival in patients with ESRD on dialysis, as well as in the subgroups based on age, race, sex, comorbidites and diabetic status. RESULTS: We analyzed 3396 patients (age of ESRD onset 56.9 ± 16.1 years, 54.2% males, 64.2% white, 30.3% African-American). Mean SAI of the entire population was 7.1 ± 2.5 (range 0-12 points). SAI was higher in whites (7.4 ± 2.4) than in African-Americans (6.5 ± 2.5) (analysis of variance, P <0.001) and greater in men (7.4 ± 2.4) than in women (6.7 ± 2.5) (t-test, P <0.001). In a Cox model adjusted for potential confounders, SAI was associated with decreased mortality [hazards ratio of 0.97 (95% confidence interval 0.95-0.99), P = 0.006]. Subgroup analysis demonstrated an association of SAI with survival in most of the subgroups. Potential limitations of the study include reverse causality, possible misclassification and retrospective design. CONCLUSION: We demonstrated that SAI is significantly associated with mortality in dialysis patients. SAI could be used to identify individuals at risk for inferior clinical outcomes.

Serum alkaline phosphatase levels associate with elevated serum C-reactive protein in chronic kidney disease.

High serum alkaline phosphatase concentrations are associated with elevated serum C-reactive protein (CRP) levels in the general population. To examine whether this association is independent of serum vitamin D levels or modified in chronic kidney disease (CKD), we determined if such associations exist using data from the National Health and Nutrition Examination Survey III of 14,420 adult participants in which 5.7% had CKD (defined as estimated glomerular filtration rate < 60 ml/min per 1.73 m²). For each doubling of serum alkaline phosphatase, the odds of elevated serum CRP (over 3 mg/l) were increased 2.73-fold in the non-chronic and 2.50-fold in the CKD sub-populations, respectively. Regression coefficients of each doubling of serum alkaline phosphatase with elevated CRP were not significantly different in between the sub-populations. Additional adjustment for the serum 25-hydroxy (OH) vitamin D level did not substantively change the results. Thus, associations of serum alkaline phosphatase with elevated CRP are independent of serum 25-OH vitamin D in the chronic and non-CKD populations. Hence, serum alkaline phosphatase might be a marker of the inflammatory milieu.

Higher serum bicarbonate levels within the normal range are associated with better survival and renal outcomes in African Americans.

Recent studies suggest that correcting low serum bicarbonate levels may reduce the progression of kidney disease; however, few patients with chronic kidney disease have low serum bicarbonate. Therefore, we examined whether higher levels of serum bicarbonate within the normal range (20-30 mmol/l) were associated with better kidney outcomes in the African American Study of Kidney Disease and Hypertension (AASK) trial. At baseline and during follow-up of 1094 patients, the glomerular filtration rates (GFR) were measured by iothalamate clearances and events were adjudicated by the outcomes committee. Mean baseline serum bicarbonate, measured GFR, and proteinuria were 25.1 mmol/l, 46 ml/min per 1.73 m(2), and 326 mg/g of creatinine, respectively. Each 1 mmol/l increase in serum bicarbonate within the normal range was associated with reduced risk of death, dialysis, or GFR event and with dialysis or GFR event (hazard ratios of 0.942 and 0.932, respectively) in separate multivariable Cox regression models that included errors-in-variables calibration. Cubic spline regression showed that the lowest risk of GFR event or dialysis was found at serum bicarbonate levels near 28-30 mmol/l. Thus, our study suggests that serum bicarbonate is an independent predictor of CKD progression. Whether increasing serum bicarbonate into the high-normal range will improve kidney outcomes during interventional studies will need to be considered.

Timing of dialysis initiation and survival in ESRD.

BACKGROUND AND OBJECTIVES: The optimal time of dialysis initiation is unclear. The goal of this analysis was to compare survival outcomes in patients with early and late start dialysis as measured by kidney function at dialysis initiation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective analysis of patients entering the U.S. Renal Data System database from January 1, 1995 to September 30, 2006. Patients were classified into groups by estimated GFR (eGFR) at dialysis initiation. RESULTS: In this total incident population (n = 896,546), 99,231 patients had an early dialysis start (eGFR >15 ml/min per 1.73 m(2)) and 113,510 had a late start (eGFR ≤5 ml/min per 1.73 m(2)). The following variables were significantly (P < 0.001) associated with an early start: white race, male gender, greater comorbidity index, presence of diabetes, and peritoneal dialysis. Compared with the reference group with an eGFR of >5 to 10 ml/min per 1.73 m(2) at dialysis start, a Cox model adjusted for potential confounding variables showed an incremental increase in mortality associated with earlier dialysis start. The group with the earliest start had increased risk of mortality, wheras late start was associated with reduced risk of mortality. Subgroup analyses showed similar results. The limitations of the study are retrospective study design, potential unaccounted confounding, and potential selection and lead-time biases. CONCLUSIONS: Late initiation of dialysis is associated with a reduced risk of mortality, arguing against aggressive early dialysis initiation based primarily on eGFR alone.