Tanushree Banerjee

High Dietary Acid Load Predicts ESRD among Adults with CKD

Small clinical trials have shown that a reduction in dietary acid load (DAL) improves kidney injury and slows kidney function decline; however, the relationship between DAL and risk of ESRD in a population-based cohort with CKD remains unexamined. We examined the association between DAL, quantified by net acid excretion (NAEes), and progression to ESRD in a nationally representative sample of adults in the United States. Among 1486 adults with CKD age≥20 years enrolled in the National Health and Nutrition Examination Survey III, DAL was determined by 24-h dietary recall questionnaire. The development of ESRD was ascertained over a median 14.2 years of follow-up through linkage with the Medicare ESRD Registry. We used the Fine-Gray competing risks method to estimate the association of high, medium, and low DAL with ESRD after adjusting for demographics, nutritional factors, clinical factors, and kidney function/damage markers and accounting for intervening mortality events. In total, 311 (20.9%) participants developed ESRD. Higher levels of DAL were associated with increased risk of ESRD; relative hazards (95% confidence interval) were 3.04 (1.58 to 5.86) for the highest tertile and 1.81 (0.89 to 3.68) for the middle tertile compared with the lowest tertile in the fully adjusted model. The risk of ESRD associated with DAL tertiles increased as eGFR decreased (P trend=0.001). Among participants with albuminuria, high DAL was strongly associated with ESRD risk (P trend=0.03). In conclusion, high DAL in persons with CKD is independently associated with increased risk of ESRD in a nationally representative population.

Dietary acid load and chronic kidney disease among adults in the United States

BackgroundDiet can markedly affect acid-base status and it significantly influences chronic kidney disease (CKD) and its progression. The relationship of dietary acid load (DAL) and CKD has not been assessed on a population level. We examined the association of estimated net acid excretion (NAEes) with CKD; and socio-demographic and clinical correlates of NAEes.MethodsAmong 12,293 U.S. adult participants aged >20 years in the National Health and Nutrition Examination Survey 1999–2004, we assessed dietary acid by estimating NAEes from nutrient intake and body surface area; kidney damage by albuminuria; and kidney dysfunction by eGFR < 60 ml/min/1.73m2 using the MDRD equation. We tested the association of NAEes with participant characteristics using median regression; while for albuminuria, eGFR, and stages of CKD we used logistic regression.ResultsMedian regression results (β per quintile) indicated that adults aged 40–60 years (β [95% CI] = 3.1 [0.3–5.8]), poverty (β [95% CI] = 7.1 [4.01–10.22]), black race (β [95% CI] = 13.8 [10.8–16.8]), and male sex (β [95% CI] = 3.0 [0.7- 5.2]) were significantly associated with an increasing level of NAEes. Higher levels of NAEes compared with lower levels were associated with greater odds of albuminuria (OR [95% CI] = 1.57 [1.20–2.05]). We observed a trend toward greater NAEes being associated with higher risk of low eGFR, which persisted after adjustment for confounders.ConclusionHigher NAEes is associated with albuminuria and low eGFR, and socio-demographic risk factors for CKD are associated with higher levels of NAEes. DAL may be an important target for future interventions in populations at high risk for CKD.

Free Levels of Selected Organic Solutes and Cardiovascular Morbidity and Mortality in Hemodialysis Patients: Results from the Retained Organic Solutes and Clinical Outcomes (ROSCO) Investigators.

Background and Objectives Numerous substances accumulate in the body in uremia but those contributing to cardiovascular morbidity and mortality in dialysis patients are still undefined. We examined the association of baseline free levels of four organic solutes that are secreted in the native kidney — p-cresol sulfate, indoxyl sulfate, hippurate and phenylacetylglutamine — with outcomes in hemodialysis patients. Design, Setting, Participants and Measurements We measured these solutes in stored specimens from 394 participants of a US national prospective cohort study of incident dialysis patients. We examined the relation of each solute and a combined solute index to cardiovascular mortality and morbidity (first cardiovascular event) using Cox proportional hazards regression adjusted for demographics, comorbidities, clinical factors and laboratory tests including Kt/VUREA. Results Mean age of the patients was 57 years, 65% were white and 55% were male. In fully adjusted models, a higher p-cresol sulfate level was associated with a greater risk (HR per SD increase; 95% CI) of cardiovascular mortality (1.62; 1.17–2.25; p=0.004) and first cardiovascular event (1.60; 1.23–2.08; p<0.001). A higher phenylacetylglutamine level was associated with a greater risk of first cardiovascular event (1.37; 1.18–1.58; p<0.001). Patients in the highest quintile of the combined solute index had a 96% greater risk of cardiovascular mortality (1.96; 1.05–3.68; p=0.04) and 62% greater risk of first cardiovascular event (1.62; 1.12–2.35; p=0.01) compared with patients in the lowest quintile. Results were robust in sensitivity analyses. Conclusions Free levels of uremic solutes that are secreted by the native kidney are associated with a higher risk of cardiovascular morbidity and mortality in incident hemodialysis patients.

Trimethylamine N-Oxide and Cardiovascular Events in Hemodialysis Patients

Cardiovascular disease causes over 50% of the deaths in dialysis patients, and the risk of death is higher in white than in black patients. The underlying mechanisms for these findings are unknown. We determined the association of the proatherogenic metabolite trimethylamine N-oxide (TMAO) with cardiovascular outcomes in hemodialysis patients and assessed whether this association differs by race. We measured TMAO in stored serum samples obtained 3-6 months after randomization from a total of 1232 white and black patients of the Hemodialysis Study, and analyzed the association of TMAO with cardiovascular outcomes using Cox models adjusted for potential confounders (demographics, clinical characteristics, comorbidities, albumin, and residual kidney function). Mean age of the patients was 58 years; 35% of patients were white. TMAO concentration did not differ between whites and blacks. In whites, 2-fold higher TMAO associated with higher risk (hazard ratio [95% confidence interval]) of cardiac death (1.45 [1.24 to 1.69]), sudden cardiac death [1.70 (1.34 to 2.15)], first cardiovascular event (1.15 [1.01 to 1.32]), and any-cause death (1.22 [1.09 to 1.36]). In blacks, the association was nonlinear and significant only for cardiac death among patients with TMAO concentrations below the median (1.58 [1.03 to 2.44]). Compared with blacks in the same quintile, whites in the highest quintile for TMAO (≥135 μM) had a 4-fold higher risk of cardiac or sudden cardiac death and a 2-fold higher risk of any-cause death. We conclude that TMAO concentration associates with cardiovascular events in hemodialysis patients but the effects differ by race.

Impact of HAART on survival, weight gain and resting energy expenditure in HIV-1-infected children in India

Abstract Background: In resource-limited countries, use of highly active antiretroviral therapy (HAART) in HIV-infected children is still poorly documented in terms of impact on survival, the immune system and growth. Since the availability of HAART, nutrition of HIV-infected children has been neglected. Aim: To evaluate the effect of HAART on survival and immune response in HIV-infected children and to investigate the response to nutritional support. Methods: In December, 2002 a cohort study was carried out on vertically HIV-1-infected children and was observed longitudinally for CD4+ T-cell count, antiretroviral treatment and weight until 31 December 2007. Z-scores were calculated for CD4+ T-cell count to account for age-related differences. Nutritional supplementation was given to all the HIV-infected children and resting energy expenditure (REE) was calculated. Mortality rates were also calculated for the perinatally infected children followed up at the HIV clinic. Results: A total of 180 children were assessed, 100 (56%) of whom were on HAART. Baseline body mass index was lower in the HAART group (p<0.05). Median duration of survival from date of diagnosis was 15.1 years. Those who received HAART survived significantly longer. The average annual mortality rate was 1.2% during 2005–2006. During HAART, a CD4 Z-score increase of 1 SD was associated with a 0.35 increase in body weight Z-score (p<0.001). The increase in daily energy intake owing to nutritional supplementation was associated with increase in weight Z-score in both the no-HAART and HAART group. REE was independently associated with weight change in the models which tested association of changes in CD4+ T-cell Z-score and daily REE/kg body weight with changes in body weight Z-score in both the HAART and no-HAART group and then separately in the two groups (p<0.001). Conclusion: Survival rates of children improved which correlated with an increase in CD4+ T-cell count concurrent with the expanded use of HAART. HAART had a positive effect on growth in HIV-1-infected children. Nutrition supplementation improved the health of children in both the no-HAART and HAART groups.

Kt/Vurea and Nonurea Small Solute Levels in the Hemodialysis Study

The Hemodialysis (HEMO) Study showed that high-dose hemodialysis providing a single-pool Kt/Vurea of 1.71 provided no benefit over a standard treatment providing a single-pool Kt/Vurea of 1.32. Here, we assessed whether the high-dose treatment used lowered plasma levels of small uremic solutes other than urea. Measurements made ≥3 months after randomization in 1281 patients in the HEMO Study showed a range in the effect of high-dose treatment compared with that of standard treatment: from no reduction in the level of p-cresol sulfate or asymmetric dimethylarginine to significant reductions in the levels of trimethylamine oxide (-9%; 95% confidence interval [95% CI], -2% to -15%), indoxyl sulfate (-11%; 95% CI, -6% to -15%), and methylguanidine (-22%; 95% CI, -18% to -27%). Levels of three other small solutes also decreased slightly; the level of urea decreased 9%. All-cause mortality did not significantly relate to the level of any of the solutes measured. Modeling indicated that the intermittency of treatment along with the presence of nondialytic clearance and/or increased solute production accounted for the limited reduction in solute levels with the higher Kt/Vurea In conclusion, failure to achieve greater reductions in solute levels may explain the failure of high Kt/Vurea treatment to improve outcomes in the HEMO Study. Furthermore, levels of the nonurea solutes varied widely among patients in the HEMO Study, and achieved Kt/Vurea accounted for very little of this variation. These results further suggest that an index only on the basis of urea does not provide a sufficient measure of dialysis adequacy.

A Proinflammatory Diet Is Associated with Systemic Inflammation and Reduced Kidney Function in Elderly Adults

BACKGROUND Diet can affect kidney health through its effects on inflammation. OBJECTIVE We tested whether the Adapted Dietary Inflammatory Index (ADII) is associated with kidney function and whether effects of diet on chronic low-grade inflammation explain this association. METHODS This was an observational analysis in 1942 elderly community-dwelling participants aged 70-71 y from 2 independent cohorts: the Uppsala Longitudinal Study of Adult Men (n = 1097 men) and the Prospective Investigation of Vasculature in Uppsala Seniors (n = 845 men and women). The ADII was calculated from 7-d food records, combining putatively proinflammatory and anti-inflammatory effects of nutrients, vitamins, and trace elements. The ADII was validated against serum C-reactive protein (CRP) concentrations. The estimated glomerular filtration rate (eGFR) was assessed from serum cystatin C (cys) and creatinine (crea). Associations between the ADII and eGFR were investigated, and CRP was considered to be a mediator. RESULTS In adjusted analysis, a 1-SD higher ADII was associated with higher CRP (β: 6%; 95% CI: 1%, 10%; P = 0.01) and lower eGFR [Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)cys: -2.1%; 95% CI: -3.2%, -1.1%; CKD-EPIcys+crea: -1.8%; 95% CI: -2.7%, -0.9%; both P < 0.001]. CRP was also inversely associated with eGFR. Mediation analyses showed that of the total effect of the ADII on kidney function, 15% and 17% (for CKD-EPIcys+crea and CKD-EPIcys equations, respectively) were explained/mediated by serum CRP. Findings were similar when each cohort was analyzed separately. CONCLUSIONS A proinflammatory diet was associated with systemic inflammation as well as with reduced kidney function in a combined analysis of 2 community-based cohorts of elderly individuals. Our results also suggest systemic inflammation to be one potential pathway through which this dietary pattern is linked to kidney function.

Results of the HEMO Study suggest that p-cresol sulfate and indoxyl sulfate are not associated with cardiovascular outcomes

Cardiovascular disease, the leading cause of mortality in hemodialysis patients, is not fully explained by traditional risk factors. To help define non-traditional risk factors, we determined the association of predialysis total p-cresol sulfate, indoxyl sulfate, phenylacetylglutamine, and hippurate with cardiac death, sudden cardiac death, and first cardiovascular event in the 1,273 participants of the HEMO Study. The results were adjusted for potential demographic, clinical, and laboratory confounders. The mean age of the patients was 58 years, 63% were Black and 42% were male. Overall, there was no association between the solutes and outcomes. However, in sub-group analyses, among patients with lower serum albumin (under 3.6 g/dl), a twofold higher p-cresol sulfate was significantly associated with a 12% higher risk of cardiac death (hazard ratio 1.12; 95% confidence interval, 0.98-1.27) and 22% higher risk of sudden cardiac death (1.22, 1.06-1.41). Similar trends were also noted with indoxyl sulfate. Trial interventions did not modify the association between these solutes and outcomes. Routine clinical and lab data explained less than 22% of the variability in solute levels. Thus, in prevalent hemodialysis patients participating in a large U.S. hemodialysis trial, uremic solutes p-cresol sulfate, indoxyl sulfate, hippurate, and phenylacetylglutamine were not associated with cardiovascular outcomes. However, there were trends of toxicity among patients with lower serum albumin.

Behavioural disorders in 6–11-year-old, HIV-infected Indian children

Abstract Background: HIV-infected children are at risk of behaviour problems. The transition of HIV from an acute, lethal disease to survival with sub-acute, chronic disease has enormous implications for the psychosocial development and requirement for support of affected children and families. Aim: To study the behavioural patterns and factors responsible for psychiatric disorders among HIV-infected and uninfected children in the age group 6–11 years. Methods: A prospective, random-sampling study was undertaken to examine the unique and combined influences of HIV and socio-demographic characteristics on the behaviour of 140 infected and 301 age- and income-matched controls. Controls were normal children recruited from government schools. The Child Behaviour Check List was used to assess behaviour patterns. Results: Multivariate analyses comparing HIV-infected children with their uninfected peers from similar backgrounds showed more subjective distress in the HIV-infected group. Behaviour problems in HIV-infected children were reported by 80.7% of primary caregivers compared with 18.3% for controls. Psychiatric behaviour in HIV-infected children as a risk factor for HIV was also identified in a significant proportion (p<0.0001). Conclusions: By analysing behaviour, a psycho-medical team can examine the extent to which psychosocial and demographic factors are involved in causing and exacerbating behaviour problems in HIV-infected children.

Dietary Patterns and CKD Progression

Background: Chronic kidney disease (CKD) patients and their clinicians seek ways to mitigate the risk of CKD progression and its associated complications. Emerging data suggest that dietary modifications may be beneficial adjuvant approaches to reducing the risk of adverse CKD outcomes. Summary: This review focuses on several different dietary patterns, including the Dietary Approaches to Stop Hypertension and Mediterranean diets, and their kidney health benefits. We discuss how healthful dietary patterns are lower in dietary acid load and how improving diet quality may slow the progression of CKD. We also discuss some barriers that may impede socially disadvantaged individuals from following healthful diets. Key Points: Dietary patterns low in dietary acid load might slow the progression of CKD. Current evidence suggests that a reduction in dietary acid load could be beneficial in patients with CKD, but the supremacy of any particular diet is yet to be established. Additional randomized controlled dietary interventions among CKD patients are needed to inform evidence-based recommendations, which can be tailored to an individuals preferences and ability to access healthful foods.