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Madhumathi Rao

Publications and source records attributed to Madhumathi Rao.

13 recordsLinked to original sources
PubMed2005

Plasma interleukin-6 predicts cardiovascular mortality in hemodialysis patients.

BACKGROUND: Interleukin-6 (IL-6) is a mediator and marker of the chronic inflammatory process that is responsible for much of the morbidity and mortality seen in hemodialysis (HD) patients. This study evaluated circulating plasma IL-6 as a predictor of all-cause mortality and cardiovascular mortality and studied its relationship to prevalent comorbidity and hypoalbuminemia, in a cohort of stable HD patients enrolled in the HEMO study. METHODS: Clinical data included demographic, medical, and routine laboratory parameters. Comorbidities were graded using the Index of Co-Existing Diseases (ICED). Outcomes of interest were all-cause mortality and cardiovascular mortality. Blood samples were drawn at enrollment and annually, and plasma IL-6 levels measured with high-sensitivity enzyme-linked immunosorbent assay. RESULTS: Median plasma IL-6 level in 206 patients was 7.9 pg/mL (range, 0.1 to 90.3 pg/mL) and was higher in patients with vascular disease ( P = 0.03), higher ICED scores ( P = 0.01), and lower Karnofsky indices ( P < 0.01). Serum albumin was inversely related to plasma IL-6 levels ( P = 0.03, r = -0.16). Unadjusted median survival time was 1,209 days in the lowest quartile of plasma IL-6 and 806 days in the highest ( P = 0.02, log rank test). A 1-log increase in plasma IL-6 was associated with a 1.19-fold higher adjusted risk for all-cause mortality ( P = 0.04; 95% confidence interval, 1.01 to 1.40) and a 1.43-fold higher adjusted risk of cardiovascular mortality ( P = 0.02; 95% confidence interval, 1.06 to 1.92). Hazard ratio estimates were higher when IL-6 levels over time were incorporated as a time-dependent covariate. CONCLUSION: Plasma IL-6 levels are strongly associated with comorbidity in HD patients and are a powerful predictor of cardiovascular and all-cause mortality.

Adolescent↗
PubMed2004

Cytokine gene promoter polymorphisms and mortality in acute renal failure.

BACKGROUND: Although cytokines play a pivotal role in the inflammatory responses that mediate the severity of acute renal failure (ARF), the importance of pro- and anti-inflammatory cytokine gene promoter polymorphisms has been unexplored. METHODS: We prospectively evaluated the relationship of single nucleotide polymorphism in the promoter region of tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) to mortality in 61 patients with ARF requiring intermittent hemodialysis. Cytokine genotyping was performed on leukocytes using PCR techniques. Cox proportional-hazards regression analysis was used to explore these relationships. RESULTS: The mean (+/-SD) APACHE II score was 24 +/- 7, MOF score 2 +/- 1, and 64% had sepsis. The TNF-alpha high producer genotype (-308 A-allele carrier) was associated with a higher risk of death after adjustment for the APACHE II score (HR=2.5; P=0.04), and the IL-10 intermediate/high producer genotype (-1082 G-allele carrier) was associated with a lower risk of death after adjustment for the MOF score (HR=0.36; P=0.03). Considering combinations of genotypes, the TNF-alpha high and IL-10 low producer genotype combination was associated with a approximately 6-fold increased risk of death compared to the TNF-alpha-low and IL-10 intermediate/high producer genotype combination, after adjustment for either APACHE II (P=0.004), MOF score (P=0.004) or sepsis (P=0.006). CONCLUSIONS: TNF-alpha and IL-10 gene polymorphisms are related to the risk of death among patients with ARF who require dialysis. Larger studies are needed to confirm these relationships.

Acute Kidney Injury↗
PubMed2004

Dialyzer membrane type and reuse practice influence polymorphonuclear leukocyte function in hemodialysis patients.

BACKGROUND: Polymorphonuclear leukocyte (PMNL) production of reactive oxygen species (ROS) has been linked to hemodialysis (HD) associated morbidity. The effect of dialyzer membrane type and reuse on PMNL function has not been clearly defined. METHODS: The present report is a cross-sectional study undertaken in a cohort of patients undergoing regular HD, at enrollment into the Hemodialysis (HEMO) Study, to study the association between patient and dialysis-related factors and PMNL function. PMNL function was assessed by measuring PMA- and N-formyl methionyl-leucyl-phenylalanine (fMLP) -induced respiratory burst, and phagocytic activity toward Staphylococcus aureus. RESULTS: PMNL from patients dialyzed with polysulphone (PS) or cuprophane (CU) membranes showed higher PMA-induced respiratory burst activity compared with those exposed to substituted cellulose (cellulose acetate, cellulose triacetate, CA/CT) membranes, regardless of dialyzer reuse. The use of bleach as a cleansing agent during reuse was associated with higher PMA-induced PMNL superoxide production, as was the use of renalin when compared to aldehydes. In a subgroup of patients using PS dialyzers, reuse itself was associated with higher fMLP-induced superoxide production. The type of bleach-germicide combination during reuse showed that use of renalin as a germicide was also associated with higher PMNL phagocytosis index. The number of years on HD correlated inversely with PMA-induced PMNL superoxide response. Weaker PMNL response to fMLP was associated with greater comorbidity and poor functional status as quantified by Index of Coexisting Diseases (ICED) and Karnofsky scores, respectively. CONCLUSION: Our results indicate that dialyzer membrane type and the reuse process influence the oxidative response of PMNL among HD patients. The implications of these observations on clinical morbidity need to be further evaluated in prospective studies.

Aged↗
PubMed2004

Cytokine gene polymorphisms in hemodialysis patients: association with comorbidity, functionality, and serum albumin.

BACKGROUND: Cytokine-orchestrated chronic inflammation plays a major role in long-term morbidity and mortality in patients with end-stage renal disease (ESRD) on hemodialysis (HD). In this cross-sectional study, we evaluated the association between specific alleles/genotypes and combinations of genotypes of interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), and IL-10 with indices of comorbidity, functional status, and other biological markers in a cohort of 183 ESRD patients recruited to the Hemodialysis (HEMO) Study from two Boston centers. METHODS: Genotyping was performed for single nucleotide polymorphisms in the promoter region of IL-6 (-174 G-->C), TNF-alpha (-308 G-->A), and IL-10 (-1082 G-->A). The relationship of specific genotypes to the index of coexistent disease (ICED) score (an index of comorbidity), Karnofsky Index (a measure of functional status), serum albumin, and nutritional indices (anthropometric measurements, body mass index, normalized protein catabolic ratio) were studied. Plasma IL-6 levels, as well as TNF-alpha and IL-10 production by endotoxin-stimulated peripheral blood mononuclear cells (PBMC), were also measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with the high producer genotypes for the proinflammatory cytokines IL-6 (G/G and G/C) and TNF-alpha (G/A and A/A) had significantly higher comorbidity (ICED scores of > or =2) and lower functional scores (Karnofsky Index) compared with patients with the low producer genotypes for these cytokines (C/C and G/G, respectively). In contrast, patients with the high and intermediate producer genotypes (G/G and G/A) for the anti-inflammatory cytokine IL-10 had a higher Karnofsky Index compared with those with the low producer genotype (A/A). Serum albumin levels were lower in patients with the TNF-alpha high producer genotype (G/A and A/A) compared with those with the low producer genotype (G/A and A/A). On multivariate analysis, the IL-6 high producer genotypes were associated with an odds ratio (OR) of 4.87 for higher comorbidity (ICED scores > or =2) (P= 0.02), and 4.9 for lower Karnofsky Index (lower functional status) (P= 0.04) compared with patients with the low IL-6 producer genotypes. Similarly, the TNF-alpha high producer genotype was associated with increased odds for a higher ICED score, lower Karnofsky Index, and lower serum albumin compared with patients with the low producer genotype for this cytokine. In contrast, the IL-10 high/intermediate producer genotype was associated with increased odds for a higher Karnofsky Index (P= 0.05). Cytokine genotype combinations-the TNF-alpha high producer and IL-6 high producer genotype combination, and the IL-6 high producer and IL-10 low producer genotype combination-were independently associated with a higher ICED score. These genotype combinations, as well as the TNF-alpha high producer and IL-10 low producer genotype combination, were also associated with a lower Karnofsky Index. CONCLUSION: In ESRD patients on long-term HD, single nucleotide polymorphisms in the promoter region of the proinflammatory cytokines IL-6 and TNF-alpha, and the regulatory monokine IL-10, show a strong association with indices of comorbidity and function, and biological and nutritional markers.

Aged↗
PubMed2004

Transforming growth factor-beta 1 gene polymorphisms and cardiovascular disease in hemodialysis patients.

BACKGROUND: Atherosclerotic vascular disease is a leading cause of morbidity and mortality in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD). Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that inhibits the atheromatous process. We studied coding region polymorphisms of the TGF-beta1 gene (+869 T --> C at codon 10 and +915 G --> C at codon 25) as genetic susceptibility factors for prevalent vascular disease and cardiac outcomes in a cohort of HD patients enrolled in the HEMO Study. METHODS: Genotyping was carried out using polymerase chain reaction-sequence specific primer (PCR-SSP) methods with a cytokine genotyping tray. Prevalent vascular disease was coded from the Index of Disease Severity (IDS) scores for ischemic heart disease (IHD), peripheral vascular disease (PVD), cerebrovascular disease (CVD), and congestive heart failure (CHF), 0 indicating absence, and 1 to 3 increasing grades of severity. The presence of any vascular disease (VD) (i.e., any degree of IHD/PVD/CVD), and the number of coexistent vascular system diseases per patient were derived. Cardiac outcomes, one of the secondary outcomes of the HEMO Study, were expressed as a composite of the first hospitalization for, or death from, cardiac causes. RESULTS: The cohort consisted of 183 patients at enrollment, 56% male, 44% African American (AA), and 40% diabetic. The mean age was 62.4 +/- 12.2 years, and median dialysis vintage 2.02 years. The most frequent genotype at codon 10 was T/C (67%), and at codon 25 was G/G (72%). IHD was present in 52% of patients; 65% had at least one vascular system involvement, and 31% had 2 or more. On both univariate and multivariate analysis, the G/C genotype at codon 25 was significantly associated with the presence and extent of vascular disease at enrollment. The median time to cardiac outcome, defined as a composite of the first hospitalization for, or death from, cardiac causes, was 411 days in patients with the G/C genotype compared with 851 days in those with the G/G genotype (P= 0.03). Patients with the G/C genotype had a 1.6-fold increased hazard for cardiac outcomes after adjustment for baseline covariates (P= 0.04). CONCLUSION: The G/C substitution at codon 25 was associated with an increased risk for prevalent vascular disease, new onset cardiac morbidity, and cardiac mortality in HD patients, and may be a genetic susceptibility factor for the development of atherosclerosis. Further studies are required to evaluate the role of TGF-beta1 as a candidate gene.

Aged↗
PubMed2003

Post-transplant hyperglycaemia: a study of risk factors.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) has several identifiable pre- and post-transplant risk factors. The link to nutritional status pre-transplant has not been explored previously. This study was conducted to identify risk factors for the development of PTDM, with emphasis on pre-transplant nutritional status and glucose tolerance. METHODS: Non-diabetic adult end-stage renal failure patients awaiting renal transplantation were studied prospectively. Their nutritional status was assessed as body mass index (BMI), serum albumin, and the evolution of these parameters over time prior to transplantation. An oral glucose tolerance test (OGTT) was performed pre- and serially post-transplant until 6 months. Pre- and post-transplant risk factors such as age, nutritional status, glucose tolerance parameters and immunosuppression were related to the development of PTDM or impaired glucose tolerance (IGT) post-transplant. RESULTS: The mean age of 174 patients studied over a 2-year period was 32.9 +/- 9.7 years. The mean post-transplant follow-up was 25.6 +/- 12.8 months. The mean BMI at recruitment was 18.3 +/- 2.4 kg/m(2). The rate of increase in BMI pre-transplant showed an inverse correlation with the baseline BMI (r = -0.34, P = 0.000) and formed an independent marker of nutritional status. PTDM developed in 21.4% patients and 24.1% had IGT. On univariate and multivariate analyses, the factors significantly associated with the development of PTDM were greater age, more rapid increase in dry weight after starting haemodialysis (HD), elevated pre-transplant OGTT responses and cyclosporin (CsA) and prednisolone doses early post-transplant. Additionally, on multivariate analysis, higher CsA trough level > 300 ng/ml at 3 months increased the risk for the development of PTDM. Of patients who developed PTDM, 57% had impairment of glucose tolerance pre-transplant (> 140 mg/dl at 2 h). Patients with a 1-h glucose value greater than the 50th percentile on pre-transplant OGTT had a 3.9-fold greater risk for the development of PTDM (P = 0.05, 95% CI = 1.03-11.1). In those patients with higher 1-h glucose (> 50th percentile) who also gained in dry weight rapidly pre-transplant, the risk increased to 5.3 (P = 0.02). Of 76 patients with abnormal OGTT early post-transplant, only 68% continued to have PTDM or IGT post-transplant, the remainder reverting to normal glucose tolerance. CONCLUSIONS: Persistent abnormal glucose tolerance after transplantation was seen in 45% of the patients. Pre-transplant factors including greater age, abnormal glucose tolerance parameters, and rapid gain in dry weight on HD, along with higher prednisolone and CsA doses early post-transplant were the important factors associated with the development of PTDM. Identification of patients with pre-transplant risks might allow modification of post-transplant immunosuppression with non-diabetogenic agents.

Adult↗
PubMed2002

A controlled trial of intermittent enteral nutrient supplementation in maintenance hemodialysis patients.

OBJECTIVE: This controlled trial was undertaken to evaluate the benefits of short-term enteral nutrient supplementation in maintenance hemodialysis (MHD) patients using a high-calorie and high-protein blend formula (low-cost home-prepared [HP] blend or a commercially available supplement) and to study its effect on selected parameters of nutritional status. The acceptability and palatability of the HP blend formula, ease of use, and cost were also assessed in comparison with the commercial nutritional supplement (CNS). DESIGN: Randomized controlled trial. SETTING: Hemodialysis (HD) unit of a tertiary referral care hospital in Southern India. PATIENTS: Nondiabetic adult MHD patients with no intercurrent illness, on regular thrice weekly MHD for at least 1 month before recruitment, with a body mass index (BMI) <20 and a serum albumin level of <4.0 g/dL. Patients were randomized into control group and experimental group, the latter in turn to recieve either CNS or HP blend. INTERVENTION: The control group received appropriate monitoring, including dietary recall and counselling for the prescribed diet (protein intake of 1.2 g/kgIBW/d and energy of 35 to 45 kcal/kgIBW/d) but no specific post-HD supplement. Patients in the supplement group received the respective supplement post-HD (providing 500 kcal and 15 g protein) for 1 month in addition to the monitored diet prescription. MAIN OUTCOME MEASURES: (1) Nutritional status parameters, BMI and serum albumin; (2) functional status on a 10-point Karnofsky scale; (3) adverse metabolic effects, hyperphosphatemia at start and end of study; and (4) subjective scoring for appetite, and acceptability of and tolerance to supplement. RESULTS: Both groups showed an improvement in dry weight and BMI. In addition, the supplement group showed a significant increase in serum albumin level and functional scoring. Mild hyperphosphatemia occurred in the supplement group. An increase in baseline food intake was seen in the control group, but not in the supplemented group. No intolerance was reported to either supplement. CONCLUSION: Enteral nutrient supplementation was shown to bring about a significant improvement in serum albumin level even in a short-term study. Use of an HP supplement was beneficial, acceptable, and inexpensive.

Adult↗
PubMedDate not supplied

The Study of Treatment for Renal Insufficiency: Data and Evaluation (STRIDE), a national registry of chronic kidney disease.

Optimization of care in patients with chronic kidney disease (CKD) could be the key to improved clinical and economic outcomes, both during the phase of CKD as well as in patients with end-stage renal disease (ESRD). CKD is a major public health problem that has been insufficiently studied. There is little published information on outcomes among CKD patients, specifically, data on mortality, morbidity, and quality of life. Indeed, recent efforts by the National Kidney Foundation (NKF) have served to define the classification, evaluation, and approach to management of CKD in practice. The Study of Treatment for Renal Insufficiency: Data and Evaluation (STRIDE) registry is an initiative to study CKD patients in nephrology practices across the country. It is a prospective observational study whose objective is to profile demographic and clinical variables, practice patterns, comorbid conditions, quality of life, and outcomes in a nationally based sample of CKD patients. This article details the design, methodology, and process of enrollment into the registry.

Data Interpretation, Statistical↗
PubMedDate not supplied

Genomic medicine, gene polymorphisms, and human biological diversity.

There is considerable variation in the prevalence of comorbid conditions such as malnutrition, inflammation, cardiovascular disease, and bone disease among end-stage renal disease (ESRD) patients on maintenance hemodialysis. Besides traditional risk factors, these differences also arise from variability in genetic factors and gene-environment interactions. Recent publication of the human genome sequence through the Human Genome and Celera projects has provided a major impetus to the field of molecular genetics and genomic medicine. This review provides a broad overview of recent developments in this field, basic information and terminology in common use, and explores the impact of genetic variations or polymorphisms on human biological diversity.

Biodiversity↗
PubMedDate not supplied

Gene polymorphism association studies in dialysis: cardiovascular disease.

Cardiovascular disease (CVD) is the most important cause of morbidity and mortality in dialysis patients. The high prevalence of CVD is due to the cumulative effects of multiple risk factors from the early stages of chronic kidney disease (CKD). Familial predispositions to CVD, CKD, and their respective risk factors are well known, and it is likely that genetic factors determine the interindividual variability in risks for disease. Advances in genomic technology have facilitated the study of genetic variation--most commonly single nucleotide polymorphisms (SNPs) in candidate genes--and their associations with disease. This review examines CVD in dialysis patients as a model of a complex disease, discusses the approach to gene polymorphism association studies, including the roles of gene-environment and gene-gene interactions and provides an overview of available studies.

Cardiovascular Diseases↗
PubMedDate not supplied

Inflammatory biomarkers and cardiovascular risk: association or cause and effect?

With the current understanding that atherosclerosis is an inflammatory disorder, markers of the associated systemic inflammatory response have been extensively studied as predictors of cardiovascular disease. Recently the use of high-sensitivity C-reactive protein (hsCRP) has been proposed for risk assessment in individuals at intermediate risk of coronary heart disease. The traditional view of inflammatory biomarkers, including CRP, regards them as risk markers rather than risk factors. Either category of marker would serve a diagnostic role, monitor disease activity, and indicate the efficacy of therapy or changing prognosis. However a risk factor with a causal role would be a potential target for therapy. This review discusses the available evidence that argues for and against a causal role for inflammatory biomarkers, with specific reference to CRP, in the atherosclerotic process.

Biomarkers↗