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Biomedical subjects

R Sreedhara

Publications and source records attributed to R Sreedhara.

11 recordsLinked to original sources
PubMed2001

Survival on hemodialysis and peritoneal dialysis over 12 years with emphasis on nutritional parameters.

We analyzed the prognostic importance of nutritional markers and mortality data in 537 hemodialysis (HD) and 422 peritoneal dialysis (PD) patients followed for up to 12 years. Patients on HD had a 44% lower risk of mortality than did those treated with PD (P: < 0.0001). The difference in mortality between the modalities was even more striking among diabetics but less striking among younger patients. Over a 12-year period, survival of dialysis patients with lower enrollment levels of albumin, creatinine, and parathyroid hormone (PTH) were significantly lower. In multivariate Cox's proportional hazards models, serum prealbumin and enrollment PTH level of <65 pg/mL were independent predictors of mortality both in HD and PD patients. In conclusion, HD patients had higher cumulative survival than PD patients over a 12-year period. Nutritional markers at enrollment continue to be strong predictors of mortality for up to 12 years.

Adult↗
PubMed1997

Reticulocyte hemoglobin content predicts functional iron deficiency in hemodialysis patients receiving rHuEPO.

Early detection of iron sufficiency at the level of the erythropoietic cell is necessary to optimize management of uremic anemia with recombinant human erythropoietin (rHuEPO). "Absolute" and "functional" iron deficiency are the most important factors causing resistance to administered rHuEPO. Transferrin saturation and serum ferritin measurements have been noted to be insensitive and inaccurate measures to detect functional iron deficiency. Recently, the reticulocyte hemoglobin content (CHr) has been shown to be a sensitive and specific indicator of functional iron deficiency in nondialysis patients treated with rHuEPO. The purpose of this study is to compare CHr with currently used indices of iron sufficiency in rHuEPO-treated hemodialysis (HD) patients. In study 1, 364 stable HD patients were studied at two outpatient dialysis centers. CHr was normally distributed, with a mean value of 28.3 pg, and was consistent over two consecutive monthly samples in each center. CHr was weakly but consistently correlated with transferrin saturation and serum ferritin. CHr and reticulocyte number were inversely correlated with red blood cell (RBC) number, suggesting that the erythropoietic stimulus of routinely administered rHuEPO may have resulted in functional iron deficiency. Month-to-month changes in CHr correlated weakly with changes in serum iron and percent transferrin saturation, but not at all with changes in serum ferritin. When we analyzed those patients with baseline CHr less than 26 pg, a level strongly suggestive of functional iron deficiency, these correlations strengthened, and in addition, month-to-month changes in CHr correlated strongly and directly with concomitant changes in RBC count, hemoglobin, and hematocrit, suggesting that rising CHr was indicative of an erythropoietic response. In study 2, 79 patients received a single-dose infusion of 500 mg iron dextran. After intravenous iron, CHr rose within 48 hours, peaked at 96 hours, and then fell toward baseline. Patients who were iron deficient by standard measures (serum ferritin < 100 ng/mL or transferrin saturation less than 20%) had a greater and a sustained CHr response to intravenous iron dextran. A CHr less than 28 pg at baseline predicted functional iron deficiency, defined as a corrected reticulocyte increase of greater than 1% to iron dextran, more accurately than transferrin saturation, ferritin, or their combination. Eighty-two percent of individuals who were iron deficient at baseline responded to intravenous iron with an increase in CHr of greater than 2 pg. Sixty percent of patients who were iron sufficient by usual iron indices also responded to intravenous iron with a CHr rise of greater than 2 pg, suggesting that they were, in fact, functionally iron deficient despite "normal" conventional iron parameters. We conclude that CHr may be a more sensitive marker of functional iron deficiency in rHuEPO-treated hemodialysis patients than percent transferrin saturation and ferritin, particularly in those with "normal" conventional iron parameters.

Anemia, Iron-Deficiency↗
PubMed1996

Uremic patients have decreased shear-induced platelet aggregation mediated by decreased availability of glycoprotein IIb-IIIa receptors.

Bleeding and platelet dysfunction are prominent features of uremia. Sh ear-induced platelet aggregation (SIPA) involves the interaction of von Willebrand factor (vWF) with platelet membrane glycoproteins (GP) Ib and IIb-IIIa, the same receptor-ligand pair involved in in vivo adhesion and aggregation of platelets in the arterial circulation. We have used a modified rotational cone-plate viscometer to measure SIPA and calcium flux in platelets. Flow cytometric analysis of the surface expression of GP Ib and IIb-IIIa was performed using flourescein isothiocyanate-conjugated monoclonal antibodies CD42b and CD41a, respectively. Uremic patients showed decreased SIPA (controls, 43% +/- 2% [mean +/- SEM]; chronic renal failure patients, 36% +/- 3%; chronic hemodialysis patients, 26% +/- 2%; P < 0.001) along with a decrease in GP IIb-IIIa (controls, chronic renal failure patients, and chronic hemodialysis patients, 840 +/- 25, 649 +/- 42, 661 +/- 38 mean flourescence intensity, respectively; P < 0.0001). Glycoprotein Ib in uremic patients was not significantly different from normal. Chronic hemodialysis patients also demonstrated increased platelet-bound fibrinogen (P < 0.001) and platelet-bound vWF (p < 0.01). Calcium flux and thromboxane B(2) generation during SIPA of uremic platelets was normal. However, uremic plasma showed twice the normal concentration of vWF (P < 0.001) and sodium dodecyl sulfate agarose gel electrophoresis revealed the presence of fibrinogen fragments. Mixing experiments demonstrated an inhibitory effect of uremic plasma on SIPA of normal platelets (decreased from 39% +/- 3% at baseline to 31% +/- 3% after incubation in uremic plasma) along with an activation-independent increase in platelet-bound fibrinogen and platelet-bound vWF. When uremic platelets were incubated in normal plasma, their SIPA increased from 12% +/- 5% at baseline to 18% +/- 4% after incubation in normal plasma; (P = 0.002), although it did not return to normal. These results suggest that the uremic platelet dysfunction results from decreased GP IIb-IIa availability due to receptor occupancy by fibrinogen fragments (and possibly vWF fragments).

Calcium↗
PubMed1996

Predictive value of nutritional markers (albumin, creatinine, cholesterol, and hematocrit) for patients on dialysis for up to 30 years.

Mortality among end-stage renal disease patients in the United States remains unacceptably high despite progress in the management of renal replacement therapy. Consequently, there are few reports of long-term survivors on dialysis. We have analyzed characteristics of long-term (10 to 15 years, N = 40) and very long-term (15 to 30 years, N = 18) survivors on hemodialysis and long-term survivors (more than 10 years, N = 28) on peritoneal dialysis and compared them with "average survivors" (< 5 years, N = 65 for hemodialysis and N = 101 for peritoneal dialysis). Among hemodialysis patients, long- and very long-term survival was associated with younger age, nondiabetic status, black race, and male gender (P < 0.05 for all variables). Enrollment creatinine was higher among long- and very long-term survivors, whereas albumin and hematocrit increased significantly during the period of observation among long- and very long-term survivors compared with average survivors. Enrollment age, nondiabetic status, and albumin level predicted prolonged survival even after adjustments for confounding variables. Among peritoneal dialysis patients, younger age and nondiabetic status predicted prolonged survival. Black race was associated with improved survival, but the association was not statistically significant. Enrollment levels of albumin and creatinine were significantly higher among long-term survivors and the cholesterol increased during the period of observation in long-term survivors. Thus, demographic and biochemical indices reflecting nutritional status can predict prolonged survival in hemodialysis and peritoneal dialysis. Patient survival for periods of up to 30 years is possible on renal replacement therapy. Analyses of these outlier patients may offer clues to prolonged survival.

Age Factors↗
PubMed1996

Enrollment parathyroid hormone level is a new marker of survival in hemodialysis and peritoneal dialysis therapy for uremia.

The relatively high morbidity and mortality during dialytic therapy for end-stage renal disease (ESRD) in the United States is the subject of current inquiry. Identified risk factors for excess mortality include advanced age, diabetes, and malnutrition exemplified by a low serum albumin level. Parathyroid hormone (PTH) has long been thought to contribute to the toxicity of the uremic syndrome. We reviewed the course of patients maintained by hemodialysis (HD) and peritoneal dialysis (PD) to detect any correlation between the level of PTH when beginning dialytic therapy and subsequent morbidity and mortality. Study cohorts consisted of 175 HD and 113 PD patients followed for up to 9 years. Demographic characteristics such as age, race, gender, diabetic status, and prior months on dialysis, as well as biochemical parameters including albumin, creatinine, cholesterol, intact PTH, calcium, and phosphorus levels at enrollment were evaluated for their effect on patient survival. Expected survival was calculated by Cox proportional hazards analysis. Older age and lower enrollment serum creatinine level were associated with increased mortality in both HD and PD patients, whereas low serum albumin and low serum cholesterol levels also predicted high mortality in HD patients. In both HD and PD, patients with enrollment PTH level of < or = 65 pg/mL had more than twice the mortality risk of those with PTH > or = 200 pg/mL. Both observed and expected survival of patients with low PTH were significantly lower than the survival in patients with higher PTH. Five-year HD survivors and four-year PD survivors had significantly higher PTH levels at initiation of dialytic therapy than did those with shorter survival. PTH level correlated with serum creatinine and serum albumin in HD but only with serum creatinine in PD, supporting the inference that patients with high enrollment PTH were better nourished than those with lower PTH.

Age Factors↗
PubMed1996

Prealbumin is the best nutritional predictor of survival in hemodialysis and peritoneal dialysis.

Patients undergoing dialytic therapy for end-stage renal disease (ESRD) have greater morbidity and mortality than age-matched individuals with similar demographics in the general population. Risk factors for early death during treatment for ESRD include advanced age, diabetes, hypertension, and malnutrition. We questioned whether the level of serum prealbumin at the start of uremia therapy might serve as a marker of subsequent survival in patients treated with maintenance hemodialysis (HD) and peritoneal dialysis (PD). Study cohorts included 111 HD and 78 PD patients followed for up to 5 years. Selected demographic characteristics and biochemical variables were tested for correlation with survival in each cohort. Variables evaluated included age, race, gender, diabetic status, and serum concentrations of albumin, creatinine, cholesterol, and prealbumin. For comparison, expected survival was calculated with Cox proportional hazards analysis, which accounts for confounding variables. We found that a higher relative risk (RR) of death in HD patients correlated with older age, the diagnosis of diabetes, and a serum prealbumin < 30 mg/dL. In PD patients, older age and the presence of diabetes correlated with a higher RR of death than in the standard population. When nutritional variables were analyzed separately, prealbumin < 30 mg/dL was the strongest variable that predicted mortality in HD patients (RR = 2.64, P = 0.002) and also predicted increased risk of mortality in PD patients (RR = 1.8, P = 0.035). Observed and expected survival was significantly higher in patients with enrollment prealbumin greater than 30 mg/dL in both HD and PD. The serum prealbumin level correlated significantly with other measures of nutrition, including serum albumin, serum creatinine, and serum cholesterol, in both HD and PD patients. Among tested markers of nutritional status, prealbumin level appears to be the single best nutritional predictor of survival in ESRD patients.

Cholesterol↗
PubMed1996

Is an elevated level of serum lipoprotein (a) a risk factor for cardiovascular disease in CAPD patients?

Cardiovascular disease (CVD) is the single most important cause of mortality in hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients. An increased lipoprotein (a) [Lp(a)] level in HD patients is associated with CVD. However, Lp(a) levels in CAPD patients are controversial, and their association with CVD has not been established. In the present study, prevalent CAPD and HD patients [excluding those who were human immunodeficiency virus (HIV)-positive] attending the Long Island College Hospital from June, 1990 to July, 1995 underwent analysis of lipid profile including Lp(a). Total and low-density lipoprotein cholesterol, triglycerides, apolipoprotein (apo) A, and apo B were all significantly increased in CAPD patients compared to HD patients. Serum Lp(a) levels were also significantly higher in CAPD patients than in HD patients (51 +/- 32 vs 34 +/- 23 mg/dL, p < 0.001). CAPD patients who had a history of myocardial infarction (MI) or coronary artery disease (CAD) at enrollment had significantly higher Lp(a) levels compared to those who did not have a history of MI or CAD. CAPD patients who died of CVD had higher Lp(a) levels than patients who died of non-CVD causes. In the Cox model with backward stepwise selection, a history of CVD was associated with a significantly elevated relative risk (RR) of mortality (RR = 1.84, p = 0.014). Expected survival by all causes of mortality and by cardiac mortality was significantly shorter in patients with a history of CVD than in those without a history of CVD. Thus, elevated Lp(a) is related to increased CVD and therefore may contribute to increased mortality in CAPD patients.

Adult↗
PubMed1995

Defective platelet aggregation in uremia is transiently worsened by hemodialysis.

Bleeding is a prominent feature of uremia and remains a significant cause of morbidity in hemodialysis (HD)-dependent patients. To measure the impact of the HD procedure, we performed a prospective cross-over study in eight patients placed consecutively for 2-week periods each on low-flux biocompatible polymethylmethacrylate, low-flux complement-activating cuprophane, and high-flux biocompatible polysulfone membranes. The primary measure of platelet function studied was shear-induced platelet aggregation (SIPA), which has been shown to be a physiologically relevant marker of platelet function and involves the interaction of von Willebrand factor (vWf) with platelet membrane glycoproteins (GP) Ib and IIb-IIIa. Flow-cytometric analysis of the surface expression of platelet membrane GP Ib and GP IIb-IIIa was performed using fluorescein isothiocyanate (FITC)-conjugated monoclonal antibodies CD42b and CD41a, respectively. Multivariate analysis did not demonstrate a statistically significant effect of the type of dialysis membrane on platelet aggregation, calcium flux, or thromboxane B2 production. There was a marked decrease of SIPA in HD patients (pre-HD, mean +/- SEM, 19% +/- 3%) compared with normal controls (43% +/- 3%, P < 0.001), with a further decrease after the HD procedure (post-HD, 12% +/- 2%, P = 0.015 compared with pre-HD). This intradialytic decrease in SIPA correlated with a decrease in GP Ib (pre-HD, 385 +/- 21 mean fluorescence intensity [MFI]; post-HD, 285 +/- 21 MFI, P = 0.0001). GP IIb-IIIa was also significantly decreased post-HD (pre-HD, 1,022 +/- 70 MFI; post-HD, 881 +/- 64 MFI, P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1994

Anti-platelet therapy in graft thrombosis: results of a prospective, randomized, double-blind study.

Hemodialysis (HD) vascular access thrombosis remains a major cause of morbidity, accounting for 17.4% of all HD patient hospital admissions in 1986. We initiated this prospective, randomized, double-blind, placebo-controlled, parallel group study to examine if dipyridamole and/or aspirin decreased the rate of thrombosis of expanded polytetrafluoroethylene (ePTFE) grafts in HD patients. Two patient groups were studied: Type I--with a new ePTFE graft; and Type II--with thrombectomy and/or revision of a previously placed ePTFE graft. One hundred and seven patients were followed for 18 months or until the first thrombotic episode. Actuarial analysis of Type I patients showed cumulative thrombosis rates (mean +/- SEM) of 21 +/- 9% on dipyridamole alone, compared with 25 +/- 11% on dipyridamole and aspirin combination, 42 +/- 13% on placebo, and 80 +/- 12% on aspirin alone. The relative risk of thrombosis with dipyridamole was 0.35 (P = 0.02) and that for aspirin was 1.99 (P = 0.18). In Type II patients, the rate of thrombosis was high in all study drug and placebo groups (overall 78% thrombosis) and actuarial analysis was not carried out because of the small number of patients enrolled. We conclude that dipyridamole is beneficial in patients with new ePTFE grafts and that aspirin does not improve the risk of thrombosis in ePTFE grafts. Neither dipyridamole nor aspirin has any beneficial effect in patients with prior thrombosis of ePTFE grafts.

Adult↗