Strong association of carotid plaques with mortality and cardiovascular morbidity in hemodialysis patients.
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Journal Article↗
Biomedical subjects
Rajnish Mehrotra
Publications and source records attributed to Rajnish Mehrotra.
Disordered mineral metabolism and vascular calcification in nondialyzed chronic kidney disease patients.
It is well established that abnormalities in mineral metabolism are apparent early in the course of chronic kidney disease (CKD) and result in clinically relevant consequences such as renal osteodystrophy. Furthermore, there is emerging evidence linking some of these abnormalities (hyperphosphatemia) to the high cardiovascular morbidity and mortality experienced by nondialyzed patients with CKD. Most studies have evaluated vascular calcification in patients with stage 5 CKD. Reports published over the last 2 years show that the process begins rather early in CKD and is particularly severe among elderly and type 2 diabetic patients. Furthermore, "calcium begets calcium", such that the calcification burden in early CKD is an important predictor of subsequent progression, including the rapid increase seen in stage 5 CKD. There is an increasing body of evidence that supports the thesis that elevated serum levels of phosphorus and calcium and deficiency of inhibitors of calcification (for example, fetuin-A) are important in the progression of vascular calcification in patients with end-stage renal disease. However, the concentrations of calcium and phosphorus shown to induce mineralization in cell culture studies are not observed in most patients until late in stage 4 or stage 5 CKD. Cross-sectional and longitudinal studies have also been unable to show a correlation between serum levels of markers of disordered mineral metabolism and severity of vascular calcification. Future studies should evaluate the pathogenetic role of phosphorus retention, which occurs early in the course of CKD, in the induction and/or progression of vascular calcification. Finally, there is a need to identify alternative pathogenetic mechanisms that may be important causes of the high calcification burden observed early in CKD.
Bone Density↗
Diabetes and progression of coronary calcium under the influence of statin therapy.
BACKGROUND: Coronary artery calcium (CAC) is a sensitive marker for the detection of coronary heart disease (CHD). Coronary artery calcification can be accurately quantified using electron beam tomography (EBT). We sought to evaluate the progression of atherosclerosis in asymptomatic persons with type 2 diabetes and measure the influence of statin therapy on CAC progression. METHODS: We evaluated 163 asymptomatic patients with type 2 diabetes (120 men, 43 women). Patients were physician referred and underwent 2 consecutive EBT scans at least 1 year apart. Demographic data, risk factors for CHD, and medication use were collected. Patients with symptoms or known CHD were excluded. RESULTS: The mean age was 65 +/- 10 years. The mean CAC score at baseline was 651 +/- 414. Only 9 (6%) of 163 of participants had scores of 0 at baseline. The time between scans averaged 27 +/- 15 months. Patients not treated with statins demonstrated a median annual increase in CAC progression of 20% (4%-44%), whereas statin-treated patients demonstrated increase of 10% (4%-25%) (P = .0001). Hemoglobin A 1c was weakly associated with CAC progression. CONCLUSIONS: Asymptomatic diabetic patients show a high prevalence of atherosclerosis based on high frequency of coronary calcification. Statin therapy induced a 50% reduction in the rate of CAC progression. As rapid CAC progression has been associated with coronary events, EBT may serve as a noninvasive method for following atherosclerosis and response to therapy.
Adult↗
Coronary artery calcification in nondialyzed patients with chronic kidney diseases.
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Calcinosis↗
Serum fetuin-A in nondialyzed patients with diabetic nephropathy: relationship with coronary artery calcification.
BACKGROUND: Fetuin-A is the most potent circulating inhibitor of calcium phosphorus precipitation and, possibly, an important mediator of insulin resistance. METHODS: In order to determine the role of fetuin-A in the high coronary artery calcification (CAC) burden seen in nondialyzed individuals with diabetic nephropathy (DN), post-hoc analyses of data collected from a cross-sectional study of 88 patients with type 2 diabetes mellitus was done [age, 40-65 years; normoalbuminuria, N= 30 (Latinos); DN, N= 58 (Latinos and African Americans)]. RESULTS: The serum levels of fetuin-A were significantly higher among Latinos with DN when compared to either African Americans with DN or Latino diabetics with normoalbuminuria. Upon adjusting the data for race/ethnicity, there was a strong, direct relationship between serum fetuin-A levels and the CAC score (r= 0.22, P= 0.038) in the study cohort; however, a strong interaction between the nephropathy status and relationship of serum fetuin-A levels with CAC score was present (DN: r= 0.36, P= 0.006; diabetic controls, r= 0.0, P= 0.98). Among individuals with DN, the significance of the association persisted even after controlling the data for other predictors of CAC (partial r= 0.33, P= 0.018). Furthermore, there was a significant direct relationship between serum fetuin-A and serum triglycerides (partial r= 0.27, P= 0.01) and albumin (partial r= 0.30, P= 0.005), and an inverse relationship with glomerular filtration rate (r=-0.24, P= 0.03). CONCLUSION: This first study in early stages of diabetic chronic kidney disease shows that the role of serum fetuin-A may be far more complex than previously described. During predialysis stage of DN, there is a direct relationship between serum fetuin-A levels and CAC score. The reasons for this association in the presence of nephropathy are unclear, but may be secondary to proatherogenic insulin resistance.
Adult↗
Patient education and access of ESRD patients to renal replacement therapies beyond in-center hemodialysis.
BACKGROUND: Nephrologists report that patients' choice should play an important role in the selection of renal replacement therapy (RRT) for end-stage renal disease (ESRD). In the United States, kidney transplant rates remain low and <10% of patients utilize home dialysis therapies. This study examined the effect of pre-ESRD processes on the selection of RRT among incident ESRD patients. METHODS: Using surveys, data were collected for all patients admitted to 229 dialysis units in ESRD Network 18 between April 1, 2002 and May 31, 2002. A total of 1365 patients began chronic dialysis and 1193 facility (87%) and 428 patient (31%) surveys were returned. RESULTS: Substantial proportions of patients were unaware of their kidney disease (36%) or were not seeing a nephrologist (36%) until <4 months before first dialysis. The presentation of treatment options was delayed (48% either after or < 1 month before the first dialysis). The majority of ESRD patients were not presented with chronic peritoneal dialysis, home hemodialysis, or renal transplantation as options (66%, 88%, and 74%, respectively). Using multivariate analyses, variables significantly associated with selection of chronic peritoneal dialysis as dialysis modality were the probability of chronic peritoneal dialysis being presented as a treatment option and the time spent on patient education. CONCLUSION: An incomplete presentation of treatment options is an important reason for under-utilization of home dialysis therapies and probably delays access to transplantation. Improvements in and reimbursement for pre-ESRD education could provide an equal and timely access for all medically suitable patients to various RRTs.
Aged↗
Progression of coronary artery calcification in diabetics with and without chronic kidney disease.
BACKGROUND: Rapid progression of coronary artery calcification (CAC) has been reported among individuals with end-stage renal disease (ESRD). There is limited information on the progression of CAC during earlier stages of diabetic chronic kidney disease (CKD). METHODS: In a prospective, cohort study of type 2 diabetic individuals (N = 90; normoalbuminuric diabetic controls, 30; diabetic nephropathy, DN, 60), electron-beam computed tomography (EBCT) was repeated at an average interval of 19 months. All scan images were acquired at end-systole to minimize interscan variability. In order to eliminate the dependence of the residual error from interscan variability on baseline CAC scores, square root transformed CAC scores were used for analyses of progression of coronary calcification. RESULTS: Repeat EBCT scans were completed in 68 subjects (diabetic controls: 23; DN: 45). There was a highly significant relationship between the proportion of subjects with progressive CAC and renal disease-DN who progressed to ESRD, 80%; DN who did not progress to ESRD, 30%; and diabetic controls, 13% (P < 0.001). Similarly, the magnitude of change was significantly related to renal disease (DN who progressed to ESRD > DN who did not progress to ESRD > diabetic controls, P < 0.001). Using logistic regression and controlling for non-dialyzed DN, ESRD and inter-scan interval, advanced age was the only significant variable associated with progression of CAC. Finally, serum creatinine and baseline CAC score emerged as independent predictors for the magnitude of increase in CAC. CONCLUSION: Progression of CAC is apparent among individuals with DN both before and after ESRD. However, the risk factors associated with progression of CAC may differ at different stages of CKD.
Calcinosis↗
Risks of chronic metabolic acidosis in patients with chronic kidney disease.
Risks of chronic metabolic acidosis in patients with chronic kidney disease. Metabolic acidosis is associated with chronic renal failure (CRF). Often, maintenance dialysis therapies are not able to reverse this condition. The major systemic consequences of chronic metabolic acidosis are increased protein catabolism, decreased protein synthesis, and a negative protein balance that improves after bicarbonate supplementation. Metabolic acidosis also induces insulin resistance and a decrease in the elevated serum leptin levels associated with CRF. These three factors may promote protein catabolism in maintenance dialysis patients. Available data suggest that metabolic acidosis is both catabolic and anti-anabolic. Several clinical studies have shown that correction of metabolic acidosis in maintenance dialysis patients is associated with modest improvements in nutritional status. Preliminary evidence indicates that metabolic acidosis may play a role in beta2-microglobulin accumulation, as well as the hypertriglyceridemia seen in renal failure. Interventional studies for metabolic acidosis have yielded inconsistent results in CRF and maintenance hemodialysis patients. In chronic peritoneal dialysis patients, the mitigation of acidemia appears more consistently to improve nutritional status and reduce hospitalizations. Large-scale, prospective, randomized interventional studies are needed to ascertain the potential benefits of correcting acidemia in maintenance hemodialysis patients. To avoid adverse events, an aggressive management approach is necessary to correct metabolic acidosis. Clinicians should attempt to adhere to the National Kidney Foundation Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines for maintenance dialysis patients. The guidelines recommend maintenance of serum bicarbonate levels at 22 mEq/L or greater.
Acidosis↗
Differential management of cardiovascular disease in ESRD by nephrologists and cardiologists.
BACKGROUND: Mortality and morbidity from cardiovascular disease are high in patients with end-stage renal disease (ESRD). The cardiovascular profile of patients with ESRD may differ from that of the general population. We examined how nephrologists and cardiologists differ in managing hypertension and cardiovascular disease in patients with ESRD. METHODS: Seven cases incorporating relevant clinical and echocardiographic findings common to this population were developed based on a chart review of an ESRD population. Each ESRD case incorporated a clinical presentation designed to test for a specific dichotomous response to a common and important clinical problem. Nine nephrology and 7 cardiology faculty members, each paired with a senior clinical fellow from the discipline, were surveyed. RESULTS: Nephrologists were less likely than cardiologists to initiate beta-blockade in patients with echocardiographic evidence of regional wall motion abnormalities if there was no history of coronary artery disease (CAD; P < 0.01). In patients with known CAD, cardiologists were more likely than nephrologists to intensify antihypertensive therapy, even in the setting of a history of fractures associated with orthostatic hypotension (P < 0.02). Decision making did not differ between subspecialists in the management of left ventricular hypertrophy, congestive heart failure, or diastolic dysfunction. CONCLUSION: Nephrologists and cardiologists differ in their management of hypertension in the presence of ischemic heart disease in the ESRD population. Only limited data specific to the ESRD population are available to assess which approach is superior. The discipline-driven differential management approaches observed emphasize the need for better evidence-based management strategies for this population.
Accidental Falls↗
Age-related decline in serum parathyroid hormone in maintenance hemodialysis patients is independent of inflammation and dietary nutrient intake.
BACKGROUND: There is a direct relationship between age and serum parathyroid hormone (iPTH) in the normal population, but several studies suggest this relationship is reversed in maintenance hemodialysis (MHD) patients. The pathophysiologic basis of this age-related decline in serum iPTH levels remains unclear, although others have proposed that it is related to low dietary phosphorus intakes. METHODS: We conducted a prospective, cross-sectional evaluation of the relationship between age and serum iPTH levels and factors affecting this relationship. All participating subjects were asked to complete a 3-day food diary. The charts were reviewed to obtain routinely measured laboratory values over the preceding 3 months, and serum was collected to measure markers of systemic inflammation. RESULTS: Ninety-two MHD patients (47 men; age, 51.3+/-14.9 [standard deviation] years; median dialysis vintage, 25.8 months) were studied. Age was inversely correlated with both serum phosphorus and iPTH; these relationships remained significant even when the data were adjusted for diabetic status, dialysis vintage, and dietary nutrient intake. However, there were no associations of age, serum phosphorus, or iPTH with dietary intakes of protein, calories, phosphorus, or calcium either on univariate or multivariate analyses. Markers of systemic inflammation (serum C-reactive protein, and alpha1 acid glycoprotein) did not correlate with age, serum phosphorus, and iPTH or dietary nutrient intake. On the other hand, serum albumin, which may reflect long-term effects of inflammation, did correlate inversely with age and positively with serum phosphorus. CONCLUSIONS: Our cross-sectional study confirms that there are age-related lower levels of both serum phosphorus and iPTH in MHD patients. The mechanisms regarding the inverse relationship between serum phosphorus and age are unclear, but may not be caused by low phosphorus intake or systemic inflammation. In elderly MHD patients, the reduced responsiveness of parathyroid glands may be related to age-dependent accumulation of uremic toxins.
Adult↗
Determinants of coronary artery calcification in diabetics with and without nephropathy.
BACKGROUND: In the general population, including those with diabetes mellitus, coronary artery calcification (CAC) correlates with atherosclerotic plaque burden. On the other hand, accumulating evidence suggests that disordered mineral metabolism significantly contributes to the vascular calcification in individuals with end-stage renal disease (ESRD). METHODS: In order to determine the relative contribution of accelerated atherosclerosis and disordered mineral metabolism to CAC in chronic kidney disease, a pilot study of 90 patients with type 2 diabetes mellitus was done [age, 40-65 years; normoalbuminuria, N= 30; diabetic nephropathy (DN), N= 60]. RESULTS: CAC was more prevalent and severe among individuals with DN compared to diabetic controls (odds ratio for prevalence 8.1, 95% CI 2.3-28.5; median scores, 66 vs. 4, P < 0.001). None of the 4 measures of disordered mineral metabolism evaluated in this study (serum calcium, phosphorus, parathyroid hormone, and 1,25 di-hydroxy vitamin D levels) correlated with the prevalence or severity of CAC, or accounted for the differences seen between DN and diabetic controls. On the other hand, the difference in the severity of hypertension (number of antihypertensive medications) appeared to account for the differences in CAC burden seen between DN and diabetic controls. CONCLUSION: This first such study of nondialyzed individuals with DN suggests that, unlike ESRD patients, the high CAC burden seen at earlier stages of diabetic chronic kidney disease is probably unrelated to disordered mineral metabolism. The relationship between the severity of hypertension and CAC burden provides a probable target for intervention in the predialysis phase of DN.
Adult↗
Quality of care in profit vs not-for-profit dialysis centers.
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Hemodialysis Units, Hospital↗
Coronary artery, aortic wall, and valvular calcification in nondialyzed individuals with type 2 diabetes and renal disease.
BACKGROUND: Individuals with end-stage renal disease (ESRD) have highly prevalent and severe vascular and valvular calcification. We undertook this study to test the hypothesis that vascular and valvular calcification begins and is often severe long before diabetic renal disease progresses to ESRD. METHODS: A total of 32 nondialyzed individuals with type 2 diabetes mellitus and diabetic renal disease (albumin excretion rate>30 microg/min) [mean glomerular filtration rate (GFR), 49.8 +/- 6.1 mL/min/1.73 m2] were identified and compared with a group of 18 normoalbuminuric diabetics. We used 3:1 matching to identify 95 nondiabetic controls without renal disease, matched for age, gender, ethnicity, and the presence/absence of dyslipidemia, hypertension, and known coronary artery disease (CAD). RESULTS: Using electron beam computed tomography (CT), the prevalence of coronary artery calcification was significantly greater among diabetic renal disease individuals (prevalence, 94% vs. 59%, P < 0.001; median score, 238 vs. 10, P < 0.001) than the nondiabetic controls. The coronary artery calcification scores were significantly more severe among diabetic renal disease individuals than either the diabetic or nondiabetic controls. Among individuals with diabetic renal disease, the coronary artery calcification and aortic wall calcification scores were several-fold greater among those with known CAD than among those without. There was also a significantly greater prevalence of aortic and mitral valve calcification among diabetic renal disease individuals than nondiabetic controls (aortic, 23% vs. 6%, P = 0.03; mitral, 25% vs. 2%, P < 0.001). Multivariate analysis using all three groups reproduced these findings and also consistently identified age and diabetic renal disease as additional predictors for the presence or severity of coronary artery and aortic wall calcification. CONCLUSION: In this first, systematic analysis among nondialyzed individuals with diabetic renal disease, these data demonstrate that vascular and valvular calcification is present and often severe long before the disease progresses to ESRD. The data also suggest that the coronary artery and aortic wall calcification may represent atherosclerosis.
Aortic Diseases↗
Metabolic acidosis in maintenance dialysis patients: clinical considerations.
Metabolic acidosis in maintenance dialysis patients: Clinical considerations. Metabolic acidosis is a common consequence of advanced chronic renal failure (CRF) and maintenance dialysis (MD) therapies are not infrequently unable to completely correct the base deficit. In MD patients, severe metabolic acidosis is associated with an increased relative risk for death. The chronic metabolic acidosis of the severity commonly encountered in patients with advanced CRF has two well-recognized major systemic consequences. First, metabolic acidosis induces net negative nitrogen and total body protein balance, which improves upon bicarbonate supplementation. The data suggest that metabolic acidosis is both catabolic and antianabolic. Emerging data also indicate that metabolic acidosis may be one of the triggers for chronic inflammation, which may in turn promote protein catabolism among MD patients. In contrast to these findings, metabolic acidosis may be associated with a decrease in hyperleptinemia associated with CRF. Several studies have shown that correction of metabolic acidosis among MD patients is associated with modest improvements in the nutritional status. Second, metabolic acidosis has several effects on bone, causing physicochemical dissolution of bone and cell-mediated bone resorption (inhibition of osteoblast and stimulation of osteoclast function). Metabolic acidosis is probably also associated with worsening of secondary hyperparathyroidism. Data on the effect of correction of metabolic acidosis on renal osteodystrophy, however, are limited. Preliminary evidence suggest that metabolic acidosis may play a role in beta2-microglobulin accumulation, as well as the hypertriglyceridemia seen in renal failure. Given the body of evidence pointing to the several systemic consequences of metabolic acidosis, a more aggressive approach to the correction of metabolic acidosis is proposed.
Acidosis↗
Protein and energy nutrition among adult patients treated with chronic peritoneal dialysis.
Protein-energy malnutrition (PEM) in adult patients treated with chronic peritoneal dialysis (CPD), which is highly prevalent and frequently severe in its manifestation, poses a significant therapeutic dilemma. The causes of PEM include inflammation, low nutrient intake, nutrient losses during dialysis, metabolic acidemia, coexisting illnesses, and possibly the endocrine disorders of uremia. Treatment strategies for PEM in CPD patients include the following: attempt to treat the potentially reversible causes of anorexia, increase nutrient intake (by nutritional counseling, oral food supplements, consideration of appetite stimulants and intraperitonial amino acid solutions), and the correction of metabolic acidosis. Coexisting illnesses engendering PEM should be treated. Experimental evidence suggests that such agents as anabolic steroids, human growth hormone, insulin-like growth factor-I, and L-carnitine may engender positive protein balance in these individuals. Finally, the use of anti-inflammatory agents to improve the nutritional status of malnourished CPD patients remains to be defined. There is a need to carry out clinical trials that examine whether an improvement in the nutritional status of CPD patients is associated with an improvement in their mortality, morbidity and/or quality of life.
Acidosis↗
Emphasizing patient choice: the modality selection project in ESRD Network 18.
ESRD Network 18 has identified numerous opportunities from improvement in the process of modality selection for incident patients commencing maintenance dialysis therapy. The overall goal for the Network is to ensure that all patients are presented with a choice for treatment in a timely manner. This in turn, would lead to better preparation of patients for RRT and hopefully, have a positive impact on the morbidity and mortality of maintenance dialysis patients.
Choice Behavior↗
Improvement of nutritional status after initiation of maintenance hemodialysis.
BACKGROUND: Recent data suggest that serum albumin concentrations increase during the several month-period that follows the initiation of maintenance hemodialysis (MHD) therapy. Some investigators have shown that the rate of increase in serum albumin level is related directly to 24-hour urine protein losses before the initiation of dialysis therapy. However, serum albumin levels increase even in patients starting MHD therapy without significant proteinuria, suggesting that this increase may be one manifestation of improving protein-energy nutritional status associated with commencing MHD therapy. We examined this question by reviewing records of all patients admitted to our outpatient dialysis unit within 30 days of initiation of MHD therapy. METHODS: Ninety-seven patients qualified for the study. Their routine laboratory test results beginning with the time of admission to the outpatient unit until month 6 of chronic dialysis therapy were analyzed. RESULTS: Between months 1 and 6, there was a statistically significant increase in values for predialysis serum albumin, iron, transferrin saturation, creatinine, and normalized protein equivalent of total nitrogen appearance (nPNA). Many of these values were still increasing by month 6. Body weight declined initially until month 4, then increased. There was a strong curvilinear relationship between mean nPNA and final serum albumin level. CONCLUSIONS: Our results suggest that an improvement in nutritional status, including an increase in dietary protein intake and serum albumin level, often occurs with the initiation of MHD therapy. The improvement in nutritional status may be related to the increase in dietary protein intake.
Adult↗
An analysis of dialysis training in the United States and Canada.
BACKGROUND: Because the prevalence of end-stage renal disease (ESRD) has progressively increased in both the United States and Canada, patients with ESRD are likely to constitute progressively larger proportions of nephrology practices. METHODS: We mailed a questionnaire to US and Canadian nephrology program directors to determine methods used in dialysis training; 53% of US and 73% of Canadian programs responded. RESULTS: Training programs in the United States enrolled a larger median number of fellows and had a lower median faculty-fellow ratio compared with programs in Canada. However, the availability of faculty in providing training in the care of patients undergoing maintenance hemodialysis (MHD) or chronic peritoneal dialysis (CPD) was similar in both countries. There were wide variations in availability of patients in both the United States and Canada. US training programs offered trainees significantly lower numbers of MHD and CPD patients; 29% of US training programs had less than five CPD patients per fellow. Similarly, there were wide variations in the amount of time trainees spent providing care to MHD and CPD patients; in 14% of US training programs, fellows spent less than 5% of their time receiving training for patients undergoing CPD. Only a small proportion of training programs had faculty resources or ensured training for fellows in the placement of percutaneous tunneled venous hemodialysis catheters or peritoneal dialysis catheters. CONCLUSIONS: To conclude, there are wide variations in dialysis training in both the United States and Canada. This survey raises concerns that many US training programs either do not have an appropriate number of CPD patients or do not allocate appropriate time to ensure the preparedness of fellows in providing independent care for patients with ESRD undergoing CPD.
Canada↗