|Effat A.E. Tony, Mohammed A Tohamy, Nabila F Amin, Amal M Abdel-Aal, Sanaa Abdel Rahim
Chronic renal failure (CRF) is defined as a slowly progressive loss of kidney functions resulting in permanent kidney failure. Patients with chronic kidney disease (CKD) are at increased risk not only for end-stage kidney disease but also for cardiovascular (CV) disease. CKD is characterized by specific metabolic abnormalities of plasma lipoproteins (LPs). These abnormalities involve all LP classes and show variations depending on the degree of renal impairment, the etiology of the primary disease, the presence of nephrotic syndrome (NS), and the method of dialysis for patients undergoing renal replacement therapy. High LP-a indicates a coagulant risk for plaque thrombosis. Thus, it predicts risk for early atherosclerosis independently of other cardiac risk factors, including low-density lipoprotein (LDL), in patients with CKD. Dyslipidemia in CKD is associated with increased thickness and stiffness of the large arteries. Thus, strict control of dyslipidemia would be beneficial in preventing CVD, at least during the early stages of CKD. The kidney has a vital role in magnesium (Mg) homeostasis, and, although renal handling of Mg is highly adaptable, this ability deteriorates when renal function declines significantly. Mg homeostasis in humans primarily depends on the balance between intestinal uptake and renal excretion. Mg may be normal or decreased in dialysis patients, which is probably due to decreased dietary intake combined with impaired intestinal absorption. In patients on chronic hemodialysis (HD), the major determinant of Mg balance is concentration of Mg in the dialysate. Thus, in patients with CKD, there may be reduced intake, impaired absorption from the intestine, use of diuretics, and acidosis, which may result in decreased serum Mg, whereas reduced renal excretion may cause accumulation of Mg, resulting in increased serum Mg levels in CRF patients. This prospective study aimed to determine the correlation of serum Mg with dyslipidemia in patients on maintenance HD.
Patients and methods
This case–control observational prospective study was conducted on 37 end-stage renal failure patients on maintenance HD (age range: 20–70 years; mean age: 47.8±13.9 years; 16 men and 21 women) who were recruited from the Renal and Dialysis Unit, Department of Internal Medicine, Assuit University Hospitals, Egypt, from 2010 to 2012. In addition, 25 apparently healthy persons (age range: 17–70 years; mean age: 42.0±13.25 years; 13 male and 12 female) recruited mainly from among the medical staff and their families who underwent a health examination at Assuit University Hospitals were enrolled in the study as a control group. The study was approved by the ethical committee of the Faculty of Medicine, Assuit University, and written informed consent was obtained from each participant. The underlying causes of CRF were chronic glomerulonephritis, diabetes mellitus, chronic pyelonephritis, obstructive uropathy, analgesic and idiopathic nephropathy, polycystic kidney disease, and lupus nephritis. The duration of HD ranged from 5 to 15 years, with a mean duration of 7.0±2.9 years. The frequency of HD was three sessions per week. The type of dialyzer membrane was polysulfone with bicarbonate dialysate and the dialysate flow rate was 500 ml/min. Blood flow ranged from 250 to 300 ml/min. The Mg concentration in the dialysate fluid was 1 mEq/l. Dialysis adequacy was assessed by measuring urea kinetic modeling (mean urea kinetic modeling: 2.38±0.44). Glomerular filtration rate was estimated by the modified MDRD equation. Patients were excluded if they had been taking diuretics and/or lipid-lowering agents or had acute or chronic infections. All participants were subjected to thorough history taking, full clinical examination, and anthropometric measurements including weight, height, and BMI. Blood samples from both patients and controls were drawn in the morning after an overnight fast of 12–16 h. Peripheral hemogram, liver function, kidney function, lipid profile, LP-a, and serum electrolytes such as Ca, phosphorus (P), and Mg were assessed. An ECG was obtained with measurement of the corrected QT interval (QTc). Transthoracic echocardiography (ECHO) was performed in all studied groups on an interdialytic day in the evaluation phase. M-mode and two-dimensional images as well as spectral pulsed and color flow Doppler recordings were obtained.
Significant renal dysfunction and lower levels of hemoglobin and platelets with higher mean corpuscular volume (MCV) and mean cell hemoglobin concentration (MCHC) with no statistical difference in the mean level of white blood cells (WBCs) were reported in our studied patients in comparison with controls. Notably, highly statistically significantly lower levels of high-density lipoprotein-cholestrol (HDL-C) with significantly lower levels of LDL-cholesterol (LDL-C) were seen in our HD patients. However, the mean levels of triglycerides (TG) and LP-a were statistically significantly higher, with no statistically significant differences in total cholesterol (TC) levels in the studied patients. The levels of P and Mg were highly statistically significantly higher, with lower Ca levels of no statistical difference, in HD patients. There were no statistically significant differences in the main levels of serum Mg among the studied patients. Lipid metabolism disturbances are frequently present in patients with CRF, representing an important factor in premature atherosclerosis development. The majority of patients with no ST-segment changes had more Mg retention and LP-a retention but with no statistical significance. Nonetheless, none of our patients had prolonged QTc interval in ECG, despite having more Mg retention and LP-a retention with no statistical significance. Left ventricular hypertrophy (LVH) was a striking finding in our patients who had more serum Mg retention and LP-a retention but with no statistical significance. A significant positive correlation between serum Mg level and ST-segment changes in ECG and a significant negative correlation between serum LP-a level and ST-segment changes in ECG were found in our studied patients. Moreover, there were positive correlations of serum Mg levels and LP-a levels with LVH in ECG and ECHO findings in our patients, with no statistical significance. The prolonged QTc interval in ECG had a significant positive correlation with the LP-a levels and a nonsignificant positive correlation with serum Mg level. A significant positive correlation of age with TC, TG, and HDL and a nonsignificant negative correlation with LDL were found in our studied patients. However, there were significant negative correlations of the duration of CKD with TC, TG, and LDL and a negative correlation with HDL in our studied patients, with no statistical significance. Nonsignificant negative correlations of BMI with LDL and HDL and significant negative correlations with TC and TG were found in our studied patients. Notably, there was a negative correlation of lipid profile with serum creatinine and blood urea. Nonsignificant negative correlations of serum calcium (Ca) and serum P with LDL were observed, whereas there were nonsignificant positive correlations of serum Ca with TC and TG and negative correlations of serum P with TC and TG, with no statistical significance. The HDL had a significant positive correlation with serum Ca and a significant negative correlation HDL was found in our studied patients, there was a significant negative correlation between HDL and serum phosphorus, however, serum Ca was positively correlated with HDL but with no statistical significance, but a significant positive correlation between LP-a level and MCHC. There were negative correlations between Mg level and hemoglobin, WBCs, and MCV, with no statistical significance, in our patients and significant negative correlations between Mg level and MCHC and platelets. In the current study, there were nonsignificant positive correlations between LP-a level and blood urea and a nonsignificant negative correlation with serum creatinine. Positive correlations of Mg level with blood urea and serum creatinine were found in the study. Notably, serum Mg was statistically significantly positively correlated with LP-a, TC, TG, and LDL-C; however, there was a highly significant negative correlation between HDL-C and serum Mg. No vascular calcification was found in any of the studied patients. Moreover, LP-a and serum Mg were statistically significantly positively correlated with TC, TG, and LDL-C, with nonsignificant negative correlation with HDL-C. A significant positive correlation of hypertension with LP-a and Mg level was found in our studied patients. Nonsignificant negative correlations of Mg level with the age of patients, height, and BMI were found in our studied patients, but significant positive correlations of LP-a with the age of patients and BMI and a nonsignificant positive correlation with weight were found. Meanwhile, there negative correlations of LP-a and serum Mg level with the duration of CKD and the height of patients. Serum P had a significant positive correlation with Mg level and a significant negative correlation with LP-a level in our study. However, a negative correlation of serum Ca with Mg and LP-a levels, with no statistical significance, was detected. In the multivariate logistic regression analysis of the association between serum Mg level, all laboratory parameters of end-stage renal disease (ESRD), and HD in the studied patients there were three factors associated with HD (Mg level, LDL-C, and LP-a). There was a 45-fold increase in the probability of HD per 1 mg/dl increase in the Mg level and this relation was statistically significant [odds ratio (OR)=45, 95% confidence interval (CI): 15.4–68.1, P<0.01]. Mg level revealed a 14% increase in the prediction level in the study sample compared with controls. There was also a 3% decrease in the probability of HD per 1 mg/dl decrease in the level of serum LDL, and this relation was statistically significant (OR=0.97, 95% CI: 0.95–0.99, P<0.05). LDL had a 5% increase in the predictive level. Moreover, there was 68% increase in the probability of HD per 1 mg/dl increase in the level of LP-a and this relation was statistically significant (OR=1.68, 95% CI: 1.01–2.3, P<0.05). LP-a revealed a 6% excess in the prediction of HD.
In essence, CKD is characterized by specific metabolic abnormalities of plasma LPs. High serum LP-a and low HDL-C are highly atherogenic and are two factors that accelerate atherosclerosis in patients with CKD and correlate with CV mortality. The kidney has a vital role in Mg homeostasis, and, although the renal handling of Mg is highly adaptable, this ability deteriorates when renal function declines significantly. Mg does not increase the LP synthesis. Patients with CKD on maintenance HD show positive correlations between serum Mg and serum HDL-C, LP-a, and TG levels. Therefore, Mg has a protective role in hypertension, arrhythmia, atherosclerosis, and vascular calcification in ESRD patients. Notably, the low serum Mg may be an independent risk factor for premature death in CKD patients. Although the exact role of Mg in bone metabolism is unclear, it may have both positive and negative effects, and it is uncertain what the optimal Mg levels are in uremic patients. Nonetheless, the dialysate Mg concentration is a major determinant of HD or peritoneal dialysis patients’ Mg balance, but the intradialytic CV and hemodynamic benefits of varying Mg concentration in patients’ dialysate are unclear. Acquired prolonged QT-interval syndrome is a highly prevalent condition in patients with CKD undergoing HD and is one of the known pathophysiological mechanisms of sudden death in this population. The high serum LP-a level and Mg depletion in CKD patients on maintenance HD displayed a high frequency of abnormal electrocardiographic findings, including a high prevalence of patients with prolonged QTc interval. Nephrologists must pay attention to identifying patients with prolongation of the QT interval and the associated clinical and laboratory conditions, such as structural changes of the heart, cardiac calcification, Mg depletion, high serum LP-a level, and the prescription of drugs that induce QT interval prolongation, particularly in patients already presenting an extended QT interval. LVH is a striking ECHO feature among our HD patients. Numerous studies now provide strong suggestive evidence for a protective role of Mg in vascular calcification, arrhythmias, and atherosclerosis in ESRD patients. Our results allow us to speculate on the possible salutary role of increasing plasma levels of Mg to facilitate the healing of vascular injuries and to prevent atherosclerosis, hypertension, arrhythmia, and chronic myocardial ischemia. Mg-based compounds have the additional advantage of being much cheaper to use than some newer alternatives. Nevertheless, in an era of numerous negative studies in nephrology, the long-term effects on either the inhibition of vascular calcifications, reduction of ischemic disease, prevention of arrhythmias, or changes in bone morphology have not been adequately investigated. Moreover, a link between BMI and the presence of Mg retention and high LP-a level was observed. New studies need to be outlined, using accurate nutritional status markers for HD patients, to better observe the possible link between malnourishment and prolonged QTc interval.
|Amr M Ebeid, Eman M Elsharkawy, Sara K El Fawal, Yasmine S Naga, Marwa F Oraby
End-stage renal disease (ESRD) patients on hemodialysis (HD) are at increased risk for developing left ventricular hypertrophy (LVH), which is a predisposing factor for premature cardiovascular mortality. Although echocardiography (ECHO) has been the most commonly used technique for assessing LVH, cardiac magnetic resonance imaging (CMR) is now considered the gold standard and the most accurate tool for volume-independent determination of left ventricular mass (LVM).
This study aimed to evaluate the agreement in LVM measurement and LVH detection between CMR and ECHO.
Patients and methods
A single-center, cross-sectional study including 30 ESRD patients on HD (group I) and 15, matched, healthy controls (group II) was performed to compare LVM measurement and LVH detection by ECHO and CMR.
In both groups, ECHO overestimated LVM and left ventricular mass index (LVMI) in comparison with CMR. The Bland–Altman analysis demonstrated wider agreement limits (38.6 to −275.9 g) in LVM measurements by ECHO and CMR in group I (mean difference, 118.63 g, P≤0.001) than in group II (mean difference, 79.29 g; limits, −23.7 to −134.8 g, P≤0.001). Agreement was poor and not statistically significant in group I. Regarding LVMI measurement, there were wider agreement limits (145.5 to −18.8 g/m2) by ECHO and CMR in group I (mean difference, 63.33 g/m2, P≤0.001) than in group II (mean difference, 44 g/m2; limits, 71.3–16.7 g/m2, P≤0.001). Agreement was fair and statistically significant in group I. LVH prevalence by ECHO and CMR was 66.6 and 36.7%, respectively, in group I and 26.6 and 0%, respectively, in group II, with moderate agreement between both techniques (P=0.004) in group I.
ECHO overestimates LVM and LVMI as well as LVH detection in comparison with CMR in ESRD patients on HD. Therefore, for accurate assessment of LVM, CMR may be a better option to detect LVH in this high cardiovascular risk group.