A. Ross Morton

Prevalence and Associations of Coronary Artery Calcification in Patients With Stages 3 to 5 CKD Without Cardiovascular Disease

BACKGROUND Patients with chronic kidney disease (CKD) have a high prevalence of coronary artery calcification, suggesting that CKD itself is a risk factor for its occurrence. Existing studies are confounded by the inclusion of patients who may not have CKD by means of diagnostic criteria and by failing to account for existing cardiovascular disease. STUDY DESIGN Cross-sectional study. PARTICIPANTS & SETTING 119 patients with CKD stages 3 to 5 (excluding dialysis) without known cardiovascular disease receiving care at a single center in Kingston, Ontario, Canada. PREDICTORS Glomerular filtration rate was estimated (eGFR) by using the 4-variable Modification of Diet in Renal Disease Study equation. Traditional and nontraditional coronary artery calcification risk factors were defined a priori. OUTCOMES Coronary artery calcification was measured by means of multislice computed tomographic scan. RESULTS Mean and median coronary artery calcification scores were 566.5 +/- 1,108 and 111 (interquartile range, 2 to 631.5), respectively. A total of 32.8% of patients showed little calcification (score, 0 to 10). Calcification correlated with age (r = 0.44; P < 0.001), body mass index (r = 0.28; P = 0.002), high-density lipoprotein cholesterol level (r = -0.23; P = 0.01), diabetes mellitus (r = 0.23; P = 0.01), and cardiovascular risk score (r = 0.35; P < 0.001). By means of multivariable linear regression controlling for eGFR and diabetes mellitus, age (beta = 0.05; 95% confidence interval, 0.03 to 0.06; P < 0.001), body mass index (beta = 0.04; 95% confidence interval, 0.02 to 0.07; P = 0.001), and serum calcium level (beta = 0.9; 95% confidence interval, 0.15 to 1.6; P = 0.02), were risk factors for coronary artery calcification. LIMITATIONS Inadequate sample size and uncontrolled confounding are possible limitations, but are unlikely to have changed the main study findings. CONCLUSIONS In this study, traditional cardiovascular disease risk factors and serum calcium level were associated with coronary artery calcification. No association was shown with eGFR. Studies exploring protective mechanisms against coronary artery calcification are needed.

Mouse to elephant: Biological scaling and Kt/v

The construct Kt/V is used by the nephrology community in prescribing dialysis dose. The concerns that have been raised as to what value of V to use in the calculation of Kt/V touch on the more central question of whether filtration rate should be normalized by a parameter other than V. Within the animal kingdom, a number of physiological variables scale to body size according to an equation of the form Y = YoMb, where Yo is a constant, M is body mass, and b is a scaling exponent. Glomerular filtration rate (GFR) in mammals weighing from 30 g to 503 kg scales to body weight with an exponent of 0.77. Hence, GFR per unit body weight (or Kt/V) decreases significantly with increasing body size. Metabolic rate also scales to body size in a wide range of mammals according to the same general equation and with a scaling exponent of 0.75. Because GFR and metabolic rate scale to body mass with virtually the same exponent, a ratio of the two yields a constant independent of body size. We propose that the ratio (filtration rate/metabolic rate) replace Kt/V. Such a ratio would underscore the linkage between filtration rate (and dialysis therapy) and the metabolic demands of the body.

Quantity of Dialysis: Quality of Life—what is the Relationship?

Health related quality of life (HRQOL) is increasingly being used to evaluate physical and psychosocial parameters in patients receiving dialysis. In patients with chronic illness, these indices are important adjuncts to biochemical measurements. Inadequate dialysis with low urea clearance (Kt/Vurea) has been linked to adverse outcomes in dialysis patients. Little is known about the relationship between dialysis adequacy and patient reported HRQOL. We evaluated HRQOL in 55 hemodialysis and 60 peritoneal dialysis patients using the RAND 36 Item Health Survey 1.0, measuring the following: physical functioning; role limitations (physical); role limitations (emotional); social functioning; emotional well being; pain; energy; and general health perceptions. Kt/V was also calculated for each patient. Mean HD Kt/V was 1.44 +/- 0.31 (range, 0.5-2.0); mean weekly PD Kt/V was 2.28 +/- 0.90 (range, 1.13-6.02). The relationship between Kt/V and HRQOL was tested using Pearsons correlation. No significant association was found for either treatment group between Kt/V and any of the domains of HRQOL. Thus, HRQOL seems to be influenced by factors other than dialysis adequacy, enhancing its role as an independent measure of patient problems otherwise undetected by traditional objective parameters.

Self-delivery of hemodialysis care: A therapy in itself

Patient autonomy, sense of control, and well-being are thought to be enhanced by self-care hemodialysis as a therapy for end-stage renal disease. Dialysis in a satellite setting reduces travel time and can diminish therapy intrusiveness. Health-related quality of life (HRQOL), in terms of functional status and well-being, was measured in a group of patients trained for self-care, and then measured again after these patients were transferred to a satellite unit. Comparison was made with an age- and comorbidity-matched cohort of full-care patients. Patients trained for self-care tended to score higher than the full-care patients in the psychosocial domains of HRQOL, such as role function, social function, and emotional well-being, before and after transfer to the satellite unit. Physiological measurements did not differ significantly between groups at any time during the study, indicating that differences in HRQOL were not attributable to differences in metabolic stability. We conclude that patients trained for self-care hemodialysis experience better subjective quality of life than their full-care counterparts. This study highlights both the usefulness of measuring HRQOL as an outcome of hemodialysis therapy and the potential benefits of therapies such as self-care and satellite dialysis.

The Problem with Kt/V: Dialysis Dose should be Normalized to Metabolic Rate not Volume

Current estimates of hemodialysis adequacy are based on calculations of small solute clearance or changes in online measurements of ionic conductance. A minimum target value of the widely used, dimensionless parameter, Kt/Vurea has been adopted nationally and internationally to represent appropriate dialysis delivery. Based on the principles of allometry, which permit the calculation of scaling equations between the mass of an organism and other parameters, we propose that dialysis dose should be normalized to waste product generation (estimated by metabolic rate). The allometric equations predict a nonlinear correlation between body mass and dialysis dose, such that smaller individuals require proportionately ‘‘more’’ dialysis than larger persons. The argument we present is congruent with outcome data as it relates to sex, race, and body size, as well as supportive of studies suggesting that certain groups (e.g., pregnant women, critically ill patients, diabetics) require greater dialysis delivery than the hemodialysis population in general.

Vasopressin Antagonists: Role in the Management of Hyponatremia

Hyponatremia is a common electrolyte disorder associated with potentially serious or life-threatening consequences. Serum osmolality and sodium concentration [Na+] are regulated by thirst, the hormone arginine vasopressin (AVP), and renal water and sodium handling. Hyponatremia is frequently caused by dysregulation of AVP, which accompanies disorders of water retention, such as congestive heart failure (CHF) and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Clinical trials with AVP receptor antagonists have confirmed the important role of AVP in the pathophysiology of hyponatremia and suggest these agents are efficacious in treating hyponatremia associated with SIADH, cirrhosis, and CHF. Acting directly at AVP receptors in the renal tubules, these agents promote aquaresis – the electrolyte-sparing excretion of free water – in patients with hyponatremia. In clinical trials, AVP receptor antagonists have been shown to increase the serum [Na+] and urine output while decreasing urine osmolality.

DRESS with delayed onset acute interstitial nephritis and profound refractory eosinophilia secondary to Vancomycin

BackgroundDrug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a relatively rare clinical entity; even more so in response to vancomycin.MethodsCase report.ResultsWe present a severe case of vancomycin-induced DRESS syndrome, which on presentation included only skin, hematological and mild liver involvement. The patient further developed severe acute interstitial nephritis, eosinophilic pneumonitis, central nervous system (CNS) involvement and worsening hematological abnormalities despite immediate discontinuation of vancomycin and parenteral corticosteroids. High-dose corticosteroids for a prolonged period were necessary and tapering of steroids a challenge due to rebound-eosinophilia and skin involvement.ConclusionPatients with DRESS who are relatively resistant to corticosteroids with delayed onset of certain organ involvement should be treated with a more prolonged corticosteroid tapering schedule. Vancomycin is increasingly being recognized as a culprit agent in this syndrome.

Insulin resistance is associated with Fibroblast Growth Factor-23 in stage 3-5 chronic kidney disease patients☆ , ☆☆

AIM To determine the associations between insulin resistance, fibroblast growth factor 23 (FGF-23), and coronary artery calcification (CAC) in chronic kidney disease (CKD) patients. INTRODUCTION FGF-23 is associated with atherosclerosis and cardiovascular disease, but its association with insulin resistance in CKD has not been explored. SUBJECTS Cross sectional study of 72 stage 3-5 CKD patients receiving care in Ontario, Canada. MATERIALS AND METHODS Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA-IR), FGF-23 was measured by carboxyl terminal enzyme linked immunoassay (ctFGF-23) and CAC was measured by multi-slice computed tomography. RESULTS Median HOMA-IR was 2.19μU/ml (interquartile range 1.19 to 3.94). Patients with HOMA-IR>2.2 had greater ctFGF-23 (179.7 vs 109.6; P=0.03), and 40% higher log CAC scores (2.09±0.87 vs 1.58±1.26; P=0.049). Multivariable linear regression adjusted for 1,25 dihydroxyvitamin D, kidney function, and parathyroid hormone revealed insulin resistance was a risk factor for greater log ctFGF-23 levels (log HOMA IR β=0.37; 95% confidence interval 0.14 to 0.59; P=0.002). CONCLUSIONS Insulin resistant CKD patients demonstrated higher FGF-23 levels, and increased CAC, while PO4 levels remained normal, suggesting a potential link between insulin resistance and PO4 homeostasis in CKD.

Reviews: Is the Calcium Correct? Measuring Serum Calcium in Dialysis Patients

Abnormalities in calcium concentration are frequent in patients receiving dialysis therapy. Most cases of both hypo‐ and hypercalcemia are mild and asymptomatic. There is concern, however, that, on the one hand, hypocalcemia can drive hyperparathyroidism and eventually lead to gland hypertrophy and autonomous function. Hypercalcemia, on the other hand, can be associated with increased extraosseous calcium and phosphate deposition leading to vascular calcification with an attendant mortality and morbidity. Calcium exists in three main forms in the blood: the physiologically active free or ionized fraction (terms often used interchangeably), a protein bound fraction, and a fraction complexed to other anions. Although the ionized calcium can readily be measured using ion‐specific electrodes, it is the total calcium that is most commonly measured because of sample handling and cost concerns. As it is the free or ionized form that is biologically active (and therefore of most relevance), a number of adjustment formulae have been derived to “correct” the total calcium for changes in albumin, protein, and complexing ion concentrations. These formulae show good statistical correlation with measured ionized calcium in populations studied as a whole, but are generally poor predictors of true ionized hypo‐ or hypercalcemia in individual patients. International guideline committees in nephrology recommend frequent assessment of calcium levels in dialysis patients and recommend that these levels be kept within the normal reference range. These guidelines are less clear on which measurement of calcium should be used to guide clinical decision making. This review examines the merits of making any adjustment to the total calcium measurement, and suggests when it is appropriate to measure the ionized or free calcium.

Body Mass Index, Coronary Artery Calcification, and Kidney Function Decline in Stage 3 to 5 Chronic Kidney Disease Patients

OBJECTIVE To determine whether body mass index (BMI) and coronary artery calcification (CAC) are risk factors for kidney function decline in predialysis chronic kidney disease (CKD) patients. DESIGN Prospective cohort study of 125 stage 3 to 5 predialysis CKD patients. SUBJECTS AND SETTING CKD patients receiving care in Kingston, Ontario, Canada. METHODS BMI, CAC, and kidney function were measured at baseline. CAC was measured by multislice computed tomography scan. Kidney function was determined by the 4-variable reexpressed Modification of Diet in Renal Disease Study equation. At study end, kidney function decline among patients was compared according to baseline BMI and CAC. MAIN OUTCOME Kidney function decline was defined as a 1-year decline in estimated glomerular filtration rate (eGFR) of ≥ 5%. RESULTS Individuals with a decline in eGFR of ≥ 5% at 1 year had higher baseline BMI (33.5 ± 8.3 vs. 28.4 ± 4.9 kg/m(2); P = .0001) and higher baseline median CAC scores (239 vs. 25 Agatston units; P = .01) compared with subjects without such a decline. BMI (r = 0.35; P < .0001) and logarithmically transformed CAC score (r = 0.22; P = .01) correlated with an eGFR decline of ≥ 5%. Both crude and adjusted logistic regression analyses showed escalating CAC (with CAC reported in quintiles and CAC score = 0 Agatston unit as the reference group) was associated with an increased risk of eGFR decline of ≥ 5%. CONCLUSIONS CAC and BMI were associated with kidney function decline over 1 year. The risk of kidney function decline was greater in those with increasing burden of CAC, which remained robust in the adjusted analysis accounting for the risk factors for CKD progression. Larger studies will be required for independent validation of the associations of BMI, CAC, and kidney function decline, and to investigate whether obesity and CAC treatment strategies are efficacious in attenuating kidney function decline in predialysis CKD patients.