Sergio Antonio Draibe

Early Control of PTH and FGF23 in Normophosphatemic CKD Patients: A New Target in CKD-MBD Therapy?

BACKGROUND AND OBJECTIVES Levels of parathyroid hormone (PTH) and the phosphaturic hormone FGF23, a fibroblast growth factor (FGF) family member, increase early in chronic kidney disease (CKD) before the occurrence of hyperphosphatemia. This short-term 6-wk dose titration study evaluated the effect of two phosphate binders on PTH and FGF23 levels in patients with CKD stages 3 to 4. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS Patients were randomized to receive over a 6-wk period either calcium acetate (n = 19) or sevelamer hydrochloride (n = 21). RESULTS At baseline, patients presented with elevated fractional excretion of phosphate, serum PTH, and FGF23. During treatment with both phosphate binders there was a progressive decline in serum PTH and urinary phosphate, but no change in serum calcium or serum phosphate. Significant changes were observed for FGF23 only in sevelamer-treated patients. CONCLUSIONS This study confirms the positive effects of early prescription of phosphate binders on PTH control. Prospective and long-term studies are necessary to confirm the effects of sevelamer on serum FGF23 and the benefits of this decrease on outcomes.

K/DOQI-recommended intact PTH levels do not prevent low-turnover bone disease in hemodialysis patients.

The guidelines proposed by the Kidney Disease Outcomes Quality Initiative (K/DOQI) suggested that intact parathyroid hormone (iPTH) should be maintained in a target range between 150 and 300 pg ml(-1) for patients with stage 5 chronic kidney disease. Our study sought to verify the effectiveness of that range in preventing bone remodeling problems in hemodialysis patients. We measured serum ionized calcium and phosphorus while iPTH was measured by a second-generation assay. Transiliac bone biopsies were performed at the onset of the study and after completing 1 year follow-up. The PTH levels decreased within the target range in about one-fourth of the patients at baseline and at the end of the study. The bone biopsies of two-thirds of the patients were classified as showing low turnover and a one-fourth showed high turnover, the remainder having normal turnover. In the group achieving the target levels of iPTH 88% had low turnover. Intact PTH levels less than 150 pg ml(-1) for identifying low turnover and greater than 300 pg ml(-1) for high turnover presented a positive predictive value of 83 and 62%, respectively. Our study suggests that the iPTH target recommended by the K/DOQI guidelines was associated with a high incidence of low-turnover bone disease, suggesting that other biochemical markers may be required to accurately measure bone-remodeling status in hemodialysis patients.

Phosphate Binder Impact on Bone Remodeling and Coronary Calcification – Results from the BRiC Study

Backgroundand Aims: Calcium-containing phosphate binders have been shown to increase the progression of vascular calcification in hemodialysis patients. This is a prospective study that compares the effects of calcium acetate and sevelamer on coronary calcification (CAC) and bone histology. Methods: 101 hemodialysis patients were randomized for each phosphate binder and submitted to multislice coronary tomographies and bone biopsies at entry and 12 months. Results: The 71 patients who concluded the study had similar baseline characteristics. On follow-up, the sevelamer group had higher levels of intact parathyroid hormone (498 ± 352 vs. 326 ± 236 pg/ml, p = 0.017), bone alkaline phosphatase (38 ± 24 vs. 28 ± 15 U/l, p = 0.03) and deoxypyridinoline (135 ± 107 vs. 89 ± 71 nmol/l, p = 0.03) and lower LDL cholesterol (74 ± 21 vs. 91 ± 28 mg/dl, p = 0.015). Phosphorus (5.8 ± 1.0 vs. 6 ± 1.0 mg/dl, p = 0.47) and calcium (1.27 ± 0.07 vs. 1.23 ± 0.08 mmol/l, p = 0.68) levels did not differ between groups. CAC progression (35 vs. 24%, p = 0.94) and bone histological diagnosis at baseline and 12 months were similar in both groups. Patients of the sevelamer group with a high turnover at baseline had an increase in bone resorption (eroded surface, ES/BS = 9.0 ± 5.9 vs. 13.1 ± 9.5%, p = 0.05), whereas patients of both groups with low turnover at baseline had an improvement in bone formation rate (BFR/BS = 0.015 ± 0.016 vs. 0.062 ± 0.078, p = 0.003 for calcium and 0.017 ± 0.016 vs. 0.071 ± 0.084 μm3/μm2/day, p = 0.010 for sevelamer). Conclusions: There was no difference in CAC progression or changes in bone remodeling between the calcium and the sevelamer groups.

Qualidade de vida de pacientes com insuficiência renal crônica em hemodiálise avaliada através do instrumento genérico SF-36

Quality of life is a new concept in the health area and controversies exist about its application to clinical practice. Studies carried out in Brazil in the nephrology area have indicated the need for further investigations. OBJECTIVE: To analyze the quality of life of patients with different times of hemodialysis. METHODS: The study consisted of application of the questionnare SF-36, collection of demographic, socioeconomic and biochemical data, as well as of the clinical characteristics. RESULTS: The study was conducted on 184 patients, 63% of them males, aged 46±15 years (X±SD), with a hemodialysis time of 30±36 months; 48% had up to 4 years of schooling and 53% belonged to the economic-social classes D and E. Impairment of the different dimensions analyzed was observed, with the poorest results being obtained for Physical Aspects and Vitality. A negative correlation was detected between Age and Functional Capacity, Physical Aspects, Pain, and Vitality, and between Hemodialysis Time and Emotional Aspects. A positive correlation was observed between Schooling and Emotional Aspects and between Hemoglobin and Vitality. We observed that diabetic patients were older than non-diabetic patients and presented lower values for the Functional Capacity and General Health condition dimensions. CONCLUSION: SF-36 proved to be a good instrument for the assessment of the quality of life of hemodialysis patients. The presence of a chronic disease, the need for continuous treatment over a long period of time, advanced age, and the presence of co-morbidities were factors that might interfere with the quality of life of this population.

Waist Circumference and Visceral Fat in CKD: A Cross-sectional Study

BACKGROUND In the general population, waist circumference was noted to be a reliable predictor of visceral fat. In addition, increased waist circumference was strongly associated with risk factors for cardiovascular disease. In patients with chronic kidney disease (CKD), the association of waist circumference with visceral fat was never tested. STUDY DESIGN Cross-sectional study. SETTING & PARTICIPANTS 122 patients with CKD not yet on dialysis therapy (75 men; diabetes mellitus, 30%; age, 55.3 +/- 11.3 years; body mass index, 27.1 +/- 5.2 kg/m(2); estimated glomerular filtration rate, 35.4 +/- 15.2 mL/min/1.73 m(2)) were studied. PREDICTOR Waist circumference. OUTCOMES & MEASUREMENTS Anthropometry, abdominal visceral fat measured by means of computed tomography, and cardiovascular disease risk factors. RESULTS Waist circumference strongly correlated with visceral fat (r = 0.75 for men, r = 0.81 for women; P < 0.01). kappa Statistic was 0.56, indicating relatively good agreement between methods. Body mass index showed a lower correlation coefficient (r = 0.68 for men, r = 0.76 for women; P < 0.01) and poor agreement (0.36) with visceral fat in comparison to waist circumference. In men, waist circumference and visceral fat similarly correlated with high-density lipoprotein cholesterol level, triacylglycerol level, and Homeostasis Model Assessment Index (P < 0.05). In women, waist circumference correlated with age, C-reactive protein level, and Homeostasis Model Assessment Index, whereas visceral fat also correlated with low-density lipoprotein cholesterol and triacylglycerol levels (P < 0.05). LIMITATIONS Findings are restricted to patients with CKD not yet on dialysis therapy from a single center. CONCLUSIONS Waist circumference was strongly associated with visceral fat in patients with CKD. Associations between waist circumference and cardiovascular disease risk factors were similar to those observed for visceral fat, particularly in men. These findings suggest that waist circumference may be a simple and inexpensive tool to be used in epidemiological studies.

Association of Changes in Bone Remodeling and Coronary Calcification in Hemodialysis Patients: A Prospective Study

BACKGROUND Vascular calcification is common and constitutes a prognostic marker of mortality in the hemodialysis population. Derangements of mineral metabolism may influence its development. The aim of this study is to prospectively evaluate the association between bone remodeling disorders and progression of coronary artery calcification (CAC) in hemodialysis patients. STUDY DESIGN Cohort study nested within a randomized controlled trial. SETTING & PARTICIPANTS 64 stable hemodialysis patients. PREDICTOR Bone-related laboratory parameters and bone histomorphometric characteristics at baseline and after 1 year of follow-up. OUTCOMES Progression of CAC assessed by means of coronary multislice tomography at baseline and after 1 year of follow-up. Baseline calcification score of 30 Agatston units or greater was defined as calcification. Change in calcification score of 15% or greater was defined as progression. RESULTS Of 64 patients, 38 (60%) of the patients had CAC and 26 (40%) did not [corrected]. Participants without CAC at baseline were younger (P < 0.001), mainly men (P = 0.03) and nonwhite (P = 0.003), and had lower serum osteoprotegerin levels (P = 0.003) and higher trabecular bone volume (P = 0.001). Age (P = 0.003; beta coefficient = 1.107; 95% confidence interval [CI], 1.036 to 1.183) and trabecular bone volume (P = 0.006; beta coefficient = 0.828; 95% CI, 0.723 to 0.948) were predictors for CAC development. Of 38 participants who had calcification at baseline, 26 (68%) had CAC progression in 1 year. Progressors had lower bone-specific alkaline phosphatase (P = 0.03) and deoxypyridinoline levels (P = 0.02) on follow-up, and low turnover was mainly diagnosed at the 12-month bone biopsy (P = 0.04). Low-turnover bone status at the 12-month bone biopsy was the only independent predictor for CAC progression (P = 0.04; beta coefficient = 4.5; 95% CI, 1.04 to 19.39). According to bone histological examination, nonprogressors with initially high turnover (n = 5) subsequently had decreased bone formation rate (P = 0.03), and those initially with low turnover (n = 7) subsequently had increased bone formation rate (P = 0.003) and osteoid volume (P = 0.001). LIMITATIONS Relatively small population, absence of patients with severe hyperparathyroidism, short observational period. CONCLUSIONS Lower trabecular bone volume was associated with CAC development, whereas improvement in bone turnover was associated with lower CAC progression in patients with high- and low-turnover bone disorders. Because CAC is implicated in cardiovascular mortality, bone derangements may constitute a modifiable mortality risk factor in hemodialysis patients.

Quality of life in patients with chronic kidney disease

AIM: To compare the dimensions of quality of life in the stages of chronic kidney disease and the influence of sociodemographic, clinical and laboratory data. INTRODUCTION: The information available on the quality of life of patients on conservative treatment and the relationship between the quality of life and glomerular filtration rate is limited. METHODS: 155 patients in stages 1–5 of chronic kidney disease and 36 in hemodialysis were studied. Quality of life was rated by the Medical Outcomes Study Short Form 36-Item (SF-36) and functional status by the Karnofsky Performance Scale. Clinical, laboratory and sociodemographic variables were investigated. RESULTS: Quality of life decreased in all stages of kidney disease. A reduction in physical functioning, physical role functioning and in the physical component summary was observed progressively in the different stages of kidney disease. Individuals with higher educational level who were professionally active displayed higher physical component summary values, whereas men and those with a higher income presented better mental component summary values. Older patients performed worse on the physical component summary and better on the mental component summary. Hemoglobin levels correlated with higher physical component summary values and the Karnofsky scale. Three or more comorbidities had an impact on the physical dimension. CONCLUSION: Quality of life is decreased in renal patients in the early stages of disease. No association was detected between the stages of the disease and the quality of life. It was possible to establish sociodemographic, clinical and laboratory risk factors for a worse quality of life in this population.

High prevalence of low bone mineral density in pre-dialysis chronic kidney disease patients: bone histomorphometric analysis.

UNLABELLED Chronic kidney disease (CKD) leads to reduced bone mineral density (BMD) in pre-dialysis and dialysis patients. A few studies have used dual-energy x-ray absorptiometry (DEXA) to assess BMD in pre-dialysis CKD patients and have shown low BMD to be highly prevalent. Until now there have been no studies reporting the histological features of low BMD in pre-dialysis CKD patients. AIM To determine the prevalence and histological features of low BMD in pre-dialysis CKD patients. METHOD Pre-dialysis CKD patients (n = 103, 46 females/57 males), median creatinine clearance of 29 (10 - 78) ml/min/ 1.73 m2, were evaluated using biochemical analysis and DEXA. Bone biopsies were obtained from those with low BMD. RESULTS Fifty (48.5%) out of the 103 patients had low BMD (LBD group) and 53 (51.5%) had normal BMD (NBD group). The risk for low BMD was increased in those patients with alkaline phosphatase levels above 190 U/l and intact-PTH (iPTH) below 70 pg/ml (p < 0.05). Demographic and biochemical parameters from both groups were comparable, except for lower body mass index (BMI) in LBD subjects (p = 0.04). Women who had been post-menopausal for at least 1 year comprised 65% (13/20) and 50% (13/26) of the LBD and NBD groups, respectively (p = NS). In 40 LBD patients, bone histomorphometry revealed adynamic bone disease (ABD, 52.5%), osteomalacia (OM, 42.5%) and mixed bone disease (MBD, 5%). Trabecular bone volume (BV/TV) was lower in ABD and OM patients. A nearly significant association was found between ABD and iPTH < or = 150 pg/ml (p = 0.056), whereas higher values of iPTH were associated with OM. Total alkaline phosphatase < or = 190 U/l was significantly associated with ABD, whereas higher values were associated with OM. No correlation was observed between BV/TV and BMD. CONCLUSION Low BMD is frequent in pre-dialysis CKD patients, and low turnover bone disease, manifesting as ABD and OM, was the hallmark of this bone loss.

Increased Resting Energy Expenditure in Hemodialysis Patients with Severe Hyperparathyroidism

Several metabolic derangements, including enhanced protein catabolism, have been suggested to be associated with increased circulating parathyroid hormone (PTH) in patients with secondary hyperparathyroidism (HPT). Such conditions, therefore, might lead to an increase in energy expenditure. The present study examined by indirect calorimetry the resting energy expenditure (REE) of 15 hemodialysis patients who have severe HPT (PTH = 1457 +/- 676 pg/ml) and were pair-matched for age and gender to 15 hemodialysis patients with mild to moderate HPT (PTH = 247 +/- 196 pg/ml). Both groups were also pair-matched for age and gender to a group of 15 healthy adult subjects (control). In six patients from the severe HPT group submitted to total parathyroidectomy, REE was determined 6 mo after the surgery. The groups were not different regarding lean body mass (LBM) measured by bioelectric impedance, serum C-reactive protein, and bicarbonate. Thyroid-stimulating hormone was within the normal range in all groups. Nonadjusted REE was significantly higher in the severe HPT group (1674 +/- 337 kcal/d) compared with patients with mild to moderate HPT (1388 +/- 229 kcal/d; P < 0.05). Both groups did not differ from the control group (1468 +/- 323 kcal/d). When adjustment of REE for LBM was performed using the multiple regression analysis, patients with mild to moderate HPT and control subjects had significantly lower REE (-231 and -262 kcal, respectively) than that of the severe HPT group. Considering all patients together, nonadjusted REE correlated directly with LBM (r = 0.61; P < 0.01). PTH correlated strongly with LBM in the severe HPT group (r = -0.82; P < 0.01). In the multiple linear regression analysis, only LBM and PTH were independent determinants of REE (n = 30; R(2) = 0.47). REE decreased significantly in the six patients who were evaluated 6 mo after parathyroidectomy (from 1617 +/- 339 to 1226 +/- 253; P = 0.02). These results demonstrate that hemodialysis patients with severe HPT have increased REE that might be reduced after parathyroidectomy.

Coronary calcification is associated with lower bone formation rate in CKD patients not yet in dialysis treatment

Vascular calcification is a strong prognostic marker of mortality in hemodialysis patients and has been associated with bone metabolism disorders in this population. In earlier stages of chronic kidney disease (CKD), vascular calcification also has been documented. This study evaluated the association between coronary artery calcification (CAC) and bone histomorphometric parameters in CKD predialysis patients assessed by multislice coronary tomography and by undecalcified bone biopsy. CAC was detected in 33 (66%) patients, and their median calcium score was 89.7 (0.4–2299.3 AU). The most frequent bone histologic alterations observed included low trabecular bone volume, increased eroded and osteoclast surfaces, and low bone‐formation rate (BFR/BS). Multiple logistic regression analysis, adjusted for age, sex, and diabetes, showed that BFR/BS was independently associated with the presence of coronary calcification [p = .009; odd ratio (OR) = 0.15; 95% confidence interval (CI) 0.036–0.619]. This study showed a high prevalence of CAC in asymptomatic predialysis CKD patients. Also, there was an independent association of low bone formation and CAC in this population. In conclusion, our results provide evidence that low bone‐formation rate constitutes another nontraditional risk factor for cardiovascular disease in CKD patients.