Fibroblast growth factor 23 in chronic kidney disease: bridging the gap between bone mineral metabolism and left ventricular hypertrophy.

BACKGROUND: Left ventricular hypertrophy (LVH) is a major cardiovascular complication in chronic kidney disease (CKD) patients. For a successful management of LVH, the comprehensive understanding of the classical and the new emerging factors associated with LVH is of paramount importance. The aim of the present study was to evaluate the clinical correlates of bone mineral metabolism with the occurrence of LVH in nondialyzed CKD patients. METHODS: This cross-sectional study included 96 patients with stages 2-4 CKD. Demographic characteristics, clinical profiles, laboratory tests and transthoracic echocardiogram were performed. RESULTS: LVH was observed in 36% of the patients. Patients with LVH were older, had a higher prevalence of hypertension, and higher levels of intact parathormone, fibroblast growth factor 23 and C-reactive protein. Serum phosphorus, alkaline phosphatase and vitamin D were not associated with the presence of LVH. In the multiple logistic regression analyses only FGF23 remained as a variable independently associated with LVH. CONCLUSION: We confirmed the high prevalence of LVH in nondialyzed CKD patients and showed that FGF23, an early marker of phosphorus load, was an important factor associated with LVH in these patients. Monitoring of FGF23 could be important for the management of LVH in this population.

Serum-soluble Fas and serum levels of erythropoietin in chronic kidney disease.

BACKGROUND: Soluble Fas levels (sFas) are increased in the serum of uremic patients and are associated with the presence of anemia and recombinant human EPO (rHuEPO) dosage in dialysis patients. It is possible that sFas levels are associated with an increased need for serum erythropoietin levels (Epo) in chronic kidney disease and dialysis patients in order to maintain hematocrit (Hct) levels. AIMS: To investigate the relationship between serum sFas levels, serum Epo levels and the ratio between Epo levels and Hct in uremic patients. METHODS: We studied 52 predialysis chronic kidney disease patients (CKD; 33 M, 57 +/- 12 years, hematocrit (Hct) = 37 +/- 7%), 29 peritoneal dialysis patients (PD; 12 M, 54 +/- 14 years, Hct = 36 +/- 7%), 29 hemodialysis patients (HD; 19 M, 47 +/- 14 years, Hct = 33 +/- 5%) and 29 healthy volunteers (control group 17 M, 50 +/- 16 years, Hct = 43 +/- 3%). We examined the relationship between Hct and serum levels of Epo, sFas, C-reactive protein, IL-6 and iron status. The ratio of serum Epo divided by Hct (Epo/Hct) was used as an indicator of Epo responsiveness. RESULTS: Compared to normal subjects, the CKD, PD and HD groups presented lower Hct levels and higher serum levels of sFas, Epo, Epo/Hct and IL-6. Serum levels of sFas correlated negatively with albumin (r = -0.24, p = 0.02), IL-6 (r = -0.18, p = 0.04) and Epo/Hct (r = -0.37, p < 0.001). In multivariate analysis, after adjusting for markers of iron store and inflammation, only sFas correlated with Epo/Hct. In the CKD group, there were negative correlations between serum levels of sFas and glomerular filtration rate (GFR) (r = -0.45, p < 0.001) and between Epo/Hct and GFR (r = -0.32; p = 0.02). There was a positive correlation between Epo/Hct and serum levels of sFas in the CKD group (r = 0.31, p = 0.03) and in the HD groups (r = 0.58, p = 0.001). CONCLUSION: Our findings show that serum sFas is associated with higher Epo/Hct ratio, suggesting that sFas may be a marker of Epo hyporesponsiveness in uremia. Further studies are needed to determine whether sFas is just a marker of Epo hyporesponsiveness or is also involved in its pathophysiology.

Nutritional status and body composition after 6 months of patients switching from continuous ambulatorial peritoneal dialysis to automated peritoneal dialysis

Our objective was to determine if automated peritoneal dialysis (APD) leads to changes in nutritional parameters of patients treated by continuous ambulatory peritoneal dialysis (CAPD). Twenty-six patients (15 males; 50.5 ± 14.3 years) were evaluated during CAPD while training for APD and after 3 and 6 months of APD. Body fat was assessed by the sum of skinfold thickness and the other body compartments were assessed by bioelectrical impedance. During the 6-month follow-up, 12 patients gained more than 1 kg (GW group), 8 patients lost more than 1 kg (LW group), and 6 patients maintained body weight (MW group). Except for length on dialysis that was longer for the LW group compared with the GW group, no other differences were found between the groups at baseline. After 6 months on APD, the LW group had a reduction in body fat (24.5 ± 7.7 vs 22.1 ± 7.3 kg; P = 0.01), body cell mass (22.6 ± 6.2 vs 21.6 ± 5.8 kg, P = 0.02) and phase angle (5.4 ± 0.9 vs 5.1 ± 0.8 degrees, P = 0.004). In the GW group, body fat (25 ± 7.6 vs 27.2 ± 7.6 kg, P = 0.001) and body cell mass (20.1 ± 3.9 vs 20.8 ± 4.0 kg, P = 0.05) were increased. In the present study, different patterns of change in body composition were found. The length of previous dialysis treatment seems to be the most important factor in determining these nutritional modifications.

High serum levels of soluble Fas (sFas) in CKD patients: effects of renal clearance, reabsorption and synthesis.

PURPOSE: Increased serum concentrations of soluble Fas (sFas) have been reported in patients with chronic kidney disease (CKD). However, little is known about the renal clearance of sFas, whether sFas is reabsorbed in the renal tubules, or the behavior of sFas synthesis in CKD. MATERIALS AND METHODS: We studied 69 patients with CKD (60+/-15 years old, creatinine clearance 37+19 ml/min/1.73 m2) and 14 healthy subjects (61+/-17 years, creatinine clearance 79+/-24 ml/min/1.73 m2). ELISA was used to measure the levels of sFas (pg/mL) and retinol binding protein (RBP - mg/L). RT-PCR was used to quantify sFasmRNA of leukocytes. RESULTS: Serum sFas levels were significantly higher in patients with CKD (2781+/-1214 vs. 2196+/-773, p=0.02). The concentrations of sFas in 24-hour urine samples (23+/-27 vs. 40+/-17, p=0.006) and sFas Clearance (0.019+/-0.022 vs. 0.036+/-0.020, p=0.01) were significantly lower in patients with CKD. sFas clearance correlated with creatinine clearance (r=0.25, p=0.02). Urine concentrations of RBP correlated with sFas concentrations in the urine (r=0.80, p<0.001). sFasmRNA were higher in patients with CKD (3.9+/-1.8 vs. 2.5+/-0.9, p<0.001). CONCLUSIONS: In CKD patients, the decrease in renal function is followed by a decrease in sFas clearance and an increase in serum sFas. In patients with proximal tubule dysfunction (high urinary RBP concentrations), urinary sFas is also increased, suggesting that sFas is reabsorbed by the proximal tubule. It is possible that an increase in sFas synthesis also contributes to the increase of serum sFas concentrations in uremia.

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.

Nutritional status and body composition after 6 months of patients switching from continuous ambulatorial peritoneal dialysis to automated peritoneal dialysis.

Our objective was to determine if automated peritoneal dialysis (APD) leads to changes in nutritional parameters of patients treated by continuous ambulatory peritoneal dialysis (CAPD). Twenty-six patients (15 males; 50.5 +/- 14.3 years) were evaluated during CAPD while training for APD and after 3 and 6 months of APD. Body fat was assessed by the sum of skinfold thickness and the other body compartments were assessed by bioelectrical impedance. During the 6-month follow-up, 12 patients gained more than 1 kg (GW group), 8 patients lost more than 1 kg (LW group), and 6 patients maintained body weight (MW group). Except for length on dialysis that was longer for the LW group compared with the GW group, no other differences were found between the groups at baseline. After 6 months on APD, the LW group had a reduction in body fat (24.5 +/- 7.7 vs 22.1 +/- 7.3 kg; P = 0.01), body cell mass (22.6 +/- 6.2 vs 21.6 +/- 5.8 kg, P = 0.02) and phase angle (5.4 +/- 0.9 vs 5.1 +/- 0.8 degrees, P = 0.004). In the GW group, body fat (25 +/- 7.6 vs 27.2 +/- 7.6 kg, P = 0.001) and body cell mass (20.1 +/- 3.9 vs 20.8 +/- 4.0 kg, P = 0.05) were increased. In the present study, different patterns of change in body composition were found. The length of previous dialysis treatment seems to be the most important factor in determining these nutritional modifications.

Evaluation of the role of severe hyperparathyroidism on coronary artery calcification in dialysis patients.

BACKGROUND: Chronic kidney disease (CKD) patients are at a high risk of dying from a cardiovascular event, mainly due to coronary calcification. Among the various uremic and dialysis-specific risk factors for coronary calcification are mineral metabolism disorders. The role that secondary hyperparathyroidism (SHPT) consequent to the altered calcium and phosphate metabolism plays in the pathogenesis of coronary calcification remains unclear. The aim of this study was to evaluate the prevalence of coronary artery calcification in dialysis patients with severe SHPT submitted to multislice coronary tomography (MSCT) and to identify risk factors for coronary calcification. METHODS: This study involved 23 adult dialysis patients (age >18 years) with severe SHPT who were candidates for parathyroidectomy (PTX). All were submitted to MSCT and bone densitometry during the month preceding PTX. Fasting blood samples were collected immediately before surgery. Markers of mineral metabolism, including ionized calcium, phosphorus, alkaline phosphatase, intact-parathyroid hormone (iPTH), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand, were analyzed. Dyslipidemia was assessed by determination of LDL, HDL and VLDL-cholesterol and triglyceride levels. Agatston units (AU) were used to calculate calcium scores. RESULTS: No coronary calcification was found in 30% of the patients. Moderate (calcium score > 100 AU) and severe (calcium score >400 AU) calcification was observed in 12 and 36% of the patients, respectively. In the univariate analysis, calcium volume correlated positively with VLDL-cholesterol (r = 0.44; p = 0.03) and, albeit less than significantly, with age (r = 0.35; p = 0.09), triglycerides (r = 0.39; p = 0.05) and Framingham risk index (r = 0.37; p = 0.07). We also found that OPG correlated negatively with bone mineral density at the L2-L4 lumbar vertebrae (r = -0.54; p = 0.007) and femoral neck (r = -0.43; p = 0.04). CONCLUSIONS: Although high levels of PTH should be considered a risk factor for cardiovascular death, the real role of severe SHPT on coronary calcification is to be clarified.

Resting energy expenditure and its determinants in hemodialysis patients.

OBJECTIVE: Chronic kidney disease is associated with several metabolic disturbances that can affect energy metabolism. As resting energy expenditure (REE) is scarcely investigated in patients on hemodialysis (HD) therapy, we aimed to evaluate the REE and its determinants in HD patients. DESIGN: Cross-sectional study. SETTING: Dialysis Unit of the Nephrology Division, Federal University of São Paulo, Brazil. SUBJECTS: The study included 55 patients (28 male, 41.4+/-12.6 years old) undergoing HD therapy thrice weekly for at least 2 months, and 55 healthy individuals pair matched for age and gender. Subjects underwent fasting blood tests, as well as nutritional assessment, and the REE was assessed by indirect calorimetry. RESULTS: REE of HD patients was similar to that of pair-matched controls (1379+/-272 and 1440+/-259 kcal/day, respectively), even when adjusted for fat-free mass (P=0.24). REE of HD patients correlated positively with fat-free mass (r=0.74; P<0.001) and body mass index (r=0.37; P<0.01), and negatively with dialysis adequacy (r=-0.46; P<0.001). No significant univariate correlation was found between REE and age, dialysis vintage, serum creatinine, urea, albumin, bicarbonate, parathyroid hormone (PTH) or high-sensitivity C-reactive protein (CRP). In the multiple linear regression analysis, using REE as dependent variable, the final model showed that besides the well-recognized determinants of REE such as fat-free mass and age, PTH and CRP were the independent determinants of REE in HD patients (R (2)=0.64). CONCLUSIONS: In this study, the REE of HD patients was similar to that of healthy individuals, even with the positive effect of secondary hyperparathyroidism and inflammation on REE of these patients.

Osteoporosis in hemodialysis patients revisited by bone histomorphometry: a new insight into an old problem.

Osteoporosis in hemodialysis patients is associated with high morbidity and mortality and, although extensively studied by noninvasive methods, has never been assessed through bone biopsy. The aim of this study was to use histomorphometry to evaluate osteoporosis and identify factors related to its development in hemodialysis patients. We conducted a cross-sectional study involving 98 patients (35 women and 63 men; mean age: 48.4 +/- 13 years) on hemodialysis for 36.9 +/- 24.7 months. Patients were submitted to transiliac bone biopsy with double tetracycline labeling. The bone metabolism factors ionized calcium, phosphorus, bone alkaline phosphatase, deoxypyridinoline, intact parathyroid hormone, and 25(OH) vitamin D were evaluated, as were the bone remodeling cytokines osteoprotegerin (OPG), soluble receptor-activator of NF-kappabeta ligand (sRANKL) and tumor necrosis factor-alpha (TNF)alpha. Osteoporosis was defined as trabecular bone volume (BV/TV) greater than 1 s.d. below normal (men <17.4%; women <14.7%). Forty-five patients (46%) presented osteoporosis, which was correlated with white race. We found BV/TV to correlate with age, OPG/sRANKL ratio, TNFalpha levels, and length of amenorrhea. In multiple regression analysis adjusted for sex and age, length of amenorrhea, white race, and OPG/sRANKL ratio were independent determinants of BV/TV. Histomorphometric analysis demonstrated that osteoporotic patients presented normal eroded surface and low bone formation rate (BFR/BS). Osteoporosis is prevalent in hemodialysis patients. Low BFR/BS could be involved in its development, even when bone resorption is normal. Cytokines may also play a role as may traditional risk factors such as advanced age, hypogonadism, and white race.

Short-term effects of a very-low-protein diet supplemented with ketoacids in nondialyzed chronic kidney disease patients.

OBJECTIVE: To evaluate the effects on the nutritional and metabolic parameters of a very-low-protein diet supplemented with ketoacids (VLPD+KA) in comparison with a conventional low-protein diet (LPD) in chronic kidney disease (CKD) patients. DESIGN: Prospective, randomized, controlled clinical study. SETTING: Outpatient Clinic of the Nephrology Division of Federal University of Sao Paulo, Brazil. SUBJECTS: The study involved 24 patients with advanced CKD (creatinine clearance <25 ml/min) that were randomly assigned to either a VLPD+KA (VLPD+KA group, 12 patients) or to a conventional LPD with 0.6 g/kg/day (LPD group, 12 patients). The patients were followed for 4 months. RESULTS: Nutritional status was adequately maintained with both diets for the studied period. Protein intake and serum urea nitrogen decreased significantly only in the VLPD+KA group (from 0.68+/-0.17 to 0.43+/-0.12 g/kg/day, P<0.05; from 61.4+/-12.8 to 43.6+/-14.9 mg/dl, P<0.001; respectively). Ionized calcium did not change in the VLPD+KA group but tended to decrease in the LPD group. Serum phosphorus tended to decrease in the VLPD+KA group probably as a result of a significant reduction in dietary phosphorus (529+/-109 to 373+/-125 mg/day, P<0.05) associated to the phosphorus-binding effect of the ketoacids. No change in these parameters was found in the LPD group. Serum parathormone increased significantly only in the LPD group (from 241+/-138 to 494+/-390 pg/ml, P<0.01). The change in PTH concentration was negatively correlated with changes in ionized calcium concentration (r=-0.75, P=0.02) and positively correlated with changes in serum phosphorus (r=0.71, P=0.03) only in the LPD group. CONCLUSION: This study indicates that a VLPD+KA can maintain the nutritional status of the patients similarly to a conventional LPD. Besides, an improvement in calcium and phosphorus metabolism and a reduction in serum urea nitrogen were attained only with the VLPD+KA. Thus, VLPD+KA can constitute another efficient therapeutic alternative in the treatment of CKD patients.

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.

Influence of renal function on spontaneous dietary intake and on nutritional status of chronic renal insufficiency patients.

OBJECTIVE: To analyze the spontaneous food intake and the nutritional parameters of patients with different degrees of chronic renal insufficiency (CRI) at the onset of predialysis treatment. DESIGN: Cross-sectional. SETTING: Outpatient Clinic of the Nephrology Division of Federal University of São Paulo, Brazil. SUBJECTS: The analysis involved 487 (187 women and 300 men) patients with moderate to advanced CRI who were evaluated in the first visit to the clinic. RESULTS: Patients were divided according to creatinine clearance (CrCl) quartiles. CrCl in the first quartile was lower than 19.9 ml/min/1.73 m(2) and in the fourth one was higher than 43 ml/min/1.73 m(2). Energy intake was significantly (P<0.05) lower in the first quartile when compared with the fourth one while protein intake estimated by protein equivalent of nitrogen appearance (PNA) was significantly lower in the first, second and third quartiles in comparison with the fourth (P<0.05). Body mass index (BMI) and percentage of ideal body weight were significantly decreased in the three lowest levels of renal function. Standard per cent of triceps skinfold thickness was lower in the first quartile when compared with the fourth one. Compared with the fourth quartile, standard per cent of midarm muscle circumference (MAMC) was lower in the second and in the third quartile. CrCl correlated directly and significantly with PNA (r=0.30; P<0.01), energy intake (r=0.17; P<0.01), and MAMC (r=0.20; P<0.01). In a multiple linear regression analysis, controlling for energy and protein intake, CrCl correlated significantly and positively with BMI and MAMC. CONCLUSION: This study suggests that a spontaneous decrease in energy and protein intake as well as in anthropometric indices follows a decline in renal function in patients with no previous dietary intervention.

Parathyroid hormone changes during phosphorus load in patients with chronic renal insufficiency with low serum parathyroid hormone or adynamic bone disease.

UNLABELLED: Adynamic bone disease (ABD) is frequently associated with low serum parathyroid hormone (PTH) concentrations. Many clinical and therapeutic conditions have been associated with ABD, and recently, a low phosphorus intake accompanied by low serum concentration of phosphorus and PTH has been described. AIM: To evaluate the parathyroid gland response of chronic renal insufficiency patients (CRI) with low serum PTH or ABD to a phosphorus load. METHODS: We examined the effects of 0.5 and 1.0 g/d of phosphorus load over a period of 60 days in 18 patients with mild CRI with a bone biopsy showing ABD (n = 7) or with low serum PTH (serum intact PTH < or = 40 ng/l) and serum phosphorus < 4.5 mg/dl (n = 11). RESULTS: Serum intact PTH increased significantly only after 1 g of phosphorus (58.5 to 83 ng/l) with a median percent increase of 72%. PTH secretion increased more in patients with lower basal PTH levels (81%). Serum phosphorus did not change significantly and urinary phosphorus increased from 487 to 1,062 mg/dl (p < 0.05). Significant decreases in serum ionized calcium (from 1.26 to 1.19 mmol/l) and calcitriol (from 34.5 to 24.9 pg/ml) were observed. Changes in PTH were inversely correlated with changes in serum ionized calcium (r = -0.54, p < 0.05) and the final PTH concentrations were positively correlated with changes in serum phosphorus (r= 0.52, p < 0.05). CONCLUSIONS: The parathyroid glands of chronic renal insufficiency patients with "relative hypoparathyroidism" or ABD responded to a phosphorus load with an increase in serum PTH levels. The decrease in serum ionized calcium and calcitriol as well as minimal changes in serum phosphorus appeared to be involved in this response.

Resting energy expenditure in pre-dialysis diabetic patients.

BACKGROUND: The metabolic derangements of diabetes mellitus (DM) associated with those of chronic renal failure (CRF) may interfere with the energy and protein balance of patients with both diseases. The aim of this study was to verify whether the resting energy expenditure (REE) of non-dialysis chronic renal failure diabetic patients differs from that of chronic renal failure patients without DM. METHODS: REE was measured by indirect calorimetry in 24 CRF diabetic patients (CRF diabetes group), matched for age, gender, and degree of renal impairment to 24 CRF patients without DM (CRF control group). RESULTS: The CRF diabetes group had a significantly higher REE (1538+/-230 kcal/day) than the CRF control group (1339+/-315 kcal/day, P = 0.009). This difference was maintained even when the REE was adjusted for lean body mass (LBM; 30.3+/-4.3 vs 26.3+/-5.4 kcal/kg LBM/day, P = 0.004). Mean protein intake was significantly higher in the CRF diabetes than in the CRF control group (0.89+/-0.20 vs 0.76+/-0.25 g/kg/day, P = 0.02). Mean protein equivalent of nitrogen appearance (PNA) was also significantly higher in the CRF diabetes patients (1.21+/-0.31 vs 1.03+/-0.22 g/kg/day, P = 0.02), reflecting a higher protein intake and/or elevated protein breakdown. Accordingly, REE was directly correlated with PNA mainly in the CRF diabetes group (r = 0.57, P < 0.003). CONCLUSION: Metabolic disturbances of poorly controlled DM may account for the higher REE observed in the CRF diabetes group. The role of the apparently higher protein breakdown in this increased REE remains to be clarified.

Risk of bacterial infection in patients under intravenous iron therapy: dose versus length of treatment.

Some studies have suggested that intravenous iron therapy may be associated with an increased risk of infection. We analyzed the incidence of bacterial infection in 111 hemodialysis patients. Group 1 (n = 39, transferrin saturation <20%) received 10 doses of 100 mg of intravenous iron saccharate, 3 doses per week (28 treatment days); Group 2 (n = 13, transferrin saturation <20%) received 20 doses, 3 doses per week (70 treatment days); and Group 3 (n = 59, transferrin saturation 20-50%) received 10 doses, 1 dose per week (70 treatment days). The follow-up was 150 days for all groups, and all infectious episodes were recorded. Pulmonary infection was the most frequent event observed in all of the groups. In an incidence-density analysis, Group 2, which received a total of 20 doses, presented a significantly higher incidence of infection than Group 3, which received only 10 doses over the same period (0.13 versus 0.06 infections per patient per month, p = 0.04). No difference was observed between Groups 1 and 2 suggesting that the risk of infection during iron therapy is dose dependent rather than time length dependent.

Customized bicarbonate buffered dialysate and replacement solutions for continuous renal replacement therapies: effect of crystallization on the measured levels of electrolytes and buffer.

The aim of this study was to investigate the impact of the addition of calcium to bicarbonate solutions for continuous renal replacement therapy (CRRT). We tested single bag (bicarbonate and calcium mixed 24 h before testing) and double bag solutions (mixed immediately before) with and without the addition of 4 mEq/L of acetate. Prescribed calcium varied from 0 to 5 mEq/L. All test solutions containing calcium showed crystallization at light microscopy. The double bag solutions decreased but did not prevent crystallization. The addition of acetate did not interfere with crystallization. Crystallization, as measured by the weight of the crystals after filtration of the solutions, showed a significant positive correlation with the calcium deficit (prescribed minus measured) and with partial pressure of carbon dioxide. The measured level of calcium was lower than expected and correlated with crystallization. Our results suggest that the use of bicarbonate solutions containing calcium as replacement fluids for CRRT is a potentially unsafe procedure.

Nutritional status of hemodialysis patients with secondary hyperparathyroidism

The repercussions of secondary hyperparathyroidism on the nutritional status of chronic renal failure patients have not been well established. Therefore, the aim of this study was to compare the nutritional indices of hemodialysis patients with and without secondary hyperparathyroidism. Sixteen hemodialysis patients with serum parathyroid hormone (PTH) levels higher than 420 pg/ml (hyperparathyroidism group) were matched for gender, age and length of dialysis treatment to 16 patients with serum PTH between 64 and 290 pg/ml (control group). The following parameters were assessed: anthropometric indices (body mass index, skinfold thickness, midarm muscle circumference and body fat), 4-day food diaries, protein catabolic rate, biochemical indices (blood urea nitrogen, serum creatinine, albumin, ionized calcium, inorganic phosphorus, serum alkaline phosphatase, PTH, pH and HCO3) and dialysis efficiency. We did not observe differences in the anthropometric indices between the two groups. Only calcium intake was significantly different between groups (307.9 mg/day for the hyperparathyroidism group vs 475.8 mg/day for the control group). Protein catabolic rate tended to be higher in the hyperparathyroidism group compared to the control group (1.3 vs 0.9 g kg-1 day-1; P = 0.08). Except for blood urea nitrogen (86.4 vs 75.7 mg/dl), alkaline phosphatase (175 vs 65 U/l) and PTH (898 vs 155 pg/ml), no other differences were found between groups in the biochemical indices studied. PTH was directly correlated with protein catabolic rate (r = 0.61; P<0.05) and length of dialysis (r = 0.53; P<0.05) only in the hyperparathyroidism group. Considering the indices used, we could not demonstrate the deleterious effect of high PTH levels on the nutritional status of hemodialysis patients. Indirect evidence, however, suggests an action of PTH on protein metabolism

Nutritional status of hemodialysis patients with secondary hyperparathyroidism.

The repercussions of secondary hyperparathyroidism on the nutritional status of chronic renal failure patients have not been well established. Therefore, the aim of this study was to compare the nutritional indices of hemodialysis patients with and without secondary hyperparathyroidism. Sixteen hemodialysis patients with serum parathyroid hormone (PTH) levels higher than 420 pg/ml (hyperparathyroidism group) were matched for gender, age and length of dialysis treatment to 16 patients with serum PTH between 64 and 290 pg/ml (control group). The following parameters were assessed: anthropometric indices (body mass index, skinfold thickness, midarm muscle circumference and body fat), 4-day food diaries, protein catabolic rate, biochemical indices (blood urea nitrogen, serum creatinine, albumin, ionized calcium, inorganic phosphorus, serum alkaline phosphatase, PTH, pH and HCO(3)) and dialysis efficiency. We did not observe differences in the anthropometric indices between the two groups. Only calcium intake was significantly different between groups (307.9 mg/day for the hyperparathyroidism group vs 475.8 mg/day for the control group). Protein catabolic rate tended to be higher in the hyperparathyroidism group compared to the control group (1.3 vs 0.9 g kg(-1) day(-1); P = 0.08). Except for blood urea nitrogen (86.4 vs 75.7 mg/dl), alkaline phosphatase (175 vs 65 U/l) and PTH (898 vs 155 pg/ml), no other differences were found between groups in the biochemical indices studied. PTH was directly correlated with protein catabolic rate (r = 0.61; P<0.05) and length of dialysis (r = 0.53; P<0.05) only in the hyperparathyroidism group. Considering the indices used, we could not demonstrate the deleterious effect of high PTH levels on the nutritional status of hemodialysis patients. Indirect evidence, however, suggests an action of PTH on protein metabolism.

Quality of life at the initiation of maintenance dialysis treatment--a comparison between the SF-36 and the KDQ questionnaires.

OBJECTIVE: To evaluate the construct validity of the Medical Outcomes Study Questionnaire 36-Item Short Form Health Survey (SF-36) and to assess the quality of life of patients with end-stage renal disease (ESRD) at the initiation of maintenance dialysis treatment. METHODS: Cross-sectional study. SETTING: Eight ambulatory dialysis units in São Paulo city, Brazil. STUDY PARTICIPANTS: Eighty ESRD patients at the initiation of chronic dialysis program and consecutively accepted for treatment in selected units in 1998. MAIN OUTCOME MEASURES: Quality of life as measured by the dimensions of the SF-36 questionnaire. The 'Kidney Disease Questionnaire' was used in a subgroup of patients to evaluate the validity of the SF-36. RESULTS: Median (range) scores of the SF-36 dimensions (ranging from 0 to 100, higher scores representing better quality of life) were: Physical Function 70 (0-100), Role Limitations due to Physical Problems 25 (0-100), Bodily Pain 62 (0-100), General Health 57 (5-100), Vitality 55 (10-100), Social Function 63 (0-100), Role Limitations due to Emotional Problems 34 (0-100) and Mental Health 68 (0-100). SF-36 dimensions correlated significantly with those of the 'Kidney Disease Questionnaire' (correlation coefficients ranging from 0.23 to 0.68). CONCLUSIONS: The SF-36 was shown to have construct validity when used in patients with ESRD in Brazil. The quality of life of ESRD patients is impaired at the initiation of dialysis treatment and this was clearly evidenced in the Role Limitations due to Physical Function and Emotional Function items. Greater attention should be given to interventions that could improve the quality of life parameters at the initiation of dialysis treatment.

Effect of etidronate treatment on bone mass of male nephrolithiasis patients with idiopathic hypercalciuria and osteopenia.

Osteopenia is frequently found among calcium stone forming (CSF) patients with hypercalciuria. We investigated the effect of a 2-year therapeutic course of etidronate, a bone-sparing agent, in 7 young male CSF patients. The treatment consisted of a cyclic intermittent administration of phosphate followed by sodium etidronate and calcium supplementation every 74 days. Bone mineral density (BMD) measured at 12-month intervals and bone biopsies performed at baseline and after 2 years were the primary efficacy parameters. Mean lumbar spine BMD increased significantly after the 1st year by 2.6 +/- 1.0% (mean +/- SE, p < 0.05) and nonsignificantly after the 2nd year by 5.6 +/- 2.6%. Nonsignificant changes were observed for femoral neck mean BMD after either the 1st or the 2nd year (decrease of 2.0 +/- 1.0% and 2.0 +/- 3.0%, respectively). Mean histomorphometric parameters showed that bone volume, osteoid volume, and eroded surfaces did not differ from baseline (13.9 +/- 2.2 vs. 12.2 +/- 1.1%, 1.2 +/- 0.7 vs. 2.6 +/- 0.7%, and 20.7 +/- 6.2 vs. 13. 7 +/- 1.3%, respectively). Osteoid surface was significantly lower than baseline values (9.5 +/- 5.2 vs. 18.8 +/- 5.3%, p < 0.05). These data suggest that etidronate given to young male CSF patients presenting with hypercalciuria and osteopenia led to a significant amelioration of BMD, evident only in the lumbar spine after 1 year of treatment. There was no histological evidence of long-term improvement in bone remodeling.