Markers of bone remodeling in the elderly subject: effects of vitamin D insufficiency and its correction

The elderly subject is prone to both vitamin B insufficiency and calcium insufficiency due to a low calcium intake and calcium malabsorption. These two alterations may lead to secondary hyperparathyroidism, and thus to increased bone loss. We investigated 72 elderly subjects (16 men and 56 women) with vitamin D insufficiency and 25 healthy elderly women with normal vitamin D status, with respect to their indices of calcium metabolism and of bone remodeling: serum total alkaline phosphates (phosphatases), bone AP (BAP), osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), urine hydroxyproline (HYP), and the 3-OH-pyridinium derivatives pyridinoline (PYD) and deoxypyridinoline (DPD), which are new markers of bone resorption. We then studied the modifications of these markers in the patients with vitamin D insufficiency at 3 months and 6 months after onset of a daily vitamin D and calcium supplementation. When compared with elderly subjects with normal vitamin D status, patients with vitamin D insufficiency had increased intact parathyroid hormone (iPTH) levels (60.1 +/- 10.2 vs 30.2 +/- 4.5, p < 0.001) and a high bone turnover as reflected by increased values of most serum and urine markers of bone remodeling. PYD and DPD levels were significantly correlated with all indices of bone turnover, unlike HYP, which showed no correlation with bone formation markers (AP, BAP, and BGP). A daily supplement of 800 IU vitamin D3 and 1 g of elemental calcium increased 25(OH)D levels and induced a dramatic decrease of iPTH levels; at 3 and 6 months, the mean iPTH level decreased by 50% (p < 0.0001), reaching the mean value of healthy vitamin D sufficient elderly women. All markers of bone turnover, except TRAP, decreased significantly at 3 and 6 months. The PYD/DPD ratio increased significantly at 3 and 6 months. The decrease of bone markers was more marked in patients with more severe hyperparathyroidism, the greatest variations being obtained with BAP (45%, p = 0.006) and DPD (43%, p = 0.036) levels. Most markers of bone remodeling are increased in elderly subjects with vitamin D insufficiently and vary with its correction. However, BAP and DPD are the most sensitive indicators of increased bone turnover due to secondary hyperparathyroidism.     

Assessment of renal osteodystrophy in dialysis patients: use of bone alkaline phosphatase, bone mineral density and parathyroid ultrasound in comparison with bone histology

Bone biopsies were studied in 73 patients to determine if a two-site radioimmunometric assay for serum bone alkaline phosphatase (BAP), total serum alkaline phosphatase (ALP), serum intact parathyroid hormone (iPTH), hand X-rays, regional bone mineral density (BMD) measurements and parathyroid enlargement detected by ultrasonography could accurately predict renal osteodystrophy. In the patients studied 57 had hyperparathyroid bone disease, 4 mixed renal osteodystrophy, 3 adynamic bone disease, 1 osteomalacia and 8 normal histology. Serum BAP, ALP and iPTH correlated positively with mineral apposition rate, osteoblastic, osteoid and eroded surface. In the diagnosis of hyperparathyroid bone disease serum iPTH was the most sensitive investigation, detecting 81% of patients at a level > 100 pg/ml but with a specificity of only 66%. Serum BAP was more sensitive, 70% at a level of > 10 ng/ml, than serum total ALP, 30% at a level of 300 IU/l, with similar specificities, 92 and 100%, respectively. Ultrasound detection of an enlarged parathyroid gland had a sensitivity of 64% and a specificity of 100% for the diagnosis of hyperparathyroid bone disease. Hand X-rays had a poor sensitivity, 47%, but a high specificity, 92%, for the detection of hyperparathyroid bone disease. The majority of patients had regional BMD values within the normal reference range and this test was of poor discriminatory value. The non-invasive markers were unable to distinguish between patients with low turnover, mild hyperparathyroidism and patients with normal histology. In conclusion the measurement of serum iPTH is a useful screening tool for the detection of hyperparathyroid bone disease which can be confirmed by the finding of a raised serum BAP or parathyroid enlargement. For definitive diagnosis, however, the gold standard remains bone biopsy and at present one cannot recommend any non-invasive method as an adequate substitute.     

Prevention of renal osteodystrophy in peritoneal dialysis

BACKGROUND: Renal osteodystrophy (ROD) is still one of the major long-term complications in end-stage renal disease leading to considerable morbidity. Despite some progress in understanding the pathogenesis of secondary hyperparathyroidism (sHPT) during recent years, prevention and treatment of ROD is still suboptimal, requiring surgical parathyroidectomy in 6 to 10% of all patients on dialysis after 10 years. In addition, the spectrum of bone lesions has changed, with non-aluminum-related adynamic bone disease (ABD) found in up to 43% of peritoneal dialysis (PD) patients. METHODS: Current recommendations concerning prevention of ROD in PD based on the literature and personal recent data were reviewed. The focus is on (i) the importance of early prophylactic intervention to prevent parathyroid gland hyperplasia, (ii) the pathogenesis of ABD, and (iii) the role of metabolic acidosis in ROD. RESULTS: There is ample evidence that sHPT starts early during the course of renal failure and results from both hypersecretion of PTH by parathyroid cells and glandular hyperplasia. As shown by experimental and clinical studies, established parathyroid cell hyperplasia is hardly reversible by pharmacological means, and therefore prevention of parathyroid cell proliferation needs to start early. Recent data from randomized trials document the efficacy and safety of low dose active vitamin D (0.125 to 0.25 microgram/day) and/or an oral calcium substitute to prevent progression of sHPT in patients with mild to moderate renal failure. Since little is known about the pathogenesis, natural course and clinical impact of ABD in PD, specific therapeutic concepts have not yet been generated. Diabetes and advanced age are established risk factors, whereas the role of calcium and vitamin D overtreatment or the type of dialysis (PD vs. HD) are still controversial. Currently no evidence for different functional behavior of the parathyroids in ABD and sHPT has been found. The role of circulating or local factors such as cytokines, growth factors or the presence of advanced glycation end-product (AGE)-modified matrix proteins for the pathogenesis of either type of ROD deserves further investigation. Avoiding oversuppression of parathyroid gland and the use of low calcium dialysate may help prevent ABD. There is growing evidence that a correction of metabolic acidosis will influence ROD by both direct effects on the bone and on parathyroid cell function. New dialysate composition for CAPD with a high HCO3 concentration will allow normalization of acid-based metabolism in PD patients. Their effects on ROD under long term conditions remain to be determined. CONCLUSION: Therapeutic efforts should aim to prevent the development of parathyroid gland hyperplasia and sHPT early during the course of renal failure, and should include the use of low dose vitamin D therapy and oral calcium substitution as well as correction of metabolic acidosis. Concerning ABD, more information is needed regarding the causes and consequences of this type of bone lesion to develop a more specific therapy.     

Prevalence of histological beta2-microglobulin amyloidosis in CAPD patients compared with hemodialysis patients

BACKGROUND: The prevalence of beta2-microglobulin amyloidosis (Abeta2m) in patients on continuous ambulatory peritoneal dialysis (CAPD) is unknown. METHODS: We prospectively obtained a median of 2 (range 1 to 4) joint samples from 26 CAPD patients aged 44 to 93 (median 73) years at post-mortem evaluation after 4.5 to 126 (median 27) months solely on CAPD (N = 19) or primarily on CAPD (that is, < or = 10% and < or = 1 year of renal replacement therapy time on other modalities; N = 7). The diagnosis of Abeta2m rested on Congo red staining (typical birefringence) and positive immunostaining of amyloid deposits by a monoclonal anti-beta2m antibody. RESULTS: Abeta2m was diagnosed in 8 of 26 patients (31%). Prevalence ranged from 20% (2 of 10 patients) within < or = 24 months CAPD to 30% (3 of 10 patients) after 24 to 48 months and 50% (3 of 6 patients) after 49 to 126 months (P = 0.11). The prevalence of Abeta2m was similar in patients without or with one or more peritonitis episodes. No significant difference in prevalence (P = 0.118) was found between CAPD patients (8+/26; 31%) and hemodialysis patients (13+/26; 50%) carefully matched for time on dialysis and age at the onset of dialysis. CONCLUSIONS: The prevalence of histological Abeta2m reaches 31% after a median duration of 27 months of CAPD. This prevalence is not significantly different from that observed in a group of HD patients matched for age and dialysis duration.     

Prevalence and risk factors for hepatitis C virus infection in continuous ambulatory peritoneal dialysis patients

BACKGROUND: Studies on hepatitis C virus antibodies (Anti-HCV) in CAPD patients are scarce and include a small number of patients. Nevertheless, risk factors related to Anti-HCV in these patients are still subject to controversy. Purpose of the study. To analyse the incidence and risk factors associated with the presence of Anti-HCV in CAPD patients. METHODS: We studied 255 patients from five different treatment centres of our region. The analysis was repeated after excluding 161 patients who had previously received haemodialysis treatment at least once. Anti-HCV testing was made by the 2nd-generation ELISA: As a supplementary test we used RIBA-4 in three centers and INNOLIA in the other two. Risk factors were analysed using logistic regression model for multivariate analysis. RESULTS: In the whole group, 29 patients (11.4%) were anti-HCV positive. Logistic regression analysis determined the following variables as independent risk factors: hepatitis previous to CAPD (P<0.001, odds ratio (OR):44.9), Anti HBc positivity (P=0.019, OR:9. 24), blood transfusions previous to CAPD (P=0.015, OR:1.05) and CAPD duration were excluded, the prevalence of HCV antibodies was 8.5% (8/94). In this group multivariate analysis showed that Anti-HCV positivity correlated with hepatitis previous to CAPD (P<0.0003, OR: 126) and Anti HBc positivity (P=0.002, OR:41.9). CONCLUSIONS: Our prevalence of hepatitis C virus (HCV) infection in CAPD patients was lower than other renal replacement therapy modalities, and correlated to events occurring mainly before starting CAPD treatment. This technique could be considered as low risk for HCV infection.     

Immunoreactive parathyroid hormone, 25-hydroxycalciferol and bone histology in renal osteodystrophy (author's transl)

Immunoreactive parathyroid hormone (iPTH) and 25-hydroxycalciferol (25(OH)D) serum levels were determined in 32 patients with renal osteopathy, they were correlated with the results of bone biopsy and other clinical parameters. iPTH was closely related to bone histology, it did not correspond to serum calcium and alkaline phosphatase, but the correlation to serum phosphate was statistically significant. 25(OH)D levels were not related to the histological findings of osteomalacia or increased bone resorption, while a correlation between the vitamin D metabolite and serum calcium could be observed. Since iPTH and 25(OH)D levels exhibited a significant correlation, an inhibitory effect of 25(OH)D on parathyroid gland function in renal failure was discussed.     

Biochemical effects of calcium supplementation in postmenopausal women: influence of dietary calcium intake

We studied the biochemical effects of calcium supplementation during a 2-mo course in postmenopausal women (x +/- SD: 64 +/- 5 y of age and 14.5 +/- 6.7 y since menopause). The effects on calcium homeostasis and bone remodeling were assessed after 1 and 2 mo of daily administration of either calcium carbonate (1200 mg elemental Ca/d, n = 60) or a placebo (n = 56). The daily dietary calcium intake assessed before the beginning of calcium supplementation was 786 mg/d. We found a significant inverse relation between baseline intact parathyroid hormone (iPTH) and dietary calcium intake before supplementation (r = -0.48, P = 0.0002). A significant increase in urinary excretion of pyridinoline was observed when the dietary calcium intake was lower than the median value. Calcium supplementation resulted in a significant increase in 24-h urinary calcium (39%, P < 0.02) and a significant reduction of bone alkaline phosphatase at 2 mo and of all bone-resorption markers (hydroxyproline, pyridinoline, and deoxypyridinoline) at I and 2 mo without significant changes in 44-68 PTH fragments or iPTH concentrations. When the dietary calcium intake was low (mean +/- SD: 576 +/- 142 mg/d), calcium supplementation was responsible for a greater increase in urinary calcium excretion and a greater decrease in markers of bone turnover. The greatest variations were observed for deoxypyridinoline at 1 and 2 mo (-18.5%, P < 0.05) and for pyridinoline at 1 mo (-16.3%, P < 0.01). Two months of calcium supplementation in postmenopausal women was efficient in reducing markers of bone turnover, with a greater effect in women with a low dietary calcium intake.     

Effect of RenaGel, a non-absorbed, calcium- and aluminium-free phosphate binder, on serum phosphorus, calcium, and intact parathyroid hormone in end-stage renal disease patients

BACKGROUND: Control of dietary phosphate absorption in end-stage renal disease patients is essential to prevent the deleterious sequelae of phosphorus retention. Efficacy of currently available calcium- and aluminium-containing phosphate binders is constrained by the side-effects associated with the absorption of calcium and aluminium. The current study examined the efficacy of RenaGel, a calcium- and aluminium-free, polymeric phosphate binder, in end-stage renal disease patients. METHODS: Administration of calcium- or aluminium-containing phosphate binders ceased during a 2-week washout period. RenaGel, at starting doses of one, two, or three 500-mg capsules three times per day with meals, was administered for 8 weeks. RenaGel dose was titrated up 1 capsule per meal at the end of each 2-week period if necessary to achieve phosphorus control. A second 2-week washout period followed the end of RenaGel treatment. RESULTS: Mean serum phosphorus rose from a pre-washout level of 6.9 mg/dl (2.23 mmol/l) to 8.1 mg/dl (2.62 mmol/l) at the end of the initial 2-week washout. With RenaGel treatment, serum phosphorus declined and returned to pre-washout levels after 4 weeks. Serum phosphorus reached a nadir of 6.5 mg/dl (2.10 mmol/l) after 7 weeks of RenaGel treatment. Serum phosphorus rose to 8.2 mg/dl (2.65 mmol/l) 2 weeks after cessation of RenaGel treatment. As anticipated, calcium declined during the initial washout period when calcium-based phosphate binders were stopped for the majority of patients. The rise in serum phosphorus and decline in serum calcium during washout resulted in an increase in median intact parathyroid hormone (iPTH) levels from 292 pg/ml to 395 pg/ml. iPTH fell to 283 pg/ml after 6 weeks of RenaGel treatment despite a persistently lower serum calcium. RenaGel treatment also reduced serum total and LDL cholesterol by 25 mg/dl (0.65 mmol/l) and 23 mg/dl (0.59 mmol/l) respectively. CONCLUSIONS: RenaGel appears to be an effective phosphate binder free of calcium and aluminium. Phosphorus control with two to four RenaGel capsules per meal appears to result in comparable phosphorus lowering seen with calcium- or aluminium-based phosphate binders. RenaGel may offer an alternative for the control of phosphorus retention in end-stage renal disease patients.     

Study on vascular calcification in patients on continuous ambulatory peritoneal dialysis (CAPD): special reference to active vitamin D (VD) treatment

Cardiovascular complications, such as vascular calcification (VC), have been a major concern in patients undergoing chronic dialysis. The pathogenesis of this VC has been attributed to the altered calcium and phosphate metabolism, but the contributing factors have not been clarified. In order to investigate these factors, 38 CAPD patients were divided into two sub-groups according to the absence of aortic calcification (Group-A; n = 18) or the presence of aortic calcification (Group-B; n = 20). The number of elderly patients was larger and the duration of CAPD was longer in Group-B than in Group-A. Calcium and phosphate metabolism and serum lipids levels did not differ significantly between groups and the number of patients given VD was 8/18 in Group-A and 14/20 in Group-B. In order to explore the progression of VC in CAPD patients given long-term treatment with VD, 22 patients who were matched for the duration of CAPD were analyzed. These were divided into two sub-groups according to whether they were treated with VD (Group-C; n = 11) or not treated with VD (Group-D; n = 11). Radiological findings (such as the degree of aortic calcification), bone mineral content, divalent ions, parathyroid hormone levels and lipid profiles were examined. The prevalence of patients with aortic calcification was significantly higher in Group-D than in Group-C (7/11 v. s. 2/11, P < 0.05). However, lipids, mineral and endocrinological parameters did not differ between the sub-groups. No significant difference in the calcium and phosphate balance was observed. The bone mineral content revealed no difference between both of the sub-groups. VD administration by conventional mode, even without significant suppression of PTH or increase of bone mineral content, may enhance vessel calcification in patients on long-term CAPD.     

Immunoreactive parathyroid hormone in early and advanced renal failure

Immunoreactive parathyroid hormone (iPTH) was measured in the serum of 20 patients with early renal failure (ERF) using three assays with different specificity. Half of these patients had elevated iPTH in one or more assays, up to twice the upper limit of normal. In contrast, 36 patients with a creatinine clearance below less than 20 ml/min had an 80% elevated iPTH, up to 5 times the upper limit of normal. The patients with ERF and elevated iPTH had a lower serum calcium but no higher serum phosphate than those with normal iPTH. The differences in iPTH in early and end-stage renal failure can be explained by known differences in metabolism of different PTH forms in uremia.     

Biochemical parameters of bone turnover in kidney transplant recipients

Impairment of bone remodelling due to chronic renal failure persists even after successful kidney transplantation. Bone turnover was assessed in 22 kidney transplant recipients by measurement of serum bone markers: total (tALP) and bone alkaline phosphatase (bALP), osteocalcin (OC), procollagen I C-terminal propeptide (PICP), collagen I C-terminal telopeptide (ICTP), and iPTH. The patients were on dialysis 56.6 +/- 43.1 months before transplantation (mean +/- SD) and 34.2 +/- 23.0 months had elapsed after transplantation. The bone markers were within the reference range in 23% of patients for iPTH, 73% for tALP and 82% for bALP, 41% for OC, 73% for PICP and 50% for ICTP. A positive correlation was found between dialysis duration and ICTP, and iPTH and bone formation markers (OC, bALP). The obtained results indicate that bone turnover was increased after kidney transplantation, with prevailing bone resorption, which seems to be influenced by dialysis duration.     

Livestock improvement: art, science, or industry?

BACKGROUND: Renal osteodystrophy includes a number of low and high turnover bone histologic patterns which require a bone biopsy for their full identification. The role of intact PTH and several classical and more recent bone markers in the non-invasive diagnosis of renal bone disease in patients with CRF in HD requires further definition since available published data are limited. METHODS: In addition to intact PTH, alkaline phosphatase (AP) and osteocalcin (BGP), bone alkaline phosphatase isoenzyme (BALP), tartrate resistant acid phosphatase (TRAP), C-terminal cross-linked peptide of collagen type 1 (ICTP) and deoxypyridinoline (DPD) were measured in the serum of 41 patients on haemodialysis, subjected at the same time to transiliac bone biopsy for histomorphometric, histodynamic and aluminium histochemical examination. Histodynamic evaluation following double tetracycline label, was carried out in 37 patients. The patients had no evidence of active cytolytic and cholestatic liver disease and a history of very limited aluminium exposure. RESULTS: The patients had differing degrees of hyper-parathyroidism, with intact PTH ranging from normal to very elevated levels. Serum values of the markers BGP, ICTP and DPD, normally excreted through the kidneys, were on average very high. The correlation coefficients of the humoral parameters vs dynamic variables, such as BFR/BS, were high. The highest values were: intact PTH 0.798, AP 0.900, BALP 0.891, ICTP 0.807. The patients, grouped in low turnover osteodystrophy (LTO; 9), mixed osteodystrophy (MO; 9) and prevalent hyperparathyroidism (HP; 23), showed significant difference in the levels of most humoral and static and dynamic parameters (ANOVA). Bone aluminium histochemistry was negative in all cases. Discrimination of LTO patients from the other groups by humoral parameters, at the highest value of accuracy, showed 100% sensitivity and 93.7% specificity with a cut-off of 12.9 ng/ml for BALP; 88.9% sensitivity and 93.7% specificity with a cut-off of 21.5 ng/ml for DPD, and 88.9% sensitivity and 90.6% specificity with a cut-off of 79.7 pg/ml for intact PTH. The other markers had lower values. A standardized z-score approach for evaluation of all humoral parameters was also carried out. Using all variables, a correct classification of MO/HP and of LTO was possible in 93.8 and 88.9% of the cases, respectively. Predictive power was 96.8 and 80%, respectively for MO/HP and LTO. When the only variables used were intact PTH and BALP, a correct classification of MO/HP and LTO was possible in 90.6% and 88.9%, respectively. Predictive value of MO/HP was 96.7% and for LTO 72.7%. Predictive values using PTH and AP were 96.3% and 57.2%, respectively. CONCLUSION: Intact PTH and several relatively new bone markers are of certain value in the non-invasive diagnosis of renal osteodystrophy. However some of the humoral markers carry the same quality of information and the use of intact PTH and BALP may be adequate in the discrimination of bone histologic patterns. In cases exempt from liver disease, PTH and AP may be used as a less costly alternative. Bone biopsy could be chiefly limited to cases with borderline humoral values and to all those with a suspected aluminium overload.     

Prostate carcinoma staging. Clinical utility of bone alkaline phosphatase in addition to prostate specific antigen

BACKGROUND: Biochemical markers of bone disease have been of interest as part of the investigation of prostate carcinoma and the monitoring of skeletal involvement. Bone isoenzyme of the alkaline phosphatase (BAP) is an indicator of the metabolism of the osteoblasts. An immunoradioanalyses with two monoclonal antibodies in sandwich was developed, allowing an accurate measurement of BAP concentration. The goal of the current study was to compare the clinical performance of BAP and prostate specific antigen (PSA) in patients with untreated prostate carcinoma and to determine whether or not BAP can provide valuable additional information to PSA regarding the degree of skeletal extension in patients with prostate carcinoma. METHODS: BAP and PSA serum concentrations were determined in 140 newly diagnosed prostate carcinoma patients (72 M0 and 68 M1-4). The efficiency of both markers in the prediction of positive bone scans was studied as well as the relationship observed between the concentrations of the two markers and the degree of skeletal involvement. To investigate the potential utility of BAP and PSA in eliminating the need for a bone scan, the negative predictive values for different cutoff points for both markers were calculated. RESULTS: BAP was more efficient than PSA in the prediction of positive bone scans and its level was significantly related to the magnitude of skeletal involvement whereas PSA was only able to distinguish between M0 and M1-4 groups of patients. The highest predictive value for a bone scan result was found for BAP cutoff values between 20 and 30 ng/mL, leading to negative and positive predictive values of 92.6% and 98.2%, respectively. The combination of BAP and PSA both set at a 20 ng/ mL cutoff value yielded a negative predictive value of 100% and the combination of BAP and PSA at 30 ng/mL and 20 ng/mL cutoff values, respectively, increased the positive predictive value to 98.5%. CONCLUSIONS: This study suggests that BAP could be a complementary marker to PSA in the diagnosis of bone disease in patients with prostate carcinoma. Its clinical utility could result in important cost saving implications, eliminating bone scan when PSA ranges from 10 to 20 ng/mL because the predictive negative value of PSA < 20 ng/mL and BAP < 20 ng/mL is 100% in this series. In addition, it could provide useful clinical information regarding the degree of skeletal involvement.     

Limitations of pulse oral calcitriol therapy in continuous ambulatory peritoneal dialysis patients

Calcitriol is increasingly used for therapy of secondary hyperparathyroidism in patients with end-stage renal disease. Its therapeutic efficacy, however, often has been limited by the associated increase in intestinal calcium and phosphorus absorption. Previous studies reported that these side effects could be avoided by intermittent administration of calcitriol in high doses, subsequently referred to as pulse therapy. The present study was designed to investigate pulse oral calcitriol therapy in a patient subgroup especially susceptible to the development of hypercalcemia and hyperphosphatemia under standard continuous calcitriol treatment. We examined 15 peritoneal dialysis patients with moderate degrees of hyperparathyroidism (intact parathyroid hormone [iPTH] levels, 150 to 903 pg/mL) ingesting between 1.5 and 6 g of calcium salts as the sole phosphate binders. Treatment consisted of 0.5 microgram calcitriol twice weekly. Eight of these patients had been previously converted to low calcium dialysate to tolerate the necessary doses of phosphate-binding calcium salts. During the study period, comprising 8 pretreatment weeks and 8 weeks of therapy, dialysates and doses of calcium salts were not changed, so that only calcitriol influenced the determined parameters. As expected, iPTH levels decreased rapidly in all patients (P < 0.0001). However, within 4 weeks of treatment a marked increase in calcium phosphorus products was observed (P < 0.0001). Overt hypercalcemia developed in five patients. We concluded that pulse oral calcitriol has to be carefully monitored in peritoneal dialysis patients receiving high doses of calcium salts because of the increased risk for hypercalcemia and hyperphosphatemia.     

Predictive value of dialysis adequacy and nutritional indices for mortality and morbidity in CAPD and HD patients. A longitudinal study

BACKGROUND: The effects of dialysis inadequacy on patient survival and nutritional status and that of malnutrition on survival have not been clearly assessed. Studies comparing dose/mortality and morbidity curves on continuous ambulatory peritoneal dialysis (CAPD) and on haemodialysis (HD) are also needed, to assess adequate treatment on CAPD. METHODS: We have evaluated the effects of age, 13 pretreatment risk factors, serum albumin, transferrin, normalized protein catabolic rate, Kt/V, normalized weekly creatinine clearance, residual renal function and subjective global assessment of nutritional status on survival and morbidity, in a 3-year prospective study of 68 CAPD and 34 HD patients. RESULTS: Survivals did not differ for CAPD and HD patients. In the Cox hazard regression model, age, peripheral vasculopathy, serum albumin < 3.5 g/dl and Kt/V < 1.0/treatment on HD and < 1.7/week on CAPD were independent factors negatively affecting survival. On the contrary, adjusted survivals were not affected by gender, modality, other comorbid factors, normalized protein catabolic rate, or subjective global assessment of nutritional status. Persistence of residual renal function significantly improved survival. Observed and adjusted survival did not significantly differ for CAPD and HD patients with either low (HD, < 1.0/treatment; CAPD, < 1.7/week) or high ( > or = 1.0 and > or = 1.7) Kt/V. On HD, adjusted survivals were similar for 1.0 < or = Kt/V < 1.2 or > or = 1.2. On CAPD, Kt/V > or = 1.96/week was associated with definitely better survival, with only one death/23 patients versus 19/45, with Kt/V < or = 1.96. Survival was not different for 1.96 < or = Kt/V < 2.03 and > or = 2.03. Normalized weekly creatinine clearance and wKt/V were positively related on CAPD (r 0.39, P < 0.01) and wKt/V = 1.96 corresponded to 58 litres of normalized weekly creatinine clearance. CONCLUSIONS: Indices of adequacy were predictors of mortality and morbidity, both on CAPD and HD, whereas normalized protein catabolic rate and subjective global assessment of nutritional status were not. Serum albumin did not decrease during dialysis; hence its predictive effect for survival is due to the predialysis condition and not to dialysis-induced malnutrition.     

A randomized, placebo-controlled trial of calcium supplementation for decreased bone density in corticosteroid-using patients with inflammatory bowel disease: a pilot study

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a high prevalence of osteoporosis. A number of studies have found that corticosteroid use is associated with the development of osteoporosis in these patients. Calcium supplementation may be of benefit in corticosteroid-induced osteoporosis and calcium may be a nutrient that patients with IBD lack. AIM: To test the benefit of calcium supplementation on bone density in a pilot study over a 1-year period, in a group of corticosteroid-using patients with IBD, in a randomized, double-blind, placebo-controlled treatment study. METHODS: Corticosteroid-using patients with IBD including males over the age of 18 years and premenopausal females, were randomized to receive either calcium carbonate 1000 mg plus vitamin D 250 IU (Oscal) or an identically matched placebo. Dual energy X-ray absorptiometry measurements of bone density were obtained at entry and at 1 year. At entry, and every 3 months thereafter, serum was collected for the measurement of haemoglobin, biochemistry and bone hormones. Simultaneously a 24-h urine collection was analysed for calcium excretion and creatinine clearance, and a 4-day food record was collected to document dietary calcium and vitamin D ingestion. RESULTS: We found a high prevalence of moderately severe decreased bone density in corticosteroid-using patients with IBD. The dose of prednisone in the year prior to study entry was inversely correlated with bone density at the hip (R = -0.67, P = 0.004). At study entry serum osteocalcin was inversely correlated with corticosteroid dose in the year prior to the study (R = -0.64, P = 0.02) and at study end, directly correlated with the percentage change in spine bone density (R = 0.59, P = 0.01). The dietary calcium intake of these patients was close to the current RDA (recommended daily intake) for premenopausal, post-adolescent adults. Calcium supplementation with small extra doses of vitamin D conferred no obvious benefit to bone density at the end of 1 year. There was no correlation between oral calcium ingestion and bone mass measurements. Both the treatment and placebo groups' bone density remained relatively stable at 1 year, suggesting that bone loss in corticosteroid-using patients may peak early into the use of the corticosteroids. CONCLUSIONS: Calcium supplementation (1000 mg/day) conferred no significant benefit to bone density at 1 year in patients with corticosteroid-using IBD patients with osteoporosis. Future investigations should explore other therapeutic avenues that may have greater effects on increasing bone density in patients who already have considerable osteoporosis.     

Usefulness of calcium acetate as a chelating of phosphorus in patients in hemodialysis with secondary hyperthyroidism

In this study, we prospectively evaluated the efficacy of calcium acetate in patients with chronic renal insufficiency on hemodialysis programme with secondary hyperparathyroidism and hyperphosphatemia, which are difficult to control by means of the usual finders (calcium carbonate and aluminium hydroxide) and who were treated with pulses of calcitriol. We studied 10 patients. The inclusion criteria were: a serum phosphorus higher than 6.5 mg/dl, a serum PTHi higher than 250 pg/ml and a serum calcium higher than 9.5. The former therapy was stopped at the time of the patient was included in the study. Calcium acetate was initially introduced with doses between 2.5-4 g/day according to previous calcium and phosphate values. Also, all patients were initially treated with intermittent subcutaneous bolus of Calcitriol were modified and adjusted according to serum concentrations of calcium, phosphorus and PTHi. The concentration of calcium in the dialyzed was of 1.25 mmol/l. Fortnightly total calcium, phosphate and alkaline phosphatase serum determinations and monthly aluminium and PTHi serum determinations were carried out. During the 6 months treatment, a decrease was observed in serum concentrations of phosphate (p < 0.01), aluminum (p < 0.02) and PTHi (p < 0.001) with no changes in the values of calcium (p = ns) nor alkaline phosphatase (p = ns). The incidence of hypercalcemia was low during the follow-up period (11% of all biochemical serum determinations) and was easily controlled. We can conclude that calcium acetate is a sure and effective finder of phosphorus with a very good tolerance. Administered together with pulses of calcitriol, and the use of a low calcium concentration in the dialysate, it does not increase the risk of hypercalcemia.     

Improvement of host response to sepsis by photobiomodulation

OBJECTIVE: To evaluate the correlation between predialysis glycemic control and clinical outcomes for type II diabetic patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Sixty type II diabetic patients on CAPD were classified into 2 groups according to the status of glycemic control. In group G (good glycemic control), more than 50% of blood glucose determinations were within 3.3-11 mmol/L and the glycosylated hemoglobin (HbA1C) level was within 5-10% at all times. In group P (poor glycemic control), fewer than 50% of blood glucose determinations were within 3.3-11 mmol/L or HbA1C level was above 10% at least once during the follow-up duration. In addition to glycemic control status, predialysis serum albumin, cholesterol levels, residual renal function, peritoneal membrane function, and the modes of glycemic control were also recorded. SETTING: Dialysis Unit, Department of Nephrology of a single university hospital. PATIENTS: From February 1988 to October 1995, 60 type II diabetic patients receiving CAPD for at least 3 months were enrolled. MAIN OUTCOME MEASURES: Morbidities before and during the dialysis period, patient survival, and causes of mortality. RESULTS: The patients with good glycemic control had significantly better survival than patients with poor glycemic control (p < 0.01). There was no significant difference in predialysis morbidity between the two groups. No significant differences were observed in patient survival between the patients with serum albumin greater than 30 g/L and those with less than 30 g/L (p = 0.77), with cholesterol levels greater or less than 5.18 mmol/L (p = 0.73), and with different peritoneal membrane solute transport characteristics evaluated by peritoneal equilibration test (p = 0.12). Furthermore, there was no significant difference in survival whether the patients controlled blood sugar by diet or with insulin (p = 0.33). Cardiovascular disease and infection were the major causes of death in both groups. Although good glycemic control predicts better survival, it does not change the pattern of mortality in diabetics maintained on CAPD. CONCLUSIONS: Glycemic control before starting dialysis is a predictor of survival for type II diabetics on CAPD. Patients with poor glycemic control predialysis are associated with increased morbidity and shortened survival.     

Automatic measurement of arterial pressure

PURPOSE: To identify patients with lymphoma at risk for tumor lysis after chemotherapy. PATIENTS AND METHODS: The case records of 102 patients receiving combination chemotherapy for non-Hodgkin's lymphoma (intermediate to high-grade histology) were reviewed. Patients were considered to have "laboratory tumor lysis" if two of the following metabolic changes occurred within 4 days of treatment: a 25% increase in the serum phosphate, potassium, uric acid, or urea nitrogen concentrations, or a 25% decline in the serum calcium concentration. "Clinical tumor lysis" was defined as laboratory tumor lysis plus one of the following: a serum potassium level greater than 6 mmol/L, a creatinine level greater than 221 mumol/L, or a calcium level less than 1.5 mmol/L, the development of a life-threatening arrhythmia, or sudden death. RESULTS: Laboratory tumor lysis occurred in 42% of patients and clinical tumor lysis in 6%. There was no statistical difference in the frequency of either tumor lysis syndrome among lymphoma subgroups. Clinical tumor lysis occurred more frequently in patients with pretreatment renal insufficiency (serum creatinine level greater than 132 mumol/L) than in patients with normal renal function (36% versus 2%; p = 0.01). The development of azotemia correlated with high pretreatment serum lactate dehydrogenase concentrations (p < 0.01; r2 = 0.11). CONCLUSION: Clinically significant tumor lysis is a rare occurrence in patients with lymphoma when they are receiving allopurinol. However, tumor lysis can occur in patients with all types of moderate to high-grade non-Hodgkin's lymphoma. Patients with a high serum lactate dehydrogenase level or renal insufficiency are at increased risk for metabolic complications after chemotherapy and should be closely monitored.     

Prevalence of renal stones in a population-based study with dietary calcium, oxalate, and medication exposures

Little is known about the epidemiology of renal stones, in spite of the relative frequency of this painful condition. This population-based study examined reported renal stone diagnosis in 1,309 women aged 20-92 years to determine whether renal stones are associated with 1) food or water exposures or 2) lower bone mineral density and an increased likelihood of fractures. Results indicated a renal stone prevalence of 3.4%. The average age at diagnosis was 42 years. Renal stone formation was not associated with community of residence, hypertension, bone mineral density, fractures, high-oxalate food consumption, or ascorbic acid from food supplements. Women with renal stones consumed almost 250 mg/day less dietary calcium (p < 0.01) than did women without stones and had a lower energy intake (p < 0.04). The authors' findings do not support the hypothesis that increased dietary calcium is associated with a greater prevalence of renal stones, nor do they identify renal stones as a risk factor for low bone mineral density. Furthermore, lack of other identifiable environmental correlates and the relatively young age at initial diagnosis suggest that genetic components of renal stone formation need further study.