Lanthanum data in perspective.
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Alanine Transaminase↗
Biomedical subjects
A J Hutchison
Publications and source records attributed to A J Hutchison.
Severe acute renal failure in adults: place of care, incidence and outcomes.
BACKGROUND: Department of Health guidelines recommend specialist critical care facilities for patients with severe single-organ failure such as acute renal failure (ARF). Prospective studies examining incidence, causes and outcomes of ARF outside of intensive care settings are lacking. AIM: To determine the incidence, causes, place of care and outcomes of severe single-organ ARF. DESIGN: Prospective observational study. METHODS: For 6 weeks in June-July 2003, renal physicians were contacted daily, and ICUs on alternate days, to identify cases of severe single-organ ARF in the Greater Manchester area. All patients with serum creatinine >or=500 micromol/l and not requiring other organ support were included. Patients with end-stage renal disease were excluded. Survivors were followed up at 90 days and 1 year from admission. Two independent consultant nephrologists assessed each case using anonymized summaries. RESULTS: Eighty-five patients had multi-organ ARF and 28 had severe single-organ ARF (380 and 125 pmp/year, respectively). Of those with single-organ ARF, 10 (36%) had known pre-existing chronic kidney disease. Renal replacement therapy (RRT) was required in 15 (54%). Total bed occupancy on ICUs relating to single-organ ARF was 59 days (range per patient 1-21). At 90 days, 18 (64%) were alive, and 17 (94%) had independent renal function. At 1 year, 4/18 had died, none receiving RRT at the time of death. Survivors all had independent renal function. In 13 (46%) cases there was an unacceptable delay in patient transfer and in 7 (25%), delays in assessment or commencement of RRT may have adversely affected patient outcome. DISCUSSION: The incidence of ARF treated with RRT is rising. Delays in transfer to renal services may result in inappropriate ICU bed use, and may adversely affect patient outcomes. There are serious problems regarding the appropriate use of expensive and limited medical resources in the critical care area, and in providing safe and effective treatment of patients with ARF.
Acute Kidney Injury↗
Efficacy, tolerability, and safety of lanthanum carbonate in hyperphosphatemia: a 6-month, randomized, comparative trial versus calcium carbonate.
BACKGROUND/AIMS: Hyperphosphatemia is an important clinical consequence of renal failure, and its multiple adverse systemic effects are associated with significantly increased risks of morbidity and mortality in dialysis patients. Existing oral phosphate binders have not permitted control of serum phosphate within currently accepted guidelines. This study compares lanthanum carbonate with calcium carbonate for control of serum phosphate in hemodialysis patients. METHODS: In this European multicentre study, 800 patients were randomised to receive either lanthanum or calcium carbonate and the dose titrated over 5 weeks to achieve control of serum phosphate. Serum levels of phosphate, calcium and parathryoid hormone were followed over the following 20 weeks. RESULTS: Around 65% of patients in each group achieved phosphate control, but in the calcium carbonate group this was at the expense of significant hypercalcemia (20.2% of patients vs. 0.4%). Consequently, calcium x phosphate product tended to be better controlled in the lanthanum group. CONCLUSION: This 6-month study demonstrates that serum phosphate control with lanthanum carbonate (750-3,000 mg/day) is similar to that seen with calcium carbonate (1,500-9,000 mg/day), but with a significantly reduced incidence of hypercalcemia. Lanthanum carbonate is well tolerated and may be more effective in reducing calcium x phosphate product than calcium carbonate.
Adult↗
Lanthanum carbonate (Fosrenol): a novel agent for the treatment of hyperphosphataemia in renal failure and dialysis patients.
Approximately 70% of patients with end-stage renal disease and dialysis have hyperphosphataemia, which is associated with renal osteodystrophy, metastatic calcification and increased mortality and morbidity. Despite dietary restriction and dialysis, most patients will require a phosphate-binding agent to treat this condition. However, phosphate control has not significantly improved over the last two decades, mainly because of the lack of an ideal phosphate-binding agent. Aluminium-based and calcium-based agents are associated with major side-effects despite their efficacy. Although sevelamer hydrochloride represents a step forward in the management of hyperphosphataemia, it has drawbacks and therefore is not the ideal phosphate binder. Lanthanum carbonate is a non-calcium, non-aluminium phosphate-binding agent. It has shown to be effective, well-tolerated and has a positive effect on bone histology.
Bone and Bones↗
Side-effects of antituberculosis drug treatment in patients with chronic renal failure.
Patients with chronic renal failure (CRF) have a high incidence of tuberculosis (TB). Those from the Indian subcontinent are at particular risk. The frequency of side-effects associated with antituberculous treatment in a group of patients with CRF was studied. All cases of TB in patients with CRF occurring over a 13-yr period at the Manchester Royal Infirmary, from 1986-1999, were identified by diagnostic coding, microbiology records and a TB database. The case notes were then reviewed. Twenty-four cases were identified, eight predialysis and 16 requiring regular dialysis. TB occurring in the dialysis group was extrapulmonary in every case. Nineteen of 24 (79%) patients were of Indian subcontinent origin and 14 of 16 (87%) dialysis patients were non-Caucasian. Adverse effects of treatment occurred in two of eight (25%) in the predialysis group and nine of 16 (56%) of the dialysis group. These were most commonly neuropsychiatric (6), hepatic (4) and gastrointestinal (4). Neuropsychiatric symptoms occurred exclusively in dialysis patients. In conclusion, a high incidence of side-effects from antituberculous medication, especially neuropsychiatric, hepatic and gastrointestinal, was identified in patients with chronic renal failure. Careful monitoring for side-effects is essential in this group, and consideration should be given to administering antituberculous chemoprophylaxis to all high-risk groups.
Adult↗
Recurrent Escherichia coli bacteraemia in a patient with chronic renal failure.
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Animals↗
Peritoneal tuberculosis in patients receiving continuous ambulatory peritoneal dialysis.
BACKGROUND: Patients with chronic renal failure have an increased risk of tuberculosis (TB). This occurs with much higher frequency within the first 12 months of initiating dialysis and is usually extrapulmonary in nature. Patients most at risk are those from susceptible ethnic groups, especially the Indian subcontinent. Peritoneal TB, otherwise relatively uncommon, has emerged as an important form of TB in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: All cases of peritoneal TB occurring at our institution in patients undergoing CAPD over a 13 year period were identified and analysed. RESULTS: Eight cases were identified, of which seven were non-Caucasian. These patients' characteristics and outcomes are presented. All were undergoing CAPD and most developed TB within 12 months of initiating dialysis. All presented with fever, but symptoms and signs were indistinguishable from bacterial peritonitis. Six were culture-positive, mainly from peritoneal dialysis fluid, but only two cases proved smear-positive. All were treated with standard anti-tuberculous chemotherapy. Three went on to permanent haemodialysis as a result of peritonitis and three have died, one of these as a result of TB. CONCLUSIONS: Peritoneal TB, whilst otherwise relatively uncommon, is an important manifestation of TB in CAPD patients and usually develops soon after commencing dialysis. The reasons for this are unknown and require further research.
Adult↗
Association of sex hormone status with the bone loss of renal transplant patients.
BACKGROUND: Bone loss is an important problem in renal transplantation recipients. The role of sex hormones in this setting has not been previously addressed. The objective was to investigate whether sex hormone status is associated with bone mass loss in renal transplant recipients. METHODS: Thirty patients (16 men and 14 women, of which eight were post-menopausal) were studied by bone densitometry and bone biopsy. In women, serum oestradiol levels and menopausal status were determined; in men, serum testosterone levels were assessed. RESULTS: Mean age was 48+/-11 years. Time on dialysis was 13+/-17 months, and time since transplantation was 125+/-67 months. Thirteen patients were on cyclosporine A (CsA) monotherapy, 12 on azathioprine plus prednisolone (PRED) dual therapy, and five on CsA, azathioprine and PRED triple therapy. In men, serum testosterone levels were 19.7+/-6.8 nmol/l (mean+/-SD). In pre-menopausal women, oestradiol serum levels were 209(128-289) pmol/l (median (percentiles 25-75%)), and in post-menopausal women 93(54-299) pmol/l (non-significant). Univariate analysis in women demonstrated that serum oestradiol levels were positively correlated with Z scores of osteoblast surface (r=0.70, P=0.005), osteoid surface (r=0.75, P=0.002) and trabecular wall thickness (r=0.68, P=0.008). In men, a weak correlation was seen between serum testosterone levels and the cumulative dose of PRED (r=-0.52, P=0.06). In the multivariate analysis, two models of multiple regression were employed (one for women and one for men), considering the densitometric and histomorphometric variables (Z scores) as dependent variables. Serum testosterone in men did not predict any of the densitometric nor histomorphometric variables analysed, while serum oestradiol in women was an independent predictor for the osteoblast surface (r=0.81, P=0.003), osteoid surface (r=0.82, P=0.009) and trabecular wall thickness (r=0.54, P=0.05). CONCLUSIONS: In female renal transplant recipients, serum oestradiol levels independently predict the bone status, while in men, factors other than testosterone seem to influence bone loss. Our results give rise to the hypothesis that sex hormone replacement therapy may play a role in prevention and/or treatment of the bone loss in women following renal transplantation.
Absorptiometry, Photon↗
Effect of 1,25-dihydroxyvitamin D3 and calcium carbonate on bone loss associated with long-term renal transplantation.
To investigate the effect of calcitriol plus calcium carbonate on the bone loss associated with long-term renal transplantation, 30 patients with serum creatinine levels less than 2.0 mg/dL were randomly allocated to a control (n = 14) or treatment group (n = 16) and studied with bone biopsy and densitometry at baseline and after 1 year of follow-up. Calcitriol (0.25 microg/d) plus calcium carbonate (500 mg/d of elemental calcium) were administered to patients in the treatment group. Comparing the baseline and final data of each group at a time, no change in bone mineral density (BMD) z score was observed at the distal radius (control, -0.8 +/- 0.8 versus -0.6 +/- 0.9; treatment, -1.0 +/- 1.0 versus -1.0 +/- 1.1). However, a significant increase (P < 0.05) was found at the lumbar spine in both groups (control, 0.1 +/- 1.6 versus 0.4 +/- 1.6; treatment, -0.1 +/- 1.5 versus 0.3 +/- 1.5) and only in the treatment group at the femoral neck (control, -0.9 +/- 1.0 versus -0.8 +/- 1.0; treatment, -0.5 +/- 0.9 versus -0.3 +/- 1.1). When BMD was compared between groups, no significant differences were observed at the evaluated anatomic sites at baseline or after 1 year of follow-up. After 1 year of follow-up, adjusting for age and sex (z score), the control group showed a trend to reduce the value of several histomorphometric parameters, including osteoblast surface (-2.2 +/- 6.1 versus -3.4 +/- 3.9), osteoid surface (-2.3 +/- 3.5 versus -3.1 +/- 3.9), and osteoclast surface (0.2 +/- 5.0 versus -1.3 +/- 3.3). Consequently, there was a significant reduction (P < 0.05) in mineralizing surface (-9.8 +/- 11.0 versus -15.8 +/- 12.3) and appositional rate (-5.8 +/- 2.7 versus -7.6 +/- 2.2). In the treatment group, a significant reduction (P < 0.05) in osteoclast surface was observed at the end of the study (3.9 +/- 6.8 versus -1.2 +/- 4.1), and although a trend to reduce osteoblast surface (-2.5 +/- 2.6 versus -3.2 +/- 5.7) and osteoid surface (-2.1 +/- 2.5 versus -3.2 +/- 2.8) was also found, patients maintained approximately the same level of wall thickness (-5.2 +/- 5.3 versus -5.3 +/- 3.3) and bone volume (-2.7 +/- 1.8 versus -2.5 +/- 1.7). However, there was no improvement in mineralizing surface (-4.2 +/- 2.9 versus -10.4 +/- 3.6) or appositional rate (-5.8 +/- 3.1 versus -8.1 +/- 2.6). No significant differences in bone histomorphometric variables were observed between groups after 1 year of follow-up. In conclusion, 1,25-dihydroxyvitamin D3 and calcium carbonate did not significantly improve bone loss in long-term renal transplant recipients. However, significant osteoclast suppression and a trend to maintain trabecular bone volume and wall thickness as well as improve the axial BMD were observed in the treatment group.
Adult↗
Down-regulation of human osteoblast PTH/PTHrP receptor mRNA in end-stage renal failure.
BACKGROUND: Resistance to the action of parathyroid hormone (PTH) has been demonstrated in end-stage renal failure and is considered to be important in the pathogenesis of secondary hyperparathyroidism. The mechanism of resistance is unknown. However, altered regulation of cellular PTH/PTH-related protein (PTH/PTHrP) receptor (PTH1R) has been assumed to be important. METHODS: We have used in situ hybridization to examine PTH1R mRNA expression by osteoblasts in human bone and have compared the expression in high- and low-turnover renal bone disease, high-turnover nonrenal bone disease (healing fracture callus and Pagetic bone), and normal bone. Bone biopsies were formalin fixed, ethylenediaminetetraacetic acid decalcified, and paraffin wax embedded. A 1.8 kb PTH1R cDNA probe, labeled with 35S, was used, and the hybridization signal was revealed by autoradiography. The density of signal over osteoblasts was quantitated using a semiautomated Leica image analysis software package. RESULTS: The mean density of PTH1R mRNA signal over osteoblasts in renal high-turnover bone was only 36% of that found in nonrenal high-turnover bone (P < 0.05) and 51% of that found in normal bone (P < 0.05). Osteoblast PTH1R mRNA signal in adynamic bone from individuals with diabetes mellitus was 28% of normal bone (P < 0.05) and 54% of that found in renal high-turnover bone (P < 0.05). CONCLUSIONS: These results demonstrate a down-regulation of osteoblast PTH1R mRNA in end-stage renal failure in comparison to normal and high-turnover bone from otherwise healthy individuals, and provide an insight into the mechanisms of "skeletal resistance" to the actions of PTH.
Adult↗
Bone loss in long-term renal transplantation: histopathology and densitometry analysis.
BACKGROUND: There is little information of the spectrum and factors implicated in the bone loss in long-term renal transplantation, and virtually no data using both histomorphometric and densitometric analysis. METHODS: Twenty-three males and 22 females (13 postmenopausal) were studied with a bone biopsy and densitometry. Sixteen patients were on cyclosporine A monotherapy, 20 on azathioprine + prednisolone, and 9 on cyclosporine A + prednisolone or triple therapy. The mean time after transplantation was 127 +/- 70 months. RESULTS: No group had a significant decrease in bone mineral density (BMD) of the axial skeleton compared with an age- and sex-matched normal population. Compared with sex-matched young controls, osteopenia was observed in all groups at the femoral neck (except premenopausal women and triple therapy) and in the triple-therapy group at the L1-L4 spine region. At the distal radius, osteopenia was found in all the groups. Histopathological diagnosis was mixed uremic osteodystrophy in 46.5%, adynamic bone in 23.2%, hyperparathyroid disease in 13.9%, and normal bone in 16.3%. The diagnosis was not different according to immunosuppressive therapy, but men tended to show more mixed uremic bone disease. There was no significant difference in BMD between histopathological subtypes. In general, patients showed slight osteoclast function increase, osteoblast function decrease, and marked retardation of dynamic parameters. The cyclosporine A monotherapy group had a significantly lower appositional rate than azathioprine + prednisolone. Men had a significantly lower bone volume than women, and premenopausal women had a significantly lower mineralizing surface than postmenopausal women and men. In the multivariate analysis, male gender, time after transplantation, old age, and time on dialysis prior to transplantation were significant predictive factors for a negative effect on bone mass. CONCLUSIONS: Long-term renal transplant-patients showed reduced BMD in both trabecular and cortical bone. This reduction in BMD was not as severe as in short-term reports and was associated with osteoclast stimulation, osteoblast suppression, and retardation of mineral apposition and bone formation rates. Bone mass loss was not different between the immunosuppression therapy groups. Male gender and age were the strongest predictive factors for low bone mass.
Absorptiometry, Photon↗
Predialysis management of divalent ion metabolism.
Disordered divalent ion metabolism has its origins in the earliest stages of renal impairment. Early intervention is essential to minimize its effects, especially in the light of recent reports demonstrating an association between serum phosphate and relative risk of mortality in dialysis patients. As the age and comorbidity of patients accepted for renal replacement therapy increases, the complexity of their management also increases. A dedicated "predialysis" enables a multidisciplinary team to intervene in an orderly and appropriate fashion to delay progression, modify comorbidity, prevent uraemic complications and prepare the patient mentally and physically for dialysis and renal transplantation. Part of this process involves the identification of patients at high risk of the skeletal and biochemical complications of renal osteodystrophy. Correction of hypocalcemia, acidosis, hyperphosphatemia and rising PTH levels should be achieved quickly. Oral calcitriol therapy is frequently necessary, and requires careful monitoring and supervision.
Calcitriol↗
Angiomyolipoma in a transplanted kidney.
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Aged↗
Calcitriol, lanthanum carbonate, and other new phosphate binders in the management of renal osteodystrophy.
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Calcitriol↗
Biochemical markers for non-invasive diagnosis of hyperparathyroid bone disease and adynamic bone in patients on haemodialysis.
UNLABELLED: The diagnostic and predictive value of serum intact parathyroid hormone (iPTH) and osteocalcin (bone Gla protein, BGP), alone or in combination, have been examined in only a small number of haemodialysis patients. METHODS: We studied prospectively 114 patients (46 women, 68 men; mean age 52 +/- 12 years) on regular haemodialysis for a mean of 55 (6-185) months. All patients underwent labelled transiliac bone biopsy, and serum levels of iPTH, BGP and alkaline phosphatase were determined. RESULTS: Seventy-one patients (62%) showed histological findings of hyperparathyroid bone disease, 24 (21%) mixed bone disease, six (5.5%) osteomalacia and 13 (11.5%) adynamic bone. Bone aluminium deposition over more than 25% of the trabecular bone interface was found in 66 patients (58%). Serum iPTH and BGP correlated with the majority of histomorphometric indices of bone formation, mineralization and resorption (r > 0.5, P < 0.01). iPTH levels > or = 200 pg/ml and BGP > or = 50 ng/ml were found to be indicative of hyperparathyroid bone disease, whilst iPTH levels < 65 pg/ml and BGP < 20 ng/ml were indicative of adynamic bone. However, the positive predictive value of these indices was limited (less than 80%), although their negative predictive value, especially when used in combination, was good (more than 90%) and the exclusion of hyperparathyroid bone disease and adynamic bone was possible. The diagnostic and predictive value of these bone markers were improved when patients with bone aluminium deposition were excluded. CONCLUSIONS: Diagnosis of hyperparathyroid bone disease and adynamic bone is difficult on the basis of iPTH and BGP, especially when bone aluminium deposition is prevalent. However, using these bone markers, preferably in combination, the exclusion of these lesions is feasible.
Adult↗
Hypercalcaemia, hypermagnesaemia, hyperphosphataemia and hyperaluminaemia in CAPD: improvement in serum biochemistry by reduction in dialysate calcium and magnesium concentrations.
Phosphate binders are necessary to control hyperphosphataemia in the majority of dialysis patients. Whilst aluminium salts are efficient phosphate binders, their use is associated with toxic side effects. Calcium salts are a widely used alternative, but hypercalcaemia is a common side effect, limiting their use and raising concern about metastatic calcification. Reduction of the dialysis fluid calcium concentration has been shown to reduce hypercalcaemia in haemodialysis patients, with an associated decrease in serum PTH. We analysed the effect of reduced calcium/magnesium (1.25/0.25 mmol/l), 40 mmol/l lactate, PD fluid (PD4) on 11 CAPD patients with uncontrollable hypercalcaemia (> 2.65 mmol/l) and hyperphosphataemia (> 1.80 mmol/l). Only 1 patient remained hypercalcaemic, while phosphate fell in 6 patients (2.23 +/- 0.16 on no binder, to 1.68 +/- 0.08 mmol/l at 6 months (p < 0.05), but was unchanged in 5 (2.10 +/- 0.15 to 2.48 +/- 0.14 mmol/l [p = NS]). Overall mean calcium x phosphate product changed little. However, in a subgroup it fell significantly (p < 0.05). Geometric mean iPTH rose, but not significantly. The subgroup of patients whose calcium x phosphate product fell, exhibited a much smaller rise in iPTH than the others (57.3-73.2 vs. 52.8-167.1 pg/ml). 1.25-Dihydroxyvitamin D3 was subnormal in all patients. Mean serum magnesium fell from 1.24 +/- 0.06 to 0.89 +/- 0.04 mmol/l (p < 0.001), whilst mean serum bicarbonate rose significantly (25.2 +/- 0.4 to 28.9 +/- 1.2 mmol/l; p < 0.01). Withdrawal of aluminium-containing phosphate binders resulted in mean serum aluminium falling significantly from 31.1 +/- 5.7 at start of PD4 to 15.4 +/- 2.7 mu g/l at 6 months (p < 0.05). In summary, in around 50% of CAPD patients with persistent hypercalcaemia and hyperphosphataemia, reduction in PD fluid calcium can produce significant improvement in phosphate, reduction of calcium x phosphate product, and enable avoidance of aluminium-containing phosphate binders. Patients whose calcium and phosphate control remains poor, still benefit from the reduction, or cessation, of oral aluminium intake.
Adult↗
Low turnover bone disease.
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Bone and Bones↗
Increased mortality due to cardiovascular disease in type 1 diabetic patients transplanted for end-stage renal failure.
The graft and patient survivals following renal transplantation in all Type 1 diabetic patients transplanted within the North-West of England between 1981 and 1990 at Manchester Royal Infirmary were studied. Fifty-two Type 1 (insulin-dependent) diabetic patients with end-stage renal failure due to diabetic nephropathy were transplanted during this period. They were compared to controls matched for age, sex, and year of transplantation and also to all 904 patients transplanted during the same period. Graft survival rates at 1 and 5 years in the diabetic patients were lower (80.8% and 62.1%, respectively), compared to controls (88.9% and 77.9%, respectively, p = 0.02) but were similar to those seen in all grafts (80.4% and 59.0%, respectively, p = NS). Actuarial patient survival rate at 5 years was lower in diabetic patients (76.3%) compared to the control group (94.2%, p = 0.003). Myocardial infarction was the main cause (60%) of death in diabetic patients. The results of this large recent series indicate that good graft and patient survival rates can be obtained in Type 1 diabetic patients, although they remain poorer than those of patients with non-diabetic renal disease. More rigorous pretransplantation cardiac assessment and treatment before acceptance of Type 1 diabetic patients for renal transplantation may help to improve patient survival.
Adult↗