Biomedical subjects

Alastair J Hutchison

Publications and source records attributed to Alastair J Hutchison.

7 recordsLinked to original sources

PubMed2005

Long-term efficacy and tolerability of lanthanum carbonate: results from a 3-year study.

BACKGROUND: Control of serum phosphate over the long term is essential in patients with end-stage renal disease. Six-month and 2-year extensions to a 6-month study evaluated the long-term safety, tolerability and efficacy of the new phosphate binder lanthanum carbonate. METHODS: Patients who participated in a 6-month, randomized trial comparing lanthanum carbonate with calcium carbonate were eligible for a 24-week, open-label extension. Lanthanum carbonate-treated patients continued taking their established maintenance dose ('continued-lanthanum group') and calcium carbonate-treated patients switched to lanthanum carbonate, 375-3,000 mg/day ('switch group'). Patients could also enter a further 2-year extension. Efficacy parameters, including serum phosphate, were monitored. RESULTS: Mean serum phosphate was approximately 1.80 mmol/l throughout the trial. The percentage of patients with controlled serum phosphate (< or =1.80 mmol/l) after the 6-month extension was 63.3 and 58.4% in the continued-lanthanum and switch groups, respectively; after the 2-year extension, 54.4% of patients had controlled serum phosphate. After discontinuation of calcium carbonate and initiation of lanthanum carbonate, the hypercalcemia incidence was 2.7%, compared with 20.2% during the double-blind phase. Calcium x phosphate product was maintained at an acceptable level. Lanthanum carbonate was well tolerated; adverse events were mild/moderate and mainly gastrointestinal. CONCLUSIONS: Lanthanum carbonate maintains effectiveness with continued tolerability for up to 3 years.

Adult↗

PubMed2005

Control of serum phosphate by oral lanthanum carbonate in patients undergoing haemodialysis and continuous ambulatory peritoneal dialysis in a short-term, placebo-controlled study.

BACKGROUND: Hyperphosphataemia in dialysis patients is associated with significant morbidity. We assessed the ability of lanthanum carbonate to control phosphate levels in patients undergoing haemodialysis or continuous ambulatory peritoneal dialysis (CAPD) in a short-term, placebo-controlled study. METHODS: This was a double-blind, placebo-controlled, parallel-group study consisting of three phases: a 2 week washout period; a 4 week, open-label, dose-titration phase; and a 4 week, double-blind, placebo-controlled phase. After washout, patients (n = 59) received lanthanum (375 mg/day), titrated up to a maintenance dose (maximum: 2250 mg) that achieved control of serum phosphate levels between 1.3 and 1.8 mmol/l (4.03-5.58 mg/dl). After titration, patients were randomized to receive their maintenance dose of lanthanum (n = 17) or placebo (n = 19) for 4 weeks. Control of serum phosphate was the primary efficacy assessment. Levels of calcium, parathyroid hormone, calcium x phosphate product and lanthanum as well as adverse events were evaluated. RESULTS: By the end of titration, 70% of patients had serum phosphate levels < or =1.8 mmol/l. Lanthanum carbonate continued to control serum phosphate levels in the double-blind phase. At the end of the study, 64.7% of lanthanum carbonate-treated patients were controlled compared with 21.4% in the placebo group. Results in patients receiving CAPD were similar to those seen in the group as a whole. Mean parathyroid hormone levels (P = 0.41) and calcium x phosphate product (P<0.001) were both higher in the placebo than the lanthanum carbonate group. CONCLUSIONS: Lanthanum carbonate is an effective phosphate binder able to control serum phosphate and calcium x phosphate product.

Administration, Oral↗

PubMed2005

Single-center experience of encapsulating peritoneal sclerosis in patients on peritoneal dialysis for end-stage renal failure.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD). It is characterized by a progressive, intra-abdominal, inflammatory process resulting in sheets of fibrous tissue that cover, bind, and constrict the viscera, thereby compromising the motility and function of the bowel. Although recent therapeutic approaches have been reported with variable success, the ability to detect reliably at an early stage patients at risk for EPS would be beneficial and allow treatment standardization. The aim of this study was to evaluate the clinical features of EPS and identify possible risk factors for its development in CAPD and APD patients. METHODS: This was a review of all cases of EPS in a single center over the last 5 years. RESULTS: There were 810 CAPD and APD patients, managed in our program over this period. We identified 27 cases of EPS, giving an overall of 3.3% in this population. The mean duration of CAPD before diagnosis of EPS was 72.6 +/- 39.7 months (range 16-172). Sixteen cases required surgical treatment and were classified as severe; others were treated conservatively (mild to moderate group). Ten patients received tamoxifen treatment with apparent benefit. The overall mortality rate was 29.6%. Eight patients from the severe group and the entire moderate group survived on hemodialysis or transplantation at 48.71 and 27.63 months follow-up, respectively. Peritonitis rates were not different between the 2 groups and peritoneal history was unremarkable compared to overall peritonitis rates in the unit. Data on small solute transport were not available in all patients in this retrospective analysis. CONCLUSION: EPS is a serious, life-threatening complication of CAPD. Most cases had PD duration of more than 4 years. Careful monitoring by CT scans of the peritoneal membrane in patients beyond 5 years, and early catheter removal in patients with peritoneal thickening should be considered for long-term CAPD patients. Treatment with tamoxifen may be of benefit in these patients.

Adult↗

PubMed2005

Lanthanum carbonate for the treatment of hyperphosphataemia in renal failure and dialysis patients.

Hyperphosphataemia is a usual accompaniment of end stage renal disease and dialysis, in the absence of dietary phosphate restriction or supplemental phosphate binders. It 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 oral phosphate-binding agent. Aluminium- and calcium-based agents are associated with major side effects, despite their undoubted efficacy. Although sevel-amer hydrochloride represents a step forward in the management of hyperphosphataemia, it is not an ideal phosphate binder due to its cost and tablet burden. Lanthanum carbonate is the most recent non-calcium, non-aluminium, phosphate-binding agent. It is effective and well-tolerated, and no negative effects on bone histology have been observed.

Clinical Trials as Topic↗

PubMed2004

Improving phosphate-binder therapy as a way forward.

Aluminium- or calcium-based phosphate-binding agents traditionally have been used to treat hyperphosphataemia in patients with end-stage renal disease. Although these agents effectively lower serum phosphorus levels, they are associated with serious side effects. Aluminium-based agents are associated with bone toxicity, renal osteodystrophy and encephalopathy, and calcium-based agents increase the risk of hypercalcaemia and cardiovascular calcification. Consequently, there remains a need for new, safe and effective non-calcium-, non-aluminium-based alternative treatments. Fortunately, several new agents are now available or are in the late stages of development, including sevelamer hydrochloride and lanthanum carbonate. Although sevelamer hydrochloride represents a step forward in the management of hyperphosphataemia, it has several drawbacks and is far from being the ideal phosphate binder. Lanthanum carbonate is the most recent non-calcium, non-aluminium phosphate binder to be developed for the treatment of hyperphosphataemia. Animal studies have shown it to be as effective as aluminium, without the associated toxicity. In clinical studies, lanthanum carbonate significantly reduced serum phosphorus levels, compared with placebo. It shows a similar efficacy to calcium carbonate in controlling serum phosphorus levels, but requires lower doses. In addition, lanthanum carbonate is at least as well tolerated as calcium carbonate, but is not associated with hypercalcaemia. Importantly, it has a positive effect on bone histology, with no evolution towards low bone turnover. Lanthanum carbonate, therefore, moves closer to the ideal phosphate binder.

Clinical Trials as Topic↗

PubMed2004

Reducing high phosphate levels in patients with chronic renal failure undergoing dialysis: a 4-week, dose-finding, open-label study with lanthanum carbonate.

BACKGROUND: The majority of patients with end-stage renal disease on dialysis are hyperphosphataemic. Lanthanum carbonate has been shown to be a highly effective phosphate binder in pre-clinical studies. A 4-week, open-label, dose-titration trial was conducted to assess the ability of lanthanum carbonate to control phosphate levels in patients with chronic renal failure. METHODS: This preliminary study was of 6 weeks duration: 2 weeks of washout followed by 4 weeks of dose titration. Patients (n = 59) were titrated on the basis of weekly serum phosphate levels from a daily dose of 375 mg lanthanum carbonate to a maximum dose of 2250 mg. Patients were maintained on the dose that controlled serum phosphate to between 1.30 and 1.80 mmol/l (4.03-5.58 mg/dl). Serum phosphate levels represented the main efficacy assessment. Safety was also evaluated. RESULTS: Most patients were successfully titrated to 1500 and 2250 mg lanthanum/day (mean dose at end of titration: 1278 mg). At completion of the study 70% of patients achieved a serum phosphate of <or=1.80 mmol/l. The use of lanthanum carbonate in patients undergoing continuous ambulatory peritoneal dialysis or haemodialysis was generally well tolerated. CONCLUSIONS: Lanthanum carbonate, a new non-aluminium, non-calcium phosphate binder, effectively reduces serum phosphate levels. Results of longer-term efficacy and safety studies are awaited with interest.

Female↗

PubMed2003

Bone histopathology and densitometry comparison between cyclosporine a monotherapy and prednisolone plus azathioprine dual immunosuppression in renal transplant patients.

BACKGROUND: No study has compared the bone histopathologic findings in renal transplant patients receiving cyclosporine A (CsA) monotherapy with those in patients receiving a non-CsA regimen. The aim of this study was to compare bone densitometry and histomorphometry findings in patients receiving CsA monotherapy versus those receiving azathioprine + prednisolone dual therapy. METHODS: A bone biopsy and densitometry were performed in 13 patients receiving CsA monotherapy and 12 patients receiving azathioprine + prednisolone, who had been on these regimens since the time of transplantation. Fourteen men and 11 women, age 51+/-12 years, with 140+/-75 months since transplantation, were included. RESULTS: A low bone mineral density (BMD) was observed in patients on both immunosuppressive schemes-most notably at the distal radius and less significantly at the lumbar spine. No significant differences in BMD were observed between immunosuppressive groups. Histopathologic analysis of the group as a whole revealed mixed uremic bone disease in 42%, adynamic bone in 29%, hyperparathyroid disease in 17%, and normal bone in 12%. Patients showed a slight increase in osteoclast number and function, decreased osteoblast number and function, and retardation of dynamic parameters. No differences in histopathologic diagnosis or histomorphometric findings were observed between the immunosuppressive therapy groups. In addition to the immunosuppressive drugs, male gender and old age negatively affected bone mass. CONCLUSIONS: Both prednisolone and CsA were associated with slight osteoclast stimulation and osteoblast suppression and marked retardation of mineral apposition and bone formation rates. Both drugs were also associated with reduced BMD at the axial and appendicular skeleton, even though a nonsignificant trend to a better-preserved lumbar spine BMD was observed in the CsA group.

Absorptiometry, Photon↗