Calcium supplements lower bone resorption after renal transplant.

AIM: Bone loss in renal transplant (RT) patients is a problem that begins during end-stage kidney disease and persists after transplantation. Suppression of parathyroid hormone (PTH) may decrease bone loss and improve fracture rate. METHODS: A single-group prospective intervention study involving 30 patients was performed at a large RT unit. Investigations included dual-emission X-ray absorptiometry scan, vertebral X-ray, calcium absorption test, 24-h urinary calcium and serum measurements of total and ionized calcium, PTH, C-telopeptide cross-links (CTX), osteocalcin, alkaline phosphatase, 25 hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D3. Patients were given 500 mg elemental calcium daily for seven d, and serum measurements were repeated. RESULTS: Two-tailed Wilcoxon rank-sum test showed significant decreases in PTH (p<0.01) and CTX (p<0.01) after calcium load. Dietary calcium, mean calcium absorption, and urinary calcium excretion were below desirable levels. Mean 25 hydroxyvitamin D (25(OH)D) was low, but levels of 1,25-dihydroxyvitamin D3 were normal. Calcium absorption significantly correlated with change in PTH (p<0.001), baseline 25(OH)D (p<0.001), and mycophenolate dose (p=0.024). CONCLUSIONS: Calcium malabsorption is prevalent in RT recipients, contributing to bone destruction and compounded by poor dietary intake and low 25(OH)D. Calcium supplementation appears to help overcome this deficiency and acutely suppress PTH. Calcium may be an effective and inexpensive therapy for bone loss in RT recipients.

Hypertension and atrial fibrillation: evidence of progressive atrial remodeling with electrostructural correlate in a conscious chronically instrumented ovine model.

BACKGROUND: Hypertension accounts for more atrial fibrillation (AF) than any other predisposing factor. OBJECTIVE: The purpose of this study was to characterize the time course, extent, and electrostructural correlation of atrial remodeling in chronic hypertension. METHODS: Thirty-two sheep were studied: 21 with induced "one-kidney, one-clip" hypertension and 11 controls. Sequential closed-chest electrophysiologic studies were performed in 12 conscious animals (6 hypertensive, 6 controls) to evaluate progressive remodeling over 15 weeks. Additional atrial structural/functional analyses were performed in 5 controls and at 5, 10, and 15 weeks of hypertension (five per time point) via histology/cardiac magnetic resonance imaging to correlate with open-chest electrophysiologic parameters. RESULTS: The hypertensive group developed a progressive increase in mean arterial pressure (P <.001). Mean effective refractory periods were uniformly higher at all time points (P <.001). Progressive biatrial hypertrophy (P = .003), left atrial dysfunction (P <.05) and greater AF inducibility were seen early with increased inflammation from 5 weeks of hypertension. In contrast, significant conduction slowing (P <.001) with increased heterogeneity (P <.001) along with increased interstitial fibrosis resulted in longer and more fractionated AF episodes only from 10 weeks of hypertension. Significant electrostructural correlation was seen in conduction abnormalities and AF inducibility with both atrial inflammation and fibrosis. CONCLUSION: Hypertension is associated with early and progressive changes in atrial remodeling. Atrial remodeling occurs at different time domains in chronic hypertension with significant electrostructural correlation of the remodeling cascade. Early institution of antihypertensive treatment may prevent formation of substrate capable of maintaining AF.

Endogenous plasma carnitine pool composition and response to erythropoietin treatment in chronic haemodialysis patients.

BACKGROUND: Anaemia is a common complication associated with haemodialysis and is usually managed by treatment with recombinant human erythropoietin (rHuEPO). However, many patients remain hyporesponsive to rHuEPO treatment despite adequate iron therapy. The effect of L-carnitine administration on rHuEPO dose and/or haematocrit in haemodialysis patients has been previously reported with equivocal results. This study examined the relationship between endogenous carnitine pool composition and rHuEPO requirements in long-term haemodialysis patients. METHODS: Pre-dialysis blood samples were collected from 87 patients and analysed for plasma L-carnitine and individual acylcarnitine levels by LCMS/MS. As an indication of rHuEPO responsiveness, erythropoietin resistance index (ERI) was calculated as rHuEPO dose/kg/week normalized for haemoglobin levels. RESULTS: A significant negative correlation between L-carnitine levels and ERI was found (P = 0.0421). All patients categorized as high ERI (>0.02 microg/kg/week/gHb) exhibited subnormal L-carnitine levels (<30 microM); conversely, patients with normal L-carnitine levels (>30 microM) displayed low ERI values (<0.02 microg/kg/week/gHb). More importantly, the ratio of non-acetyl acylcarnitines/total carnitine was significantly positively correlated with ERI (P = 0.0062). CONCLUSIONS: These data illustrate the relationship between carnitine levels and response to rHuEPO treatment in haemodialysis patients, in particular, the importance of the proportion of long-chain acylcarnitines within the plasma carnitine pool. This proportion may be more indicative of the response to L-carnitine supplementation than absolute L-carnitine levels alone.

L-carnitine supplementation in the dialysis population: are Australian patients missing out?

It has been widely established that patients with end-stage renal disease undergoing chronic haemodialysis therapy exhibit low endogenous levels of L-carnitine and elevated acylcarnitine levels; however, the clinical implication of this altered carnitine profile is not as clear. It has been suggested that these disturbances in carnitine homeostasis may be associated with a number of clinical problems common in this patient population, including erythropoietin-resistant anaemia, cardiac dysfunction, and dialytic complications such as hypotension, cramps and fatigue. In January 2003, the Centers for Medicare and Medicaid Services (USA) implemented coverage of intravenous L-carnitine for the treatment of erythropoietin-resistant anaemia and/or intradialytic hypotension in patients with low endogenous L-carnitine concentrations. It has been estimated that in the period of 1998-2003, 3.8-7.2% of all haemodialysis patients in the USA received at least one dose of L-carnitine, with 2.7-5.2% of patients receiving at least 3 months of supplementation for one or both of these conditions. The use of L-carnitine within Australia is virtually non-existent, which leads us to the question: Are Australian haemodialysis patients missing out? This review examines the previous research associated with L-carnitine administration to chronic dialysis patients for the treatment of anaemia, cardiac dysfunction, dyslipidaemia and/or dialytic symptoms, and discusses whether supplementation is warranted within the Australian setting.