McCarthy, James T.

Muscle wasting and weakness occur frequently in patients with chronic renal failure. The mechanism(s) by which these abnormalities occur is unclear. We hypothesized that such findings were due to defective muscle protein synthesis. We measured synthetic rates of mixed muscle proteins, myosin heavy chain, and mitochondrial proteins in serial muscle biopsy samples during a continuous infusion ofl[1-13C]leucine from 12 patients with chronic renal failure and 10 healthy control subjects under identical study conditions. Patients with chronic renal failure have significantly lower synthetic rates of mixed muscle proteins and myosin heavy chain (27 and 37% reductions, respectively, P < 0.05 and P < 0.02). Significant declines in the synthetic rates of muscle mitochondrial protein (27%) ( P < 0.05), muscle cytochrome c-oxidase activity (42%) ( P < 0.007), and citrate synthase (27%) ( P < 0.007) were also observed in patients with chronic renal failure. The synthetic rates of muscle proteins and activity of mitochondrial enzymes were negatively correlated to the severity of renal failure. These results indicate that in chronic renal failure there is a decrease in the synthesis of muscle contractile and mitochondrial proteins and a decrease in muscle mitochondrial oxidative enzymes. Reduced synthetic rate of several muscle proteins is the likely biochemical basis of muscle loss and muscle weakness in people with chronic renal failure.

AbstractBackgroundRecent studies suggest that calciphylaxis is a thrombotic condition in which arteriolar thrombosis leads to painful skin infarcts and consequent morbidity and mortality. Paradoxically, warfarin is implicated as a risk factor for calciphylaxis. Our objective is to report the use of oral direct thrombin and factor Xa inhibitors (termed direct oral anticoagulants [DOACs]) in patients with calciphylaxis.MethodsWe retrospectively reviewed records of 16 patients with calciphylaxis who received concomitant administration of novel anticoagulants. Patient data, including demographics, comorbidities, other treatments, and adverse events, were abstracted from the health records.ResultsEleven patients (69%) had chronic kidney disease (stage ≥3A), and eight (50%) received dialysis. Apixaban was the most frequently used agent (n = 11 [69%]). Dabigatran (n = 4 [25%]) and rivaroxaban (n = 2 [13%]) were reserved for patients with mild renal impairment (stage ≤2). One clinically relevant but nonmajor bleeding event occurred. There were no major bleeding events. Nine patients (56%) were alive at last follow‐up, and five (31%) had complete resolution of their calciphylaxis (mean follow‐up, 523 days; range, 26–1884 days).ConclusionDOACs were safe and well tolerated in patients with calciphylaxis, in this initial experience. Several patients had improvement or resolution of calciphylaxis in response to therapy that included DOACs. The degree of renal impairment should guide DOAC choice. Randomized trials are required to determine treatment efficacy.

Abstract A desferrioxamine (DFO) infusion test, using a DFO dose of 36.9±11.2 mg/kg (mean ±SD), was performed in 50 consecutive dialysis patients undergoing diagnostic bone biopsy. In 30 patients whose bones stained positively for aluminium the serum aluminium level increased by an average of 373±250.4 ng/ml. The increase in 20 aluminium-negative patients was 231±179.2 ng/ml (p≪0.05). Aluminium-positive patients had lower levels of immunoreactive parathyroid hormone (336±442 μleq/ml) than aluminium-negative patients (1278±1400 μleq/ml; p≪0.05). A change in serum aluminium level of &gt; 200 ng/ml after the administration of DFO was 73 percent sensitive and 50 percent specific, and had a positive predictive value of 69 percent for detecting positive bone aluminium staining. The combination of a baseline immunoreactive parathyroid hormone level ≪200 leq/ml and a change in serum aluminium of &gt; 200 ng/ml after DFO was 90 percent specific and had a positive predictive value of 85 percent. In the second phase of our study, 28 dialysis patients with aluminium toxicity received longterm therapy (11.0±4.3 months) with DFO at an average starting dose of 41.7±17.1 mg/kg, administered once weekly. The four deaths which occurred during this treatment involved the only patients who had advanced dialysis dementia. Seven patients with less severe neurological symptoms responded favourably. Fractures decreased from 1.7 fractures/patient/year to 0.1 fracture/patient/year. Muscular strength and overall functional class were improved or stable in 25 patients; myalgias and arthralgias were also stable or improved in 19 patients. After 5–7 months of treatment, serum aluminium levels decreased from 401±262 ng/ml to 245±217 ng/ml (p≪0.01); erythrocyte mean corpuscular volume increased from 86.3±10.91 fl to 94.1±9.23 fl (p≪0.02); and serum calcium decreased from 10.4±0.94 mg/dl to 9.9±0.70 mg/dl (p≪0.02). Serum immunoreactive parathyroid hormone levels remained stable in 25 patients, but severe hyperparathyroidism developed rapidly in three patients. Eight patients with transfusional iron overload had no change in serum ferritin levels. Iron depletion developed in six patients, with a decrease in serum ferritin from 251±229.8μg/l to 45±29.3μg/l, and they required parenteral iron supplementation. Significant side-effects occurring during long-term

AbstractAimsThe number of elderly persons with end‐stage renal disease is increasing with many requiring hospitalizations. This study examines the causes and predictors of hospitalization in older haemodialysis patients.MethodsWe reviewed hospitalizations of older (≥65 years) incident chronic haemodialysis patients initiating therapy between 1 January 2007 and 31 December 2009 under the care of a single Midwestern United States dialysis provider.ResultsOf 125 patients, the mean age was 76 ± 7 years and 72% were male. At first dialysis, 68% used a central venous catheter (CVC) and 51% were in the hospital. Mean follow‐up was 1.8 ± 1.0 years. At least one hospitalization occurred in 89 (71%) patients and half of all patients were hospitalized once within the first 223 days. Total hospital admission rate was 1.48 per patient year with hospital days totalling 8.54 days per patient year. The three most common reasons for first admission were cardiac (33%), infection (18%) and gastrointestinal (12%). Predictors of future hospitalization included the first dialysis occurring in hospital (hazard ratios (HR) 2.1, 95% CI 1.4–3.3, P = 0.0005) and the use of a CVC at first haemodialysis (HR 2.6, CI 1.6–4.4, P < 0.0001).ConclusionHospitalizations are common in older incident haemodialysis patients. Access preparation and overall burden of illness leading to the initial hospitalization appear to play a role. Identification of additional factors associated with hospitalization will allow for focused interventions to reduce hospitalization rates and increase the value of care.

Abstract Background Calciphylaxis is a rare, painful, life-threatening problem of cutaneous necrosis and refractory healing seen in patients with uraemia and secondary hyperparathyroidism. The pathogenesis involves abnormalities in calcium and phosphorus metabolism, and acute deposition of calcium in tissues. Methods The clinical course of 16 patients diagnosed with calciphylaxis at this institution from 1994 to 1998 was reviewed. Results Fourteen women and two men, with a mean age of 56 (range 39–70) years, presented with chronic renal disease of various causes, hyperparathyroidism and characteristic skin lesions. All patients underwent intensive medical therapy, including haemodialysis (n = 16), parathyroidectomy (PTX) (n = 7) and skin debridement of cutaneous lesions (n = 8). Mean preoperative serum values in surgical (PTX) versus non-surgical patients were: calcium 9·9 and 9·3 mg dl−1 (P = 0·25); phosphorus 5·8 and 4·9 mg dl−1 (P = 0·04); calcium–phosphorus product 61·6 and 45·2 (P = 0·03); and parathyroid hormone (PTH) 56·8 and 5·9 pmol l−1 (P = 0·0001) respectively. Mean postoperative values for calcium (8·7 mg dl−1), phosphorus (4·2 mg dl−1), calcium–phosphorus product (30·5) and PTH (4·0 pmol l−1) in surgical patients changed significantly (P &lt; 0·05). Median overall survival was 9·4 months with 15 patients now deceased. Median survival was 14·8 and 6·3 months for PTX versus no PTX (P = 0·22), 14·1 and 6·1 months for skin debridement versus no debridement (P = 0·08), 12·4 and 6·6 months for proximal versus distal skin lesions (P = 0·60), and 6·5 and 13·9 months for diabetic versus non-diabetic patients was (P = 0·11). Conclusion Calciphylaxis appears to have a female preponderance with a very dismal prognosis. A multidisciplinary approach using frequent haemodialysis to normalize serum calcium and phosphorus levels, and local debridement of skin lesions seems prudent. PTX cannot be recommended routinely in all such patients unless severe secondary hyperparathyroidism with poorly controlled metabolic disturbance mandates surgery. The exact indications for PTX for calciphylaxis remain unclear.