Evidence for persistent vitamin D 1-alpha-hydroxylation in hemodialysis patients: evolution of serum 1,25-dihydroxycholecalciferol after 6 months of 25-hydroxycholecalciferol treatment.

BACKGROUND: End-stage renal disease (ESRD) patients are thought to have impaired 1-alpha-hydroxylase capacity, but an extrarenal source of 1,25(OH)(2)D has been recognized. OBJECTIVE: The aim of this study was to assess the evolution of serum 1,25(OH)(2)D in hemodialysis (HD) patients with vitamin D deficiency after 6 months of 25(OH)D(3) supplementation, and to identify the factors associated with persistent 1,25(OH)(2)D production. METHODS: HD patients in a HD center with vitamin D deficiency (i.e. 25(OH)D <75 nmol/l) who were not receiving any vitamin D derivatives or calcimimetics were studied. Patients who had previously undergone parathyroidectomy or nephrectomy or those with uncontrolled hypercalcemia or hyperphosphatemia were excluded from this study. The patients were administrated a dose of 10-30 microg/day of oral 25(OH)D(3) based on the severity of their deficiency. The serum levels of 25(OH)D and 1,25(OH)(2)D evolution after 6 months were recorded. Responders were defined as patients with an increase in serum 1,25(OH)(2)D levels greater than the median value. Changes in mineral metabolism parameters were compared with those in the nonresponders. RESULTS: Of the 253 patients, 225 (89%) were vitamin D-deficient, and 43 met the inclusion criteria. The patients were 72.6 +/- 10 years old and had been on dialysis for 71 +/- 70 months; 39% of the patients were female and 45% were diabetics. From baseline to 6 months of treatment, serum 25(OH)D levels increased from 27.8 +/- 18 to 118 +/- 34 nmol/l (p < 0.001) and serum 1,25(OH)(2)D levels increased from 7.7 +/- 5 to 30.5 +/- 15 pmol/l (p < 0.001) with a median increase of 20 pmol/l. The mean serum calcium level increased from 2.19 +/- 0.1 to 2.25 +/- 0.1 mmol/l (p = 0.009), the intact parathyroid hormone (iPTH) level decreased from 144 +/- 108 to 108 +/- 63 pg/ml (p = 0.05), and the bone alkaline phosphatase (BALP) level remained unchanged. The serum phosphate level increased slightly from 1.22 +/- 0.3 to 1.34 +/- 0.2 mmol/l (p = 0.04) with reduced hypophosphatemia. Compared with the responders (n = 24), most of the nonresponders (n = 19) were diabetic (63 vs. 29%, p = 0.02) and had a lesser increase of their 25(OH)D serum level. The serum level of FGF-23 was not significant. A positive correlation was observed between serum 1,25(OH)(2)D and serum 25(OH)D levels after 6 months of 25(OH)D(3) treatment (p = 0.02). CONCLUSION: The Kidney Disease Outcomes Quality Improvement (KDOQI) guidelines do not recommend checking and treating vitamin D deficiency in chronic kidney disease (CKD) stage 5 patients due to the supposed lack of 1,25(OH)(2)D production. These data confirm persistent renal or extra-renal production of 1,25(OH)(2)D in HD patients after 6 months of 25(OH)D(3) administration. Diabetes is the main factor associated with impaired 1,25(OH)(2)D production. 25(OH)D(3 )administration corrects vitamin D deficiency with few effects on mineral metabolism and stability of bone turnover markers.

[Extra cellular volume assessment methods in dialysis, a critical analysis]. / Analyse critique des méthodes de mesures du volume extra-cellulaire en dialyse.

The extra cellular volume is strictly proportional to the amount of sodium present in the body. Its clinical evaluation on dialysis (through clinical story, weight and blood pressure changes) often needs probing for dry weight by reducing progressively the post dialysis weight down to the point where hypotension regularly occurs. Common critics addressed to the clinical assessment of dry weight include lack of sensitivity, of objectivity and of repeatability. But non clinical methods are far from perfect. They are non invasive, but they are poorly sensitive and reproducible (except for bio impedance, but in very strictly equal operational conditions). Most of them (natriuretic peptides, inferior vena cava echography, on-line volemia) measure exclusively the plasma volume but not the extra cellular volume. Besides, they increase dialysis complexity and cost. None of them is so far validated for dialysis. The accurate and absolute value of extra cellular volume is useless in clinical daily practice. What is needed is a simple fast evaluation of the actual extra cellular volume relative to its ideal level (dry weight). The clinical method based on two very simple, costless objective measurements, weight and blood pressure, allows for fulfilling the goal, the continuous adjustment of extra cellular volume and blood pressure normalization.

[Non-pharmacologic treatment of arterial hypertension in hemodialysis patients]. / Traitement non médicamenteux de l'hypertension artérielle en hémodialyse.

High blood pressure in dialysis patients is related to extracellular volume excess and the related increase of systemic vascular resistances. Scribner has early described the treatment of hypertension with ultrafiltration and low salt diet, without any drugs. The dry weight method relies on the progressive reduction of the postdialysis body weight until blood pressure is normalized. Additional measures are needed such as low salt diet, neutral sodium balance during dialysis treatment, stop of antihypertensive drugs, adequate length of the dialysis session, and patient education. It may exist a lag time between the normalization of the extracellular volume and blood pressure. It is related to the correction of the hemodynamic consequences of the extracellular volume overload. Moreover, the dry weight may potentially vary in patients undergoing catabolic intercurrent events. The complications of these changes (severe hypertension, pulmonary oedema) must be anticipated by the nephrologist and the staff to avoid additional morbidity to the patient.

[Low sodium diet for dialysis patients: myth or reality?]. / Diététique hyposodée chez le patient dialysé: mythe ou réalite?

Low salt diet for dialysis patients was recommended at the very beginning of dialysis treatment. It was issued from Kempner and Guyton studies who have established the relationship between salt, hypertension, and the role of the kidney in sodium balance. This recommendation vanished from dialysis literature during the seventies and eighties and is currently on the way back. Salt intake has been evaluated in a small number of patients, found between 8.3 to 14.1 gram/day. Interventional studies for salt intake restriction have been efficient to reduce high blood pressure and decrease the interdialytic weight gain. In our unit, salt restriction is systematically prescribed to chronic kidney failure patients. We have evaluated from food recall or 3-day questionnaires the salt intake in 91 hemodialysis patients during the year 2005. Daily salt intake, not including salt added during cooking, was found at 3.8 g/day. This intake is correlated to interdialytic weight gain, water and phosphate intakes, and to BMI. Then a significant reduction in salt intake is possible in dialysis patients. This result may be obtained by the fruitful collaboration involving nurses, dietitians and the nephrologists.

[Metabolic complications of chronic kidney disease]. / Complications métaboliques de l'insuffisance rénale chronique.

Patients with Chronic Kidney Disease (CKD) are at risk of various metabolic complications, which can lead to health issues and even be life-threatening if not correctly treated, whereas they can be anticipated. Through clinical cases of patients taken from the daily practice, we propose to look into three of these common complications, namely hypocalcemia, hyperkalemia and metabolic acidosis. From the diagnostic approach to the patient care, these cases provide the opportunity to recall the fundamentals of these disorders and to present the recent literature date enlightening the knowledge related to them.

Clinical characterization of familial isolated pituitary adenomas.

CONTEXT: Familial pituitary adenomas occur rarely in the absence of multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). OBJECTIVE: Our objective was to characterize the clinical and genealogical features of non-MEN1/CNC familial isolated pituitary adenomas (FIPA). DESIGN AND SETTING: We conducted a retrospective study of clinical and genealogical characteristics of FIPA cases and performed a comparison with a sporadic population at 22 university hospitals in Belgium, Italy, France, and The Netherlands. RESULTS: Sixty-four FIPA families including 138 affected individuals were identified [55 prolactinomas, 47 somatotropinomas, 28 nonsecreting adenomas (NS), and eight ACTH-secreting tumors]. Cases were MEN1/PRKAR1A-mutation negative. First-degree relationships predominated (75.6%) among affected individuals. A single tumor phenotype occurred in 30 families (homogeneous), and heterogeneous phenotypes occurred in 34 families. FIPA cases were younger at diagnosis than sporadic cases (P = 0.015); tumors were diagnosed earlier in the first vs. the second generation of multigenerational families. Macroadenomas were more frequent in heterogeneous vs. homogeneous FIPA families (P = 0.036). Prolactinomas from heterogeneous families were larger and had more frequent suprasellar extension (P = 0.004) than sporadic cases. Somatotropinomas occurred as isolated familial somatotropinoma cases and within heterogeneous FIPA families; isolated familial somatotropinoma cases represented 18% of FIPA cases and were younger at diagnosis than patients with sporadic somatotropinomas. Familial NS cases were younger at diagnosis (P = 0.03) and had more frequently invasive tumors (P = 0.024) than sporadic cases. CONCLUSIONS: Homogeneous and heterogeneous expression of prolactinomas, somatotropinomas, NS, and Cushing's disease can occur within families in the absence of MEN1/CNC. FIPA and sporadic cases have differing clinical characteristics. FIPA may represent a novel endocrine neoplasia classification that requires further genetic characterization.

Changes in the emergency workload of the London Ambulance Service between 1989 and 1999.

OBJECTIVES: To examine changes in the emergency workload of the London Ambulance Service (LAS) between 1989 and 1999. METHODS: All emergency responses by the LAS during week 16 in each of 1989, 1996, and 1999 were studied. For each week, 999 call responses were analysed by time and day of call, and age/sex of the patient. Call response rates were calculated using age/sex census population estimates for London. Changes in call rates over time were calculated as rate ratios. RESULTS: Emergency responses increased from 6624 to 13 178 in the index weeks of 1989-1999. The ratio of response rates (1999/1989) was 1.91 (95% CI: 1.85 to 1.96). The proportion of out of hours calls increased significantly, from 68.8% in 1989 to 71.3% in 1999 (p = 0.0003). Response rates rose significantly more steeply for male patients than female patients from 1989 to 1999: rate ratio (95% CI); male patients 2.00 (1.91 to 2.08), female patients 1.69 (1.62 to 1.77), p<0.0001. Response rates varied by age in each of the three years investigated. Rates were consistently highest for patients aged 75 and above, and lowest for those aged 5-14. However, there was no evidence that call rates had increased disproportionately in any particular age group (p = 0.79). CONCLUSIONS: Demand for emergency ambulance services in London has doubled in a decade. This increase is similar for all age groups, with no evidence of a greater rise in demand among older people. Call rates have increased more steeply in men than in women. Demographic changes do not explain the observed increases in demand.

Nutritional effects of carnitine supplementation in hemodialysis patients.

AIMS: Carnitine is involved in fatty acid metabolism and it is cleared by dialysis. As it plays a role in energy utilization and because malnutrition is a frequent complication of HD treatment, we studied the effects of carnitine supplementation on several nutritional parameters in HD patients. MATERIAL AND METHODS: The main selection criterion was a body mass index (BMI; body weight/(height)2) < 22 kg/m2. Fifty-three patients were enrolled to participate in this open and randomized study. For 6 months, 28 patients received 15 mg/kg of intravenous L-carnitine at the end of each hemodialysis (HD) treatment (Group A), the remaining 25 patients were controls (Group B). The measured parameters were the post-dialysis body weight, serum albumin concentration (nephelemetry), food intake assessed by a 3-day food questionnaire, nPNA (normalized protein equivalent of nitrogen appearance), creatinine generation, and anthropometry. RESULTS: Forty-five patients completed the study (Group A: 14 F/9 M, 66.7 years old; Group B: 11 F/11 M, 65.2 years old). At the beginning of the study, there were no differences between the groups for age, gender, HD duration, BMI, diabetes prevalence, plasma carnitine levels and measured nutritional parameters. 65.2% and 77.3% in each group were carnitine-deficient (plasma total carnitine level < 35 micromol/l). After 6 months of L-carnitine supplementation, none of the nutritional parameters had changed in either group, except that serum albumin concentration decreased in both groups. Dividing each group according to their respective median serum albumin concentrations, daily energy and protein intakes, creatinine generation or triceps skinfold thickness did not show any difference in the various nutritional parameters with or without carnitine supplementation. CONCLUSION: Carnitine supplementation, despite normalization of plasma carnitine levels, has no effect on the nutritional status of HD patients.

Role of sodium in dialysis.

The total amount of sodium present in the body conditions the extracellular compartment volume. In advanced renal failure and in dialysis the sodium balance becomes positive and the extracellular volume inflates. This leads to hypertension and to direct cardiac and vascular changes that explain for a large part the excessive cardiovascular morbidity and mortality in dialysis patients. Controlling body sodium content and extracellular volume allows to reduce hypertension, cardiovascular changes and to improve dialysis patients survival. This can be achieved by reducing the sodium input (low sodium diet and reasonably low sodium dialysate) and/or by increasing sodium output (ultrafiltration by convection in hemodialysis or hemofiltration and osmotic drive in peritoneal dialysis). The intermittent nature of hemodialysis (and hemofiltration) conditions the saw-tooth volume fluctuations that drove to conceiving and implementing the concept of a dry weight, corresponding to normal extracellular volume and blood pressure.

Oxidants and antioxidants in long-term haemodialysis patients.

Survival for decades is now possible in end-stage renal disease patients (ESRD) treated with haemodialysis (HD). Long-term survivors may present dialysis-related pathology (DRP). Alterations in lipid metabolism and oxidative stress are recognized as important risk factors that could be prevented or reduced by optimal therapy. We have studied markers of oxidative stress in patients receiving HD treatment for more than 20 years. In order to evaluate a preventive intervention against oxidative damage we measured the factors implied for the prooxidative and antioxidative mechanisms in haemodialysis patients. Ten long-term HD survivors (HD duration: 274.2 months) and ten patients with recent onset of HD (HD duration: 17.8 months), had blood drawn for plasma vitamins A and E, malondialdehyde (MDA), plasma and RBC glutathione peroxidase (GPx), RBC superoxide dismutase (SOD), plasma and erythrocyte glutathione reductase (GSSG-R), oxidized and reduced glutathione (GSH) assessment. Despite normal levels of antioxidant vitamins, an usual finding in this setting, increased MDA, and oxidized GSH, and decreased plasma GPx and reduced GSH show that oxidant stress is markedly present in both recent onset and long-term HD patients. It would appear highly advantageous to reduce complications of long-term dialysis patients with preventing modalities.

[Primary biliary cirrhosis and idiopathic thrombopenic purpura. A new association]. / Cirrhose biliaire primitive et purpura thrombopénique idiopathique. Une association inédite.

A case of primary biliary cirrhosis with stage III histological changes associated with an asymptomatic thrombocytopenic purpura with raised antiplatelet antibody levels is described. This new association of two conditions in which an autoimmune participation is generally accepted suggests a predisposition to this form of disease and/or the intervention of common trigger factors; however, an analysis of known etiological mechanisms does not exclude the possibility of a fortuitous association.

[Renal needle biopsy: a comparative study of fluoroscopic and echographic guidance]. / La ponction-biopsie rénale: étude comparative du guidage fluoroscopique et échographique.

The authors report a comparative study of two renal biopsy procedures: fluoroscopic guided biopsy and ultrasound guided biopsy. Results were similar with an interpretability rate of 90%. Morbidity was found to be equal in the two group. However, ultrasound guided biopsy is superior to fluoroscopy guided biopsy in two respects: for patients with renal failure in whom IVP is not possible; for the medical team and patient, who are not exposed to radiation.

[Emergency vascular access in patients with renal failure. Apropos of 32 implantations of permcath]. / L'abord vasculaire de secours chez l'insuffisant rénal. A propos de 32 implantations de permcath.

Central venous catheters allow for the most rapid hemodialysis procedure with sparing of peripheral blood vessels. 32 flexible, double-lumen "permcath" catheters were implanted to 27 patients over a period spanning 42 months (February 86-August 89). Catheter placement was definitive in 2 cases while another 30 provided previsory intravenous access for plasmapheresis (25 cases), acute renal insufficiency (7 cases), and chronic renal failure (17 cases). The mean utilization time per patient was 10.7 +/- 8.01 (SE) weeks. As respects chronic renal failure, this provided a time-opportunity for prospective maturation of conventional venous routes of access or transplantation. Permcath thrombosis occurred in 6 instances (18.75%), 5 times unremittingly (15.4%). Infection occurred in 6 patients (18.75%), leading to ablation of the permcath only once. Thus, permcath ensures safe, effective access for hemodialysis and enables maturation of a conventional venous cutdown. It may be used directly as a permanent vascular approach in case of limited life expectancy or of an extremely precarious vascular bed.

[The French clinician's guide to the Kidney disease: Improving global outcomes (KDIGO) for chronic kidney disease-mineral and bone disorders (CKD-MBD)]. / L'essentiel des nouvelles recommandations des kidney disease: improving global outcomes (KDIGO) pour les désordres du métabolisme minéral et osseux à l'usage du clinicien francophone.

The new recommendations of "Kidney disease: improving global outcomes" for the definition and classification of chronic kidney disease and mineral and bone disorders were released in August 2009. We report the most important of these recommendations and a brief comment from a clinician's point of view. The main points to be noted with regard to the new recommendations are as follows: serum calcium should be in the normal range; phosphorus concentration should be lowered toward the normal range and serum parathyroid hormone (PTH) levels should be two to nine times the upper limit of the normal range; bone remodelling can be assessed using alkaline phosphatase; the use of calcium-phosphorus (Ca x P) product as an index is not recommended anymore; at any stage of CKD, vitamin D deficiency and insufficiency must be corrected; vascular calcification should be detected in a simple way using lateral abdominal radiography and echocardiography; a bone biopsy should be performed before therapy with bisphosphonates; the prescription of dialysate calcium should be individualized within the range of 1.25-1.5 mmol/l; the phosphate binder (calcium- or non-calcium-based) and the other treatments for secondary hyperparathyroidism should be individualized based on a global strategy. A majority of these recommendations are not based on evidence and their feasibility and relevance need to be assessed.

Prevention of secondary hyperparathyroidism in hemodialysis patients: the key role of native vitamin D supplementation.

Secondary hyperparathyroidism (SHPT) is a frequent complication in chronic kidney disease, especially in hemodialysis (HD) patients. Treatments for SHPT include calcitriol analogues (CA), phosphate binders, cinacalcet (CC), and surgical parathyroidectomy (PTX). This study aimed to assess the incidence and prevalence of SHPT in a single center during the period when native vitamin D (N-VitD) supplementation and CC treatment became available. All incident and prevalent HD patients were prospectively recorded and compared using 3 periods from 2004 to 2005 (period 1), 2006 to 2007 (period 2), and 2008 to 2009 (period 3). SHPT was diagnosed with serum parathyroid hormone (PTH) levels >300 pg/mL or the need for CA, CC, or PTX. Between periods 1 and 3, in incident patients (n=120 and 101), N-VitD prescription increased from 11% to 68% (P<0.0001), CA prescription remained stable (40%), and patients with PTH>300 pg/mL decreased from 40% to 12% (P<0.0001). In prevalent HD patients (n=235), N-VitD treatment increased from 55% to 91% (P<0.0001), whereas treatment with CA decreased from 67% to 17% (P<0.0001). Patients with serum PTH>300 pg/mL decreased from 38% to 13% (P<0.001), whereas patients with PTH<150 pg/mL remained stable (<30%). New CC prescriptions decreased from 45 to 3 (P<0.0001). Since 2004, SHPT has decreased drastically in incident and prevalent HD patients. The preventive role of N-VitD supplementation appears to be obvious and represents one more argument for its general recommendation in CKD patients.