Increased levels of serum parathyroid hormone and fibroblast growth factor-23 are the main factors associated with the progression of vascular calcification in long-hour hemodialysis patients.

The aim of the present study was to assess the frequency and factors associated with the progression of vascular calcifications (VCs) using a semiquantitative X-ray score. We included all prevalent hemodialysis patients with initial radiological scores ranging from 0 to 3 according to the severity of the VCs. Patients were classified as non-progressors or progressors after 3 years. Among the 85 patients, 44.7% were classified as progressors. Only exhibiting high levels of serum intact parathyroid hormone (PTH, >190 pg/ml) and fibroblast growth factor (FGF)-23 levels (>3,000 RU/ml) is associated with the risk of VC progression (OR 5.8, 95% CI 1.7-19.8, p = 0.004). Calcitriol analogs (38%), cinacalcet (15%), dialysate calcium (mean 1.48 mmol/l), dialysis session time (4-8 h) and calcium- (10%) and non-calcium-based phosphate binders (38%) were prescribed on an individual basis. Hyperphosphatemia (<10%) and, especially, hypercalcemia (1%) and hyperparathyroidism (>585 pg/ml = 0%) were infrequently observed. In conclusion, the main factor associated with VC progression was the association of higher serum PTH and FGF-23 levels. It remains to be seen whether patients should be treated to lower their PTH value, even within the target range, using calcitriol analogs, calcimimetics, parathyroidectomy, or by modifying the Klotho-FGF-23 axis.

[How to deal with those low parathyroid hormone values in dialysis patients?]. / Que faire de ces valeurs d'hormones parathyroïdiennes réputées trop basses chez les patients dialysés ?

BACKGROUND: The target for serum parathyroid (PTH) hormone level in dialysis patients is higher than that in the normal population in order to prevent adynamic bone disease (ABD) that is associated with more frequent cardiovascular and bone disease. Based on biological and clinical data, we aimed at identifying the different types of low PTH (L-PTH) in order to determine the best therapeutic strategies in these patients. METHODS: Between 2004 and 2010, all haemodialysis (HD) patients were assessed. Patients with serum L-PTH (<130pg/mL) were classified into five groups as follows : 'PTX' for patients with a history of parathyroidectomy (PTX); 'HypoMed' for patients with a tendency to hypocalcemia without PTX; 'IatroMed' for patients who had undergone excessive PTH-lowering treatments (calcium, vitamin D, or cinacalcet); 'EndoG' for patients with endogenous hypercalcaemia (immobilization, cancer, or granulomatosis); and 'SponT' for patients with L-PTH without evident causes and with 'normal' biology in most cases. RESULTS: From 520 charts, 163 (31.3 %) L-PTH cases were recorded, with 17.7% of PTX in younger patients with longer dialysis times; 2.4% of HypoMed in older women with high co-morbidities (these two groups needed calcium and vitamin D therapy to prevent hypocalcaemia); 22.6% of IatroMed in diabetic patients receiving excessive PTH-lowering treatments; 3% of EndoG in hypercalcaemic patients, more frequently in the hospitalization ward; and 54% of SponT, more frequently comprising old diabetic patients not receiving PTH-lowering treatment and without biological signs of ABD. Treatment changes were necessary only in cases of IatroMed and EndoG, requiring a lowered prescription of PTH-lowering therapies and the addition of bisphosphonates for EndoG. CONCLUSION: In our HD population, we could identify five types of L-PTH based on medical conditions and biological data. Only two types, i.e. approximately 25% of patients needed therapeutic modifications. For the other patients, L-PTH could be maintained without decreasing the calcium and vitamin D intake that can lead to osteomalacia or administering recombinant PTH 1-34 or calcium-receptor inhibitors that need to be assessed in HD patients.

Total and bone-specific alkaline phosphatases in haemodialysis patients with chronic liver disease.

OBJECTIVE: The Kidney Disease: Improving Global Outcomes "KDIGO" recommends regular sampling of bone turnover markers (BTMs) such as total alkaline phosphatases (t-ALP) and bone-specific alkaline phosphatase (b-ALP) in the case of haemodialysis (HD) patients. DESIGN AND METHODS: We present our results of the regular assessment of t-ALP, b-ALP, and PTH, obtained for existing HD patients with chronic liver disease (LD). RESULTS: 76 prevalent HD patients were examined. Linear regression showed that b-ALP and t-ALP levels were closely related (r²: 0.6; p<0.0001), even when the serum PTH level was <250 pg/mL (r²: 0.56; p<0.001). The b-ALP/t-ALP ratio was 0.07 ± 0.12 and correlated poorly with PTH levels (r²: 0.03; p=0.01). Both b-ALP and t-ALP levels did not correlated with PTH levels. CONCLUSION: Our results did not confirm the KDIGO recommendation for using b-ALP as BTM in the special cases of HD patients with LDs.

[Clinical and biological forms of secondary hyperparathyroidism in dialysis patients]. / Les formes cliniques et biologiques de l'hyperparathyroïdie secondaire en dialyse.

The diagnosis and treatment of hyperparathyroidism (HPT) are not yet well standardized in chronic renal failure patients. The aim of this study was to identify the main types of HPT on the basis of clinical and biological findings in a haemodialysis population. Between 2004 and 2010, all patients undergoing haemodialysis were observed and treated using the same strategy: conventional therapy with vitamin D supplements, phosphate binders, dialysate calcium adjusted to serum parathyroid hormone (PTH) level and calcitriol analogues (CA), along with regular bone marker analysis. Wherever required, cinacalcet (CC) was administered and parathyroidectomy (PTX) was performed. Of the 520 patients, 158 were classified as having HPT (30%) with a serum PTH level greater than 300 pg/mL. From this population, we identified five main types of HPT: (1) HPT with 'no bone impact' had normal or low bone marker levels (n=28, 17.7%); (2) 'secondary' HPT had elevated bone marker levels, but showed favorable response to CT (n=59, 37.7%); (3) 'tertiary' HPT was accompanied with hypercalcemia and required CC or PTX in case of CT failure (n=11, 6.9%); (4) 'mixed' HPT could not be completely treated with CT and required CC or PTX (n=57, 36%); (5) 'resistant' HPT did not show hypercalcemia, but required PTX after CT and CC failure (n=3, 1.8%). CC was prescribed in 51% cases, CA in 76%, and PTX in 7% of cases. We typified HPT on the basis of physiopathology and stages of HPT progression. Further studies on HPT that focus on bone marker levels are required to establish well-defined treatment strategies. In our study, HPT cases did not show uniform findings in Hémodialyse (HD) patients because of the variation in the stages of the disease at the time of diagnosis.

Fluid overload correction and cardiac history influence brain natriuretic peptide evolution in incident haemodialysis patients.

OBJECTIVES: Brain natriuretic peptide (BNP) is a cardiac peptide secreted by ventricle myocardial cells under stretch constraint. Increased BNP has been shown associated with increased mortality in end-stage renal disease patients. In patients starting haemodialysis (HD), both fluid overload and cardiac history are frequently present and may be responsible for a high BNP plasma level. We report in this study the evolution of BNP levels in incident HD patients, its relationship with fluid removal and cardiac history as well as its prognostic value. METHODS: Forty-six patients (female/male: 21/25; 68.6 ± 14.5 years old) surviving at least 6 months after HD treatment onset were retrospectively analysed. Plasma BNP (Chemoluminescent Microparticule ImmunoAssay on i8200 Architect Abbott, Paris, France; normal value < 100 pg/mL) was assessed at HD start and during the second quarter of HD treatment (Q2). RESULTS: At dialysis start, the plasma BNP level was 1041 ± 1178 pg/mL (range: 14-4181 pg/mL). It was correlated with age (P = 0.0017) and was significantly higher in males (P = 0.0017) and in patients with cardiac disease history (P = 0.001). The plasma BNP level at baseline was not related to the mortality risk. At Q2, predialysis systolic blood pressure (BP) decreased from 140.5 ± 24.5 to 129.4 ± 20.6 mmHg (P = 0.0001) and the postdialysis body weight by 7.6 ± 8.4% (P < 0.0001). The BNP level decreased to 631 ± 707 pg/mL (P = 0.01) at Q2. Its variation was significantly correlated with systolic BP decrease (P = 0.006). A high BNP level was found associated with an increased risk of mortality. CONCLUSIONS: Hence, plasma BNP levels decreased during the first months of HD treatment during the dry weight quest. Whereas initial BNP values were not associated with increased mortality risk, the BNP level at Q2 was independently predictive of mortality. Hence, BNP is a useful tool to follow patient dehydration after dialysis start. Initial fluid overload may act as a confounding factor for its value as a prognostic marker because of cardiac disease.

Influence of inflammation on total energy expenditure in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Studies show that inflammation can contribute to an increase in resting energy expenditure in patients with chronic kidney disease; however, findings about total energy expenditure (TEE) have not been reported. The aim of this study was to evaluate the effects of inflammation on TEE and physical activity energy expenditure in hemodialysis (HD) patients. DESIGN: This was a cross-sectional study. SETTING: This study was conducted from Hôpital Edouard Herriot, Lyon, France. PATIENTS: This study included 24 HD patients and 18 healthy subjects. MAIN OUTCOME MEASURE: TEE and step counts were measured over a 7-day period by the SenseWear Pro2 Armband in 24 HD patients (15 patients with C-reactive protein <5 mg/L, aged 67.0 ± 14.7 years, and 9 with C-reactive protein >5 mg/L, aged 69.0 ± 18.0 years) and compared with 18 healthy subjects (62.3 ± 15.3 years). RESULTS: Mean estimated TEE measured with SenseWear Pro2 Armband was significantly lower (25.5 ± 4.1 kcal/kg/day) in patients with inflammation when compared with those without inflammation (32.0 ± 6.7 kcal/kg/day) and with healthy subjects (31.8 ± 7.0 kcal/kg/day) (P = .012). There was a difference in the physical activity (step counts) between patient groups (P < .05). Healthy subjects and patients without inflammation walked more (8,107 ± 5,419 and 6,016 ± 3,752 steps/day, respectively) as compared with patients with inflammation (2,801 ± 2,754 steps/day, P = .001). CONCLUSION: Our findings suggest that patients with inflammation have a lower TEE when compared with healthy subjects and patients without inflammation. TEE is influenced by physical activity because patients with inflammation appear to be less active.

[Treatment of secondary hyperparathyroidism resistant to conventional therapy and tertiary hyperparathyroidism with Cinacalcet: an efficiency strategy]. / Traitement de l'hyperparathyroïdie secondaire, résistante aux thérapeutiques conventionnelles, et de l'hyperparathyroïdie tertiaire par le cinacalcet: une stratégie efficace.

INTRODUCTION: The treatment of secondary hyperparathyroidism (SHPT) in dialysis patients has changed with the introduction of cinacalcet (CC), which represents a medical alternative to surgical parathyroidectomy (PTX). The aim of our study is to prospectively assess the tolerance and efficacy of CC in patients, treated in one centre using long haemodialysis, with SHPT who do not respond to conventional therapy. PATIENTS AND METHODS: We prospectively observed all patients treated with CC between September 2004 and 2009. The characteristics of the patients were compared with that recorded for the patients non treated with CC. Biological factors and the efficacy of the treatment in the patients were compared before (T-0) and after (T-End) CC therapy. The haemodialysis (HD) schedule was 3 x 5 to 3 x 8 h per week. The biological criteria for CC prescription were a serum PTH level greater than 300 pg/ml, calcium level greater than 2.45 mmol/l and bone alkaline phosphatase level greater than 20 microg/l or, in cases of tertiary hyperparathyroidism (THPT), a calcium level greater than 2.55 mmol/l. RESULTS: Eighty-one (14.7%) among the 550 HD patients were treated with CC. As compared to the untreated population, these patients were younger and had higher body mass index (BMI) and higher protein-catabolic rate (nPCR). The treatment failed in 6.1% of the treated patients; 12.3% had severe gastrointestinal side effects and 10% underwent PTX. The treatment was successful in 81.4% patients who were prescribed a mean final CC dosage of 51+/-30 mg/day. Between T-0 and T-End (18+/-15) months), the serum PTH levels decreased by 77%, calcaemia levels decreased by 10% and phosphataemia levels decreased by 14%. Therefore, the percentage of patients with normal biological parameters increased significantly : serum PTH (150-300 pg/ml: 0 to 50%), calcaemia (2.1-2.37 mmol/l: 6 to 77%) and phosphataemia (1.15-1.78 mol/l: 58 to 84%). After 12 months, eight patients (10%) successfully weaned from CC therapy. No episodes of hypocalcaemia (<2.0 mmol/l) occurred. Treatments with alfacalcidol (68 to 40%) and sevelamer (72 to 50%) decreased, treatments with CaCO(3) remained stable (20%), those with native vitamin D increased (55 to 95%). CONCLUSION: The treatment of HD patients having SHPT and THPT with CC and vitamin D derivatives was efficacious and well tolerated in a majority of cases after the failure of conventional therapies. These treatments improved mineral metabolism significantly.

New measurements of energy expenditure and physical activity in chronic kidney disease.

The accurate estimation of total daily energy expenditure (TEE) in chronic kidney patients is essential to allow the provision of nutritional requirements; however, it remains a challenge to collect actual physical activity and resting energy expenditure in maintenance dialysis patients. The direct measurement of TEE by direct calorimetry or doubly labeled water cannot be used easily so that, in clinical practice, TEE is usually estimated from resting energy expenditure and physical activity. Prediction equations may also be used to estimate resting energy expenditure; however, their use has been poorly documented in dialysis patients. Recently, a new system called SenseWear Armband (BodyMedia, Pittsburgh, PA) was developed to assess TEE, but so far no data have been published in chronic kidney disease patients. The aim of this review is to describe new measurements of energy expenditure and physical activity in chronic kidney disease patients.

Un enfoque eficaz de la epidemia de enfermedad renal crónica: la red de salud / An effective approach to the epidemic of chronic renal failure: a health network

La red de salud Tircel (multidisciplinaria y que combina la medicina pública y privada), está destinada a pacientescon insuficiencia renal crónica (IRC) de la ciudad de Lyon y comunidades adheridas, de la región Rhone- Alpes, Francia. Su función es coordinar la detección, el tratamiento y la prevención de la progresión de la IRC. Para ello, participa de acciones de formación de profesionales de la salud y de información al público y a los pacientes;también interviene en estudios de investigaciones médicas o socioeconómicas. El historial clínico de todos los pacientes adheridos está computadorizado, y los profesionalesactuantes tienen acceso al mismo a través de Internet. Se presentan en este estudio los resultados, al cabo de 3años de actividad de la misma. Se observó una disminución de la velocidad de progresión de la IRC, una mejorade la presión arterial diastólica y de los niveles de hemoglobina plasmática (estadísticamente significativos),y una tendencia a la disminución de la proteinuria). En el 82% de los pacientes la función renal (FR) (evaluadacomo aclaramiento de creatinina por fórmula de Cockroft y Gault) permaneció estable, en 10% disminuyó y en el 8% mejoró. En los pacientes que tuvieron al menos 4 valores informados de FR, la velocidad de pérdida de lamisma fue de – 3.47 al/min./año en los 6 primeros meses, y de – 0.13 ml/min./año a partir del año de seguimiento (p=0.026). El número de pacientes que recibieron medicamentos con acción sobre el eje renina angiotensina también se incrementó.Estos resultados confirman los efectos beneficiosos que resultan de estar adheridos a una red de salud destinada abrindar tratamiento por IRC.

An effective approach to the epidemic of chronic renal failure: a health network.The health network TIRCEL (multidisciplinary, that combinesprivate and public medicine structures) is directed to patients with chronic kidney disease (CKD); it is locatedin the city of Lyon and adhered communities, of Rhone- Alpes Region, Francia. The net mission is to coordinatethe detection, treatment and prevention of progression of CKD; to fulfill its mission, it is involved in actions directedto improve health professional formation, to inform the patients and the community, and to intervene in medicaland socio-economic research. The clinical data of all the adhered patients is computadorized, and can be accessedby the involved professional through Internet. After three years of running, a reduction in the speed of CKD’s progression, as well as diastolic arterial pressure, and an increase in the levels of plasmatic hemoglobin (allstatistically significant) were observed. Renal function (RF) stayed without modifications in 82% of the patients,deteriorated in 10% and improved in 8%. In patients in whom, al least, 4 determinations of RF, estimated throughCockroft & Gault formula, were done, the deterioration was – 3.47 ml/min/year during the first 6 months, and – 0.13 ml/min/year alter 1 year of follow-up (p=0.026). A tendency to a reduction of proteinuria was observedtoo, as well as an increase in the number of patients that received drugs acting over the renin angiontensin axis.These facts confirmed the benefits obtained through patient’s adhesion to a multidisciplinary health net directedto the treatment of CKD.

Un enfoque eficaz de la epidemia de enfermedad renal crónica: la red de salud / An effective approach to the epidemic of chronic renal failure: a health network

La red de salud Tircel (multidisciplinaria y que combina la medicina pública y privada), está destinada a pacientescon insuficiencia renal crónica (IRC) de la ciudad de Lyon y comunidades adheridas, de la región Rhone- Alpes, Francia. Su función es coordinar la detección, el tratamiento y la prevención de la progresión de la IRC. Para ello, participa de acciones de formación de profesionales de la salud y de información al público y a los pacientes;también interviene en estudios de investigaciones médicas o socioeconómicas. El historial clínico de todos los pacientes adheridos está computadorizado, y los profesionalesactuantes tienen acceso al mismo a través de Internet. Se presentan en este estudio los resultados, al cabo de 3años de actividad de la misma. Se observó una disminución de la velocidad de progresión de la IRC, una mejorade la presión arterial diastólica y de los niveles de hemoglobina plasmática (estadísticamente significativos),y una tendencia a la disminución de la proteinuria). En el 82% de los pacientes la función renal (FR) (evaluadacomo aclaramiento de creatinina por fórmula de Cockroft y Gault) permaneció estable, en 10% disminuyó y en el 8% mejoró. En los pacientes que tuvieron al menos 4 valores informados de FR, la velocidad de pérdida de lamisma fue de ¹ 3.47 al/min./año en los 6 primeros meses, y de ¹ 0.13 ml/min./año a partir del año de seguimiento (p=0.026). El número de pacientes que recibieron medicamentos con acción sobre el eje renina angiotensina también se incrementó.Estos resultados confirman los efectos beneficiosos que resultan de estar adheridos a una red de salud destinada abrindar tratamiento por IRC. (AU)

An effective approach to the epidemic of chronic renal failure: a health network.The health network TIRCEL (multidisciplinary, that combinesprivate and public medicine structures) is directed to patients with chronic kidney disease (CKD); it is locatedin the city of Lyon and adhered communities, of Rhone- Alpes Region, Francia. The net mission is to coordinatethe detection, treatment and prevention of progression of CKD; to fulfill its mission, it is involved in actions directedto improve health professional formation, to inform the patients and the community, and to intervene in medicaland socio-economic research. The clinical data of all the adhered patients is computadorized, and can be accessedby the involved professional through Internet. After three years of running, a reduction in the speed of CKDs progression, as well as diastolic arterial pressure, and an increase in the levels of plasmatic hemoglobin (allstatistically significant) were observed. Renal function (RF) stayed without modifications in 82% of the patients,deteriorated in 10% and improved in 8%. In patients in whom, al least, 4 determinations of RF, estimated throughCockroft & Gault formula, were done, the deterioration was ¹ 3.47 ml/min/year during the first 6 months, and ¹ 0.13 ml/min/year alter 1 year of follow-up (p=0.026). A tendency to a reduction of proteinuria was observedtoo, as well as an increase in the number of patients that received drugs acting over the renin angiontensin axis.These facts confirmed the benefits obtained through patients adhesion to a multidisciplinary health net directedto the treatment of CKD. (AU)

[Role of health networks in the screening and management of chronic kidney disease]. / Rôle des réseaux de santé dans le dépistage et la prise en charge de la maladie rénale chronique.

Chronic kidney disease is a public health problem in terms of both the number of patients treated with dialysis or transplantation and the cost of renal replacement therapies, and the excess cardiovascular risk associated with it even at earliest stages. The population of people with chronic renal insufficiency (defined by a glomerular filtration rate<60 mL/min) and therefore exposed to the risk of progression towards end-stage renal failure and excess cardiovascular risk includes roughly 5% of the general population. There are currently effective treatments to slow the progression of chronic kidney disease, delay or avoid dialysis, and prevent cardiovascular events. These treatments are most effective when begun earliest and when followed by professionals aware of the risk factors and the intermediate efficacy criteria: blood pressure, proteinuria, diet, anemia, etc. (Anaes, 2004). Screening for chronic kidney disease is currently facilitated by the routine estimate of creatinine clearance with Cockcroft's formula at every serum creatinine assay (Anaes, 2002). Nephrologists play an essential role when kidney disease is discovered, for it is they who must recognize diseases related to specific treatments and thus to define the long-term risk prevention strategy. Chronic kidney disease develops over years, during which time the patient will see a variety of different healthcare professionals. The transmission of medical information between them is a prerequisite for the continuity of nephroprotective treatment, the prevention of avoidable causes of aggravation (drugs, contrast products, etc.), and the quality of preparation for substitution treatment and transplantation. Because of late referral to nephrologists and insufficient information, an elevated proportion (about 40%) of patients start dialysis in emergency conditions, which reduces their chance of maintaining their independence and using a home-based dialysis method. The system of health networks should provide responses particularly appropriate to the needs of patients with chronic kidney disease. In particular, these networks promote continued medical education, consistent and thorough patient information, and evaluation of practices (HAS, 2006).

[Differences in cardiac troponin I and T levels measured in asymptomatic hemodialysis patients with last generation immunoassays]. / Comparaison des taux de troponines cardiaques I et T mesurés chez des patients hémodialysés asymptomatiques selon différents immunodosages de dernière génération.

Previous studies reported cardiac troponin I (cTnI) and T (cTnT) levels to be higher than normal in a significant proportion of asymptomatic chronic hemodialysis (HD) patients without evidence of acute myocardial injury. We have therefore evaluated in such patients the accuracy of cTnI and cTnT determinations measured with last generation assays. Fifty chronic HD patients (34 males) without symptoms of acute myocardial ischemia were studied. Their mean age (+/-SD) was 64.4+/-12.7 years, 22 patients (44%) had an history of cardiac ischemic disease and 19 (38%) were diabetics. Serum cardiac markers were measured with last generation assays before and after a single HD session and in a control group including 30 hospitalized patients without renal failure. The cTnI were determined with Dimension RxL "Improved method" assay (Dade Behring), the cTnT with Elecys "Third generation" assay (Roche Diagnostics) and the creatine kinase (CK) with Integra (Roche Diagnostics). The cTnI were also simultaneously determined with the assay previously used at our institution (Dimension RxL, Dade Behring), indicated as old-method-cTnI. With the last generation assay only 1 patient (2%) had elevated cTnI (>0.1 microg/l) in the study group compared to none in the control group (P=NS). Instead, with the old-method-cTnI assay 11 patients (22%) had elevated (>0.3 microg/l) predialysis cTnI levels (P<0.01 compared to the "Improved method" assay). The predialysis cTnT levels were higher than normal (>0.1 microg/l) in 23 patients (46%), compared to none in the control group (P<0.01). The CK levels were elevated (>170 IU/L) in 4 dialysis patients (8%) compared to one (3,3%) in the control group (P=NS). The cTnT levels slightly but non-significantly diminished during dialysis (from 0.102+/-0.070 to 0.085+/-0.067 mug/l, P=NS), while in the same time no changes were observed for cTnI and CK levels. In conclusion, the specificity of cTnI determinations in HD patients is greatly improved by the last generation assay (from 78 to 98%), and is actually similar to that observed in a population with normal renal function. Therefore cTnI, determined with the last generation assay used in the present study, can be reliably used for the diagnosis of acute coronary syndromes in HD patients. Instead, cTnT levels remain higher than normal in a significant proportion of asymptomatic HD patients (46%) and the reasons for this fact need further investigations.