Solenne Pelletier

Nutrition and chronic kidney disease.

The incidence of malnutrition disorders in chronic kidney disease (CKD) appears unchanged over time, whereas patient-care and dialysis techniques continue to progress. Despite some evidence for cost-effective treatments, there are numerous caveats to applying these research findings on a daily care basis. There is a sustained generation of data confirming metabolic improvement when patients control their protein intake, even at early stages of CKD. A recent protein-energy wasting nomenclature allows a simpler approach to the diagnosis and causes of malnutrition. During maintenance dialysis, optimal protein and energy intakes have been recently challenged, and there is no longer an indication to control hyperphosphatemia through diet restriction. Recent measurements of energy expenditure in dialysis patients confirm very low physical activity, which affects energy requirements. Finally, inflammation, a common state during CKD, acts on both nutrient intake and catabolism, but is not a contraindication to a nutritional intervention, as patients do respond and improve their survival as well as do noninflamed patients.

The Relation between Renal Function and Serum Sclerostin in Adult Patients with CKD

BACKGROUND AND OBJECTIVES Sclerostin, a bone antianabolic peptide involved in osteoporosis, is elevated in patients undergoing maintenance dialysis. However, there are no data for patients with early CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Between January and July 2010, serum sclerostin and GFR (calculated by inulin clearance) were measured in 90 patients with CKD. Fasting blood samples were also drawn for determination of calcium, phosphorus, parathyroid hormone, bone alkaline phosphatase, and 25-OH vitamin D. RESULTS Median GFR was 66.5 (interquartile range, 40.0-88.3) ml/min per 1.73 m(2). Median sclerostin level was 53.5 (interquartile range, 37.5-77.2) pmol/L, was higher in patients with a GFR <60 ml/min per 1.73 m(2), and was highest in those with ESRD. Sclerostin levels were significantly more elevated in men than women (P<0.05). An inverse relationship was found between sclerostin and GFR (r=-0.58; P<0.001), and a positive correlation was seen with age (r=0.34; P<0.01) and serum phosphate (r=0.26; P=0.02). In multiple regression analyses, GFR, sex, and serum phosphate were the only variables associated with serum sclerostin (P<0.001). Age lost its relationship with sclerostin level. CONCLUSIONS This is the first study reporting higher serum sclerostin levels starting at CKD stage III. GFR, sex, and serum phosphate were the only measures associated with sclerostin level, suggesting that the effect of age reported in the literature might instead be attributable to the altered renal function in the elderly. Correcting the serum phosphorus level may be associated with lower sclerostin levels.

Control of mineral metabolism and bone disease in haemodialysis patients: which optimal targets?

BACKGROUND There is a high drug treatment burden on patients receiving long-term dialysis therapy. Abnormalities of calcium and phosphate metabolism are associated with increased mortality, and attempts to correct these disturbances may improve survival. METHODS We prospectively evaluated the targets of the currently used Kidney Disease: Improving Global Outcomes (KDIGO) guidelines in 8377 prevalent patients receiving intermittent haemodialysis therapy in France from July 2007 to December 2009. RESULTS Adjusted Cox analyses showed that only one among six targets was predictive of mortality, i.e. a serum intact parathyroid hormone (iPTH) <130 pg/mL. A continuous risk analysis using fractional polynomials showed a 10% increase in hazard ratio (HR) for mortality for a serum phosphate <0.71 (2.2) and >1.98 (6.14) mmol/L (mg/dL), a non-corrected serum calcium <1.59 (6.37) and >2.41 (9.66) mmol/L (mg/dL) and a serum iPTH <100 and >1090 pg/mL. CONCLUSION The findings of our observational study confirm the existence of a grey zone, in which precise biochemical targets are difficult to define, with the exception of avoiding extreme values. Given the absence of intervention trials proving the clinical usefulness of phosphorus control, and pending the results of large clinical trials on the effect of optimal PTH and calcium control on hard outcomes, the present findings may help to refine future recommendations for the treatment of chronic haemodialysis patients.

Mineral and bone metabolism in dialysis: towards unified patient care?

Since the mid-1990s, a tremendous effort has been made to improve the mineral and bone metabolism abnormalities in patients with chronic kidney disease (CKD). In addition to the technological advances in dialysis, (high performance, larger and more biocompatible membranes, and water quality), as well as frequency and duration, many drugs were also launched in a very short span (Figure 1). International guidelines have also attracted the interest and addressed the concerns of physicians in charge of maintenance dialysis patients, and due to the frequent use of new software and informatization of dialysis care, mineral and bone disease management has been considerably improved. However, clinical trials have not been performed quick enough to allow the generation of robust end points such as mortality. It is noticeable that for most of the mineral and bone disorder medications currently being used, 5–15 years after becoming available on the market, no survival benefits have been clearly shown in quality clinical trials. We only rely then on epidemiological reports from which a large number do not present a good methodological structure (retrospective design, missing values, confounding factors, selection biases, etc.). That said, however, from a biological point of view, serum phosphate control has considerably improved these past years. Whereas the first large retrospective studies were published in 1998 analysing data from 1995 [1,2], year for year thereafter, studies showed that the mean serum phosphate had improved from 2.0 to ~1.5 mmol/L in 2008 [2–5]. The December 2009 cross-sectional serum phosphate median value in 9500 French maintenance haemodialysis patients was 1.47 mmol/L, crossing below, for the first time, the symbolic level of 1.50 mmol/L (annual meeting of the Société de Néphrologie and the Société Francophone de Dialyse, Bruxelles, Belgium, 30 September 2010). This fact cannot be ignored, and improving any laboratory abnormality by 25% in less than 15 years is a success story in the medical field. As in other fields (hypertension, coronary artery disease, lipid control, etc.), and in response to a continuous improvement of serum abnormalities towards normal values, it will be more and more difficult to show survival benefits of new drugs, and future trials will have to enrol a much larger number of patients. Mendelssohn and colleagues [5] address four interesting issues in this field: first, they analyze how daily practice can affect laboratory results on a day to day basis level; second, they evaluate medication prescription at the country level, and compare it to prescription in other countries; third, they analyse the role of healthcare budget restriction in patients’ conformity to current guidelines; and fourth, they challenge guidelines if the gap between theory and practice does not improve substantially over time or with the use of new treatments. Numerous kinds of software have been created in order to help physicians gather laboratory data and allow automatic analyses and warnings. Among them, the Photograph software [3] allows the generation of an instant picture of the dialysis unit after entering serum values of phosphate, calcium, parathyroid hormone and phosphocalcic product, among other dialysis and nutritional parameters (see Figure 1 in the paper of Mendelssohn et al. [5]). If the data are entered regularly, e.g. every 3, 6 or 12 months, it allows the physician to compare the unit compliance to the guideline targets and check for improvement over time. This scheme allows self-control of medication prescription, since every physician would want their patients to come closer to the recommendations, and most prospective reports show a continuous improvement in reaching targets (see Figure 2 in the paper of Mendelssohn et al). What would be of additional interest is to see how phosphate and calcium parameters behave in centres which did not use the Photograph software. The second point is the variability in patient care when independent local administrative rules apply. Mendelssohn et al. analysed serum values of mineral metabolism according to the possibility of prescribing drugs with more or less restriction in Canada, and showed that patients were better controlled when less restrictions applied. These variations were associated with differences in prescriptions: serum phosphate was more ‘on target’ when sevelamer was prescribed to more patients (40% in less restricted vs 14% in more restricted areas), whereas this did not have an influence on serum calcium or parathyroid hormone. Cinacalcet, although prescribed in <3% of patients in Canada, may have also had an impact on these results if heterogeneously administered between regions [6]. This report is not really surprising since heterogeneity in drug prescription is high in CKD–MBD: in the recent ECHO

Optimizing bone health in chronic kidney disease

Phosphocalcic metabolism disorders often complicate chronic kidney disease (CKD) and worsen as kidney function declines, with a consequence on bone structural integrity. The risk of fracture exceeds that of the normal population in both patients with pre-dialysis CKD and end-stage renal disease (ESRD). The increasing incidence of CKD, the high mortality rate induced by hip fracture, the decreased quality of life and economic burden of fragility fracture make the renal bone disorders a major problem of public health around the world. Optimizing bone health in CKD patients should be a priority. Bone biopsy is invasive. Dual-energy X-ray absorptiometry, commonly used to screen individuals at risk of fragility fracture in the general population, is not adequate to assess advanced CKD because it does not discriminate fracture status in this population. New non-invasive three-dimensional high-resolution imaging techniques, distinguishing trabecular and cortical bone, appear to be promising in the assessment of bone strength and might improve bone fracture prediction in this population. Therapeutic intervention in the chronic kidney disease-mineral and bone disorders (CKD-MBD) should begin early in the course of CKD to maintain serum concentration of biological parameters involved in mineral metabolism in the normal recommended ranges, prevent the development of parathyroid hyperplasia, prevent extra-skeletal calcifications and preserve skeletal health. In this paper, we review studies of mineral and bone disorders in patients with CKD and ESRD, the utility of current techniques to assess bone health and the preventive and therapeutic strategies for managing CKD-MBD.

Serum sclerostin: relation with mortality and impact of hemodiafiltration

Background The glycoprotein sclerostin (Scl; 22 kDa), which is involved in bone metabolism, may play a role in vascular calcification in haemodialysis (HD) patients. In the present study, we investigated the relation between serum Scl (sScl) and mortality. The effects of dialysis modality and the magnitude of the convection volume in haemodiafiltration (HDF) on sScl were also investigated. Methods In a subset of patients from the CONTRAST study, a randomized controlled trial comparing HDF with HD, sScl was measured at baseline and at intervals of 6, 12, 24 and 36 months. Patients were divided into quartiles, according to their baseline sScl. The relation between time-varying sScl and mortality with a 4-year follow-up period was investigated using crude and adjusted Cox regression models. Linear mixed models were used for longitudinal measurements of sScl. Results The mean (±standard deviation) age of 396 test subjects was 63.6 (±13.9 years), 61.6% were male and the median follow-up was 2.9 years. Subjects with the highest sScl had a lower mortality risk than those with the lowest concentrations [adjusted hazard ratio 0.51 (95% confidence interval, CI, 0.31-0.86, P = 0.01)]. Stratified models showed a stable sScl in patients treated with HD (Δ +2.9 pmol/L/year, 95% CI -0.5 to +6.3, P = 0.09) and a decreasing concentration in those treated with HDF (Δ -4.5 pmol/L/year, 95% CI -8.0 to -0.9, P = 0.02). The relative change in the latter group was related to the magnitude of the convection volume. Conclusions (i) A high sScl is associated with a lower mortality risk in patients with end-stage kidney disease; (ii) treatment with HDF causes sScl to fall; and (iii) the relative decline in patients treated with HDF is dependent on the magnitude of the convection volume.

Exercise Training Alters the Bone Mineral Density of Hemodialysis Patients.

Abstract Marinho, SM, Moraes, C, Barbosa, JEdSM, Eduardo, JCC, Fouqe, D, Pelletier, S, and Mafra, D. Exercise training alters the bone mineral density of hemodialysis patients. J Strength Cond Res 30(10): 2918–2923, 2016—Patients with chronic kidney disease undergoing hemodialysis (HD) frequently present low bone mineral density (BMD), and exercise may be useful for treating bone loss. This study aimed to assess the effects of an intradialytic resistance exercise training program (RETP) on BMD in HD patients. Twenty-one patients were enrolled into 2 groups; 10 patients performed exercise (80.0% men; 46.9 ± 12.1 years; 27.0 ± 3.4 kg·m−2) and 11 patients were in the control group (54.5% men; 50.5 ± 11.5 years; 24.1 ± 8.7 kg·m−2). Dual-energy x-ray absorptiometry was used to measure the BMD, lean mass, and body fat before and after the supervised RETP (performed with elastic bands and ankle cuffs in both lower limbs 3 times a week for 24 weeks—72 sessions). In the exercise group, 30.0% of patients presented with osteopenia and 20.0% osteoporosis and in the control group, 45.5% osteopenia and 36.4% osteoporosis. Only in the exercise group, the osteoporosis percentage was reduced to 10.0% and the femoral neck BMD and T-score improved from 0.89 ± 0.1 to 0.93 ± 0.1 g·cm−2 and from −1.3 ± 0.8 to −1.0 ± 0.8 g·cm−2 (p ⩽ 0.05), respectively, after the intervention. In contrast, these parameters were reduced in the control group. The results suggest that resistance exercise may be useful for improving the BMD in HD patients. In summary, 24 weeks of the supervised RETP played a role in improving the BMD of HD patients.

Immune, metabolic and epidemiological aspects of vitamin D in chronic kidney disease and transplant patients.

Chronic kidney disease strongly impacts on mineral and bone metabolism. Despite numerous medications, the biological targets recommended by international guidelines are often unmet. Among the treatment armamentarium, native or nutritional vitamin D (25OHD3) has been rediscovered in the early 2000s, and its general and specific actions further studied. Effects on bone, immunity, infection prevention, muscle function and phosphocalcic metabolism have been reviewed. Assessment of nutritional vitamin D status showed very low serum 25OHD3 levels and increase in nutritional vitamin D prescription led to improvement in these levels. However, about 45% of adult CKD patients still have insufficient serum 25OHD3 levels. Epidemiological studies should be enforced to describe further the mineral and bone disease management in CKD.

Teenagers and young adults with nephropathic cystinosis display significant bone disease and cortical impairment

BackgroundBone impairment appears to be a novel complication of nephropathic cystinosis despite cysteamine therapy. Its exact underlying pathophysiology is nevertheless unclear. The objective of this study was to evaluate bone status among patients included in the French Crystobs study.MethodsIn addition to clinical data, bone status was evaluated using biomarkers (ALP, PTH, 25-D, 1-25D, FGF23), DXA (spine and total body), and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the tibia and radius. Results were compared to age- and gender-matched healthy controls (1:2 basis) from the local reference cohorts.ResultsAt a median age of 22.5 (10.2–34.6) years, 10 patients with nephropathic cystinosis were included (2 receiving conservative therapies, 2 undergoing hemodialysis, 6 with a past of renal transplantation); 7 out of 10 patients complained of a bone symptom (past of fracture, bone deformations, and/or bone pain). Biochemicals and spine DXA did not show any significant abnormalities. Using HR-pQCT, significant decreases in cortical parameters (e.g., cortical thickness 850 (520–1100) versus 1225 (480–1680) μm; p < 0.05) and total volumetric bone mineral density (290 (233–360) versus 323 (232–406) mg/cm3; p < 0.05) were observed in cystinotic patients in comparison to controls at the tibia. There were no differences for trabecular parameters. Similar results were observed at the radius.ConclusionsIn this pilot study, bone impairment (rather cortical than trabecular) is a significant clinical problem in nephropathic cystinosis; 70% of patients displayed significant bone symptoms, during teenage or young adulthood. This new complication should be known by physicians because of its potential dramatic impact on quality of life.

Membranous glomerulonephritis as a novel paraneoplastic syndrome in a young man with chronic myeloid leukemia

1 Department of Nephrology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-B é nite, France, 2 Department of Paediatric Haemato-oncology, Bristol Royal Hospital for Children, University Hospitals Bristol, Bristol, UK, 3 Pathology department, Hospices Civils de Lyon, H ô pital Edouard Herriot, Lyon, France, 4 Hematology department 1G, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre B é nite & INSERM U1052, CRCL, Lyon, France, 5 Carmen, Cens, Universit é de Lyon, Lyon, France, and 6 Paediatric Haematology, Institut Hematologie et Oncologie Pediatrique, Hospices Civils de Lyon, Groupement Hospitalier Est, France