[How to manage arterial hypertension in 2024 to optimize cardiorenal protection]. / Comment prendre en charge une hypertension artérielle en 2024 pour optimiser la protection cardio-rénale.

The latest guidelines for the management of arterial hypertension, the silent killer, were published in summer 2023. They particularly emphasize again the quality of blood pressure measurement which ideally should always be automated using oscillometric device and an arm cuff already in the consulting room. They remind you how to manage the blood pressure of a patient whose hypertension has been confirmed, to stimulate drug compliance and to avoid therapeutic inertia. A holistic view of the patient with all his or her risk factors is always required. The general practitioner is the key player in the diagnosis, treatment and monitoring of the hypertensive patient whose therapeutic education has been as complete as possible with practice of self-measurement of blood pressure at home if possible. The goal is to normalize blood pressure within the first three months of treatment initiation and to reduce as much as possible the cardiovascular risk of the treated patient in the frame of preventive medicine.

Les dernières directives de prise en charge de l'hypertension artérielle, le tueur silencieux, ont été publiées à l'été 2023. Elles insistent particulièrement, à nouveau, sur la qualité de la mesure de la pression artérielle qui, idéalement, doit être automatisée toujours à l'aide d'un brassard et ce, déjà au cabinet de consultation. Elles rappellent comment gérer la pression artérielle d'un patient dont l'hypertension a bien été confirmée, comment stimuler l'adhérence au traitement et éviter l'inertie thérapeutique. Une vue globale du patient avec tous ses facteurs de risque est toujours de rigueur. Le médecin généraliste est l'acteur-clé du diagnostic, du traitement et du suivi du patient hypertendu dont l'éducation thérapeutique a été la plus complète possible avec pratique de l'automesure tensionnelle à domicile si possible. Le but est de normaliser la pression artérielle dans les trois premiers mois de la prise en charge et de réduire le plus possible le risque cardiovasculaire et rénal du patient traité dans le cadre d'une médecine préventive.

[Functional disorder and arterial hypotension]. / Les troubles fonctionnels et l'hypotension artérielle constitutionnelle.

Arterial hypotension discovery (blood pressure < 110/60 mmHg for man and < 100/60 mmHg for woman) on the occasion of medical appointments for faintness is often considered as the cause of the medical problem. That causal relationship is yet far from being always established. If a disease is identified generating arterial hypotension, the symptoms reported such as loss of energy, fatigue and/or depressive mood can of course be the consequence. However, asymptomatic chronic hypotension exists. Symptoms appearance in a hypotensive patient such as fatigue, loss of vital energy, alteration of quality of life must lead to look for another explanation than (chronic) low blood pressure. This article will discuss that point.

La découverte d'une hypotension artérielle (pression artérielle < 110/60 mmHg chez l'homme et < 100/60 mmHg chez la femme) lors de consultations pour malaise est souvent considérée comme la cause du problème médical. Cette relation causale est, cependant, loin d'être toujours établie. Si une pathologie est identifiée créant une hypotension, les symptômes rapportés comme la perte d'énergie, la fatigue et/ou l'humeur dépressive peuvent, bien sûr, en être la conséquence. Cependant une hypotension chronique asymptomatique existe. L'apparition de symptômes, chez un sujet hypotendu préalablement, tels que fatigue, perte d'élan vital, altération de la qualité de vie, doit faire rechercher une autre raison que la baisse (chronique) de la pression artérielle. Cet article va discuter cette problématique.

[Blood pressure variability : useful, trivial or potentially dangerous ?] / La variabilité tensionnelle : utile, futile ou potentiellement dangereuse ?

Usually, blood pressure variability is an adaptive physiological process allowing optimal perfusion of internal organs every time and in every clinical situation. This variability may nevertheless be excessive and then be associated with a poor cardiovascular and renal but also neurological prognosis. An excess in blood pressure variability may also be responsible for unpleasant symptoms in some patients. The different types of blood pressure variability, their causes and consequences as well as the mean to improve its control will be discussed in this article.

La variabilité tensionnelle est habituellement un processus physiologique adaptatif permettant une perfusion optimale des organes internes en tout temps et en toute situation clinique. Cette variabilité peut néanmoins être excessive, ce qui est associé à un mauvais pronostic cardiovasculaire et rénal, mais aussi neurologique. Une variabilité tensionnelle excessive peut également être responsable d'une symptomatologie gênante chez certains patients. Les différents types de variabilité tensionnelle, leurs causes et conséquences ainsi que la manière de mieux la contrôler seront discutés dans cet article.

Estimating urine albumin to creatinine ratio from protein to creatinine ratio using same day measurement: validation of equations.

OBJECTIVES: Severity of chronic kidney disease is defined by glomerular filtration rate (GFR) and albuminuria (ACR) by the KDIGO and are related to cardiovascular outcomes and end-stage-kidney-failure. However, proteinuria (PCR) is more often available than ACR in records. Recently, equations were developed to estimate ACR from PCR. We investigated their performances in our population. METHODS: In the academic medical hospital of Liège, we retrospectively analysed same day measurement of ACR and PCR and staged them according to the KDIGO A1-A2-A3 categories. Analyser Roche Cobas (R) gathered 2,633 urinalysis (May 2018-May 2019) and analyser Abbott Alinity (A) 2,386 urinalysis (May 2019-March 2020). We compared the KDIGO staging of mACR and eACR obtained from Weaver's and Sumida's equations. RESULTS: Median age was 63 [52;71]/64 [53;72] years old, 43/42% were female; 78/74% had diabetes; proportion of mACR-A1 was 65.6%/64.2%, A2 was 25.5%/25.5% and A3 was 8.8%/10.3% (Method R/A, respectively). Both equations gave similar distribution of KDIGO staging of eACR. Overall agreements were higher than 88% regardless of the analyser or of the equation. Performances in between equations were equivalent according to the multi-level AUC (multinomial logistic regression model). CONCLUSIONS: Good concordance was observed between mACR and eACR regardless of the equation or of the analyser. No patient with an A3-measured ACR was estimated within the KDIGO A1 category. Though ACR should be measured when clinically needed, it may be reasonably estimated from the PCR through these equations, for epidemiologic retrospective studies or research purposes.

Does kidney transplantation with a standard or expanded criteria donor improve patient survival? Results from a Belgian cohort.

BACKGROUND: Changes in recipient and donor factors have reopened the question of survival benefits of kidney transplantation versus dialysis. METHODS: We analysed survival among 3808 adult Belgian patients waitlisted for a first deceased donor kidney transplant from 2000 to 2012. The primary outcome was mortality during the median waiting time plus 3 years of follow-up after transplantation or with continued dialysis. Outcomes were analysed separately for standard criteria donor (SCD) and expanded criteria donor (ECD) kidney transplants. We adjusted survival analyses for recipient age (20-44, 45-64 and ≥65 years), sex and diabetes as the primary renal disease. RESULTS: Among patients ≥65 years of age, only SCD transplantation provided a significant survival benefit compared with dialysis, with a mortality of 16.3% [95% confidence interval (CI) 13.2-19.9] with SCD transplantation, 20.5% (95% CI 16.1-24.6) with ECD transplantation and 24.6% (95% CI 19.4-29.5) with continued dialysis. Relative mortality risk was increased in the first months after transplantation compared with dialysis, with equivalent risk levels reached earlier with SCD than ECD transplantation in all age groups. CONCLUSIONS: The results of this study suggest that older patients might gain a survival benefit with SCD transplantation versus dialysis, but any survival benefit with ECD transplantation versus dialysis may be small.

Performance of creatinine- or cystatin C-based equations to estimate glomerular filtration rate in sub-Saharan African populations.

Glomerular filtration rate (GFR) is the best index for kidney function; however, the applicability of GFR estimating equations in sub-Saharan African populations remains unclear. In a cross-sectional study of adults living in Kinshasa, Democratic Republic of Congo (n=210) and Abidjan, Ivory Coast (n=284), we evaluated the performance of creatinine and cystatin C-based equations using plasma clearance of iohexol as the reference standard. The race coefficient did not improve the performance of creatinine-based GFR estimates; in fact, both the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology (CKD-EPI) equations performed better without the race coefficient in participants with GFR ≥60 mL/min/1.73m2. The CKD-EPI and Full Age Spectrum (FAS) equations were unbiased and had similar precision (SD of 17.9 versus 19 mL/min/1.73 m2) and accuracy within 30% (P30, 86.7% versus 87.4%) in participants with GFR ≥60 mL/min/1.73m2. Both equations performed poorly in the subgroup with measured GFR < 60 mL/min/1.73m2 (n=80), but the FAS equation had smaller bias (-4.8 mL/min/1.73m2 versus -7.7 mL/min/1.73m2 for CKD-EPI) and higher P30 (56.3% versus 31.3% for CKD-EPI). The corresponding equations including cystatin C alone or in combination with creatinine had similar performance. In a sub-Saharan African population, adjustment for race did not improve the performance of GFR estimating equations. The creatinine-based FAS and CKD-EPI equations performed reasonably well and were comparable when GFR was ≥ 60 mL/min/1.73m2. Cystatin C did not improve performance. The FAS equation may be preferable when GFR is < 60 mL/min/1.73m2, but this should be confirmed in larger studies.

Myostatin and Insulin-Like Growth Factor 1 Are Biomarkers of Muscle Strength, Muscle Mass, and Mortality in Patients on Hemodialysis.

OBJECTIVE: Muscle strength is frequently altered in hemodialysis patients. In the present work, five potential muscle biomarkers have been studied in their ability to assess muscular strength, muscular mass and to predict mortality of hemodialysis patients: activin-A, procollagen III N-terminal peptide, follistatin, myostatin and insulin-like growth factor-1 (IGF-1). DESIGN AND METHODS: Three independent cohorts of prevalent hemodialysis patients (2 from Liège, Belgium and 1 from Marseille, France) were considered in this observational prospective study. The biomarkers were first measured in the Liege1 cohort. Two of them, myostatin and IGF-1, were then assessed in the whole population of patients (Liege1, Liege2 and Marseille). Muscle strength was assessed with handgrip strength (HGS) and muscle mass with bioimpedance analysis. One-year mortality predictive value of biomarkers was also studied in the Liège1 and Marseille cohorts. RESULTS: In the Liège1 cohort (n=67), HGS was only associated with concentrations of myostatin and IGF-1. These associations were confirmed in the whole population of 204 patients (r=0.37, P<0.001 and r=0.46, P<0.001, respectively) and remained significant (P<0.05) in multivariable models. The association between muscle mass and concentrations of myostatin and IGF-1were also significant. The ability of myostatin, IGF-1 and serum creatinine to detect a low HGS compared by Receiver Operating Characteristic curves analysis were not significantly different. Both myostatin and IGF-1 had a significant and comparable area under the curve to predict one-year mortality: 0.73 (95% CI: 0.64 to 0.83) and 0.72 (95% CI: 0.61 to 0.82), respectively. CONCLUSION: Our results suggest that myostatin and IGF-1 are two biomarkers of interest to assess muscle status of dialysis patients. Both biomarkers are associated with HGS, muscular mass, and one-year mortality.

What we need to know about lipid-associated injury in case of renal ischemia-reperfusion.

Renal segmental metabolism is reflected by the complex distribution of the main energy pathways along the nephron, with fatty acid oxidation preferentially used in the cortex area. Ischemia/reperfusion injury (IRI) is due to the restriction of renal blood flow, rapidly leading to a metabolic switch toward anaerobic conditions. Subsequent unbalance between energy demand and oxygen/nutrient delivery compromises kidney cell functions, resulting in a complex inflammatory cascade including the production of reactive oxygen species (ROS). Renal IRI especially involves lipid accumulation. Lipid peroxidation is one of the major events of ROS-associated tissue injury. Here, we briefly review the current knowledge of renal cell lipid metabolism in normal and ischemic conditions. Next, we focus on renal lipid-associated injury, with emphasis on its mechanisms and consequences during the course of IRI. Finally, we discuss preclinical observations aiming at preventing and/or attenuating lipid-associated IRI.

Sclerostin and chronic kidney disease: the assay impacts what we (thought to) know.

Background: Sclerostin, a 22-kDa protein secreted by osteocytes, acts as a potent inhibitor of osteoblast activity. In chronic kidney disease (CKD), sclerostin is a putative driver of the bone-vascular axis. However, large discrepancies between sclerostin assays have been described. Methods: We compared four different assays [Biomedica (BM), TecoMedical (TE), R&D (RD) and MesoScaleDiscovery (MSD)] in an analytical study and addressed the question whether bioassay choice affects the correlation between circulating sclerostin and clinical and biochemical determinants. Circulating sclerostin levels were determined in 39 prevalent dialysis patients and 82 non-dialysis patients referred for glomerular filtration rate measurement. Results: In the 82 non-dialysis patients, we observed large differences in median (interquartile range) sclerostin concentrations (in pg/mL): BM, 984 [interquartile range (IQR) 648]; TE, 629 (IQR 237); RD, 154 (IQR 84) and MSD, 36 (IQR 19). The concordance correlation coefficient between assays was poor (0.1-0.44). The same discrepancies were observed in dialysis patients. A significant negative rank correlation was found between glomerular filtration rate and sclerostin measured by BM and TE but not by MSD and RD. Associations between sclerostin and age, gender, weight or parathormone were also different according to the assay considered. Conclusions: Clinical inference relating sclerostin levels found in the general, CKD and dialysis populations is largely influenced by the assay used to measure this biomarker.

[Screening and management of metabolic acidosis in patients with chronic kidney disease]. / Intérêt du dépistage et du traitement de l'acidose métabolique chez l'insuffisant rénal chronique.

Metabolic acidosis is a frequent and early biological abnormality of chronic kidney disease (CKD). Chronic metabolic acidosis affects the global homeostasis of the human body, including the metabolism of bone and muscles. Numerous studies have proved a causal relationship between metabolic acidosis and accelerated CKD progression. Hence, the measure of serum bicarbonate level should be part of the systematic follow-up of CKD patients of whom glomerular filtration rate decreases below 50 ml/min/1.73m². Both screening and treatment of metabolic acidosis are easy and cheap. Correcting metabolic acidosis, namely by the daily administration of sodium bicarbonate, helps slow down kidney decline.

L'acidose métabolique est une anomalie biologique fréquente et précoce de l'insuffisance rénale chronique (IRC). Les complications liées à cet état sont multiples et touchent notamment l'os, le muscle et le métabolisme protidique, sans parler du risque accru d'hyperkaliémie. Une causalité entre acidose métabolique et accélération du déclin rénal a été démontrée. La mesure du taux de bicarbonate sérique doit, dès lors, faire partie du suivi biologique systématique du patient en IRC dont le taux de filtration glomérulaire s'abaisse en dessous de 50 ml/min/1,73 m². Le dépistage et le traitement de l'acidose métabolique sont en effet simples et peu coûteux. La correction de l'acidose métabolique, notamment par le bicarbonate de sodium, permet de ralentir la progression de l'insuffisance rénale.

The closure of arteriovenous fistula in kidney transplant recipients is associated with an acceleration of kidney function decline.

Background: The creation of arteriovenous fistula (AVF) may retard chronic kidney disease progression in the general population. Conversely, the impact of AVF closure on renal function in kidney transplant recipients (KTRs) remains unknown. Methods: From 2007 to 2013, we retrospectively categorized 285 KTRs into three groups: no AVF (Group 0, n = 90), closed AVF (Group 1, n = 114) and left-open AVF (Group 2, n = 81). AVF closure occurred at 653 ± 441 days after kidney transplantation (KTx), with a thrombosis:ligation ratio of 19:95. Estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease equation. Linear mixed models calculated the slope and intercept of eGFR decline versus time, starting at 3 months post-KTx, with a median follow-up of 1807 days (95% confidence interval 1665-2028). Results: The eGFR slope was less in Group 1 (-0.081 mL/min/month) compared with Group 0 (-0.183 mL/min/month; P = 0.03) or Group 2 (-0.164 mL/min/month; P = 0.09). Still, the eGFR slope significantly deteriorated after (-0.159 mL/min/month) versus before (0.038 mL/min/month) AVF closure (P = 0.03). Study periods before versus after AVF closure were balanced to a mean of 13.5 and 12.5 months, respectively, with at least 10 observations per patient ( n = 99). Conclusions: In conclusion, a significant acceleration of eGFR decline is observed over the 12 months following the closure of a functioning AVF in KTRs.

IgG4-related membranous glomerulonephritis and generalized lymphadenopathy without pancreatitis: a case report.

BACKGROUND: IgG4-related disease is a recently described pathologic entity. This is the case of a patient with nephrotic syndrome and lymphadenopathy due to IgG4-related disease. Such a kidney involvement is quite peculiar and has only been described a few times recently. Renal biopsy showed a glomerular involvement with membranous glomerulonephritis in association with a tubulo-interstitial nephropathy. Moreover, the patient was not suffering from pancreatitis. CASE PRESENTATION: The patient is a middle-aged man of Moroccan origin. He has developed recurrent episodes of diffuse lymphadenopathies, renal failure and nephrotic syndrome. Renal biopsies showed membranous glomerulonephritis. DISCUSSION AND CONCLUSION: The diagnostic approach of this atypical presentation is discussed in this case report as well as diagnostic criteria, therapeutic strategies, biomarkers and pathophysiology of IgG4-related disease. IgG4-related membranous glomerulonephritis is a well-established cause of membranous glomerulonephritis. It must be sought after in every patient with a previous diagnosis of IgG4-related disease and in every patient with this histological finding on renal biopsy. Corticoids are still the first-line treatment of IgG4-related disease. New therapeutic strategies are needed to avoid glucocorticoids long term side-effects. Interestingly, the patient was prescribed cyclophosphamide in addition to glucocorticoids for an immune thrombocytopenia. This treatment had a very good impact on his IgG4-related disease.

Implications of the calcium-sensing receptor in ischemia/reperfusion.

The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) which was first isolated from bovine parathyroid glands. Its complex structure has been well characterized, which helped to better understand its function. The CaSR activity can be modulated by various ligands, either activators (also called "calcimimetics") or inhibitors (or "calcilytics"). The main role of the CaSR concerns Ca2+ homeostasis. In bone, intestine and kidney, the CaSR acts as a sensor for extracellular ionized Ca2+ concentration ([Ca2+]e) to keep it stable. Such a homeostatic function is well illustrated by human inherited diseases caused by mutations in CASR gene, characterized by Ca2+ balance disturbances. Interestingly, the CaSR is also expressed in numerous tissues which are not directly involved in Ca2+ regulation. There, the CaSR has been implicated in regulatory pathways, including cell proliferation, differentiation and apoptosis. Moreover, recent observations suggest that the CaSR may be involved in ischaemia/reperfusion (I/R) cascades. In cardiomyocytes, the expression and activation of the CaSR are significantly induced at the time of I/R, which induces apoptotic pathways. Likewise, the activation of the CaSR in I/R in brain, liver and kidney has been associated with increased cell death and aggravated structural and functional damage. The present review summarizes these observations and hypothesizes a novel therapeutic option targeting the CaSR in I/R.

[Proton-pump inhibitors and risk of kidney disease]. / Inhibiteurs de la pompe à protons et risque d'insuffisance rénale.

Regarded as safe and effective for management of upper peptic ulcer disease due to gastric acid secretion, the proton pump inhibitors are among the most commonly prescribed drugs. Their use, however, is not without concerns. Acute kidney injury, mainly due to acute interstitial nephritis, could happen 1.5 to 2 times more frequently when using these drugs. Moreover, a risk for chronic kidney disease has also be noted with proton pump inhibitor use (1.15 to 1.8 increased risk), although biases may exist due to confounding factors related to the observational nature of the studies. So, caution is required before available results from good prospective randomized studies are available. Renal function should be checked when using these medications and timely cessation should be advised when there is no more clear indication for use.

Considérés comme sûrs et efficaces dans le traitement des pathologies gastroduodénales liées à une sécrétion acide, les inhibiteurs de la pompe à protons (IPP) sont très souvent prescrits. Ils ne sont pas sans danger. L'insuffisance rénale aiguë, notamment due à la néphrite interstitielle aiguë, surviendrait 2 à 3 fois plus souvent avec la prise de ces médicaments. Par ailleurs, un risque possible, multiplié par 1,15 à 1,75, d'insuffisance rénale chronique est aussi apparu. Des biais liés au caractère observationnel des études d'où proviennent ces données peuvent exister. Il est cependant conseillé d'être prudent avec la prescription de ces médicaments en attendant les résultats d'études randomisées de qualité et de surveiller la fonction rénale. Il faut rester vigilant et arrêter les IPP dès que l'indication de leur utilisation n'est plus évidente.

Creatinine-based equations for the adjustment of drug dosage in an obese population.

AIM: For drug dosing adaptation, the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend using estimated glomerular filtration rate (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, after 'de-indexation' by body surface area (BSA). In pharmacology, the Cockcroft-Gault (CG) equation is still recommended to adapt drug dosage. In the context of obesity, adjusted ideal body weight (AIBW) is sometimes preferred to actual body weight (ABW) for the CG equation. The aim of the present study was to compare the performance of the different GFR-estimating equations, non-indexed or de-indexed by BSA for the purpose of drug-dosage adaptation in obese patients. METHODS: We analysed data from patients with a body mass index (BMI) higher than 30 kg m(-2) who underwent a GFR measurement. eGFR was calculated using the CKD-EPI and Modification of Diet in Renal Disease (MDRD) equations, de-indexed by BSA, and the CG equation, using either ABW, AIBW or lean body weight (LBW) for the weight variable and compared with measured GFR, expressed in ml min(-1). RESULTS: In our population of obese patients, use of the AIBW instead of the ABW in the CG equation, markedly improved the overall accuracy of this equation [57% for CGABW and 79% for CGAIBW (P < 0.05)]. For high BMI (over 40 kg m(-2)), the accuracy of the CG equations is no different when using LBW than when using AIBW. The MDRD and CKD-EPI equations de-indexed by the BSA also performed well, with an overall higher accuracy for the MDRD de-indexed equation [(80% and 76%, respectively (P < 0.05)]. CONCLUSIONS: The de-indexed MDRD equation appeared to be the most suitable for estimating the non-indexed GFR for the purpose of drug dosage adaptation in obese patients.

Incidence and outcomes of acute kidney injury after cardiac surgery using either criteria of the RIFLE classification.

BACKGROUND: Adult cardiac surgery is significantly associated with the development of acute kidney injury (AKI). Still, the incidence and outcomes of AKI vary according to its definition. Our retrospective monocentric study comparatively investigates the yield of RIFLE definition, which is based on the elevation of serum creatinine levels (SCr) or the reduction of urine output (UO), taking into account only one or both criteria. Pre- and per-operative risk factors for post-operative AKI were evaluated. METHODS: All adult patients undergoing cardiac surgery, with or without cardiopulmonary bypass, from April 2008 to March 2009 were included. Clinical, biological and surgical features were recorded. Baseline serum creatinine was determined as its value on day 7 before surgery. Post-operative AKI was diagnosed and scored based upon the highest serum creatinine and/or the lowest urine output. RESULTS: 443 patients (Male/Female ratio, 2.3; median age, 69y) were included, with 221 (49.9%) developing postoperative AKI. Elevated serum creatinine (AKISCr) and oliguria (AKIUO) was observed in 9.7% and 40.2%, respectively. AKI patients had a significantly higher BMI and baseline SCr. In comparison to AKIUO, AKISCr mostly occurred in patients with co-morbidities, and was associated with an increased mortality at 1-year post surgery. CONCLUSIONS: The use of standard RIFLE definition of AKI in a cohort of 443 patients undergoing cardiac surgery resulted in an incidence reaching 50%. Still, significant discrepancies were found between AKISCr and AKIUO regarding the incidence and outcomes. In line with previous reports, our data questions the utility of urine output as a criterion for AKI diagnosis and management after cardiac surgery.

Mesenchymal stromal cell therapy in conditions of renal ischaemia/reperfusion.

Acute kidney injury (AKI) represents a worldwide public health issue of increasing incidence, with a significant morbi-mortality. AKI treatment mostly relies on supportive manoeuvres in the absence of specific target-oriented therapy. The pathophysiology of AKI commonly involves ischaemia/reperfusion (I/R) events, which cause both immune and metabolic consequences in renal tissue. Similarly, at the time of kidney transplantation (KT), I/R is an unavoidable event which contributes to early graft dysfunction and enhanced graft immunogenicity. Mesenchymal stromal cells (MSCs) represent a heterogeneous population of adult, fibroblast-like multi-potent cells characterized by their ability to differentiate into tissues of mesodermal lineages. Because MSC have demonstrated immunomodulatory, anti-inflammatory and tissue repair properties, MSC administration at the time of I/R and/or at later times has been hypothesized to attenuate AKI severity and to accelerate the regeneration process. Furthermore, MSC in KT could help prevent both I/R injury and acute rejection, thereby increasing graft function and survival. In this review, summarizing the encouraging observations in animal models and in pilot clinical trials, we outline the benefit of MSC therapy in AKI and KT, and envisage their putative role in renal ischaemic conditioning.

Clinical and biological determinants of sclerostin plasma concentration in hemodialysis patients.

BACKGROUND: Sclerostin is a potent inhibitor of bone formation, but the meaning of its serum levels remains undetermined. We evaluated the association between sclerostin levels and clinical or biological data in hemodialyzed patients (HD), notably parathormone (PTH), biomarkers of bone turnover, vascular calcifications and mortality after 2 years. METHODS: 164 HD patients were included in this observational study. The calcification score was assessed with the Kauppila method. Patients were followed for 2 years. RESULTS: Median sclerostin levels were significantly (p < 0.0001) higher in HD versus healthy subjects (n = 94) (1,375 vs. 565 pg/ml, respectively). In univariate analysis a significant association (p < 0.05) was found between sclerostin and age, height, dialysis vintage, albumin, troponin, homocysteine, PTH, C-terminal telopeptide of collagen type I, bone-specific alkaline phosphatase and osteoprotegerin, but not with the calcification score. In a multivariate model, the association remained with age, height, dialysis vintage, troponin, homocysteine, phosphate, PTH, but also with vascular calcifications. Association was positive for all variables, except PTH and vascular calcifications. The baseline sclerostin concentration was not different in survivors and non-survivors. CONCLUSIONS: We confirm a higher concentration of sclerostin in HD patients, a positive association with age and a negative association with PTH. A positive association with phosphate, homocysteine and troponin calls for additional research. The clinical interest of sclerostin to assess vascular calcifications in HD is limited and no association was found between sclerostin and mortality.

Dephosphorylated-uncarboxylated Matrix Gla protein concentration is predictive of vitamin K status and is correlated with vascular calcification in a cohort of hemodialysis patients.

BACKGROUND: Matrix Gla protein (MGP) is known to act as a potent local inhibitor of vascular calcifications. However, in order to be active, MGP must be phosphorylated and carboxylated, with this last process being dependent on vitamin K. The present study focused on the inactive form of MGP (dephosphorylated and uncarboxylated: dp-ucMGP) in a population of hemodialyzed (HD) patients. Results found in subjects being treated or not with vitamin K antagonist (VKA) were compared and the relationship between dp-ucMGP levels and the vascular calcification score were assessed. METHODS: One hundred sixty prevalent HD patients were enrolled into this observational cohort study, including 23 who were receiving VKA treatment. The calcification score was determined (using the Kauppila method) and dp-ucMGP levels were measured using the automated iSYS method. RESULTS: dp-ucMGP levels were much higher in patients being treated with VKA and little overlap was found with those not being treated (5604 [3758; 7836] vs. 1939 [1419; 2841] pmol/L, p < 0.0001). In multivariate analysis, treatment with VKA was the most important variable explaining variation in dp-ucMGP levels even when adjusting for all other significant variables. In the 137 untreated patients, dp-ucMGP levels were significantly (p < 0.05) associated both in the uni- and multivariate analysis with age, body mass index, plasma levels of albumin, C-reactive protein, and FGF-23, and the vascular calcification score. CONCLUSION: We confirmed that the concentration of dp-ucMGP was higher in HD patients being treated with VKA. We observed a significant correlation between dp-ucMGP concentration and the calcification score. Our data support the theoretical role of MGP in the development of vascular calcifications. We confirmed the potential role of the inactive form of MGP in assessing the vitamin K status of the HD patients. TRIAL REGISTRATION: B707201215885.