[Diagnostic approach to rhabdomyolysis]. / Vignette diagnostique de l'étudiant. Approche diagnostique de la rhabdomyolyse.

Rhabdomyolysis is a clinical syndrome related to the damage of skeletal muscle. The symptomatology is often poor, but it classically includes muscle weakness, myalgia and red-brown urine. The causes may be multiple but are most frequently traumatic : the so-called "crush syndrome". The diagnosis is based on the increase in serum creatine kinase, which is sometimes associated with myoglobinuria. Rhabdomyolysis may cause severe complications, such as ionic disorders or acute kidney injury which can lead to the death of the patient.

La rhabdomyolyse est un syndrome clinique lié à la destruction du muscle squelettique. La symptomatologie est souvent pauvre et associe classiquement une faiblesse musculaire, des myalgies et des urines noirâtres. Les causes peuvent être multiples, mais sont le plus fréquemment traumatiques et regroupées sous le terme anglophone de «crush syndrome¼. Le diagnostic repose sur la majoration sérique de la créatine kinase, à laquelle s'associe parfois une myoglobinurie. Rarement bénigne, la rhabdomyolyse peut engendrer des complications sévères, telles que des troubles ioniques ou une insuffisance rénale pouvant mener au décès du patient.

[Renal manifestations of syphilis]. / Manifestations rénales de la syphilis.

Syphilis is an acquired or congenital systemic pathology, currently on the rise in Europe. The clinical manifestations of syphilis are not very specific and variable over time. In this case report, we describe two renal presentations of syphilis in patients followed in a Pre-Exposure Prophylaxis (PrEP) program for the prevention of HIV infection. The specificity of the renal involvement of syphilis, the diagnostic and the therapeutic management will be discussed in this article.

La syphilis est une pathologie systémique acquise ou congénitale, actuellement en recrudescence en Europe. Les manifestations cliniques de la syphilis sont souvent peu spécifiques et variables au cours du temps. Nous décrivons ici deux présentations rénales de la syphilis survenues chez des patients suivis dans un programme de Pre-Exposure Prophylaxis (PrEP) de prévention contre l'infection VIH. La spécificité de l'atteinte rénale de la syphilis, la mise au point diagnostique et la prise en charge thérapeutique seront discutées dans cet article.

"Acute kidney dysfunction with no rejection" is associated with poor renal outcomes at 2 years post kidney transplantation.

BACKGROUND: "Acute kidney dysfunction with no rejection" (ADNR) corresponds to acute kidney injury without histological evidence of acute rejection (AR) in kidney transplant recipients (KTR). The prognosis of ADNR is unknown. METHODS: From 2007 to 2015, we categorized KTR with for-cause kidney biopsy within the first 12 months post kidney transplantation (KTx) into ADNR (n = 93) and biopsy-proven AR (n = 22). Controls (C, n = 135) included KTR with no ADNR or AR within the first 24 months post-KTx. A piecewise linear regression with a single fixed-knot at 12 months served to establish intercepts and slopes of MDRD-eGFR variations from 12 to 24 months. The percentage of KTR with ≥30% reduction of eGFR from 12 to 24 months was calculated as a surrogate marker of future graft loss. RESULTS: The median time for for-cause biopsy was 22 [10-70] and 13 [7-43] days for ADNR and AR, respectively. At 12 months, eGFR was significantly higher in C (57.6 ± 14.9 mL/min/1.73m2) vs. ADNR (43.5 ± 15.4 mL/min/1.73m2, p < 0.0001) and vs. AR (46.5 ± 15.2 mL/min/1.73m2, p < 0.0065). The proportion of KTR with ≥30% reduction in eGFR from 12 to 24 months reached 16.3% in C vs. 29.9% in ADNR (p = 0.02) and vs. 15% in AR (not significant). CONCLUSIONS: ADNR is associated with poor outcomes within 2 years post-KTx.

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.

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.

In-depth phenotyping of a Donnai-Barrow patient helps clarify proximal tubule dysfunction.

BACKGROUND: The megalin/cubilin/amnionless complex is essential for albumin and low molecular weight (LMW) protein reabsorption by renal proximal tubules (PT). Mutations of the LRP2 gene encoding megalin cause autosomal recessive Donnai-Barrow/facio-oculo-acoustico-renal syndrome (DB/FOAR), which is characterized by LMW proteinuria. The pathophysiology of DB/FOAR-associated PT dysfunction remains unclear. CLINICAL CASE: A 3-year-old girl presented with growth retardation and proteinuria. Clinical examination was unremarkable, except for a still-opened anterior fontanel and myopia. Psychomotor development was delayed. At 6, she developed sensorineural hearing loss. Hypertelorism was noted when she turned 12. Blood analyses, including renal function parameters, were normal. Urine sediment was bland. Proteinuria was significant and included albumin and LMW proteins. Immunoblotting analyses detected cubilin and type 3 carbonic anhydrase (CA3) in the urine. Renal ultrasound was unremarkable. Optical examination of a renal biopsy did not disclose any tubular or glomerular abnormality. Electron microscopy revealed that PT apical endocytic apparatus was significantly less developed. Immunostaining for megalin showed a faint signal in PT cytosol contrasting with the distribution of cubilin at the apical membrane. The diagnostic procedure led to identifying two mutations of the LRP2 gene. CONCLUSIONS: The functional loss of megalin in DB/FOAR causes PT dysfunction characterized by increased urinary shedding of CA3 and cubilin.

Sclerostin within the chronic kidney disease spectrum.

Sclerostin is sometimes presented as a promising biomarker in assessing bone health both in the general population and chronic kidney disease patients. However, it is still unclear whether it has any true added value compared to existing bone biomarkers in predicting bone turnover and/or bone density in chronic kidney disease patients. A wealth of papers has been published to evaluate the association between sclerostin and vascular calcifications development or even as prognostic biomarker for mortality, but often with conflicting results. Standardization and harmonization of analytical techniques is a prerequisite to advance clinical knowledge in sclerostin.