Renal and major clinical outcomes and their determinants after nephrectomy in patients with pre-existing chronic kidney disease: A retrospective cohort study.

The consequences of partial nephrectomy (PN) compared to radical nephrectomy (RN) are less documented in patients with pre-existing chronic kidney disease (CKD) or with solitary kidney (SK). We assessed renal outcomes, and their determinants, after PN or RN in a retrospective cohort of patients with moderate-to-severe CKD (RN-CKD and PN-CKD) or SK (PN-SK). All surgical procedures conducted between 2013 and 2018 in our institution in patients with pre-operative estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m2 or with SK were included. The primary outcome was a composite criterion including CKD progression or major adverse cardio-vascular events (MACE) or death, assessed one year after surgery. Predictors of the primary outcome were determined using multivariate analyses. A total of 173 procedures were included (67 RN, and 106 PN including 27 SK patients). Patients undergoing RN were older, with larger tumors. Preoperative eGFR was not significantly different between the groups. One year after surgery, PN-CKD was associated with lower rate of the primary outcome compared to RN-CKD (43% vs 71% p = 0.007). In multivariate analysis, independent risk factors for the primary outcome were postoperative AKI (stage 1 to stage 3 ranging from OR = 8.68, 95% CI 3.23-23.33, to OR = 28.87, 95% CI 4.77-167.61), larger tumor size (OR = 1.21 per cm, 95% CI 1.02-1.45), while preoperative eGFR, age, sex, diabetes mellitus, and hypertension were not. Postoperative AKI after PN or RN was the major independent determinant of worse outcomes (CKD progression, MACE, or death) one year after surgery.

Nedosiran Safety and Efficacy in PH1: Interim Analysis of PHYOX3.

Introduction: Primary hyperoxaluria (PH) is a rare genetic disorder of hepatic glyoxylate metabolism. Nedosiran is an RNA interference (RNAi) therapeutic that the US Food and Drug Administration has approved for treatment of PH1. PHYOX3 is a trial evaluating monthly nedosiran in patients with PH. Methods: In this PHYOX3 interim analysis, participants with PH1 who continued from a single-dose nedosiran trial (PHYOX1), with no previous kidney or liver transplantation, dialysis, or evidence of systemic oxalosis were eligible. The safety and efficacy of once-monthly nedosiran was assessed over 30 months. Results: Thirteen participants completed PHYOX1 and continued into PHYOX3. At baseline, the mean (SD) and median (range) age was 24.2 (6.6) years and 23.0 (14-39) years, respectively; 53.8% were female and 61.5% were White. Mean estimated glomerular filtration rate (eGFR) remained stable (62-84.2 mL/min per 1.73 m2) to month 30. Mean 24-hour urinary oxalate (Uox) excretion showed a sustained reduction from baseline of ≥60% at every visit (months 2-30). From month 2, at least 10 of 13 (76.9%) participants achieved normal (<0.46 mmol/24h; upper limit of assay-normal [ULN]) or near-normal (≥0.46 to <0.60 mmol/24h; ≥ULN to <1.3 × ULN) 24-hour Uox excretion. All participants experienced ≥1 adverse event (AE), mostly mild or moderate in severity (primarily, injection site events). Three serious, not treatment-related AEs were reported; there were no deaths or study discontinuations due to AEs. Conclusion: Nedosiran was well-tolerated in patients with PH1, and treatment resulted in a sustained, substantial reduction in Uox excretion for at least 30 months in this long-term study. No safety signals have been identified to date. The PHYOX3 study is ongoing.

The use of 1E12, a monoclonal anti-platelet factor 4 antibody, to improve the diagnosis of vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a complication of adenoviral-based vaccine against SARS-CoV-2 due to prothrombotic immunoglobulin (Ig) G antibodies to platelet factor 4 (PF4) and may be difficult to distinguish from heparin-induced thrombocytopenia (HIT) in patients treated with heparin. OBJECTIVES: We assessed the usefulness of competitive anti-PF4 enzyme immunoassays (EIAs) in this context. METHODS: The ability of F(ab')2 fragments of 1E12, 1C12, and 2E1, 3 monoclonal anti-PF4 antibodies, to inhibit the binding of human VITT or HIT antibodies to PF4 was evaluated using EIAs. Alanine-scanning mutagenesis was performed to define the amino acids involved in the interactions between the monoclonal antibodies and PF4. RESULTS: A strong inhibition of VITT IgG binding to PF4 was measured with 1E12 (median inhibition, 93%; n = 8), whereas it had no effect on the binding of HIT antibodies (median, 6%; n = 8). In contrast, 1C12 and 2E1 inhibited VITT (median, 74% and 76%, respectively) and HIT antibodies (median, 68% and 53%, respectively) binding to PF4. When a competitive anti-PF4 EIA was performed with 1E12 for 19 additional VITT samples, it strongly inhibited IgG binding to PF4, except for 1 patient, who had actually developed HIT according to the clinical history. Epitope mapping showed that 1E12 interacts with 5 key amino acids on PF4, of which 4 are also required for the binding of human VITT antibodies, thus explaining the competitive inhibition. CONCLUSION: A simple competitive anti-PF4 EIA with 1E12 could help confirm VITT diagnosis and distinguish it from HIT in patients when both diagnoses are possible.

Fibromuscular dysplasia of the renal arteries: what do we know in 2024? / Dysplasie fibromusculaire des artères rénales : que savons-nous en 2024 ?

Fibromuscular dysplasia (FMD) is a rare nonatherosclerotic, noninflammatory vascular disease affecting mostly renal and carotid arteries and is the second most frequent cause of renal artery stenosis. The symptomatology is dominated by arterial hypertension due to the frequent involvement of the renal arteries and depends on the location of the lesions. Most of the cases are middle-aged women of Caucasian origin. There are two subtypes based on angiographic aspect: multifocal FMD (80% of the cases) and focal FMD (rarer with a more balanced sex ratio). Angioplasty of the renal arteries is generally disappointing with less than 50% cure of hypertension. It appears necessary to improve our knowledge of the FMD and to optimize the selection of eligible patients for revascularization with transdisciplinary collegial therapeutic decision.

La dysplasie fibromusculaire (DFM) est une maladie rare caractérisée par des sténoses segmentaires non artérioscléreuses, non inflammatoires, des artères de moyens calibres, touchant surtout les artères rénales et les carotides. Elle constitue la seconde cause de sténoses des artères rénales. La symptomatologie dépend de la localisation des lésions et est dominée par l'hypertension artérielle (HTA) en raison de l'atteinte fréquente des artères rénales. Cette pathologie touche majoritairement les femmes caucasiennes d'âge moyen. Il en existe deux sous-types, basés sur l'aspect angiographique : la DFM multifocale (80 % des cas) et la DFM focale (plus rare, sex ratio plus équilibré). Les résultats des prises en charge interventionnelles s'avèrent globalement décevants avec moins de 50 % de guérison de l'HTA. Il est nécessaire d'améliorer nos connaissances sur la physiopathologie de la DFM et d'optimiser la sélection des patients éligibles à une revascularisation par une prise de décision thérapeutique collégiale, en réunion de concertation pluridisciplinaire.

Redefining the concept of residual renal function with kidney sodium MRI: a pilot study.

RATIONALE & OBJECTIVE: The concept of residual kidney function (RKF) is exclusively based upon urine volume and small solute clearance, making RKF challenging to assess in clinical practice. The aim of this study was to test the technical feasibility of obtaining useable 23Na-MRI kidney images in hemodialysis (HD) participants. STUDY DESIGN: We conducted an exploratory prospective study to quantify the cortico-medullary sodium gradient in healthy and HD participants. Participants fasted for eight hours prior to their study visit. Urine samples were collected to measure urinary osmolarity, before MRI. Proton and sodium pictures were merged; ROIs were delineated for the medulla and cortex when feasible. In cases where cortex could not be identified, we considered the cortico to medulla gradient (CMG) to be no longer present, resulting in a medulla-to-cortex ratio of 1. SETTING & PARTICIPANTS: 17 healthy volunteers and 21 HD participants. FINDINGS: Median (IQR) fasting medulla to cortex ratio was significantly higher 1.56 [1.5-1.61] in healthy volunteers compared to HD patients 1.22 [1.13-1.3], p < 0.0001. Medulla to cortex ratio and median urinary osmolarity were correlated (r = 0.87, p < 0.0001) in the whole population. We found a significant association between HD vintage and medulla to cortex ratio whereas we did not find any association with urine volume. Sodium signal intensity distribution within healthy kidney describes two different peaks- relating to well defined cortex and medulla; whereas HD participants displays only a single peak indicative of the markedly lower sodium concentration. LIMITATIONS: This study is only an exploratory study with a modest number of patients. CONCLUSIONS: the application of kidney sodium MRI to the study of RKF in patients receiving maintenance HD is practical and provides a previously unavailable ability to interrogate the function of remnant tubular function.

Fibromuscular dysplasia of the renal arteries: what do we know in 2024? / Dysplasie fibromusculaire des artères rénales : que savons-nous en 2024 ?

Fibromuscular dysplasia (FMD) is a rare nonatherosclerotic, noninflammatory vascular disease affecting mostly renal and carotid arteries and is the second most frequent cause of renal artery stenosis. The symptomatology is dominated by arterial hypertension due to the frequent involvement of the renal arteries and depends on the location of the lesions. Most of the cases are middle-aged women of Caucasian origin. There are two subtypes based on angiographic aspect: multifocal FMD (80% of the cases) and focal FMD (rarer with a more balanced sex ratio). Angioplasty of the renal arteries is generally disappointing with less than 50% cure of hypertension. It appears necessary to improve our knowledge of the FMD and to optimize the selection of eligible patients for revascularization with transdisciplinary collegial therapeutic decision.

La dysplasie fibromusculaire (DFM) est une maladie rare caractérisée par des sténoses segmentaires non artérioscléreuses, non inflammatoires, des artères de moyens calibres, touchant surtout les artères rénales et les carotides. Elle constitue la seconde cause de sténoses des artères rénales. La symptomatologie dépend de la localisation des lésions et est dominée par l'hypertension artérielle (HTA) en raison de l'atteinte fréquente des artères rénales. Cette pathologie touche majoritairement les femmes caucasiennes d'âge moyen. Il en existe deux sous-types, basés sur l'aspect angiographique : la DFM multifocale (80 % des cas) et la DFM focale (plus rare, sex ratio plus équilibré). Les résultats des prises en charge interventionnelle s'avèrent globalement décevants avec moins de 50 % de guérison de l'HTA. Il est nécessaire d'améliorer nos connaissances sur la physiopathologie de la DFM et d'optimiser la sélection des patients éligibles à une revascularisation par une prise de décision thérapeutique collégiale, en réunion de concertation pluridisciplinaire.

Circulating Oxalate Levels in Short Bowel Syndrome as a Severity Marker of CKD.

Introduction: Patients with short bowel syndrome (SBS) may exhibit enteric hyperoxaluria (EH), and the prevalence of oxalate nephropathy in SBS is likely underestimated. Plasma oxalate (POx) is a surrogate of systemic oxalate deposition and, consequently, may increase the risk of developing chronic kidney disease (CKD). The main objective of this study was to explore the distribution of POx levels in patients with SBS. Methods: Patients followed for SBS were recruited prospectively in the OXAGO study (NCT04119765) to assess POx during their annual renal follow-up including iohexol clearance. The inclusion criteria were age ≥18 years, and SBS type 2 and type 3 for more than 6 months. Results: A total of 47 patients were included but only 45 patients has a measured POx (55% males, 80% SBS type 2, 66% parenteral nutrition, 61% kidney stone history). POx levels were 6.8 ± 4.4 µmol/l, 29% of patients had POx ≥5 µmol/l. In the whole cohort, mean urinary oxalate (UOx) was 648±415 and 54% were >500 µmol/24h. In the group of patients with high POx levels (HPO), 24-hour urine oxalate was significantly higher than in the group with normal POx levels (NPO) (919 ± 566 vs. 526 ± 257 µmol/l; P = 0.003). Glomerular filtration rate (GFR) was 66 ± 22 ml/min per 1.73 m2, and 91% had CKD. GFR was significantly lower in the HPO than in the NPO group (49 ± 23 vs. 73 ± 18 ml/min per 1.73 m2; P = 0.0005. Conclusion: Patients with SBS can display increased POx levels even with GFR >30 ml/min per 1.73 m2. POx may be an interesting biomarker to assess the severity of EH.

An Open-Label Phase 2 Study of Eneboparatide, a Novel PTH Receptor 1 Agonist, in Hypoparathyroidism.

CONTEXT: Hypoparathyroidism is a rare disorder characterized by a deficiency in parathyroid hormone (PTH) resulting in hypocalcemia, hyperphosphatemia, and hypercalciuria. Eneboparatide is an investigational peptide agonist of the PTH1 receptor for the treatment of chronic hypoparathyroidism (HP). OBJECTIVE: To evaluate the efficacy, safety, and tolerability of eneboparatide in HP patients. DESIGN: Open-label, phase 2 study. PARTICIPANTS: Twenty-eight patients (21 women, 7 men), mean age (range): 58 years (28-72), with HP were enrolled into 2 consecutive cohorts (C1, n = 12, and C2, n = 16). INTERVENTION: Following an optimization period, daily subcutaneous injections of eneboparatide were administered for 3 months at 20 µg/day (C1) or 10 µg/day (C2) starting dose. Conventional therapy was progressively removed and eneboparatide could be titrated up to 60 µg (C1) or 80 µg (C2). MAIN OUTCOMES: Proportion of patients achieving independence from conventional therapy, albumin-adjusted serum calcium (ADsCa), 24-h urine calcium (uCa), serum bone turnover markers (s-CTX and P1NP), bone mineral density (BMD), and adverse events (AEs). RESULTS: After 3 months, ≥ 88% patients achieved independence from conventional therapy while mean ADsCa was maintained within target range (7.8-9 mg/dL). Eneboparatide induced a rapid and sustained reduction of mean 24-hour uCa, even among patients with hypercalciuria. Bone turnover markers slightly increased and BMD remained unchanged, consistent with progressive resumption of physiologic bone turnover. Eneboparatide was well tolerated with no serious AEs. CONCLUSION: Eneboparatide allowed independence from conventional therapy and maintenance of serum calcium within a target range, while normalizing uCa excretion and producing a balanced resumption of bone turnover.

The highlights in nephrology in 2023 / Les temps forts en néphrologie en 2023

This article aims to summarize the "Quoi de neuf en néphrologie?" session held at the 2023 SFNDT Congress in Liège and sessions focused on updates regarding IgA nephropathy (NIgA) and ANCA-associated vasculitis. The agenda for the nephrology "Quoi de neuf en néphrologie?" session this year was to review key publications from non-nephrology journals, discussing topics such as nephroprotection, treatment of glomerulopathies (IgA and APOL1), clinical trials on arterial hypertension, urinary lithiasis, and other areas of renal physiology, including glomerular filtration rate estimation.

Cet article a pour but de résumer d'une part la session « Quoi de neuf en néphrologie ? ¼ qui a eu lieu au congrès de la Société francophone de néphrologie, dialyse et transplantation (SFNDT) 2023 à Liège en Belgique, mais également les sessions portant sur les actualités de la néphropathie à IgA (NIgA) et des vascularites associées aux anticorps anticytoplasme des polynucléaires neutrophiles (ANCA). Le cahier des charges du « Quoi de neuf en néphrologie ? ¼ cette année était de reprendre les principaux articles publiés dans des revues hors néphrologie et s'est articulé sur les publications autour de la néphroprotection, du traitement des glomérulopathies (IgA et APOL1), des essais cliniques sur l'hypertension artérielle ou dans la lithiase urinaire, ou dans d'autres champs de la physiologie rénale comme l'estimation du débit de filtration glomérulaire.

X-linked hypophosphatemia: The value of feedback focus groups to assess patient and caregiver needs.

X-linked hypophosphatemia (XLH) is a rare, multi-systemic, invalidating disease requiring a multi-disciplinary approach. No specific action in XLH, neither for the patients' specific needs nor for the methodology for the evaluation of these were found. Thus, to identify the needs of XLH patients and their caregivers, we organised focus groups in our reference centre with a view to build educational sessions. Focus groups including either XLH children, XLH adults, or caregivers ran in parallel. Each group was led by a person trained in therapeutic education (nurse, paediatric nephrologist) with another healthcare provider specialised in XLH (rheumatologist, nephrologist). One additional person with knowledge of XLH (clinical research associate, paediatric resident) took minutes. The duration of each session was 1.5h; XLH patients/caregivers were asked to answer age-adapted "open questions" on their daily life and quality of life. At the end, a global restitution was made. The needs identified were later grouped and analysed, which allowed us to build the educational sessions. The XLH children group included 5 children, the XLH adults group included 10 adults, and the caregivers group included 6 parents or partners. Major needs were identified: knowledge of XLH, treatment, dental care and adapted physical activity, with additional questions on socio-professional adaptations and financial support in adults. Partner patients were also identified to co-build the support programme. The study allowed us to identify the needs of XLH patients and their caregivers using the focus group method and then, using these needs, to build educational sessions and a therapeutic education programme for XLH patients.

Is shrunken pore syndrome also a reality in children?

BACKGROUND: Shrunken pore syndrome (SPS) is defined as cystatin C-based-eGFR (eGFRcys)/creatinine-based-eGFR (eGFRcreat) <0.6 or 0.7 and is associated with an increased cardiovascular risk. SPS has been described in children, but no link to increased morbi-mortality was demonstrated. OBJECTIVES: Study the prevalence of SPS in a pediatric population using several glomerular filtration rate (GFR) estimating formulas and measured GFR and evaluate the potential link with cardiovascular risk. METHODS: In 307 renal risk pediatric patients, we studied prevalence of SPS either with CKiDU25creat and cyst or with FAScreat and cyst and EKFCcreat. The characteristics of patients with SPS (defined with Full-age spectrum equation (FAS) and/or European Kidney Function Consortium equation (EKFC)) were compared. RESULTS AND CONCLUSION: The prevalence of SPS varies widely depending on the threshold and the formulas used. Higher C-reactive protein (CRP) and phosphate levels and smaller size are observed in children with SPS defined with FAS and/or EKFC and might be associated with long-term increased cardiovascular risk. Further studies in wider general pediatric populations are warranted.

Extending the cystatin C based EKFC-equation to children - validation results from Europe.

BACKGROUND: A new cystatin C based European Kidney Function Consortium (EKFCCysC) equation was recently developed for adults, using the same mathematical form as the previously published full age spectrum creatinine based EKFC-equation (EKFCCrea). In the present study the cystatin C based EKFC-equation is extended to children, by defining the appropriate cystatin C rescaling factor QCysC. METHODS: Rescaling factor QCysC for cystatin C was defined as: a) 0.83 mg/L, exactly as it was defined for young adults in the adult equation, and b) a more complex QCysC-age relationship based on 4th degree cystatin C-age polynomials after evaluation of data from Uppsala, Stockholm and Canada and aggregated data from Germany. The EKFCCysC equation was then validated in an independent dataset in European children (n = 2,293) with measured GFR, creatinine, cystatin C, age, height and sex available. RESULTS: The EKFCCysC with the simple QCysC-value of 0.83 had a bias of -7.6 [95%CI -8.4;-6.5] mL/min/1.73 m2 and a P30-value of 85.8% [95%CI 84.4;87.3] equal to the EKFCCysC with the more complex 4th degree QCysC-value. The arithmetic mean of the EKFCCrea and EKFCCysC with the simple QCysC of 0.83 had a bias of -4.0 [95%CI -4.5;-3.1] mL/min/1.73 m2 and P30 of 90.4% [95%CI 89.2;91.6] similar to using the more complex 4th degree QCysC-polynomial. CONCLUSION: Using exactly the same QCysC of 0.83 mg/L, the adult EKFCCysC can easily be extended to children, with some bias but acceptable P30-values. The arithmetic mean of EKFCCrea and EKFCCysC results in bias closer to zero and P30 slightly over 90%.

Reassuring Data on the Cardiovascular Risk in Adults With X-linked Hypophosphatemia Receiving Conventional Therapy.

CONTEXT: X-linked hypophosphatemia (XLH) is a rare genetic disorder that results in increased plasma levels of fibroblast growth factor 23 (FGF23). Several studies have demonstrated a direct association between FGF23 and cardiovascular mortality in cohorts of patients with chronic renal failure. However, in patients with XLH, studies on the cardiovascular impact of the disease are rare, with contradictory results. OBJECTIVE: The aim was to assess whether the disease led to an increased cardiovascular risk. METHODS: We conducted a single-center retrospective observational study on a local cohort of adult patients with XLH. The primary endpoint was a composite endpoint of the frequency of left ventricular hypertrophy (LVH) or presence of high blood pressure. Our secondary objectives were to assess echocardiographic, pulse wave velocity, and central blood pressure data as other markers of CV health. Independently of this cohort, tissue sodium content with magnetic resonance imaging was studied in 2 patients with XLH before and after burosumab. RESULTS: Twenty-two patients were included. Median serum phosphate was 0.57 (0.47-0.72) mmol/L and FGF23 94 pg/L (58-2226). Median blood pressure was 124 (115-130)/68 (65-80) mm Hg, with only 9% of patients being hypertensive. A majority of patients (69%) had no LVH, only 1 had a left ventricular mass >100 g/m² and 25% of patients had left ventricular remodeling. Pulse wave velocity was normal in all patients. No differences in skin and muscle sodium content were observed before and after burosumab in the 2 patients who underwent sodium magnetic resonance imaging. CONCLUSION: We found no elevated risk of developing hypertension or LVH in patients with XLH.

Average creatinine-urea clearance: revival of an old analytical technique?

Background: Creatinine-based equations such as the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) are recommended for estimating glomerular filtration rate (eGFR) in clinical practice, but have reduced performance in advanced stages of chronic kidney disease. However, only rarely studies have evaluated the performance of eGFR by measuring the average of the urinary clearances of creatinine and urea (mClUN-cr) compared with the eGFR equations. Methods: This cross-sectional study evaluated the usefulness of mClUN-cr in a population of 855 participants who performed a GFR measurement by urinary inulin clearance. The performance of mClUN-cr was compared with those of CKD-EPI 2009 and CKD-EPI 2021, considering three criteria: bias, precision and accuracy. Results: In the whole sample, the mClUN-cr performed similarly to CKD-EPI equations (2009 and 2021) [precision: 11.5 (95% CI 10.5; 12.5) vs 19.0 (95% CI 17.2; 20.1) and 19.1 (95% CI 17.4; 20.4), and accuracy P30: 97.0 (95% CI 95.8; 98.0) vs 82.0 (95% CI 79.2; 84.4) and 77.2 (95% CI 74.5; 80.0)]. The CKD-EPI equations (2009 and 2021) had the best performance when mGFR was >60 mL/min/1.73 m2. In contrast, the mClUN-cr performed better than others with lowest mGFR values, more noticeable when mGFR was <60 mL/min/1.73 m2. Conclusions: The study described the best performance of mClUN-cr at GFR levels below 60 mL/min/1.73 m2 and a satisfactory result in the overall cohort. The findings point to a role of this tool, especially for estimating GFR in chronic kidney disease patients in developing countries, when reference measurement of GFR is not available.

Heat Shock Protein 70 Is Involved in the Efficiency of Preconditioning with Cyclosporine A in Renal Ischemia Reperfusion Injury by Modulating Mitochondrial Functions.

Cyclosporine A (CsA) preconditioning is known to target mitochondrial permeability transition pore and protect renal function after ischemia reperfusion (IR). The upregulation of heat-shock protein 70 (Hsp70) expression after CsA injection is thought to be associated with renal protection. The aim of this study was to test the effect of Hsp70 expression on kidney and mitochondria functions after IR. Mice underwent a right unilateral nephrectomy and 30 min of left renal artery clamping, performed after CsA injection and/or administration of the Hsp70 inhibitor. Histological score, plasma creatinine, mitochondrial calcium retention capacity, and oxidative phosphorylation were assessed after 24 h of reperfusion. In parallel, we used a model of hypoxia reoxygenation on HK2 cells to modulate Hsp70 expression using an SiRNA or a plasmid. We assessed cell death after 18 h of hypoxia and 4 h of reoxygenation. CsA significantly improved renal function, histological score, and mitochondrial functions compared to the ischemic group but the inhibition of Hsp70 repealed the protection afforded by CsA injection. In vitro, Hsp70 inhibition by SiRNA increased cell death. Conversely, Hsp70 overexpression protected cells from the hypoxic condition, as well as the CsA injection. We did not find a synergic association between Hsp70 expression and CsA use. We demonstrated Hsp70 could modulate mitochondrial functions to protect kidneys from IR. This pathway may be targeted by drugs to provide new therapeutics to improve renal function after IR.

Oxalate: from physiology to pathology / Oxalate : de la physiologie à la pathologie

Hyperoxaluria is defined by an increase of urinary oxalate, leading to kidney stones, nephrocalcinosis and/or chronic kidney disease. There are different diseases related to hyperoxaluria: (1) kidney stones, 50% of them being explained by intermittent hyperoxaluria, secondary to dietary mistakes such as low hydration, excess of oxalate consumption and/or low calcium consumption; (2) primary hyperoxaluria, a genetic orphan disease inducing a massive production of oxalate by the liver, leading to increased plasma oxalate increase and saturation, and further systemic oxalosis with oxalate deposition, nephrocalcinosis and ultimately kidney failure, the management of this disease being currently dramatically modified by the onset of new therapeutic tools such as RNA interference; and (3) enteric hyperoxaluria, resulting from increased intestinal oxalate absorption because of intestinal malabsorption (short bowel syndrome, bariatric surgery, exocrine pancreatic insufficiency, etc.). Diagnosis and therapeutic management of these diseases require a full understanding of oxalate physiology that we detail in this review.

L'hyperoxalurie, définie par une élévation de l'oxalate urinaire, favorise la survenue d'une maladie lithiasique, d'une néphrocalcinose et/ou d'une insuffisance rénale chronique. L'hyperoxalurie peut témoigner de différentes maladies : (1) l'hyperoxalurie diététique, responsable de 50 % de la maladie lithiasique par le biais d'erreurs alimentaires (hydratation insuffisante, consommation excessive d'oxalate et/ou consommation insuffisante de calcium) ; (2) les hyperoxaluries primaires, maladies génétiques orphelines responsables d'une production massive d'oxalate aboutissant à des dépôts tissulaires précoces (dès l'enfance) et sévères (à l'origine d'une insuffisance rénale terminale puis d'une thésaurismose avec atteinte multiviscérale) et dont le pronostic est aujourd'hui transformé par les nouvelles thérapies (ARN interférents) ; (3) l'hyperoxalurie entérique, résultant d'une augmentation de l'absorption digestive de l'oxalate dans une situation de malabsorption (syndrome du grêle court, chirurgie bariatrique, insuffisance pancréatique exocrine, etc.). La physiologie de l'oxalate, détaillée dans cet article, permet d'appréhender la prise en charge diagnostique et thérapeutique de ces maladies.