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In nephrology, rare disorders are frequently encountered. In children, about 60% of the renal disorders are rare, with congenital abnormalities of the kidney and urinary tract disorders (CAKUT), being highly prevalent. In adults, about 22% of the disorders leading to renal replacement therapies are rare and include glomerulonephritis and genetic disorders. Rarity may preclude the rapid and extensive access to care for patients suffering of renal disorders, especially in Switzerland, which is small and fragmented. Only collaborative network and access to databases, shared resources and to specific competence may help patient management. Lausanne and Geneva University Hospitals have started specialized outpatient clinics for rare renal disorders several years ago and are part of national and international networks., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Antiphospholipid antibody syndrome (APLS) is a rare autoimmune disease characterized by recurrent arterial and venous thromboembolic events, pregnancy related complications as well as the persistent detection of antiphospholipid antibodies at a 12 week interval. Renal complications tend to occur in 3% of APLS patients, with renal artery stenosis being the most common kidney related complication. Renal pathology may be subdivided into macro as well as microvascular thrombotic complications with stenosis, thrombosis and infarction representing the principle macrovascular events and APLS nephropathy representing the predominant microvascular complication. APLS related kidney disease may present with an array of heterogenous manifestations ranging from hematuria and non-nephrotic range proteinuria to hypertension or as part of a severe, life threatening and fulminant multiorgan failure disorder known as catastrophic antiphospholipid antibody syndrome (CAPS). Management of APLS related renal complications depends on the site of vascular injury, the thromboembolic risk profile based on the subtype, isotype and titer of the autoantibodies as well as the severity of the injury. Primary prophylaxis in these patients primarily revolves around the use of low dose aspirin, with prophylactic anticoagulation during events that increase thromboembolic like surgery and hospitalization. Anticoagulation is the cornerstone of treatment of APLS related kidney disease with INR targets varying depending on the associated venous or arterial thrombosis. Immunosuppression with the likes of rituximab, mTOR inhibitors, eculizumab and belimumab have been used with some success, but lack randomized control trial validation for their use. Pulsed corticosteroids with Plasmapheresis and intravenous immunoglobulins is the recommended treatment for CAPS., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Kidney cortical interstitial fibrosis (IF) is highly predictive of renal prognosis and is currently assessed by the evaluation of a biopsy. Diffusion magnetic resonance imaging (MRI) is a promising tool to evaluate kidney fibrosis via the apparent diffusion coefficient (ADC), but suffers from inter-individual variability. We recently applied a novel MRI protocol to allow calculation of the corticomedullary ADC difference (ΔADC). We here present the validation of ΔADC for fibrosis assessment in a cohort of 164 patients undergoing biopsy and compare it with estimated glomerular filtration rate (eGFR) and other plasmatic parameters for the detection of fibrosis., Methods: This monocentric cross-sectional study included 164 patients undergoing renal biopsy at the Nephrology Department of the University Hospital of Geneva between October 2014 and May 2018. Patients underwent diffusion-weighted imaging, and T1 and T2 mappings, within 1 week after biopsy. MRI results were compared with gold standard histology for fibrosis assessment., Results: Absolute cortical ADC or cortical T1 values correlated poorly to IF assessed by the biopsy, whereas ΔADC was highly correlated to IF (r=-0.52, P < 0.001) and eGFR (r = 0.37, P < 0.01), in both native and allograft patients. ΔT1 displayed a lower, but significant, correlation to IF and eGFR, whereas T2 did not correlate to IF nor to eGFR. ΔADC, ΔT1 and eGFR were independently associated with kidney fibrosis, and their combination allowed detection of extensive fibrosis with good specificity., Conclusion: ΔADC is better correlated to IF than absolute cortical or medullary ADC values. ΔADC, ΔT1 and eGFR are independently associated to IF and allow the identification of patients with extensive IF., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Cheap and easy to access, ethylene glycol is used in the synthesis of antifreezes. Intoxication has potentially irreversible morbid consequences. Ingestion of a small amount can lead to death. Due to its ubiquitous distribution and potential complications, it is of paramount importance for the practitioner to recognize its manifestations and metabolic complications in order to implement its therapy in partnership with the nephrologist and the intensivist. A successful treatment depends on rapid and multidisciplinary management, as reviewed in this article., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Impact of gliflozines and rituximab in the treatments of diabetic and membranous nephropathies respectively has been confirmed. Roxadustat may be the new promising treatment of renal anemia. Long-acting erythropoietins may be associated with a higher death rate than short-acting ones in hemodialysis patients. Kidneys of HCV-seropositive donors can be proposed to any wait-listed patient for renal transplantation. Immunosupression minimizing the use of calcineurin inhibitors may be achieved with an everolimus-based protocol., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Purpose: To compare readout-segmented echo-planar imaging (EPI) (RESOLVE) to single-shot EPI (ss-EPI) diffusion-weighted imaging (DWI) for the assessment of renal interstitial fibrosis., Materials and Methods: A phantom, eight healthy volunteers (under 30 years to avoid age-fibrosis related) and 27 chronic kidney disease (CKD) patients (scheduled for kidney biopsy) were scanned (at 3T) with ss-EPI and 5-shot RESOLVE DWI (resolution: 2 × 2 × 5 mm 3 , 10 b-values). The cortico-medullary difference for each DW parameter from a monoexponential fit (ΔADC) or, segmented biexponential fit (ΔD, ΔD*, ΔF p ) were compared between both sequences. A fibrosis threshold of 40% was defined to separate all 35 subjects into low and high fibrosis groups. The linear relationship between DW parameters and percentage fibrosis (up to 80%) from Masson trichrome was assessed with the Pearson product-moment correlation coefficient. Fisher Z-transform was used for R 2 correlation comparison., Results: A coefficient of variation between ADCs of 3% was measured between both sequences in the phantom. In healthy volunteers, no significant difference was measured for all DW parameters. Both sequences separated low to high level of fibrosis with a significant decrease of ΔADC (RESOLVE P = 3.1 × 10 -6 , ss-EPI P = 0.003) and ΔD (RESOLVE P = 8.2 × 10 -5 , ss-EPI P = 0.02) in the high level of fibrosis. However, RESOLVE ΔADC had a stronger negative correlation (P = 0.04 for R 2 comparison) with fibrosis than ss-EPI ΔADC (RESOLVE R 2  = 0.65, P = 5.9 × 10 -9 , ss-EPI R 2  = 0.29, P = 8.9 × 10 -4 ). ΔD (RESOLVE) was correlated (moderately) with fibrosis (R 2  = 0.29, P = 9.2 × 10 -4 ); however, ΔD* and ΔF p did not show, in our population, a significant correlation with interstitial fibrosis (0.01 < R 2 < 0.08)., Conclusion: ΔADC derived from both sequences correlated with fibrosis. ΔADC from RESOLVE showed better correlation with fibrosis than ΔADC from ss-EPI and therefore has potential to monitor CKD., Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1631-1640., (© 2017 International Society for Magnetic Resonance in Medicine.)

NADPH oxidase 4 (NOX4) is highly expressed in kidney proximal tubular cells. NOX4 constitutively produces hydrogen peroxide, which may regulate important pro-survival pathways. Renal ischemia reperfusion injury (IRI) is a classical model mimicking human ischemic acute tubular necrosis. We hypothesized that NOX4 plays a protective role in kidney IRI. In wild type (WT) animals subjected to IRI, NOX4 protein expression increased after 24 hours. NOX4 KO (knock-out) and WT littermates mice were subjected to IRI. NOX4 KO mice displayed decreased renal function and more severe tubular apoptosis, decreased Bcl-2 expression and higher histologic damage scores compared to WT. Activation of NRF2 was decreased in NOX4 KO mice in response to IRI. This was related to decreased KEAP1 oxidation leading to decreased NRF2 stabilization. This resulted in decreased glutathione levels. In vitro silencing of NOX4 in cells showed an enhanced propensity to apoptosis, with reduced expression of NRF2, glutathione content and Bcl-2 expression, similar to cells derived from NOX4 KO mice. Overexpression of a constitutively active form of NRF2 (caNRF2) in NOX4 depleted cells rescued most of this phenotype in cultured cells, implying that NRF2 regulation by ROS issued from NOX4 may play an important role in its anti-apoptotic property.

A need exists to noninvasively assess renal interstitial fibrosis, a common process to all kidney diseases and predictive of renal prognosis. In this translational study, Magnetic Resonance Imaging (MRI) T1 mapping and a new segmented Diffusion-Weighted Imaging (DWI) technique, for Apparent Diffusion Coefficient (ADC), were first compared to renal fibrosis in two well-controlled animal models to assess detection limits. Validation against biopsy was then performed in 33 kidney allograft recipients (KARs). Predictive MRI indices, ΔT1 and ΔADC (defined as the cortico-medullary differences), were compared to histology. In rats, both T1 and ADC correlated well with fibrosis and inflammation showing a difference between normal and diseased kidneys. In KARs, MRI indices were not sensitive to interstitial inflammation. By contrast, ΔADC outperformed ΔT1 with a stronger negative correlation to fibrosis (R(2) = 0.64 against R(2) = 0.29 p < 0.001). ΔADC tends to negative values in KARs harboring cortical fibrosis of more than 40%. Using a discriminant analysis method, the ΔADC, as a marker to detect such level of fibrosis or higher, led to a specificity and sensitivity of 100% and 71%, respectively. This new index has potential for noninvasive assessment of fibrosis in the clinical setting.

Suspected renal inherited disorders are regularly evaluated in nephrology consultations both in adults and children. A positive family history and/or a typical phenotype should lead to genetic investigations. A confirmatory diagnosis integrated in a multidisciplinary genetic counseling approach gives patient guidance for further pregnancy. It also allows physician to better stratify disease risk and indicates treatment in some cases. The time to diagnosis and costs have been dramatically reduced thanks to next generation sequencing in several cases of complex inherited nephrologic syndromes.

Sodium chloride 0.9%, often incorrectly called physiological saline, contains higher concentration of chloride compared to plasma. It is known that the administration of sodium chloride 0.9% can cause hyperchloremic metabolic acidosis in a reproducible manner. The elevated chloride concentration in 0.9% NaCl solution can also adversely affect renal perfusion. This effect is thought to be induced by hyperchloremia that causes renal artery vasoconstriction. For these reasons, the use of 0.9% NaCl solution is raising attention and some would advocate the use of a more "physiological" solution, such as balanced solutions that contain a level of chloride closer to that of plasma. Few prospective, randomized, controlled trials are available today and most were done in a perioperative setting. Some studies suggest that the chloride excess in 0.9% NaCl solution could have clinical consequences; however, this remains to be established by quality randomized controlled trials.

Isotonic saline and buffered crystalloid solutions may carry an equivalent risk of acute kidney injury in critically ill patients. In hemodialyzed patients, highly dialyzable beta-blockers are less cardioprotective than non-dialyzable beta-blockers, cooling the dialyzate may protect their cerebral white matter and too much parenteral iron may be deleterious. A promising treatment for amyloid deposits is underway. A well tolerated treatment for hyperkalemia has emerged. Low serum magnesium and diminished phosphaturia may be associated with an increased risk of chronic kidney disease. Moderate hyponatremia should be considered as a serious public health problem.

ANCA-associated vasculitis are systemic disorders characterized by inflammation predominantly involving small vessels. They are the most frequent cause of rapidly progressive glomerulonephritis in the elderly. They originate from complex interactions between genes and environment, resulting in autoimmunity and the generation of antibodies directed against neutrophil cytoplasmic antigens (ANCA), which may have pathogenic potential. Immunosuppressant agents, particularly cyclophosphamide, have considerably improved the prognosis, but infectious complications and relapses remain frequent. Recently, rituximab has been shown to be a good alternative to cyclophosphamide to induce remission. Additional knowledge should result in better clinical outcomes, minimizing side effects.

NADPH oxidases synthesize reactive oxygen species that may participate in fibrosis progression. NOX4 and NOX2 are NADPH oxidases expressed in the kidneys, with the former being the major renal isoform, but their contribution to renal disease is not well understood. Here, we used the unilateral urinary obstruction model of chronic renal injury to decipher the role of these enzymes using wild-type, NOX4-, NOX2-, and NOX4/NOX2-deficient mice. Compared with wild-type mice, NOX4-deficient mice exhibited more interstitial fibrosis and tubular apoptosis after obstruction, with lower interstitial capillary density and reduced expression of hypoxia-inducible factor-1α and vascular endothelial growth factor in obstructed kidneys. Furthermore, NOX4-deficient kidneys exhibited increased oxidative stress. With NOX4 deficiency, renal expression of other NOX isoforms was not altered but NRF2 protein expression was reduced under both basal and obstructed conditions. Concomitant deficiency of NOX2 did not modify the phenotype exhibited by NOX4-deficient mice after obstruction. NOX4 silencing in a mouse collecting duct (mCCD(cl1)) cell line increased TGF-β1-induced apoptosis and decreased NRF2 protein along with expression of its target genes. In addition, NOX4 silencing decreased hypoxia-inducible factor-1α and expression of its target genes in response to hypoxia. In summary, these results demonstrate that the absence of NOX4 promotes kidney fibrosis, independent of NOX2, through enhanced tubular cell apoptosis, decreased microvascularization, and enhanced oxidative stress. Thus, NOX4 is crucial for the survival of kidney tubular cells under injurious conditions.

Background: Sickle cell disease (SCD) leads to tissue hypoxia resulting in chronic organ dysfunction including SCD associated nephropathy. The goal of our study was to determine the best equation to estimate glomerular filtration rate (GFR) in SCD adult patients., Methods: We conducted a prospective observational cohort study. Since 2007, all adult SCD patients in steady state, followed in two medical departments, have had their GFR measured using iohexol plasma clearance (gold standard). The Cockcroft-Gault, MDRD-v4, CKP-EPI and finally, MDRD and CKD-EPI equations without adjustment for ethnicity were tested to estimate GFR from serum creatinine. Estimated GFRs were compared to measured GFRs according to the graphical Bland and Altman method., Results: Sixty-four SCD patients (16 men, median age 27.5 years [range 18.0-67.5], 41 with SS-genotype were studied. They were Sub-Saharan Africa and French West Indies natives and predominantly lean (median body mass index: 22 kg/m2 [16-33]). Hyperfiltration (defined as measured GFR >110 mL/min/1.73 m2) was detected in 53.1% of patients. Urinary albumin/creatinine ratio was higher in patients with hyperfiltration than in patients with normal GFR (4.05 mg/mmol [0.14-60] versus 0.4 mg/mmol [0.7-81], p = 0.01). The CKD-EPI equation without adjustment for ethnicity had both the lowest bias and the greatest precision. Differences between estimated GFRs using the CKP-EPI equation and measured GFRs decreased with increasing GFR values, whereas it increased with the Cockcroft-Gault and MDRD-v4 equations., Conclusions: We confirm that SCD patients have a high rate of glomerular hyperfiltration, which is frequently associated with microalbuminuria or macroalbuminuria. In non-Afro-American SCD patients, the best method for estimating GFR from serum creatinine is the CKD-EPI equation without adjustment for ethnicity. This equation is particularly accurate to estimate high GFR values, including glomerular hyperfiltration, and thus should be recommended to screen SCD adult patients at high risk for SCD nephropathy.