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Background Creatinine-based equations such as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) are recommended for estimating GFR (eGFR) in clinical practice but have reduced performance in advanced stages of CKD. However, rare studies have evaluated the performance of eGFR by measuring the average of the urinary clearances of creatinine and urea (mClUN-cr) compared to 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, 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 > 60 mL/min/1.73m2. In contrast, the mClUN-cr performed better than others, with lowest mGFR values, more noticeable when mGFR < 60 mL/min/1.73m2. Conclusions The study described the best performance of mClUN-cr at GFR levels below 60 mL/min/1.73m2 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.

Background and Aims Among ST-segment elevation myocardial infarction (STEMI) patients, the respective impact of the baseline renal function, of the development of acute kidney injury (AKI), and of their combination, on the long-term cardiovascular outcomes, remain unclear. Method The present study was based on a post hoc analysis of the CIRCUS trial database, a multicentre randomized study which gathered 969 patients with anterior STEMI treated by primary percutaneous intervention (PPCI) within 12 hours of symptoms onset. Uni and multivariate regressions were performed to identify if the estimated glomerular filtration rate (eGFR) at admission and the development of AKI were associated with (1) cardiovascular death and heart failure (HF) at one year and (2) sub-optimal treatment prescription at discharge. Results A total of 822 patients were included. The mean baseline eGFR was 86 ± 19 mL/min/1.73m2. AKI occurred in 97 patients (11.8%). Baseline eGFR Conclusion In anterior STEMI patients undergoing PPCI, the development of AKI was the strongest independent predictor of poor clinical outcome at one year. The study suggests the need for a tailored monitoring of STEMI patients with AKI or baseline kidney dysfunction.

Background and Aims Renal ischemia-reperfusion can lead to acute kidney injury (AKI), increasing the risk of developing chronic kidney disease (CKD) through inflammation and vascular lesions. Serum urea or creatinine level routinely used as diagnostic indices of renal function are always delayed from the onset of the disease. Therefore, we currently lack reliable markers to early detect AKI, especially in animals. We aimed to show that non-invasive renal contrast-enhanced ultrasound (CEUS) could be a reliable tool to assess early and chronic changes of renal perfusion after renal ischemia-reperfusion. Method Male C57BL6 mice underwent 15 minutes of unilateral renal ischemia by clamping of the left renal vascular pedicle (n = 7), or a sham procedure (n = 3), under inhaled general anesthesia by Sevoflurane. A renal ultrasound was performed on the left ischemic kidney at baseline 1 week before the surgery, then, 20 minutes after reperfusion to assess early modifications of renal perfusion, and 1 month after reperfusion to follow chronic modifications. CEUS was performed in supine position by using a high-resolution ultrasonic imaging system (VEVO 3100 Fujifilm Visualsonics, Toronto, Canada) with a MX550D probe fixed in place with an iron support, ensuring the constant imaging plane throughout acquisition. First, a continuous infusion of microbubbles (VS-11913, Fujifilm Visualsonics, Toronto, Canada) was done through the tail vein, then a high mechanical index burst was given to destroy microbubbles when the contrast enhancement had reached a steady state, and finally, low mechanical-index imaging mode was used until, and 30 sec after the contrast agent concentration reached the plateau. Images were recorded and were analyzed using the “destruction-replenishment” fitting model of the Vevo LAB software (Fujifilm Visualsonics, Toronto, Canada). Renal perfusion was estimated by the total renal Blood Volume (rBV) parameter and was expressed as percentage of the baseline value for each animal. Renal function was also assessed by serum urea concentration 1 month after reperfusion, and the long axis lengths of both the kidneys were measured ex vivo after the mice were euthanized. Results Renal perfusion of the ischemic kidney measured by CEUS was significantly decreased as soon as 20 minutes of reperfusion compared to baseline (median 28,8% of baseline value; interquartiles [20,1 – 69,8%]). 1 month after reperfusion, renal perfusion recovered partially but was still significantly decreased compared to baseline (median 79,9% of baseline value; interquartiles [52,8 – 99,9%]) (Figure A). In sham operated mice, renal perfusion did not differ from baseline at 20 minutes or 1 month (p > 0.05). The renal function, assessed by serum urea, was mildly but significantly impaired 1 month after ischemia-reperfusion compared with sham (median serum urea 9,8 vs. 7,6 mmol/L) (p = 0.02), and this was consistent with the observed kidney atrophy in the ischemic group when compared to the contralateral kidney (median long axis length 7,5 vs 10,8 mm) (p = 0.03). Moreover, the decrease of renal perfusion 20 minutes after reperfusion was significantly correlated with the impairment of renal perfusion 1 month after reperfusion (Pearson r = 0.836, p = 0.005) and with the serum urea level at 1 month (Pearson r = -0.710, p = 0.03) (Figure B-C). Conclusion Renal CEUS was able to detect early impairment of renal perfusion as soon as 20 minutes after 15 minutes of renal ischemia in mice, and perfusion was still decreased 1 month after reperfusion, compared to baseline. This early impairment of perfusion was correlated with the chronic decrease of renal perfusion and renal function 1 month after reperfusion. This was also associated with a significant kidney atrophy. CEUS is an interesting non-invasive tool to assess renal lesions dynamically after ischemia-reperfusion.

Background and Aims Glomerulonephritis is common in ANCA associated vasculitis (GN-AAV). There is extensive published data on the renal prognosis of these conditions. However, few authors have described predictive factors for end-stage renal disease (ESRD) in patients with GN-AAV. Many authors suggest that renal biopsy should be abandoned in patients whose diagnosis would be established by antibody positivity alone. The aim of the study was to establish a prognostic score for renal damage during ANCA vasculitis and demonstrate need for prognostic renal biopsy. Method One Hundred and eighteen patients referred to 2 french nephrology departments in Lyon between January 2003 and January 2019 were retrospectively analysed. Patients were randomly divided in 2 cohorts at a ratio of 70/30: training and validation cohorts. ESRD was defined as glomerular filtration rate (eGFR) ≤ 15mL/min/1.73m2,need of chronic dialysis or renal transplantation. Results Of the 118 patients, 38 (32.20%) developed ESRD. We identified 3 criteria associated with development of ESRD in patients with GN-AAV. One point was assigned to each criterion according to a threshold value: eGFR at the time of renal biopsy ≤ 15 mL/min; percentage of sclerotic glomeruli ≥ 11% and percentage of normal glomeruli < 20%. A new prognostic renal score was established in patients with GN-AAV. It classifies patients into 3 categories at risk of developing ESRD: low (≤ 1 point), moderate (2 points) and high (3 points). Conclusion Two of the three criteria of our score are histological. Biopsy remains, when possible, an essential tool for diagnosis and especially to predict renal prognosis of ANCA vasculitis with renal impairment.

Background and Aims Fabry Disease (FD) is an X linked lysosomal storage disease due to pathogenic α-galactosidase A (GLA) variants. It leads to damage in kidney and other organs. Numerous prevalence studies have been conducted over the past twenty years in ESRD patients in different countries. However, many screening studies did not perform confirmatory GLA variant analyses, and included recently recognized ‘benign/likely-benign’ variants, thereby inflating prevalence estimates. Thus, the prevalence of Fabry disease in patients with end-stage renal disease remains controversial. The FABRYDIAL study aimed to measure the prevalence of Fabry disease in patients aged 18 to 75 years and treated by chronic dialysis, either hemodialysis or peritoneal dialysis. Method The study was conducted in France in 5 geographic sectors (Aquitaine, Ile-de-France, Rhône-Alpes and Picardie regions, and the Gard department). One hundred and twenty-four dialysis centers participated in the study, which targeted patients undergoing chronic dialysis during the week of November 20, 2017. The exclusion criteria were the existence of a proven nephropathy unrelated to FD (polycystic kidney disease, type 1 diabetes or biopsy-proven IgA nephropathy, membranous glomerulonephritis or ANCA-associated vasculitis), the absence of health insurance coverage or guardianship or tutelage. α-galactosidase A in men, and both α-galactosidase A and lyso-GL3 in women, were measured on a drop of dried blood during the usual care of patients. GLA gene sequencing was performed in patients in whom one biological value was outside normal values. If a genetic variant was identified, a multidisciplinary Diagnosis Validation Committee (DVC) concluded, based on precise literature, clinical, biological and genetic data, as to the reality of Fabry disease. Results Among the 6,032 patients aged 18 to 75 years under chronic dialysis during the period considered, 714 were no longer treated in the participating centers when the research staff visited for eligibility assessment. 1,121 had non-inclusion criteria, which in 89% of cases were a confirmed diagnosis of kidney disease (by renal biopsy or other means) making the existence of Fabry disease very unlikely. 4,197 patients met the inclusion criteria, of which 3,088 were included (1,888 men and 1,200 women). Valid biological analyzes were available for 2815 patients (1721 men and 1094 women), and a genetic test was indicated for 91 patients (52 men and 39 women). Ninety-seven percent of the samples were analyzed with a unique assay technique in a unique laboratory. Five patients had a genetic variant (4 men and one woman). After discussion in the DVC, one male patient was considered to have a confirmed Fabry disease. He presented early signs of the disease (first-degree family history of cardiac or unexplained death, hypohidrosis, heat intolerance, tendency to chronic diarrhea, angiokeratoma, hypoacousia and tinnitus) which could have been identified earlier. The GLA variant was c.1185dupG / p.Phe396Glyfs, a clearly pathogenic frameshift variant. The prevalence of FD in included patients with biological data was 0.035% [0.006; 0.201] (0.058% [0.010; 0.33] in men, 0.000 % [0,000; 0.350] in women). If we consider that patients who were not included because of a specific renal diagnosis unrelated to FD did not have FD, the estimated prevalence decreased to 0.028% [0.006; 0.121]. Conclusion The estimated prevalence of FD in a cohort of French dialysis patients is 0.035% [0.006; 0.201], and by sex 0.058% in men [0.010; 0.328] and 0,000% in women [0,000; 0.35]. Although it appears extremely low, it remains justified to bring up this diagnosis in the event of an evocative sign, whether for the patient or his relatives as FD benefit of effective specific treatments. Funding for this Investigator Sponsored Study was provided by Sanofi Genzyme

Background and Aims Renal ischemia reperfusion (RIR) can induce mitochondrial stress triggering cell death and eventually leading to acute kidney injury (AKI). It has been suggested that mild hypothermia could be protective in RIR without clear underlying mechanisms. We aimed to show that mild hypothermia (34°C) during RIR protects renal mitochondrial function and prevents AKI. Method Male C57BL6 mice were assigned to 4 groups: normothermic ischemic (RIR-37°C) group (n=14) and hypothermic ischemic (RIR-34°C) group (n=14) with body temperature maintained at respectively 37°C or 34°C during 20 minutes of renal ischemia by bilateral renal clamping under general anesthesia; normothermic sham (Sham-37°C) group (n=10) and hypothermic sham (Sham-34°C) group (n=10) with only anesthesia and laparotomy at 37°C or 34°C respectively. Renal function (serum urea concentration) and isolated renal mitochondria function (capacity of mitochondria to retain calcium i.e. calcic retention capacity (CRC), and oxidative phosphorylation capacity of electron transport chain complexes (complex I, II and IV)) were assessed 2 hours and 24 hours after reperfusion. All animal procedures were approved by local Ethics Committee. Data are presented as median with IQR. Results All the parameters monitored were not modified by the temperature in the sham groups, and there was no mortality in those 2 groups. Mortality was 33% in the RIR-37°C group and 11% in the RIR-34°C group 24 hours after reperfusion (p=0.58). Renal ischemia was responsible for a significant increase of serum urea level 2 hours after reperfusion at 37°C [18.7 (17.3–19.0) mmol/L] compared to sham groups (p=0.02), whereas no significant increase was observed in the RIR-34°C group. After 24 hours of reperfusion serum urea level was improved in the RIR-34°C group [22.7 (11.5–42.0) mmol/L] compared to RIR-37°C [60.8 (58.0–69.7) mmol/L, p=0.001]. CRC was not modified by RIR after 2 hours of reperfusion in both groups. CRC was preserved 24 hours after reperfusion in the RIR-34°C group [260 (210–320) nmol Ca2+/mg protein] with no difference compared to Sham-37°C [320 (280–360) nmol Ca2+/mg protein p=0.18] whereas CRC was significantly decreased in the RIR-37°C group compared to Sham-37°C [120 (0–130) vs 320 (280–360) nmol Ca2+/mg protein p=0.004). Complexes I, II and IV were lowered after 2 hours of reperfusion in the RIR-37°C group (p Conclusion Mild hypothermia (34°C) during RIR significantly protected renal mitochondrial respiration and mitochondrial stress, associated with a preserved renal function after 2 hours of reperfusion and an improved renal function 24 hours after reperfusion compared to normothermic mice (37°C).

Background Reduction of renal blood flow (RBF) due to a renal artery stenosis (RAS) can lead to renal ischemia and atrophy. However in pigs, there are no data describing the relationship between the degree of RAS, the reduction of RBF, and the increase of systemic plasma renin activity (PRA). Therefore, we conducted a study in order to measure the effect of acute and gradual RAS on RBF, mean arterial pressure (MAP), and systemic PRA in pigs. Methods RAS was induced experimentally in six pigs using an occluder placed around the renal artery downstream of an ultrasound flow probe. The vascular occluder was inflated gradually to reduce RBF. At each inflation step, percentage of RAS was measured by digital subtraction angiography (DSA) with simultaneous measurements of RBF, MAP, and PRA. Data were normalized to baseline values obtained before RAS induction. Piecewise regression analysis was performed between percentage of RAS and relative RBF, MAP, and PRA, respectively. Results In all pigs, the relationship between the degree of RAS and RBF was similar. RBF decreased over a threshold of 42% of RAS, with a rapid drop in RBF when RAS reached 70%. PRA increased dramatically over a threshold of 58% of RAS (+1,300% before occlusion). MAP increased slightly (+15% before occlusion) without identifiable threshold. Conclusions This study emphasizes that the relation between the degree of RAS and RBF and systemic PRA is not linear and that a high degree of RAS must be reached before the occurrence of significant hemodynamic and humoral effects.