Denis Fouque

The discovery of Cystic Fibrosis Transmembrane conductance Regulator (CFTR) modulators has revolutionized the management and clinical outcomes of cystic fibrosis. However, the pleiotropic effects of these new treatments outside the lungs are still largely unknown. Here we report two unusual cases of acute kidney injury in patient with cystic fibrosis (pwCF) following a first exposure to aminoglycoside while under triple correction therapy. We hypothesize that CFTR modulator therapy restored the reabsorption of aminoglycoside in the proximal tubule of the kidneys, a process that is primarily deficient in patients with cystic fibrosis, thus exacerbating the toxicity of these molecules.

Background: Obesity is a growing public health concern and an independent contributor to chronic kidney disease, with obesity-related glomerulopathy (ORG) representing a distinct but insufficiently characterized entity. This study aimed to comprehensively describe the spectrum of kidney histological damage in patients with obesity and overt kidney disease. Methods: We reviewed 503 native kidney biopsies performed at Hospices Civils de Lyon between 2019 and 2022, identifying 103 adults with obesity. Glomerular histology was compared to 206 controls matched 2:1 for age, sex, hypertension, and diabetes. Results: In the cohort with obesity, mean body mass index (BMI) was 35.1 kg/m²; 83% had hypertension and 33% had diabetes. Biopsies were performed for active urinary sediment (56%), proteinuria (49%), and acute or chronic kidney failure (31% of cases each). The mean estimated glomerular filtration rate was 47 ml/min/1.73 m², and proteinuria was 3.13 g/day. The post-biopsy complication rate was similar between groups. A wide spectrum of renal lesions was observed: hypertensive nephrosclerosis (34%), acute tubular necrosis (34%), diabetic nephropathy (17%), IgA nephropathy (13%), and other glomerulonephritides. ORG was identified in 25.2% of cases, isolated in 6.8% and associated with other lesions in 18.4%, while 74.8% had alternative diagnoses. Although no significant difference in glomerular size was observed between patients with obesity and controls, glomerular diameter was positively correlated with BMI (P = .049). Conclusion: ORG is not the predominant cause of kidney disease in patients with obesity. Given the wide range of alternative diagnoses and the safety of the procedure, renal biopsy should be considered to guide accurate diagnosis and optimize management.

The transition from advanced chronic kidney disease (CKD) to kidney failure requires comprehensive management to optimize patient outcomes. This crucial period, in practical terms defined by CKD stages G4 and G5, involves complex decision-making regarding kidney replacement therapy, pre-emptive kidney transplantation and conservative kidney management. Patient preferences, quality of life, and comorbidities, especially cardiovascular disease, are essential considerations when making treatment decisions. Importantly, nephroprotective therapies should be continued even at advanced stages of CKD to stabilize kidney function and prevent cardiovascular events. Pre-emptive kidney transplantation, when feasible, offers the best outcomes and should be prioritized. Dialysis initiation should be based on clinical symptoms and shared decision-making with the patient, rather than laboratory values alone. For some, particularly older, patients with substantial comorbidities, conservative kidney management, emphasizing symptom management without kidney replacement therapy, might be preferred. Considerable disparities in access to care exist globally, especially in low- and middle-income countries, highlighting the need for tailored strategies. Registry and cohort studies have provided most of the scientific understanding in this area, but more randomized clinical trials are needed to guide advanced CKD management.

Background: In early chronic kidney disease (CKD), a low-protein diet (LPD) may reduce glomerular hyperfiltration and delay progression, however, long-term studies in middle-income countries are limited. This study evaluates the impact of adherence to an LPD on CKD progression in Brazilian patients. Methods: A total of 438 patients were studied from a single centre in Brazil between 2010 and 2024, comprising 306 patients who adhered to the LPD (0.88 g/kg/day), based on calculations from 24-hour dietary recalls. The primary outcome was CKD progression, evaluated by the annual decrease in estimated glomerular filtration rate (eGFR). Progression was analysed both as a continuous variable (rate of eGFR decline over time) and by classification into normal decline (0–4.9 ml/min/year) or fast decline (>5 ml/min/year). A linear mixed model was used to evaluate the impact of adherence to an LPD on eGFR decline over time, adjusting for potential confounders. Results: The eGFR was comparable between groups, with adherent participants having a mean of 33.58 ± 13.71 ml/min/1.73 m2 and a mean age of 63.5 ± 13.8 years and the non-adherent group having a mean of 31.54 ± 13.18 ml/min/1.73 m2 and a mean age of 62.9 ± 15.3 years at baseline. Regarding protein intake and eGFR decline classification, no significant differences were observed between the groups. However, in the adjusted analysis, participants who adhered to the LPD had a significantly slower annual decline in eGFR compared with non-adherent individuals. The estimated mean annual change in eGFR was −0.29 ml/min/1.73 m2 for adherent participants and −1.40 ml/min/1.73 m2 for non-adherent participants. The absolute adjusted difference between groups was 1.10 ml/min/1.73 m2 (95% confidence interval 0.34–1.87; P = .0048). Conclusions: The findings support the potential nephroprotective role of LPD adherence in prolonging kidney function, reinforcing the importance of dietary management in CKD treatment.

Background: Arterial hypertension is highly prevalent among patients with chronic kidney disease (CKD), acting both as a cause and consequence of declining kidney function, and significantly increasing cardiovascular risk. Among modifiable risk factors, diet—particularly excessive sodium intake—plays a central role in the prevention and personalized management of CKD. Methods: This study aimed to develop an innovative, digitally accessible tool to estimate sodium intake in stages 3 to 5 CKD patients, using 24-h urinary sodium excretion as the reference standard. Results: Twenty-five clinical, biological, therapeutic, and dietary variables were collected from 493 patients followed across 6 French centers. A probabilistic Tree-Augmented Naive Bayes model was used to develop the tool based on the 15 most informative variables. The model demonstrated an internal accuracy of 71%, indicating that predicted and observed sodium intake categories matched in 71% of cases. Conclusions: This AI-based prediction model offers a promising clinical tool to estimate daily sodium intake in patients with stages 3 to 5 CKD. However, external validation using independent national and international datasets is essential to establish its robustness and generalizability prior to implementation in routine clinical practice.