Nephrologie & therapeutique最新文献

Introduction: Acute rejection remains a major threat to long-term graft survival. Subclinical forms may go undetected without histological assessment, leading to progressive injury. This study evaluates the role of protocol biopsies in detecting subclinical rejection and preserving graft function and examines the prognostic significance of early histological findings and estimated glomerular filtration rate (eGFR) at discharge.

Methods: A retrospective, single-center study of kidney transplant recipients who underwent an early protocol biopsy. Clinical, immunological, and histopathological data were collected, including induction therapy, renal function (eGFR), and Banff inflammatory scores. Associations between histology, renal recovery, and long-term outcomes were analyzed.

Results: Among the 99 patients, rejection was detected in 20.2%, predominantly T-cell mediated (90%). Early intervention significantly improved renal function, with a mean eGFR increase from 36.0±23.1 to 51.0±21.7 mL/min/1.73 m² (p<0.001). The change in eGFR (ΔeGFR) was significantly greater in patients with rejection compared to those without (11.1 vs 1.2 mL/min/1.73 m²; p<0.01). Higher eGFR at discharge was strongly associated with better long-term renal function (p<0.001).

Conclusions: Protocol biopsies are key for early detection of subclinical rejection, enabling timely intervention. Discharge eGFR strongly predicts long-term outcomes.

Background: Long-term management strategies for IgA Nephropathy (IgAN) remain insufficiently studied. This study aims to address this gap by comparing patients with persistent proteinuria who did not receive additional treatment with those whose persistent proteinuria led to on-demand immunosuppressive treatment.

Methods: This retrospective cohort study included 264 propensity score-matched patients with IgAN treated between January 2003 and December 2016, with a follow-up through August 2024. Patients with proteinuria ≥1g/day without a 40% decline in eGFR over the previous 3 months, despite adequate supportive therapy, were considered eligible for on-demand immunosuppressive therapy during follow-up. Effective regimens-including glucocorticoids, cyclophosphamide, or mycophenolate mofetil, alone or in combination with other immunosuppressive drugs-were considered distinct treatment courses only if separated by at least six months. Survival was analyzed using the Kaplan-Meier estimator, and the primary composite endpoint was analyzed using the Cox proportional hazards model.

Results: Over a median follow-up of 9.9 years (interquartile range, 7.3-12.8 years), 65 of 264 (25%) experienced the primary composite endpoint. Risk was lower among patients who consistently received on-demand immunosuppressive therapy compared with those who did not (10/132 [8%] vs. 55/132 [42%]; hazard ratio, 0.11; 95% CI, 0.05-0.21; p < 0.001). The incidence of the primary endpoint increased progressively with the number of missed on-demand immunosuppressive therapy: 27/34 (79%), 17/34 (50%), and 11/64 (17%) among patients who missed 3 or more, 2, or 1 treatment(s) respectively. Of the 281 missed on-demand treatment opportunities, 107 (38%) were attributable to patient-related factors and 174 (62%) to physician-related factors.

Conclusions: On-demand immunosuppressive therapy is associated with improved long-term outcomes in patients with IgAN.

Until 2009, atypical hemolytic uremic syndrome (aHUS), a disease mediated by complement-induced endothelial activation, had a poor renal prognosis, with common progression to kidney failure and frequent recurrence after kidney transplantation, condemning often young patients to lifelong dialysis. Initially developed for paroxysmal nocturnal hemoglobinuria, anti-C5 monoclonal antibodies – eculizumab and later ravulizumab – were rapidly evaluated for the management of atypical HUS. Clinical development was based on uncontrolled studies, but with effects on microangiopathy and renal function recovery that were clearly more favorable than the spontaneous course of the disease.Nowadays, the use of anti-C5 monoclonal antibodies is recommended as first-line therapy for thrombotic microangiopathy associated with atypical HUS and for relapse prevention, particularly in the context of kidney transplantation, in both adults and children. Ravulizumab appears to have the same efficacy as eculizumab while allowing injections to be spaced every 8 weeks instead of every 2. Finally, the most feared adverse effect of these treatments is meningococcal infection, whose frequency is fortunately low thanks to prophylactic vaccination strategies and antibiotic prevention.

We report the case of a 17-year-old male with an unremarkable medical history, admitted for acute nephritic syndrome associated with acute renal failure. His presentation occurred three weeks after a generalized febrile cutaneous rash that had been diagnosed as measles. Renal biopsy revealed acute glomerulonephritis (AGN) with cellular crescents; the outcome was favorable under treatment.Measles is a highly contagious disease, and a resurgence in its prevalence has been observed worldwide, including in Morocco. Although the measles virus is known to be nephritogenic and may lead to AGN, its association with glomerular involvement remains uncommon and has been infrequently documented in the medical literature.

L’infection à cytomégalovirus (CMV) est la principale infection opportuniste après transplantation rénale. Des nouveautés dans les stratégies de sa prise en charge chez le patient transplanté rénal existent désormais. En effet, dans les dernières recommandations internationales, le létermovir peut être proposé lors d’une stratégie prophylactique chez des patients à haut risque de CMV (donneur séropositif/receveur séronégatif). Le rôle potentiel des inhibiteurs de la mTOR dans la prévention de l’infection à CMV chez les transplantés rénaux CMV séropositifs a également été souligné. Chez ces patients, si la mesure de l’immunité spécifique anti-CMV par les techniques Quantiferon-CMV ou l’ELISpot est positive à un mois post-transplantation, la durée de la prophylaxie peut être réduite, tout en continuant une surveillance par biologie moléculaire. Le traitement de l’infection à CMV repose toujours sur le (val)ganciclovir en première intention. Cependant, en cas d’intolérance à ce traitement, le maribavir ou le foscarnet représentent des alternatives de deuxième intention. En cas de CMV résistant/réfractaire, le maribavir est le traitement de première intention, sauf en cas d’atteinte du système nerveux central, de rétinite à CMV ou de virémie élevée. Dans ces cas, le foscarnet doit être préféré. L’utilisation du maribavir en vie réelle en France a montré des résultats identiques à ceux de l’étude pivotale Solstice avec une incidence moindre de résistance au maribavir.

The year 2025 confirms the transition of kidney transplantation toward a precision-­medicine paradigm, marked by major advances in pathophysiology, diagnostics, and therapeutics. The study by Sablik et al. redefined the spectrum of antibody-mediated rejection (ABMR) by highlighting the prognostic importance of microvascular inflammation, even in the absence of DSA or C4d deposition. Circulating biomarkers (donor-derived cell-free DNA [dd-cfDNA] and transcriptomic signatures) are now established as key tools for detecting and monitoring rejection, while anti-CD38 antibodies and intravenous immunoglobulins open new therapeutic perspectives in chronic active ABMR. Antiviral immunomonitoring and virus-specific cellular therapies represent a decisive step toward targeted restoration of antiviral immunity, and SGLT2 inhibitors are emerging as cornerstone agents for cardio-renal protection. Advances in quantitative imaging enable non-invasive assessment of graft fibrosis. Finally, xenotransplantation has entered a phase of experimental validation, with the first detailed immunologic characterizations in humans. Together, these developments confirm the convergence of molecular, immunologic, and technological approaches toward truly individualized management of kidney-transplant recipients.

Cardiovascular mortality among hemodialysis patients remains strikingly high—around 10% per year—despite substantial advances in dialysis technology and medical care. Historically, several strategies extrapolated from the general population have failed to improve outcomes: The landmark 4D and AURORA trials showed no cardiovascular or survival benefit from statin therapy in dialysis patients, whereas high-volume online hemodiafiltration (ESHOL, CONVINCE) significantly reduced all-cause mortality, though without a specific reduction in cardiovascular deaths. More recently, large randomized controlled trials have again underscored the difficulty of improving cardiovascular outcomes in dialysis through pharmacological means: The ACHIEVE and ALCHEMIST trials found no clinical benefit from low-dose spironolactone on cardiovascular mortality or heart-failure hospitalization, and the DIALIZE-Outcomes trial showed that improved potassium control with sodium zirconium cyclosilicate did not reduce sudden cardiac death or arrhythmic events. Taken together, these neutral findings emphasize the complex, multifactorial nature of cardiovascular risk in dialysis, driven by “non-traditional” mechanisms such as inflammation, vascular calcification, oxidative stress, and intradialytic myocardial ischemia. In this context, recent studies from the Avignon group in France have identified intradialytic and pre-­dialysis exercise as a promising non-pharmacological intervention capable of mitigating myocardial stunning and improving cardiac function. In summary, while classical cardioprotective strategies continue to fall short, emerging evidence highlights the potential of innovative, physiology-based approaches—optimizing dialysis modalities and leveraging exercise-induced cardioprotection—to address the persistent cardiovascular burden of uremia.

In 2025, nephrology saw major advances in diagnosing and managing chronic kidney diseases. A new diagnostic framework, CKDx (chronic kidney disease of unexplained cause), was proposed to standardize patient evaluation by integrating genetic and histological tests. Therapeutic progress includes the demonstrated efficacy of atrasentan, an endothelin type A receptor antagonist, in IgA nephropathy, as well as that of iptacopan, an oral inhibitor of factor B, in IgA nephropathy and C3-deposit glomerulopathy. Obinutuzumab, a humanized anti-CD20 antibody, has also shown efficacy in lupus nephritis. Nephroprotective strategies, such as the finerenone-empagliflozin combination, have revealed significant benefits. Finally, emerging molecules such as baxdrostat, an aldosterone synthase inhibitor, and oral semaglutide, a GLP-1 analog, have demonstrated efficacy in resistant hypertension and in cardiovascular-risk reduction, respectively. These two molecules are currently being evaluated for preventing the progression of chronic kidney disease. However, challenges persist, including unequal access to innovative treatments, gaps in early screening, and the impact of climate change on kidney function. These results highlight the need for an integrated approach, combining innovation, equity, and adaptation to environmental changes to improve the care of patients with kidney diseases.