After acute kidney injury (AKI), renal function continues to deteriorate in some patients. In a pro-inflammatory and profibrotic environment, the proximal tubules are subject to maladaptive repair. In the AKI-to-CKD transition, impaired recovery from AKI reduces tubular and glomerular filtration and leads to chronic kidney disease (CKD). Reduced kidney secretion capacity is characterized by the plasma accumulation of biologically active molecules, referred to as uremic toxins (UTs). These toxins have a role in the development of neurological, cardiovascular, bone, and renal complications of CKD. However, UTs might also cause CKD as well as be the consequence. Recent studies have shown that these molecules accumulate early in AKI and contribute to the establishment of this pro-inflammatory and profibrotic environment in the kidney. The objective of the present work was to review the mechanisms of UT toxicity that potentially contribute to the AKI-to-CKD transition in each renal compartment.

Acute kidney injury (AKI) is a frequent disease encountered in the hospital, with a higher incidence in intensive care units. Despite progress in renal replacement therapy, AKI is still associated with early and late complications, especially cardiovascular events and mortality. The role of gut-derived protein-bound uremic toxins (PBUTs) in vascular and cardiac dysfunction has been extensively studied during chronic kidney disease (CKD), in particular, that of indoxyl sulfate (IS), para-cresyl sulfate (PCS), and indole-3-acetic acid (IAA), resulting in both experimental and clinical evidence. PBUTs, which accumulate when the excretory function of the kidneys is impaired, have a deleterious effect on and cause damage to cardiovascular tissues. However, the link between PBUTs and the cardiovascular complications of AKI and the pathophysiological mechanisms potentially involved are unclear. This review aims to summarize available data concerning the participation of PBUTs in the early and late cardiovascular complications of AKI.

Background and objectives: Activation of the complement system is involved in the pathogenesis of anti-glomerular basement membrane (anti-GBM) disease. Glomerular deposits of complement 3 (C3) are often detected on kidney biopsies. The primary objective of this study was to analyze the prognostic value of the serum C3 level and the presence of C3 glomerular deposits in patients with anti-GBM disease.Methods: We conducted a retrospective cohort study of 150 single-positive patients with anti-GBM disease diagnosed between 1997 and 2017. Patients were categorized according to the serum C3 level (forming a low C3 (C3<1.23 g/L) and a high C3 (C3≥1.23 g/L) groups) and positivity for C3 glomerular staining (forming the C3+ and C3- groups). The main outcomes were kidney survival and patient survival.Results: Of the 150 patients included, 89 (65%) were men. The median [interquartile range (IQR)] age was 45 [26–64]. At diagnosis, kidney involvement was characterized by a median [IQR] peak serum creatinine (SCr) level of 578 [298–977] µmol/L, and 106 (71%) patients required dialysis. Patients in the low C3 group (72 patients) had more severe kidney disease at presentation, as characterized by higher prevalences of oligoanuria, peak SCr ≥500 µmol/L (69%, vs. 53% in the high C3 group; p=0.03), nephrotic syndrome (42%, vs. 24%, respectively; p=0.02) and fibrous forms on the kidney biopsy (21%, vs. 8%, respectively; p=0.04). Similarly, we observed a negative association between the presence of C3 glomerular deposits (in 52 (41%) patients) and the prevalence of cellular forms (83%, vs. 58% in the C3- group; p=0.003) and acute tubulo-interstitial lesions (60%, vs. 36% in the C3- group; p=0.007). When considering patients not on dialysis at diagnosis, the kidney survival rate at 12 months was poorer in the C3+ group (50% [25-76], vs. 91% [78-100] in the C3- group; p=0.01), with a hazard ratio [95% confidence interval] of 5.71 [1.13-28.85] (p=0.04, after adjusting for SCr).Conclusion: In patients with anti-GBM disease, a low serum C3 level and the presence of C3 glomerular deposits were associated with more severe disease and histological kidney involvement at diagnosis. In patients not on dialysis at diagnosis, the presence of C3 deposits was associated with worse kidney survival.

In patients presenting with anti-glomerular basement membrane (GBM) disease with advanced isolated kidney involvement, the benefit of intensive therapy remains controversial due to adverse events, particularly infection. We aim to describe the burden of severe infections (SI) (requiring hospitalization or intravenous antibiotics) and identify predictive factors of SI in a large cohort of patients with anti-GBM disease. Among the 201 patients (median [IQR] age, 53 [30–71] years) included, 74 had pulmonary involvement and 127 isolated glomerulonephritis. A total of 161 SI occurred in 116 patients during the first year after diagnosis. These infections occurred during the early stage of care (median [IQR] time, 13 [8–19] days after diagnosis) with mainly pulmonary (45%), catheter-associated bacteremia (22%) and urinary tract (21%) infections. In multivariable analysis, positive ANCA (HR [95% CI] 1.62 [1.07−2.44]; p = 0.02) and age at diagnosis (HR [95% CI] 1.10 [1.00–1.21]; p = 0.047) remained independently associated with SI. Age-adjusted severe infection during the first three months was associated with an increased three-year mortality rate (HR [95% CI] 3.13 [1.24–7.88]; p = 0.01). Thus, SI is a common early complication in anti-GBM disease, particularly in the elderly and those with positive anti-neutrophil cytoplasmic antibodies (ANCA). No significant association was observed between immunosuppressive strategy and occurrence of SI.

Introduction: Les traitements immunosuppresseurs ont révolutionné la survie des patients atteints de maladie à anticorps anti-membrane basale glomérulaire (anti-MBG), néanmoins le pronostic rénal reste sombre. Chez les patients avec atteinte rénale isolée sévère, le bénéfice d’un traitement intensif reste discutable, notamment en regard du risque infectieux. L’objectif de cette étude était d’évaluer la survie globale et les complications infectieuses dans cette population. Méthodes: Il s’agit d’une étude multicentrique rétrospective française portant sur 201 patients ayants présenté une maladie à anti-MBG entre 1997 et 2017. Les critères de jugement étaient la mortalité globale à 3 ans et les infections sévères à 1 an. Résultats obtenus ou attendus La population a été divisée en 2 groupes en fonction de l’âge (>ou< à 60 ans) ; groupe 1 (n = 82 ; âge médian 73,5 ans) et groupe 2 (n = 119 ; âge médian 35 ans). Les patients du groupe 1 présentaient une atteinte rénale plus sévère (85 % contre 66 % de patients dialysés), plus d’ANCA positif contre plus d’hémorragie alvéolaire chez les plus jeunes. Le traitement intensif, combinant corticoïdes, échanges plasmatiques et immunosuppresseurs, a été réalisé chez 56 et 72 % des patients des groupes 1 et 2. À 1 an, 140 infections sévères ont été répertoriées chez 116 patients. Les facteurs indépendant associés au risque d’infections à 1 an étaient la présence d’ANCA (HR 1,66) et le taux de CRP au diagnostic (HR 1,02 tous les 10 points). La médiane de suivi était de 73 mois et la survie estimée à 3 ans était de 89 %. Après ajustement sur l’âge, les facteurs associés au décès étaient le diabète (HR 3,15) et l’indice de Charlson modifié (HR 1,38), l’HTA (HR 2,62) et l’infection précoce (HR 3,13). Conclusion: La maladie à anticorps anti-MBG est associée à une survie globale satisfaisante conditionnée essentiellement par l’âge, les comorbidités cardiovasculaires et l’infection. Le risque infectieux à 1 an reste important, notamment chez les patients ANCA positifs.