L'épuration extra-rénale chez les patients diabétiques de type I (modalités de la prise en charge néphrologique)

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

La doxycycline ou comment faire du neuf avec du vieux ?

Les tétracyclines sont des antibiotiques à large spectre interférant avec la synthèse des protéines. Ils ont d’abord été largement prescrits par les dermatologues au début des années 1950 dans le traitement de l’acné. Plus récemment, les actions biologiques sur l’inflammation, la protéolyse, l’angiogenèse, l’apoptose, la chélation des métaux, ionophorèse, et le métabolisme osseux ont été étudiés. Les métalloprotéinases matricielles (MMP) représentent une famille d’enzymes protéolytiques qui dégradent les différents composants de la matrice extracellulaire (MEC). Les MMPs ont des effets directs ou indirects de MMP sur l’endothélium vasculaire et sur le système de contraction-relaxation vasculaire. Les effets thérapeutiques des tétracyclines et analogues ont été étudiés au cours de la rosacée, les dermatoses bulleuses, les maladies neutrophiles, la pyoderma gangrenosum, la sarcoïdose, les anévrismes de l’aorte, les métastases de cancer, la parodontite et les maladies auto-immunes comme la polyarthrite rhumatoïde et la sclérodermie. De plus, la régulation négative de MMP utilisant la doxycycline pourrait être bénéfique dans la réduction de la dysfonction vasculaire médiée par les MMPs et les dommages progressifs de la paroi vasculaire. Nous passons en revue les propriétés non-antibiotiques de la doxycycline et ses applications cliniques potentielles

Nephrotic Syndrome Associated with Lung Cancer: A Rare Case of Malignancy Associated with AA Amyloidosis

Nonhematologic malignancies are rarely reported to be associated with AA amyloidosis. Although the association between renal cell carcinoma and systemic AA amyloidosis has been established, the evidence linking pulmonary cancer to AA amyloidosis is scarce. Here, a case of biopsy-proven renal AA amyloidosis complicated with nephrotic syndrome associated with lung carcinoma is reported

Carfilzomib-Induced Thrombotic Microangiopathy Treated with Eculizumab: A Case Report and Rapid Literature Review

Background: Thrombotic microangiopathies (TMAs) can be induced by drugs. Recent works have indicated proteasome inhibitors, including carfilzomib, as a possible new causative agent. Although the physiopathology and management of carfilzomib-induced TMA are still unknown, eculizumab seems to be efficient. Results: We report a clinical case of TMA during carfilzomib treatment for multiple myeloma, possibly triggered by a concomitant influenza infection, suggesting a multi-hit process. Histologic analysis of the kidney biopsy proved renal TMA. Eculizumab allowed rapid and long-lasting renal and hematologic recovery. We enriched our work with a systemic review of published cases of carfilzomib-induced TMA treated by eculizumab. Twelve patients were included, all of whom presented acute renal failure and nine of them required hemodialysis. Eculizumab led to TMA resolution in eleven patients and complete renal recovery with hemodialysis withdrawal for seven of them within a month. One patient died from multiple myeloma progression. Two patients presented inter-current viral infection. Soluble complement fragment Bb and C5b9s were found in two patients and genetic benign variant of Factor H (CFH3–CFH1) in four. Conclusion: Our results suggest that eculizumab is effective in carfilzomib-induced TMA, which could support its inclusion as a treatment option. Further studies are required to clarify its physiopathology, complement role, and management

Carfilzomib-Induced Thrombotic Microangiopathy Treated with Eculizumab: A Case Report and Rapid Literature Review

Background: Thrombotic microangiopathies (TMAs) can be induced by drugs. Recent works have indicated proteasome inhibitors, including carfilzomib, as a possible new causative agent. Although the physiopathology and management of carfilzomib-induced TMA are still unknown, eculizumab seems to be efficient. Results: We report a clinical case of TMA during carfilzomib treatment for multiple myeloma, possibly triggered by a concomitant influenza infection, suggesting a multi-hit process. Histologic analysis of the kidney biopsy proved renal TMA. Eculizumab allowed rapid and long-lasting renal and hematologic recovery. We enriched our work with a systemic review of published cases of carfilzomib-induced TMA treated by eculizumab. Twelve patients were included, all of whom presented acute renal failure and nine of them required hemodialysis. Eculizumab led to TMA resolution in eleven patients and complete renal recovery with hemodialysis withdrawal for seven of them within a month. One patient died from multiple myeloma progression. Two patients presented inter-current viral infection. Soluble complement fragment Bb and C5b9s were found in two patients and genetic benign variant of Factor H (CFH3–CFH1) in four. Conclusion: Our results suggest that eculizumab is effective in carfilzomib-induced TMA, which could support its inclusion as a treatment option. Further studies are required to clarify its physiopathology, complement role, and management

The predictive performance of the ANCA renal risk score in patients over 65 years of age with renal ANCA-associated vasculitis

International audienceBackground The anti-neutrophil cytoplasmic antibody (ANCA) renal risk score (ARRS) for predicting renal survival in ANCA-associated vasculitis (AAV) had not previously been validated in adults over 65 years of age and presenting impairments associated with an aging kidney, a high cardiovascular comorbidity burden, and prevalent microscopic polyangiitis. Methods We retrospectively studied a cohort of 192 patients over 65 years of age (median [interquartile range] age: 73 [68; 78]), including 17.2% with renal-limited vasculitis, 49.5% with microscopic polyangiitis and 33.3% with granulomatosis with polyangiitis, at six centres of northern France. The primary study endpoint was the cumulative incidence of end-stage kidney disease (ESKD, maintenance of dialysis for at least 3 months) at 12 months, with death considered as a competing event. Results The median serum creatinine concentration at diagnosis was 300 [202; 502] µmol/L, and 48 (25.0%) patients required dialysis at presentation. The ARRS was high in 43 (22.4%) patients, medium in 106 (55.2%), and low in 43 (22.4%). The cumulative incidence of ESKD at 12 months was 0% in the low-risk group, 13.0% [7.6–20.0] in the medium-risk group, and 44.0% [29.0–58.0] in the high-risk group (p < 0.001). In the subgroup of 149 patients presenting a medium or high score, the ARRS had a C-index of 0.66 [0.58–0.74] for the prediction of ESKD at 12 months; this rose to 0.86 [0.80–0.90] when dialysis status at diagnosis was included. Conclusion The ARRS was a poor predictor of kidney survival at 12 months among patients over 65 years of age with renal AAV involvement—especially in the high ARRS group. The addition of dialysis status at diagnosis as an additional clinical parameter might improve the ARRS's predictive performance

Renal β-intercalated cells maintain body fluid and electrolyte balance

Inactivation of the B1 proton pump subunit (ATP6V1B1) in intercalated cells (ICs) leads to type I distal renal tubular acidosis (dRTA), a disease associated with salt- and potassium-losing nephropathy. Here we show that mice deficient in ATP6V1B1 (Atp6v1b1-/- mice) displayed renal loss of NaCl, K+, and water, causing hypovolemia, hypokalemia, and polyuria. We demonstrated that NaCl loss originated from the cortical collecting duct, where activity of both the epithelial sodium channel (ENaC) and the pendrin/Na+-driven chloride/bicarbonate exchanger (pendrin/NDCBE) transport system was impaired. ENaC was appropriately increased in the medullary collecting duct, suggesting a localized inhibition in the cortex. We detected high urinary prostaglandin E2 (PGE2) and ATP levels in Atp6v1b1-/- mice. Inhibition of PGE2 synthesis in vivo restored ENaC protein levels specifically in the cortex. It also normalized protein levels of the large conductance calcium-activated potassium channel and the water channel aquaporin 2, and improved polyuria and hypokalemia in mutant mice. Furthermore, pharmacological inactivation of the proton pump in β-ICs induced release of PGE2 through activation of calcium-coupled purinergic receptors. In the present study, we identified ATP-triggered PGE2 paracrine signaling originating from β-ICs as a mechanism in the development of the hydroelectrolytic imbalance associated with dRTA. Our data indicate that in addition to principal cells, ICs are also critical in maintaining sodium balance and, hence, normal vascular volume and blood pressure

Sodium bicarbonate (NaHCO 3 ) prescription and extracellular volume increase: real‐world data results from the AlcalUN study

International audienceOral alkalization with sodium bicarbonate (NaHCO3) or citrate is prescribed for conditions ranging from metabolic acidosis to nephrolithiasis. While most nephrologists/urologists use this method routinely, extracellular volume (ECV) increase is the main feared adverse event reported for NaHCO3. Thus far, no trial has specifically studied this issue in a real-world setting. AlcalUN (NCT03035812) is a multicentric, prospective, open-label cohort study with nationwide (France) enrollment in 18 (public and private) nephrology/urology units. Participants were adult outpatients requiring chronic (>1 month) oral alkalization by either NaHCO3-containing or no-NaHCO3-containing agents. The ECV increase (primary outcome) was judged based on body weight increase (ΔBW), blood pressure increase (ΔBP), and/or new-onset edema at the first follow-up visit (V1). From 02/2017 to 02/2020, 156 patients were enrolled. After a median 106 days of treatment, 91 (72%) patients reached the primary outcome. They had lower systolic (135 [125, 141] vs. 141 [130, 150], p=0.02) and diastolic (77 [67, 85] vs. 85 [73, 90], p=0.03) BP values, a higher plasma chloride (106.0 [105.0, 109.0] vs. 105.0 [102.0, 107.0], p=0.02) at baseline, and a less frequent history of nephrolithiasis (32 vs. 56%, p=0.02). Patients experienced mainly slight increases in blood pressure (ΔBP<10 mmHg). The primary outcome was not associated (p=0.79) with the study treatment (129 received NaHCO3, 27 received citrate). We subsequently developed 3 different models of propensity score matching; each confirmed our results. Chronic oral alkalization with NaHCO3 is no longer associated with an ECV increase compared to citrate in real-life settings

Imported Malaria, Collapsing Glomerulopathy, and Focal and Segmental Glomerulosclerosis

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