Senot Noémie, Gibier Jean Baptiste, Rabant Marion, Esteve Emmanuel, Ferriere Elsa, Dessaix Kathleen, Colombat Magali, Perrochia Helene, Olagne Jerome, Goujon Jean Michel, Wayolle Nicolas, Wemeau Mathieu, Carpentier Benjamin, Pinson Pierre, Beeker Nathanael, Bridoux Frank, Cohen Camille
Department of Internal Medicine, APHP, HôpitalEuropéen Georges Pompidou, Paris, France.
Institute of Pathology, Centre Hospitalier Universitaire de Lille, Lille, France.
Nephrol Dial Transplant. 2025 Jun 30;40(7):1396-1407. doi: 10.1093/ndt/gfae285.
Kidney involvement, along with cardiac disease, is the most frequent manifestation of systemic AL amyloidosis, usually resulting in nephrotic-range proteinuria. Rarely, deposits predominantly or exclusively affect the intrarenal arterioles or arteries, with these vascular-limited forms following a distinct clinical course, but very little is known about these forms. Our work planned to better characterize renal vascular-limited AL amyloidosis.
By mining a French Paris hospital database, we found that this unusual phenotype accounts for approximatively 9% of renal AL amyloidosis cases. We retrospectively studied 35 patients with the renal vascular-limited variant of AL amyloidosis on kidney biopsy.
All showed predominant or only (n = 21) intra-renal vascular deposits, of lambda isotype in 63%. At diagnosis, median urine protein/creatinine ratio was 0.5 g/g, with serum creatinine of 181 (133-216) µmol/L and estimated glomerular filtration (eGFR) rate of 36.2 (24.3-49.6) mL/min/1.73 m2. Cardiac involvement was present in 67% of cases. A serum and/or urine monoclonal gammopathy was identified in all but one patient and 31 (88%) had an abnormal free light chain ratio. Among 28 treated patients, hematological and renal response rates were 75% (including deep hematological response in 43%) and 18%, respectively. Median time from diagnosis to renal event, defined be a composite criterion composed of end-stage renal disease or >40% decrease in eGFR, was 56 months. Median overall survival was 59 months-significantly longer in patients who achieved a deep hematological response (178 vs 20 months, P = .002).
Renal vascular-limited AL amyloidosis is a probably underdiagnosed disease with markedly reduced eGFR, low-grade proteinuria and severe overall prognosis. Rapid achievement of a deep hematological response is required to preserve long-term renal and patient outcomes.
肾脏受累与心脏疾病一样，是系统性AL淀粉样变性最常见的表现，通常导致肾病范围的蛋白尿。很少有沉积物主要或仅影响肾内小动脉或动脉，这些血管受限形式遵循独特的临床病程，但对这些形式了解甚少。我们的研究旨在更好地描述肾血管受限型AL淀粉样变性。
通过挖掘法国巴黎一家医院的数据库，我们发现这种不寻常的表型约占肾AL淀粉样变性病例的9%。我们对35例经肾活检确诊为肾血管受限型AL淀粉样变性的患者进行了回顾性研究。
所有患者均表现为主要或仅（n = 21）肾内血管沉积物，其中63%为λ亚型。诊断时，尿蛋白/肌酐比值中位数为0.5 g/g，血清肌酐为181（133 - 216）µmol/L，估计肾小球滤过率（eGFR）为36.2（24.3 - 49.6）mL/min/1.73 m²。67%的病例存在心脏受累。除1例患者外，所有患者均检测到血清和/或尿单克隆丙种球蛋白病，31例（88%）患者游离轻链比值异常。在28例接受治疗的患者中，血液学和肾脏反应率分别为75%（包括43%的深度血液学反应）和18%。从诊断到肾脏事件（定义为终末期肾病或eGFR下降>40%的综合标准）的中位时间为56个月。中位总生存期为59个月，深度血液学反应患者的生存期显著延长（178个月对20个月，P = 0.002）。
肾血管受限型AL淀粉样变性可能是一种诊断不足的疾病，eGFR明显降低、蛋白尿程度低且总体预后严重。需要迅速实现深度血液学反应以维持长期肾脏和患者预后。
