Epidemiological and clinicopathological characteristics of vascular-limited renal AL amyloidosis.

Background and hypothesis: 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, these vascular-limited forms following a distinct clinical course, but very little is known about these forms. Our work plan at better characterizing renal vascular limited AL amyloidosis.

Methods: By mining 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.

Results: 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 167 (127-213) 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 FLC 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 (OS) was 59 months, significantly longer in patients who achieved a deep hematological response (178 vs 20 months, p = 0.002).

Conclusion: 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.