Outcome of patients with severe AL amyloidosis and biopsy-proven renal involvement ineligible for bone marrow transplantation

Abstract

INTRODUCTION: AL amy loidosis is caused by a plasma cell clone. Due to the impact of the disease on patient survival, careful evaluation of organ involvement is essential. Treat ment of A L amy loidosis should be adapted to the patient's degree of risk. AIM : We analy zed the clinical, laboratory and histological characteristics of 21 elderly patients (pts) (mean age 74.7 ± 7.97 yrs, range 55-81) with AL amylo idosis, including 17 patients (81%) with biopsy-proven renal involvement, who were ineligib le for bone marro w transplantation, and evaluated the impact of renal impairment on survival. RESULTS: Card iac and renal involvement was found in 67% of cases. Among the 17 patients with renal involvement, 12 had renal failure with proteinuria, and 1 showed isolated renal failu re and vascular amylo id deposition. Hematological response was 57.1 % at first line therapy (75% after three cycles). With regard to renal outcome, 6 of the 17 patients with renal involvement responded: proteinuria decreased fro m 4.2 to 1.1 gr/24 h (range 0.2-3 gr/ 24 h) with stabilization or improvement of serum Creatinine (sCr) levels. Applying the Staging System for Renal Outcome in AL A mylo idosis to our pts with biopsy-proven renal amylo idosis proved to be unreliable. Only severe renal failu re at d iagnosis was found to directly influence patient survival. CONCLUSIONS: To our knowledge this is the only case series in which the whole cohort of patients with urinary or functional abnormalit ies underwent a histological evaluation. None of the patients were elegible for bone marro w transplantation. Hematologic response was 57.1%, wh ile renal response was much lower (35%).Of note, the Staging System d id not comp letely apply to this peculiar setting of patients in who m renal involvement was not presumptive but actually biopsy-proven. More aggressive approaches are needed in these patients to avoid the inexorable progression of the disease.

Chinese collaborative study of survival analysis in 980 patients with AL amyloidosis

“…Although the prognosis value of lower eGFR is controversial [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36], renal response has been shown to be associated with overall survival [22]. Superior OS was observed in patients with proteinuria reduction >75% [23].…”

“…The increase in the afterload of CKD patients is related to the increase in NT-pro BNP [28]. Furthermore, CKD patients reduce the sensitivity of treatment [26], and it is difficult to obtain the expected treatment effect and indicates poor prognosis. The role of eGFR expands the predictable population, providing a new model suitable for screening patients with heart and kidney involvement.…”

“…[25] indicated that the outcome of patients with renal and cardiac involvement death depends on the NT‐proBNP and eGFR values at the time of diagnosis. Importantly, the renal response rate after treatment is lower than that of the heart [26], indicating that patients with renal involvement may need more active treatment. In the group of patients with eGFR <60 mL/min/1.73 m 2 in our cohort, 75% of them exhibited the values of NT‐proBNP and cTNI below the cut‐off.…”

Renal Involvement in Transthyretin Amyloidosis: The Double Presentation of Transthyretin Amyloidosis Deposition Disease

“…Renal biopsy and gene se-quencing are both critical in diagnosing ATTR. The kidney is one of the most vulnerable organs for AL amyloidosis [1] but is seldom taken into consideration as a potential target for TTR deposition. Especially when 99mTc-PYP scintigraphy and electromyography are positive, renal biopsy has to be considered in any subject presenting with initial evidence of renal impairment and even mild urinary abnormalities.…”

“…Systemic amyloidosis is a cluster of disorders characterized by tissue deposition of amyloid, categorized upon etiology as primary (AL) amyloidosis, secondary (AA) amyloidosis (or reactive amyloidosis), familial amyloidosis (hereditary amyloidosis), dialysis-related amyloidosis, and senile amyloidosis [1][2][3]. Inherited types of amyloidosis are autosomal dominant, and transthyretin (TTR) amyloidosis (ATTR) is the most frequent hereditary pattern [4].…”