CLINICOPATHOLOGICAL SPECTRUM AND OUTCOMES OF RENAL AMYLOIDOSIS: A SYSTEMATIC REVIEW

Abstract

Background: Renal amyloidosis is a heterogeneous collection of disorders defined by the accumulation of misfolded protein fibrils within the kidney. This condition leads to proteinuria, nephrotic syndrome, and ultimately kidney failure. Although improvements have been made in the diagnosis and treatment of amyloidosis, there continues to be an incomplete understanding of the overall clinicopathological spectrum and long-term prognosis associated with renal amyloidosis. To develop a better understanding of these issues, this systematic review provides a detailed synthesis of the epidemiology, pathological subtypes, clinical manifestations, renal pathology, prognostic indicators and treatment results for patients with renal amyloidosis. Methods: In order to find relevant literature, we searched MEDLINE (PubMed), EMBASE, Cochrane Library, and Web of Science from their beginning to March 2025 with no language restrictions. Included in our analyses were studies that provided original data about renal amyloidosis (including cohorst studies, case series of ≥10 patients and RCTs). Two independent reviewers screened titles, abstracts and full texts of all found candidates for this form of data collection. Data were extracted on demographics, amyloid subtype, pathological findings, clinical features, renal outcomes, and therapeutic interventions. Quality was assessed using the Newcastle–Ottawa Scale (NOS) for observational studies and the Cochrane Risk of Bias tool for RCTs. Results: Twenty-five studies comprising 4,863 patients met inclusion criteria. AL amyloidosis was the most prevalent subtype in Western cohorts (60–70%), followed by AA amyloidosis (15–25%), particularly in developing nations and in patients with chronic inflammatory diseases. Nephrotic-range proteinuria (mean 6.8 g/day) was the dominant clinical presentation across subtypes. Pathologically, glomerular deposits were universal, with mesangial and capillary wall involvement in AL and predominantly mesangial deposition in ATTR. End stage renal disease (ESRD) occurred in 20–40% of AL patients at five years and was nearly universal in untreated fibrinogen Aα-chain amyloidosis. Suppression of the causative protein — haematologic response in AL (particularly complete response) — was the strongest independent predictor of renal response. Novel therapies, including daratumumab-based regimens, achieved haematologic complete response rates exceeding 50% and significantly improved renal outcomes. Conclusions: Renal amyloidosis is a clinicopathologically diverse condition whose outcomes are primarily determined by amyloid subtype, organ burden at presentation, and depth of treatment response. Accurate tissue typing using mass spectrometry-based proteomics is essential for optimal management. Future research should focus on standardising renal response criteria, evaluating amyloid-clearing biologics, and conducting prospective registries across amyloid subtypes.