Renal amyloidosis: a new time for a complete diagnosis

Abstract

Amyloidoses are a group of disorders in which soluble proteins aggregate and deposit extracellularly in tissues as insoluble fibrils, causing organ dysfunction. Clinical management depends on the subtype of the protein deposited and the affected organs. Systemic amyloidosis may stem from anomalous proteins, such as immunoglobulin light chains or serum amyloid proteins in chronic inflammation or may arise from hereditary disorders. Hereditary amyloidosis consists of a group of rare conditions that do not respond to chemotherapy, hence the identification of the amyloid subtype is essential for diagnosis, prognosis, and treatment. The kidney is the organ most frequently involved in systemic amyloidosis. Renal amyloidosis is characterized by acellular pathologic Congo red-positive deposition of amyloid fibrils in glomeruli, vessels, and/or interstitium. This disease manifests with heavy proteinuria, nephrotic syndrome, and progression to end-stage kidney failure. In some situations, it is not possible to identify the amyloid subtype using immunodetection methods, so the diagnosis remains indeterminate. In cases where hereditary amyloidosis is suspected or cannot be excluded, genetic testing should be considered. Of note, laser microdissection/mass spectrometry is currently the gold standard for accurate diagnosis of amyloidosis, especially in inconclusive cases. This article reviews the clinical manifestations and the current diagnostic landscape of renal amyloidosis.

Membranous nephropathy with systemic light-chain amyloidosis of remission after rituximab therapy: A case report

“…Early detection and early intervention are particularly important. In middle-aged or elderly patients with nephrotic syndrome who do not respond to standard diuretic, antihypertensive, and urinary protein-lowering drugs, those with heart failure whose ejection fraction does not decrease, those with hypotension, macroglossia, and hepatomegaly, we would consider combined amyloidosis[ 19 ]. In our case, a middle-aged male was admitted with nephrotic syndrome and found to be positive for serum PLA2R antibodies; hence, the patient was considered to have PLA2R-related MN.…”

Predictors of Developing Renal Dysfunction Following Diagnosis of Transthyretin Cardiac Amyloidosis

“…Further, serum creatinine was used to evaluate kidney function which may lend toward an overestimation of GFR, given general muscle wasting is expected in patients with amyloidosis. In addition, other indicators of wRF, such as proteinuria/microalbuminuria, cystatin c, and free light chain measurements, which may represent more sensitive indicators of the early stages of renal dysfunction, were not included in this study (1,3). Regardless of these limitations, the study included a relatively large overall population size with longitudinal follow-up.…”

“…Transthyretin cardiac amyloidosis (ATTR-CA) is a rare, progressive, and ultimately fatal disease that results from the misfolding and aggregation of amyloidogenic transthyretin (TTR) proteins in the myocardial extracellular space (1,2). ATTR-CA can result from an idiopathic subtype, also known as wild-type (wtATTR-CA), or a hereditary subtype (hATTR-CA) resulting from a pathogenic genetic mutation (1–3). Irrespective of the subtype, deposition of protein in patients with ATTR-CA not uncommonly extends beyond myocardial tissue to other organ systems.…”

“…Irrespective of the subtype, deposition of protein in patients with ATTR-CA not uncommonly extends beyond myocardial tissue to other organ systems. The kidney, nervous system, and gastrointestinal tract, among others, can suffer from protein deposition, leading to a wide array of phenotypic manifestations of the disease with an equally broad array of morbidity and disability burdens (1,3).…”

“…Direct renal involvement is primarily described in hATTR-CA, occurring to a much lesser extent in wtATTR-CA(1, [3][4][5]. Tissue deposition of misfolded ATTR in the glomeruli, renal vasculature, and interstitium is well-documented as a potential mechanism for worsening renal function (wRF) (3)(4)(5). However, the renal impacts of this systemic disease extend beyond local tissue effects.…”