A 16-year Survey of Clinicopathological Findings, Electron Microscopy, and Classification of Renal Amyloidosis

Abstract

Background: Electron microscopy (EM) is a valuable tool in the diagnosis of renal amyloidosis, particularly in the early stages of the disease. In Iran, studies on EM and the clinical features of renal amyloidosis are scarce. The objective of the present study was to survey EM investigations, pathological classifications, and clinical features of renal amyloidosis.

Methods: This cross-sectional study was performed in Shiraz, Iran, during 2001-2016. Out of 2,770 kidney biopsies, 27 cases with a diagnosis of renal amyloidosis were investigated. EM investigation and six staining procedures for light microscopy (LM) were performed. Two pathological classifications based on glomerular, peritubular, perivascular, and interstitial involvement were made. Finally, the association between these classifications and the clinical features was assessed. Chi-square, Fisher's exact, Independent t test, and Multiple logistic regression analysis were used. P values<0.05 were considered statistically significant.

Results: In 51.9% of the cases, the clinical diagnosis was nephrotic syndrome. Proteinuria and edema were the most prevalent clinical manifestations. The role of EM investigation for diagnosis was graded "necessary" or "supportive" in 48.2% of the patients. In the classification based on glomerular classes, variables such as the mean blood pressure (P=0.003), history of hypertension (P=0.02), creatinine >1.5 (P=0.03), and severe tubular atrophy (P=0.03) were significantly higher in class B (advanced amyloid depositions).

Conclusion: EM plays an important role in the diagnosis of renal amyloidosis. EM in conjunction with LM investigation with Congo red staining is recommended, to prevent misdiagnosis of patients with a clinical suspicion of renal amyloidosis. Among different pathological features of renal amyloidosis, the severity of glomerular amyloid depositions had a clear relationship with clinical presentations.

Keywords: Amyloidosis; Electrons; Kidney; Microscopy; Nephrotic syndrome; Proteinuria.

Figure 1

A) Underlying diseases, B) clinical diagnosis, C) drug consumption history, and D) clinical manifestations of patients with renal amyloidosis from 2001 to 2016. FMF: Familial Mediterranean fever, CKD: Chronic kidney disease, GN: Glomerulonephritis, MPGN: Membranoproliferative glomerulonephritis, NSAID: Nonsteroidal anti-inflammatory drug

Figure 2

Photomicrographs of plastic sections of the kidney needle biopsy of renal amyloidosis shows depositions of pale blue homogenous amyloid material (asterisk) in A) the glomerulus, B) perivascular, C) peritubular, and D) interstitial areas by toluidine blue staining (magnification ×400).

Figure 3

Light microscopy findings of renal biopsies are shown. A) An asterisk indicates eosinophilic, homogenous, and acellular materials of amyloid depositions in the glomerulus stained with hematoxylin and eosin; original magnification ×200. B) Weakly positive deposition of amyloid material on periodic acid-Schiff staining in the glomerular region (asterisk); original magnification ×200 is illustrated. C) Acellular, pale, eosinophilic, silver-negative material deposits within the glomerulus (arrow) by Jones silver staining; original magnification ×200 are shown. D) Weakly positive amyloid deposition on Masson staining in the glomerular region (asterisk); original magnification ×200 is illustrated. E) Amyloid deposition in the glomerular and mesangial region (arrow) stained with brick red or salmon color with Congo red; original magnification ×200 is shown.

Figure 4

Photomicrographs of electron microscopy of glomerular amyloidosis are illustrated. A) Homogenous electron-pale material deposition in the mesangial area (arrow) is shown. There are some red blood cells in the lumen of the capillary (asterisk); original magnification ×2,700. B) The nucleus of the mesangial cell is visible (indicator); magnification ×3,500. C) Homogenous pale material is deposited diffusely infiltrating glomerular basement membranes (arrow); magnification ×4,500. D) Amyloid deposits extensively in the mesangial and intramembranous area; magnification ×7,700 are shown. E) Amyloid fibrils are indicated in the mesangial area (asterisk); magnification ×16,700. F) Non-branching straight amyloid fibrils with a diameter of 8-12 nm are randomly oriented in the mesangial area; magnification ×50,000.