Autoinflammatory diseases and the kidney

Abstract

The kidney represents an important target of systemic inflammation. Its involvement in monogenic and multifactorial autoinflammatory diseases (AIDs) vary from peculiar and relatively frequent manifestations to some rare but severe features that may end up requiring transplantation. The pathogenetic background is also very heterogeneous ranging from amyloidosis to non-amyloid related damage rooted in inflammasome activation. Kidney involvement in monogenic and polygenic AIDs may present as renal amyloidosis, IgA nephropathy, and more rarely as various forms of glomerulonephritis (GN), namely segmental glomerulosclerosis, collapsing glomerulopathy, fibrillar, or membranoproliferative GN. Vascular disorders such as thrombosis or renal aneurysms and pseudoaneurysms may be encountered in patients with Behcet's disease. Patients with AIDs should be routinely assessed for renal involvement. Screening with urinalysis, serum creatinine, 24-h urinary protein, microhematuria, and imaging studies should be carried out for early diagnosis. Awareness of drug-induced nephrotoxicity, drug-drug interactions as well as addressing the issue of proper renal adjustment of drug doses deserve a special mention and should always be considered when dealing with patients affected by AIDs. Finally, we will explore the role of IL-1 inhibitors in AIDs patients with renal involvement. Targeting IL-1 may indeed have the potential to successfully manage kidney disease and improve long-term prognosis of AIDs patients.

Keywords: Amyloidosis; Autoinflammatory diseases (AIDs); Drug-induced nephrotoxicity; Inflammasome; Interleukin-1 inhibitors; Kidney involvement; Nephropathy.

Fig. 1

(A: H&E – ×400): 55 years male patient with FMF. A glomerulus shows abundant mesangial as well as capillary wall deposits of amorphous eosinophilic material. (B: PAS-×400): The deposited material is PAS negative. (C: Congo red-×400): Congo red stain reveals organophilic glomerular deposits; with polarized light an apple green birefringence is seen. (D: Immunoperoxidase, AA protein-x400): The tufts are strongly positive for amyloid associated protein (Courtesy of Dr. Wael M. Hamza, Department of Pathology, Cairo University)

Fig. 2

(A: H&E – ×400): 38 years male patient with FMF. A glomerulus shows mesangial hypercellularity and hypertrophied epithelial cells. Increased intraluminal leukocytes and congestion are also evident. (B: IF, IgA-×400): The immunofluorescence study reveals dominant mesangial deposits for IgA. (C &D: IF, C3 & IgG-×400): Subtle deposits of C3 (image C), while IgG was negative (image D). (Courtesy of Dr. Wael M. Hamza, Department of Pathology, Cairo University)

Fig. 3

(A: H&E & B: JMS – ×400): 32 years female patient with FMF. Two glomeruli show compressed tufts by cellular crescents. (C & D: IF-×400): Immunofluorescence study reveals positive glomerular deposits for IgG (image C) and IgM (image D). (Courtesy of Dr. Wael M. Hamza, Department of Pathology, Cairo University)