De novo glomerular diseases after renal transplantation: How is it different from recurrent glomerular diseases?

Abstract

The glomerular diseases after renal transplantation can occur de novo, i.e., with no relation to the native kidney disease, or more frequently occur as a recurrence of the original disease in the native kidney. There may not be any difference in clinical features and histological pattern between de novo glomerular disease and recurrence of original glomerular disease. However, structural alterations in transplanted kidney add to dilemma in diagnosis. These changes in architecture of histopathology can happen due to: (1) exposure to the immunosuppression specifically the calcineurin inhibitors (CNI); (2) in vascular and tubulointerstitial alterations as a result of antibody mediated or cell-mediated immunological onslaught; (3) post-transplant viral infections; (4) ischemia-reperfusion injury; and (5) hyperfiltration injury. The pathogenesis of the de novo glomerular diseases differs with each type. Stimulation of B-cell clones with subsequent production of the monoclonal IgG, particularly IgG3 subtype that has higher affinity to the negatively charged glomerular tissue, is suggested to be included in PGNMID pathogenesis. De novo membranous nephropathy can be seen after exposure to the cryptogenic podocyte antigens. The role of the toxic effects of CNI including tissue fibrosis and the hemodynamic alterations may be involved in the de novo FSGS pathophysiology. The well-known deleterious effects of HCV infection and its relation to MPGN disease are frequently reported. The new concepts have emerged that demonstrate the role of dysregulation of alternative complement pathway in evolution of MPGN that led to classifying into two subgroups, immune complex mediated MPGN and complement-mediated MPGN. The latter comprises of the dense deposit disease and the C3 GN disease. De novo C3 disease is rather rare. Prognosis of de novo diseases varies with each type and their management continues to be empirical to a large extent.

Keywords: De novo glomerulonephritis; New concepts of therapy; Renal transplantation.

Figure 1

Any type of kidney injury can cause tissue damage. The danger signals released by the damaged tissue alert the recognition receptors, which activate the inflammatory cells and mediators of the innate immunity system. In this inflammatory environment, hidden podocyte antigens may be exposed, whereas dendritic cells become mature, migrate to lymphatic system, and present the antigen to immune competent cells. T cells cooperate with B cells favoring the production of antibodies directed against the exposed antigens planted in the subepithelium, with in situ formation of immune complexes, activation of complement, formation of free oxygen radicals, and inflammation. Adapted from: Ponticelli et al[10], 2012. De novo membranous nephropathy (MN) in kidney allografts. A peculiar form of all immune disease? With permission.

Figure 2

Glomerular capillaries are greatly distorted and thickened by the presence of numerous, sometimes large and/or confluent subendothelial electron-dense deposits (arrows). The electron-dense deposits have a variegated (“two-toned”) appearance and are finely granular, but they do not show organized substructures. Adapted from: Al-Rabadi et al[73] (2015) (open access).

Figure 3

Diffuse irregular granular and pseudo linear deposition of IgG (3+/4+) (arrows). No staining is found in Bowman’s capsule or the tubular BM. Adapted from: Al-Rabadi et al[73] (2015) (open access).

Figure 4

Kappa light chains stain strongly positive (3+/4+) (Rt side, red arrows) along the peripheral capillary walls and mesangial areas. Lambda light chains are negative in the deposits (Lt side, blue arrow). Adapted from: Al-Rabadi et al[73] (2015) (open access).