• IgG2 kappa
• Membranoproliferative glomerulonephritis
• Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits

Primary IgA nephropathy (IgAN) with light chain λ restriction in the mesangial deposits (IgAN-λ) has unique immunofluorescence (IF) features. Nevertheless, its clinicopathology and prognosis are still ambiguous.

From January 2002 to December 2020, the clinical and pathologic data of 3872 patients who were diagnosed with having primary IgAN by renal biopsy in our hospital were reviewed. A total of 187 patients who met the selection criteria for IgAN-λ were enrolled to conduct a retrospective single-center study. The selection criteria were that IF features conform to light chain λ restriction in the mesangial deposits. According to age, sex, renal function (estimated glomerular filtration rate [eGFR]), and follow-up time, the control group was constructed with 1:3 matched cases of IgAN. The clinicopathologic and prognostic differences between the 2 groups were analyzed.

Compared with that in the IgAN group, the serum fibrinogen level in the IgAN-λ group was significantly higher (P < 0.001). Furthermore, cluster analysis indicated the different clusters involved in fibrinogen between the IgAN-λ and IgAN groups and that fibrinogen is associated with factors reflecting renal function in IgAN-λ but proteinuria levels in IgAN. The light chain λ deposit in the mesangium is associated with the formation of crescents in those with IgAN-λ, but complement C3 deposition in those with IgAN. Our Kaplan-Meier analysis revealed that the prognosis of the IgAN-λ group was significantly worse than that of the IgAN group within >6 years of follow-up (P = 0.02). The multi-Cox analysis revealed that the light chain λ restriction in the mesangial deposits was an independent risk factor for poor outcomes (eGFR decreased from the baseline ≥ 30% continuously or reached end-stage renal disease [ESRD] or died).

The prognosis of those with IgAN-λ was worse than that of those with IgAN, which may be attributed to the light chain λ restriction in the mesangial deposits inducing a significant systemic inflammation manifested as severe clinical features and frequent crescent.

• Glomerulonephritis/diagnosis
• Glomerulonephritis/epidemiology
• Glomerulonephritis/etiology
• Glomerulonephritis, IGA
• Glomerulonephritis, Membranoproliferative
• Glomerulonephritis, Membranous
• Glomerulosclerosis, Focal Segmental/diagnosis
• Glomerulosclerosis, Focal Segmental/epidemiology
• Humans
• Kidney Transplantation/adverse effects
• Recurrence

• Bleeding complications after kidney biopsy
• Indication of kidney biopsy in adults
• Indication of kidney biopsy in children
• Kidney biopsy
• Open (surgical) kidney biopsy and laparoscopic kidney biopsy
• Percutaneous native kidney biopsy under the ultrasonic guidance
• Relative contraindication for percutaneous native kidney biopsy

The prevalence, pathogenesis, predictors, and natural course of patients with recurrent glomerulonephritis (GN) occurring after kidney transplantation remains incompletely understood, including whether there are differences in the outcomes and advances in the treatment options of specific GN subtypes, including those with de novo GN. Consequently, the treatment options and approaches to recurrent disease are largely extrapolated from the general population, with responses to these treatments in those with recurrent or de novo GN post-transplantation poorly described. Given a greater understanding of the pathogenesis of GN and the development of novel treatment options, it is conceivable that these advances will result in an improved structure in the future management of patients with recurrent or de novo GN. This review focuses on the incidence, genetics, characteristics, clinical course, and risk of allograft failure of patients with recurrent or de novo GN after kidney transplantation, ascertaining potential disparities between “high risk” disease subtypes of IgA nephropathy, idiopathic membranous glomerulonephritis, focal segmental glomerulosclerosis, and membranoproliferative glomerulonephritis. We will examine in detail the management of patients with high risk GN, including the pre-transplant assessment, post-transplant monitoring, and the available treatment options for disease recurrence. Given the relative paucity of data of patients with recurrent and de novo GN after kidney transplantation, a global effort in collecting comprehensive in-depth data of patients with recurrent and de novo GN as well as novel trial design to test the efficacy of specific treatment strategy in large scale multicenter randomized controlled trials are essential to address the knowledge deficiency in this disease.

• allograft failure
• de novo glomerulonephritis
• glomerulonephritis
• kidney transplantation
• recurrent disease
• recurrent glomerulonephritis

• c3 glomerulonephritis
• de novo glomerulonephritis
• kidney transplantation
• proliferative glomerulonephritis with monoclonal igg deposits
• recurrent glomerulonephritis

• PGNMID
• membranoproliferative glomerulonephritis
• monoclonal gammopathy
• recurrent glomerulonephritis
• renal allograft

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.

• De novo glomerulonephritis
• Renal transplantation
• New concepts of therapy

• IgM
• MPGN
• Monoclonal
• PGNMID
• PGNMIMD

• De novo disease
• Immunoglobulin deposition
• Kidney allograft

• de novo glomerulonephritis
• post-transplant lymphoproliferative disorder
• proliferative glomerulonephritis with monoclonal immunoglobulin G deposits
• protocol biopsy
• renal transplantation

• Kappa
• lambda
• monoclonal IgG
• proliferative glomerulonephritis

• Kidney transplantation
• Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID)
• Recurrent glomerular disease