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

Table 1 Prevalence of the de novo vs recurrent membranoproliferative glomerulonephritis according to the new membranoproliferative glomerulonephritis pathological classification depending on the mechanism of glomerular injury instead of deposits distribution[14,59]

No.	MPGN subtype	Pathological criteria	Recurrent MPGN	De novo MPGN
1	ICGN (immune complex-mediated GN)	Contains immune complexes + complement compounds	More common (most of the recurrent cases are ICGN)	Reported (3.25%)
2	CGN (complement-mediated GN)	Contains complement compounds only	Less prevalent (change from one type to another)	Not reported (Ponticelli et al[14], 2014)

MPGN: Membranoproliferative glomerulonephritis; ICGN: Immune complex mediated glomerulonephritis; CGN: Complement-mediated glomerulonephritis.

Table 2 Case reports in the literatures on de novo proliferative glomerulonephritis with monoclonal IgG deposits in renal allografts

Case	Age at diagnosis	Gender	Onset time (mo)	Type of IgG deposits	C1q deposition	Native kidney disease	Pattern of glomerular injury	Monoclonal gammopathy	Ref.
1	24	M	43	IgG3κ	N/A	T1DM	MPGN	None	Albawardi et al[64] (2011)
2	68	F	156	IgG1κ	N/A	PKD	MPGN	None	Albawardi et al[64] (2011)
3	38	F	72	IgG3κ	1+	T1DM	MesGN or EC	N/A	Hussain et al[72] (2017)
4	61	F	98	IgG3κ	C1q	MPGN	EC	None	Al-Rabadi et al[73] (2015)
5	40	F	132	IgG3κ	N/A	MPGN	MPGN	None	Al-Rabadi et al[73] (2015)
6	46	M	49	IgG1κ	1+	FSGS	MesGN	N/A	Li et al[77] (2017)
7	69	M	6	IgG3κ	1+	Obesity (FSGS?)	MPGN	N/A	Merhi et al[75] (2017)

EPGN: Endocapillary proliferative glomerulonephritis; FSGS: Focal segmental glomerulosclerosis; MesGN: Mesangioproliferaitve glomerulonephritis; MPGN: Membranoproliferative glomerulonephritis; N/A: Not available; PGNMID: Proliferative glomerulonephritis with monoclonal IgG deposits; PKD: Polycystic kidney disease; T1DM: Type 1 diabetes mellitus; EC: Endocapillary proliferative; M: Male; F: Female.

Table 3 Main characteristics of the more frequent de novo glomerulonephritis after transplantation (minimal change disease, nephrotic syndrome, membranous nephropathy, membranoproliferative glomerulonephritis, hepatitis C virus, IgAN)

Disease	Presentation	Time of onset	Difference with native GN	Treatment	Prognosis
MN	Proteinuria sometimes in nephrotic range	Late after transplant	Associated with trans-plant complications; IgG1 deposits instead of IgG4	No specific treatment	Slowly progressive
MPGN	Proteinuria, hematuria, NS, nephritic sediment	Months or years after transplant	Often associated with HCV, or with other diseases	Steroids + cytotoxic drugs if crescentic GN (?)	Slowly progressive; poor with many crescents.
FSGS	Proteinuria, rarely in nephrotic range	Months or years after transplant	NS is rare; signs of rejection or CNI toxicity at biopsy	Removal of associated events	Usually poor, particularly in collapsing GN
MCD	NS	Early after transplant	Mild mesangial sclerosis, hypercellularity	Steroids	Good

Adapted from: Ponticelli et al[14] (2014). De novo Glomerular Diseases after Renal Transplantation. Clin J Am Soc Nephrol 2014; 9: 1479-1487, with permission. MCD: Minimal change disease; NS: Nephrotic syndrome; MN: Membranous nephropathy; MPGN: Membranoproliferative GN; HCV: Hepatitis C virus.

Table 4 The risk of recurrence of de novo glomerulonephritis after retransplantation is unknown

Disease	Indications to retransplant
MN	In view of the slow progression, there is no contraindication to retransplant
MPGN	The risk of recurrence is high in carriers of HCV, active autoimmune disease, or monoclonal gammopathy. These risk factors should be removed or inactivated before retransplant
FSGS	If FSGS was caused by calcineurin inhibitor or mTOR inhibitor toxicity, there is no contraindication to retransplant, but the dosage of the offending drug should be minimized. If FSGS was associated with AMR, the risk of recurrence is increased. Circulating antibodies should be removed before retransplant
Collapsing nephropathy	Risk of recurrence is probably high. Antiviral and/or removal of circulating AB before retransplant are recommended according to the possible role played by virus infection or AMR in the 1st transplant
MCD	In view of the favorable prognosis, there is no contraindication to retransplant
IgAN	No contraindication to retransplant

Adapted from: Ponticelli et al[14] (2014), De Novo Glomerular Diseases after Renal Transplantation. Clin J Am Soc Nephrol 2014; 9: 1479-1487. Published online 2014, with permission. MCD: Minimal change disease; NS: Nephrotic syndrome; MN: Membranous nephropathy; MPGN: Membranoproliferative GN; HCV: Hepatitis C virus; FSGS: Focal segmental glomerulosclerosis.