Table 1.

Monoclonal gammopathy of renal significance glomerular lesions: Clinical features, pathologic characteristics, and outcomes

Renal LesionClinical FeaturesPathologic CharacteristicsOutcomes and Post-Transplant Course
Ig-related amyloidosis (AL, AHL, AH)Proteinuria, NS, CKDLM: PAS (−), Ag (−) acellular depositsPRD and ESRD common; worse outcomes if concurrent cardiac involvement
HTN and hematuria uncommonIF: LC and/or HC restrictedRecurrence in transplant uncommon
EM: random, nonbranching fibrils (7–12 nm)
Congo red (+)
Fibrillary GNProteinuria, HTN, hematuria, CKD, NSLM: MesGN, mesangial expansion, MGN, MPGN, PAS (+), Ag (−)PRD and ESRD common
IF: polyclonal IgG >80%Recurrence in transplant common if monoclonal gammopathy is present
EM: random fibrils (9–26 nm)
Congo red (−)
Immunotactoid GN/GOMMIDProteinuria, NS, CKD, hematuriaLM: MPGN, MGN, ECPGN, PAS (weak), Ag (−)PR common, PRD, ESRD
HypocomplementemiaIF: IgG, C3, LC restrictedRecurrence in transplant
EM: parallel, hollow microtubules (8–60 nm)
Congo red (−), cryoglobulin (−)
Type 1 cryoglobulinemic GNProteinuria, hematuriaLM: MPGN, ECPGN, subendothelial and intracapillary, PAS (+)CR common, frequent relapse, CKD, ESRD, recurrence in transplant
Nephritic/nephrotic syndrome, AKI, CKD, HTN, purpura, arthralgias, hypocomplementemiaIF: monoclonal IgG/IgM and C3, C4, and C1q deposits
EM: curvilinear microtubules, 10–50 nm
Monoclonal Ig deposition disease (LCDD, LHCDD, HCDD)Proteinuria, NS, CKD, AKILM: PAS (+), Ag (+), mesangial expansion, nodular GS, thickened TBMPR common, ESRD
HTN and hematuria uncommonIF: linear LC- and/or HC-restricted deposits in TBM, GBM, and vascular wallRecurrence in transplant common
EM: punctate, powdery electron dense deposits
Proliferative GN with monoclonal Ig depositsProteinuria, hematuria, NS, CKD, AKILM: MPGN, ECPGN, MesGN, MGN, crescents (occasionally)PRD, PR, ESRD
IF: IgG (rarely IgM and IgA), LC and HC restricted (mostly IgG3)Recurrence in transplant common
EM: mesangial, subendothelial, and intramembranous deposits
C3 glomerulopathyHematuria, proteinuria, CKDLM: MPGN, ECPGN, MesGN, MGNPRD and ESRD common
 C3 GNLow C3 level and normal C4 level commonIF: granular C3 deposits, little or no Ig or C1q depositsC3GN: recurrence in transplant most common
 DDDEM: DDD, intramembranous “sausage-shaped deposits”; C3 GN, mesangial, subendothelial, and subepithelial depositsDDD: recurrence in transplant
Thrombotic microangiopathyProteinuria, hematuria, CKDLM: double contour of GBM, mesangiolysis, ATN, thrombi in GCESRD common, PRD
Anemia, thrombocytopenia, schistocytesCourse in transplant: insufficient evidence
IF: fibrinogen material in GC lumen and wall
EM: double contour of GBM, subendothelial “fluff”
  • Most common symptoms: The findings are sorted on the basis of order of frequency. AL, Ig light chain amyloidosis; AHL, Ig heavy and light chain amyloidosis; AH, Ig heavy chain amyloidosis; NS, nephrotic syndrome; HTN, hypertension; LM, light microscopy; PAS, periodic acid–Schiff; Ag, silver stain; IF, immunofluorescence; LC, light chain; HC, heavy chain; EM, electron microscopy; PRD, progressive renal disease: failure to meet criteria for either complete response or partial response but not reaching ESRD, including patients with unremitting proteinuria or progressive CKD; MesGN, mesangial proliferative GN; MGN, membranous GN; MPGN, membranoproliferative GN; GOMMID, GN with organized microtubular Ig deposits; ECPGN, endocapillary proliferative GN; PR, partial response: reduction in proteinuria by at least 50% and to <2 g/d with stable renal function (≤20% increase in serum creatinine); CR, complete remission: remission of proteinuria to <500 mg/d with normal renal function; LCDD, light-chain deposition disease; LHCDD, light- and heavy-chain deposition disease; HCDD, heavy-chain deposition disease; GS, glomerulosclerosis; TBM, tubular basement membrane; GBM, glomerular basement membrane; C3G, C3 glomerulopathy; DDD, dense deposits disease; ATN, acute tubular necrosis; GC, glomerular capillary.