MGRS Crib Sheet

The following is intended to aid with the recruitment of Monoclonal Gammopathy of Renal Significance (MGRS) patients. 

PDF Crib Sheet

 

More than one disease below can occur in a single patient. Please select the most clinically relevant under Primary Diagnosis and put any others in the Comments box

 

Light chain cast nephropathy (myeloma cast nephropathy PRD code 2584 biopsy proven)

Myeloma cast nephropathy confirmed on renal biopsy. (Formally called myeloma kidney)


Light chain Fanconi Syndrome ORPHA:91136 Acquired monocloncal Immunoglobulin light-chain associated Fanconi Syndrome

Fanconi syndrome (light chain proximal tubulopathy) confirmed through serum and urine testing with evidence of abnormal clone (paraprotein and/or serum free light chains), rod or rhomboid shaped light chain crystals are localised within proximal tubular cells.


Proximal tubulopathy without crystals no code

Evidence of a proximal tubulopathy in serum and urine testing and no crystals seen on renal histology


Crystal-storing histiocytosis no code

Histology shows crystal laden histiocytes in the interstitium or glomerular capillary loops or mesangium with evidence of a plasma cell clone.


AL amyloidosis  – AL (light chain amyloidosis renal biopsy proven) 2521 PRD code ORPHA :85443

AH amyloidosis (heavy chain amyloidosis ORPHA: 442582

AHL amyloidosis (light and heavy chain amyloidosis) (2509 renal amyloidosis)

Amyloid confirmed on histology of any tissue with evidence of renal involvement on either;  SAP imaging, histology, proteinuria or declining renal function. Immunohistochemistry should have confirmed Kappa or lambda staining. Ideally patient has had confirmation at the NAC but not essential for recruitment to RaDaR.

Distinguishing between AL, AH or AHL is required on histology of any tissue.


Immunotactoid/Glomerulonephritis with Monoclonal Immunoglobulin Deposits (GOMMID) PRD code 2606

Renal biopsy histology diagnosis with microtubules on electron microscopy (fibrils are 30 to 50nm in diameter). EM is therefore required to confirm this as a diagnosis.


Fibrillary Glomerulonephritis PRD code 2606 ORPHA : 97566

Renal biopsy required with electron microscopy essential for diagnosis. EM shows random fibrillary deposits in the mesangium and glomerular capillary walls. (Fibrils are 16-24nm) Evidence of a monoclonal gammopathy is required to classify as an MGRS lesion.


Type 1 cryoglobulinaemic Glomerulonephritis (PRD 1591 cryoglobulinaemia secondary to systemic disease)

Membrano proliferative pattern on renal biopsy with intra lumen thrombi


(Cryo)crystalglobulin-induced nephropathy (PRD 1591 cryoglobinulinaemia secondary to systemic disease – histologically proven)

Light chains crystallize within podocytes. Focal segmental glomerulosclerosis is the most common pattern with additional crystalline deposits within other cells in the kidney, including proximal tubular cells, endothelial cells and mesangial cells.


Non amyloid Monoclonal Immunoglobulin Deposition Disease ORPHA:86861 (MIDD) consisting of either  (Light chain deposition disease – LCDD PRD 2597 ORPHA:93558, Heavy chain deposition disease – HCDD ORPHA: 93556, Light and Heavy chain Deposition Disease – LHCDD ORPHA:93557)

Histology shows non organized deposits which are eosinophilic and granular. Immunoflourescence should show monotypic fixation of kappa or lambda along the tubular basement membrane.

 EM is required to confirm the diagnosis. Granular, electron dense deposits are seen on the outer aspect of the tubular basement membrane. In glomeruli electron dense material is seen in the mesangial nodules and along the GBM.


Proliferative glomerulonephritis with monoclonal immunoglobulin deposits – PGNMID (mesangial proliferative GN PRD 1349)

Mimics immune complex GN. Membranoproliferative or endocapillary proliferative glomerulonephritis with membranous features. Immunoflourescence reveals granular deposits that stain positive for a single light-chain isotype and single heavy chain subtype. EM shows granular, non organsized deposits.


C3 glomerulonephritis with monoclonal gammopathy no code (C3 Glomerulonephritis ORPHA:329931)

C3 glomerulonephritis or dense deposit disease with evidence of a monoclonal gammopathy. If no evidence of an abnormal clone patients need to be registered under C3 glomerulopathy in the separate RaDaR cohort.


Thrombotic Microangiopathy with monoclonal gammopathy no code (Thrombotic Microangiopathy ORPHA: 93573)

Evidence of a thrombotic microangiopathy on renal biopsy in conjunction with a monoclonal protein.

 

MGRS Crib Sheet Version 1 Updated July 2018
Written by the MGRS Rare Disease Group