Paraproteinemic kidney diseases

Group of different, chronic kidney diseases (glomerular and/or interstitial nephropathies) associated with deposits of intact or fragmentary immunoglobulins (heavy and light chains), e.g. in multiple myeloma, plasmocytoma or Waldenstrom's disease.

Paraproteinemic kidney diseases include (Kanzaki G et al. 2019):

• Monoclonal immunoglobulin depositiondisease (MIDD): At the time of diagnosis most patients already have renal failure.
• Nephropathy in AL or AH amyloidosis: 50% of patients develop nephropathy)
• Glomerulonephritis associated with type I cryoglobulinemia (membranoproliferative glomerulonephritis)
• Myeloma kidney (cast nephropathy; proliferative glomerulonephritis with monoclonal IgG deposits; PGNMID)
• Immunotactoid glomerulopathy and fibrillary glomerulonephritis: 1% of biopsied patients.
• As well as very rare:
  • Monoclonal crystalline glomerulopathy
  • Paraprotein-related thrombotic microangiopathy
  • Membranous-like glomerulopathy with masked IgGκ deposits

Of clinical relevance for nephrotoxic monoclonal proteins is that their nephrotoxicity is independent of whether they are generated by a malignant or non-malignant cell clone. In this respect, the non-prejudicial term: "monoclonal gammopathy of renal significance" has become established (see also Monoclonal gammopathy of indeterminate significance = MGUS). Based on these findings, therapeutic approaches with "clone-directed strategies" such as rituximab (directed against CD20-expressing B cells) and bortezomib (directed against plasma cell clones, see below proteasome inhibitors) have become established. These clone-adapted therapeutic approaches are also more effective in "nonmonoclonal protein-related kidney diseases" than the unspecific immunosuppressive therapeutic approaches (Leung N et al. (2018)

1. Huang X et al (2016) Bortezomib with dexamethasone as first-line treatment for AL amyloidosis withrenal involvement. Amyloid 23:51-57.
2. Leung N et al (2018) Dysproteinemias and Glomerular Disease. Clin J Am Soc Nephrol 13:128-139.
3. Luan H et al (2019) Cast nephropathy associated with monoclonal immunoglobulin M-secreting mucosa-associated lymphoid tissue B-cell lymphoma
.Clin Nephrol doi: 10.5414/CN109682.
4. Sallée M et al (2019) Myeloma cast nephropathy: the dusk of high cutoff haemodialysis. Lancet Haematol 6:e174-e176.