Topic Discussion: Proximal Tubulopathies with monoclonal light chains

Proximal tubule is a commonly involved part of the kidney in myeloma.  Classically, they are noted more with light chains compared to heavy chains.  A recent article sheds light on the four mechanisms on how they might impact the proximal tubule and lead to four distinct clinical settings. I have summarized the four types in a table format here.

Type	Proximal tubulopathy without cytoplasmic inclusions	Proximal tubulopathy with interstitial inflammation(AIN variant)	Proximal tubulopathy with cytoplasmic inclusions	Proxmial tubulopathy with lysosomal indigestion
Pathology	Vacuolization of tubular cells and perhaps some necrosis	Vacuolization but AIN as well. Lymphocytes mainly	Swollen proximal tubular cells and EM shows rectangular or angulated inclusions in cytoplasm appear crystalline in nature	Enlarged proximal cells, EM shows lysosome was occupied by substance.
Predominant light chain	Kappa more than lambda	Kappa more than lambda	Kappa and one case of lambda	All kappa
Seen with MGUS	Yes	Yes	Yes	Yes
Clinical	Slowly progressive renal failure, some non nephrotic proteinuria	ARF, more patients requiring dialysis, non nephrotic proteinuria	Slowly progressive renal failure,glucosuria, phosphaturia and non nephrotic range proteinuria	Slowly progressive, glucosuria and phosphaturia
Unique features	Second most prevalent, older age	Most prevalent, older age	Younger age	Least prevalent, younger age