Thread by @AliMehdiMD

1/ Paraproteinemic kidney disease: Cast nephropathy, myeloma kidney, MGUS, MGRS, LCCN, AL, AH, MIDD, LCPT…)

Lost in the alphabet soup!!!

Time for an #MGRS #tweetorial
#NephTwitter #Hemetwitter #MedTwitter #Onconephrology #NSMC

2/ Let’s start with a poll: which of the following disease states can cause MGRS (monoclonal gammopathy of renal significance):

3/ Before we get to the answer, let’s dissect the term MGRS:

Monoclonal Gammopathy:
⚡️Signifies the presence of a "monoclonal" immunoglobulin or its components
⚡️Seen as a spike in the "gamma" region on protein electrophoresis

link.springer.com/referenceworke…

4/ Renal Significance:
⚡️The monoclonal immunoglobulin “proves” to be toxic to the kidney (pathologically)

⚡️Toxicity that can take MANY different faces depending on the physicochemical properties of the antibody!!

nature.com/articles/s4158…

5/ Ok that’s simple enough! MGRS is a state where a monoclonal antibody is causing kidney damage!
Yes with an asterix****

6/ To better understand this, we need to go back to 2012 when the term MGRS was coined:

⚡️ Why did the International Kidney and Monoclonal Gammopathy Research Group (IKMG) feel a new entity was needed! Let’s dive more into the “why”

ashpublications.org/blood/article/…

7/ ⚡️Various kidney diseases were being recognized among MGUS patients
⚡️Without heme treatment, pts had progressive kidney disease and high recurrence after transplant
⚡️MGRS proposed to distinguish these “kidney toxic” conditions from what’s truly MGUS
ashpublications.org/blood/article/…

8/ ⚡️So MGRS as an entity created to separate it from its benign counterpart MGUS
⚡️The malignant diseases with higher clone burden (Myeloma) are a separate entity and DO NOT fall under MGRS

9/ This point was further refined in the 2019 consensus statement with the concept of the “dangerous small clone”:
⚡️SIze is not everything: even the slightest paraprotein can cause significant kidney damage
nature.com/articles/s4158…

10/ Let’s take a pit stop: “MG-RS”:
⚡️Monoclonal gammopathy present: monoclonal antibody or a component of it
⚡️Antibody is kidney toxic (Biopsy proven)
⚡️Underlying disease is presumably benign (as in MGUS)
⚡️A malignant underlying disease (as in myeloma) EXCLUDES MGRS

11/ Ok great. So MGRS was created to distinguish it from MGUS.
But can MGRS happen outside MGUS?

12/ ⚡️I used to equate monoclonal gammopathy with plasma cell neoplasms (MGUS, myeloma). But this is where it gets interesting...and confusing!
⚡️The origin of the monoclonal immunoglobulin can be a plasma cell, a B cell, or a lymphoplasmacytic cell

cjasn.asnjournals.org/content/11/12/…

13/ ⚡️So monoclonal gammopathy is NOT equivalent to plasma cell disorder!
⚡️It is certainly seen with plasma cell disorders
⚡️It can also be seen with B cell neoplasms and lymphoplasmacytic neoplasms as well.

nature.com/articles/s4158…

14/ ⚡️ Some of these disorders are considered benign or premalignant
⚡️They are associated with “low clone” burden and as such are usually followed without treatment
nature.com/articles/s4158…

15/ ⚡️ But size does not matter when it comes to kidney toxicity!!
⚡️Any monoclonal gammopathy, and as such any of these diseases, can cause kidney toxicity!!
⚡️Toxicity is irrespective of size or clone burden!

nature.com/articles/s4158…

16/⚡️So, is MGRS restricted to MGUS with kidney toxicity? This was a major point of confusion following the 2012 definition.

⚡️This was clarified in the 2019 consensus statement! @SethiRenalPath @VincentRK
ashpublications.org/blood/article/…
nature.com/articles/s4158…

17/⚡️MGRS is NOT restricted to MGUS!
⚡️MGRS refers to any B cell or plasma cell disease where:
-The monoclonal antibody proves kidney toxic
-The underlying disease would usually NOT require treatment had it not been for the kidney damage
nature.com/articles/s4158…

18/ ⚡️ So bottom line: what diseases can cause MGRS?
⚡️Smoldering diseases, low grade CLL, and low grade B cell lymphomas (NOT JUST MGUS)
⚡️Diseases that DO NOT MEET HEMATOLOGIC CRITERIA FOR THERAPY
⚡️Summary table below:
nature.com/articles/s4158…

19/ Let’s wrap it up with key takeaways:
⚡️MGRS is not just MGUS with kidney toxicity
⚡️Monoclonal gammopathy can be associated with B cell disorders (not just plasma cell disorders)
⚡️MGRS: the underlying disease does not meet hematologic criteria for treatment

20/ Let’s end where we started with the poll: which of the following disease states states can cause MGRS (monoclonal gammopathy of renal significance):

21/ Thank you for scrolling through. Hope you found this helpful.
Stay tuned for more tweetorials on MGRS associated kidney lesions in the near future.
Many thanks for all the #NSMC mentors for their guidance! #Nephforward #Onconephrology