Thread by @AliMehdiMD, 1/ Paraproteinemic kidney disease: Cast nephropathy, myeloma kidney, MGUS, MGRS, LCCN, AL, [...]

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

https://link.springer.com/referenceworkentry/10.1007%2F978-3-662-46875-3_3824

3/ Before we get to the answer, let’s dissect the term MGRS: Monoclonal Gammopathy: Signifies the presence of a "monoclonal" immunoglobulin or its componentsSeen as a spike in the "gamma" region on protein electrophoresis https://link.springer.com/referenceworkentry/10.1007%2F978-3-662-46875-3_3824

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!!

https://www.nature.com/articles/s41581-018-0077-4

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!! https://www.nature.com/articles/s41581-018-0077-4

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”

https://ashpublications.org/blood/article/120/22/4292/73069/Monoclonal-gammopathy-of-renal-significance-when

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” https://ashpublications.org/blood/article/120/22/4292/73069/Monoclonal-gammopathy-of-renal-significance-when

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
https://ashpublications.org/blood/article/120/22/4292/73069/Monoclonal-gammopathy-of-renal-significance-when

7/ Various kidney diseases were being recognized among MGUS patientsWithout heme treatment, pts had progressive kidney disease and high recurrence after transplantMGRS proposed to distinguish these “kidney toxic” conditions from what’s truly MGUS https://ashpublications.org/blood/article/120/22/4292/73069/Monoclonal-gammopathy-of-renal-significance-when

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
https://www.nature.com/articles/s41581-018-0077-4

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 https://www.nature.com/articles/s41581-018-0077-4

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

https://cjasn.asnjournals.org/content/11/12/2280

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 https://cjasn.asnjournals.org/content/11/12/2280

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.

https://www.nature.com/articles/s41581-018-0077-4

13/ So monoclonal gammopathy is NOT equivalent to plasma cell disorder! It is certainly seen with plasma cell disordersIt can also be seen with B cell neoplasms and lymphoplasmacytic neoplasms as well. https://www.nature.com/articles/s41581-018-0077-4

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
https://www.nature.com/articles/s41581-018-0077-4

14/ Some of these disorders are considered benign or premalignantThey are associated with “low clone” burden and as such are usually followed without treatment https://www.nature.com/articles/s41581-018-0077-4

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!

https://www.nature.com/articles/s41581-018-0077-4

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! https://www.nature.com/articles/s41581-018-0077-4

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
https://ashpublications.org/blood/article/120/22/4292/73069/Monoclonal-gammopathy-of-renal-significance-when
https://www.nature.com/articles/s41581-018-0077-4

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 https://ashpublications.org/blood/article/120/22/4292/73069/Monoclonal-gammopathy-of-renal-significance-when https://www.nature.com/articles/s41581-018-0077-4

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
https://www.nature.com/articles/s41581-018-0077-4

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 https://www.nature.com/articles/s41581-018-0077-4

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:
https://www.nature.com/articles/s41581-018-0077-4

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 THERAPYSummary table below: https://www.nature.com/articles/s41581-018-0077-4

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

19/ Let’s wrap it up with key takeaways:MGRS is not just MGUS with kidney toxicityMonoclonal 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

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