Tuesday, November 23, 2021

KDIGO 2021- GN Management Guidelines: MPGN

 The recent KDIGO guidelines are here

One of the most important changes is getting rid of the MPGN1, 2 and 3 classification and using the novel pathophysiology based classification and recognizing that MPGN is a pattern of injury

The diagnosis of the C3GN and DDD is tough and requires the extensive assays and testing on complement cascade.

Treatment really depends on the cause.

For idiopathic causes of MPGN pattern of injury, consider a limited course of steroids
For RPGN of idiopathic cause, steroids + cyclophosphamide
For MPGN with low GFR< 30, supportive treatment only

For C3GN, and no signs of MGRS, and failed MMF and steroids, eculizumab should be considered

Monday, November 22, 2021

Topic Discussion: Pre eclampsia and APOL1

 This ASN 2021, I heard an interesting lecture and realized some novel associations with pre-eclampsia(PEC) and APOL1 gene mutations. 

Here are some interesting findings.

1. Black women have a higher risk of PEC their White counterparts.
2. Reidy et all showed that it is the FETAL not maternal APOL1 renal risk variant that is associated with PEC in Black women.

3. Some other studies showed that PEC was associated with the maternal G1 and not the G2 allele

4. In Blacks in Ohio, INFANT APOL1 genotype was associated with PEC

5. Recent study in AJKD, found that APOL1 kidney risk variants in Black mother and infant pairs of women of African American origin had higher risk of PEC compared to Haitian women. PEC was higher with maternal and fetal APOL1 genotype discordance, an effect driven by the African American mother-infant pairs. 

6. None of the published studies assessed if the mother’s APOL1 genotype conferred preeclampsia risk independently of the fetal APOL1 genotype, although in African Americans both the maternal and fetal APOL1 renal risk variants appear to increase risk if an APOL1 genotype discordance exists.

7. Experimental data support the hypothesis that APOL1 renal risk variants mediate preeclampsia. APOL1 levels, APOL1-derived peptides, and APOL1 autoantibodies have been linked to preeclampsia. Sedor's team showed that transgenic mice that expressed APOL1 using the nephrin promoter developed a pregnancy-associated phenotype characterized by hypertension, proteinuria, and seizures, which was more severe in transgenic animals with an APOL1 kidney risk variants transgene compared to reference. 

Overall, this is fascinating as we learn regarding the risk of PEC and APOL1 risk variants. It appears that fetal variants of the gene may be more important here.. the story continues to evolve... Stay tuned..

Thursday, October 28, 2021

KDIGO 2021- GN Management Guidelines: Infection associated GN

The recent KDIGO update 2021

Bacterial infection associated GN- 4 main types

Post infectious GN
Shunt nephritis
Endocarditis associated GN
IgA dominant infection related GN

All 4 of them usually have low complement levels.  No RCT for treatment
Antibiotics or surgical treatment for respective infections

Viral infection associated GN- 

Hep B- Hep B DNA >2000 IU/ml, need treatment with anti Hep B agent and no avoid immunosuppressive agents as can accelerate the viral infection.

HIV disease: HAART therapy is recommended for all HIVAN and HIVICK diseases.

Hep C associated GN:  A kidney biopsy should be performed in HCV-positive patients with clinical evidence of glomerular disease. Patients with mild or moderate forms of HCV-associated GN with stable kidney function and/or non-nephrotic proteinuria should be managed first with a DAA regimen. Patients with severe cryoglobulinemia or severe glomerular disease induced by HCV (i.e., nephrotic proteinuria or rapidly progressive kidney failure) should be treated with immunosuppressive agents (generally with rituximab as the first-line agent) and/or plasma exchange in addition to DAA therapies. Patients with HCV-related glomerular disease who do not respond to or are intolerant of antiviral treatment should also be treated with immunosuppressive agents.

Wednesday, October 27, 2021

In the News: Performance trends of Nephrology fellows in certification exams

 A news flash paper published recently in JASN showcased the down trending test scores of nephrology fellows in certification exams. The authors analyzed the data from 2010-2019 and found that the pass rate has been falling below the bench marks. Interestingly, they found that the factors associated with this decline were lower internal medicine exam scores, older age and training in a smaller program. In addition, female sex and being IMG were also associated with a lower board score. 

The IM board score as a predictor can make sense as both exams evaluate knowledge and skills of reasoning. Age over 33 performed less well than younger candidates is interesting. This could be because of non medical factors. Even since 2009 when I took my boards, the knowledge level has changed. There is more and more to read and more diseases to understand in medicine. Residency has not changed, Fellowship years have not changed. While knowledge and science has advanced, we have not changed our ways to teach and perhaps even consider changing the timeline of residency and fellowship. Fellows have family and other commitments as well and a well balanced life-work-training is critical for our trainees. 

The fact that graduates of the least competitive nephrology fellowship programs(smaller programs) performed worse after regression adjustment indicates there might be a peer effect, or advantages of a structured program at a larger academic center. 

IMGs were less likely to score high.  The field of Nephrology has seen an increase in IMG applicants.  In 2019, IMGs comprised nearly 70% of those taking the nephrology exam for the first time, an increase of more than eight percentage points from 2010. We keep forgetting that everyone learns differently- not everyone has a structure of learning in multiple choice questions in rest of the world; there are language barriers and other factors that play a role as well. Fellowship programs need to explore non ppt format of teaching and novel ways to teach the same material for varied type of learners. 

Finally, women were found to have lesser scores. To my knowledge, not sure of any published papers showing this difference in test taking strategies. I don't think we need to take any stake in these findings as these might be not of any significance. The editorial nicely reminds us to not take this finding seriously. 

What should be done?
Why can't we test the fellows on what we really encounter rather than esoteric rare and confusing diseases. Why can't the tests really mirror the life of a renal fellow and attending?
Institutions need to take ownership on better techniques and strategies to help their fellows. Many residencies may not be training them in proper test taking techniques. 
Institutional and program resources must support trainees’ needs, protect their time, and ensure education is prioritized.  

I can say from my personal example of few fellow I trained- had trouble passing the boards due to their test taking abilities. Their patient satisfaction scores as attendings are off the roof and their overall understanding of both patient care and medicine is excellent. They may not be a good test taker, but they can manage a good census, take care of patients and call for help when needed and effectively communicate with other doctors. They win patient trusts, they do well with following up and most important of all- they care! and want to be Nephrologists that matter. 

While test scores are important, failures sometimes teach us to be better and improve our abilities to be the best at what we do. But regardless, this is a wake up call for our field to improve as instructors and teachers and not disappoint our students. 

Monday, October 25, 2021

KDIGO 2021- GN Management Guidelines: FSGS

 FSGS has been the waste basket diagnosis for years. KDIGO finally has adopted the primary vs secondary FSGS way of thinking to make it easier to treat FSGS and diagnose the 99% of the secondary causes. Check out these amazing figures from the supplement

Treatment wise:  If primary FSGS- steroids 1mg/kg dosing for 4 weeks and then taper over 6 months
If not, then try CNI( cyclosporine vs tacrolimus)- goal 100-175 or 5-10 range for each drug
After 6 months, no response- considering MMF, anti cd20 agents but data on both is small. 
If secondary cause- treat the secondary cause or conservative management. SGLT2i may make it there next iteration. 

Thursday, October 21, 2021

KDIGO 2021: GN Management Guidelines: Membranous Nephropathy

MN management has changed in 2020 onwards thanks to two trials published in 2020-2021 that showed that cyclophosphamide/steroids is superior and rituximab is not the main player yet. 
The figures below summarize the main points of the GN 2021 KDIGO update 

Detective Nephron: Next Venture Oct 2021

 Here is the next DN case of AKI


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