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.

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. 

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. 

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

http://onlinedigeditions.com/publication/?m=15191&i=724592&p=36&ver=html5

KDIGO 2021: GN Management Guidelines: IgA nephropathy

 

The three figures from the recent KI GN update 2021 summarizes IgA nephropathy.

Basically, At this point, given negative studies for steroids, only thing we have that has strong evidence is conservative management. Interestingly, SGLT2i did not make it to the guidelines.  ACEI/ARB+ SGLT2i might be the best treatment options we have for IgA Nephropathy. 

The one place where immunosuppressive meds will help is Crescentic IgA nephropathy and IgA with MCD. 

Here is the final table on all meds and their data from KDIGO

Does immunosuppressive meds help IgA nephropathy? Do we await the budesonide directed therapy approval, do we await more supportive agents such as ET1 antagonists or Aldo antagonists? Time will tell. Till then, IgA nephropathy is still the hardest GN to treat as we don't have clear options for treating the pathophysiology of the disease. 

Consult Rounds: Hyponatremia and AKI- need CRRT- what do we do??

 

Hyponatremia correction is challenging but manageable.
Offering and prescribing CRRT in the ICU is also doable by most nephrologists.

Here comes the challenge.

You are called, “ anuric patient, Na 110, K 5.4, BUN 90, Crt 6.0mg/dl) and altered mental status”
Now you are confronted with correcting the Na slowly and providing good dialytic clearance as well given anuria and hyperkalemia.

CRRT has advantages in its ability to correct plasma sodium values in a predictable and slow manner. Compared with standard hemodialysis machines, where the lowest dialysate sodium concentration is 130 mEq/l, CRRT solutions can be customized to any desired sodium level, allowing for personalized therapy. 

To act on these advantages and prescribe CRRT to target an increase in serum sodium no >6 mEq/L per day, there are three options: either (1) customize the CRRT circuit or (2) customize CRRT solutions. (3) add D5W infusion separate line with standard CRRT

So how is this rate calculated if we were to use Method 3( the easiest of the 3 options)

If D5W rate will be used – the formula is (140 -- target Na value)/( 140 X clearance)
So if we take 110 meq/L as the starting Na value and goal is in 24 hours to be 118. Given the patient was symptomatic, using 3% saline bolus- we get him to 112-113meq/L range. Then if we do 30cc/kg/hour clearance of CVVHDF, that would be roughly 2.4 liters/hour and hence the rate of D5W would need be 375cc/hour. If we use clearance of 25cc/kg/hour- then around 300cc/hr of D5W would be needed.

In an article by Rosner et al, in CJASN, method 1 is well discussed using this figure- changing the post filter fluid or replacement fluid to sterile water( d5W) and rate calculated similarly as stated above.

For method 2: Adding sterile water to commercial dialysis solutions to achieve a desired final sodium concentration would be next way. For instance, if a 5-L bag of replacement solution has a sodium concentration of 140 mEq/L, then the addition of 1 L of water would result in a final sodium solution of the replacement solution of 116.7 mEq/L. 

An important caveat, once desired Na is reached, D5W needs to be changed back to standard replacement fluids and or D5W drip discontinued. 

In the NEWS: Immunotherapy and the Kidney( new data in 2021)- AKI and electrolytes

Immune checkpoint inhibitors (ICI) are a novel class of immunotherapy drugs that have vastly improved cancer care for patients. Data on AKI has been evolving. 

In a multicenter international study just published in JITC by Gupta et al involving 30 sites across 10 countries, researchers collected data on 429 patients with ICI-AKI and 429 control patients who did not develop ICI-AKI. Armed with the largest ICI-AKI database to date, the team of researchers was able to identify predictors, recovery potential and survival outcomes of those patients with ICI-AKI.

One of the most important findings from the two-year study reveals that among patients who take ICI again – even after an episode of ICI-AKI – only 16.5 percent developed recurrent ICI-AKI, which shows that most patients can still take these life-saving medications safely.

Additional findings show that in renal-recovery occurs in approximately two-thirds of patients with ICI-AKI. Early treatment with corticosteroid is associated with a higher likelihood of renal recovery. Lower baseline kidney function, proton pump inhibitor use and extrarenal immune-related adverse events are independent risk factors for developing ICI-AKI.

A related paper recently published in the journal Kidney International by Wanchoo et al looking at the scope of electrolyte disorders that are seen with ICI. Hyponatremia, hypokalemia and hypercalcemia were the most common findings. SIADH is the most common cause of hyponatremia and adrenal disorders led the way in the cause of hypercalcemia.