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. 

Hypocomplementemia and the Kidney

 When we are faced with AKI and classically low c3 and c4, certain diseases come to mind.

A classic figure that has been used for years is below:

I think we can divide the low complement diseases and the kidney with glomerular processes and non glomerular processes

The glomerular diseases that are classically associated with low complements are:

MPGN pattern( all forms, c3GN, DDD, immune complex related MPGN), Lupus related GN, Cyro related GN, infection associated GN( both post strep and endocarditis), but we should not forget Fibrillary GN ( especially if MPGN pattern of injury is noted) and heavy chain deposition disease(HCDD). Finally, we should not forget TMA with complement disorders can cause low c3 in some cases.  In other words, immune complex is the main pathology that is driving the hypocomplementemia. 

Non glomerular diseases that can be associated with low complements should be kept in mind- classically atheroembolic disease and IgG4 diseases( fair amount have low complements)

Here is a mnemonic that many use- CHAMPS ( created by NephSim)