Elena Cervantes Profile picture
Oct 31, 2021 19 tweets 9 min read Read on X
1/
🚨Is sodium bicarbonate useful to prevent Rhabdomyolysis induced AKI ❓❓🚨

We get asked this all the time! But in order to understand it, let's start with a simple question

What is the mechanism of AKI in rhabdomyolysis ❓❓
2/
1⃣What happens in rhabdo?
⚡️Muscle necrosis → release of intracellular components (enzymes-CK, electrolytes & myoglobin)
⚡️Fluid sequestration within damaged muscle → volume depletion →🚨 RAAS➕SNS
⚡️Oxidative injury →⬆️ in vascular mediators → ⬇️renal blood flow
3/
We might see ⬆️Creatine Kinase (CK) levels somewhat frequently...

BUT...

Is there a CK level that predicts AKI❓
⚡️There is no defined threshold value of CK
⚡️CK levels < 15,000 to 20,000 U/ L on admission usually have a low risk of AKI

pubmed.ncbi.nlm.nih.gov/16490621/
4/
More on pathophys...
2⃣What is MYOGLOBIN?
⚡️17.8 kDa protein
⚡️Enters tubular epithelial cells through endocytosis
⚡️⬆️Reactive Oxygen Species (ROS) and free radicals
⚡️Precipitates with the Tamm-Horsfall protein (THP) in the distal tubular lumen
pubmed.ncbi.nlm.nih.gov/19571284/
5/
The pathophysiology of AKI involves
⚡️Renal Vasoconstriction
⚡️Myoglobin induced oxidative injury
⚡️Intratubular cast obstruction

🚨Myoglobin induced direct cytotoxicity AND the formation of pigmented granular casts are favored by an ACIDIC URINE!! 🚨
6/
Before we dive into prevention 🚫 & treatment 💊 of AKI

🧪Beware of electrolyte complications...
- There is a ⬆️in serum K, Phos, Mg, uric acid
- There is a ⬇️in serum bicarbonate & Ca (initially⬇️then⬆️)
7/
The main strategy for 🚫prevention of AKI is:

💧IV volume repletion → target UO of 200-300 cc/hr
💧No difference between IVF solutions
8/
What other strategies would you use to prevent AKI?
9/
The role of bicarbonate for prevention of pigment nephropathy is perhaps one of the most common questions we get asked as nephrologists...
10/
Based on the mechanisms of AKi, alkalinizing the urine would prevent:
⚡️Precipitation of myoglobin -THP complexes → ⬇️intratubular cast formation
⚡️Reduction-oxidation cycling of myoglobin ---> ⬇️tubular injury
⚡️Metmyoglobin formation (vasoconstrictor) → ⬇️vasoconstriction
11/
So why don’t we give bicarbonate to everyone❓❓
12/
It turns out that alkalemia has been associated with higher mortality ☠️

pubmed.ncbi.nlm.nih.gov/3589765/
13/
Some of the downsides of alkalemia include:
🚫Depression of respiratory center
🚫Low iCa
🚫Low Myocardial Contractility
🚫Low Cerebral Blood Flow
14/
Since alkalemia is detrimental. Is there any evidence behind urine alkalinization❓

An animal model from 1952 by Perri GC and Gorini P showed that animals on an acidifying diet had a urine pH < 6 and developed AKI due to myoglobin precipitation

europepmc.org/backend/ptpmcr…
15/
In 1984, findings from animal models were reproduced in humans by Ron et.al
⚡️Urine alkalinization (target urine pH > 6.5) was used to treat 7 patients with rhabdomyolysis
⚡️None of them developed AKI by day 5
🚨 No control group
pubmed.ncbi.nlm.nih.gov/6696564/
16/
Different studies compared preventive & therapeutic regimens:
⚡️Early initiation of therapy with volume repletion is better
⚡️No difference between NS 🆚 NS +bicarb+mannitol
⚡️No difference between LR 🆚NS.
Both got bicarb if urine pH < 6.5. NS group required more bicarb
17/
SUMMARY:
⚡️AKI d/t rhabdo can be d/t vasoconstriction, oxidative injury & intratubular casts
⚡️Acidic urine ⬆️myoglobin toxicity in the proximal tubule AND precipitation of myoglobin-THP casts
⚡️CK levels < 15,000 to 20,000 U/ L on admission usually have a low risk of AKI
18/
SUMMARY:
⚡️Beware of electrolyte abnormalities!!
⚡️Aggressive IVF repletion is the 🗝️
⚡️A urine pH > 6.5 has been suggested to decrease the risk of AKI (limited data)
pubmed.ncbi.nlm.nih.gov/19571284/
19/
I hope you enjoyed this overview on the prevention of AKI in rhabdomyolysis 🤓

Special thanks to @NSMCinternship, #GroupofHenle @amyaimei @Nephro_Sparks @docanjuyadav @drM_sudha @jamiekwillows

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More from @Elena_Cervants

Mar 5, 2022
1/
Let's be honest...
💥💥“THE TISSUE IS THE ISSUE” 💥💥
#Nephropath #NephMadness

This region features:
🔎PLA2R 🆚Other Membranous Antigens

🔎DNAJB9 🆚IgG4 Disease

READY???👇👇
ajkdblog.org/2022/03/01/nep…
2/
Matchup 1⃣: PLA2R 🆚Other MN Antigens

PLA2R facts
✅Present in healthy human podocytes
✅70-80% 👥with 1ry MN & ~ 60% of ALL MN
✅Serum Ab are measured via ELISA & IF
💡💡DX:
🧪ELISA > 14 RU/mL or
🧪ELISA 2 - 14 RU/mL WITH a positive IFA
pubmed.ncbi.nlm.nih.gov/34556256/
3/
Check this beautiful Visual Abstract by @Vernisartan on the serology based approach to MN

A few more words on Anti-PLA2R titers:
✅>150 RU/mL- ⏫ risk of progression
✅> 45 RU/mL- ⏫risk of recurrence post transplant

💡 Titers are part of the risk stratification algorithm💡
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