1/n🚨🔊 Hey #nephtwitter #medtwitter #Onconephrology! Tweetorial alert!
🏥What do nephrologists👩⚕️, haem- oncologists 👩⚕️,@TheSkeletonKG have in common?
Lysing 🎆tumor cells have a story🔖!
Let's read the🔖:Intricacies of pathogenesis, diagnosis & Rx of tumor lysis syndrome -TLS
2/n A 13y 👦presented with
👉1 month of intermittent fever🌡️🤒
👉exertional dyspnea
👉significant weight loss⚖️.
On physical examination: He looked pale & volume-depleted.
🩸Labs were as follows:
3/n Further investigations showed
🩸Hb = 6.3 g/dL,
🩸total WBC count = 210,000/ mm3
🩸platelet = 10,000/mm3.
🩻CXR = mediastinal mass.
🦴PS & bone marrow examination = suggestive of B-cell type acute lymphoblastic leukemia (ALL).
4/n The metabolic profile was suggestive of:
🩸hypercalcemia,
🩸hypophosphatemia,
🩸hyperuricemia, and
🩸AKI with high anion-gap metabolic acidosis.
5/n 🗳️Poll: Why do you think the boy had low phosphate?
6/n
Ans: 4. Due to ⏫PO4 uptake by rapidly dividing leukemic cells associated 👉 aggressive tumor genesis.
Why does the boy have ↑ calcium❓
👉It's Malignancy-associated hypercalcemia!!
caused by 3 main mechanisms:
🦴↑PTHrP,
🦴↑osteoclast activating factors
🦴↑Vit D3
7/n We don't stop at that...now, why does he have hyperuricemia?
🧬Intracellular purine nucleic acids are catabolized to xanthine & hypoxanthine👉 converted to uric acid by the enzyme xanthine oxidase.
🧬↑ leukemic cell lysis leads to ↑ uric acid.
8/n So a myriad of electrolyte abnormalities has created a potpourri for AKI!!
Poll: What are the causes of AKI in this boy?
9/n Ans: 4
💎Uric acid precipitates in kidney tubules 👉obstruction ➡️AKI.
💎Uric acid also directly exacerbates AKI by causing vasoconstriction, ↓ blood flow to the kidneys
💎↑PO4 & alkalinization therapy promote CaPo4 crystal deposition causing nephrocalcinosis & AKI
10/n TLS is an oncological emergency 🚑due to the massive lysis🎆 of tumor cells➡️⏫ K+, PO4, & nucleic acids into the blood.
🚨High risk for TLS:
⚡️↑ tumor burden
⚡️↑ proliferative rate
⚡️↑ chemosensitivity
Usually associated with hematologic malignancies -NHL, ALL, CLL.
11/n
Diagnostic criteria: Cairo-Bishop definition (2004)
🩸Lab TLS: 2 or > of the criteria proposed 👇, 3 days before or 7 days after chemotherapy.
🩺Clinical TLS: lab TLS + any 1 of the following: AKI, arrhythmia, seizure
pubmed.ncbi.nlm.nih.gov/15384972/
12/n
🛑Drawback of this criteria:
🚧Criteria are defined relative to the timing of cytotoxic therapy. Hence, it does not consider spontaneous TLS.
🚧It defines AKI as 1.5 X UL of S.creat which is a poor indicator of true AKI and can include CKD patients as well.
13/n
Prophylactic measures in tumors at high risk for TLS:
🚿IV hydration - ⏫urine output to prevent precipitation of uric acid & CaPo4 💎 in the tubules.
💊hypouricemic agents - allopurinol, febuxostat,rasburicase
🩸monitoring lab parameters
pubmed.ncbi.nlm.nih.gov/18509186/
14/n
Urine alkalinization:
🛑This approach is no longer favored🛑
1 experimental study 👉maintaining ⏫distal urine flow with water/ solute diuresis was as effective as alkalinization of urine in preventing uric acid precipitation and stones.
pubmed.ncbi.nlm.nih.gov/16037/
15/n Uric Acid Lowering:
💉Rasburicase (preferred)- recombinant urate oxidase 👉breaks down uric acid 👉allantoin, which is water-soluble and non-nephrotoxic.
💊Allopurinol: xanthine oxidase inhibitor👉
xanthine accumulation and xanthine stone formation.
pubmed.ncbi.nlm.nih.gov/11342423/
16/n
Kidney replacement therapy (KRT)
Indications:
📍oliguria or anuria,
📍volume overload,
📍refractory hyperkalemia,
📍CaXPo4 > 70 mg2/dL
Which modality of KRT is preferred?
17/n Ans: 3. CRRT may be a better option but large studies comparing different modalities of KRT in TLS are currently lacking.
Rx:
He was initiated on hydration therapy with NS which was continued for 2 days until recovery of kidney function.
Why was KRT not considered here?
18/n Ans: 4
🪣UO was maintained at 2 mL/kg/hr or at least 3lts/d during the treatment.
🌟Kidney function normalized in 3 days🌟
19/n 💌Take home message:
🔥TLS 👉oncological emergency arising from the successful treatment of malignancy.
🔥Dynamic electrolyte imbalances & AKI occur before and after Rx - Watch out!!
🔥Rasburicase has improved outcomes.Cheers!🍻
🔥Need research on KRT modalities in TLS❓
20/n Check out the complete blogpost here: renalfellow.org/2022/07/11/ske…
VA by me @nephromythri
Thanks @RenalFellowNtwk @SKG @chichu @jamiekwillows @nepherson @DTomacruzMD @Nephro_Sparks @kidney_boy @onconephsociety @raad_chowdhury @SaiAchi1
Following initiation of chemo, our boy went on to develop TLS…
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