Thread by @nephromythri

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…