Onconephrology Basics
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Direct answer
Tumour lysis syndrome sets the template for onconephrology: high-burden, treatment-sensitive malignancies (Burkitt lymphoma, acute lymphoblastic leukaemia with high counts) release potassium, phosphate and uric acid into the circulation faster than the kidneys can clear them, producing hyperkalaemia, hyperphosphataemia with symptomatic hypocalcaemia, and acute kidney injury from crystal deposition — prevented with saline hydration plus allopurinol in medium-risk and rasburicase in high-risk patients, and defined by Cairo-Bishop laboratory criteria or their clinical complications. Around that emergency sit the other renal faces of cancer: myeloma cast nephropathy (avoid NSAIDs and contrast, hydrate, treat the clone rapidly), obstructive uropathy, direct infiltration, electrolyte paraneoplastic syndromes (SIADH from small-cell lung cancer, hypercalcaemia from PTHrP-secreting squamous cancers), and chemotherapy nephrotoxicity from cisplatin, ifosfamide and the checkpoint inhibitors.
What you must remember
- TLS definition: laboratory TLS — two or more of uric acid above 8 mg/dL, potassium above 6, phosphate above 6.5 (children) or 4.5 (adults) mg/dL, calcium below 7 mg/dL (or 25% rise/fall as Cairo-Bishop criteria frame it), within days of therapy; clinical TLS adds AKI, arrhythmia or seizure.
- Prevention protocol: IV saline 2-3 L/m²/day hydration; allopurinol for medium-risk (reduces uric acid formation but not existing levels); rasburicase (recombinant urate oxidase) for high-risk disease — it dissolves existing uric acid and is contraindicated in G6PD deficiency (haemolysis, methaemoglobinaemia).
- Myeloma kidney: light-chain casts in distal tubules precipitated by volume depletion; avoid NSAIDs and iodinated contrast like the plague, hydrate aggressively, consider high-cutoff haemodialysis in selected units, and start clone-directed therapy (bortezomib-based) urgently.
- Obstructive uropathy: pelvic and retroperitoneal malignancy, retroperitoneal fibrosis, and bilateral ureteric obstruction presenting as AKI with hydronephrosis — decompress with nephrostomy or stents; post-obstructive diuresis follows.
- Paraneoplastic electrolytes: SIADH (small-cell lung cancer), humoral hypercalcaemia of malignancy via PTHrP (squamous cancers of lung, head and neck, oesophagus), hypokalaemia from ACTH-driven cortisol excess, and protein-losing states.
- Chemotherapy nephrotoxics: cisplatin (ATN, Mg-wasting), ifosfamide (Fanconi-type proximal tubulopathy), methotrexate (precipitation at high dose with acidic urine — alkalinise and hydrate), gemcitabine and mitomycin C (thrombotic microangiopathy), and anti-VEGF/VEGFR agents (hypertension, proteinuria, TMA).
- Checkpoint inhibitor nephritis: immune-related AIN or glomerulonephritis in patients on pembrolizumab-nivolumab class drugs — withhold the drug, biopsy, and treat with steroids; the modern addition to every AIN differential.
- Bone-marrow-to-kidney crossovers: cast nephropathy, AL amyloidosis (presenting with nephrotic-range proteinuria) and cryoglobulinaemic disease each give a distinct biopsy signature.
Running the prevention-to-treatment pathway
A 22-year-old with Burkitt lymphoma and a high tumour burden starts chemotherapy. Before the first dose: saline at 3 L/m²/day, rasburicase (after confirming normal G6PD status), cardiac monitoring and electrolytes every six hours for 48-72 hours. He develops potassium 6.4 and phosphate 7.1 on day two with rising creatinine — clinical TLS: calcium gluconate, insulin-dextrose, and renal replacement for refractory hyperkalaemia or overload; dialysis in TLS holds the fort while chemotherapy does the definitive work.
His ward-neighbour shows the other half: a 64-year-old with myeloma and creatinine 4.5 mg/dL. The plan avoids everything that worsens cast nephropathy — no NSAIDs, no contrast CT, aggressive hydration — while bortezomib-dexamethasone attacks the clone within days. Between these two beds sits the whole field: prevent the predictable, withdraw the toxic, decompress the obstructed, and treat the cancer as the nephrological treatment.
Where students slip
The rasburicase-G6PD interaction is the single most-tested factoid in onconephrology — the drug that rescues TLS haemolyses the G6PD-deficient patient, so the answer "check G6PD before rasburicase" beats reflex drug administration every time. Second, the myeloma hydration principle: candidates choose "NSAIDs for analgesia" or "contrast CT for staging" in myeloma AKI stems, both planted errors. Third, the methotrexate alkalinisation logic (solubility of the drug and its metabolites in alkaline urine) still appears, usually as a mechanism one-liner. Indian examiners add a regional nuance — allopurinol and rasburicase access differs across Indian centres, so the allopurinol-plus-hydration default is the operationally correct answer when rasburicase is unavailable, a distinction that separates textbook recall from programmatic sense.
Frequently asked questions
What defines tumour lysis syndrome?
Two or more laboratory abnormalities (uric acid over 8 mg/dL, potassium over 6 mEq/L, phosphate above age-based thresholds, low calcium) within three days before or seven days after therapy, or any such abnormality plus AKI, arrhythmia or seizure.
Why is rasburicase contraindicated in G6PD deficiency?
It generates hydrogen peroxide while converting uric acid to allantoin, and G6PD-deficient red cells cannot detoxify the oxidant stress, resulting in severe haemolysis and methaemoglobinaemia.
How is myeloma cast nephropathy prevented and treated?
Force hydration, strict avoidance of NSAIDs and iodinated contrast, urgent bortezomib-based clone reduction, and supportive dialysis as needed — the cast dissolves only when light chains stop coming.
Which chemotherapy drugs cause thrombotic microangiopathy?
Mitomycin C, gemcitabine, and anti-VEGF/VEGFR agents such as bevacizumab — presenting with anaemia, schistocytes, thrombocytopenia and renal impairment.
What renal syndromes accompany checkpoint inhibitor therapy?
Acute interstitial nephritis most commonly, occasionally glomerulonephritis — managed by holding the checkpoint inhibitor, biopsy confirmation, and corticosteroids.