Introduction:
Acute lymphoblastic leukemia (ALL), the commonest pediatric malignancy, is a heterogeneous hematologic disease characterized by the proliferation of immature lymphoid cells in the bone marrow, peripheral blood, and other organs. Renal dysfunction in Acute leukemias is attributable to factors like AKI (sepsis, tumor lysis, ATN , obstructive causes, chemotherapy), Nephrotic syndrome (MCD, FSGS), Reno-vascular thrombosis, electrolyte disturbances and direct involvement due to Leukemic infiltration.Nephrotic syndrome (NS) in hematological malignancies usually manifests in association with use of induction chemotherapy agents. NS as an initial presentation of ALL is uncommon and mechanisms associated with it need to be elucidated further. We present a case of a 5-year-old girl with B cell- ALL who developed nephrotic syndrome, UTI, Acute Kidney disease and a renal infarct posing a treatment challenge.
Methods:
A 5-year-old girl presented with fever, fatigue and leg swelling. Her initial workup showed significant leukocytosis and dipstick 3+ proteinuria. On further evaluation she was diagnosed with Pre-B Cell Acute Lymphoblastic leukemia, with MLL gene re-arrangements, ETV6-RUNX1 and PBX1-TCF3. She had pitting lower limb edema, was hemodynamically stable and maintained an adequate urine output. Initial laboratory evaluation showed normal serum creatinine of 0.4 mg/dl, dyslipidemia and hypoalbuminemia(serum albumin of 2.6 g/dl). Urinalysis showed no RBCs or casts, but had spot urine protein-to-creatinine ratio of 6.4 mg/g.
Results:
For B-cell ALL, the patient was started on steroid and chemotherapy as per Berlin-Frankfurt-Munich protocol (prednisolone 60mg/m2/day, Vincristine, Daunorubicin, Methotrexate, L-Asparaginase ). She tolerated her induction chemotherapy well, showed good response for leukemia and decrease in proteinuria (UPCR 2.3 mg/mg). Her further course was complicated with development of urosepsis (candiduric and serum galactomannan positive) and her chemotherapy was temporary discontinued. Subsequently, her proteinuria worsened (UPCR 9 mg/g) and she developed severe hypoalbuminemia (1.6 mg/dL). Due to ongoing sepsis and thrombocytopenia, renal biopsy was deferred. CECT showed no contrast uptake of entire right kidney and middle and lower pole of left kidney and part of spleen suggestive of infarct possibly due to prothrombotic state secondary to severe hypoalbuminemia. She was started on anticoagulants and antibiotics (Meropenem and Liposomal Amphotericin B) with renal dosing. Over the next few weeks, her sepsis resolved, and she went into partial remission of leukemia and decrease in protenuria(UPCR 1.2mg/g). However, her renal derangement persisted (serum creatinine 0.9 mg/dL and measured GFR by DTPA scan: left kidney 31ml/min and right kidney 6ml/min).
Conclusions:
Nephrotic syndrome as an initial presentation of ALL is uncommon. At present patient continues to be in partial remission and is planned for further chemotherapy regimen with renal dosing for B-cell ALL.High index of suspicion and timely renal intervention can guide regarding underlying pathology and treatment. Management of Pre-B Cell Acute Lymphoblastic leukaemia on the background of multifactorial renal dysfunction (low GFR, possible nephrotic syndrome, urosepsis, renal vascular thrombosis) poses a hindrance to reinstitution of chemotherapy. The risk of leukaemia relapse and further deterioration of kidney function with chemotherapy needs to be elucidated further.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.