Keywords
Acute lymphoblastic leukemia - acute renal failure - lymphoblastic lymphoma - lymphoma
Introduction
Acute lymphoblastic leukemia (ALL) is the most frequent childhood malignancy.[1] Leukemic infiltration of the kidneys is more common in the late stage of ALL and
lymphoblastic lymphomas in all age groups and is reported to occur in 7%–42% of childhood
leukemia cases.[2],[3] Acute renal failure has a variety of etiologies, but when associated with acute
leukemia, it is typically due to therapy-related side effects, metabolic changes arising
from chemotherapy, septicemias, nephrotoxic drugs, and leukemic infiltration of kidneys.[4] Acute renal failure with hyperuricemia is a well-recognized complication of tumor
lysis syndrome, and it occurs before or after the initiation of chemotherapy.[4] However, initial presentation of acute leukemia as bilateral renal enlargement with
renal failure with normal uric acid level is rather rare.[2],[3] Here, we report one such case.
Case Report
A 6-year-old boy presented to us with a history of fever for a month. Fever was high-grade
intermittent not associated with rigors. Over next few days, he developed hurried
breathing and was admitted to a local hospital and started on intravenous antibiotics
for suspected pneumonia. Investigations showed hemoglobin of 6.8 g%, high white blood
count (WBC) of 22,200 cells/cumm (neutrophils 38%, lymphocytes 59%, and eosinophils
3%), and platelet count of 1.1 lakhs/cumm. His chest X-ray was normal. However, renal
functions were altered with serum creatinine of 2 mg/dl, sodium of 132 mEq/L, and
serum potassium of 2.8 mEq/L. The bone profile showed calcium of 7.6 mg/dl and alkaline
phosphatase of 450 IU. Urine analysis showed pH of 7.5 with no evidence of urine infection.
The blood and urine cultures were negative. Abdominal ultrasonogram revealed bulky
kidneys with the right kidney of 9 cm × 6 cm and left kidney of 10 cm × 5 cm. He was
thought to have renal tubular acidosis with renal failure in view of compensated metabolic
acidosis and started on sodium bicarbonate tablets, calcium, and Vitamin D supplements.
However, the child continued to have low-grade fever with tachypnea for over 2 weeks
and so was transferred to a tertiary care hospital. His initial investigations showed
hemoglobin - 7.3 g%, WBC - 10,800 cells/cumm (neutrophils - 44%, lymphocytes - 54%,
and eosinophils - 2%), serum creatinine - 1.6 mg/dl, and erythrocyte sedimentation
rate (ESR) - 130 mm/h, and peripheral smear was normal with no evidence of abnormal
cells. Repeat ultrasound abdomen confirmed bilateral enlarged kidneys with coarse
echotexture. Abdominal computed tomography scan confirmed the large-sized kidneys
[Figure 1]a. His electrolytes, liver function test, calcium (7.8 mg/dl), phosphorous (3.2 mg/dl),
lactate dehydrogenase (256 U/L), and uric acid (1.2 mg/dl) done were within normal
range. The chest X-ray showed moderate left-sided pleural effusion [Figure 1]b. Arterial blood gas analysis showed pH - 7.38, pCO2 - 26 mmHg, pO2 - 54 mmHg, bicarbonate
- 18.3 mEq/L, and base excess - 6.8 mEq. The child was thought to have disseminated
tuberculosis (TB) in view of persistent fever spike, cough, pleural effusion, high
ESR, and hepatosplenomegaly and started on antitubercular treatment. Urine culture
showed no growth. As the respiratory distress was increasing, video-assisted thoracoscopic
surgery was done, and pleural fluid was sent for acid-fast bacilli and for GeneXpert
TB test. Pleural fluid cytology showed plenty of lymphoblasts and GeneXpert test was
negative for TB. Antitubercular treatment was stopped and was transferred to pediatric
oncology department. The bone marrow aspiration done 8 days after starting treatment
showed 12% of blasts. He was diagnosed with T-cell leukemia and started on chemotherapy
under regimen C of UKALL 2003 protocol. His renal function normalized after chemotherapy
was started and renal size became normal for the age by the end of induction. Day
29 of induction minimal residual disease was <0.01%. Currently, he is on the third
maintenance cycle of ALL therapy and is doing well.
Figure 1: (a) Abdominal computed tomography images showing the bulky kidneys performed
on admission to the tertiary hospital. (b) The chest X‑ray showing left-sided pleural
effusion
Discussion
Acute renal failure due to tumor lysis is a more common manifestation in ALL.[5],[6],[7] It usually occurs by two mechanisms. The first one is uric acid nephropathy due
to intratubular precipitation of uric acid causing mechanical obstruction, direct
toxicity to epithelial and endothelial cells, and potentially activation of the innate
immune system.[5],[6],[7] The second one is hyperphosphatemia causing intrarenal calcium phosphate precipitation
and direct tubular toxicity of phosphate.[8],[9] Standard prophylaxis of oral allopurinol to block uric acid formation or injection
rasburicase (urate oxidase) coupled with intravenous hydration has dramatically reduced
the incidence of uric acid nephropathy but not eliminated it.[10]
Leukemic infiltration of the kidneys is reported to occur in 7%–42% of childhood leukemia
cases. It usually seen in the late stages of ALL in all age groups.[2],[3] In contrast, bilateral symmetrical renal enlargement at the time of diagnosis of
ALL or lymphoblastic lymphoma is an infrequent finding, being present in 3%–5% of
cases.[11] A potential mechanism for leukemic infiltration due to interaction of the chemokine
receptor CXCR4, which is expressed on ALL cells, and its ligand stromal cell-derived
factor-1 produced by stromal cells in bone marrow and extramedullary organs. Crazzolara
et al.[12] reported that CXCR4 and its ligand play an important role in extramedullary invasion.[12]
There are different opinions about prognosis for children with leukemic renal involvement
and resultant bulky kidneys. D′Angelo et al.[13] assessed the prognostic value of bulky kidneys in children at time of diagnosis
with ALL. They reported poorer event-free survival in a group with nephromegaly that
was treated with nonintensive protocols than in a group without nephromegaly. In contrast
to these findings, Neglia et al.[14] found that when kidney size was analyzed as a single variable and when it was considered
after adjustment for the known prognostic factors of age, sex, and initial WBC count,
enlarged kidney size at diagnosis of ALL in childhood was not associated with overall
poorer survival.
Conclusion
As a conclusion, few cases of bilateral bulky kidneys in childhood acute leukemia
were reported in literature. Renal involvement of acute leukemia or lymphoma should
be considered in a child presenting with unexplained bilateral renal enlargement and
fever with or without renal function abnormalities. Bone marrow examination should
be included in the workup. With the availability of current evidence, we do not know
the prognostic value of bulky kidneys in children with ALL.
