Severe Infiltration of the Kidneys With Ultrasonic Abnormalities in Acute Lymphoblastic Leukemia Ten Suan Goh, MB, BS, FRCP(C); Kwan Yuen Wong, MB, BS
Garry
W.
\s=b\ A 3-year-old boy with acute lymphoblastic leukemia had enlarged kidneys with impairment of renal function and hypertension as the presenting features of relapse. Ultrasound demonstrated multiple nodular areas of echolucency within enlarged kidneys that reverted to normal when the patient was in remission but then recurred during relapse. This noninvasive procedure may be useful in patients with acute lymphoblastic leukemia to determine the incidence and prognostic significance of renal involvement at the time of diagnosis, and to follow the course of those who have demonstrable
changes. (Am J Dis Child 132:1204-1205, 1978) in acute lymleukemia is usually due to uric acid nephropathy. Leukemic infiltration of the kidneys is suspected when an elevation of the blood pressure is observed, although this is a rare complication.' The kidneys may or may not be palpably enlarged, and renal function is usually
insufficiency Renalphoblastic '
From the Departments of Pediatrics and Radiology, University of Cincinnati College of Medicine, and the Children's Hospital Medical
Center, Cincinnati. Reprint requests to Hematology-Oncology Division, Children's Hospital Research Foundation, Elland and Bethesda avenues, Cincinnati, OH 45229 (Dr Goh).
LeQuesne, MB, BS, MRACR;
severely disturbed.2 Radiologie generally show enlargement kidneys with elongation and stretching of the renal pelves, infundibula, and calyces, which may simu¬ late the appearance of polycystic disease.' Biopsy of the kidney for confirmation of the abnormality is usually not attempted because of an associated thrombocytopenia. Thus, not
studies of the
the actual incidence of leukemic infil¬ tration of the kidneys in acute lymphoblastic leukemia is unknown. We are reporting here the results of studies in a child with acute lympho¬ blastic leukemia who had considerable enlargement of his kidneys with impairment of renal function and ultrasonic changes in the kidneys as the presenting features of relapse. REPORT OF A CASE This 3-year-old boy with acute lympho¬ blastic leukemia had anemia, easy bruis¬ ing, and hepatosplenomegaly. Blood pres¬ sure was 80/50 mm Hg. Serum uric acid level was 5.0 mg/dl; creatinine level, 0.7 mg/dl; and BUN level 14 mg/dl. He responded well to treatment with predni¬ sone and vincristine sulfate, and remission was achieved after four weeks. He then received prophylactic treatment to the CNS in the form of whole brain irradiation with 2,400 rads and five doses of methotrexate intrathecally over a two-week peri-
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od. Maintenance drugs were mercaptopurine and methotrexate. Sixteen months after diagnosis, on a routine clinic visit, he was found to be hypertensive: blood pressure was 120 to 140/90 to 110 mm Hg. Both kidneys were markedly enlarged. Hemoglobin level was 11.0 gm/dl; white blood cell count was 5,400/cu mm, with 66% neutrophils, 17% lymphocytes, 5% eosinophils, and 12% monocytes. Platelets were quantitatively normal on the smear. The BUN level was 21 mg/dl; serum creatinine level, 1.2 mg/dl; and uric acid level, 6.0 mg/dl. Urinalysis showed a pH of 6.0, specific gravity of 1.012, albumin of 1 + On a centrifuged urine specimen there were three to four RBCs per high power field. Urine culture was negative for bacteria. The excretory urogram demonstrated poor visualization of the kidneys; however, both kidneys were enlarged and the calyces were stretched and poorly filled. The collecting systems were not dilated and there was no evidence of obstruction. The bone marrow was 75% replaced with lymphoblasts. A specimen of urine exam¬ ined after cytocentrifugation disclosed the presence of blast cells. During the period of laboratory evaluation, there was progres¬ sion of renal impairment: BUN level increased to 33 mg/dl and serum creatinine concentration to 2.2 mg/dl. He was treated with prednisone and vincristine. Within five days, his blood pressure returned to normal and the kidneys were no longer palpable. He was in remission after six .
Fig 1.—Ultrasonic appearance of right kidney at time of presentation: a, renal outline; b, echoes arising from normal
Fig 2.—After six weeks of treatment, appearance of renal parenchyma is now normal: a, renal outline; b, echoes arising from normal structures in renal sinus.
Fig 3.—Second relapse
weeks of chemotherapy and was main¬ tained with cyclophosphamide. His remis¬ sion lasted only four months, at which time his bone marrow contained many blast forms, and he was treated with prednisone, vincristine, asparaginase, and doxorubicin hydrochloride (Adriamycin). During this period he became hypertensive again. He had a transient partial response only and died of progression of his leukemia. Autop¬ sy was not done.
was
accompanied by loss of the nodu¬ lar pattern, corresponding to the partial response in the bone marrow, but the appearance of the renal paren¬ chyma did not return entirely to normal.
The recommended treatment for leukemic infiltration of the kidneys is radiotherapy.*" We have demon¬ strated in our case the rapid response of the renal leukemia to systemic chemotherapy, but the recurrence in our patient raises the question of whether chemotherapy alone is ade¬ quate. Further information on the incidence of renal leukemia is needed in order to evaluate its prognostic significance and the proper therapy.
structures in renal sinus; c, nodular areas of echolucency separated by strands of compressed renal tissue showing in¬ creased echogenicity.
ULTRASONIC FINDINGS
Ultrasonic examination of the kid¬ neys at the time of original recogni¬ tion of the patient's hypertension confirmed the physical findings of
enlarged kidneys. renal outlines were
In
were
addition, the nodular, and there
multiple areas of relative echolu¬
cency up to 3
cm
in diameter within
the
kidneys (Fig 1). Repeated ultrasonic
examination after two weeks of chemotherapy showed a 4-cm reduction in renal length. The nodular pattern had disappeared although some areas of ultrasonic abnormality persisted with¬ in the kidneys. When the patient was in bone marrow remission, after six weeks of treatment, the echographic pattern of the kidneys was normal (Fig 2), as was the excretory urogram.
The kidneys were not clinically enlarged at the time when hyperten¬ sion recurred during the second relapse. However, a 1-cm increase in renal length, together with a nodular pattern of the renal parenchyma, was again demonstrated with ultrasonic examination (Fig 3). The changes bore a striking resemblance to those seen in the original study, but were not as severe in degree. Further treatment
COMMENT
Marked enlargement of the kidneys with impairment of renal function and hypertension is extremely unu¬ sual as a sign of relapse in acute lymphoblastic leukemia.4·5 The radiologic findings may not be specific. Transonic areas in the kidneys have been described in leukemia." The improvement of the ultrasonic pattern of the kidneys corresponding with the clinical response to treatment of leukemia and its recurrence during relapse in our case suggests that the ultrasonic pattern was indicative of leukemic infiltration. Thus, it appears that ultrasonic examination of the kidneys may be a useful method for following the course of the disease in patients with acute lymphoblastic leu¬ kemia. Also, it is possible that the incidence of renal involvement and its prognostic significance could be deter¬ mined by obtaining ultrasonic exami¬ nations at the time of diagnosis. Cytocentrifugation has been shown to be useful in the diagnosis and management of meningeal leukemia.7 The presence of blast cells in the urine in the absence of a bleeding diathesis suggests leukemic infiltration of the kidneys. However, the absence of blast cells in the urine in our patient during the subsequent relapse, despite
the echographic changes, suggests that cytocentrifugation is helpful only if there is severe renal involvement.
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four months later. Ultrasound shows recurrence of nodular pattern (c) in renal parenchyma, although less marked than previously.
This investigation was supported in part by general research support grant 5 SOI RR 05535-15 from the National Institutes of Health.
Nonproprietary Name and Trademark of Drug Vincristine sulfate—Oncovin.
References 1. Lascari AD: Leukemia in Childhood. Springfield, Ill, Charles C Thomas Publisher, 1973, p 34. 2. Gilbert EF, Rice EC, Lechaux PA: Renal function in children with leukemia. Am J Dis Child 93:150-156, 1957. 3. Gowdey JF, Neuhauser EBD: The roentgen diagnosis of diffuse leukemic infiltration of the kidneys in children. Am J Roentgenol Radium Ther Nucl Med 60:13-21, 1948. 4. Koch K, Reiquam CW, Beatty EC Jr: Acute childhood leukemia: Unusual complications. Rocky Mt Med J 63:55-60, 1966. 5. Widagdo IW, Markum AH: Leukemic infiltration of the kidney. Pediatr Indonesia 14:159\x=req-\ 162, 1974. 6. Walls WJ, Roberts FF, Templeton AW: B-scan diagnostic ultrasound in the pediatric patient. Am J Roentgenol Radium Ther Nucl Med 120:431-437, 1974. 7. Komp DM: Cytocentrifugation in the management of central nervous system leukemia. J Pediatr 81:992-994, 1972. 8. Stoffel TJ, Nesbit ME, Levitt SH: The role of radiotherapy in renal involvement in acute childhood leukemia. Radiology 117:687-694, 1975. 9. Lampkin BC, McWilliams NB, Mauer AM: Treatment of acute leukemia. Pediatr Clin North Am 19:1123-1140, 1972.
Garry
W.
\s=b\ A 3-year-old boy with acute lymphoblastic leukemia had enlarged kidneys with impairment of renal function and hypertension as the presenting features of relapse. Ultrasound demonstrated multiple nodular areas of echolucency within enlarged kidneys that reverted to normal when the patient was in remission but then recurred during relapse. This noninvasive procedure may be useful in patients with acute lymphoblastic leukemia to determine the incidence and prognostic significance of renal involvement at the time of diagnosis, and to follow the course of those who have demonstrable
changes. (Am J Dis Child 132:1204-1205, 1978) in acute lymleukemia is usually due to uric acid nephropathy. Leukemic infiltration of the kidneys is suspected when an elevation of the blood pressure is observed, although this is a rare complication.' The kidneys may or may not be palpably enlarged, and renal function is usually
insufficiency Renalphoblastic '
From the Departments of Pediatrics and Radiology, University of Cincinnati College of Medicine, and the Children's Hospital Medical
Center, Cincinnati. Reprint requests to Hematology-Oncology Division, Children's Hospital Research Foundation, Elland and Bethesda avenues, Cincinnati, OH 45229 (Dr Goh).
LeQuesne, MB, BS, MRACR;
severely disturbed.2 Radiologie generally show enlargement kidneys with elongation and stretching of the renal pelves, infundibula, and calyces, which may simu¬ late the appearance of polycystic disease.' Biopsy of the kidney for confirmation of the abnormality is usually not attempted because of an associated thrombocytopenia. Thus, not
studies of the
the actual incidence of leukemic infil¬ tration of the kidneys in acute lymphoblastic leukemia is unknown. We are reporting here the results of studies in a child with acute lympho¬ blastic leukemia who had considerable enlargement of his kidneys with impairment of renal function and ultrasonic changes in the kidneys as the presenting features of relapse. REPORT OF A CASE This 3-year-old boy with acute lympho¬ blastic leukemia had anemia, easy bruis¬ ing, and hepatosplenomegaly. Blood pres¬ sure was 80/50 mm Hg. Serum uric acid level was 5.0 mg/dl; creatinine level, 0.7 mg/dl; and BUN level 14 mg/dl. He responded well to treatment with predni¬ sone and vincristine sulfate, and remission was achieved after four weeks. He then received prophylactic treatment to the CNS in the form of whole brain irradiation with 2,400 rads and five doses of methotrexate intrathecally over a two-week peri-
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Iowa User on 06/13/2015
od. Maintenance drugs were mercaptopurine and methotrexate. Sixteen months after diagnosis, on a routine clinic visit, he was found to be hypertensive: blood pressure was 120 to 140/90 to 110 mm Hg. Both kidneys were markedly enlarged. Hemoglobin level was 11.0 gm/dl; white blood cell count was 5,400/cu mm, with 66% neutrophils, 17% lymphocytes, 5% eosinophils, and 12% monocytes. Platelets were quantitatively normal on the smear. The BUN level was 21 mg/dl; serum creatinine level, 1.2 mg/dl; and uric acid level, 6.0 mg/dl. Urinalysis showed a pH of 6.0, specific gravity of 1.012, albumin of 1 + On a centrifuged urine specimen there were three to four RBCs per high power field. Urine culture was negative for bacteria. The excretory urogram demonstrated poor visualization of the kidneys; however, both kidneys were enlarged and the calyces were stretched and poorly filled. The collecting systems were not dilated and there was no evidence of obstruction. The bone marrow was 75% replaced with lymphoblasts. A specimen of urine exam¬ ined after cytocentrifugation disclosed the presence of blast cells. During the period of laboratory evaluation, there was progres¬ sion of renal impairment: BUN level increased to 33 mg/dl and serum creatinine concentration to 2.2 mg/dl. He was treated with prednisone and vincristine. Within five days, his blood pressure returned to normal and the kidneys were no longer palpable. He was in remission after six .
Fig 1.—Ultrasonic appearance of right kidney at time of presentation: a, renal outline; b, echoes arising from normal
Fig 2.—After six weeks of treatment, appearance of renal parenchyma is now normal: a, renal outline; b, echoes arising from normal structures in renal sinus.
Fig 3.—Second relapse
weeks of chemotherapy and was main¬ tained with cyclophosphamide. His remis¬ sion lasted only four months, at which time his bone marrow contained many blast forms, and he was treated with prednisone, vincristine, asparaginase, and doxorubicin hydrochloride (Adriamycin). During this period he became hypertensive again. He had a transient partial response only and died of progression of his leukemia. Autop¬ sy was not done.
was
accompanied by loss of the nodu¬ lar pattern, corresponding to the partial response in the bone marrow, but the appearance of the renal paren¬ chyma did not return entirely to normal.
The recommended treatment for leukemic infiltration of the kidneys is radiotherapy.*" We have demon¬ strated in our case the rapid response of the renal leukemia to systemic chemotherapy, but the recurrence in our patient raises the question of whether chemotherapy alone is ade¬ quate. Further information on the incidence of renal leukemia is needed in order to evaluate its prognostic significance and the proper therapy.
structures in renal sinus; c, nodular areas of echolucency separated by strands of compressed renal tissue showing in¬ creased echogenicity.
ULTRASONIC FINDINGS
Ultrasonic examination of the kid¬ neys at the time of original recogni¬ tion of the patient's hypertension confirmed the physical findings of
enlarged kidneys. renal outlines were
In
were
addition, the nodular, and there
multiple areas of relative echolu¬
cency up to 3
cm
in diameter within
the
kidneys (Fig 1). Repeated ultrasonic
examination after two weeks of chemotherapy showed a 4-cm reduction in renal length. The nodular pattern had disappeared although some areas of ultrasonic abnormality persisted with¬ in the kidneys. When the patient was in bone marrow remission, after six weeks of treatment, the echographic pattern of the kidneys was normal (Fig 2), as was the excretory urogram.
The kidneys were not clinically enlarged at the time when hyperten¬ sion recurred during the second relapse. However, a 1-cm increase in renal length, together with a nodular pattern of the renal parenchyma, was again demonstrated with ultrasonic examination (Fig 3). The changes bore a striking resemblance to those seen in the original study, but were not as severe in degree. Further treatment
COMMENT
Marked enlargement of the kidneys with impairment of renal function and hypertension is extremely unu¬ sual as a sign of relapse in acute lymphoblastic leukemia.4·5 The radiologic findings may not be specific. Transonic areas in the kidneys have been described in leukemia." The improvement of the ultrasonic pattern of the kidneys corresponding with the clinical response to treatment of leukemia and its recurrence during relapse in our case suggests that the ultrasonic pattern was indicative of leukemic infiltration. Thus, it appears that ultrasonic examination of the kidneys may be a useful method for following the course of the disease in patients with acute lymphoblastic leu¬ kemia. Also, it is possible that the incidence of renal involvement and its prognostic significance could be deter¬ mined by obtaining ultrasonic exami¬ nations at the time of diagnosis. Cytocentrifugation has been shown to be useful in the diagnosis and management of meningeal leukemia.7 The presence of blast cells in the urine in the absence of a bleeding diathesis suggests leukemic infiltration of the kidneys. However, the absence of blast cells in the urine in our patient during the subsequent relapse, despite
the echographic changes, suggests that cytocentrifugation is helpful only if there is severe renal involvement.
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Iowa User on 06/13/2015
four months later. Ultrasound shows recurrence of nodular pattern (c) in renal parenchyma, although less marked than previously.
This investigation was supported in part by general research support grant 5 SOI RR 05535-15 from the National Institutes of Health.
Nonproprietary Name and Trademark of Drug Vincristine sulfate—Oncovin.
References 1. Lascari AD: Leukemia in Childhood. Springfield, Ill, Charles C Thomas Publisher, 1973, p 34. 2. Gilbert EF, Rice EC, Lechaux PA: Renal function in children with leukemia. Am J Dis Child 93:150-156, 1957. 3. Gowdey JF, Neuhauser EBD: The roentgen diagnosis of diffuse leukemic infiltration of the kidneys in children. Am J Roentgenol Radium Ther Nucl Med 60:13-21, 1948. 4. Koch K, Reiquam CW, Beatty EC Jr: Acute childhood leukemia: Unusual complications. Rocky Mt Med J 63:55-60, 1966. 5. Widagdo IW, Markum AH: Leukemic infiltration of the kidney. Pediatr Indonesia 14:159\x=req-\ 162, 1974. 6. Walls WJ, Roberts FF, Templeton AW: B-scan diagnostic ultrasound in the pediatric patient. Am J Roentgenol Radium Ther Nucl Med 120:431-437, 1974. 7. Komp DM: Cytocentrifugation in the management of central nervous system leukemia. J Pediatr 81:992-994, 1972. 8. Stoffel TJ, Nesbit ME, Levitt SH: The role of radiotherapy in renal involvement in acute childhood leukemia. Radiology 117:687-694, 1975. 9. Lampkin BC, McWilliams NB, Mauer AM: Treatment of acute leukemia. Pediatr Clin North Am 19:1123-1140, 1972.
