November 1975
720
The Journal of P E D I A T R I C S
Myelofibrosis in children with chronic renal insufficiency During investigation of splenomegaly in a boy with chronic renal failure and osteodystrophy, bone marrow aspirates resulted in "dry taps, "" whereas biopsied material provided evidence that the marrow had been replaced by fibrous tissue. In a study of six other children with chronic renal failure, similar changes were observed. These findings suggest that the anemia of chronic renal failure may in part be a result of myelofibrosis, and the resulting reduction of functional bone marrow may limit the tolerance to immunosuppressive agents in patients who undergo renal transplantation.
Neil Schlackman, Alexander A. Green, and J. Lawrence Naiman,*Philadelphia, Pa.
M u c H has been written about the effects of chronic renal insufficiency on the skeletal and hematopoietic systems. Several studies have documented the variety of skeletal changes and the role of secondary hyperparathyroidism in their genesis. ~ The anemia of chronic renal disease has been well studied andresults from the interaction of several factors~: (1) impaired production of red blood cells, due to decreased production of erythropoietin, decreased responsiveness to erythropoietin, and impaired utilization of iron; (2) shortened survival of red blood cells, due to changes in the chemical composition of the plasma and also to mechanical trauma sustained during their passage through narrowed small blood vessels (associated with hypertension); (3) blood loss; and (4) hemodilution (from fluid retention). We have observed an additional factor in a number of patients with renal osteodystrophy. The first of these patients, a 16-year-old boy (Table I, Case 1) was referred to the hematology service for evaluation of splenomegaly. Teardrop erythrocytes were seen in the peripheral blood smear. Repeated attempts to aspirate bone marrow were unsuccessful, and a needle biopsy of the marrow was performed; the specimen revealed extensive myelofibroFrom St. Christopher's Hospital for Children, and the Department of Pediatrics, Temple University School of Medicine. Supported in part by Grants T1-HD-66 and RR-75 from the United States Public Health Service. *Reprint address: St. Christopher's Hospitalfor Children, 2600 iV. Lawrence St., Philadelphia, Pa. 19133.
Ifol. 87, No. 5, pp. 720-724
sis. This observation suggested that the impairment of erythropoiesis in chronic renal insufficiency may in part be a result of replacement of marrow hematopoietic tissue by fibrosi s, a possibility not heretofore recognized. To test this possibility, a study of several other children with anemia due to chronic renal insufficiency was carried out, the results of which form the basis of this report. SUBJECTS Seven children with chronic renal insufficiency, anemia, and osteodystrophy were studied (Table II). Pathology of the bone marrow was suggested by the presence of hepatomegaly and/or splenomega!y, teardrop cells seen in the peripheral blood smear, and hypocellular or "dry taps" from bone marrow aspirates. Of the seven patients, two were boys and five were girls. Their ages varied from 3 to 16 years; six of the seven patients were 10 years old or more at the time of study. Five of the children had renal disease on a congenital basis: posterior urethral valves, polycystic disease of the kidney, agenesis of one kidney and hydronephrosis of the other one, renal hypoplasia, and the cerebro-ocular-renal syndrome, One patient had acquired renal disease (chronic pyelonephritis) and one had bilateral hydroncphrosis of unknown etiology. Six of the seven children were below the third percentiles for height and weight according to the anthropometric chart of Stuart in use at the Children's Hospital Medical Center, Boston. The diagnosis of renal disease was made at ages varying from one month to 389 years. In three of the seven
Volume 87 Number 5
Myelofibrosis in renal insufficiency
721
Table I. Clinical data
Case No.
Sex
Age studied (yr)
1
M
16
2 3 4 5" 6 7
F M F F F F
II 12 ll 12 10 3
Diagnosis
Height and weight (%-ile)
Liver (era)*
Spleen (em)*
< 3
0
10
10-25
720
The Journal of P E D I A T R I C S
Myelofibrosis in children with chronic renal insufficiency During investigation of splenomegaly in a boy with chronic renal failure and osteodystrophy, bone marrow aspirates resulted in "dry taps, "" whereas biopsied material provided evidence that the marrow had been replaced by fibrous tissue. In a study of six other children with chronic renal failure, similar changes were observed. These findings suggest that the anemia of chronic renal failure may in part be a result of myelofibrosis, and the resulting reduction of functional bone marrow may limit the tolerance to immunosuppressive agents in patients who undergo renal transplantation.
Neil Schlackman, Alexander A. Green, and J. Lawrence Naiman,*Philadelphia, Pa.
M u c H has been written about the effects of chronic renal insufficiency on the skeletal and hematopoietic systems. Several studies have documented the variety of skeletal changes and the role of secondary hyperparathyroidism in their genesis. ~ The anemia of chronic renal disease has been well studied andresults from the interaction of several factors~: (1) impaired production of red blood cells, due to decreased production of erythropoietin, decreased responsiveness to erythropoietin, and impaired utilization of iron; (2) shortened survival of red blood cells, due to changes in the chemical composition of the plasma and also to mechanical trauma sustained during their passage through narrowed small blood vessels (associated with hypertension); (3) blood loss; and (4) hemodilution (from fluid retention). We have observed an additional factor in a number of patients with renal osteodystrophy. The first of these patients, a 16-year-old boy (Table I, Case 1) was referred to the hematology service for evaluation of splenomegaly. Teardrop erythrocytes were seen in the peripheral blood smear. Repeated attempts to aspirate bone marrow were unsuccessful, and a needle biopsy of the marrow was performed; the specimen revealed extensive myelofibroFrom St. Christopher's Hospital for Children, and the Department of Pediatrics, Temple University School of Medicine. Supported in part by Grants T1-HD-66 and RR-75 from the United States Public Health Service. *Reprint address: St. Christopher's Hospitalfor Children, 2600 iV. Lawrence St., Philadelphia, Pa. 19133.
Ifol. 87, No. 5, pp. 720-724
sis. This observation suggested that the impairment of erythropoiesis in chronic renal insufficiency may in part be a result of replacement of marrow hematopoietic tissue by fibrosi s, a possibility not heretofore recognized. To test this possibility, a study of several other children with anemia due to chronic renal insufficiency was carried out, the results of which form the basis of this report. SUBJECTS Seven children with chronic renal insufficiency, anemia, and osteodystrophy were studied (Table II). Pathology of the bone marrow was suggested by the presence of hepatomegaly and/or splenomega!y, teardrop cells seen in the peripheral blood smear, and hypocellular or "dry taps" from bone marrow aspirates. Of the seven patients, two were boys and five were girls. Their ages varied from 3 to 16 years; six of the seven patients were 10 years old or more at the time of study. Five of the children had renal disease on a congenital basis: posterior urethral valves, polycystic disease of the kidney, agenesis of one kidney and hydronephrosis of the other one, renal hypoplasia, and the cerebro-ocular-renal syndrome, One patient had acquired renal disease (chronic pyelonephritis) and one had bilateral hydroncphrosis of unknown etiology. Six of the seven children were below the third percentiles for height and weight according to the anthropometric chart of Stuart in use at the Children's Hospital Medical Center, Boston. The diagnosis of renal disease was made at ages varying from one month to 389 years. In three of the seven
Volume 87 Number 5
Myelofibrosis in renal insufficiency
721
Table I. Clinical data
Case No.
Sex
Age studied (yr)
1
M
16
2 3 4 5" 6 7
F M F F F F
II 12 ll 12 10 3
Diagnosis
Height and weight (%-ile)
Liver (era)*
Spleen (em)*
< 3
0
10
10-25
