Nephromegaly in Hemophilia 1
Murray K. Dalinka, M.D., James F. Lally, M.D., Lee F. Rancier, M.D.,2 and Julio Mata, M.D. 3 Various renal abnormalities have been reported in patients with hemophilia. Findings in four patients with hemophilia and nonobstructive renal enlargement are described. Three of these patients also had pseudotumors of the iliac bone. The one factor common to all of these patients and patients with sickle cell anemia or thalassemia with large kidneys is multiple blood transfusions. INDEX TERMS: lassemia
Hemophilia. Kidneys, hypertrophy • Sickle cell disease (SS, SC) • Tha-
Radiology 115:337-340, May 1975
is a well-recognized manifestation of the generalized bleeding diathesis in the hemophiliac patient. Various renal abnormalities consequent to urinary tract bleeding have previously been detailed in the literature (1, 3, 6). Changes in renal size have been noted as incidental autopsy findings in hemophiliac patients (6). Renal enlargement without obstruction, however, is not an uncommon finding in this entity. The authors have observed nonobstructive renal enlargement in four patients with hemophilia; our experience with these cases is the subject of this communication.
CASE REPORTS CASE I: A. T. is a 51-year-old hemophiliac with severe Factor VIII deficiency who had numerous episodes of painless hematuria in the past, at times requiring transfusions. During one of these episodes in October 1962, an excretory urogram showed an obstructive nephrographic pattern on the right side. The right kidney measured 15 cm in length, the left measured 14.6 cm. A pseudotumor of the left iliac wing was noted (Fig. 1). In March 1972, the patient presented with right flank pain, fever, hematuria, and bacteruria. Intravenous urography revealed an obstructing right ureteral calculus with an associated prolonged nephrographic pattern (Fig. 2). The right kidney measured 17 cm. Nephrolithiasis without obstruction was noted in the left kidney which measured 16.6 ern, an increase of two centimeters from the previous urogram in 1962. Four months subsequent to this, the patient died from ruptured esophageal varices secondary to post-necrotic cirrhosis and portal hypertension. At autopsy, the left kidney weighed 200 grams. Multiple renal stones were also present. The pelvicalyceal system was normal. Microscopy demonstrated mild diffuse glomerular hypertrophy; hemosiderin deposition was not present. The right kidney weighed 120 grams and was severely hydronephrotic with marked pyelocaliectasis and cortical atrophy.
phromegaly and calculi. At the postmortem examination, the left kidney was large and the right demonstrated obstructive atrophy. There was an absolute increase of two centimeters in size of the left kidney during the ten-year period. Nonspecific glomerular hypertrophy was identified in the enlarged kidney. CASE II: J. D., a 46-year-old patient with severe Factor VIII deficiency, had received multiple blood transfusions in the past, usually for hemarthrosis. During the last six years, he has had mild hypertension and occasional episodes of hematuria. In March 1973, epididymitis with an acute urinary tract infection developed. An excretory urogram showed an enlarged left kidney measuring 17 cm in length; the right kidney measured 15 cm. Bilateral pyelocaliectasis was present and the ureters were of normal caliber. There was no evidence of blood clot within the collecting system (Fig. 3). A large hemophilic pseudotumor was present in the right iliac wing.
Comment: Bilaterally enlarged kidneys were present without evidence of obstruction. This patient also demonstrated an iliac wing pseudotumor. CASE III: W. R. is a 39-year-old hemophiliac with Factor VIII deficiency. His clinical history included numerous episodes of hemarthrosis and hematuria prior to his hospital admission in February 1973. Symptoms included gross hematuria and severe left flank pain radiating to the inguinal region. He was mildly hypertensive. Hematocrit was 36.1 %; blood urea nitrogen (BUN) was 13 mg/ 100 ml. Excretory urography showed a prolonged nephrogram on the left with nonvisualization of the collecting system. The left kidney measured 17.5 cm; the right was 19 cm in length. Excretory urography was repeated 18 days later following the subsidence of symptoms. The left kidney measured 18 cm in length, the right kidney 19 cm. A hemophiliac pseudotumor was present in the left iliac wing (Fig. 4).
Comment: Bilateral nephromegaly was present with unilateral renal obstruction. The kidney remained en-
The urogram demonstrated bilateral ne-
From the Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pa. Accepted for publication in November 1974. Present address: Department of Radiology, Community Medical Center, P.O. Box 1123, Scranton, Pa. 18501. Present address: Department of Radiology, Children's Medical Center, 1935 Amelia Street, Dallas, Texas 75235. dk
MURRAY K. DALINKA AND OTHERS
Fig. 1. CASE I. Ten-minute film from excretory urogram reveals nonvisualization of the right kidney with a small right ureteral calculus. The left kidney is of normal size. Note pseudotumor of left ilium. Fig. 2. CASE I. Same patient ten years later. There is a large right ureteral calculus with a dense nephrographic pattern on the right side. The left kidney has increased in size two centimeters since the previous examination. Note the iliac pseudotumor (arrows).
larged following the alleviation of the obstruction. In this patient, as in the first two, an iliac wing pseudotumor was present. CASE IV: W. J. is a 33-year-old'man with Factor VIII deficient hemophilia. His clinical course included many episodes of bleeding into the joints and repeated episodes of retroperitoneal hemorrhage. He has had occasional gross hematuria, but renal function had consistently been normal. Numerous antihemophiliac globulin transfusions had been required. Excretory urography was performed in December 1972, following retroperitoneal hemorrhage on the right side. There was no urinary tract obstruction. The left kidney measured 16.7 cm in length and the right measured 15.8 cm (Fig. 5). No subsequent urography was performed.
Comment: This is the only patient in this series with hemophilia and nephromeqaly without an iliac pseudotumor. DISCUSSION
The association of nephromegaly and hemophilia prompted us to review all the urograms of patients with this entity in our institution. In the past 12 years, excretory urography was performed in 12 patients with hemophilia, and renal enlargement was seen in four cases (TABLE I). Since hematuria, spontaneous or secondary to trauma and/or infection, is a relatively frequent complaint of hemophiliacs, a wide spectrum of urographic abnormalities has previously been described (1, 3, 4, 6). The most commonly encountered urographic abnormality is
obstructive uropathy (1, 6). Calyceal defects resembling papillary necrosis were described by Beck and Evans (1). It is of interest that clot formation can be seen in the urinary tract despite abnormal clotting elsewhere. This phenomenon is particularly common following the administration of amino epsilonocaproic acid. Wright et al. described a patient with hemophilia and bilateral renal enlargement secondary to numerous cortical cysts (6). Prentice et al. described two patients with unilateral renal enlargement secondary to intrarenal hematomas (3). There was no suggestion of multiple cyst formation in our cases. The homogeneous nephrographic pattern without calyceal distortion excluded the possibility of intrarenal hematoma. Prentice et al. reported a case of hemophilia with amyloidosis confined to the liver and kidneys (4). The kidneys were not enlarged in that patient. This prompted us to review the autopsy findings in CASE I and in four additional unselected patients who died of hemophilia at our institution. There was no evidence of renal amyloidosis in any of these five cases. In Prentice's case (4) Table I: Patient
A.T. J.D. W.R. W.J.
Renal Enlargement in Four Patients with Hemophilia ~-Kidney Size----...
Right 17 cm
17 cm 19 cm 15.8cm
Left 16.6 cm 15 cm 18 cm 16.7cm
Expected Kidney Size* 15.5 cm 14.0 cm 15.0 ern 12.9cm
* Mean ratio (kidney length over height of L2 plus disk-3.03.1)(5).
NEPHROMEGALY IN HEMOPHILIA
Factor VIII inhibitors and incompatible immunoglobulin led to recurrent transfusion reactions. Since abnormal immunoglobulin complexes are not rare in the hemophiliac, one can only speculate about their chronic effect on the kidneys as no supporting pathologic data are available. Two of the five unselected autopsy cases demonstrated slight bilateral renal enlargement with renal weights ranging between 175 and 190 grams. One of these patients exhibited diffuse nephrocalcinosis and the other had diffuse glomerular hypertrophy with endothelial proliferation. Beck and Evans (1) felt that obstructive uropathy could occur secondary to ureteral fibrosis from incomplete resorption of a retroperitoneal hematoma. This should lead to renal atrophy rather than nephromegaly. Compensatory hypertrophy could account for unilateral renal enlargement, but this is unlikely in our cases because severe atrophy was not present in the opposite kidney and the degree of enlargement was excessive for compensatory hypertrophy in adults. We are unable to explain the findings and relate them to the pseudotumors of the ilium present in three of our cases. None of our cases revealed obstructive changes which could be attributed to the pseudotumor. The one factor common to all our patients is multiple transfusions. It is of interest that renal enlargement has been reported in sickle cell anemia (2), and' we have seen it in thalassemia. Patients with these entities also received multiple transfusions. Plunket (2) felt that the renal en-
Fig. 3. CASE II. Ten-minute film from excretory urogram demonstrates an enlarged left kidney and minimally enlarged right kidney with slight pyelocaliectasis bilaterally. Gallstones are present in the right upper quadrant of the abdomen and extreme hypertrophic changes are seen in the lumbar spine. A pseudotumor is present in the right iliac wing.