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Renal Vein Thrombosis in the Newborn
THE JOURNAL OF UROLOGY
Vol. 73, No. 5, May 1953 Printed in U.S.A.
RENAL VEIK THROMBOSIS IN THE NEWBORN B. A. SMITH, JR.
U rologic awareness of the syndrome of renal vein thrombosis in the newborn has been wanting. No reference devoted to it has appeared in the recent urologic literature1 , 2 , 3 , 4 , 5 until August 1954 6 . The pediatric literature has a number of articles upon the subject, but it behooves the urologist to be familiar with the disease. McClelland and Hughes7 state, "thrombosis of the renal veins in infants causes a rarely diagnosed syndrome characterized by sudden onset of hematuria or anuria, shock, and the appearance of palpable lateral abdominal masses in an infant usually suffering from dehydration as a result of a severe diarrheal disorder." If this sentence is remembered, the clinical diagnosis will be made more frequently and the prognosis improved. CASE REPORT
lVI. S., a white male infant, was hospitalized by Dr. Harold Hermann January 24, 1954 at the age of 13 days. Birth history was normal. Anorexia and then projectile vomiting began 3 days before admission. Stools were frequent, small, and soft without m.elena. Onset of acute colicky abdominal pain was noted about 9:00 p.m., January 23, 1954, and when first seen by Dr. Hermann a mass in the right side of the abdomen was present. Temperature was 97.4F. The baby was dehydrated, eyes were sunken, and the facies drawn and ashen gray. There ,vas a tender, firm mass the size of a baby's fist in the right side of the abdomen. No blood was noted on rectal examination. Hemoglobin upon admission was 21.6 gm. per cent, white blood cells numbered 23,900/cu. mm. with 74 per cent polymorphonuclear leukocytes. The urine was pink and contained 2 plus albumin; many white blood cells and red blood cells were present upon n1.icroscopic examination. The patient ,vas hydrated and transfused, and when stabilized in regard to shock, barium enema excluded intussusception. January 25, the hemoglobin had fallen to 15.9 gm. per cent, and leukocytes numbered 39,800/cu. mm. An excretory urogram was made but no definite excretion of dye was seen and renal shadows could not be outlined. vVhen seen by me that evening the mass was as described, the abdomen was distended, and Read at annual meeting, North Central Section of American Urological Association, Detroit, Mich. October 7-9, 1954. 1 Aschner, P. W.: Thrombosis and thrombophlebitis of the renal vein. J. Urol., 17: 309-327, 1927. 2 Hepler, A. B.: Thrombosis of the renal veins. J. Urol., 31: 527-546, 1934. 3 Melick, W. F. and Vitt, A. E.: Thrombosis of the renal vein. J. Urol., 51: 587-596, 1944. 4 Abeshouse, B. S.: Thrombosis and thrombophlebitis of the renal veins. Urol. & Cu tan. Rev., 49: 661-675, 1945. 5 Regan, F. C. and Crabtree, E. G.: Renal infarction: a .clinical and possible surgical entity. J. Urol., 59: 981-1014, 1948. 6 Stevens, R. C. and Tomsykoski, A. J.: Thrombosis of the inferior vena cava and renal veins with hemorrhagic renal infarction. J. Urol., 72: 120-126, 1954. 7 McClelland, C. Q. and Hughes, J. P.: Thrombosis of the renal vein in infants. J. Pediat., 36: 214-227, 1950. 765
766
B. A. SMITH, JR.
Fm. 1. Right retrograde pyelogram. Note blotchy extravasation of dye through mushy lower pole and medial displacement of ureter and bowel.
abdorn.inal veins were prominent. There was opisthotonos but the fontanelle did not bulge. Temperature was 102.6F. A diagnosis of right renal vein thrombosis with possible vena caval thrombosis was proposed. Antibiotics were begun. January 26, 1954 the abdomen was softer, the mass questionably larger, and the distention of the abdominal veins had disappeared. The opisthotonos was more marked. Hemoglobin was 9.5 gm. per cent and blood urea nitrogen was 65 mg. per cent. Cystoscopy without anesthesia revealed pink urine in the bladder. The left ureteral orifice spurted regularly and the jets were tinged with a trace of indigo carmine. A little bloody fluid escaped from the right ureter upon passage of a catheter. Another x-ray showed more displacement of the bowel toward the midline by the right abdominal mass than previously. The retrograde pyelo-ureterogram showed blotchy extravasation of dye through parenchyrna and medial displacement of the ureter (fig. 1). Following the injection of dye, the patient appeared to be in collapse and the renal mass seemed larger. Right renal washings showed hemolytic paracolon bacillus upon culture. Blood culture was not taken. Impairment of left renal function was presumed to be on the basis of shock and anoxia (lower nephron nephrosis). Following stabilization of the child's condition by the further administration of oxygen and blood, nephrectomy was done through a right lumbar incision with intratracheal anesthesia. The kidney was markedly enlarged, purplish-red, tense yet soft, and there were small subcapsular hematomas and perinephric ecchymosis. No thrombus was palpable in the vena cava. Immediately after operation, marked improvement took place in the baby and several of us noted that his anxious facies became peaceful, and the opisthotonos much less. Convalescence was smooth and at the time of discharge, February 6, 1954, the urine was negative on microscopic and cultural examination, and the blood urea
RE!\AL VEIN THROMBOSIS
767
FIG. 2. Gross specimen. Black and white prints show kidney in massive thrombosis as a l>lack glob ,vith little contrast. This is apparent in other reports also. The sectioned kidney reproduced even more poorly.
nitrogen was 16 mg. per cent. vVhen checked by Dr. Hermann in August 1954 the boy was developing normally. The kidney weighed 32 gm. (normal 15) and ·was darkly hemorrhagic with obliteration of the markings (fig. 2). On microscopic examination there was :almost complete obliteration of all architectural details because of hemorrhagic necrosis. There ·was fresh laminated thrombus completely occluding the renal vein and its principal branches (fig. 3, A). Inflammatory changes were inconspicuous; the arteries were normal. Gram stain of the tissue showed large numbers of pleomorphic gram-negative rods, scattered and in clusters in the tissue (because of necrosis, exact relation to type of tissue not determined) and in the thrombus (fig. 3, B). COMMENTS
The condition is uncomn1on, but McClelland and Hughes found, in 328 autopsies on infants, 3 cases among the 31 deaths due to diarrhea. Barenberg et al.8 reported 5 cases in 25 autopsies during an epidemic of diarrhea in the newborn. The syndrome occurs in children up to 3 years of age, but is quite uncommon beyond the age of 1 month. It may occur rarely in the postpartum mother. There is no predilection as to sex or side of involvement. Fifty per cent of the cases are bilateral with a very grave prognosis although Fallon9 reported a res Barenberg, L. H., Greenstein, N. M., Levy, W. and Rosenbluth, S. B.: Renal thrombosis with infarction complicating diarrhea of the newborn. Am. J. Dis. Child., 62: 362372, 1941. 9 Fallon, M. L.: Renal venous thrombosis in the newborn. Arch. Dis. Child., 24: 125128, 1949.
768
B. A. SMITH, JR.
Fm. 3. A, portion of thrombus of one of veins at hilus. B, oil immersion field of thrombus (A) showing bacilli. (Counter stain of methylene blue. Gram stain did not photograph well.)
covery. The mortality in unilateral cases has been estimated at 95 per cent without surgery and 25 per cent with surgery. Death usually occurs within a very few days after appearance of abdominal mass, unilateral or bilateral. PATHOGENESIS AND ETIOLOGY
Primary thrombosis may occur with or without infarction depending upon degree and rate of thrombosis. Massive infarction may occur without thrombosis.
RENAL VEIN THROMBOSIS
769
Infarction may occur secondary to pyelonephritis with or without thrombosis, and Hepler 2 believed all cases were of this origin, but most believe this to be very uncommon. Secondary or ascending thrombosis does not enter the scope of this paper. Certain factors are common to most of the cases. Infection in the form of enterocolitis, omphalitis, skin infections (forceps lacerations), pneumonia, pharyngitis, and otitis media usually antedates the onset. Dehydration due to diarrhea, vomiting, fever, and feeding problems (thrush) is present, superimposed upon the physiologic dehydration of the newborn (6-10 per cent weight loss). This promotes further concentration of the normally polycythemic status ·of the newborn. Venous and capillary pressures are normally low in the neonatal period. Bed rest increases thromboplastin. These factors promote sludging. The
There is little agreement as to the veins first involved. Campbell 16 believes the peripheral and glomerular vessels are first involved. General opinion accepts thrombosis in the small or medium sized veins with appearance of symptoms when the main vein is involved. 15 • 16 Two of Barenberg's cases had thrombi only in the main veins. Depending upon the duration and completeness of the process, -canalization may occur. With massive infarction, the kidney is enlarged two or three times normal size. It is reddish purple in color, soft and mushy, and may have subcapsular hemorrhages with perirenal ecchymosis or hematoma. Regan and Crabtree 5 state most of the clots are infected. Finklestein17 , and Czerny and Moser18 found organisms in the thrombi. Barenberg et al. did not find bacteria in the thrombi or in tissue, Oppenheim: Quoted by Barenberg. u Clatworthy, H. W., Jr., Dickens, D.R. and McClave, C.R.: Renal thrombosis complicating epidemic diarrhea of the newborn. New Eng. J. Med., 248: 628-630, 1953. 12 Jones, D. B. and Loring, W. E.: Glomerular thrombosis. Am. J. Path., 27: 841-855, 1951. 13 Zuelzer, W. W., Charles, S., Kurnetz, R., Newton, W. A. Jr. and Fallon, R.: Circulatory diseases of the kidneys in infancy and childhood. Am. J. Dis. Child., 81: 1-46, 1951. 14 Warren, H., Birdsong, McL. and Kelley, R. A.: Renal vein thrombosis in infants. J. A. M.A., 152: 700-701, 1953. 15 Sandblom, Ph.: Renal thrombosis with infarction in the newborn, two different forms. Acta paediat., 35: 160-167, 1948. 16 Campbell, M.: Clinical Pediatric Urology. Philadelphia: W. B. Sanders Co., 1951, pp. 441-444. 17 Finklestein: Quoted by Barenberg. 18 Czerny and Moser: Quoted by Barenberg. 10
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B. A. SMITH, JR.
nor did Kobernick et al. 19 ; most observers report no notable infectious process in the vein walls when the lesion is recent. Culture of the thrombus has been found sterile. 20 The medulla suffers most and first, but renal architecture is lost or masked by the extensive hemorrhage. Necrosis in sudden, massive infarction involves all the parenchyma except a negligible subcapsular zone. Thrombosis of the opposite or second kidney may be of the same origin or may occur by extension by the vena cava. Adrenal infarction is a frequent companion. The uninvolved kidney may suffer (and probably commonly does) from so-called lower nephron nephrosis due to shock and anoxia as noted by McClelland and Hughes and Milburn. 21 Pulmonary emboli were found by Morison22 in 9 of 14 cases that had thrombi in the renal vein; emboli or thrombi were found in the pulmonary arteries in two of 3 cases reported by McClelland and Hughes, and three of 4 cases described by Kobernick et al. SYMPTOMS AND FINDINGS
Infection and dehydration are usually present. The patient appears marasmic and hematuria usually is gross. A picture of shock appears when the infarction occurs and the mass is noted. Opisthotonos has been observed, but the fontanelle is depressed. Restlessness is common. Fever is the rule. Urinalysis in massive infarction shows red blood cells, white blood cells usually (and almost always later), albumin, casts and, in most of the cultures, bacteria. Leukocytosis occurs and hemoglobin falls. Acidosis and uremia in varying degree are present. X-rays usually show a mass and the displacement of the bmvel shadows. Flecks of blood in the stool are common, and together with a right abdominal mass often prompt a barium enema to exclude intussusception. Excretory urography shows no function on the involved side, and may or may not show function on the "good" side depending upon the gas shadows of the newborn, and the renal function (lower nephron nephrosis). Retrograde pyelography shows first a tendency for the ureter only to fill because of compression of the collecting system3, & by parenchymal swelling. If injection is carried further, dye extravasates through the mushy kidney in irregular collections larger than seen with the usual pyelovenous or pyelotubular extravasation, as described by Campbell. 15 DIFFERENTIAL DIAGNOSIS
Differential diagnosis includes hemorrhage into Wilms' tumor, infected or noninfected hydronephrosis, renal dysplasia with cystic mass, unilateral or bilateral polycystic disease, renal or perinephric abscess. Retrograde pyelography should establish the diagnosis. 19 Kobernick, S. D., Moore, J. R. and Wiglesworth, F. W.: Thrombosis of the renal veins with massive hemorrhagic infarction of the kidneys in childhood. Am. J. Path., 27: 435-453, 1951. 20 Thrombosis of the renal vein with infarction of the kidney. (Clinical conference.) J. Pediat., 36: 519-521, 1950. 21 Milburn, C. L., Jr.: Hemorrhagic infarction of the kidneys in infants. J. Pediat., 41: 133-140, 1952. 22 Morison, J. E.: Renal venous thrombosis and infarction in the newborn. Arch. Dis. Child., 20: 129-134, 1945.
RENAL VEIN THROMBOSIS
771
TREATMENT
Preoperative therapy demands hydration, transfusion if anemia is present, balance of electrolytes, and measures to combat infection. If the thrombosis is bilateral, surgery is contraindicated. In unilateral thrombosis, nephrectomy should be done as soon as the diagnosis is established and the patient's condition is stable. In the cases with infection, time is of great importance. Lumbar incision is very satisfactory for this condition. The renal vein should be severed medial to thrombus and Sandblom removed thrombotic extension from the vena cava. Following operation, improvement in the patient's condition is usually immediate and dramatic. Attention is given to fluid and electrolyte balance, blood, and control of infection. Anticoagulant therapy in the postoperative period to prevent extension of thrombus, new thrombus formation, and to discourage propagation of silent, small, contralateral thrombi has been suggested by a munber of authors and heparin was employed by Parry 23 but was discontinued after 3 days because of -wound bleeding. Because hemorrhage into the kidney is so marked with nrnssive infarction and furthermore may be a factor in extending thrombus formation, 13 anticoagulant therapy in unoperated or bilateral cases is a two-edged sword. Grtineberg24 reported in 1932 the first nephrectomy with cure to come to my attention. Campbell2 5 performed nephrectomy -with cure in 2 cases, and first made the preoperative diagnosis in the second case. Since then 9 cases have been reported 15 , 20 , 26 , 23 , 14 ( 2 cases), 27 , 28 , 11 with one questionable case in regard to outcome, 29 a total of 12 or 13 cases cured by nephrectomy. The only case of recovery with a clinical diagnosis of bilateral thrombosis was reported by Fallon. 9 Renal function gradually improved over months. She questions the advisability of surgery in all unilateral cases unless infection is present. The possibility of cure probably depends upon a slow rate of occlusion or accessory vessels, uninvolved. DISCUSSION
A pediatrician whose brother 20 (pathologist) had encountered a case of renal vein thrombosis cured by nephrectomy once told me he didn't want to overlook such a diagnosis. I was forced to look up Campbell's writings to acquaint myself with the subject. Once aware of the existence of such a condition, the rather typical history and findings made the presumptive diagnosis quite apparent. The prominence of dilated veins in the abdominal wall (mentioned by others) suggested vena caval involvement but rather disappeared with decrease in 23 Parry, E:. W.: Unilateral renal vein thrombosis treated by nephrectomy and postoperative heparin. Arch. Dis. Child., 26: 358-361, 1951. 24 Griineberg, H.: Nierenvenenthromhose linkerseits. J\1iinchen. med. Wchnschr., 79: 1054, 1932. 25 Campbell, M. and Mathews, W. F.: Renal thrombosis in infancy. J. Pediat., 20: 604-615, 1942. 26 Thurston, W. D.: Quoted by Campbell. 16 27 Clark, C. D. and Pickup, J. D.: Haemorrhagic infarction of the kidney treated by nephrectomy. Arch. Dis. Child., 28: 302-303, 1953. 28 Mills, W. G. Q. and Owen, T. K.: Renal thrombosis complicating pink disease: Cure by nephrectomy. Arch. Dis. Child., 28: 300-301, 1953. 29 Buchtel, H.: Quoted by Campbell. 16
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B. A. SMITH, JR.
distention (also noted by others). The opisthotonos was marked and proposed the question of meningismus due to cranial sinus thrombosis or encephalitis or meningitis. The normal soft fontanelle in the presence of adequate hydration was somewhat reassuring, and spinal fluid was not examined. The rate of fall in the hemoglobin was remarkable and beyond the change in hydration. The baby seemed to become "shocky" co-incident with retrograde pyelography, and the mass seemed to increase in size at that time. Retrograde pyelography in suspected renal infarction with bilateral masses would seem contraindicated. The presence of organisms in the tissue sections would explain the dramatic improvement immediately following nephrectomy. Antibiotics might control the systemic infection, but would not be expected to eradicate infection in a hemorrhagic renal mass deprived of circulation. SUMMARY
Renal vein thrombosis with massive infarction should be readily recognized if the condition is considered although the associated infection and prostration may mask it somewhat. The possibility of renal vein thrombosis should be anticipated in all infants with infection and dehydration, and abdominal palpation and urine inspection should be routine. Approximately one-half of the cases will be unilateral, and three-fourths of these may be expected to survive with proper treatment. Correction of dehydration, electrolyte imbalance, and anemia, and measures to control infection are essential. The diagnosis may be established by retrograde pyelography, but this is contraindicated when masses are bilateral. Treatment at this time is nephrectomy in unilateral cases, and is urgent when infection is present. Postoperative anticoagulant therapy would seem advisable.
305 Medical Arts Bldg., Minneapolis 2, Minn.
Vol. 73, No. 5, May 1953 Printed in U.S.A.
RENAL VEIK THROMBOSIS IN THE NEWBORN B. A. SMITH, JR.
U rologic awareness of the syndrome of renal vein thrombosis in the newborn has been wanting. No reference devoted to it has appeared in the recent urologic literature1 , 2 , 3 , 4 , 5 until August 1954 6 . The pediatric literature has a number of articles upon the subject, but it behooves the urologist to be familiar with the disease. McClelland and Hughes7 state, "thrombosis of the renal veins in infants causes a rarely diagnosed syndrome characterized by sudden onset of hematuria or anuria, shock, and the appearance of palpable lateral abdominal masses in an infant usually suffering from dehydration as a result of a severe diarrheal disorder." If this sentence is remembered, the clinical diagnosis will be made more frequently and the prognosis improved. CASE REPORT
lVI. S., a white male infant, was hospitalized by Dr. Harold Hermann January 24, 1954 at the age of 13 days. Birth history was normal. Anorexia and then projectile vomiting began 3 days before admission. Stools were frequent, small, and soft without m.elena. Onset of acute colicky abdominal pain was noted about 9:00 p.m., January 23, 1954, and when first seen by Dr. Hermann a mass in the right side of the abdomen was present. Temperature was 97.4F. The baby was dehydrated, eyes were sunken, and the facies drawn and ashen gray. There ,vas a tender, firm mass the size of a baby's fist in the right side of the abdomen. No blood was noted on rectal examination. Hemoglobin upon admission was 21.6 gm. per cent, white blood cells numbered 23,900/cu. mm. with 74 per cent polymorphonuclear leukocytes. The urine was pink and contained 2 plus albumin; many white blood cells and red blood cells were present upon n1.icroscopic examination. The patient ,vas hydrated and transfused, and when stabilized in regard to shock, barium enema excluded intussusception. January 25, the hemoglobin had fallen to 15.9 gm. per cent, and leukocytes numbered 39,800/cu. mm. An excretory urogram was made but no definite excretion of dye was seen and renal shadows could not be outlined. vVhen seen by me that evening the mass was as described, the abdomen was distended, and Read at annual meeting, North Central Section of American Urological Association, Detroit, Mich. October 7-9, 1954. 1 Aschner, P. W.: Thrombosis and thrombophlebitis of the renal vein. J. Urol., 17: 309-327, 1927. 2 Hepler, A. B.: Thrombosis of the renal veins. J. Urol., 31: 527-546, 1934. 3 Melick, W. F. and Vitt, A. E.: Thrombosis of the renal vein. J. Urol., 51: 587-596, 1944. 4 Abeshouse, B. S.: Thrombosis and thrombophlebitis of the renal veins. Urol. & Cu tan. Rev., 49: 661-675, 1945. 5 Regan, F. C. and Crabtree, E. G.: Renal infarction: a .clinical and possible surgical entity. J. Urol., 59: 981-1014, 1948. 6 Stevens, R. C. and Tomsykoski, A. J.: Thrombosis of the inferior vena cava and renal veins with hemorrhagic renal infarction. J. Urol., 72: 120-126, 1954. 7 McClelland, C. Q. and Hughes, J. P.: Thrombosis of the renal vein in infants. J. Pediat., 36: 214-227, 1950. 765
766
B. A. SMITH, JR.
Fm. 1. Right retrograde pyelogram. Note blotchy extravasation of dye through mushy lower pole and medial displacement of ureter and bowel.
abdorn.inal veins were prominent. There was opisthotonos but the fontanelle did not bulge. Temperature was 102.6F. A diagnosis of right renal vein thrombosis with possible vena caval thrombosis was proposed. Antibiotics were begun. January 26, 1954 the abdomen was softer, the mass questionably larger, and the distention of the abdominal veins had disappeared. The opisthotonos was more marked. Hemoglobin was 9.5 gm. per cent and blood urea nitrogen was 65 mg. per cent. Cystoscopy without anesthesia revealed pink urine in the bladder. The left ureteral orifice spurted regularly and the jets were tinged with a trace of indigo carmine. A little bloody fluid escaped from the right ureter upon passage of a catheter. Another x-ray showed more displacement of the bowel toward the midline by the right abdominal mass than previously. The retrograde pyelo-ureterogram showed blotchy extravasation of dye through parenchyrna and medial displacement of the ureter (fig. 1). Following the injection of dye, the patient appeared to be in collapse and the renal mass seemed larger. Right renal washings showed hemolytic paracolon bacillus upon culture. Blood culture was not taken. Impairment of left renal function was presumed to be on the basis of shock and anoxia (lower nephron nephrosis). Following stabilization of the child's condition by the further administration of oxygen and blood, nephrectomy was done through a right lumbar incision with intratracheal anesthesia. The kidney was markedly enlarged, purplish-red, tense yet soft, and there were small subcapsular hematomas and perinephric ecchymosis. No thrombus was palpable in the vena cava. Immediately after operation, marked improvement took place in the baby and several of us noted that his anxious facies became peaceful, and the opisthotonos much less. Convalescence was smooth and at the time of discharge, February 6, 1954, the urine was negative on microscopic and cultural examination, and the blood urea
RE!\AL VEIN THROMBOSIS
767
FIG. 2. Gross specimen. Black and white prints show kidney in massive thrombosis as a l>lack glob ,vith little contrast. This is apparent in other reports also. The sectioned kidney reproduced even more poorly.
nitrogen was 16 mg. per cent. vVhen checked by Dr. Hermann in August 1954 the boy was developing normally. The kidney weighed 32 gm. (normal 15) and ·was darkly hemorrhagic with obliteration of the markings (fig. 2). On microscopic examination there was :almost complete obliteration of all architectural details because of hemorrhagic necrosis. There ·was fresh laminated thrombus completely occluding the renal vein and its principal branches (fig. 3, A). Inflammatory changes were inconspicuous; the arteries were normal. Gram stain of the tissue showed large numbers of pleomorphic gram-negative rods, scattered and in clusters in the tissue (because of necrosis, exact relation to type of tissue not determined) and in the thrombus (fig. 3, B). COMMENTS
The condition is uncomn1on, but McClelland and Hughes found, in 328 autopsies on infants, 3 cases among the 31 deaths due to diarrhea. Barenberg et al.8 reported 5 cases in 25 autopsies during an epidemic of diarrhea in the newborn. The syndrome occurs in children up to 3 years of age, but is quite uncommon beyond the age of 1 month. It may occur rarely in the postpartum mother. There is no predilection as to sex or side of involvement. Fifty per cent of the cases are bilateral with a very grave prognosis although Fallon9 reported a res Barenberg, L. H., Greenstein, N. M., Levy, W. and Rosenbluth, S. B.: Renal thrombosis with infarction complicating diarrhea of the newborn. Am. J. Dis. Child., 62: 362372, 1941. 9 Fallon, M. L.: Renal venous thrombosis in the newborn. Arch. Dis. Child., 24: 125128, 1949.
768
B. A. SMITH, JR.
Fm. 3. A, portion of thrombus of one of veins at hilus. B, oil immersion field of thrombus (A) showing bacilli. (Counter stain of methylene blue. Gram stain did not photograph well.)
covery. The mortality in unilateral cases has been estimated at 95 per cent without surgery and 25 per cent with surgery. Death usually occurs within a very few days after appearance of abdominal mass, unilateral or bilateral. PATHOGENESIS AND ETIOLOGY
Primary thrombosis may occur with or without infarction depending upon degree and rate of thrombosis. Massive infarction may occur without thrombosis.
RENAL VEIN THROMBOSIS
769
Infarction may occur secondary to pyelonephritis with or without thrombosis, and Hepler 2 believed all cases were of this origin, but most believe this to be very uncommon. Secondary or ascending thrombosis does not enter the scope of this paper. Certain factors are common to most of the cases. Infection in the form of enterocolitis, omphalitis, skin infections (forceps lacerations), pneumonia, pharyngitis, and otitis media usually antedates the onset. Dehydration due to diarrhea, vomiting, fever, and feeding problems (thrush) is present, superimposed upon the physiologic dehydration of the newborn (6-10 per cent weight loss). This promotes further concentration of the normally polycythemic status ·of the newborn. Venous and capillary pressures are normally low in the neonatal period. Bed rest increases thromboplastin. These factors promote sludging. The
There is little agreement as to the veins first involved. Campbell 16 believes the peripheral and glomerular vessels are first involved. General opinion accepts thrombosis in the small or medium sized veins with appearance of symptoms when the main vein is involved. 15 • 16 Two of Barenberg's cases had thrombi only in the main veins. Depending upon the duration and completeness of the process, -canalization may occur. With massive infarction, the kidney is enlarged two or three times normal size. It is reddish purple in color, soft and mushy, and may have subcapsular hemorrhages with perirenal ecchymosis or hematoma. Regan and Crabtree 5 state most of the clots are infected. Finklestein17 , and Czerny and Moser18 found organisms in the thrombi. Barenberg et al. did not find bacteria in the thrombi or in tissue, Oppenheim: Quoted by Barenberg. u Clatworthy, H. W., Jr., Dickens, D.R. and McClave, C.R.: Renal thrombosis complicating epidemic diarrhea of the newborn. New Eng. J. Med., 248: 628-630, 1953. 12 Jones, D. B. and Loring, W. E.: Glomerular thrombosis. Am. J. Path., 27: 841-855, 1951. 13 Zuelzer, W. W., Charles, S., Kurnetz, R., Newton, W. A. Jr. and Fallon, R.: Circulatory diseases of the kidneys in infancy and childhood. Am. J. Dis. Child., 81: 1-46, 1951. 14 Warren, H., Birdsong, McL. and Kelley, R. A.: Renal vein thrombosis in infants. J. A. M.A., 152: 700-701, 1953. 15 Sandblom, Ph.: Renal thrombosis with infarction in the newborn, two different forms. Acta paediat., 35: 160-167, 1948. 16 Campbell, M.: Clinical Pediatric Urology. Philadelphia: W. B. Sanders Co., 1951, pp. 441-444. 17 Finklestein: Quoted by Barenberg. 18 Czerny and Moser: Quoted by Barenberg. 10
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B. A. SMITH, JR.
nor did Kobernick et al. 19 ; most observers report no notable infectious process in the vein walls when the lesion is recent. Culture of the thrombus has been found sterile. 20 The medulla suffers most and first, but renal architecture is lost or masked by the extensive hemorrhage. Necrosis in sudden, massive infarction involves all the parenchyma except a negligible subcapsular zone. Thrombosis of the opposite or second kidney may be of the same origin or may occur by extension by the vena cava. Adrenal infarction is a frequent companion. The uninvolved kidney may suffer (and probably commonly does) from so-called lower nephron nephrosis due to shock and anoxia as noted by McClelland and Hughes and Milburn. 21 Pulmonary emboli were found by Morison22 in 9 of 14 cases that had thrombi in the renal vein; emboli or thrombi were found in the pulmonary arteries in two of 3 cases reported by McClelland and Hughes, and three of 4 cases described by Kobernick et al. SYMPTOMS AND FINDINGS
Infection and dehydration are usually present. The patient appears marasmic and hematuria usually is gross. A picture of shock appears when the infarction occurs and the mass is noted. Opisthotonos has been observed, but the fontanelle is depressed. Restlessness is common. Fever is the rule. Urinalysis in massive infarction shows red blood cells, white blood cells usually (and almost always later), albumin, casts and, in most of the cultures, bacteria. Leukocytosis occurs and hemoglobin falls. Acidosis and uremia in varying degree are present. X-rays usually show a mass and the displacement of the bmvel shadows. Flecks of blood in the stool are common, and together with a right abdominal mass often prompt a barium enema to exclude intussusception. Excretory urography shows no function on the involved side, and may or may not show function on the "good" side depending upon the gas shadows of the newborn, and the renal function (lower nephron nephrosis). Retrograde pyelography shows first a tendency for the ureter only to fill because of compression of the collecting system3, & by parenchymal swelling. If injection is carried further, dye extravasates through the mushy kidney in irregular collections larger than seen with the usual pyelovenous or pyelotubular extravasation, as described by Campbell. 15 DIFFERENTIAL DIAGNOSIS
Differential diagnosis includes hemorrhage into Wilms' tumor, infected or noninfected hydronephrosis, renal dysplasia with cystic mass, unilateral or bilateral polycystic disease, renal or perinephric abscess. Retrograde pyelography should establish the diagnosis. 19 Kobernick, S. D., Moore, J. R. and Wiglesworth, F. W.: Thrombosis of the renal veins with massive hemorrhagic infarction of the kidneys in childhood. Am. J. Path., 27: 435-453, 1951. 20 Thrombosis of the renal vein with infarction of the kidney. (Clinical conference.) J. Pediat., 36: 519-521, 1950. 21 Milburn, C. L., Jr.: Hemorrhagic infarction of the kidneys in infants. J. Pediat., 41: 133-140, 1952. 22 Morison, J. E.: Renal venous thrombosis and infarction in the newborn. Arch. Dis. Child., 20: 129-134, 1945.
RENAL VEIN THROMBOSIS
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TREATMENT
Preoperative therapy demands hydration, transfusion if anemia is present, balance of electrolytes, and measures to combat infection. If the thrombosis is bilateral, surgery is contraindicated. In unilateral thrombosis, nephrectomy should be done as soon as the diagnosis is established and the patient's condition is stable. In the cases with infection, time is of great importance. Lumbar incision is very satisfactory for this condition. The renal vein should be severed medial to thrombus and Sandblom removed thrombotic extension from the vena cava. Following operation, improvement in the patient's condition is usually immediate and dramatic. Attention is given to fluid and electrolyte balance, blood, and control of infection. Anticoagulant therapy in the postoperative period to prevent extension of thrombus, new thrombus formation, and to discourage propagation of silent, small, contralateral thrombi has been suggested by a munber of authors and heparin was employed by Parry 23 but was discontinued after 3 days because of -wound bleeding. Because hemorrhage into the kidney is so marked with nrnssive infarction and furthermore may be a factor in extending thrombus formation, 13 anticoagulant therapy in unoperated or bilateral cases is a two-edged sword. Grtineberg24 reported in 1932 the first nephrectomy with cure to come to my attention. Campbell2 5 performed nephrectomy -with cure in 2 cases, and first made the preoperative diagnosis in the second case. Since then 9 cases have been reported 15 , 20 , 26 , 23 , 14 ( 2 cases), 27 , 28 , 11 with one questionable case in regard to outcome, 29 a total of 12 or 13 cases cured by nephrectomy. The only case of recovery with a clinical diagnosis of bilateral thrombosis was reported by Fallon. 9 Renal function gradually improved over months. She questions the advisability of surgery in all unilateral cases unless infection is present. The possibility of cure probably depends upon a slow rate of occlusion or accessory vessels, uninvolved. DISCUSSION
A pediatrician whose brother 20 (pathologist) had encountered a case of renal vein thrombosis cured by nephrectomy once told me he didn't want to overlook such a diagnosis. I was forced to look up Campbell's writings to acquaint myself with the subject. Once aware of the existence of such a condition, the rather typical history and findings made the presumptive diagnosis quite apparent. The prominence of dilated veins in the abdominal wall (mentioned by others) suggested vena caval involvement but rather disappeared with decrease in 23 Parry, E:. W.: Unilateral renal vein thrombosis treated by nephrectomy and postoperative heparin. Arch. Dis. Child., 26: 358-361, 1951. 24 Griineberg, H.: Nierenvenenthromhose linkerseits. J\1iinchen. med. Wchnschr., 79: 1054, 1932. 25 Campbell, M. and Mathews, W. F.: Renal thrombosis in infancy. J. Pediat., 20: 604-615, 1942. 26 Thurston, W. D.: Quoted by Campbell. 16 27 Clark, C. D. and Pickup, J. D.: Haemorrhagic infarction of the kidney treated by nephrectomy. Arch. Dis. Child., 28: 302-303, 1953. 28 Mills, W. G. Q. and Owen, T. K.: Renal thrombosis complicating pink disease: Cure by nephrectomy. Arch. Dis. Child., 28: 300-301, 1953. 29 Buchtel, H.: Quoted by Campbell. 16
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distention (also noted by others). The opisthotonos was marked and proposed the question of meningismus due to cranial sinus thrombosis or encephalitis or meningitis. The normal soft fontanelle in the presence of adequate hydration was somewhat reassuring, and spinal fluid was not examined. The rate of fall in the hemoglobin was remarkable and beyond the change in hydration. The baby seemed to become "shocky" co-incident with retrograde pyelography, and the mass seemed to increase in size at that time. Retrograde pyelography in suspected renal infarction with bilateral masses would seem contraindicated. The presence of organisms in the tissue sections would explain the dramatic improvement immediately following nephrectomy. Antibiotics might control the systemic infection, but would not be expected to eradicate infection in a hemorrhagic renal mass deprived of circulation. SUMMARY
Renal vein thrombosis with massive infarction should be readily recognized if the condition is considered although the associated infection and prostration may mask it somewhat. The possibility of renal vein thrombosis should be anticipated in all infants with infection and dehydration, and abdominal palpation and urine inspection should be routine. Approximately one-half of the cases will be unilateral, and three-fourths of these may be expected to survive with proper treatment. Correction of dehydration, electrolyte imbalance, and anemia, and measures to control infection are essential. The diagnosis may be established by retrograde pyelography, but this is contraindicated when masses are bilateral. Treatment at this time is nephrectomy in unilateral cases, and is urgent when infection is present. Postoperative anticoagulant therapy would seem advisable.
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