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Bilateral renal cortical necrosis in the newborn infant: Roentgenographic diagnosis
October, 1971 T h e Journal o[ P E D I A T R I C S
623
Bilateral renal cortical necrosis in the ne vborn infant: Roentgenograpbic diagnosis Bilateral renal cortical necrosis [ollowing shock and renal cortical ischemia in the neonatal period is usually ]atal. Improvement in medical care has led to longer survivals, and radiographic diagnosis can now be made during life by demonstration o[ a characteristic pattern o[ bilateral and symmetrical calcification o[ the renal cortex, which appears a [ew weeks a#er the onset o[ renal [allure.
John c. Leonidas, M.D.,* Walter E. Berdon, M.D., and Donald Gribetz, M.D. NEW YORK,
N. Y.
B I L AT E R AL renal cortical necrosis (BRCN) is a rare frequently fatal disorder characterized by ischemic coagulative necrosis of the cortex of both kidneys? -s Experimental and clinical evidence indicates that it is caused by severe and prolonged renal cortical ischemia associated with circulatory failure a n d / o r disseminated intravascular coagulation, x, 4-8 B R C N has been almost uniformly fatal, and until recently the diagnosis had been made only after death. T h e diagnosis of B R C N has now been established during life, and improved management of renal failure has resulted in longer survivals of these patients. Roentgenographically a characteristic pattern of bilateral and symmetrical calcification of the renal cortex has been demonstrated a From the Departments of Radiology and Pediatrics, the Mount Sinai School o[ Medicine o[ the City University o[ New York, and the Department o[ Radiology, Columbia University College o[ Physicians and Surgeons. eAddress: Department oI Radiology, Mount $1na~ Hospital, 11 g. lOOthSt., New York, N. Y. 10029.
few weeks after the onset of acute renal failure.Z, 3, 7, s B R C N can occur in the newborn infant, but thus far the diagnosis has been made only at autopsy2, lo T h e purpose of this report is to describe two neonates with BRCN in whom the diagnosis was made by the characteristic appearance of renal cortical calcification on plain roentgenograms. T o our knowledge, this is the first report of the antemortem roentgenographic diagnosis of this condition during the neonatal period.
CASE REPORTS Case 1. A male infant was born by cesarean section performed because of placenta praevia; gestational age was 33 weeks and birth weight was 1,625 Gm. The baby was severely anemic at birth (hemoglobin 6.0 Gin.). Bilirubin was 4 nag. per 100 ml. A transfusion of 35 ml. of compatible fresh whole blood was given, and the hemoglobin concentration rose to 14.2 Gin. At the age of 17 days the infant was transferred to Babies Hospital. Vol. 79, No. 4, pp. 623-627
624
Leonidas, Berdon, and Gribetz
The Journal o[ Pediatrics October 1971
Fig. 1. Case 1. A~ Detail from plain film of abdomen. Note rim calcification of right renal cortex (upper and lower arrow). Middle arrow demonstrates calcified nodule within substance of liver. B, Cone-down view of left kidney. Arrows point to rim of calcium outlining the left renal cortex. Pertinent physical findings on admission included retardation of growth, marked pallor, tachypnea, and tachycardia. Hemoglobin was 7.7 Gin., white blood cells 30,100 per cubic millimeter, platelets 368,000 per cubic millimeter, and reticulocytes 6.6 per cent. Prothrombin time, partial thromboplastin time, and fibrinogen levels were normal. Blood and urine cultures were sterile. Urinalysis revealed albuminuria and microscopic hematuria. Blood urea nitrogen was 125 mg. per 100 ml. There was metabolic acidosis (pH 7.080, base excess -25.7), hyperkalemia (K 6.5 mEq. per liter), hypocalcemia (Ca 6.9 mg. per 100 ml.), and hypoproteinemia (total protein 4.8 Gin. per 100 ml.). An intravenous pyelogram was performed on the second hospital day. On the preliminary film both kidneys were sharply outlined by a rim of calcification extending throughout the outer cortex, as if the kidneys were "pencilled in" (Fig. 1, A and B). A dense calcified nodule was seen within the substance of the liver suggesting a phlebolith (Fig. 1, A). Injection of 12 ml. of 50 per cent sodium diatrizoate (Hypaque 50) intravenously failed to show any visualization; voiding cystourethrogram was normal. Slow improvement followed treatment of acidosis, hypoealcemia, and anemia. During the third hospital week blood urea nitrogen ranged between 20 and 30 mg. per 100 ml. Follow-up examinations to the age of 18 months have shown persistence of renal failure and growth retardation. Comment. Hematuria and renal failure in this
newborn infant, following perinatal hemorrhage, suggest a severe renal circulatory disturbance at birth. The characteristic pattern of calcification of the cortex of both kidneys on x-ray examination led to the diagnosis of BRCN. Case 2. A female infant was born at term following a normal pregnancy and premature rupture of membranes 24 hours prior to delivery, which was otherwise unremarkable. Apgar score was 9 at 1 minute. Weight was 3,070 Gm. Immediately thereafter the baby developed apnea and marked bradycardia. She was ressuscitated successfully. At the age of 20 hours she developed massive rectal and vaginal bleeding, hematemesis, and oozing of blood from venipuncture sites. Pertinent laboratory findings were thrombocytopenia (platelets 35,000 per cubic millimeter), prolongation of partial thromboplastin time (93/79), anemia, hyperkalemia, and hypocalcemia. On the sixth day of life blood urea nitrogen was 114 mg. and creatinine 5.6 mg. per 100 mh Blood and urine cultures were sterile. 9 intravenous pyelogram showed only a very faint nephrogram but no distinct opacification of collecting tracts. Both kidneys were normal in size. A presumptive diagnosis of neonatal septicemia and consumption coagulopathy was made, and the patient was treated with penicillin and kanamycin. At the age of 26 days renal cortical calcification was noted bilaterally on plain abdominal roentgenograms. The patient was transferred to Mount Sinai
Volume 79 Number 4
Hospital at the age of 9 weeks. Physical examination revealed growth failure and pallor but was otherwise unremarkable. Plain films of the abdomen showed extensive patchy calcification of the entire cortex of both kidneys. Both adrenals were also caIcified, and there was deposition of calcium in the soft tissue adjacent to the left iliac crest (Fig. 2, A). Intravenous pyelography with 12 ml. of methyglucamine dialtrizoate 60 per cent (Renographin 60) showed only faint opacification of the left upper collecting system and of the bladder (Fig. 2, B). Renal size was reduced in comparison with previous films, particularly on the right, where calcification was also more prominent. The roentgenographic findings were consistent with BRCN. Laboratory values at this time were: hemoglobin, 8.6 Gin.; white blood cells, 18,700 per cubic millimeter with a normal differential count; platelets, 264,000; and reticulocytes, 1.7 per cent. Urine pH was 5.5. to 6.0 with persistently low specific gravity. There was albuminuria and microscopic hematuria. Blood urea nitrogen was 84 Gm. per 100 ml. and creatinine was 2.6 mg. Blood and urine cuItures were sterile. Coagulation studies showed initially prolongation of partial thromboplastin time (112/50); this returned to normal during the third hospital week. The patient received an oral citrate mixture and iron supplementation. Initially there was improvement of both clinical and laboratory manifestations of renal failure. However, approximately 5 months after discharge, it was apparent that renal failure was progressing. Blood urea nitrogen was 96 rag. per 100 ml. serum calcium 7.4 mg., serum phosphate 7.8 rag., and alkaline phosphatase greater than 350 I.U. There was also anemia (hemoglobin 7.0 Gin.), and x-ray evidence of progressive skeletal demineralization. The baby died suddenly at the age of 9 months. Autopsy performed elsewhere confirmed the diagnosis of biIateral renal cortical and medullary necrosis with extensive calcification of the renal cortex. Comment. NeonataI shock and anoxia in this infant precipitated disseminated intravascular coagulation with generalized hemorrhagic manifestations. Renal cortical ischemia led to BRCN which was recognized before death by characteristic roentgenographic signs. Adrenal and soft tissue calcification detected radiographically offered further evidence of generalized vascular insult.
Renal cortical necrosis
625
Fig. 2. Case 2. A, Plain film of abdomen. Note extensive calcification or renal cortices bilaterally. Intravenous pyelogram. B, 10 minute film. Faint nephrogram and opacification of left renal pelvis. Also contrast in bladder. Bilateral renal cortical and adrenal calcification evident. DISCUSSION I n a n i m a l experiments, hypotenslve shock causes r e d i s t r i b u t i o n of renal blood flow, w i t h restriction or cessation of flow to the o u t e r two thirds of the renal cortex, while circulation t h r o u g h the m e d u l l a a n d the j u x t a m e d u l l a r y n e p h r o n s is m a i n t a i n e d , 11, as
626
Leonidas, Berdon, and Gribetz
Angiography has shown a similar response of the underperfused human kidney? a These observations explain the distribution of necrosis in the kidney in renal ischemia associated with circulatory failure, as well as the preservation of renal function by the juxtamedullary nephrons. Collateral circulation through capsular vessels has been shown to maintain flow in a zone of subcapsnlar tissue of the ischemic kidney? 4 Thus a rim of the outer renal cortex remains viable in BRCN?, a In many instances, and for poorly understood reasons, renal ischemia may cause acute tubular necrosis, or various de~ grees of combined cortical and medullary necrosis,9, as and yet cortical lesions predominate. Most cases of BRCN have been described in pregnant women in association with third trimester bleeding, usually abruptio placentae.Z, 2, s-7 However, many other conditions leading to severe systemic hypotension may cause BRCN. s, ~, ~ Severe infections may precipitate BRCN. Experimentally BRCN has been produced as part of the "generalized Schwartzman reaction" and "endotoxin shock ''*, ~r, *s with fibrin deposition in renal cortical vessels. In infancy BRCN has been described as a complication of diarrhea and dehydrationS, ,0, ,s, ~9 hemorrhagic and anoxic shock, infection, and the hemolytic uremic syndrome a, 20 Most cases have occurred in the neonatal period, and in this group of patients the diagnosis has been made after death. 9 In the two neonates described here, BRNC was diagnosed during life by characteristic radiographic findings. Review of the literature indicates that on the basis of roentgenographic findings one may distinguish between the predominantly tubular and papillary lesions and those mainly involving the renal cortex. In renal tubular and papillary necrosis renal function is usually adequate for good visualization of the kidneys by excretory urography. A prolonged nephrogram may be noted during the acute phase; renal scarring and roentgen signs of papillary necrosis have been shown to follow at a later date. 21, 22 However, when
The ]ournal of Pediatrics October 1971
renal cortical necrosis is the predominant lesion, there is severe impairment of renal function, with failure to visualize the kidneys on intravenous pyelography, and subsequently the distinct pattern of calcification of the renal cortexY, 8, s, ~9, 2o ROENTGENOGRAPHIC
FINDINGS
The characteristic pattern of bilateral and symmetrical renal cortical calcification (Figs. 1 and 2) may be observed on plain films within a few weeks. Calcium deposition is limited to the renal cortex with occasional streaks radiating towards the medulla, representing the calcified columns of Berdn? Calcification may be extensive, scattered or patchy, "tram line," or in the form of a calcified renal cortical shellY, 8 Intravenous pyelography shows very poor excretion of the contrast medium and poor visualization of the kidneys and upper tracts because of severely compromised renal function. Other forms of nephrocalcinosis (renal tubular acidosis, hyperparathyroidism, chronic pyelonephritis, and tuberculosis) are extremely rare in the neonate. They can usually be distinguished from BRCN at any age clinically, and renal calcification in these entities is medullary, universal, or focal and asyrrmletrical.S, 2~ Renal vein thrombosis is frequently unilateral, and early nephrectomy eliminates the possibility of follow-up x-ray examinations. With conservative therapy renal atrophy may ensue, yet radiographically visible calcifications of the kidney are notably rareY ~, 25 In the case described by Nahum and associates,25 there was roentgenographic evidence or linear and radial calcifications corresponding to the distribution of the renal veins. Chronic glomerulonephritis or hereditary nephropathy may present with cortical calcification indistinguishable from that of BRCN, yet they are easily recognized clinically and pose no problem of differential diagnosis in the neonatal period. CONCLUSION
The most urgent problem during the acute phase of BRCN in the neonate is
Volume 79 Number 4
m a n a g e m e n t of the acute renal failure; this is essentially the same irrespective of the exact nature of underlying renal pathology. Accurate diagnosis m a y be obtained subsequently by needle biopsy of the kidney, zs' 28 but this procedure is attended with risk in a usually critically ill neonate. T h u s roentgenographic diagnosis, as outlined above, m a y be of definite value in establishing the diagnosis of B R C N in the patient who has survived the acute episode. I t m a y also define the gross extent of renal injury and thereby offer aid in long-term management and some indication of prognosis.
1. 2.
3.
4. 5.
6.
7.
8. 9.
10.
11. 12.
REFERENCES Lanier, D. P., and Schreiner, G. E.: Bilateral renal cortical necrosis, Amer. J. Med. 24: 519, 1958. McAllister, W. H., and Nedelman, S. H.: The roentgen manifestations of bilateral renal cortical necrosis, Amer. J. Roentgen. 86: 129, 1961. Whelan, J. G., Ling, J. T., and Davis, L. A.: Ante mortem roentgen manifestations of bilateral renal cortical necrosis, Radiology 69: 682, 1967. Abilgaard, C. F.: Recognition and treatment of intravascular coagalation, J. PEDIAT. 74: 163, 1969. McKay, D. G.: Disseminated intravascular coagulation. An intermediary mechanism of disease, New York, 1965, Hoeber Medical Division, Harper & Row, Publishers, Inc., p. 431. Wells, J. D., Margolin, E. G., and Gall, E. A.: Renal cortical necrosis. Clinical and pathologic features in twenty-one cases, Amer. J. Med. 29: 257, 1960. Mo~l, H.: Gross bilateral renal cortical necrosis during long periods of oliguria anurla. Roentgenologic observations in two cases, Acta Radlol. 48: 355, 1957. Palmer, E. J.: Renal cortical calcification, Clin. Radiol. 21: 175, 1970. Bernstein, J., and Meyer, R.: Congenital abnormalities of the urinary system. Renal cortical and medullary necrosis, J. PEDIAT. 59: 657, 1961. Zueltzer, W. W., Charles, S., Kurnetz, R., Newton, W. A., and Fallon, R.: Circulatory diseases of the kidneys in infancy and childhood, Amer. J. Dis. Child. 81: 1, 1951. Kupic, E. A., and Abrams, H. L.: Renal vascular alterations induced by hemorrhagic hypotension, Invest. Radlol. 3: 345, 1968. Lavender, J. P., Sherwood, T., and Russel,
Renal cortical necrosis
13. 14. 15. 16. 17. 18.
19.
20.
21.
22.
93.
24.
25. 26. 97.
28.
62 7
S.: In vivo renal microanglography. An experimental technique to study renal cortical perfusion during hemorrhagic shock, Brit. J. Radiol. 42: 247, 1969. Siegelman, S. S., and Goldman, A. G.: The Trueta phenomenon. Angiographic documentation in man, Radiology 90: 1084, 1969. Abrams, H. L., and Cornell, S. /-I.: Patterns of collateral flow in renal ischemia, Radiology 84: 1001, t965. Marks, I. M.: Renal medullary necrosis following exsanguinatlon, Lancet 2: 680, 1960. Eskeland, G., and Skogrand, A.: Bilateral renal cortical necrosis of the kidneys in infancy, Acta Paedlat. 48: 278, 1959. Hodes, H. L.: Care of the critically ill child. Endotoxin shock, Pediatrics 44: 248, 1969. Schneider, B., Rosenhelm, S., and Margaretten, W.: Renal arteriography in the generalized Schwartzman reaction, Invest. Radiol. 3: 23, 1968. Moschos, A., Tzortzatou, F., DanelatouAthanasiadou, C., Billis, A., and Zerefos, N.: Prolonged peritoneal dlalysis in an infant, Ann. Clin. Paediat. Univers. Athenlensis (Greece) 17: 265, 1970. Remy, J., Bombart, E., Stelandre, G., and Gosselin, B.: Los manifestations radiologiques de la n4crose eorticale r~nale du nourlsson, Pediatrle 93: 801, 1968. Maner, S. M., and Nogrady, M. B.: Renal papillary and cortical necrosis in a newborn infant. Report of a survivor with roentgenographic documentation, J. P~DIAT. 74: 750, 1969. Chrispin, A. R., Hull, D., Lillie, J. G., and Ridson, R. A.: Renal tubular necrosis and papillary necrosis after gastroenteritls in infants, Brit. Med. J. 1: 410, 1970. Arons, W. L., Christensen, W. R., and Sosman, M. C.: Nephrocalci-nosis visible by Xray associated with chronic glomerulonephrltis, Ann. Intern. Med. 42: 960, 1955. Belman, A. B., Susmano, D. F., Burden, J. J., and Kaplan, G. W.: Nonoperative treatment of unilateral renal vein thrombosis in the newborn, J.A.M.A. 211: 1165, 1970. Nahum, H., Gubler, J. P., and Rodier, J.: Thrombose veineuse r~nale unilat~rale du nouveau-n~, Ann. Radlol. 12: 293, 1969. Efferesoe, P., Gormsen, H., Iversen, P., and Raaschou, F.: Nyrebiopsy of dlalyseproblemer, Ugeskr. Laeg. 116: 1715, 1954. Gormsen, H., Iversen, P., and Raaschou, F.: Kidney biopsy in acute anuria with case of acute bilateral cortical necrosis, Amer. J. Med. 19: 209, 1955. Boucot, N. G., Guild, W. R., and Merrill, J. P.: Bilateral renocortical necrosis with recovery, New Eng. J. Med. 957: 416, 1957.
623
Bilateral renal cortical necrosis in the ne vborn infant: Roentgenograpbic diagnosis Bilateral renal cortical necrosis [ollowing shock and renal cortical ischemia in the neonatal period is usually ]atal. Improvement in medical care has led to longer survivals, and radiographic diagnosis can now be made during life by demonstration o[ a characteristic pattern o[ bilateral and symmetrical calcification o[ the renal cortex, which appears a [ew weeks a#er the onset o[ renal [allure.
John c. Leonidas, M.D.,* Walter E. Berdon, M.D., and Donald Gribetz, M.D. NEW YORK,
N. Y.
B I L AT E R AL renal cortical necrosis (BRCN) is a rare frequently fatal disorder characterized by ischemic coagulative necrosis of the cortex of both kidneys? -s Experimental and clinical evidence indicates that it is caused by severe and prolonged renal cortical ischemia associated with circulatory failure a n d / o r disseminated intravascular coagulation, x, 4-8 B R C N has been almost uniformly fatal, and until recently the diagnosis had been made only after death. T h e diagnosis of B R C N has now been established during life, and improved management of renal failure has resulted in longer survivals of these patients. Roentgenographically a characteristic pattern of bilateral and symmetrical calcification of the renal cortex has been demonstrated a From the Departments of Radiology and Pediatrics, the Mount Sinai School o[ Medicine o[ the City University o[ New York, and the Department o[ Radiology, Columbia University College o[ Physicians and Surgeons. eAddress: Department oI Radiology, Mount $1na~ Hospital, 11 g. lOOthSt., New York, N. Y. 10029.
few weeks after the onset of acute renal failure.Z, 3, 7, s B R C N can occur in the newborn infant, but thus far the diagnosis has been made only at autopsy2, lo T h e purpose of this report is to describe two neonates with BRCN in whom the diagnosis was made by the characteristic appearance of renal cortical calcification on plain roentgenograms. T o our knowledge, this is the first report of the antemortem roentgenographic diagnosis of this condition during the neonatal period.
CASE REPORTS Case 1. A male infant was born by cesarean section performed because of placenta praevia; gestational age was 33 weeks and birth weight was 1,625 Gm. The baby was severely anemic at birth (hemoglobin 6.0 Gin.). Bilirubin was 4 nag. per 100 ml. A transfusion of 35 ml. of compatible fresh whole blood was given, and the hemoglobin concentration rose to 14.2 Gin. At the age of 17 days the infant was transferred to Babies Hospital. Vol. 79, No. 4, pp. 623-627
624
Leonidas, Berdon, and Gribetz
The Journal o[ Pediatrics October 1971
Fig. 1. Case 1. A~ Detail from plain film of abdomen. Note rim calcification of right renal cortex (upper and lower arrow). Middle arrow demonstrates calcified nodule within substance of liver. B, Cone-down view of left kidney. Arrows point to rim of calcium outlining the left renal cortex. Pertinent physical findings on admission included retardation of growth, marked pallor, tachypnea, and tachycardia. Hemoglobin was 7.7 Gin., white blood cells 30,100 per cubic millimeter, platelets 368,000 per cubic millimeter, and reticulocytes 6.6 per cent. Prothrombin time, partial thromboplastin time, and fibrinogen levels were normal. Blood and urine cultures were sterile. Urinalysis revealed albuminuria and microscopic hematuria. Blood urea nitrogen was 125 mg. per 100 ml. There was metabolic acidosis (pH 7.080, base excess -25.7), hyperkalemia (K 6.5 mEq. per liter), hypocalcemia (Ca 6.9 mg. per 100 ml.), and hypoproteinemia (total protein 4.8 Gin. per 100 ml.). An intravenous pyelogram was performed on the second hospital day. On the preliminary film both kidneys were sharply outlined by a rim of calcification extending throughout the outer cortex, as if the kidneys were "pencilled in" (Fig. 1, A and B). A dense calcified nodule was seen within the substance of the liver suggesting a phlebolith (Fig. 1, A). Injection of 12 ml. of 50 per cent sodium diatrizoate (Hypaque 50) intravenously failed to show any visualization; voiding cystourethrogram was normal. Slow improvement followed treatment of acidosis, hypoealcemia, and anemia. During the third hospital week blood urea nitrogen ranged between 20 and 30 mg. per 100 ml. Follow-up examinations to the age of 18 months have shown persistence of renal failure and growth retardation. Comment. Hematuria and renal failure in this
newborn infant, following perinatal hemorrhage, suggest a severe renal circulatory disturbance at birth. The characteristic pattern of calcification of the cortex of both kidneys on x-ray examination led to the diagnosis of BRCN. Case 2. A female infant was born at term following a normal pregnancy and premature rupture of membranes 24 hours prior to delivery, which was otherwise unremarkable. Apgar score was 9 at 1 minute. Weight was 3,070 Gm. Immediately thereafter the baby developed apnea and marked bradycardia. She was ressuscitated successfully. At the age of 20 hours she developed massive rectal and vaginal bleeding, hematemesis, and oozing of blood from venipuncture sites. Pertinent laboratory findings were thrombocytopenia (platelets 35,000 per cubic millimeter), prolongation of partial thromboplastin time (93/79), anemia, hyperkalemia, and hypocalcemia. On the sixth day of life blood urea nitrogen was 114 mg. and creatinine 5.6 mg. per 100 mh Blood and urine cultures were sterile. 9 intravenous pyelogram showed only a very faint nephrogram but no distinct opacification of collecting tracts. Both kidneys were normal in size. A presumptive diagnosis of neonatal septicemia and consumption coagulopathy was made, and the patient was treated with penicillin and kanamycin. At the age of 26 days renal cortical calcification was noted bilaterally on plain abdominal roentgenograms. The patient was transferred to Mount Sinai
Volume 79 Number 4
Hospital at the age of 9 weeks. Physical examination revealed growth failure and pallor but was otherwise unremarkable. Plain films of the abdomen showed extensive patchy calcification of the entire cortex of both kidneys. Both adrenals were also caIcified, and there was deposition of calcium in the soft tissue adjacent to the left iliac crest (Fig. 2, A). Intravenous pyelography with 12 ml. of methyglucamine dialtrizoate 60 per cent (Renographin 60) showed only faint opacification of the left upper collecting system and of the bladder (Fig. 2, B). Renal size was reduced in comparison with previous films, particularly on the right, where calcification was also more prominent. The roentgenographic findings were consistent with BRCN. Laboratory values at this time were: hemoglobin, 8.6 Gin.; white blood cells, 18,700 per cubic millimeter with a normal differential count; platelets, 264,000; and reticulocytes, 1.7 per cent. Urine pH was 5.5. to 6.0 with persistently low specific gravity. There was albuminuria and microscopic hematuria. Blood urea nitrogen was 84 Gm. per 100 ml. and creatinine was 2.6 mg. Blood and urine cuItures were sterile. Coagulation studies showed initially prolongation of partial thromboplastin time (112/50); this returned to normal during the third hospital week. The patient received an oral citrate mixture and iron supplementation. Initially there was improvement of both clinical and laboratory manifestations of renal failure. However, approximately 5 months after discharge, it was apparent that renal failure was progressing. Blood urea nitrogen was 96 rag. per 100 ml. serum calcium 7.4 mg., serum phosphate 7.8 rag., and alkaline phosphatase greater than 350 I.U. There was also anemia (hemoglobin 7.0 Gin.), and x-ray evidence of progressive skeletal demineralization. The baby died suddenly at the age of 9 months. Autopsy performed elsewhere confirmed the diagnosis of biIateral renal cortical and medullary necrosis with extensive calcification of the renal cortex. Comment. NeonataI shock and anoxia in this infant precipitated disseminated intravascular coagulation with generalized hemorrhagic manifestations. Renal cortical ischemia led to BRCN which was recognized before death by characteristic roentgenographic signs. Adrenal and soft tissue calcification detected radiographically offered further evidence of generalized vascular insult.
Renal cortical necrosis
625
Fig. 2. Case 2. A, Plain film of abdomen. Note extensive calcification or renal cortices bilaterally. Intravenous pyelogram. B, 10 minute film. Faint nephrogram and opacification of left renal pelvis. Also contrast in bladder. Bilateral renal cortical and adrenal calcification evident. DISCUSSION I n a n i m a l experiments, hypotenslve shock causes r e d i s t r i b u t i o n of renal blood flow, w i t h restriction or cessation of flow to the o u t e r two thirds of the renal cortex, while circulation t h r o u g h the m e d u l l a a n d the j u x t a m e d u l l a r y n e p h r o n s is m a i n t a i n e d , 11, as
626
Leonidas, Berdon, and Gribetz
Angiography has shown a similar response of the underperfused human kidney? a These observations explain the distribution of necrosis in the kidney in renal ischemia associated with circulatory failure, as well as the preservation of renal function by the juxtamedullary nephrons. Collateral circulation through capsular vessels has been shown to maintain flow in a zone of subcapsnlar tissue of the ischemic kidney? 4 Thus a rim of the outer renal cortex remains viable in BRCN?, a In many instances, and for poorly understood reasons, renal ischemia may cause acute tubular necrosis, or various de~ grees of combined cortical and medullary necrosis,9, as and yet cortical lesions predominate. Most cases of BRCN have been described in pregnant women in association with third trimester bleeding, usually abruptio placentae.Z, 2, s-7 However, many other conditions leading to severe systemic hypotension may cause BRCN. s, ~, ~ Severe infections may precipitate BRCN. Experimentally BRCN has been produced as part of the "generalized Schwartzman reaction" and "endotoxin shock ''*, ~r, *s with fibrin deposition in renal cortical vessels. In infancy BRCN has been described as a complication of diarrhea and dehydrationS, ,0, ,s, ~9 hemorrhagic and anoxic shock, infection, and the hemolytic uremic syndrome a, 20 Most cases have occurred in the neonatal period, and in this group of patients the diagnosis has been made after death. 9 In the two neonates described here, BRNC was diagnosed during life by characteristic radiographic findings. Review of the literature indicates that on the basis of roentgenographic findings one may distinguish between the predominantly tubular and papillary lesions and those mainly involving the renal cortex. In renal tubular and papillary necrosis renal function is usually adequate for good visualization of the kidneys by excretory urography. A prolonged nephrogram may be noted during the acute phase; renal scarring and roentgen signs of papillary necrosis have been shown to follow at a later date. 21, 22 However, when
The ]ournal of Pediatrics October 1971
renal cortical necrosis is the predominant lesion, there is severe impairment of renal function, with failure to visualize the kidneys on intravenous pyelography, and subsequently the distinct pattern of calcification of the renal cortexY, 8, s, ~9, 2o ROENTGENOGRAPHIC
FINDINGS
The characteristic pattern of bilateral and symmetrical renal cortical calcification (Figs. 1 and 2) may be observed on plain films within a few weeks. Calcium deposition is limited to the renal cortex with occasional streaks radiating towards the medulla, representing the calcified columns of Berdn? Calcification may be extensive, scattered or patchy, "tram line," or in the form of a calcified renal cortical shellY, 8 Intravenous pyelography shows very poor excretion of the contrast medium and poor visualization of the kidneys and upper tracts because of severely compromised renal function. Other forms of nephrocalcinosis (renal tubular acidosis, hyperparathyroidism, chronic pyelonephritis, and tuberculosis) are extremely rare in the neonate. They can usually be distinguished from BRCN at any age clinically, and renal calcification in these entities is medullary, universal, or focal and asyrrmletrical.S, 2~ Renal vein thrombosis is frequently unilateral, and early nephrectomy eliminates the possibility of follow-up x-ray examinations. With conservative therapy renal atrophy may ensue, yet radiographically visible calcifications of the kidney are notably rareY ~, 25 In the case described by Nahum and associates,25 there was roentgenographic evidence or linear and radial calcifications corresponding to the distribution of the renal veins. Chronic glomerulonephritis or hereditary nephropathy may present with cortical calcification indistinguishable from that of BRCN, yet they are easily recognized clinically and pose no problem of differential diagnosis in the neonatal period. CONCLUSION
The most urgent problem during the acute phase of BRCN in the neonate is
Volume 79 Number 4
m a n a g e m e n t of the acute renal failure; this is essentially the same irrespective of the exact nature of underlying renal pathology. Accurate diagnosis m a y be obtained subsequently by needle biopsy of the kidney, zs' 28 but this procedure is attended with risk in a usually critically ill neonate. T h u s roentgenographic diagnosis, as outlined above, m a y be of definite value in establishing the diagnosis of B R C N in the patient who has survived the acute episode. I t m a y also define the gross extent of renal injury and thereby offer aid in long-term management and some indication of prognosis.
1. 2.
3.
4. 5.
6.
7.
8. 9.
10.
11. 12.
REFERENCES Lanier, D. P., and Schreiner, G. E.: Bilateral renal cortical necrosis, Amer. J. Med. 24: 519, 1958. McAllister, W. H., and Nedelman, S. H.: The roentgen manifestations of bilateral renal cortical necrosis, Amer. J. Roentgen. 86: 129, 1961. Whelan, J. G., Ling, J. T., and Davis, L. A.: Ante mortem roentgen manifestations of bilateral renal cortical necrosis, Radiology 69: 682, 1967. Abilgaard, C. F.: Recognition and treatment of intravascular coagalation, J. PEDIAT. 74: 163, 1969. McKay, D. G.: Disseminated intravascular coagulation. An intermediary mechanism of disease, New York, 1965, Hoeber Medical Division, Harper & Row, Publishers, Inc., p. 431. Wells, J. D., Margolin, E. G., and Gall, E. A.: Renal cortical necrosis. Clinical and pathologic features in twenty-one cases, Amer. J. Med. 29: 257, 1960. Mo~l, H.: Gross bilateral renal cortical necrosis during long periods of oliguria anurla. Roentgenologic observations in two cases, Acta Radlol. 48: 355, 1957. Palmer, E. J.: Renal cortical calcification, Clin. Radiol. 21: 175, 1970. Bernstein, J., and Meyer, R.: Congenital abnormalities of the urinary system. Renal cortical and medullary necrosis, J. PEDIAT. 59: 657, 1961. Zueltzer, W. W., Charles, S., Kurnetz, R., Newton, W. A., and Fallon, R.: Circulatory diseases of the kidneys in infancy and childhood, Amer. J. Dis. Child. 81: 1, 1951. Kupic, E. A., and Abrams, H. L.: Renal vascular alterations induced by hemorrhagic hypotension, Invest. Radlol. 3: 345, 1968. Lavender, J. P., Sherwood, T., and Russel,
Renal cortical necrosis
13. 14. 15. 16. 17. 18.
19.
20.
21.
22.
93.
24.
25. 26. 97.
28.
62 7
S.: In vivo renal microanglography. An experimental technique to study renal cortical perfusion during hemorrhagic shock, Brit. J. Radiol. 42: 247, 1969. Siegelman, S. S., and Goldman, A. G.: The Trueta phenomenon. Angiographic documentation in man, Radiology 90: 1084, 1969. Abrams, H. L., and Cornell, S. /-I.: Patterns of collateral flow in renal ischemia, Radiology 84: 1001, t965. Marks, I. M.: Renal medullary necrosis following exsanguinatlon, Lancet 2: 680, 1960. Eskeland, G., and Skogrand, A.: Bilateral renal cortical necrosis of the kidneys in infancy, Acta Paedlat. 48: 278, 1959. Hodes, H. L.: Care of the critically ill child. Endotoxin shock, Pediatrics 44: 248, 1969. Schneider, B., Rosenhelm, S., and Margaretten, W.: Renal arteriography in the generalized Schwartzman reaction, Invest. Radiol. 3: 23, 1968. Moschos, A., Tzortzatou, F., DanelatouAthanasiadou, C., Billis, A., and Zerefos, N.: Prolonged peritoneal dlalysis in an infant, Ann. Clin. Paediat. Univers. Athenlensis (Greece) 17: 265, 1970. Remy, J., Bombart, E., Stelandre, G., and Gosselin, B.: Los manifestations radiologiques de la n4crose eorticale r~nale du nourlsson, Pediatrle 93: 801, 1968. Maner, S. M., and Nogrady, M. B.: Renal papillary and cortical necrosis in a newborn infant. Report of a survivor with roentgenographic documentation, J. P~DIAT. 74: 750, 1969. Chrispin, A. R., Hull, D., Lillie, J. G., and Ridson, R. A.: Renal tubular necrosis and papillary necrosis after gastroenteritls in infants, Brit. Med. J. 1: 410, 1970. Arons, W. L., Christensen, W. R., and Sosman, M. C.: Nephrocalci-nosis visible by Xray associated with chronic glomerulonephrltis, Ann. Intern. Med. 42: 960, 1955. Belman, A. B., Susmano, D. F., Burden, J. J., and Kaplan, G. W.: Nonoperative treatment of unilateral renal vein thrombosis in the newborn, J.A.M.A. 211: 1165, 1970. Nahum, H., Gubler, J. P., and Rodier, J.: Thrombose veineuse r~nale unilat~rale du nouveau-n~, Ann. Radlol. 12: 293, 1969. Efferesoe, P., Gormsen, H., Iversen, P., and Raaschou, F.: Nyrebiopsy of dlalyseproblemer, Ugeskr. Laeg. 116: 1715, 1954. Gormsen, H., Iversen, P., and Raaschou, F.: Kidney biopsy in acute anuria with case of acute bilateral cortical necrosis, Amer. J. Med. 19: 209, 1955. Boucot, N. G., Guild, W. R., and Merrill, J. P.: Bilateral renocortical necrosis with recovery, New Eng. J. Med. 957: 416, 1957.