May 1976
The Journal o f P E D I A T R I C S
851
Renal failure following perinatal anoxia Ira M. Dauber, B.A., Alfred N. Krauss, M.D., Paul S. Symchych, M.D., and Peter A. M . Auld, M. D., N e w Y o r k , N . Y .
T rt E SY N D R O ME of renal failure is well recognized in adults but only rarely in newborn infants. The more frequent causes of renal failure in infants are gastroenteritis,1, ~ congenital anomalies, ~,~ hemolytic-uremic syndrome, 3-' septicemia, 1-~ severe hemorrhage (both maternal antepartum hemorrhage and neonatal)), G diarrhea and dehydration, 7 renal vein thrombosis, ~ and perinatal anoxia. 1 Renal failure is often recognized only at postmortem examination because of the severity of the primary disease. The clinical presentation of renal failure in neonates is often subtle. Lack of recognition of its occurrence has made this especially true when renal failure follows perinatal anoxia. Gruenwald 9 did not consider the kidney a site of pathology in asphyxic shock and only Bernstein and Meyer 6 have recognized a consistent association of renal failure with shock caused by perinatal anoxia. Perinatal anoxia remains a poorly recognized cause of renal failure. The following report presents seven cases of perinatal renal failure in an effort to increase clinical awareness of this syndrome. CASE MATERIAL Seven infants transferred to the Neonatal Intensive Care Unit at the New York Hospital-Cornell Medical Center during 1973 and 1974 have been selected for presentation. All infants weighed over 2,000 gm at birth and were of appropriate size for gestational age. All were born following complicated or traumatic deliveries, all had one-minute Apgar scores of 5 or less, and all required resuscitation at birth (Table I). Fetal monitoring with scalp electrodes or fetal heart rate equipment had not been performed on any of these infants. Three of the seven infants were meconium stained at birth. None had From the Departments of Pediatrics and Pathology, New York Hospital-Cornell Medical Center. Reprint address: 1300 York Ave., New York, N. Y. 10021.
clinical hyaline membrane disease, although three (Cases 4, 6, and 7) developed respiratory distress owing to aspiration of meconium. Three infants had cephalhematomas, and seizures were present in five of the seven infants. Two were noted to be edematous, and two had slight renal enlargement. On admission to the Intensive Care Unit, all infants were placed on a regimen of fluid intake consisting of 100 ml/kg/24 hours of 10% dextrose in water. After 24 hours this solution was replaced with appropriate solution of electrolytes given at the same rate. Although all seven infants developed oliguria during the first 24 hours of life, this was often recognized only in retrospect. Delay or absence of urination was noted in all patients by 48 hours of age.
See related articles, pp. 845 and 856. Laboratory data included an initial blood urea nitrogen concentration of 20 to 59 m g / d l of blood. Concurrent serum sodium values were frequently reduced (range 108136 mEq/1), whereas initial serum potassium concentrations were generally at the upper limits of normal (range 3 . 8 - 6.2 mEq/1). Initial urinalyses revealed hematuria and proteinuria in four of six infants when urine could be obtained. One surviving infant with normal renal function developed hydrocephalus and is severely retarded. Two other survivors, who had normal neurologic examinations on follow-up, have impaired renal function at three months and 12 months of age, respectively. Two other infants had normal neurologic and renal functions at discharge or follow-up. These data are summarized in Table II. Two infants died. Each had a complete postmortem examination. One infant (case 4) had severe anoxic encephalopathy with minimal renal changes. The brain was swollen and soft. There was necrosis of neurons in the cortex, hippocampus, basal ganglia, and dentate nucleus.
Vol. 88, No. 5, pp. 851-855
Dauber el aL
85 2
The Journal of Pediatrics May 1976
T a b l e I. Obstetrical i n f o r m a t i o n
Case No.
Birth weight (gin)
Gestational age (wk)
Complications of pregnancy
1 2
2,440 3,780
36 44
3 4
3,160 3,870
40 40
5
2,500
36
6
2,040
35
7
4,200
36
Abruptio placenta Maternal pre-eclampsia (BP 180/110); cord around the neck and meconium staining Severe birth trauma Passage of meconium during labor Mother, a 38-year-old primigravida Marginal placenta previa; premature placental separation Meconium staining during labor
1 minute~5 minute Apgar score
Mode @delivery Cesarean section Spontaneous vaginal
1/not done 5/7
Breech delivery with Piper forceps Cesarean section for transverse position Assisted frank breech
0/2 2/2
Spontaneous vaginal
5/7
Low forceps
5/8
4/8
T a b l e II. Clinical data
Case Resuscitation No. ~ a t birth 1
2 3
4
5
6
7
Positive pressure Oz
Physical examination
Edema of legs; kidneys not enlarged IPPB with O~ Cephalhematoma; dry peeling skin Suction; IPPB Edematous, newith O~; 4 crotic labia; mEq arreflexic, NaHCOa decerebrate posturing 25 ml NaHCOa Pneumothorax; poor muscle tone, absent cry; apneic at birth IPPB with 02; Cephalhematoma; 5 mt poor muscle NaHCQ tone; no spontaneous activity; pallor IPPB with O2 Tachypnea, grunting; kidneys slightly enlarged IPPB with Oz; Cyanosis in room suction air; floppy, lethargic, recurrent apnea; cephalhematoma bilaterally
Blood pressure (ram Hg)
Age at onset of oliguria," duration (days)
60/42 day 3 82/50 day 7
Day 1; 21 days
No
3 7
100 100
0 0
0 0
1+ 3+
60/40 day 3
Day 1; I day
Yes
1
0
0
0
0
-
D a y l ; 16 days
Yes
3 7
8-15 Many
0 0
0 0
3+ 2+
-
Day 1; 20 days
Yes
1 4
20-25 0
15 25-30
0 I-2
2+ 1+
No
3 10
100 15-20
0
0
3+
0
0
1+
0 0
0 0
0 0
0 0
65/35 day 3 70/40 day 7 90/40 day 30
60/35 day 3 70/40 day 7 80/30 day 18
Day 1; 6 days
Yes
4 9
Day 1; 4 .days
Yes
Anuric
Volume 88 Number 5
Renal failure following perinatal anoxia
The basal ganglia and other deep gray areas were frankly necrotic with astrocytosis, gliosis, and neovascularity. In the kidneys there were only minimal vacuolation and cloudy swelling of the cortical tubular cells. In Case 7 there were severe anoxic encephalopathy and pneumonia related to aspiration o f meconium. N e u r o n a l necrosis was present in the cortex, basal ganglia, hippocampus, and olivary nuclei. In both kidneys there was massive proximal tubular necrosis. DISCUSSION The seven patients in this report had two factors in common. (1) All infants were t h e products of difficult deliveries and all required resuscitation in the delivery room. This suggests that the initial episode of shock and renal anoxia which triggered the renal failure occurred at birth. (2) Although there was severe oliguria in all patients during the first 24 hours of life, the lack of urination was
853
often overlooked or ignored. Maintenance of inappropriate fluid regimens often resulted in edema and hyponatremia and made subsequent m a n a g e m e n t of both seizures and fluid administration more difficult. The kidney is very sensitive to oxygen deprivation. Within 24 hours of an ischemic episode, renal insufficiency will occur. The condition is reversible, but prolonged renal insuff• will cause increased damage leading to irreversible cortical or medullary necrosis 10, 11 Ischemia is one of the major causes o f renal failure. Obvious cellular changes in the kidney may not be present. Milder episodes m a y involve reversible tubular changes seen microscopically as cloudy swelling and hydropic degeneration. More severe injury involves the glomerulus and entire nephron via infarction (corticomedullary necrosis). Renal ischemia is caused by the decrease in renal blood flow associated with the shock
Blood chemical values Intravenous pyelogram, sonography, angiography
Age (days)
BUN (rag)
Na (mEq)
(m~q)
Creatinine (mg)
3 7 30
59 60 25
108 131 141
6.2 5.7 4.2
7.7 7.6
25 22 22
132 -
4.3
1.6 1.4 0.8
Not done
5 9 3 7 30
45 54 12
122 132 143
5.2 4.0 4.8
6.2
Small, irregular kidneys on sonography; normal collecting system in IVP with poor visualization of left kidney
2 8 I4 3 6 30 2 6 13
20 17
133 146 143 120 129 136 136 148 145 131 121 122
4.2 4.1 5.1 4.7 6.0 3.8 4.3 4.2 5.1 5.0 5.4
2.5 1.1 -4.3 6.5 3.1 1.4 0.8
1
40 56 41 25 7 3
1
--
1
--
2
30
K
1.l
--
--
Nonvisualization on Day 5; faint visualization with small kidneys, diminished cortex at 6 months
Not done
Sonogram suggestive of slight renal enlargement; nonvisualization on IVP at 3 months Delayed function on IVP with normal renal configuration Not done
Course and follow-up At 1 year of age, patient is in tenth percentile for height and weight; BUN is 44 mg; normal neurol0gic examination at 1 year Seizure free at 1 month with normal neurologic examination at 3 months; normal urinalyses and BUN Renal function returned to normal prior to discharge; however, head rapidly enIarged and hydrocephalus treated with a ventriculoperitoneal shunt; severe psychomotor retardation at 6 months of age Child became comatose and died at 3 weeks of age; postmortem examination revealed anoxic encephalopathy Anuria, followed by oliguria during first week of age; at 3 months of age BUN 35 mg/dl Oliguria for 2 days; normal renal function prior to discharge Infant developed progressive bradycardia; anuric for 48 hours prior to death at 3 days of age; postmortem examination revealed anoxic encephalopathy, acute tubular necrosis, aspiration pneumonia
8 54
Dauber et al.
state. The exact pathogenesis of the decreased blood flow is unsettled/. 11.1~ Leading hypotheses include thrombosis of cortical arteries, dilatation of glomerular capillaries, arteriolar vasospasm, and disseminated intravascular coagulation. Anoxia causes renal ischemia by two methods: directly via hypoxemia and indirectly by causing shock which decreases renal blood flow, owing to pooling of blood and diversion of blood flow. The kidney of the newborn infant may be in an especially precarious position with respect to alterations in blood flow. Dawes 13 has shown that the kidney of the fetal lamb receives a smaller portion of the resting cardiac output than does the adult kidney. Rudolph 14 has demonstrated a fall of 50% in renal blood flow in fetal lambs following anoxia produced by maternal hemorrhage. Neonatal renal failure will remain poorly recognized and poorly managed so long as the major means of detection is postmortem study. Detection still hinges on an acute awareness of the possibility of renal failure. Signs of renal failure. The manifestations of renal failure can be divided into three categories. Clinical. The cardinal feature of renal failure is oliguria?- ~- 7. 1~. 15.16 In one study the average duration was 12.7 days. 17 It can be as short as two to three days. This phase is often followed by polyuria? .... Anuria is an ominous sign suggesting bilateral renal dysgenesis, complete urinary tract obstruction, or severe ischemic necrosis? 5 0 l i g u r i a is commonly hidden by the precipitating disorder or missed entirely, if it is of short duration. The kidneys may be palpably enlarged. 7. . . . . . . . There may be edema or dehydration (depending on the sodium and water intake), owing to inability to maintain sodium balance. The infants are floppy and lethargic, and seizures may occur. Laboratory. The laboratory findings include elevated concentrations of blood urea nitrogen and serum creatinine?. 3. 6. 7.1~. 17 Elevated values usually peak at four to five days. Serum sodium concentration is decreased though not consistently so. Serum concentration of potassium is consistently elevated, often iatrogenically/. 15, ~ Hematuria is more common with renal vein thrombosis and hemolytic-uremic syndrome, but can occur in anoxic shock/-6. ~ Proteinuria is variable. Hypocalcemia and reduced serum bicarbonate concentration are common? ~ Hemolytic anemia has been reported in one study/ Increased numbers of nucleated red blood cells are present in some infants? Kwittken and Reiner feel that urinary casts are a strong indicator of ischemic renal injury and should alert the physician to the need for vigorous ~ countermeasures? ~ Casts in the urine are strongly correlated with perinatal distress and renal hypoxia. They are the hallmark of anoxic renal tubular
The Journal of Pediatrics May 1976
injury. Owing to the efficiency of the placenta as a kidney, plasma electrolytes and blood urea nitrogen are often normal following birth. These may be abnormal if the anoxic episode preceding delivery is prolonged. Radiographic. Chrispin I found that heavy medullary opacification on excretory urography is a sign of acute medullary damage. A uniform increase in kidney density is an indicator of the degree of acute tubular necrosis accompanying the medullary damage. Urography may not distinguish among renal vein thrombosis, occlusion of the renal artery, or other transient renal shutdown. Often an initial enlargement of the kidneys can be seen followed by a gradual decrease in size, with irregularity of the surface appearing later/ Calcification within necrotic areas does not occur until one to two months afterward and is not useful diagnostically. Retrograde pyelography and renal arteriography may be normal initially. The secretory phase is absent or minimal on serial renograms. Confirmation of suspected cases of renal failure can be achieved by noting improvement of the condition with peritoneal dialysis? 7, s0 Prevention. Acute renal failure is best prevented. This entails early recognition and aggressive treatment of the episode of shock which often precedes renal failure. Since most of the patients experienced abnormal labor and delivery, fetal monitoring with prompt recognition of fetal distress is vital in the prevention of this syndrome. Resuscitation in the delivery room should be prompt, especially with regard to oxygenation and correction of acidosis. Close monitoring of the infant following resuscitation should include monitoring of blood pressure, determination of blood gas values until stable, evaluation of serum concentration o f electrolytes, and observation of fluid intake and urinary output. Initial fluid therapy should consist of 100-150 ml/kg/24 hours, but this amount must be altered in response to urinary output, serum electrolytes, and serum and urine osmolalities. If replacement of blood volume is indicated for anemia or hypotension, this should be undertaken promptly. Prevention and early detection are the two cornerstones on which successful therapy Of renal failure after perinatal anoxia is based. The clinician should be aware that any infant ~experiencing severe perinataI anoxia and any infant requiring admission to a neonatal intensive care center is at risk for the development of renal failure. REFERENCES
1. Chrispin AR: Medullary necrosis in infancy, Br Med Bull 28:233, t972. 2. Eskeland G, and Skogrand A: Bilateral cortical necrosis of the kidneys in infancy, Acta Pediatr Scand 48:278, 1959. 3. Lloyd-StillJD, and Atwell JD: Renal failure in infancy with
Volume 88 Number 5
4.
5.
6.
7.
8. 9. 10.
1t.
12.
special reference to the use of peritoneal dialysis, J Pediatr Surg 1:466, 1966. Gianantonio CA, Vitacco M, Mendilaharzo F, and Rutty A: Acute renal failure in infancy and childhood, J PEDIATR 61:660, 1962. Sanerkin NG, and Evans JM: Bilateral renal cortical necrosis in infants associated with maternal antepartum hemorrhage, J Pathol 90:209, 1965. Bernstein J, and Meyer R" Congenital abnormalities of the urinary system. II. Renal cortical and medullary necrosis, J PEDIATR 59:657, 1961. Zuelzer WW, Charles S, Kurnetz R, Newton WA, and Fallon R: Circulatory diseases of kidneys in infancy and childhood: symmetrical cortical necrosis, Am J Dis Child 81:1, 1951. Aurelius G: Renal vein thrombosis in a newborn infant of a diabetic mother, Acta Pediatr Scand 58:80, 1969. Gruenwald P: Asphyxia, trauma, and shock at birth, Arch Pediatr 67:103, 1950. Groshong TD, Taylor AA, Nolph KD, Esterly J, and Maher JF: Renal function following cortical necrosis in childhood, J PEDIATR 79:267, 1971. Rubin M, and Calcagno P: Acute renal failure: Pathogenesis and management, Pediatr Clin North Am 9:155, 1962. Ponticelli C, Imbriscati E, Tarantine A, Graziani G: Post-
Renal failure following perinatal anoxia
13. 14.
15. 16.
17.
18. 19.
20.
855
partum renal failure with microangiopathic hemolytic anemia, Lancet 2:1034, 1970. Dawes GS: Foetal and neonatal physiology, Yearbook Medical Publishers, Inc, 1968, Chicago, p 171. Rudolph AM: The course and distribution of the foetal circulation, in Wolstenholme GEW, and O'Connor M, editors: Foetal autonomy, London, 1969, JA Churchill, Ltd, pp 147-156. Barratt TN: Renal failure in the first year of life, Br Med Bull 27:115, 1971. Lugo G, Ceballos R, Brown W, Polhill R, and Cassady G: Acute renal failure in the neonate managed by peritoneal dialysis: preliminary report of 2 cases, Am J Dis Child 118:655, 1969. Manley GL, and Collipp PJ: Renal failure in the newborn. Treatment with peritoneal dialysis, Am J Dis Child 115:107, 1968. Barratt TM: Renal failure in children, Proc R Soc Med 64:1045, 1971. Kwittken J, and Reiner L: Acute tubular necrosis in the newborn--a manifestation of anoxia, Pediatrics 33:380, 1964. Rennie ID, and Cameron JS: Peritoneal dialysis for traumatic renal failure in a 3-week old infant, Guys' Hosp Rep 115:449, 1966.
The Journal o f P E D I A T R I C S
851
Renal failure following perinatal anoxia Ira M. Dauber, B.A., Alfred N. Krauss, M.D., Paul S. Symchych, M.D., and Peter A. M . Auld, M. D., N e w Y o r k , N . Y .
T rt E SY N D R O ME of renal failure is well recognized in adults but only rarely in newborn infants. The more frequent causes of renal failure in infants are gastroenteritis,1, ~ congenital anomalies, ~,~ hemolytic-uremic syndrome, 3-' septicemia, 1-~ severe hemorrhage (both maternal antepartum hemorrhage and neonatal)), G diarrhea and dehydration, 7 renal vein thrombosis, ~ and perinatal anoxia. 1 Renal failure is often recognized only at postmortem examination because of the severity of the primary disease. The clinical presentation of renal failure in neonates is often subtle. Lack of recognition of its occurrence has made this especially true when renal failure follows perinatal anoxia. Gruenwald 9 did not consider the kidney a site of pathology in asphyxic shock and only Bernstein and Meyer 6 have recognized a consistent association of renal failure with shock caused by perinatal anoxia. Perinatal anoxia remains a poorly recognized cause of renal failure. The following report presents seven cases of perinatal renal failure in an effort to increase clinical awareness of this syndrome. CASE MATERIAL Seven infants transferred to the Neonatal Intensive Care Unit at the New York Hospital-Cornell Medical Center during 1973 and 1974 have been selected for presentation. All infants weighed over 2,000 gm at birth and were of appropriate size for gestational age. All were born following complicated or traumatic deliveries, all had one-minute Apgar scores of 5 or less, and all required resuscitation at birth (Table I). Fetal monitoring with scalp electrodes or fetal heart rate equipment had not been performed on any of these infants. Three of the seven infants were meconium stained at birth. None had From the Departments of Pediatrics and Pathology, New York Hospital-Cornell Medical Center. Reprint address: 1300 York Ave., New York, N. Y. 10021.
clinical hyaline membrane disease, although three (Cases 4, 6, and 7) developed respiratory distress owing to aspiration of meconium. Three infants had cephalhematomas, and seizures were present in five of the seven infants. Two were noted to be edematous, and two had slight renal enlargement. On admission to the Intensive Care Unit, all infants were placed on a regimen of fluid intake consisting of 100 ml/kg/24 hours of 10% dextrose in water. After 24 hours this solution was replaced with appropriate solution of electrolytes given at the same rate. Although all seven infants developed oliguria during the first 24 hours of life, this was often recognized only in retrospect. Delay or absence of urination was noted in all patients by 48 hours of age.
See related articles, pp. 845 and 856. Laboratory data included an initial blood urea nitrogen concentration of 20 to 59 m g / d l of blood. Concurrent serum sodium values were frequently reduced (range 108136 mEq/1), whereas initial serum potassium concentrations were generally at the upper limits of normal (range 3 . 8 - 6.2 mEq/1). Initial urinalyses revealed hematuria and proteinuria in four of six infants when urine could be obtained. One surviving infant with normal renal function developed hydrocephalus and is severely retarded. Two other survivors, who had normal neurologic examinations on follow-up, have impaired renal function at three months and 12 months of age, respectively. Two other infants had normal neurologic and renal functions at discharge or follow-up. These data are summarized in Table II. Two infants died. Each had a complete postmortem examination. One infant (case 4) had severe anoxic encephalopathy with minimal renal changes. The brain was swollen and soft. There was necrosis of neurons in the cortex, hippocampus, basal ganglia, and dentate nucleus.
Vol. 88, No. 5, pp. 851-855
Dauber el aL
85 2
The Journal of Pediatrics May 1976
T a b l e I. Obstetrical i n f o r m a t i o n
Case No.
Birth weight (gin)
Gestational age (wk)
Complications of pregnancy
1 2
2,440 3,780
36 44
3 4
3,160 3,870
40 40
5
2,500
36
6
2,040
35
7
4,200
36
Abruptio placenta Maternal pre-eclampsia (BP 180/110); cord around the neck and meconium staining Severe birth trauma Passage of meconium during labor Mother, a 38-year-old primigravida Marginal placenta previa; premature placental separation Meconium staining during labor
1 minute~5 minute Apgar score
Mode @delivery Cesarean section Spontaneous vaginal
1/not done 5/7
Breech delivery with Piper forceps Cesarean section for transverse position Assisted frank breech
0/2 2/2
Spontaneous vaginal
5/7
Low forceps
5/8
4/8
T a b l e II. Clinical data
Case Resuscitation No. ~ a t birth 1
2 3
4
5
6
7
Positive pressure Oz
Physical examination
Edema of legs; kidneys not enlarged IPPB with O~ Cephalhematoma; dry peeling skin Suction; IPPB Edematous, newith O~; 4 crotic labia; mEq arreflexic, NaHCOa decerebrate posturing 25 ml NaHCOa Pneumothorax; poor muscle tone, absent cry; apneic at birth IPPB with 02; Cephalhematoma; 5 mt poor muscle NaHCQ tone; no spontaneous activity; pallor IPPB with O2 Tachypnea, grunting; kidneys slightly enlarged IPPB with Oz; Cyanosis in room suction air; floppy, lethargic, recurrent apnea; cephalhematoma bilaterally
Blood pressure (ram Hg)
Age at onset of oliguria," duration (days)
60/42 day 3 82/50 day 7
Day 1; 21 days
No
3 7
100 100
0 0
0 0
1+ 3+
60/40 day 3
Day 1; I day
Yes
1
0
0
0
0
-
D a y l ; 16 days
Yes
3 7
8-15 Many
0 0
0 0
3+ 2+
-
Day 1; 20 days
Yes
1 4
20-25 0
15 25-30
0 I-2
2+ 1+
No
3 10
100 15-20
0
0
3+
0
0
1+
0 0
0 0
0 0
0 0
65/35 day 3 70/40 day 7 90/40 day 30
60/35 day 3 70/40 day 7 80/30 day 18
Day 1; 6 days
Yes
4 9
Day 1; 4 .days
Yes
Anuric
Volume 88 Number 5
Renal failure following perinatal anoxia
The basal ganglia and other deep gray areas were frankly necrotic with astrocytosis, gliosis, and neovascularity. In the kidneys there were only minimal vacuolation and cloudy swelling of the cortical tubular cells. In Case 7 there were severe anoxic encephalopathy and pneumonia related to aspiration o f meconium. N e u r o n a l necrosis was present in the cortex, basal ganglia, hippocampus, and olivary nuclei. In both kidneys there was massive proximal tubular necrosis. DISCUSSION The seven patients in this report had two factors in common. (1) All infants were t h e products of difficult deliveries and all required resuscitation in the delivery room. This suggests that the initial episode of shock and renal anoxia which triggered the renal failure occurred at birth. (2) Although there was severe oliguria in all patients during the first 24 hours of life, the lack of urination was
853
often overlooked or ignored. Maintenance of inappropriate fluid regimens often resulted in edema and hyponatremia and made subsequent m a n a g e m e n t of both seizures and fluid administration more difficult. The kidney is very sensitive to oxygen deprivation. Within 24 hours of an ischemic episode, renal insufficiency will occur. The condition is reversible, but prolonged renal insuff• will cause increased damage leading to irreversible cortical or medullary necrosis 10, 11 Ischemia is one of the major causes o f renal failure. Obvious cellular changes in the kidney may not be present. Milder episodes m a y involve reversible tubular changes seen microscopically as cloudy swelling and hydropic degeneration. More severe injury involves the glomerulus and entire nephron via infarction (corticomedullary necrosis). Renal ischemia is caused by the decrease in renal blood flow associated with the shock
Blood chemical values Intravenous pyelogram, sonography, angiography
Age (days)
BUN (rag)
Na (mEq)
(m~q)
Creatinine (mg)
3 7 30
59 60 25
108 131 141
6.2 5.7 4.2
7.7 7.6
25 22 22
132 -
4.3
1.6 1.4 0.8
Not done
5 9 3 7 30
45 54 12
122 132 143
5.2 4.0 4.8
6.2
Small, irregular kidneys on sonography; normal collecting system in IVP with poor visualization of left kidney
2 8 I4 3 6 30 2 6 13
20 17
133 146 143 120 129 136 136 148 145 131 121 122
4.2 4.1 5.1 4.7 6.0 3.8 4.3 4.2 5.1 5.0 5.4
2.5 1.1 -4.3 6.5 3.1 1.4 0.8
1
40 56 41 25 7 3
1
--
1
--
2
30
K
1.l
--
--
Nonvisualization on Day 5; faint visualization with small kidneys, diminished cortex at 6 months
Not done
Sonogram suggestive of slight renal enlargement; nonvisualization on IVP at 3 months Delayed function on IVP with normal renal configuration Not done
Course and follow-up At 1 year of age, patient is in tenth percentile for height and weight; BUN is 44 mg; normal neurol0gic examination at 1 year Seizure free at 1 month with normal neurologic examination at 3 months; normal urinalyses and BUN Renal function returned to normal prior to discharge; however, head rapidly enIarged and hydrocephalus treated with a ventriculoperitoneal shunt; severe psychomotor retardation at 6 months of age Child became comatose and died at 3 weeks of age; postmortem examination revealed anoxic encephalopathy Anuria, followed by oliguria during first week of age; at 3 months of age BUN 35 mg/dl Oliguria for 2 days; normal renal function prior to discharge Infant developed progressive bradycardia; anuric for 48 hours prior to death at 3 days of age; postmortem examination revealed anoxic encephalopathy, acute tubular necrosis, aspiration pneumonia
8 54
Dauber et al.
state. The exact pathogenesis of the decreased blood flow is unsettled/. 11.1~ Leading hypotheses include thrombosis of cortical arteries, dilatation of glomerular capillaries, arteriolar vasospasm, and disseminated intravascular coagulation. Anoxia causes renal ischemia by two methods: directly via hypoxemia and indirectly by causing shock which decreases renal blood flow, owing to pooling of blood and diversion of blood flow. The kidney of the newborn infant may be in an especially precarious position with respect to alterations in blood flow. Dawes 13 has shown that the kidney of the fetal lamb receives a smaller portion of the resting cardiac output than does the adult kidney. Rudolph 14 has demonstrated a fall of 50% in renal blood flow in fetal lambs following anoxia produced by maternal hemorrhage. Neonatal renal failure will remain poorly recognized and poorly managed so long as the major means of detection is postmortem study. Detection still hinges on an acute awareness of the possibility of renal failure. Signs of renal failure. The manifestations of renal failure can be divided into three categories. Clinical. The cardinal feature of renal failure is oliguria?- ~- 7. 1~. 15.16 In one study the average duration was 12.7 days. 17 It can be as short as two to three days. This phase is often followed by polyuria? .... Anuria is an ominous sign suggesting bilateral renal dysgenesis, complete urinary tract obstruction, or severe ischemic necrosis? 5 0 l i g u r i a is commonly hidden by the precipitating disorder or missed entirely, if it is of short duration. The kidneys may be palpably enlarged. 7. . . . . . . . There may be edema or dehydration (depending on the sodium and water intake), owing to inability to maintain sodium balance. The infants are floppy and lethargic, and seizures may occur. Laboratory. The laboratory findings include elevated concentrations of blood urea nitrogen and serum creatinine?. 3. 6. 7.1~. 17 Elevated values usually peak at four to five days. Serum sodium concentration is decreased though not consistently so. Serum concentration of potassium is consistently elevated, often iatrogenically/. 15, ~ Hematuria is more common with renal vein thrombosis and hemolytic-uremic syndrome, but can occur in anoxic shock/-6. ~ Proteinuria is variable. Hypocalcemia and reduced serum bicarbonate concentration are common? ~ Hemolytic anemia has been reported in one study/ Increased numbers of nucleated red blood cells are present in some infants? Kwittken and Reiner feel that urinary casts are a strong indicator of ischemic renal injury and should alert the physician to the need for vigorous ~ countermeasures? ~ Casts in the urine are strongly correlated with perinatal distress and renal hypoxia. They are the hallmark of anoxic renal tubular
The Journal of Pediatrics May 1976
injury. Owing to the efficiency of the placenta as a kidney, plasma electrolytes and blood urea nitrogen are often normal following birth. These may be abnormal if the anoxic episode preceding delivery is prolonged. Radiographic. Chrispin I found that heavy medullary opacification on excretory urography is a sign of acute medullary damage. A uniform increase in kidney density is an indicator of the degree of acute tubular necrosis accompanying the medullary damage. Urography may not distinguish among renal vein thrombosis, occlusion of the renal artery, or other transient renal shutdown. Often an initial enlargement of the kidneys can be seen followed by a gradual decrease in size, with irregularity of the surface appearing later/ Calcification within necrotic areas does not occur until one to two months afterward and is not useful diagnostically. Retrograde pyelography and renal arteriography may be normal initially. The secretory phase is absent or minimal on serial renograms. Confirmation of suspected cases of renal failure can be achieved by noting improvement of the condition with peritoneal dialysis? 7, s0 Prevention. Acute renal failure is best prevented. This entails early recognition and aggressive treatment of the episode of shock which often precedes renal failure. Since most of the patients experienced abnormal labor and delivery, fetal monitoring with prompt recognition of fetal distress is vital in the prevention of this syndrome. Resuscitation in the delivery room should be prompt, especially with regard to oxygenation and correction of acidosis. Close monitoring of the infant following resuscitation should include monitoring of blood pressure, determination of blood gas values until stable, evaluation of serum concentration o f electrolytes, and observation of fluid intake and urinary output. Initial fluid therapy should consist of 100-150 ml/kg/24 hours, but this amount must be altered in response to urinary output, serum electrolytes, and serum and urine osmolalities. If replacement of blood volume is indicated for anemia or hypotension, this should be undertaken promptly. Prevention and early detection are the two cornerstones on which successful therapy Of renal failure after perinatal anoxia is based. The clinician should be aware that any infant ~experiencing severe perinataI anoxia and any infant requiring admission to a neonatal intensive care center is at risk for the development of renal failure. REFERENCES
1. Chrispin AR: Medullary necrosis in infancy, Br Med Bull 28:233, t972. 2. Eskeland G, and Skogrand A: Bilateral cortical necrosis of the kidneys in infancy, Acta Pediatr Scand 48:278, 1959. 3. Lloyd-StillJD, and Atwell JD: Renal failure in infancy with
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