Hyperuricemia in the Hemolytic-Uremic Syndrome Bernard S.
Kaplan, MD, BCh, FCP(SA),
Peter D.
\s=b\ Elevated serum uric acid concentrations were found in 18 children with hemolytic-uremic syndrome. The highest recorded level in each patient ranged from 10 to 29 mg/100 ml, and nine patients had concentrations of greater than 20 mg/100 ml. During a 53-hour period of peritoneal dialysis, 5.5 gm of uric acid was removed from one infant. Although acute renal failure was probably the major factor, erythrocyte destruction and hyperlacticacidemia may also have been important in the pathogenesis of the
hyperuricemia. (Am J Dis Child 130:854-856, 1976)
Thomson, MB, BCh, FCP(SA)
Biochemical abnormalities include ele¬ vation of blood urea nitrogen (BUN),
creatinine, potassium, phospho¬ ion, and lipid concentra¬ tions, and depression of serum cal¬ cium, bicarbonate, and albumin serum
rus, hydrogen
levels.
Although hyperuricemia has been found in patients with acute renal failure,1 there is only passing mention of its occurrence in infants with hemolytic-uremic syndrome." Indeed, there is very little information on hyperuri¬ cemia in any form of acute renal failure in children. In this article we report the finding of elevated serum uric acid concentrations in 18 patients with the hemolytic-uremic syndrome. '
The
hemolytic-uremic syndrome is characterized by the triad of nephropathy, microangiopathic hemolytic anemia, and thrombocytopenia. The degree of renal damage deter¬ mines the immediate and long-term prognosis of patients with this syn¬ drome. The features of this nephrop¬ athy are hematuria, proteinuria, oliguria or anuria, and hypertension.
SUBJECTS AND METHODS
Eighteen patients with hemolyticuremic syndrome were studied at the Transvaal Memorial Hospital for Children, Johannesburg, South Africa, and at the Montreal Children's Hospital, Montreal. This group consisted of all the patients with
Received for publication March 20, 1975; accepted July 9. From the Department of Nephrology, McGill University-Montreal Children's Hospital Research Institute, Montreal (Dr Kaplan), and the Department of Pediatrics, Transvaal Memorial Hospital for Children and University of the Witwatersrand, Johannesburg, South Africa (Dr
Thomson). Reprint requests
Department of NephrolHospital, 2300 Tupper St, Montreal, Quebec, Canada (Dr Kaplan). to
ogy, Montreal Children's
hemolytic-uremic syndrome
in whom uric acid concentrations were mea¬ sured at least once. Serum uric acid levels were measured by a phosphotungstic acid method.' All the other tests were done by standard tech¬ niques. Normal serum uric acid concentra¬ tions for children aged 3 months to 5 years were 2.5 to 4.5 mg/100 ml, and normal serum lactic acid concentrations were 6 to 16 mg/100 ml. serum
''
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Serial determinations of serum uric acid,
BUN, and creatinine levels
were deter¬ mined in 14 infants; in addition, serial serum lactic acid levels were measured in one infant. Peritoneal clearances of uric acid and creatinine were measured in two patients, and the renal clearances öf uric acid and creatinine were calculated in a third patient.
RESULTS
The 12 boys and six girls ranged from 4 months to 5 years and 6 months of age. The patients were divided into two groups on the basis of severity. Mildly affected patients were those who had hemolytic anemia, thrombocytopenia, and an elevated BUN concentration. These infants may also have had one of the following compli¬ cations: hypertension, convulsions, or oliguria. Severely affected patients had this triad and anuria, or had all three complications.'1 Eleven patients were classified as severely affected and six as mildly affected. One patient could not be assigned to either category. Eleven infants were treated with peritoneal dialysis; in ten, this procedure was begun within 24 hours of the onset of anuria or severe oligu¬ ria. None were treated with heparin sodium or streptokinase. Chlorothiazide therapy was not used during the first week of the illness in any of the
patients.
Laboratory studies obtained on ad¬ mission to hospital are shown in Table 1. Fourteen of 15 patients had hyper¬ uricemia, with serum uric acid concen¬ trations ranging from 12 to 29 mg/100 ml. In one patient, the value on admis¬ sion was 5.6 mg/100 ml, but rose to 27.4 mg/100 ml 14 days later. The serum uric acid levels were not measured on admission in three patients, but were 20.4 mg/100 ml on day 7, 12.4 mg/100 ml on day 2, and 12.4 mg/100 ml on day 4, respective-
Table
Hemoglobin, gm/100 ml Reticulocytes, % White blood cell count, 1,000/cu mm Platelet count, 1,000/cu mm BUN, mg/100 ml Serum creatinine, mg/100 ml Serum uric acid, mg/100 ml
hemolytic-uremic syndrome.7
Peritoneal Clearances of Urate and Creatinine Case 1.—This child was anurie or oliguric for 14 days, and underwent peritoneal dial¬ ysis for a total of 171 hours. His laboratory studies on admission to hospital showed the following levels: hemoglobin, 5.7 gm/100 ml; white blood cell (WBC) count, 16,600/cu
reticulocyte count, 5.4%; platelet count, 155,000/cu mm (this fell to 69,000/cu mm;
mm the following day); BUN, 122 mg/100 ml; creatinine, 6 mg/100 ml; uric acid, 20 mg/100 ml; phosphorus, 15 mg/100 ml; and serum calcium, 10 mg/100 ml. The serum BUN, creatinine, and uric acid concentra¬
tions were obtained at about the midpoint of each dialysis period. During the first 53 hours of dialysis, a total of 5.5 gm of uric acid was removed, and the serum uric acid concentration decreased from 20 to 11.6 mg/100 ml. The peritoneal clearance of uric acid during five periods ranged from 3.6 to 21 ml/min, and that of creatinine from 0.9
on
Admission to
Hospital
No of Patients 15
Mean Value
Range
7.1 7.8
5-11.1 3-21
10 13 15 14 15
20.2 70.3 106 4.7 16.6
8.7-38.0 11.0-155.0 44-180 1.S
1.1
5.6-29
Table 2.—Blood Urea Nitrogen, Serum Creatinine, and Urate Concentrations in Mildly and Severely Affected Infants*
ly-
The BUN, serum creatinine, and uric acid levels of five mildly affected and 12 severely affected patients are compared in Table 2. These were obtained on admission in 14 infants, and on days 2, 4, and 7 in three. Severely affected patients had signif¬ icantly higher BUN and serum crea¬ tinine concentrations than mildly af¬ fected patients, but similar uric acid levels. Serial uric acid concentrations were measured in 14 patients. The levels returned to normal in 13 of these, but rose progressively in one patient. This infant could not be prospectively clas¬ sified as either mildly or severely affected, since he had only mild involvement on admission to hospital but gradually deteriorated, and was the only child of the 18 who died. Two of his siblings had also died from the
1.—Laboratory Studies
BUN, mg/100 ml Serum creatinine, mg/100 ml Uric acid, mg/100 ml
Mildly Affected Infants (N = 5) 73 ± 25f
*
One patient could not be classified t Standard deviation.
Severely Affected Infants (N 12) =
120.4 ±42 5.2 ± 2.0 19.9 ±4.4
2.2 ±0.8 15.1 ±4.5 into either of the two
to 57 ml/min. The ratios of urate to crea¬ tinine clearance varied from 14.5:1 on day 2 to 0.06:1 on day 8. Case 2.—On admission to hospital, this
boy had the following laboratory values: hemoglobin, 9.6 gm/100 ml; WBC count, 22,400/cu mm; platelets, 30,000/cu mm; BUN, 102 mg/100 ml; creatinine, 4.0 mg/ 100 ml; and uric acid, 21 mg/100 ml. Uric
acid and creatinine clearances were mea¬ sured on three aliquote of peritoneal fluid on days 1, 2, and 3 after admission. The clearance of uric acid was 0.2 to 0.3 ml/min. The ratios of uric acid to creatinine clear¬ ance on days 2 and 3 were 0.15:1. Case 3.—This boy did not have anuria and did not undergo dialysis during the course of his illness. Laboratory data on admission to hospital showed the following levels: hemoglobin, 5.6 gm/100 ml; WBC count, 19,000/cu mm; platelet count, 139,000/cu mm; BUN, 26 mg/100 ml; creat¬ inine, 1.3 mg/100 ml; and uric acid, 6.7 mg/ 100 ml. Despite the fact that he had a mild form of hemolytic-uremic syndrome, his creatinine clearance was 7 ml/min, and his urate clearance was 1.0 ml/min on day 2. These increased to 13.0 and 7.0 ml/min for creatinine and urate clearances, re¬ spectively, by day 8.
Lactic Acid Concentrations
Serial uric acid, lactic acid, creati¬ nine, and BUN concentrations were measured in one patient, and are shown in Table 3. All were elevated on day 1, and then decreased at a similar rate.
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Kaplan, MD, BCh, FCP(SA),
Peter D.
\s=b\ Elevated serum uric acid concentrations were found in 18 children with hemolytic-uremic syndrome. The highest recorded level in each patient ranged from 10 to 29 mg/100 ml, and nine patients had concentrations of greater than 20 mg/100 ml. During a 53-hour period of peritoneal dialysis, 5.5 gm of uric acid was removed from one infant. Although acute renal failure was probably the major factor, erythrocyte destruction and hyperlacticacidemia may also have been important in the pathogenesis of the
hyperuricemia. (Am J Dis Child 130:854-856, 1976)
Thomson, MB, BCh, FCP(SA)
Biochemical abnormalities include ele¬ vation of blood urea nitrogen (BUN),
creatinine, potassium, phospho¬ ion, and lipid concentra¬ tions, and depression of serum cal¬ cium, bicarbonate, and albumin serum
rus, hydrogen
levels.
Although hyperuricemia has been found in patients with acute renal failure,1 there is only passing mention of its occurrence in infants with hemolytic-uremic syndrome." Indeed, there is very little information on hyperuri¬ cemia in any form of acute renal failure in children. In this article we report the finding of elevated serum uric acid concentrations in 18 patients with the hemolytic-uremic syndrome. '
The
hemolytic-uremic syndrome is characterized by the triad of nephropathy, microangiopathic hemolytic anemia, and thrombocytopenia. The degree of renal damage deter¬ mines the immediate and long-term prognosis of patients with this syn¬ drome. The features of this nephrop¬ athy are hematuria, proteinuria, oliguria or anuria, and hypertension.
SUBJECTS AND METHODS
Eighteen patients with hemolyticuremic syndrome were studied at the Transvaal Memorial Hospital for Children, Johannesburg, South Africa, and at the Montreal Children's Hospital, Montreal. This group consisted of all the patients with
Received for publication March 20, 1975; accepted July 9. From the Department of Nephrology, McGill University-Montreal Children's Hospital Research Institute, Montreal (Dr Kaplan), and the Department of Pediatrics, Transvaal Memorial Hospital for Children and University of the Witwatersrand, Johannesburg, South Africa (Dr
Thomson). Reprint requests
Department of NephrolHospital, 2300 Tupper St, Montreal, Quebec, Canada (Dr Kaplan). to
ogy, Montreal Children's
hemolytic-uremic syndrome
in whom uric acid concentrations were mea¬ sured at least once. Serum uric acid levels were measured by a phosphotungstic acid method.' All the other tests were done by standard tech¬ niques. Normal serum uric acid concentra¬ tions for children aged 3 months to 5 years were 2.5 to 4.5 mg/100 ml, and normal serum lactic acid concentrations were 6 to 16 mg/100 ml. serum
''
Downloaded From: http://archpedi.jamanetwork.com/ by a Michigan State University User on 06/16/2015
Serial determinations of serum uric acid,
BUN, and creatinine levels
were deter¬ mined in 14 infants; in addition, serial serum lactic acid levels were measured in one infant. Peritoneal clearances of uric acid and creatinine were measured in two patients, and the renal clearances öf uric acid and creatinine were calculated in a third patient.
RESULTS
The 12 boys and six girls ranged from 4 months to 5 years and 6 months of age. The patients were divided into two groups on the basis of severity. Mildly affected patients were those who had hemolytic anemia, thrombocytopenia, and an elevated BUN concentration. These infants may also have had one of the following compli¬ cations: hypertension, convulsions, or oliguria. Severely affected patients had this triad and anuria, or had all three complications.'1 Eleven patients were classified as severely affected and six as mildly affected. One patient could not be assigned to either category. Eleven infants were treated with peritoneal dialysis; in ten, this procedure was begun within 24 hours of the onset of anuria or severe oligu¬ ria. None were treated with heparin sodium or streptokinase. Chlorothiazide therapy was not used during the first week of the illness in any of the
patients.
Laboratory studies obtained on ad¬ mission to hospital are shown in Table 1. Fourteen of 15 patients had hyper¬ uricemia, with serum uric acid concen¬ trations ranging from 12 to 29 mg/100 ml. In one patient, the value on admis¬ sion was 5.6 mg/100 ml, but rose to 27.4 mg/100 ml 14 days later. The serum uric acid levels were not measured on admission in three patients, but were 20.4 mg/100 ml on day 7, 12.4 mg/100 ml on day 2, and 12.4 mg/100 ml on day 4, respective-
Table
Hemoglobin, gm/100 ml Reticulocytes, % White blood cell count, 1,000/cu mm Platelet count, 1,000/cu mm BUN, mg/100 ml Serum creatinine, mg/100 ml Serum uric acid, mg/100 ml
hemolytic-uremic syndrome.7
Peritoneal Clearances of Urate and Creatinine Case 1.—This child was anurie or oliguric for 14 days, and underwent peritoneal dial¬ ysis for a total of 171 hours. His laboratory studies on admission to hospital showed the following levels: hemoglobin, 5.7 gm/100 ml; white blood cell (WBC) count, 16,600/cu
reticulocyte count, 5.4%; platelet count, 155,000/cu mm (this fell to 69,000/cu mm;
mm the following day); BUN, 122 mg/100 ml; creatinine, 6 mg/100 ml; uric acid, 20 mg/100 ml; phosphorus, 15 mg/100 ml; and serum calcium, 10 mg/100 ml. The serum BUN, creatinine, and uric acid concentra¬
tions were obtained at about the midpoint of each dialysis period. During the first 53 hours of dialysis, a total of 5.5 gm of uric acid was removed, and the serum uric acid concentration decreased from 20 to 11.6 mg/100 ml. The peritoneal clearance of uric acid during five periods ranged from 3.6 to 21 ml/min, and that of creatinine from 0.9
on
Admission to
Hospital
No of Patients 15
Mean Value
Range
7.1 7.8
5-11.1 3-21
10 13 15 14 15
20.2 70.3 106 4.7 16.6
8.7-38.0 11.0-155.0 44-180 1.S
1.1
5.6-29
Table 2.—Blood Urea Nitrogen, Serum Creatinine, and Urate Concentrations in Mildly and Severely Affected Infants*
ly-
The BUN, serum creatinine, and uric acid levels of five mildly affected and 12 severely affected patients are compared in Table 2. These were obtained on admission in 14 infants, and on days 2, 4, and 7 in three. Severely affected patients had signif¬ icantly higher BUN and serum crea¬ tinine concentrations than mildly af¬ fected patients, but similar uric acid levels. Serial uric acid concentrations were measured in 14 patients. The levels returned to normal in 13 of these, but rose progressively in one patient. This infant could not be prospectively clas¬ sified as either mildly or severely affected, since he had only mild involvement on admission to hospital but gradually deteriorated, and was the only child of the 18 who died. Two of his siblings had also died from the
1.—Laboratory Studies
BUN, mg/100 ml Serum creatinine, mg/100 ml Uric acid, mg/100 ml
Mildly Affected Infants (N = 5) 73 ± 25f
*
One patient could not be classified t Standard deviation.
Severely Affected Infants (N 12) =
120.4 ±42 5.2 ± 2.0 19.9 ±4.4
2.2 ±0.8 15.1 ±4.5 into either of the two
to 57 ml/min. The ratios of urate to crea¬ tinine clearance varied from 14.5:1 on day 2 to 0.06:1 on day 8. Case 2.—On admission to hospital, this
boy had the following laboratory values: hemoglobin, 9.6 gm/100 ml; WBC count, 22,400/cu mm; platelets, 30,000/cu mm; BUN, 102 mg/100 ml; creatinine, 4.0 mg/ 100 ml; and uric acid, 21 mg/100 ml. Uric
acid and creatinine clearances were mea¬ sured on three aliquote of peritoneal fluid on days 1, 2, and 3 after admission. The clearance of uric acid was 0.2 to 0.3 ml/min. The ratios of uric acid to creatinine clear¬ ance on days 2 and 3 were 0.15:1. Case 3.—This boy did not have anuria and did not undergo dialysis during the course of his illness. Laboratory data on admission to hospital showed the following levels: hemoglobin, 5.6 gm/100 ml; WBC count, 19,000/cu mm; platelet count, 139,000/cu mm; BUN, 26 mg/100 ml; creat¬ inine, 1.3 mg/100 ml; and uric acid, 6.7 mg/ 100 ml. Despite the fact that he had a mild form of hemolytic-uremic syndrome, his creatinine clearance was 7 ml/min, and his urate clearance was 1.0 ml/min on day 2. These increased to 13.0 and 7.0 ml/min for creatinine and urate clearances, re¬ spectively, by day 8.
Lactic Acid Concentrations
Serial uric acid, lactic acid, creati¬ nine, and BUN concentrations were measured in one patient, and are shown in Table 3. All were elevated on day 1, and then decreased at a similar rate.
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