0022-5347/79/1215-0672$02.00/0 Vol. 121, May Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1979 by The Williams & Wilkins Co.
Case Reports URINARY KALLIKREIN EXCRETION IN IDIOPATHIC NEPHROTIC SYNDROME BEN H. BROUHARD,* ROBERT J. CUNNINGHAM, THOMAS W. PETRUSICK, MICHAEL BERGER LUTHER B. TRAVIS
AND
From the Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas
ABSTRACT
The plasma kallikrein-kinin system, a potent vasodilator, has been implicated in causing the protein loss of the idiopathic nephrotic syndrome. However, the kidney possesses a kallikreinkinin system separate from the plasma system. Thus, urinary kallikrein may reflect more accurately intrarenal events. Using a radiochemical esterolytic assay we measured the urinary kallikrein excretion in a patient with a minimal lesion nephrotic syndrome during relapse. Protein excretion was initially elevated (8.1 plus or minus 2.0 gm. per 24 hours) as was urinary kallikrein excretion (96.4 plus or minus 46.6 EU per 24 hours). After initiation of steroid therapy protein and kallikrein excretion decreased significantly (p less than O. 05). During the entire study kallikrein excretion was significantly correlated with protein excretion (r equals 0.89, p less than 0.01). It is tempting to speculate that activation of the intrarenal kallikrein-kinin system participates in the protein loss characteristic of the nephrotic syndrome. The mechanism of protein loss in the idiopathic nephrotic syndrome is unknown. Various vasoactive hormones have been implicated in vasodilatation and subsequent protein loss. 1 Kallen and Lee have implicated the plasma kallikreinkinin system in the proteinuria of the nephrotic syndrome. 2 However, there are several kallikrein systems, including plasma, glandular and renal. Furthermore, previous studies have shown that the renal kallikrein-kinin system is separate from the plasma system. 3 In addition, urinary kallikrein has been shown to be identical to the kallikrein synthesized by renal tissue. 4 Therefore, since urinary kallikrein may reflect more accurately intrarenal events, we measured urinary kallikrein in a patient with the idiopathic nephrotic syndrome during relapse and remission. CASE REPORT
G. L., U.H. 131103-P, an 8-year-old white boy with biopsy evidence of a minimal lesion nephrotic syndrome since he was 18 months old, was asymptomatic until 2 days before hospitalization when his mother noticed the onset of edema. Abdominal pain, anorexia, vomiting and fever occurred the following day. Physical examination revealed a height of 136 cm. (90 percentile), weight 37.4 kg. (>97 percentile), blood pressure 105/74, pulse 108 and temperature 38C. The patient showed generalized edema and abdominal examination revealed tenderness to palpation, rebound tenderness, a fluid wave and decreased bowel sounds. The remainder of the examination was unremarkable. Initial laboratory studies showed the urine to have a pH of 5.0, specific gravity 1.029, 2+ protein, negative for blood, ketones and glucose, 0 to 2 white and no Accepted for publication July 14, 1978. Supported in part by Biomedical Research Support Grant RR05427. * Requests for reprints: Department of Pediatrics, The University of Texas Medical Branch, Galveston, Texas 77550. 672
red blood cells per high power field. Hemoglobin was 13.9 with a peripheral white count of 17,600 with 65 per cent neutrophils, 30 per cent stabs, 4 per cent lymphocytes and 1 per cent monocytes. Serum creatinine was 0.4 mg. per cent. Total serum protein was 3.6 gm. per cent, albumin 0.6 gm. per cent and a-2-globulin 1.5 gm. per cent. Cholesterol was 307 mg. per cent. Peritoneal fluid revealed 3 to 4 white blood cells per high power field and no organisms were seen on Gram stain. The diagnosis of peritonitis was confirmed by peritoneal fluid cultures that yielded Streptococcus pneumoniae. Urine culture was sterile. The patient was treated with ampicillin intravenously. After the fever and abdominal tenderness were resolved 60 mg. prednisone daily in divided doses was begun (day 4). The patient responded with decreased proteinuria and weight loss. At the time of discharge from the hospital he weighed 31 kg., sodium intake was restricted to 2 gm. per day without other restrictions and fluid was limited initially until diuresis occurred. METHODS
Starting on the third day of hospitalization continuous 24hour urine specimens were collected and refrigerated under toluene for sodium, potassium, protein, amylase and kallikrein determinations. Sodium and potassium were measured by flame photometry with lithium as an internal standard. t Protein was determined by the biuret method,5 amylase by the method of O'Neal and Gochman, 6 and kallikrein by the esterolytic radioassay of Margolius and associates. 7 Purified, human urinary kallikrein served as the standard. P values were calculated by the Student test for unpaired data and correlation coefficients and the p values for these coefficients were calculated by standard statistical methods. 8 P values
THE JOURNAL OF UROLOGY
Copyright © 1979 by The Williams & Wilkins Co.
Case Reports URINARY KALLIKREIN EXCRETION IN IDIOPATHIC NEPHROTIC SYNDROME BEN H. BROUHARD,* ROBERT J. CUNNINGHAM, THOMAS W. PETRUSICK, MICHAEL BERGER LUTHER B. TRAVIS
AND
From the Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas
ABSTRACT
The plasma kallikrein-kinin system, a potent vasodilator, has been implicated in causing the protein loss of the idiopathic nephrotic syndrome. However, the kidney possesses a kallikreinkinin system separate from the plasma system. Thus, urinary kallikrein may reflect more accurately intrarenal events. Using a radiochemical esterolytic assay we measured the urinary kallikrein excretion in a patient with a minimal lesion nephrotic syndrome during relapse. Protein excretion was initially elevated (8.1 plus or minus 2.0 gm. per 24 hours) as was urinary kallikrein excretion (96.4 plus or minus 46.6 EU per 24 hours). After initiation of steroid therapy protein and kallikrein excretion decreased significantly (p less than O. 05). During the entire study kallikrein excretion was significantly correlated with protein excretion (r equals 0.89, p less than 0.01). It is tempting to speculate that activation of the intrarenal kallikrein-kinin system participates in the protein loss characteristic of the nephrotic syndrome. The mechanism of protein loss in the idiopathic nephrotic syndrome is unknown. Various vasoactive hormones have been implicated in vasodilatation and subsequent protein loss. 1 Kallen and Lee have implicated the plasma kallikreinkinin system in the proteinuria of the nephrotic syndrome. 2 However, there are several kallikrein systems, including plasma, glandular and renal. Furthermore, previous studies have shown that the renal kallikrein-kinin system is separate from the plasma system. 3 In addition, urinary kallikrein has been shown to be identical to the kallikrein synthesized by renal tissue. 4 Therefore, since urinary kallikrein may reflect more accurately intrarenal events, we measured urinary kallikrein in a patient with the idiopathic nephrotic syndrome during relapse and remission. CASE REPORT
G. L., U.H. 131103-P, an 8-year-old white boy with biopsy evidence of a minimal lesion nephrotic syndrome since he was 18 months old, was asymptomatic until 2 days before hospitalization when his mother noticed the onset of edema. Abdominal pain, anorexia, vomiting and fever occurred the following day. Physical examination revealed a height of 136 cm. (90 percentile), weight 37.4 kg. (>97 percentile), blood pressure 105/74, pulse 108 and temperature 38C. The patient showed generalized edema and abdominal examination revealed tenderness to palpation, rebound tenderness, a fluid wave and decreased bowel sounds. The remainder of the examination was unremarkable. Initial laboratory studies showed the urine to have a pH of 5.0, specific gravity 1.029, 2+ protein, negative for blood, ketones and glucose, 0 to 2 white and no Accepted for publication July 14, 1978. Supported in part by Biomedical Research Support Grant RR05427. * Requests for reprints: Department of Pediatrics, The University of Texas Medical Branch, Galveston, Texas 77550. 672
red blood cells per high power field. Hemoglobin was 13.9 with a peripheral white count of 17,600 with 65 per cent neutrophils, 30 per cent stabs, 4 per cent lymphocytes and 1 per cent monocytes. Serum creatinine was 0.4 mg. per cent. Total serum protein was 3.6 gm. per cent, albumin 0.6 gm. per cent and a-2-globulin 1.5 gm. per cent. Cholesterol was 307 mg. per cent. Peritoneal fluid revealed 3 to 4 white blood cells per high power field and no organisms were seen on Gram stain. The diagnosis of peritonitis was confirmed by peritoneal fluid cultures that yielded Streptococcus pneumoniae. Urine culture was sterile. The patient was treated with ampicillin intravenously. After the fever and abdominal tenderness were resolved 60 mg. prednisone daily in divided doses was begun (day 4). The patient responded with decreased proteinuria and weight loss. At the time of discharge from the hospital he weighed 31 kg., sodium intake was restricted to 2 gm. per day without other restrictions and fluid was limited initially until diuresis occurred. METHODS
Starting on the third day of hospitalization continuous 24hour urine specimens were collected and refrigerated under toluene for sodium, potassium, protein, amylase and kallikrein determinations. Sodium and potassium were measured by flame photometry with lithium as an internal standard. t Protein was determined by the biuret method,5 amylase by the method of O'Neal and Gochman, 6 and kallikrein by the esterolytic radioassay of Margolius and associates. 7 Purified, human urinary kallikrein served as the standard. P values were calculated by the Student test for unpaired data and correlation coefficients and the p values for these coefficients were calculated by standard statistical methods. 8 P values
