Pediatric Nephrology
Pediatr Nephrol (1992) 6:44-45 9 IPNA 1992
Original article Normal renal sensitivity to atrial natriuretic peptide in Gordon's syndrome Matti V'filimikil, Risto Pelkonenl, Ilkka Tikkanen2, and Frej Fyhrquist2 1 Third and 2 Fourth Departments of Medicine, University Central Hospital of Helsinki, SF-00290 Helsinki, Finland Received September 4, 1990; received in revised form May 16, 1991; accepted May 20, 1991
Abstract. To test the hypothesis that renal sensitivity to atrial natriuretic peptide (ANP) is impaired in G o r d o n ' s s y n d r o m e (hypertension and hyperkalaemia with normal glomerular filtration rate) we infused o~-hANP into two patients with this syndrome (a sister and a brother, 19 and 18 years o f age). For comparison, 11 healthy volunteers were also examined. The infusion of a - h A N P increased urinary v o l u m e and excretion o f sodium similarly in the patients and controls. The excretion o f potassium did not change in either the patients or the controls. The infusion of o~-hANP had no effect on the serum potassium levels or the plasma CO2 content in the patients. The present results do not confirm the hypothesis o f lack of sensitivity to A N P as a pathophysiological concept in G o r d o n ' s syndrome.
Key words: G o r d o n ' s s y n d r o m e - Atrial natriuretic h o r m o n e - Hypertension - Hyperkalaemia - Acidosis
Introduction G o r d o n ' s s y n d r o m e [hypertension and hyperkalaemia with normal glomerular filtration rate (GFR)] is a rare disorder in which hyperkalaemia o f renal origin occurs in the absence o f g l o m e m l a r insufficiency or renal sodium wasting, and in which hyperchloraemic acidosis, hypertension and hyporeninaemia coexist [ 1]. The pathophysiological mechanism underlying the syndrome is incompletely understood. A lack o f natriuretic or chlorouretic factors has been suggested [1]. Accordingly, we pointed out that both the basal and the volume-stimulated plasma concentrations o f atrial natriuretic peptide (ANP) were low in two Finnish patients with G o r d o n ' s s y n d r o m e [2]. Recently, S e m m e k rot and his coworkers [3] infused A N P into a 14-year-old boy and did not find any effect on electrolyte excretion. T h e y suggested that lack o f sensitivity to A N P offers a new
Offprint requests to: M. V'ilimiki
pathophysiological concept in G o r d o n ' s syndrome [3]. W e tested this hypothesis in our two patients.
Patients and methods The patients have been described in detail previously [2]. They were a sister and a brother, 19 and 18 years of age. At the time of the diagnosis both of them had mild hyperkalaemia (5.8 and 5.3 mmol/1), hyperchloraemia (112 mmol/1 in both) and mild acidosis (plasma total COz content 20 mmol/1 in both). The sister had hypertension and hyporeninaemia. Her raised blood pressure as well as hyperkalaemia and acidosis were promptly corrected by hydrochlorothiazide, and the treatment was discontinued several months before ANP infusion. Eleven healthy male volunteers, aged 27-53 (mean = 34) years, served as controls, The study protocol was approved by our ethical committees. The subjects continued their normal diet until the morning of the study. After eating their usual breakfast, they drank 200 ml of tap water every hour until the start of the study (1300 hours) to ensure continuous diuresis. Thereafter they ingested 100 ml every haft hour until the end of the 1.5-h study period (1430 hours). They did not eat lunch. At the beginning of the experiment (1300 hours) the subjects passed urine. They remained upright for 30 rain, lying supine thereafter for 60 min until the end of the study except for short periods for passing urine. After a 30-rain supine rest, cz-hANP (Bissendorf Peptide, Wedemark, FRG) was infused intravenously in 0.9% sodium chloride as described previously [4]. c~-hANP was given as a bolus of 125 ng/kg body weight, followed by an infusion of 50 ng/kg per minute for 30 min from 1400 to 1430 hours. Urine was collected from 1300 to 1400 hours and from 1400 to 1430 hours. The GFR was measured by the endogenous clearance of creatinine. Plasma aldosterone was measured using a radioimmunoassay (RIA) kit from Sorin International CIS (St. Quentine Yvelines Cedex, France). In plasma renin assay angiotensin I was measured using a RIA kit obtained from Medix (Espoo, Finland). Plasma atrial natriuretic peptide was determined as described before [5].
Results In the patients the basal and peak levels o f A N P were 16 and 18 pg/ml and 524 and 638 pg/ml, respectively. In the controls they ranged from 10 to 86 pg/ml (median = 34) and from 54 to 682 pg/ml (median = 360), respectively. As presented in Table 1, the infusion o f r increased the urinary volume and the excretion o f sodium similarly in the
45 Table 1. The urinary volume, the excretion of sodium and potassium, and the glomenflar filtration rate in the patients and the controls before and during atrial natriuretic peptide (ANP) infusion
TaMe 2. Serum potassium, plasma total CO2 content, renin activity and aldosterone in the patients before and after ANP infusion Sister
Sister Urine volume (ml/h) Before During Sodium excretion (mmol/h) Before During
320 980
Brother
280 740
Controls (n = 11) Median (range) 218 (52-405) 543 (350-972)
4.1 32.4
5.3 19.2
6.3 (2.3-19.7) 19.7 (4.4-41.0)
Potassium excretion (mmol/h) Before 8.3 During 6.9
3.6 3.2
4.0 (1.6-10.1) 3.4 (1.6-6.8)
Glomerular filtration rate (ml/min) B efore 112 During 147
94 157
m
m
patients and the controls. In the sister the response to cz-hANP seemed to be even exaggerated. However, the excretion of potassium did not change significantly in either the patients or the controls (Table 1). GFR was measured only in the patients and was found to be increased (Table 1). Blood pressure remained stable in the brother and the controls (data not shown) but fell from 120/95 to 100/85 mmHg in the sister. As shown in Table 2, short-term infusion of c~-hANP had no effect on serum potassium levels or the plasma CO2 content in the patients. In the sister, the serum aldosterone level fell from 321 pmol/1 before infusion to 124 pmol/1 after infusion but remained stable in the brother. In neither of the patients did plasma renin levels change during infusion (Table 2).
Discussion A lack of natriuretic or chlorouretic factors has been suggested as a pathophysiological concept in Gordon's syndrome [1]. This may mean either a quantitative deficiency of these factors or a resistance to their action, or both. In our earlier report we described low basal and volumestimulated plasma concentrations of ANP in the present patients [2]. Tunny et al. [6] also described one patient with
Potassium (mmol/1) CO2 content (mmol/1) Renin ([.tg 1-1 h -1) Aldosterone (pmol/1)
Brother
before
after
before
after
4.9 20
Pediatr Nephrol (1992) 6:44-45 9 IPNA 1992
Original article Normal renal sensitivity to atrial natriuretic peptide in Gordon's syndrome Matti V'filimikil, Risto Pelkonenl, Ilkka Tikkanen2, and Frej Fyhrquist2 1 Third and 2 Fourth Departments of Medicine, University Central Hospital of Helsinki, SF-00290 Helsinki, Finland Received September 4, 1990; received in revised form May 16, 1991; accepted May 20, 1991
Abstract. To test the hypothesis that renal sensitivity to atrial natriuretic peptide (ANP) is impaired in G o r d o n ' s s y n d r o m e (hypertension and hyperkalaemia with normal glomerular filtration rate) we infused o~-hANP into two patients with this syndrome (a sister and a brother, 19 and 18 years o f age). For comparison, 11 healthy volunteers were also examined. The infusion of a - h A N P increased urinary v o l u m e and excretion o f sodium similarly in the patients and controls. The excretion o f potassium did not change in either the patients or the controls. The infusion of o~-hANP had no effect on the serum potassium levels or the plasma CO2 content in the patients. The present results do not confirm the hypothesis o f lack of sensitivity to A N P as a pathophysiological concept in G o r d o n ' s syndrome.
Key words: G o r d o n ' s s y n d r o m e - Atrial natriuretic h o r m o n e - Hypertension - Hyperkalaemia - Acidosis
Introduction G o r d o n ' s s y n d r o m e [hypertension and hyperkalaemia with normal glomerular filtration rate (GFR)] is a rare disorder in which hyperkalaemia o f renal origin occurs in the absence o f g l o m e m l a r insufficiency or renal sodium wasting, and in which hyperchloraemic acidosis, hypertension and hyporeninaemia coexist [ 1]. The pathophysiological mechanism underlying the syndrome is incompletely understood. A lack o f natriuretic or chlorouretic factors has been suggested [1]. Accordingly, we pointed out that both the basal and the volume-stimulated plasma concentrations o f atrial natriuretic peptide (ANP) were low in two Finnish patients with G o r d o n ' s s y n d r o m e [2]. Recently, S e m m e k rot and his coworkers [3] infused A N P into a 14-year-old boy and did not find any effect on electrolyte excretion. T h e y suggested that lack o f sensitivity to A N P offers a new
Offprint requests to: M. V'ilimiki
pathophysiological concept in G o r d o n ' s syndrome [3]. W e tested this hypothesis in our two patients.
Patients and methods The patients have been described in detail previously [2]. They were a sister and a brother, 19 and 18 years of age. At the time of the diagnosis both of them had mild hyperkalaemia (5.8 and 5.3 mmol/1), hyperchloraemia (112 mmol/1 in both) and mild acidosis (plasma total COz content 20 mmol/1 in both). The sister had hypertension and hyporeninaemia. Her raised blood pressure as well as hyperkalaemia and acidosis were promptly corrected by hydrochlorothiazide, and the treatment was discontinued several months before ANP infusion. Eleven healthy male volunteers, aged 27-53 (mean = 34) years, served as controls, The study protocol was approved by our ethical committees. The subjects continued their normal diet until the morning of the study. After eating their usual breakfast, they drank 200 ml of tap water every hour until the start of the study (1300 hours) to ensure continuous diuresis. Thereafter they ingested 100 ml every haft hour until the end of the 1.5-h study period (1430 hours). They did not eat lunch. At the beginning of the experiment (1300 hours) the subjects passed urine. They remained upright for 30 rain, lying supine thereafter for 60 min until the end of the study except for short periods for passing urine. After a 30-rain supine rest, cz-hANP (Bissendorf Peptide, Wedemark, FRG) was infused intravenously in 0.9% sodium chloride as described previously [4]. c~-hANP was given as a bolus of 125 ng/kg body weight, followed by an infusion of 50 ng/kg per minute for 30 min from 1400 to 1430 hours. Urine was collected from 1300 to 1400 hours and from 1400 to 1430 hours. The GFR was measured by the endogenous clearance of creatinine. Plasma aldosterone was measured using a radioimmunoassay (RIA) kit from Sorin International CIS (St. Quentine Yvelines Cedex, France). In plasma renin assay angiotensin I was measured using a RIA kit obtained from Medix (Espoo, Finland). Plasma atrial natriuretic peptide was determined as described before [5].
Results In the patients the basal and peak levels o f A N P were 16 and 18 pg/ml and 524 and 638 pg/ml, respectively. In the controls they ranged from 10 to 86 pg/ml (median = 34) and from 54 to 682 pg/ml (median = 360), respectively. As presented in Table 1, the infusion o f r increased the urinary volume and the excretion o f sodium similarly in the
45 Table 1. The urinary volume, the excretion of sodium and potassium, and the glomenflar filtration rate in the patients and the controls before and during atrial natriuretic peptide (ANP) infusion
TaMe 2. Serum potassium, plasma total CO2 content, renin activity and aldosterone in the patients before and after ANP infusion Sister
Sister Urine volume (ml/h) Before During Sodium excretion (mmol/h) Before During
320 980
Brother
280 740
Controls (n = 11) Median (range) 218 (52-405) 543 (350-972)
4.1 32.4
5.3 19.2
6.3 (2.3-19.7) 19.7 (4.4-41.0)
Potassium excretion (mmol/h) Before 8.3 During 6.9
3.6 3.2
4.0 (1.6-10.1) 3.4 (1.6-6.8)
Glomerular filtration rate (ml/min) B efore 112 During 147
94 157
m
m
patients and the controls. In the sister the response to cz-hANP seemed to be even exaggerated. However, the excretion of potassium did not change significantly in either the patients or the controls (Table 1). GFR was measured only in the patients and was found to be increased (Table 1). Blood pressure remained stable in the brother and the controls (data not shown) but fell from 120/95 to 100/85 mmHg in the sister. As shown in Table 2, short-term infusion of c~-hANP had no effect on serum potassium levels or the plasma CO2 content in the patients. In the sister, the serum aldosterone level fell from 321 pmol/1 before infusion to 124 pmol/1 after infusion but remained stable in the brother. In neither of the patients did plasma renin levels change during infusion (Table 2).
Discussion A lack of natriuretic or chlorouretic factors has been suggested as a pathophysiological concept in Gordon's syndrome [1]. This may mean either a quantitative deficiency of these factors or a resistance to their action, or both. In our earlier report we described low basal and volumestimulated plasma concentrations of ANP in the present patients [2]. Tunny et al. [6] also described one patient with
Potassium (mmol/1) CO2 content (mmol/1) Renin ([.tg 1-1 h -1) Aldosterone (pmol/1)
Brother
before
after
before
after
4.9 20
