Scandinavian Journal of Clinical and Laboratory Investigation
ISSN: 0036-5513 (Print) 1502-7686 (Online) Journal homepage: http://www.tandfonline.com/loi/iclb20
Glomerular filtration rate in pregnancy: a study in normal subjects and in patients with hypertension, preeclampsia and diabetes E. Krutzén, P. Olofsson, S.-E. Bäck & P. Nilsson-Ehle To cite this article: E. Krutzén, P. Olofsson, S.-E. Bäck & P. Nilsson-Ehle (1992) Glomerular filtration rate in pregnancy: a study in normal subjects and in patients with hypertension, preeclampsia and diabetes, Scandinavian Journal of Clinical and Laboratory Investigation, 52:5, 387-392 To link to this article: http://dx.doi.org/10.3109/00365519209088374
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 55
View related articles
Citing articles: 5 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=iclb20 Download by: [Deakin University Library]
Date: 09 November 2015, At: 10:59
Scand J Clin Lab Invest 1992; 52: 387-392
Glomerular filtration rate in pregnancy: a study in normal subjects and in patients with hypertension, preeclampsia and diabetes E. KRUTZEN, P. OLOFSSON,* S.-E. BACK & P. NILSSON-EHLE
Downloaded by [Deakin University Library] at 10:59 09 November 2015
Departments of Clinical Chemistry and "Obstetrics and Gynecology, University of Lund, Lund, Sweden
Krutzen E, Olofsson P, Back S-E, Nilsson-Ehle P. Glomerular filtration rate in pregnancy: a study in normal subjects and in patients with hypertension, preeclampsia and diabetes. Scand J Clin Lab Invest 1992; 52: 387-392. We have studied renal function during pregnancy using plasma clearance of iohexol to determine the glomerular filtration rate (GFR). In normal pregnancy, GFR was elevated by 40% throughout pregnancy and during the first week post parturn, and fell to levels similar to those in nonpregnant women within 1 month. The development of GFR in diabetic pregnant women and in women with gestational hypertension was similar to that recorded in normal pregnancy. In subjects with preeclampsia the rise in GFR observed in normal pregnancy was absent, and no change in GFR was recorded after delivery. We conclude that the development of proteinuria and fluid retention typical of preeclampsia is paralleled by a deterioration of GFR. Key words: contrast media; diabetes; glomerular filtration rate; hypertension; iohexol clearance; pregnancy; renal function Peter Nilsson-Ehle, M D , Department of Clinical Chemistry, University Hospital, S-221 85 Lund, Sweden.
Pregnancy is associated with marked alterations of maternal organ functions. Changes in renal function are particularly pronounced, with marked increases in renal blood flow and glomerular filtration rate (GFR) [l-31. Complications of pregnancy may further modify the physiological changes in renal performance. In preeclampsia glomerular filtration may deteriorate [4, 51, but it is not yet established if some patients are at particular risk of developing renal dysfunction. Similarly, diabetes is associated with an increased risk of pregnancy complications. This disease carries an increased risk of development of glomerulosclerosis, lead-
ing to impaired renal function; however, in the early stages of the disease, GFR is frequently increased [6, 71. Little information is available on the changes of renal function in pregnant diabetic women. This may partly be ascribed to the cumbersome (e.g. insulin clearance) or imprecise (e.g. creatinine clearance) methods hitherto available for measurement of GFR in pregnant women. The purpose of this investigation was to compare the time-course for renal function changes in healthy and diabetic women during and after pregnancy; to describe alterations in GFR in patients developing hypertension or 387
388
E. KrutzCn et al.
preeclampsia; and to compare these findings to traditional indicators of complications during pregnancy. Precise GFR determinations were made by a new method using iohexol, a recently developed X-ray contrast medium, as a marker for GFR [8].
MATERIALS AND METHODS
Downloaded by [Deakin University Library] at 10:59 09 November 2015
Subjects We studied 13 healthy women with uncomplicated pregnancies, eight women with gestational hypertension (blood pressure 2 140/90 mmHg for at least three consecutive days; measured with a broad cuff in subjects with arm circumferences 232 cm), 12 women with preeclampsia (hypertension asabove in combination with proteinuria) and 20 diabetic pregnant women. Maternal clinical data are shown in Table I. Five of the women in the hypertensive group were initially normotensive but developed gestational hypertension during the third trimester. Three had essential hypertension with superimposed gestational hypertension. Eleven of the women with preeclampsia developed hypertension and proteinuria ( 2 0 . 3 g protein I-' urine) during the last trimester. One of the preeclamptic women had essential hypertension. There were no coincident complications that were considered of importance for renal function. Three of the diabetic women were classified as White class AB (one diagnosed during early pregnancy), one class B, seven class C, four class D, and five class F. The mean duration of diabetes was 12.3 years. There was no case of
essential hypertension, but one woman developed gestational hypertension, two preeclampsia and one eclampsia. Three women had urinary tract infections, but otherwise there were no coincident complications that were considered to be of importance for renal function. At a 2-6 months follow-up post parturn, two women had persistent hypertension, one with proteinuria as well. There were two preterm deliveries in the hypertensive group, three in the preeclamptic group (all before 30 weeks), and one in the normal pregnancy group. One severely growthretarded infant (27 weeks, 490 g, in the hypertensive group) died due to respiratory distress syndrome.
Blood sumpling and laboratory investigations Serial determinations at different gestational ages were performed in most subjects, but since hypertension and preeclampsia occur late in pregnancy, data from this group were only obtained in the third trimester. When possible, investigations were also performed L month post partum and 6-24 months postpartum, i.e. when all women had stopped breast feeding. GFR was determined by measurement of iohexol clearance, as described by Krutzen et al. [Sl. An injection of 5 ml iohexol (Nycomed AS, Oslo, Norway) was given in an antecubital vein, and samples for determination of iohexol plasma concentrations were drawn after 180, 200, 220 and 240 min to allow calculation of plasma clearance. GFR is expressed as ml (minx1.73 m2)-' body surface area. The reference ranges for GFR [ X l - 150 ml(min x 1.73m2)-' body surface area] were derived from
TABLE I. Clinical maternal data of 13 healthy (A), eight hypertensive (B), 12 preeclamptic (C), and 20 diabetic women (D), studied with iohexol clearance during pregnancy -
Maternal age (years) Maternal prepregnancy weight (kg) Weight gain during pregnancy (kg) Weight gain in % of prepregnancy weight Data are given as mean (range).
~
A
B
C
D
31.5 (24-40)
31.1 (24-38)
57.4
72.5 (5547)
31.2 (23-41) 61.2 (44- xs ) 11.9 (3.5-21) 20.X (4-36)
21.9 (21-37) 62.6 (42-X9)
(4% 7 1) 12. I (8- I X ) 21.2 (13-2X)
9.4 (4.4- 15.5) 12.9
(7- 17)
11.7 (2.5- 17) 19.2 (5-34)
Downloaded by [Deakin University Library] at 10:59 09 November 2015
Glornerular filtration rate in pregnancy observations in 21 healthy non-pregnant women with a mean age of 28.6 years (range 20-42). Concentrations of albumin in urine and serum, urate and creatinine in serum and thrombocytes and HbAI, in blood were measured with methods routinely used at the Department of Clinical Chemistry. Wilcoxon's rank sum test was used to evaluate differences between groups. The study was approved by the Ethics Committee of the University of Lund. The women gave their written consent to the investigation.
RESULTS Figure 1 illustrates G F R in healthy women during and after uncomplicated pregnancies. During the second and third trimester G F R was significantly higher than in the reference group (p
ISSN: 0036-5513 (Print) 1502-7686 (Online) Journal homepage: http://www.tandfonline.com/loi/iclb20
Glomerular filtration rate in pregnancy: a study in normal subjects and in patients with hypertension, preeclampsia and diabetes E. Krutzén, P. Olofsson, S.-E. Bäck & P. Nilsson-Ehle To cite this article: E. Krutzén, P. Olofsson, S.-E. Bäck & P. Nilsson-Ehle (1992) Glomerular filtration rate in pregnancy: a study in normal subjects and in patients with hypertension, preeclampsia and diabetes, Scandinavian Journal of Clinical and Laboratory Investigation, 52:5, 387-392 To link to this article: http://dx.doi.org/10.3109/00365519209088374
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 55
View related articles
Citing articles: 5 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=iclb20 Download by: [Deakin University Library]
Date: 09 November 2015, At: 10:59
Scand J Clin Lab Invest 1992; 52: 387-392
Glomerular filtration rate in pregnancy: a study in normal subjects and in patients with hypertension, preeclampsia and diabetes E. KRUTZEN, P. OLOFSSON,* S.-E. BACK & P. NILSSON-EHLE
Downloaded by [Deakin University Library] at 10:59 09 November 2015
Departments of Clinical Chemistry and "Obstetrics and Gynecology, University of Lund, Lund, Sweden
Krutzen E, Olofsson P, Back S-E, Nilsson-Ehle P. Glomerular filtration rate in pregnancy: a study in normal subjects and in patients with hypertension, preeclampsia and diabetes. Scand J Clin Lab Invest 1992; 52: 387-392. We have studied renal function during pregnancy using plasma clearance of iohexol to determine the glomerular filtration rate (GFR). In normal pregnancy, GFR was elevated by 40% throughout pregnancy and during the first week post parturn, and fell to levels similar to those in nonpregnant women within 1 month. The development of GFR in diabetic pregnant women and in women with gestational hypertension was similar to that recorded in normal pregnancy. In subjects with preeclampsia the rise in GFR observed in normal pregnancy was absent, and no change in GFR was recorded after delivery. We conclude that the development of proteinuria and fluid retention typical of preeclampsia is paralleled by a deterioration of GFR. Key words: contrast media; diabetes; glomerular filtration rate; hypertension; iohexol clearance; pregnancy; renal function Peter Nilsson-Ehle, M D , Department of Clinical Chemistry, University Hospital, S-221 85 Lund, Sweden.
Pregnancy is associated with marked alterations of maternal organ functions. Changes in renal function are particularly pronounced, with marked increases in renal blood flow and glomerular filtration rate (GFR) [l-31. Complications of pregnancy may further modify the physiological changes in renal performance. In preeclampsia glomerular filtration may deteriorate [4, 51, but it is not yet established if some patients are at particular risk of developing renal dysfunction. Similarly, diabetes is associated with an increased risk of pregnancy complications. This disease carries an increased risk of development of glomerulosclerosis, lead-
ing to impaired renal function; however, in the early stages of the disease, GFR is frequently increased [6, 71. Little information is available on the changes of renal function in pregnant diabetic women. This may partly be ascribed to the cumbersome (e.g. insulin clearance) or imprecise (e.g. creatinine clearance) methods hitherto available for measurement of GFR in pregnant women. The purpose of this investigation was to compare the time-course for renal function changes in healthy and diabetic women during and after pregnancy; to describe alterations in GFR in patients developing hypertension or 387
388
E. KrutzCn et al.
preeclampsia; and to compare these findings to traditional indicators of complications during pregnancy. Precise GFR determinations were made by a new method using iohexol, a recently developed X-ray contrast medium, as a marker for GFR [8].
MATERIALS AND METHODS
Downloaded by [Deakin University Library] at 10:59 09 November 2015
Subjects We studied 13 healthy women with uncomplicated pregnancies, eight women with gestational hypertension (blood pressure 2 140/90 mmHg for at least three consecutive days; measured with a broad cuff in subjects with arm circumferences 232 cm), 12 women with preeclampsia (hypertension asabove in combination with proteinuria) and 20 diabetic pregnant women. Maternal clinical data are shown in Table I. Five of the women in the hypertensive group were initially normotensive but developed gestational hypertension during the third trimester. Three had essential hypertension with superimposed gestational hypertension. Eleven of the women with preeclampsia developed hypertension and proteinuria ( 2 0 . 3 g protein I-' urine) during the last trimester. One of the preeclamptic women had essential hypertension. There were no coincident complications that were considered of importance for renal function. Three of the diabetic women were classified as White class AB (one diagnosed during early pregnancy), one class B, seven class C, four class D, and five class F. The mean duration of diabetes was 12.3 years. There was no case of
essential hypertension, but one woman developed gestational hypertension, two preeclampsia and one eclampsia. Three women had urinary tract infections, but otherwise there were no coincident complications that were considered to be of importance for renal function. At a 2-6 months follow-up post parturn, two women had persistent hypertension, one with proteinuria as well. There were two preterm deliveries in the hypertensive group, three in the preeclamptic group (all before 30 weeks), and one in the normal pregnancy group. One severely growthretarded infant (27 weeks, 490 g, in the hypertensive group) died due to respiratory distress syndrome.
Blood sumpling and laboratory investigations Serial determinations at different gestational ages were performed in most subjects, but since hypertension and preeclampsia occur late in pregnancy, data from this group were only obtained in the third trimester. When possible, investigations were also performed L month post partum and 6-24 months postpartum, i.e. when all women had stopped breast feeding. GFR was determined by measurement of iohexol clearance, as described by Krutzen et al. [Sl. An injection of 5 ml iohexol (Nycomed AS, Oslo, Norway) was given in an antecubital vein, and samples for determination of iohexol plasma concentrations were drawn after 180, 200, 220 and 240 min to allow calculation of plasma clearance. GFR is expressed as ml (minx1.73 m2)-' body surface area. The reference ranges for GFR [ X l - 150 ml(min x 1.73m2)-' body surface area] were derived from
TABLE I. Clinical maternal data of 13 healthy (A), eight hypertensive (B), 12 preeclamptic (C), and 20 diabetic women (D), studied with iohexol clearance during pregnancy -
Maternal age (years) Maternal prepregnancy weight (kg) Weight gain during pregnancy (kg) Weight gain in % of prepregnancy weight Data are given as mean (range).
~
A
B
C
D
31.5 (24-40)
31.1 (24-38)
57.4
72.5 (5547)
31.2 (23-41) 61.2 (44- xs ) 11.9 (3.5-21) 20.X (4-36)
21.9 (21-37) 62.6 (42-X9)
(4% 7 1) 12. I (8- I X ) 21.2 (13-2X)
9.4 (4.4- 15.5) 12.9
(7- 17)
11.7 (2.5- 17) 19.2 (5-34)
Downloaded by [Deakin University Library] at 10:59 09 November 2015
Glornerular filtration rate in pregnancy observations in 21 healthy non-pregnant women with a mean age of 28.6 years (range 20-42). Concentrations of albumin in urine and serum, urate and creatinine in serum and thrombocytes and HbAI, in blood were measured with methods routinely used at the Department of Clinical Chemistry. Wilcoxon's rank sum test was used to evaluate differences between groups. The study was approved by the Ethics Committee of the University of Lund. The women gave their written consent to the investigation.
RESULTS Figure 1 illustrates G F R in healthy women during and after uncomplicated pregnancies. During the second and third trimester G F R was significantly higher than in the reference group (p
