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Chronic renal disease and pregnancy
Chronic renal disease and pregnancy Case report of azotemia, hemodialysis, and delivery of viable infant
KARL R. HERWIG, M.D.* JOHN P. MERRILL, M.D. RUBY L. JACKSON, M.D. DONALD E. OKEN, M.D. Boston, Massachusetts
we had the opportunity of caring for a pregnant woman who had developed severe azotemia in the last trimester of pregnancy. The fetal heart tones were full and regular, and we assumed that the fetus might be viable if pregnancy could be prolonged. Because of the high fetal mortality rate associated with azotemia of such a degree, a program of periodic hemodialysis was undertaken in an attempt to improve the likelihood of providing a live infant. This case illustrates the fact that fetal death does not always occur when the mother is severely azotemic. We believe this to be the first successful attempt to use repeated hemodialysis in a pregnant woman with chronic renal failure who eventually delivered a viable infant.
lwen noted during the third month of gestation, at which time she was treated with Rauwolfia alkaloid. Peripheral edema and a 20 pound weight gain occurred in the sixth month of pregnancy. Treated with chlorothiazide, she lost 10 pounds of weight and the blood pressure decreased to 140 j80. During this time, however, she developed an intractable cough and shortness of breath for which she was ultimately hospitalized. The nonprotein nitrogen was reported to be 47 mg. per cent. Urinalysis revealed 3+ proteinuria and 20 to 30 red blood cells per high power microscopic field. Three days later, one week before referral to this hospital, the nonprotein nitrogen had risen to 127 mg. per cent. The first 3 pregnancies had been uncomplicated. During the fourth pregnancy, however, 5 years before the present one, she developed albuminuria of 450 mg. per cent, although the nonprotein nitrogen was only 35 mg. per cent and there were no other complications. She had not consulted a physician between pregnancies, so that it is unknown whether the urinary abnormalities persisted after pregnancy. At the time of admission to the Peter Bent Brigham Hospital, the blood pressure was 140/85. The uterus was enlarged to the expected size and fetal heart tones were regular at 140 beats per minute. The skin was dry, waxy, and darkened. Retinal examination showed minimal arteriovenous compression. The heart was of normal size but an apical systolic murmur was present which was thought to be hemic in origin. There was no evidence of congestive heart failure or peripheral edema. The remainder of the physical examination was within normal limits.
REcENTLY
Case report A 33-year-old housewife was admitted to the Peter Bent Brigham Hospital during the thirtysecond week of her fifth pregnancy because of azotemia. Pyuria, proteinuria, and blood pressure elevation to 170 systolic and 90 diastolic had From the Departments of Medicine and Obstetrics, Harvard Medical School, the Cardiorenal Laboratory, Peter Bent Brigham Hospital, and the Department of Obstetrics, Boston Lying-In Hospital. This work supported in part bv the Public Health Service Grant No. 5ROI-HE-08260-0l. *Present address: Uni1•enity Ho>pital. Ann Arbor, Michigan.
1117
1118
80
90"
7.5
80
~
70
70
~
65
60
'
z
~
August Ll. 19(i.-, .\Ill .
1001
" 50~ "'
Herwig et a/.
c
BUN
60
55
I
40:....
5.0
30 ~
45
I
20 ~
4.0 35
25
27 29
31
30
Fig. 1. Blood urea nitrogen (BUN) and serum creatinine concentrations of the mother in the pre~ and postpartum period. BUN is depicted hy circles.
.f.
Ob~t. & {~\Ill'(',
The blood urea nitrogen t'Oil<'l'lllration of tlw infant fell to 10 mg. pt'r cent within 3 dan. while that of the mother filS<' slowly aftn delivery to 76 mg. per rent 4 davs post parttllll. The serum creatinine concentration at this time wa' 7.6 mg. pn cent. Cystoscopy and rl'lrograde pyelogram revealed small contracted kidn1'\' with normal calyc1·s. The artniovenous 'hunt wa.' n·movcd, and the patient w;IS dischar,l(·l·d o11 th1· fourteenth postpartum cby. At the time nf this \\Titing. ti months after tfw deliwn, tlw infant is Wl'll and apparently has .suffer.·d 1111 ill 1'ffects. The mother, hu\1·1·n-r. sho\\·s "'\.I'll' renal inSitfficiency with a l,lood mea nitrng1·n CIHICt'lltration nf I 93 mg. per C<'lll and ;111 1'11dogenous creatinilll· clearann· of 2 1111. p•·r lllin11!1'.
Comment
Laboratory findings included a hematocrit of 28.5 per cent, blood urea nitrogn1 of I 04 mg. pN cent, normal serum dectrolytes except for a depressed blood CO" content of 16 mM. JWr liter, uric acid 9.4 mg. per cent, serum creatinine 7.8 mg. per cent, and serum cholesterol 398 mg. per cent. Total serum proteins were 6.6 Gm. prr crnt with a 1.7: I albumin to globulin ratio. Corrrcted erythrocyt<' sedimentation rate was 32 mm. per hour. Urinalysis showed 3+ pro~ teinuria and a few red blood cells. The creatinine clearance was 8 mi. per minute. Urine osmolality ranged from 220 to 320 mOsm. per kilogram. The urine was sterile. Two lupus prythematosus preparations were ncgatiw. An artPriovt>nous shunt was placed in the lt>ft forearm to facilitate repeated hemodialys:s. Dialysis was performed 4 tirnt>s during the next 3 weeks with the use of a singlP coil of a twin coil artificial kidney (Fig. l). Following th1' first dialysis, the utPrus ht>came tense and mild uterine contractions ensued. The contractions subsided in the nrxt 12 hours. Pregnancy was terminated by cesarean sPrtion 3 wet>ks aftn dialysis was instituted. ThP placf'nta was noted to be normal in both gross and microscopic appearance; the amnion contained 6 L. of fluid. Exploration of the abdomen revealPd small, firm kidneys without hydronephrosis. Tubular ligation for sterilization was performed. The infant weig-hed 4 pounds, 10 ounces and was activP. The blood urea nitrogen concentration of the infant and mother was 56 mg. per cent and that of the amniotic fluid 76 mg. per cent. The postoperativP period was uncomplicatPd.
Toxemia of pregnancy 1s an archaic term applied to the complex of edema, proteinuria, and hypertension usually occurring after the twenty-fourth week of gestation. 1 The term remains in general use even though it dot's not describe the underlying pathophysiology. Toxemia is classified as being a primarv complication of pregnancy or secondary to renal cardiovascular disease which is usually present before conception occurs." Pregnancv and chronic renal disease are rarely seen together, however, the incidence having been reported to vary bctw·een 0.0-l- per cent and ~i per cent of all pregnancies."· 1 ''· " · 1 ' If proteinuria and edema occur before the twentyfourth week of gestation or if present before conception, one must consider intrinsic renal disease to be present."' The frequency with which renal disease is reported to be associated with toxemia varies from 2 per cent to 25 per cent.'- '· ''· 18 The lower figure is fwm more n'Ct'nt literature and probably represents a truer figure. Those patients who do conceive have a high incidence of spontaneous abortion, toxemia, and stillbirths. Frequently, when renal disease is severe, thev de\'t'lop apparent progression of their renal clisea<;e and azotemia. Because of these complications there is an increased mortality:'· '' Pregnancy is a very delicate test of renal function."' During- pregnancy, the glomerular filtration rate normally incrPases ahout :)()
VoimiH' ~:.! ~ltmber
B
pvr cent while renal blood flow increases by SO per cent."" These parameters of renal
function reach their peak by the fifth month of gestation and then return toward normal, hut because the renal blood flow decreases toward normal faster than the glomerular filtration rate, the filtration fraction is particularly increased in the last trimester. u• When a woman with underlying renal disease becomes pregnant, however, she does not respond to the stress of pregnancy as a normal woman can. Werko"" found that women with chronic renal disease not characterized by nitrogen retention do show a rise in glomerular filtration rate and renal blood flow. One must be aware, however, that their glomerular filtration rate and renal blood flow not only are abnormal at the beginning of pregnancy but also fail to exhibit as great a physiologic increase as that of normal women. Since none of his cases had renal disease of sufficient severity to cause azotemia, however, he could draw no conclusion as to the changes in glomerular filtration rate and renal blood flow which occur during pregnancy in azotemic patients. Many investigators state that pregnancy has a deleterious effect on the maternal renal disease."· 7 • 11 • " 0 • ~~In MacKay's 11 series, renal impairment was permanent in 27 per cent of 90 patients who showed deterioration of renal function with pregnancy. Whether this was the result of pregnancy or manifested natural progression of the patient's renal Jisease could not be determined. 11 Other investigators hold to the opinion that pregnancy has no permanent deleterious effect on renal disease.'"·'· 1 "· 17 • "" It is difficult, howeYer. to compare these two conflicting views because reference is rarely made to the type and degree of renal disease present. Parsons 1 n had 4 patients with urea clearances of 40 per cent who showed no increased renal impairment with pregnancy. Goodall," in 1933, presented 5 cases of "nephritis" which actually improved symptomatically and functionally during pregnancy. Unfortunately, no detail of the cause of the "nephritis" was reported. When chronic renal disease presents as the nephrotic syndrome during pregnancy,
Chronic renal disease and pregnancy
1119
the prognosis is much better. Most observers find no deleterious effects on renal function, and the process often is remediable with steroids.t''· 1 ' It is apparent, however, that the effects of pregnancy on other types of renal disease are not definitely known. The state of the renal disease prior to conception may be of significance in determining the subsequent course. It must be recognized that women with chronic renal disease can become pregnant, though many observers state that they are usually infertile. 1 e. 14 • 18 With azotemia there is an increased incidence of prematurity and stillbirths which is attributed to placental ischemia. The placenta usually is small, fibrotic, and frequently infarcted. "1 The ultimate factor influencing fetal sun·ival is the adequacy of blood flow through the placenta. This, in turn, depends on uterine blood flow and the function of the placenta itself.'' In a large series of patients with renal impairment collected over a 10 year period by MacKay, 11 the over-all fetal mortality was 39 per cent, an incidence much less than the 72 per cent found by Hamilton" 10 years earlier. Sabin, Parliament, and Stream," in a recent large series of pregnant patients with prior renal disease, found a fetal mortality rate of 63 per cent. It is remarkable, however, that in MacKay's 11 series no patient with azotemia to the degree of a blood urea of 60 mg. per cent or over was delivered of a live baby. The approach to therapy of pregnant women with chronic renal disease varies. Dieckmann, McCartney, and Harrod" haw always believed that patients with nephrosclerosis, chronic glomerulonephritis, or chronic pyelonephritis should have abortions because of the high pregnancy loss and the incidt'nce of renal damage which results when the pregnancy is continued. Herrick, 7 in 1938, states that "except for syphilis no malady so threatens the life of the fetus as chronic nephritis. Whenever nitrogen retention or albuminuria are present speedy fetal death can be predicted." Kuder and Stander10 , in 1934, advocated radical treatment consisting of termination of pregnancy with sterilization for all
Au~ml 1.).
1120 Herwig et al.
patients with chronic nephritis. Again, documentation to support these views is sparse. A more conservative approach can be followed with diet regulation, rest, diuretics, and antihypertensive drugs used as indicated. Progesterone or its derivatives can be used in an attempt to maintain placental function.'' One must, however, be constantly alert to the development of symptoms of preeclampsia or azotemia. Tenny and Dandrow~ 1 state that the infant must be delivered if the mother's serum nonprotein nitrogen rises to a value greater than 60 mg. per cent and remains elevated for one week. The viability of the infant is not considered. Even if such infants live until term, there is a high fetal loss during labor and in the neonatal period. On the other hand, because of the danger of intrauterine death during the last ~ weeks of pregnancy. patients with definite renal disease should be delivered at :)6 weeks of gestation.~'
The state of this patient's renal function just prior to pregnancy is unknown. It is presumed, however. that she did not have significant azotemia at the time of conception since the nonprotein nitrogen was only ~5 mg. per cent at the twenty-sixth week of pregnancy. The presence of proteinuria in the third month of gestation indicates that renal disease was present at that time. The etiology of this renal disease has not been ascertained with certainty, although the finding of contracted kidneys without calyceal deformity, microscopic hematuria, and marked proteinuria suggest that chronic glomerulonephritis is the basic lesion. The blood urea nitrogen content rose at an alarming rate at 30 weeks of gestation reaching 10~ mg. per cent 2 weeks later. Whether the
REFERENCES
1. Assali, N. S.: Toxemia of pregnancy. Address to Obstetrical and Gynecological Assembly of Southern California, 1953. 2. Dieckmann, W. J.: The toxemia of pregnancy, St. Louis, 1952, The C. V. Mosby Company. 3. Dieckmann. W. J., McCartney, C. P., and Harrod, J. P., Jr.: A11>r. ]. 0BST. & GYNEC. 75: 643, 1958.
\ru.
J.
19ii:i
()h..,t. & Cyrw<".
rapid development of azotemia may he attributed to a deleterious effect of pregnancy on the renal disease or to a natural progression of the renal disease was not dt>monstrated. From previous experience and from reports in the literature, the probability of obtaining a viable baby at :12 weeks of gc~ tation with conservative therapy is small. With consideration of the known deleterious effects of maternal uremia on fetal survival. hemodialysis was attempted in the hope of improving the fetal environment and obtaining a live infant at 36 weeks of gestation. There appeared to be little additional risk to the mother in delaying delivery for an additional 3 weeks under close medical observation. Hemodialysis rather than peritoneal dialysis was chosen because of the technical difficulty encountered in pregnant women with the latter techniq ue.l.' Regional heparinization was used to decrease the chance of hidden bleeding from abruptio placentae to which thesP patiPnts are predisposed." Having been maintained with intermittent hemodialysis for :'1 weeks, she was delivered of a viable infant. Because one cannot predict the course of the chronic renal disease in individual patients with any accuracy, little can be said of the eiTects on the mother of the prolongation of pregnancy. Renal functional impairment has progressively increased in the postpartum period. however, to the point of severe urenua. Summary
A case of chronic renal disease, azotemia. and pregnancy is presented. The pertinent literature is reviewed. The use of intermittent hemodialysis is described as an adjunct in the therapy of these patients.
4. Gibson, G. B., and Platt. R.: Brit. M. ]. II: 159, 1959. 5. Coodall, J. R.: AM. J. OnsT. & Gv;o;Ec. 26: 556, 1933. 6. Hamilton, F. H.: J. Obst. & Gynaec. Brit. Emp. 59: 25. 1952. 7. Herrick. W. W.: Bull. New York Acad. Mf•d. 14: 129, 1939. il. Hooper. J .. Jr., Farquhar. M. C., Yamauchi,
Chronic renal disease and pregnancy
Volume Y2 Number B
H., Moon, H. D., and Page, E. W.: Obst. & Gynec. 17: 271, 1961. 9. Kerr, D. N. S., and Elliott, W.: Practitioner
34: 5, 1963. 10. Kuder, K., and Stander, J.: New York State J. Med. 34: 5, 1934. 11. MacKay, E. V.: Australian & New Zealand J. Obst. & Gynaec. 3: 21, 1963. 12. Madsin, J. R., and Anderson, G. V.: Obst. & Gynec. 18: 492, 1964. 13. Marcus, S. L.: Obst. & Gynec. 18: 511, 1963. 14. Mateer, F. M., Borecky, D. C., Balash, W. R., Bonessi, J. V., and Danowski, T. S.: AM. J. 0BST. & GYNEC. 86: 249, 1963. 15. Merrill, J. P.: Unpublished data. 16. Parsons, F. M.: Proc. Roy. Soc. Med. 56: 111, 1963. 17. Sabin, M., Parliament, D., and Stream, G. J.: ...............
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18. Schewitz, L. J., Siftel, H. C., and Icasson, C.: South African M. J. 35: 341, 1961. 19. Sims, E. A.. H.: ~rhe kidney in pregnancy. In Strauss, M. B., and Welt, L. G., editors: Disease of the kidney, Boston, 1963, Little Brown & Company. 20. Sims, E. A. H.: Ann. Int. Med. 52: 693, 1960. 21. Tenny, B., and Dandrow, R. V.: AM. J. OBsT. & GYNEC. 81: 8, 1961. 22. Tillman, A. J. B.: M. Clin. North America 35: 677, 1951. 23. Werko, L.: Acta med. scandinav. 153: 177. 1956.
721 Huntington Avenue Boston 15> Massachusetts
KARL R. HERWIG, M.D.* JOHN P. MERRILL, M.D. RUBY L. JACKSON, M.D. DONALD E. OKEN, M.D. Boston, Massachusetts
we had the opportunity of caring for a pregnant woman who had developed severe azotemia in the last trimester of pregnancy. The fetal heart tones were full and regular, and we assumed that the fetus might be viable if pregnancy could be prolonged. Because of the high fetal mortality rate associated with azotemia of such a degree, a program of periodic hemodialysis was undertaken in an attempt to improve the likelihood of providing a live infant. This case illustrates the fact that fetal death does not always occur when the mother is severely azotemic. We believe this to be the first successful attempt to use repeated hemodialysis in a pregnant woman with chronic renal failure who eventually delivered a viable infant.
lwen noted during the third month of gestation, at which time she was treated with Rauwolfia alkaloid. Peripheral edema and a 20 pound weight gain occurred in the sixth month of pregnancy. Treated with chlorothiazide, she lost 10 pounds of weight and the blood pressure decreased to 140 j80. During this time, however, she developed an intractable cough and shortness of breath for which she was ultimately hospitalized. The nonprotein nitrogen was reported to be 47 mg. per cent. Urinalysis revealed 3+ proteinuria and 20 to 30 red blood cells per high power microscopic field. Three days later, one week before referral to this hospital, the nonprotein nitrogen had risen to 127 mg. per cent. The first 3 pregnancies had been uncomplicated. During the fourth pregnancy, however, 5 years before the present one, she developed albuminuria of 450 mg. per cent, although the nonprotein nitrogen was only 35 mg. per cent and there were no other complications. She had not consulted a physician between pregnancies, so that it is unknown whether the urinary abnormalities persisted after pregnancy. At the time of admission to the Peter Bent Brigham Hospital, the blood pressure was 140/85. The uterus was enlarged to the expected size and fetal heart tones were regular at 140 beats per minute. The skin was dry, waxy, and darkened. Retinal examination showed minimal arteriovenous compression. The heart was of normal size but an apical systolic murmur was present which was thought to be hemic in origin. There was no evidence of congestive heart failure or peripheral edema. The remainder of the physical examination was within normal limits.
REcENTLY
Case report A 33-year-old housewife was admitted to the Peter Bent Brigham Hospital during the thirtysecond week of her fifth pregnancy because of azotemia. Pyuria, proteinuria, and blood pressure elevation to 170 systolic and 90 diastolic had From the Departments of Medicine and Obstetrics, Harvard Medical School, the Cardiorenal Laboratory, Peter Bent Brigham Hospital, and the Department of Obstetrics, Boston Lying-In Hospital. This work supported in part bv the Public Health Service Grant No. 5ROI-HE-08260-0l. *Present address: Uni1•enity Ho>pital. Ann Arbor, Michigan.
1117
1118
80
90"
7.5
80
~
70
70
~
65
60
'
z
~
August Ll. 19(i.-, .\Ill .
1001
" 50~ "'
Herwig et a/.
c
BUN
60
55
I
40:....
5.0
30 ~
45
I
20 ~
4.0 35
25
27 29
31
30
Fig. 1. Blood urea nitrogen (BUN) and serum creatinine concentrations of the mother in the pre~ and postpartum period. BUN is depicted hy circles.
.f.
Ob~t. & {~\Ill'(',
The blood urea nitrogen t'Oil<'l'lllration of tlw infant fell to 10 mg. pt'r cent within 3 dan. while that of the mother filS<' slowly aftn delivery to 76 mg. per rent 4 davs post parttllll. The serum creatinine concentration at this time wa' 7.6 mg. pn cent. Cystoscopy and rl'lrograde pyelogram revealed small contracted kidn1'\' with normal calyc1·s. The artniovenous 'hunt wa.' n·movcd, and the patient w;IS dischar,l(·l·d o11 th1· fourteenth postpartum cby. At the time nf this \\Titing. ti months after tfw deliwn, tlw infant is Wl'll and apparently has .suffer.·d 1111 ill 1'ffects. The mother, hu\1·1·n-r. sho\\·s "'\.I'll' renal inSitfficiency with a l,lood mea nitrng1·n CIHICt'lltration nf I 93 mg. per C<'lll and ;111 1'11dogenous creatinilll· clearann· of 2 1111. p•·r lllin11!1'.
Comment
Laboratory findings included a hematocrit of 28.5 per cent, blood urea nitrogn1 of I 04 mg. pN cent, normal serum dectrolytes except for a depressed blood CO" content of 16 mM. JWr liter, uric acid 9.4 mg. per cent, serum creatinine 7.8 mg. per cent, and serum cholesterol 398 mg. per cent. Total serum proteins were 6.6 Gm. prr crnt with a 1.7: I albumin to globulin ratio. Corrrcted erythrocyt<' sedimentation rate was 32 mm. per hour. Urinalysis showed 3+ pro~ teinuria and a few red blood cells. The creatinine clearance was 8 mi. per minute. Urine osmolality ranged from 220 to 320 mOsm. per kilogram. The urine was sterile. Two lupus prythematosus preparations were ncgatiw. An artPriovt>nous shunt was placed in the lt>ft forearm to facilitate repeated hemodialys:s. Dialysis was performed 4 tirnt>s during the next 3 weeks with the use of a singlP coil of a twin coil artificial kidney (Fig. l). Following th1' first dialysis, the utPrus ht>came tense and mild uterine contractions ensued. The contractions subsided in the nrxt 12 hours. Pregnancy was terminated by cesarean sPrtion 3 wet>ks aftn dialysis was instituted. ThP placf'nta was noted to be normal in both gross and microscopic appearance; the amnion contained 6 L. of fluid. Exploration of the abdomen revealPd small, firm kidneys without hydronephrosis. Tubular ligation for sterilization was performed. The infant weig-hed 4 pounds, 10 ounces and was activP. The blood urea nitrogen concentration of the infant and mother was 56 mg. per cent and that of the amniotic fluid 76 mg. per cent. The postoperativP period was uncomplicatPd.
Toxemia of pregnancy 1s an archaic term applied to the complex of edema, proteinuria, and hypertension usually occurring after the twenty-fourth week of gestation. 1 The term remains in general use even though it dot's not describe the underlying pathophysiology. Toxemia is classified as being a primarv complication of pregnancy or secondary to renal cardiovascular disease which is usually present before conception occurs." Pregnancv and chronic renal disease are rarely seen together, however, the incidence having been reported to vary bctw·een 0.0-l- per cent and ~i per cent of all pregnancies."· 1 ''· " · 1 ' If proteinuria and edema occur before the twentyfourth week of gestation or if present before conception, one must consider intrinsic renal disease to be present."' The frequency with which renal disease is reported to be associated with toxemia varies from 2 per cent to 25 per cent.'- '· ''· 18 The lower figure is fwm more n'Ct'nt literature and probably represents a truer figure. Those patients who do conceive have a high incidence of spontaneous abortion, toxemia, and stillbirths. Frequently, when renal disease is severe, thev de\'t'lop apparent progression of their renal clisea<;e and azotemia. Because of these complications there is an increased mortality:'· '' Pregnancy is a very delicate test of renal function."' During- pregnancy, the glomerular filtration rate normally incrPases ahout :)()
VoimiH' ~:.! ~ltmber
B
pvr cent while renal blood flow increases by SO per cent."" These parameters of renal
function reach their peak by the fifth month of gestation and then return toward normal, hut because the renal blood flow decreases toward normal faster than the glomerular filtration rate, the filtration fraction is particularly increased in the last trimester. u• When a woman with underlying renal disease becomes pregnant, however, she does not respond to the stress of pregnancy as a normal woman can. Werko"" found that women with chronic renal disease not characterized by nitrogen retention do show a rise in glomerular filtration rate and renal blood flow. One must be aware, however, that their glomerular filtration rate and renal blood flow not only are abnormal at the beginning of pregnancy but also fail to exhibit as great a physiologic increase as that of normal women. Since none of his cases had renal disease of sufficient severity to cause azotemia, however, he could draw no conclusion as to the changes in glomerular filtration rate and renal blood flow which occur during pregnancy in azotemic patients. Many investigators state that pregnancy has a deleterious effect on the maternal renal disease."· 7 • 11 • " 0 • ~~In MacKay's 11 series, renal impairment was permanent in 27 per cent of 90 patients who showed deterioration of renal function with pregnancy. Whether this was the result of pregnancy or manifested natural progression of the patient's renal Jisease could not be determined. 11 Other investigators hold to the opinion that pregnancy has no permanent deleterious effect on renal disease.'"·'· 1 "· 17 • "" It is difficult, howeYer. to compare these two conflicting views because reference is rarely made to the type and degree of renal disease present. Parsons 1 n had 4 patients with urea clearances of 40 per cent who showed no increased renal impairment with pregnancy. Goodall," in 1933, presented 5 cases of "nephritis" which actually improved symptomatically and functionally during pregnancy. Unfortunately, no detail of the cause of the "nephritis" was reported. When chronic renal disease presents as the nephrotic syndrome during pregnancy,
Chronic renal disease and pregnancy
1119
the prognosis is much better. Most observers find no deleterious effects on renal function, and the process often is remediable with steroids.t''· 1 ' It is apparent, however, that the effects of pregnancy on other types of renal disease are not definitely known. The state of the renal disease prior to conception may be of significance in determining the subsequent course. It must be recognized that women with chronic renal disease can become pregnant, though many observers state that they are usually infertile. 1 e. 14 • 18 With azotemia there is an increased incidence of prematurity and stillbirths which is attributed to placental ischemia. The placenta usually is small, fibrotic, and frequently infarcted. "1 The ultimate factor influencing fetal sun·ival is the adequacy of blood flow through the placenta. This, in turn, depends on uterine blood flow and the function of the placenta itself.'' In a large series of patients with renal impairment collected over a 10 year period by MacKay, 11 the over-all fetal mortality was 39 per cent, an incidence much less than the 72 per cent found by Hamilton" 10 years earlier. Sabin, Parliament, and Stream," in a recent large series of pregnant patients with prior renal disease, found a fetal mortality rate of 63 per cent. It is remarkable, however, that in MacKay's 11 series no patient with azotemia to the degree of a blood urea of 60 mg. per cent or over was delivered of a live baby. The approach to therapy of pregnant women with chronic renal disease varies. Dieckmann, McCartney, and Harrod" haw always believed that patients with nephrosclerosis, chronic glomerulonephritis, or chronic pyelonephritis should have abortions because of the high pregnancy loss and the incidt'nce of renal damage which results when the pregnancy is continued. Herrick, 7 in 1938, states that "except for syphilis no malady so threatens the life of the fetus as chronic nephritis. Whenever nitrogen retention or albuminuria are present speedy fetal death can be predicted." Kuder and Stander10 , in 1934, advocated radical treatment consisting of termination of pregnancy with sterilization for all
Au~ml 1.).
1120 Herwig et al.
patients with chronic nephritis. Again, documentation to support these views is sparse. A more conservative approach can be followed with diet regulation, rest, diuretics, and antihypertensive drugs used as indicated. Progesterone or its derivatives can be used in an attempt to maintain placental function.'' One must, however, be constantly alert to the development of symptoms of preeclampsia or azotemia. Tenny and Dandrow~ 1 state that the infant must be delivered if the mother's serum nonprotein nitrogen rises to a value greater than 60 mg. per cent and remains elevated for one week. The viability of the infant is not considered. Even if such infants live until term, there is a high fetal loss during labor and in the neonatal period. On the other hand, because of the danger of intrauterine death during the last ~ weeks of pregnancy. patients with definite renal disease should be delivered at :)6 weeks of gestation.~'
The state of this patient's renal function just prior to pregnancy is unknown. It is presumed, however. that she did not have significant azotemia at the time of conception since the nonprotein nitrogen was only ~5 mg. per cent at the twenty-sixth week of pregnancy. The presence of proteinuria in the third month of gestation indicates that renal disease was present at that time. The etiology of this renal disease has not been ascertained with certainty, although the finding of contracted kidneys without calyceal deformity, microscopic hematuria, and marked proteinuria suggest that chronic glomerulonephritis is the basic lesion. The blood urea nitrogen content rose at an alarming rate at 30 weeks of gestation reaching 10~ mg. per cent 2 weeks later. Whether the
REFERENCES
1. Assali, N. S.: Toxemia of pregnancy. Address to Obstetrical and Gynecological Assembly of Southern California, 1953. 2. Dieckmann, W. J.: The toxemia of pregnancy, St. Louis, 1952, The C. V. Mosby Company. 3. Dieckmann. W. J., McCartney, C. P., and Harrod, J. P., Jr.: A11>r. ]. 0BST. & GYNEC. 75: 643, 1958.
\ru.
J.
19ii:i
()h..,t. & Cyrw<".
rapid development of azotemia may he attributed to a deleterious effect of pregnancy on the renal disease or to a natural progression of the renal disease was not dt>monstrated. From previous experience and from reports in the literature, the probability of obtaining a viable baby at :12 weeks of gc~ tation with conservative therapy is small. With consideration of the known deleterious effects of maternal uremia on fetal survival. hemodialysis was attempted in the hope of improving the fetal environment and obtaining a live infant at 36 weeks of gestation. There appeared to be little additional risk to the mother in delaying delivery for an additional 3 weeks under close medical observation. Hemodialysis rather than peritoneal dialysis was chosen because of the technical difficulty encountered in pregnant women with the latter techniq ue.l.' Regional heparinization was used to decrease the chance of hidden bleeding from abruptio placentae to which thesP patiPnts are predisposed." Having been maintained with intermittent hemodialysis for :'1 weeks, she was delivered of a viable infant. Because one cannot predict the course of the chronic renal disease in individual patients with any accuracy, little can be said of the eiTects on the mother of the prolongation of pregnancy. Renal functional impairment has progressively increased in the postpartum period. however, to the point of severe urenua. Summary
A case of chronic renal disease, azotemia. and pregnancy is presented. The pertinent literature is reviewed. The use of intermittent hemodialysis is described as an adjunct in the therapy of these patients.
4. Gibson, G. B., and Platt. R.: Brit. M. ]. II: 159, 1959. 5. Coodall, J. R.: AM. J. OnsT. & Gv;o;Ec. 26: 556, 1933. 6. Hamilton, F. H.: J. Obst. & Gynaec. Brit. Emp. 59: 25. 1952. 7. Herrick. W. W.: Bull. New York Acad. Mf•d. 14: 129, 1939. il. Hooper. J .. Jr., Farquhar. M. C., Yamauchi,
Chronic renal disease and pregnancy
Volume Y2 Number B
H., Moon, H. D., and Page, E. W.: Obst. & Gynec. 17: 271, 1961. 9. Kerr, D. N. S., and Elliott, W.: Practitioner
34: 5, 1963. 10. Kuder, K., and Stander, J.: New York State J. Med. 34: 5, 1934. 11. MacKay, E. V.: Australian & New Zealand J. Obst. & Gynaec. 3: 21, 1963. 12. Madsin, J. R., and Anderson, G. V.: Obst. & Gynec. 18: 492, 1964. 13. Marcus, S. L.: Obst. & Gynec. 18: 511, 1963. 14. Mateer, F. M., Borecky, D. C., Balash, W. R., Bonessi, J. V., and Danowski, T. S.: AM. J. 0BST. & GYNEC. 86: 249, 1963. 15. Merrill, J. P.: Unpublished data. 16. Parsons, F. M.: Proc. Roy. Soc. Med. 56: 111, 1963. 17. Sabin, M., Parliament, D., and Stream, G. J.: ...............
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18. Schewitz, L. J., Siftel, H. C., and Icasson, C.: South African M. J. 35: 341, 1961. 19. Sims, E. A.. H.: ~rhe kidney in pregnancy. In Strauss, M. B., and Welt, L. G., editors: Disease of the kidney, Boston, 1963, Little Brown & Company. 20. Sims, E. A. H.: Ann. Int. Med. 52: 693, 1960. 21. Tenny, B., and Dandrow, R. V.: AM. J. OBsT. & GYNEC. 81: 8, 1961. 22. Tillman, A. J. B.: M. Clin. North America 35: 677, 1951. 23. Werko, L.: Acta med. scandinav. 153: 177. 1956.
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