A 31 year old female with hypertension and proteinuria secondary to IgA nephropathy, currently treated with an ARB, presents to clinic stating that she would like to become pregnant.
What is the risk of fetal morbidity in the setting of ARBs/ACE-inhibitors? What antihypertensive medications are used during pregnancy? At what point would you switch a patient’s medications if she is trying to become pregnant? What is the natural course of IgA nephropathy during pregnancy?
-Minisha Sood MD, PGY-3
Pregnancy and Chronic Kidney Disease
Commentary by Sergio Obligado MD, Renal Fellow
Chronic kidney disease (CKD) carries significant risks to the mother and fetus in pregnancy. Diseases such as IgA nephropathy (which frequently occurs in the second and third decades of life) and diabetic glomerulosclerosis, are sufficiently common that reproductive-age women with these diseases present to their primary care doctors. The overall incidence of pregnancy and CKD has been estimated to be in the range of .03 to .12% in different populations. 1
During the first trimester, the physiology of normal pregnancy is characterized by decreased blood pressure, increased glomerular filtration rate and renal plasma flow, and sodium and water retention.1 Although normal pregnant woman will achieve this increased GFR without an increase in glomerular capillary pressure, women with renal disease tend to have increases in proteinuria, even during early stages of pregnancy. During the second and third trimesters, when blood pressure starts to rise and GFR falls in normal women, women with kidney disease can manifest dangerous elevations in blood pressure and dramatic increases in proteinuria.2
Although systemic diseases can significantly influence the maternal and fetal outcomes (i.e. diabetes, SLE), there isn’t any strong evidence that the type of glomerular disease independently effects pregnancy outcomes.3, 4 However, most retrospective and observational studies written on pregnancy and CKD clearly document that the risks are inversely related to GFR at onset of pregnancy. Women with creatinine < 1.3 seem to do quite well, with relatively insignificant changes in GFR and proteinuria.1 A study in the NEJM in 1996 followed 86 pregnancies in women with moderate to severe non-diabetic renal disease (creatinine > 1.4).5 They found that the mean creatinine rise was 1.9 to 2.6, and 20% of women had worsening hypertension and severe proteinuria by the third trimester. 8 of the women required dialysis by 1 year post-partum. The vast majority of the maternal morbidity occurred in the women who had a creatinine > 1.9 at initiation of pregnancy. The remaining small studies show similar outcomes; a third of women with creatinine > 1.5 have irreversible renal decline. Certainly, complications of pregnancy are more frequent as well. Preeclampsia has been reported to occur in up to 40% of women with CKD; although the definition of preeclampsia in a woman who begins a pregnancy with hypertension and proteinuria, in my opinion, is somewhat arbitrary.
Fetal outcomes can be severely affected by maternal kidney disease. Overall fetal mortality is between 5 to 10% in studies, and is dependent on maternal GFR and control of hypertension in the third trimester.1 In the NEJM study mentioned above, fetal mortality was 7%, and 48% of births were premature.5
Controlling hypertension during pregnancy is particularly important in women with kidney disease as it has been found to be an independent predictor of maternal GFR decline and aggravates fetal outcome. α Methyldopa remains the drug of choice as it has the best experience and reasonable long-term follow up data (7 years of children exposed in utero).6 Data with β-blockers is conflicting, but labetalol appears to be the safest and recommended by some agencies as the second-line agent. Hydralazine also has excellent experience by obstetricians, and few case reports of poor fetal outcomes.7 Diuretics, although often necessary in pregnant women with CKD, are frowned upon due to fear of unfavorable hemodynamic alterations in pre-eclamsia.6
ACE inhibitors and ARBs are extremely important for slowing progression of both diabetic and non-diabetic kidney disease; all women with proteinuria should be on one (or both) of these types of drugs. However, the teratogenicity of these agents in the second and third trimester is well documented. Oligohydramnios, fetal growth retardation, pulmonary hypoplasia, joint contractures, hypocalvaria and death have been documented with use of both ACE inhibitors and ARB in the second half of pregnancy.8 Until recently, fetopathy in earlier pregnancy had not been demonstrated and studies in mice have corroborated this. Cooper et al analyzed Medicaid records from 29,096 pregnancies to find any evidence of teratogenicity of ACE inhibitors in the first trimester.9 They found that among women who were exposed to ACE inhibitors (n=209), the RR of congenital malformation was 2.71, compared to no antihypertensive medication or other types of antihypertensive medication. Until more data is available, this study strongly suggests that any woman of child-bearing age who is on ACE inhibitors or ARBs should be counseled on risks and placed on appropriate contraceptives.
Although pregnant women with CKD have historically been relatively rare, understanding the prognosis and general principles in management are important as CKD is being increasingly recognized in the general population. General Internists need to be able to counsel women with CKD of the significant maternal and fetal risks so women can make appropriate decisions regarding their reproductive health.
1. Fischer MJ: Chronic kidney disease and pregnancy: maternal and fetal outcomes. Adv Chronic Kidney Dis 2007; 14(2): 132-45.
2. Hou S: Pregnancy in chronic renal insufficiency and end-stage renal disease. Am J Kidney Dis 1999; 33(2): 235-52.
3. Katz AI, Davison JM, Hayslett JP, Singson E, Lindheimer MD: Pregnancy in women with kidney disease. Kidney Int 1980; 18(2): 192-206.
4. Jungers P, Chauveau D, Choukroun G, et al.: Pregnancy in women with impaired renal function. Clin Nephrol 1997; 47(5): 281-8.
5. Jones DC, Hayslett JP: Outcome of pregnancy in women with moderate or severe renal insufficiency. N Engl J Med 1996; 335(4): 226-32.
6. Umans JG: Medications during pregnancy: antihypertensives and immunosuppressives. Adv Chronic Kidney Dis 2007; 14(2): 191-8.
7. Podymow T, August P: Hypertension in pregnancy. Adv Chronic Kidney Dis 2007; 14(2): 178-90.
8. Friedman JM: ACE inhibitors and congenital anomalies. N Engl J Med 2006; 354(23): 2498-500.
9. Cooper WO, Hernandez-Diaz S, Arbogast PG, et al.: Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med 2006; 354(23): 2443-51.
3 comments on “How should you approach a pregnant patient with chronic kidney disease?”
I am a 26 year old woman with FSGS, and I have made the decision to attempt to conceive with a current creatinine level of 3.1. I have been discouraged by both ob gyn, and nephrologist, to pursue a pregnancy, however, they have both been more than supportive. I am hoping to find stories of women who have been in similar situations, and to learn of their outcome. I want to be prepared for the nitty gritty of caring for an infant while possibly facing esrd, or renal failure.
I am a 33 year old woman with fsgs. I was diagnosed in the early stages of my first pregnancy(2002). Pregnancy was successful with no adverse effects for self or baby. Baby was born by cs and weighed 3.3kg. Fell pregnant again in 2004 and continued pregnancy against advice of nephrologist. Another successful pregnancy, baby full term cs (3.0kg). Elevated proteinuria which decreased within six months of giving birth. Am stable at present. Best of luck
30 (now) year old woman diagnosed with fsgs in 1st pregnancy (2004), no complications other than the high protein loss up to a 4plus at one point. Dr. induced pregnancy vaginal birth healthy 6lb 1 ounce baby. Pregnant again 2 1/2 years later delivered healthy baby girl vaginally 6lbs 9ounces, no complications just induced. Just found out I’m pregnant AGAIN, not sure how far along since I hadn’t had a cycle due to breastfeeding youngest baby. Protein at loss at this point 3 plus. Never had preeclampsia in any of my pregnancies. You will do fine! Good luck.
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