RENAL FAILUREVol. 26, No. l,pp. 29-34, 2004

CLINICAL STUDY

Pregnancy in Patients with Chronic Renal Insufficiency atHospital de Clinicas of Porto Alegre, Brazil

Glaucia Trevisan, M.A.,* Jose Geraldo Lopes Ramos, Ph.D.,Sergio Martins-Costa, M.D., and Elvino Jose Guardao Barros, Ph.D.

Gynecology and Obstetrics and Internal Medicine Department, NehrologyCare Section, Hospital de Clinicas, Federal University of Rio

Grande do Sul, Porto Alegre, Brazil

ABSTRACT

Chronic renal insufficiency (CRI) decreases reproductive capability. The biggestchallenge in monitoring pregnant women with renal disease is to keep the intrauterineenvironment favorable to the fetus. One of the common prognosis in this kind ofpregnancy involves premature birth, restricted growth and mental retardation. Also,the risk of developing complications is higher for the mother. This study focuses onevaluating CRI patients' clinical conditions during pregnancy, checking fetaldevelopment and birth and verifying the prevalence of CRI in pregnant womenattended at Hospital de Clinicas of Porto Alegre-Brazil (HCPA). This is aretrospective study with both a control and an case group of pregnant women withCRI who delivered their babies at HCPA from 1989 to 1999. The case group iscomposed of pregnant women with CRI, while the control group was paired accordingto matemal and gestational ages and to the time of the delivery, which should be thesame both in the experimental and in the control group. Among the criteria usuallyused to identify CRI, we chose the creatinine level higher than 1.5 mg/dL.Significance was established in 0.05%. Our results demonstrate that the prevalenceof CRI was 6/10,000 births. Average matemal age was 28. Sixty five per cent ofthe patients, in both the groups, underwent prenatal monitoring, 40% presentedpreeclampsia, 48% presented urinary infection. Among the CRI complications, 48%of the cases presented anemia and 56% presented systemic hypertension. Averagehematocrit was 24% while hemoglobin was 6.7 g/dL, which leads us to the conclusionthat patients presented anemia during pregnancy. Average creatinine was 4.61 mg/dL.It is relevant that 64% of the CRI cases migrated to a substitutive renal therapymethod. As for the fetus evolution in the case group, we confirmed the findings of

*Correspondence: Glaucia Trevisan, Rua Veador Porto, n. 392/303 Bairro Santana, CEP: 90610-200, Porto Alegre, Rio Grande doSul, Brazil; E-mail: glauciat@cpovo.net.

29

DOI: I0.IO81/JDI-I2O028540Copyright © 2004 by Marcel Dekker, Inc.

0886-022X (Print); 1525-6049 (Online)www.dekker.com

30 Trevisan et al.

previous studies, such as larger number of premature births (newboms younger than36 weeks in 60% of the cases), larger number of cesarean section (56%), lower weightat birth (1980 gr. in average), lower APGAR scores in the first and fifth minute (4.13and 5.08, respectively) in comparison to the control group (7.52 and 8.63,respectively). We can state that babies bom from CRI patients present under-development. Also, mothers with CRI develop more complications during pregnancy.

Key Words:mortality.

Pregnancy; Chronic renal insufficiency; Fetus mortality; Maternal

INTRODUCTION

Chronic renal insufficiency (CRI) significantlydecreases reproductive capability.''^ Many years ago,renal disease meant termination of gestation due to ma-temal risk of death. Our biggest challenge in monitoringpregnant women with renal disease is to keep theintrauterine environment favorable to the fetus. Whenit is not possible, premature delivery, restricted fetalgrowth and mental retardation might occur. Not onlythe fetus is at higher risk, but also the mother developsmore complications during pregnancy when CRI ispresent.'̂ ^

Renal disease might become more severe duringpregnancy.'''^ In this case, when there is total loss ofrenal function, the substitutive renal therapy, throughdialysis, might be necessary at different times duringgestation. In these patients, a large number of fetal andmatemal complications is reported. Some of these com-plications lead to termination of gestation and othersinvolve high risk of death for the mother.'̂ ^

Lately, many studies have reported successfulpregnancies in women who undergo dialysis.'^^ Thesewomen usually present a lower incidence of gestation,and their babies usually present lower weight atbirth.'*-' Among patients who undergo dialysis, a highincidence of premature birth is reported. Most babiesare bom before the 36th week.'̂ ^

The present study focuses on verifying the prev-alence of CRI and evaluating the patients' clinical con-ditions during pregnancy. We also studied birth condi-tions and fetal development in CRI patients.

METHODS

We carried out a retrospective study with both acontrol group and an experimental group composed ofpregnant women with CRI who delivered their babiesat Hospital the Clinicas of Porto Alegre-Brazil(HCPA) from 1989 to 1999. The case group is com-posed of pregnant women CRI. The control group is

composed of pregnant women with normal renal func-tion. They were paired according to maternal and ges-tational age and to the time of the delivery, whichshould be the same both in the experimental and in thecontrol group. CRI patients were in pre-dialysis phase,on dialysis or had undergone kidney transplantation.

The Committee for Ethics in Research of thehospital approved this study.

Gestational age was classified according to criteriaestablished by the World Health Organization, whichconsiders abortion a pregnancy that lasts for up to 20weeks; pre-viable preterm delivery when it lasts for20-28 weeks; viable preterm delivery when it lasts for28-36 weeks; and, successfully carried out deliverywhen pregnancy lasts for more than 36 weeks.

Diagnosis of CRI was established whenever semmcreatinine was > 1.5 mg/dL. Patients whose hemoglo-bin level was < 10.5 g/dL were considered anemic.

The variables studied were maternal age, race,basic disease, prenatal monitoring, presence of pre-eclampsia, presence of urinary infection, complicationsof CRI, hematocrit and hemoglobin levels, proteinurialevel, patients' present condition, creatinine level, ges-tational age, blood pressure.

In the statistical analysis. Fisher's F test andStudent's T test were applied, as well as Cliffs non-parametric test of dominance and Wilcoxon-Mann-Whitney non-parametric U test. Significance level wasestablished as 0.05.

RESULTS

The total number of deliveries in the period stud-ied was 36.459 which represents an average of 320deliveries per month. Prevalence of CRI patients was 6in 10,000 pregnancies (25 cases).

Average age was 29 ±4.9 in the experimentalgroup, and 29 ±5.5 in the control group (NS). WhiteCRI patients were 92%, while 86.54% of the mothersin the control group were white. Sixty four per cent ofthe patients in the experimental group underwent

Chronic Renal Insufficiency 31

prenatal monitoring, while in the control group theywere 67.31% (NS).

Forty per cent of CRI patients presented preeclamp-sia, while in the control group this complication wasidentified in 5.77% {p = 0.0002) of the cases. Urinarytract infection was observed in 48% of the patients in thecase group, while in the control group UTI occurred in7.69% (p< 0.0001) of the cases (Table 1).

The cause of CRI in pregnant patients was sys-temic hypertension in 56% of the cases, diabetes mel-litus in 12%, systemic Lupus erythematosus in 8%. Thernorphologic alteration observed was the presence ofpolycystic kidneys in 4% of the cases.

Anemia was the most prevalent complication inCRI patients, it was observed in 48% of the cases.Average hematocrit was 24% ±11, and hemoglobinwas 6.7 ± 4.5 g/dL. Average proteinuria in the experi-mental group was 1567.75 mg in 24 hours and averagecreatinine was 4.61 mg/dL.

As for the gestational age, 16% of pregnancieswere not maintained up to 20 weeks, 20% of patientspresented gestational age of 20 to 28 weeks, 24% ofpregnancies lasted 28 to 36 weeks and 32% of patientsmaintained pregnancy for more than 36 weeks.Average gestational age was 30.96 weeks in theexperimental group and 36.42 weeks in the controlgroup (p = 0.0013).

Fifty six per cent of patients in the case groupunderwent to cesarean section, while in the controlgroup caesarians occurred in 38.46% of the cases. Fiftysix per cent of the newboms in the case group weremale, while 55.77% were male in the control group.Average weight at birth was 1981 grams in the casegroup and 2690 grams (p - 0.0069) in the controlgroup. Average Apgar score in the first minute was4.13 in the experimental group and 7.52 (p = 0.0004)in the control group. In the fifth minute, average Apgar

Table 2. Characteristics of the births.

Characteristic

Caesarian (%)Sex male (%)Weight

(x ± SD)APGAR r

(x ± SD)APGAR 5'

(x ± SD)

CRI patients(n = 25)

56521980.79 ±

1012.064.13 ±4.04

5.08 ±4.47

Control group(n = 50)

38.4655.772689.80 ±

925.097.52 ±2.46

8.63 ± 2.24

P

NSNS0.0033

0.0004

< 0.0001

CRI—chronic renal insufficiency.

score was 5.08 in the case group and 8.63 (p < 0.0001)in the control group (Table 2).

As for previous pregnancy data, we observed that28% of the patients in the case group were in their firstpregnancy, while in the control group they were28.85% (NS). Abortion history occurred in 32% ofthe cases in the experimental group and in 26.93% inthe control group (NS). Average number of caesarianswas 40% in the case group and 21.15% in the controlgroup (p - 0.2231). Thirty six per cent of the patientsin the case group had dead fetuses, while in the controlgroup they were 3.85% (p - 0.0001).

Average systolic pressure was 154.44 mmHg inthe case group and 118.12 mmHg (p < 0.0001) in thecontrol group. Diastolic pressure was 91.58 mmHg inthe case group and 73.90 mmHg in the control group(p < 0.0001) (Table 3).

After gestational period, 8% of the patients re-mained being attended in the ambulatory, 20% startedperitoneal dialysis treatment, 20% started hemodialysis,24% had undergone kidney transplantation and 28%

Table 1. Patients' characteristics. Table 3. Gestational history.

Characteristic

Age (x ± SD)years

Race (%) whitePrenatal

(%)—yesPreeclampsia

(%)—yesUTI (%)—yes

CRI patients(n = 25)

29 ± 4.9

9264

40

48

CRI—chronic renal insufficiency.

Control group(n = 50)

29 ±5.5

8767

6

8

P

NS

NSNS

0.0002

< 0.0001

Characteristic

First pregnancy(%)

Abortion (%)Caesarian (%)Dead fetus (%)Systolic p.

(x ± SD)Diastolic p.

(x ± SD)

CRI patients(n = 25)

28

324036154.44 ±28.33

91.58 ±27.74

Control group(n = 50)

28.85

26.9321.153.85118.12± 12.48

73.90 ±9.96

P

NS

NS0.22310.0001< 0.0001

< 0.0001

UTI—urinary tract infection. CRI—chronic renal insufficiency.

32 Trevisan et al.

of the cases were undetermined because they did notcome back to be evaluated at the hospital after thestudy period.

DISCUSSION

Significant adaptations of renal physiology andanatomy occur in the renal system during pregnancy.Laboratory results demonstrated some alterations inblood and glomerular filtration. Women with pasthistory of renal disease present a decrease in the renalfunction, which leads to a higher risk of perinatalmortality and morbidity.^^'

Glomerular filtration rate (GFR) and effectiverenal plasma flow (ERPF) are 35 to 50% higher thanin women who are not pregnant 24-hour creatininedepuration increases soon after the first menstrual flowis absent, reaching its peak of 40 to 50% above pre-conception level between the 9th and 11th week.

Renal hemodynamics increments during gestationpose the following clinical implications: creatinine andurea nitrogen levels decrease from an average of 0.7and 12 mg/dL to 0.5 and 9.0 mg/dL, respectively. GFRand ERPF increase also explains the increasedexcretion of glucose, amino acids and hydrosolublevitamins, which increases the chance of bacteriaproliferation. It is considered as normal excretion ofproteins during pregnancy double the top limit for non-pregnant women, that is, 300 mg/24 hours.'̂ '̂

Gestation in end-stage renal disease patients is anunusual occurrence due to lack of ovulation,^'°^ particu-larly in women who need dialysis.̂ ^^ When pregnancyoccurs, common results are premature births and lowweight. Elective abortion is also a common result.

Chan̂ ^̂ reported that 74% of the expectant womenin their study started dialysis during pregnancy. Theycompared fetal survival in women who underwentperitoneal dialysis and hemodialysis, but no differencewas found.

Abbassi'̂ '̂ reports that the frequent complicationsdeveloped during pregnancy bring along a high risk ofhemorrhage and of increased maternal anemia. Thefetus ends up presenting chronic hypoxia due tomatemal anemia, which leads to fetal complicationsalready described in this study.

Reports that erythrocyte production increasesduring pregnancy. However, due to an even higherincrease in the blood volume, there is hemodiluting.The number of red blood cells decreases early, in thefirst weeks. Average hemoglobin in this study was6.7 ±4.5 g/dL. Bagon^"' states that erythropoietindoses should be increased until hemoglobin reaches

and maintains a level of 11 g/dL. Chao (2001) dem-onstrated that the use of erythropoietin did not causehypertension.'̂ '̂ ^ Average hematocrit was 24 ± 11.09%.Thus, we can conclude that the patients in the presentstudy presented anemia during pregnancy. Studies thatdescribe the changes in the dialysis program duringpregnancy report that the use of erythropoietin is im-portant to keep anemia at an acceptable level, whichprevents blood transfusions.'̂ ^^ Even among pregnantwomen who had undergone kidney transplantation,anemia is present in 65.5% of the cases, according toTan's study.f'̂ ^

The presence of residual renal function is impor-tant to determine gestational success.'̂ '°^ Many patientswho start dialysis after conception present good ma-temal and fetal progress.

Significant proteinuria level is above 300 mg in24 hours, which is associated with increased peri-natal mortality. The proteinuria level we observed was1567.75 ±1651.79 mg.

The presence of renal disease is confirmed whencreatinine is higher than 1.5 mg/dL. A successfulgestation with lower risk to the fetus is associated withcreatinine level of about 3 mg/dL. The increased cre-atinine level during pregnancy occurs due to severalfactors. Other less relevant factors, such the use ofmedicine that alter creatinine clearance, are also de-scribed by Keller.'''*^ Bagon'̂ "^ reported successfulpregnancies in 93% of the cases when average cre-atinine was 2.5 mg/dL and residual renal function waspresent. Average creatinine found in the present studywas 4.61 ±3.36 mg/dL.

There are many diseases that lead to renal functionloss. Hypertension syndrome occurs in 10 to 15% ofthe gestations and causes matemal death in 30% ofthe cases and neonatal death in 20%.'̂ '̂ ^ In the presentstudy, 56% of the CRI patients presented systemichypertension as basic disease, which might make itmore severe during pregnancy.

The impact of pregnancy on the progress ofdiabetes nephropathy has been studied in the longrun. The conclusion was that pregnancy does not haveany impact either on renal function or on matemalsurvival in pregnant diabetes patients whose renalfunction is well preserved (normal serum creatinine). Inthe present study, we identified diabetes mellitus in12% of the CRI patients.

In 8% of the CRI cases, we observed systemic Lupuserythematosus as basic disease. Moroni and collabo-rators'"'^ reported the progress of pregnant Lupuspatients. Fetal loss occurred in 36% of the cases, andthere were 13 pre-term newboms. Three patients de-veloped acute renal insufficiency, one of them with

Chronic Renal Insufficiency 33

irreversible loss of renal function. The other patientsrecovered from the disease after immunosuppressivetherapy. The conclusion is that proteinuria, hypertensionand the presence of antiphospholipids are independentpredictors of adverse results to the fetus.

Among morphologic alterations, we verified preg-nancy in a patient with polycystic kidney disease.Hassan '̂̂ ^ observed a pregnant women with polycystickidney disease and verified that it was not necessaryto make use of prophylactic dialysis and there wasno acceleration in the renal function deterioration. Thenewborn was delivered successfully and presentednormal weight. We believe that the effective con-trol of blood pressure and the pre-dialysis phasetreatment might be enough to achieve successful resultsin pregnancy.

It is widely acknowledged that fetal developmentand intrauterine growth is restricted in CRI patients.Keeping intrauterine environment adequate and favor-able to the fetus is still a big challenge to the staff thatmonitors these patients during pregnancy.'^' Theexplanation for the larger number of premature birthsin CRI patients might be in the failure to keepplasmatic urea level between 100 and 140 mg/dL andmight also be in other factors that influence gestationalsuccess. In the present study, the proportion ofdeliveries at a gestational age over 36 weeks is notthe same in the experimental and in the control group.Overall data collected in the city of Porto Alegre in1999 demonstrate that 87% of the deliveries occur after37 weeks of gestation. This information confirmsseveral previous studies that report a larger numberof premature births in CRI patients.

Chronic renal disease interfered with intrauterinegrowth and development—newborns present low weightat birth. Overall data collected at HCPA in 1999demonstrate that only 12.3% of the newboms weightedless than 2500 g,'̂ '̂ ' while average weigh in CRI caseswas 1980 g.

All evidence suggests that babies bom from CRImothers present underdevelopment, which is demon-strated by APGAR scores at birth. APGAR score in thefirst minute in the control group is significantly higherthan in the experimental group. Data from HCPA' '^^

demonstrate that only 17.8% of the newboms presentApgar score below 7 in the first minute. APGAR scorein the fifth minute in the control group is alsosignificantly higher than in the case group 96.4% ofthe newboms at HCPA present Apgar score in tbe fifthminute above 8.

We can affirm that CRI patients' babies presentchronic fetal suffering due to both low weight and lowApgar score at birth.

In relation to maternal progress immediately afterdelivery, it is relevant to point out that 64% of thecases migrated to a substitutive renal therapy, whichleads us to the conclusion that renal disease becomesmore severe during pregnancy. Eight per cent of thepatients remained monitored in the ambulatory, afterthe study period, to control renal function. We believethat only 28% of the cases did not present loss of therenal function since patients did not come back to beevaluated in the hospital after the study period.

In summary, the prevalence of CRI was 6 in 10.000births occurred at HCPA. Average maternal age was 28.Forty per cent of the cases presented preeclampsia, and48% presented urinary infection during pregnancy. Asbasic disease, 56% of the cases presented systemichypertension and 12% presented diabetes mellitus.Among CRI complications, anemia occurred in 48% ofthe cases. Average hemoglobin was 6.67 g/dL, whichsuggests the presence of anemia. Average creatinine was4.61 mg/dL. Sixty four per cent of the cases migrated to asubstitutive renal therapy, which leads to the conclusionthat renal disease becomes more severe during pregnan-cy. Weight at birth in the experimental group wassignificantly lower than in the control group, which leadsto the conclusion that chronic renal disease interfereswith intrauterine growth and development. APGARscores in the first and fifth minutes are significantlylower in CRI patients' babies.

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