In a fictional case, a 31-year-old woman with IgA nephropathy arrives at the outpatient clinic with a direct question: can I get pregnant? The estimated filtration rate is 50 mL/min/1.73 m², blood pressure is controlled with an angiotensin-converting enzyme inhibitor, and proteinuria persists. She wants numbers, and the doctor needs to know where they come from.

Chronic kidney disease (CKD) complicates up to 3 percent of pregnancies, a frequency similar to that of pre-eclampsia (Piccoli et al., 2018). Even so, it often receives less attention in prenatal care, partly because it is silent and because the physiology of pregnancy masks the loss of kidney function.

This text organizes the reasoning into three questions: what is the risk for the mother, for the baby and for the kidney; what to discuss before conception; and how to separate worsening kidney disease from superimposed pre-eclampsia.

Key points

• The risk of preterm birth and of a baby small for gestational age already increases in stage 1 CKD and grows as the disease advances (Piccoli et al., 2018).
• In CKD stages 3 to 5, chronic hypertension and proteinuria predicted poor outcomes better than the stage itself (Wiles et al., 2021).
• In this cohort, pregnancy brought forward the need for dialysis or transplantation by an average of 2.5 years (Wiles et al., 2021).
• Preconception counseling reviews teratogenic medications, discusses low-dose aspirin and plans contraception (Wiles et al., 2015; Attini et al., 2020).
• The WHO recommends low-dose aspirin for pregnant women at high risk of pre-eclampsia, and prior kidney disease is among the risk factors (WHO, pre-eclampsia).
• Separating pre-eclampsia from kidney worsening is difficult, and the sFlt-1/PlGF ratio can help because early CKD usually has normal placentation (Cabiddu et al., 2016).

Summary

• Why CKD changes pregnancy
• The risk according to CKD stage
• What pregnancy does to the kidney
• Counseling before getting pregnant
• Preventing pre-eclampsia
• Kidney worsening or superimposed pre-eclampsia?
• Dialysis and transplantation
• How NEXO helps train this reasoning
• Frequently asked questions
• Take-home messages

Why CKD changes pregnancy

A common and underrecognized problem

The WHO estimates that pre-eclampsia affects 3 to 8 percent of women who give birth worldwide (WHO, pre-eclampsia). An international review, written for World Kidney Day 2018, notes that the estimated prevalence of CKD in pregnancy, around 3 percent, is as high as that (Piccoli et al., 2018).

The authors add that this estimate came from high-income countries and may be underestimated in middle- and low-income countries, where CKD tends to be more prevalent (Piccoli et al., 2018). Therefore, prenatal care can be a valuable occasion to diagnose CKD, especially in disadvantaged populations (Piccoli et al., 2018).

The maternal health context

In 2023, about 260,000 women died during or after pregnancy and childbirth, and most of these deaths could have been prevented (WHO, maternal mortality). Hypertensive disorders accounted for about 16 percent of maternal deaths worldwide, equivalent to about 42,000 deaths in 2023 (WHO, pre-eclampsia).

The inequality is large. The maternal mortality ratio was 346 per 100,000 live births in low-income countries, versus 10 per 100,000 in high-income countries (WHO, maternal mortality). Pregnancy outcomes in CKD also depend on the health system and on access to nephrology, obstetrics and neonatal intensive care (Piccoli et al., 2018).

What physiology hides

In normal pregnancy, creatinine clearance rises by about 50 percent and serum creatinine falls (Wiles et al., 2021). Therefore, "normal" values outside pregnancy should be read with caution, and CKD in stages 2 and 3 may go unnoticed if the doctor uses the reference for non-pregnant women (Piccoli et al., 2018).

The absence of this hyperfiltration is itself a clue to early loss of kidney function (Piccoli et al., 2018). Staging the disease before pregnancy, by filtration and albuminuria, as described in the text on staging CKD by KDIGO 2024, avoids this trap.

The risk according to CKD stage

The risk starts early

The risk of poor outcomes in pregnancy exists from the early stage of CKD, even without hypertension and without proteinuria, which justifies multidisciplinary follow-up for all patients (Cabiddu et al., 2016). The incidence of preterm birth and small babies is already higher in stage 1 than in the general population and increases as stages advance (Piccoli et al., 2018).

By contrast, malformations in general are as frequent as in the general population, apart from hereditary diseases and diabetic nephropathy, and maternal death is exceptional, at least in countries with many resources (Piccoli et al., 2018). The risk of maternal death appears almost only in systemic lupus erythematosus and in vasculitis (Cabiddu et al., 2016).

What a cohort of advanced CKD shows

A cohort from six nephrology centers in the United Kingdom studied 178 pregnancies in 159 women with CKD stages 3 to 5 who passed 20 weeks (Wiles et al., 2021). The live birth rate was 98 percent, but 56 percent of the babies were born before 37 weeks (Wiles et al., 2021).

Outcome	CKD 3a	CKD 3b	CKD 4 and 5
Birth before 37 weeks	41 percent	62 percent	88 percent
Birth before 34 weeks	20 percent	25 percent	40 percent
Weight below the 10th percentile	24 percent	32 percent	64 percent
Median gestational age at birth	37.4 weeks	35.9 weeks	34.7 weeks

The data in the table come from this British cohort, stratified by stage before pregnancy (Wiles et al., 2021). In total, 35 percent of the babies needed admission to a neonatal unit (Wiles et al., 2021).

Hypertension and proteinuria weigh more than the stage

The most useful finding for counseling is this: chronic hypertension, proteinuria before or at the start of pregnancy and the absence of a fall in creatinine during pregnancy predicted poor outcomes better than the CKD stage (Wiles et al., 2021).

• Chronic hypertension: among hypertensive women, 32 percent gave birth before 34 weeks, against none among normotensive women (Wiles et al., 2021).
• Creatinine that does not fall: in hypertensive women, a fall of less than 10 percent in creatinine during pregnancy doubled the risk of birth before 34 weeks, from 20 to 40 percent (Wiles et al., 2021).
• Proteinuria: a protein/creatinine ratio above 100 mg/mmol, close to 1 g per day, was the strongest predictor of birth weight below the 10th percentile (Wiles et al., 2021).

Stage, hypertension and proteinuria are linked to each other, but each is also an independent risk factor (Cabiddu et al., 2016).

The type of kidney disease matters

Glomerulonephritis and immune diseases carry a higher risk of proteinuria and hypertension appearing or worsening, a picture that is hard to separate from pre-eclampsia (Cabiddu et al., 2016). The risk is higher when the immune disease is active or when it is diagnosed or reactivates during pregnancy (Cabiddu et al., 2016).

Kidney malformations, autosomal dominant polycystic kidney disease, lithiasis and previous upper urinary tract infections, on the other hand, increase the risk of urinary infection, which in turn is associated with prematurity (Cabiddu et al., 2016). When kidney disease begins in childhood, the transition to adult care includes this conversation, as discussed in the text on CKD in children.

What pregnancy does to the kidney

The loss of function measured in years

In the British cohort, estimated filtration fell on average 4.5 mL/min/1.73 m² between before pregnancy and the postpartum period, more than the previous annual decline of 1.8 mL/min/1.73 m² per year (Wiles et al., 2021). There was a step drop in kidney function linked to pregnancy in 80 percent of the women (Wiles et al., 2021).

The authors translated this loss into years of disease. The effect of pregnancy was equivalent to 1.7, 2.1 and 4.9 years of kidney disease in stages 3a, 3b and 4 and 5, respectively, and brought forward the need for kidney replacement therapy by an average of 2.5 years (Wiles et al., 2021).

Who loses more function

One year after delivery, 46 percent of the women had lost at least 25 percent of their pre-pregnancy filtration or needed kidney replacement therapy (Wiles et al., 2021). The loss was greater in women with chronic hypertension and in those whose creatinine fell by less than 10 percent during pregnancy (Wiles et al., 2021).

Dialysis was rare: 3 percent of the women started it during pregnancy and 7 percent in the first year after delivery (Wiles et al., 2021). Women in stages 4 and 5 whose progression would lead to dialysis within 5 years should know that pregnancy probably brings that need forward to the pregnancy itself or the immediate postpartum period (Wiles et al., 2021).

Preeclampsia also leaves its mark on the kidney

The relationship also runs in the opposite direction. In a Swedish registry of more than 1.9 million women followed for a median of 20.7 years, preeclampsia was associated with almost double the risk of developing CKD (adjusted hazard ratio 1.92) (Barrett et al., 2020).

The risk was higher for hypertensive and diabetic CKD and grew after preterm, recurrent or obesity-associated preeclampsia (Barrett et al., 2020). For this reason, obstetric history is part of the kidney assessment of every woman, and follow-up of blood pressure and kidney function continues after delivery.

Counseling before pregnancy

How a counseling visit works

In a London preconception counseling clinic, 179 women with CKD were seen between 2003 and 2011 by an obstetrician and a nephrologist together, in 30 to 45 minute visits with the partner invited (Wiles et al., 2015). The visit described the possible outcomes, the mode of delivery and the short- and long-term effect on kidney function (Wiles et al., 2015).

The same visit reviewed medications for teratogenicity, discussed aspirin to prevent preeclampsia, advised folic acid before conception and offered contraceptive counseling (Wiles et al., 2015). Half of the women were using some teratogenic medication (Wiles et al., 2015).

What the women thought

Among the 72 who answered the questionnaire, 90 percent found the visit informative and 92 percent said it helped them decide about pregnancy (Wiles et al., 2015). At the same time, 17 percent found the multidisciplinary process intimidating, and the free-text comments mentioned difficulties of access and emotional impact (Wiles et al., 2015).

Even with the preparation, the subsequent pregnancies had more complications than those of controls at the same hospital: 20 percent preeclampsia versus 4 percent, and 31 percent deliveries before 37 weeks versus 8 percent (Wiles et al., 2015). Giving these numbers honestly is part of good clinical decision-making.

Reviewing medications

The Italian kidney and pregnancy group recommends stopping angiotensin-converting enzyme inhibitors and angiotensin receptor blockers at the first positive pregnancy test, between the 4th and 6th week, in women with proteinuric CKD (Cabiddu et al., 2016). The strategy allows protection against proteinuria to be maintained until conception, at least in adherent patients (Cabiddu et al., 2016).

Mycophenolate causes severe malformations and should be switched to azathioprine before pregnancy, as the KDIGO and European guidelines cited by the group suggest (Cabiddu et al., 2016). The same review notes that cyclophosphamide contraindicates pregnancy and can cause premature menopause and sterility (Cabiddu et al., 2016).

Contraception for those who do not want to become pregnant yet

Fertility is lower in CKD, but conception and delivery are possible at all stages, and an unplanned pregnancy can have lasting effects (Attini et al., 2020). For this reason, individualized contraception should be offered to all women of childbearing age with CKD who do not want to become pregnant (Attini et al., 2020).

• Estroprogestogens: can be used in early CKD without proteinuria, excluding lupus and immune diseases with a high risk of thrombosis and hypertension (Attini et al., 2020).
• Progestogen alone: generally safe, with intermenstrual bleeding as the main adverse effect (Attini et al., 2020).
• Hormone-free intrauterine device: a good alternative, carefully assessing the risk of pelvic infection (Attini et al., 2020).
• Condom: the only method that also protects against sexually transmitted infections (Attini et al., 2020).

Preventing pre-eclampsia

Low-dose aspirin

The WHO recommends low-dose aspirin for pregnant women at high risk of pre-eclampsia, started by 20 weeks or when prenatal care begins (WHO, pre-eclampsia). Previous kidney disease appears on the organization's list of risk factors, alongside hypertension and diabetes (WHO, pre-eclampsia).

The Italian group indicates low-dose aspirin in patients with proteinuria and in those with advanced CKD, lupus or IgA nephropathy (Cabiddu et al., 2016). The best time to start is controversial: many guidelines suggest after the first trimester, but some authors argue for an earlier start, and the group proposes that obstetricians and nephrologists at each service define a common policy (Cabiddu et al., 2016).

Other WHO measures

In addition to aspirin, the WHO recommends calcium supplementation during pregnancy in places with low dietary calcium intake, treating previous hypertension with antihypertensive drugs and using magnesium sulfate to prevent eclampsia (WHO, pre-eclampsia). Magnesium sulfate reduces the risk of eclampsia by more than half, but its use is still limited in many low-resource settings (WHO, pre-eclampsia).

Prenatal care for women with CKD also includes the measures of any pregnancy, such as vaccines during pregnancy and guidance on exercise during pregnancy, adjusted to the kidney condition.

Blood pressure control

The Italian group suggests strict blood pressure control, with an ideal target below 130/80 mmHg and an acceptable one below 140/90 mmHg, under careful monitoring and preferably with home measurement (Cabiddu et al., 2016). Treatment follows a stepwise approach, starting with the drugs that have fewer contraindications in pregnancy, and avoids excessive correction, which can impair fetal growth (Cabiddu et al., 2016).

Kidney worsening or superimposed pre-eclampsia?

Why the distinction is difficult

Pre-eclampsia is diagnosed by new-onset hypertension, from 140/90 mmHg, with proteinuria of 0.3 g in 24 hours or more, after 20 weeks of pregnancy (WHO, pre-eclampsia). In women with CKD, hypertension and proteinuria often already exist beforehand, and both criteria lose strength.

The difficulty is so great that the British cohort gave up on assigning the ICD-10 code for pre-eclampsia: without diagnostic criteria defined in national or international guidelines for superimposed pre-eclampsia in those with previous hypertension or proteinuria, the diagnosis was impossible to confirm in the chart review (Wiles et al., 2021). In the same cohort, proteinuria rose by a median of 23 percent already at the start of pregnancy (Wiles et al., 2021).

The clues that help

The reasoning starts from pathophysiology. Since pre-eclampsia arises from a defect in placentation, analysis of uteroplacental flow and fetal growth can help: altered flow and impaired growth suggest pre-eclampsia, while normal flow and growth favor CKD (Cabiddu et al., 2016).

The sFlt-1/PlGF ratio is considered one of the most promising markers to support this differential diagnosis, because CKD, at least in its early stages, has normal placentation (Cabiddu et al., 2016). The use of the marker in pregnant women in general is covered in the text on the sFlt-1/PlGF ratio in the diagnosis of pre-eclampsia.

When biopsy is not an option

Kidney biopsy is not recommended during pregnancy, according to a systematic review cited by the Italian group, because of the risk of severe bleeding (Cabiddu et al., 2016). Without the reference standard, the diagnosis relies on the sum of clinical, laboratory and ultrasound clues, and the decision to deliver early weighs maternal risk against prematurity. A rapid drop in filtration also raises the hypothesis of acute kidney injury, whose current criteria are in the text on what KDIGO 2026 changed in acute kidney injury, and blood gas analysis shows whether metabolic acidosis is already present, with a detailed reading in the step by step of the anion gap.

This is probabilistic reasoning, in which each clue changes the chance of each hypothesis, as in reading tests by pretest probability. When no clue decides, strategies for dealing with diagnostic uncertainty help choose the next step safely.

Dialysis and transplant

Pregnancy on dialysis

A systematic review of pregnancies on chronic dialysis between 2010 and 2020 found 71.4 percent live births among 402 pregnancies with complete data (Baouche et al., 2023). Preterm birth was the most common complication, in 82.8 percent of births, and pre-eclampsia occurred in 11.9 percent of pregnancies (Baouche et al., 2023).

More dialysis hours were associated with better fetal outcomes, and a midweek predialysis urea below 35 mg/dL can guide adjustment of the prescription (Baouche et al., 2023). The Canadian experience suggests at least 36 hours of dialysis per week in those without residual kidney function, but this strategy needs adaptation where access to dialysis is limited or distances are great (Piccoli et al., 2018).

Pregnancy after transplant

Fertility usually returns quickly after kidney transplant. A meta-analysis of 6712 pregnancies in 4174 recipients found 72.9 percent live births, 21.5 percent pre-eclampsia and 43.1 percent preterm births (Shah et al., 2019). The interval of 2 to 3 years after transplant had more neonatal mortality and fewer live births than the interval above 3 years (Shah et al., 2019).

The ideal candidate for pregnancy after transplant is young, without obesity, normotensive, with normal kidney function, without proteinuria, without recent rejection, adherent to treatment and with at least two years since transplant (Piccoli et al., 2018). In the British cohort, transplant was not independently associated with worse obstetric or kidney outcomes (Wiles et al., 2021).

Back to the case

The patient from the start has CKD 3a, chronic hypertension and persistent proteinuria. The data from the British cohort allow telling her that the chance of a live baby is high, that preterm birth is likely and that pregnancy may bring forward the loss of kidney function by about 1.7 years of disease (Wiles et al., 2021).

Management includes better control of blood pressure and proteinuria before conception, stopping the angiotensin-converting enzyme inhibitor at the first positive test, discussing aspirin, starting folic acid and ensuring contraception until the decision (Cabiddu et al., 2016; Wiles et al., 2015). Recording this management clearly helps the prenatal team, as the text on organizing the reasoning in the medical record shows.

How NEXO helps train this reasoning

In NEXO, the case of the day is fictional, with a real clinical presentation and up to six progressive clues, and you propose the diagnosis by searching for the ICD-10 code. Separating pre-eclampsia from kidney worsening requires the same exercise: gathering clues from history, blood pressure, urine and ultrasound before closing the hypothesis, as in training differential diagnosis with clues.

The limits of using the game are described on the NEXO Economy page. If you research teaching of clinical reasoning, the page for Researcher explains how to get in touch. Professionals who write or review cases find information in Curator and in Creators, and institutions can learn about the proposal on the partnerships page. Searching for the right ICD-10 code completes this training.

Frequently asked questions

Can women with CKD get pregnant?

Yes. Pregnancy is possible at all stages of CKD, including on dialysis and after transplant, but the risk of complications is higher and requires specialized follow-up (Piccoli et al., 2018).

What weighs more in the risk: the stage or other factors?

In CKD stages 3 to 5, chronic hypertension and proteinuria predicted poor outcomes better than the stage (Wiles et al., 2021).

Does pregnancy worsen kidney function?

It can worsen. In CKD stages 3 to 5, pregnancy brought forward the need for dialysis or transplant by an average of 2.5 years (Wiles et al., 2021).

When should the angiotensin-converting enzyme inhibitor be stopped?

The Italian group recommends stopping it at the first positive pregnancy test, between the 4th and 6th week, in patients with proteinuria (Cabiddu et al., 2016).

Should every pregnant woman with CKD take aspirin?

The WHO recommends low-dose aspirin for pregnant women at high risk of pre-eclampsia, and prior kidney disease is a risk factor; the indication is individual (WHO, pre-eclampsia).

How do you tell pre-eclampsia apart from worsening kidney function?

By adding up the clues: uteroplacental flow, fetal growth and markers such as the sFlt-1/PlGF ratio, since early CKD usually has normal placentation (Cabiddu et al., 2016).

Take-home messages

• Ask every woman of childbearing age with CKD about her desire to become pregnant and offer contraception to those who do not want to conceive (Attini et al., 2020).
• Use hypertension, proteinuria and stage to estimate the risk, and remember that the first two weigh more (Wiles et al., 2021).
• Review the medications before conception and plan the suspension of renin-angiotensin system blockade (Cabiddu et al., 2016).
• Discuss low-dose aspirin to prevent pre-eclampsia (WHO, pre-eclampsia).
• Read the pregnant woman's creatinine through the physiology of pregnancy, and be suspicious when it does not fall (Wiles et al., 2021).
• Follow blood pressure and kidney function after delivery, especially after pre-eclampsia (Barrett et al., 2020).

Milestone inventory

• 1970s: first successful delivery by a patient on chronic hemodialysis (Baouche et al., 2023).
• 2015: a London outpatient clinic publishes nine years of preconception counseling for women with CKD (Wiles et al., 2015).
• 2016: the Italian kidney and pregnancy group publishes its best practice position statement (Cabiddu et al., 2016).
• 2018: World Kidney Day takes women's health and kidney disease as its theme (Piccoli et al., 2018).
• 2020: a Swedish registry links pre-eclampsia to the risk of CKD decades later (Barrett et al., 2020).
• 2021: a British cohort measures in years the effect of pregnancy on kidney function in advanced CKD (Wiles et al., 2021).

References

1. World Health Organization. Pre-eclampsia. Fact sheet. Geneva: WHO. Full text.
2. World Health Organization. Maternal mortality. Fact sheet. Geneva: WHO. Full text.
3. Wiles K, Webster P, Seed PT, et al. The impact of chronic kidney disease Stages 3-5 on pregnancy outcomes. Nephrol Dial Transplant. 2021;36(11):2008-2017. PMID 33313680. DOI 10.1093/ndt/gfaa247.
4. Wiles KS, Bramham K, Vais A, et al. Pre-pregnancy counselling for women with chronic kidney disease: a retrospective analysis of nine years' experience. BMC Nephrol. 2015;16:28. PMID 25880781. DOI 10.1186/s12882-015-0024-6.
5. Cabiddu G, Castellino S, Gernone G, et al. A best practice position statement on pregnancy in chronic kidney disease: the Italian Study Group on Kidney and Pregnancy. J Nephrol. 2016;29(3):277-303. PMID 26988973. DOI 10.1007/s40620-016-0285-6.
6. Piccoli GB, Zakharova E, Attini R, et al. Pregnancy in Chronic Kidney Disease: Need for Higher Awareness. A Pragmatic Review Focused on What Could Be Improved in the Different CKD Stages and Phases. J Clin Med. 2018;7(11):415. PMID 30400594. DOI 10.3390/jcm7110415.
7. Attini R, Cabiddu G, Montersino B, et al. Contraception in chronic kidney disease: a best practice position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology. J Nephrol. 2020;33(6):1343-1359. PMID 32166655. DOI 10.1007/s40620-020-00717-0.
8. Shah S, Venkatesan RL, Gupta A, et al. Pregnancy outcomes in women with kidney transplant: Metaanalysis and systematic review. BMC Nephrol. 2019;20(1):24. PMID 30674290. DOI 10.1186/s12882-019-1213-5.
9. Baouche H, Jais JP, Meriem S, et al. Pregnancy in women on chronic dialysis in the last decade (2010-2020): a systematic review. Clin Kidney J. 2023;16(1):138-150. PMID 36726433. DOI 10.1093/ckj/sfac204.
10. Barrett PM, McCarthy FP, Evans M, et al. Hypertensive disorders of pregnancy and the risk of chronic kidney disease: A Swedish registry-based cohort study. PLoS Med. 2020;17(8):e1003255. PMID 32797043. DOI 10.1371/journal.pmed.1003255.

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