Pregnancy in IgA Nephropathy: A Blessing or Curse?

Kidney disease was historically considered a contraindication to pregnancy, and termination of pregnancy was often recommended. However, the data on successful outcomes in pregnant women with CKD are increasing. The first successful pregnancy in a dialysis patient was reported in 1971. In a recent study published in AJKD, Liu et al analyzed the impact of pregnancy on kidney disease progression and identified risk factors for adverse pregnancy outcomes in IgA nephropathy. Corresponding authors Drs. Jicheng Lv (JL) and Hong Zhang (HZ) discuss the study with Dr. Ritu Soni (eAJKD), eAJKD Contributor.

eAJKD: What inspired you to analyze the outcomes of pregnancy, particularly in patients with IgA nephropathy?

JL&HZ: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide, especially in China where it accounts for nearly half of the primary glomerulonephritides. Pregnancy is a major concern in female patients. However, the outcomes of pregnancy in this IgA population remains uncertain. We created an IgAN database about 10 years ago in Peking University First Hospital in North China. The cohort recruited 1245 patients followed in our clinics. This has given us an opportunity to assess the outcomes of pregnancy in young women with IgAN.

eAJKD: Can you summarize the major findings of your study?

JL&HZ: This cohort study included 62 women with 69 pregnancies and 62 matched controls. After a mean follow-up of 45.7 months, we found pregnancy was not an independent risk factor for kidney disease progression events (HR = 1.2; 95% CI 0.3 to 5.7) in patients with preserved kidney function. There was also no significant difference in the median rate of estimated glomerular filtration rate (eGFR) decline in the two groups (−2.5 versus −2.4 mL/min/1.73 m2 per year, P = 0.7). Adverse pregnancy outcomes were observed in 15 patients. Proteinuria during pregnancy (OR 1.39, CI 0.96 to 2.01) was a borderline predictor of adverse pregnancy outcomes. Additionally, only 10 kidney failure events occurred in this cohort: 4 in the pregnancy group and 6 in the controls. These results suggest that pregnancy doesn’t seem to adversely influence kidney disease progression in patients with preserved kidney function. However, our small sample size limits our ability to detect a difference in kidney failure events.  Encouraged by the promising results, an extended follow-up including more participants is currently underway at our center. We hope to report these data in the future.

eAJKD: Did you compare outcomes across various stages of chronic kidney disease (CKD)? Can these results be extrapolated to patients with CKD from other etiologies?

JL&HZ: Another major limitation of the study is that most of the subjects had nearly normal kidney function (eGFR >60 mL/min/1.73 m2), which was also the case in other similar studies. Hence, we didn’t analyze the safety of pregnancy in women with IgA nephropathy with moderate-to-severe GFR loss. We are currently conducting a systematic review and meta-analysis of patients with CKD from different etiologies (excluding lupus nephritis and vasculitis).

eAJKD: Previous studies have shown that over 90% of women with mild CKD (pre-pregnancy serum creatinine <1.5 mg/dL) have successful kidney outcomes, with the major predictor of kidney disease progression being hypertension. In your study, most of the subjects had preserved kidney function with serum creatinine <1.0 mg/dL. Did you find any association between hypertension and adverse maternal/fetal outcomes?

JL&HZ: In our study, we didn’t find any association between time-average mean arterial pressure (TA-MAP) during pregnancy and adverse maternal/fetal outcomes. We had established this prospective cohort about 10 years ago, and all the patients were regularly followed. Patients’ blood pressure was closely monitored by treating physicians and was well-controlled during pregnancy (mean artery pressure 85.9 ± 9.9 mmHg). This could probably explain why we didn’t identify blood pressure as a risk factor for adverse pregnancy outcomes in our study.

eAJKD: You found in your study that proteinuria correlated with adverse fetal outcomes. Can you please elaborate on that?  Did you identify a threshold for proteinuria beyond which the risk was significant?

JL&HZ: Patients with greater proteinuria may be more susceptible to the potentially harmful effects of hemodynamic adaptation during pregnancy, which, in turn, may impact both maternal and fetal outcomes. An attractive hypothesis that might explain this is that these women are more prone to develop superimposed preeclampsia. However, we didn’t identify a threshold of proteinuria beyond which the risk was significant. We have listed the risk stratified by the degree of proteinuria.

Outcome based on categorical grouping of TA 24-h urine protein excretion during pregnancy.

Group (n) TA-Proteinuria (g/24 h) Adverse fetal outcomes (Hazard (95% CI))
1 0 to 1 Reference
2 1 to 2 2.58 (0.5, 13.29)
3 2 to 3 1.72 (0.15, 19.48)
4 > 3 8.61 (1.61, 46.07)

(These data were not shown in the paper)

We confirmed these results in our follow-up study (OR 2.9; 95% CI 1.3 to 6.6; P= 0.007) which included 79 patients and 86 pregnancy events. We found that the risk is continuous and a threshold can’t be identified.

eAJKD: These results demonstrate that pregnancy does not pose a risk for progression of kidney disease in patients with IgA nephropathy with preserved kidney function. Based on these data, would you recommend clinicians modify their approach to pre-conception counseling of women with CKD contemplating pregnancy?

JL&HZ: The results from our study and other similar studies are promising for pregnancy in patients with preserved kidney function. We have done a systematic review and meta-analysis of pregnancy in IgAN, including other Asian and Caucasian populations. These studies reported 307 pregnancies in 211 patients, and 209 IgAN patients who did not conceive. The pooled results showed that pregnancy didn’t increase the risk of kidney failure events (RR 1.20, 95% CI 0.66 to 2.16; P = 0.55) in females with preserved kidney function with no evidence of heterogeneity (I2 = 0.0%, P =0.70). These results inform clinicians and patients that pregnancy doesn’t adversely influence kidney disease progression for patients with nearly normal kidney function. However, clinicians should keep in mind that pregnancy in these women, even those with preserved kidney function, results in a relatively higher risk of adverse pregnancy outcomes (22%) as compared to the general population. More studies with a longer follow-up are needed to confirm these results.

eAJKD: How will the results from your study guide future research?

JL&HZ: Most studies about pregnancy in patients with IgAN have small numbers and short follow-up. Our systematic review showed that these studies reported only 211 patients with pregnancy. A larger multicenter prospective cohort (more than 400) with improved study power is still needed to confirm the findings. We also need to know the outcomes in patients with moderate or even advanced kidney disease (eGFR <60 mL/min/1.73m2), although such a study would be difficult in clinical practice. Since only small case series have reported pregnancy outcomes in patients with impaired kidney function, a multicenter registry is needed to collect these data before a study is initiated. Finally, we need to identify risk factors of pregnancy in patients with IgAN using a larger database, and develop a risk score system to help clinicians counsel patients who plan to become pregnant.

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