A retrospective study of kidney disease in Alport syndrome during and after pregnancy

Abstract

Background: During pregnancy, hyperfiltration and other factors are hypothesized to contribute to the progression of kidney disease in women with Alport syndrome. To evaluate the status of kidney disease, clinical data from mothers with Alport syndrome in China and Europe over the pregnancy were analyzed.

Methods: This retrospective observational study collected data to evaluate proteinuria, kidney function and Alport stage prior to, during, and after pregnancy, respectively.

Results: A total of 74 women were enrolled, 82% of them with X-linked Alport syndrome and 11% with autosomal Alport syndrome (unknown in 5 patients). Detailed information on the course of pregnancy was available for 62 pregnancies from 52 different women. No fetal malformations were observed. Mean gestational age was 37.9 ± 2.7 weeks (n = 55). Complications included high blood pressure (n = 8), abortion (n = 5), preeclampsia (n = 5), gestational diabetes (n = 3), nephrotic syndrome (n = 2), cervical insufficiency with fetal growth delay (n = 2), premature rupture of membranes (n = 1) and acute intrauterine fetal distress (n = 1). Median proteinuria was 350 (30-2465) mg/day prior to pregnancy, 2390 (450-11,450) mg/day during pregnancy, and 590 (40-2650) mg/day at a mean postpartum follow-up time of 4.5 ± 2.1 years. Mean estimated glomerular filtration rate (eGFR) decreased by 17.2 ± 16.7 ml/min/1.73 m², from 96.1 ± 32.9 to 78.9 ± 37 ml/min/1.73 m² after pregnancy (n = 15; p = 0.003). The eGFR loss was higher in women with eGFR < 90 ml/min/1.73 m² prior to pregnancy compared to women with normal renal function (- 21.5 ± 9.8 vs. - 14 ± 20 ml/min/1.73 m²), and in women with severe variants compared to women with less severe variants (- 21.5 ± 20.2 vs. - 11.3 ± 19.0 ml/min/1.73 m²). Progression of Alport stage after pregnancy was observed in 42% of the women, 31% remained in stage 0-1, and 23% remained in stage 2.

Conclusions: This study provides important data on the natural history of Alport syndrome in women who have undergone a pregnancy. Women with severe variants of Alport syndrome, and women with eGFR below 90 ml/min/1.73 m² face greater risks of kidney disease progression after pregnancy. Further prospective studies are required to confirm these findings.

Keywords: Alport syndrome; Pregnancy; Proteinuria; Women.

Fig. 1

24-h urine protein quantification in women before and after pregnancy. a Proteinuria before pregnancy (n = 17; median 350 mg/day, range 30–2465 mg/day), during pregnancy (n = 7; median 2390 mg/day, range 450–11450 mg/day), one year after delivery (n = 13; median 880 mg/day, range 110–4000 mg/day) and last follow-up (n = 21; median 590 mg/day, range 40–2650 mg/day; median 5 years, range 1–9 years after delivery). b Intra-individual course of proteinuria, paired samples, Wilcoxon test (p < 0.05)

Fig. 2

Course of eGFR before and after pregnancy. a eGFR before pregnancy (n = 22; 105.4 ± 30.7 ml/min/1.73 m²), one year after delivery (n = 17; 86.9 ± 36.7 ml/min/1.73 m²) and at last follow-up (n = 32; 85.0 ± 29.5 ml/min/1.73 m²; median 5 years, range 1–27 years after delivery). b Intra-individual course of eGFR, paired samples, Wilcoxon test (p < 0.05)

Fig. 3

Disease stages in pregnant women with Alport syndrome. a Alport stages prior to pregnancy (n = 52); b Alport stages during pregnancy (n = 52); c Alport stages after pregnancy (n = 52)

Fig. 4

Visualization of disease progression of Alport patients in the various Alport stages prior to pregnancy. The central area shows the composition of Alport stages before pregnancy (stage 0-1 n = 29, stage 2 n = 17, stage 3 n = 2, N/A n = 4); the middle area shows the disease stage during pregnancy (stage 0-1 n = 16, stage 2 n = 27, stage 3 n = 6, N/A n = 3); and the outer ring shows disease stage after delivery (stage 0-1 n = 16, stage 2 n = 22, stage 3 n = 12, N/A n = 2)