Pregnancy was associated with increased risk of first symptomatic kidney stone, with the highest risk immediately after delivery before returning to baseline one year after delivery, researchers found.
A symptomatic kidney stone is the most common non-obstetric hospital admission diagnosis for pregnant women, and they have the potential to cause pregnancy complications including preterm delivery, premature rupture of membranes, gestational hypertension, pre-eclampsia, urinary tract infection, and pregnancy loss, Andrew D. Rule, MD, MSc, of the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, and colleagues explained in the American Journal of Kidney Diseases. However, despite the fact that kidney stones are relatively common among pregnant women, whether or not pregnancy itself increases the risk of symptomatic kidney stone is unclear.
Several physiological factors of pregnancy could potentially contribute to kidney stone development, but prior studies on the subject have lacked control groups, validation of kidney stone episodes, and analysis of the temporal relationship between the pregnancy and the kidney stone episode. To fill in these knowledge gaps, Rule and colleagues conducted a population-based case-control study to determine whether the risk of first-time symptomatic kidney stone increased during pregnancy and if the risk varied across various time periods before, during, and after pregnancy.
“This study identified pregnancy as an important risk factor for a first-time symptomatic kidney stone,” the study authors wrote. “An elevated risk of a symptomatic stone is noted beginning in the second trimester, peaking right after delivery, and returning to baseline by a year after delivery. This finding does not support the previously reported hypothesis that risk of a kidney stone is not increased during pregnancy. Moreover, as young woman have been shown to have a 2- to 3-fold increase in the incidence of symptomatic kidney stones over recent decades, the increased risk of kidney stones with pregnancy is important for prenatal counseling, particularly for women who have other risk factors for kidney stones such as obesity.”
For their analysis, Rule and colleagues recruited a cohort of 945 women ages 15-45 with first-time symptomatic kidney stone and 1,890 age-matched controls from the Rochester Epidemiology Project (REP), a medical record linkage system from Olmstead County, Minnesota from 1984-2021. The index date was the date of onset of a symptomatic kidney stone for both the case and their matched controls. All pregnancies resulting in a livebirth or stillbirth among cases and controls were identified electronically using the REP birth database, and medical records were reviewed in a random order to identify pregnancies with delivery dates within approximately two years of the index date.
The mean age of study participants was 31 years, and those who developed kidney stones were more likely to be White, and have diabetes, hypertension, obesity, and a past pregnancy compared to the control group, Rule and colleagues found.
“Compared to non-pregnant women, the odds of a symptomatic kidney stone in women was similar in the first trimester (OR=0.92; P=0.81), began to increase during the second trimester (OR=2.00; P=0.007), further increased during the third trimester (OR=2.69; P=0.001), peaked at 0-3 months after delivery (OR 3.53; P<0.001), and returned to baseline by 1-year after delivery,” the study authors reported. “These associations persisted after adjustment for age and race or for diabetes mellitus, hypertension, and obesity. These results did not significantly differ by age, race, time period, or number of prior pregnancies. Having a prior pregnancy (delivery date >1 year ago) was also associated with a first-time symptomatic kidney stone (OR=1.27; P=0.01).”
Kidney stone compositions were more likely to be calcium phosphate during pregnancy, they added. Kidney stone imaging studies were less frequently obtained during pregnancy and, when obtained, were more likely to be ultrasound. The stone was less likely to be seen on imaging during pregnancy, and kidney stones during pregnancy were less bilateral and fewer in number, though they noted that this difference might reflect the preferential use of ultrasound for imaging during pregnancy.
Rule and colleagues noted that prior research reported that the prevalence of kidney stones increases with the number of prior pregnancies, even after adjusting for age and comorbidity. A prior pregnancy (longer than one year ago) was also associated with a modest increase in the risk of first-time symptomatic kidney stone, but that risk did not further increase with multiple prior pregnancies, a fact that the study authors said “might be explained by two competing factors.”
They hypothesized that “a prior pregnancy may lead to an asymptomatic stone formation, but this stone may not grow and pass until a subsequent pregnancy. At the same time, each pregnancy is possibly a “stress test” for kidney stones; a woman who repeatedly does not have kidney stone episodes with multiple pregnancies may be inherently more resistant to stone formation.” They also noted that several physiological changes during pregnancy could explain the increased risk of kidney stone formation. For example, the uterer is compressed by the enlarging uterus against the fixed iliac vessels, and ureteral peristasis is impaired by elevated progesterone levels—these two factors “contribute to the hydronephrosis seen in up to 90% of pregnancies.” Urinary stasis caused by hydronephrosis prolongs contact time between calcium in the urine, enhancing crystallization and stone formation.
Other factors that could contribute to stone formation included:
- The increase in glomerular filtration rate, leading to an increase in the filtered load of calcium.
- Increased gastrointestinal absorption and bone mobilization of calcium due to elevated 1,25-(OH)2 vitamin D production.
- Less kidney reabsorption of filtered calcium due to suppression of parathyroid hormone caused by elevated 1,25-(OH)2 vitamin D.
- Calcium and vitamin D supplements recommended for use during pregnancy.
- Higher urine pH due to a progesterone-induced chronic respiratory alkalosis.
In fact, Rule and colleagues argued that they likely underestimated the true risk of kidney stones with pregnancy due to the preferential use of ultrasound in order to avoid radiation exposure, which may have resulted in missed stones.
Study limitations included a largely White study population and that the exact timing of stone formation could not be determined, as some stones may have formed asymptomatically before becoming symptomatic over the course of pregnancy.
Pregnant women saw a higher risk of first-time symptomatic kidney stone than non-pregnant women in a population-based matched case-control study.
Kidney stone risk increased in the second and third trimesters and peaked 0-3 months after delivery before returning to baseline by one-year post-delivery.
John McKenna, Associate Editor, BreakingMED™
The study authors had no relevant relationships to disclose.
Cat ID: 41
Topic ID: 83,41,730,127,41,192,925