Interpretation
Pregnancy causes structural and functional changes in maternal kidneys.
During the first half of pregnancy, maternal cardiac output, RPF, and
GFR increase and systemic vascular resistance decreases; as a result,
the mean serum creatinine concentration is lower than that of
non-pregnant women4,7,8. Several mechanisms have been
reported to contribute to decreased vascular resistance. During
pregnancy, vascular expression of angiotensin-2 receptors, which causes
vasodilation rather than vasoconstriction in response to angiotensin-2,
increases17. During normal pregnancy, nitric oxide
synthesis increases, which contributes to systemic and renal
vasodilation10. Relaxin, which is secreted in large
amounts by the placenta and decidua in response to human gonadotropin
during pregnancy, increases endothelin and nitric oxide production in
the renal circulation, leading to generalized renal vasodilation,
decreased renal afferent and efferent arteriole resistance, and a
subsequent increase in renal blood flow and GFR18.
Conversely, during the second half of pregnancy, RPF decreases slightly,
resulting in an increased filtration fraction and
proteinuria8,12,19,20. However, not all studies
support an increase in the filtration fraction during the third
trimester of pregnancy, and the mechanisms that drive the physiological
increase in urinary protein excretion during pregnancy are not
well-understood. In addition, physical pressure on the blood vessels and
organs by the pregnant uterus occurs, especially during the late
pregnancy period. This may have a negative effect on the maternal renal
function.
This is the first study, to the best of our knowledge, to show that twin
pregnancy itself is a significant factor associated with maternal renal
dysfunction during the latter half of pregnancy. Below, we discuss how
twin pregnancies can cause maternal renal dysfunction. First, the
cardiac output of women with twin pregnancies is 20% higher than that
in singleton pregnancies, and peaks at 30 weeks of
gestation21. On the other hand, compared with the left
lateral decubitus position, the supine position can lower cardiac output
by as much as 25–30% due to compression of the IVC by the gravid
uterus22. Therefore, because of the larger uterus in
twin pregnancies compared to singleton pregnancies, the longer the
patient is in the supine position, the highly pronounced IVC compression
is likely to result in a greater reduction in cardiac output and thus
RPF. Decreased RPF can result in decreased GFR. However, there were no
data on the posture of the pregnant women in this study, and future
studies are needed to investigate this aspect.
Second, hydroureter and hydronephrosis occurs in approximately 80% of
pregnant women and is more pronounced on the right side than on the
left23. Hydroureters and hydronephrosis during
pregnancy have been attributed to hormonal influences, external
compression, and intrinsic changes in the ureteral
wall24. Progesterone reduces ureteral tone,
peristalsis, and contraction pressure, which are further increased in
twin pregnancies. As pregnancy advances, an enlarged uterus may cause
the ureters to become elongated, tortuous, and laterally displaced. As
mentioned above, twin pregnancies are more prominent than singleton
pregnancies because of urinary tract compression. Occasionally,
obstruction of the ureters by the uterus is sufficient to cause kidney
failure25. Acute kidney injury due to urinary
obstruction resulting from enlarged uterine fibroids during pregnancy
has been reported26, which can be resolved by
insertion of a ureteric stent or delivery of the
fetus27. In summary, we can assume that twin
pregnancies are more likely to cause urinary tract obstruction and,
therefore, maternal renal dysfunction. Third, during pregnancy,
especially in the third trimester, proteinuria increases, and the rate
of pathological proteinuria (300 mg/day or greater) is greater in twin
pregnancies than that in singleton pregnancies (adjusted OR =
9.13)20. In recent years, the usefulness of the urine
albumin-to-creatinine ratio (UACR) has been introduced, which is
strongly predictive of significant proteinuria. The diagnostic accuracy
of the UACR (using a threshold between 20 and 60 mg albumin/g
creatinine) and the urine protein-to-creatinine ratio (UPCR)
(>300 mg protein/day by 24-hour urine collection) are
approximately equal, and the UACR is increasingly being replaced by
UPCR28-30. Increased albuminuria reflects the impaired
permselectivity of glomerular
capillaries to macromolecules, which is reported to be a marker of
kidney damage31. This suggests that an increase in
proteinuria (albuminuria) due to twin pregnancies causes kidney damage,
resulting in renal dysfunction. Unfortunately, we have no data regarding
proteinuria (albuminuria) in this study, and further investigation is
warranted.