Maternal adaptations to pregnancy: Renal and

urinary tract physiology

Authors:
Ravi I Thadhani, MD, MPH
Sharon E Maynard, MD
Section Editors:
Richard J Glassock, MD, MACP
Richard H Sterns, MD
Deputy Editor:
Alana Chakrabarti, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2021. | This topic last updated: Apr 29, 2020.

INTRODUCTION Normal pregnancy is characterized by profound changes in

almost every organ system to accommodate the demands of the fetus. Thus, pregnancy
results in both structural and functional changes of the kidney and urinary tract. This
topic will review physiologic changes in the kidney and urinary tract.

Related topics on kidney disease in pregnancy and other maternal adaptations can be
found separately.

●(See "Pregnancy in women with nondialysis chronic kidney disease".)

●(See "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic
changes".)
●(See "Maternal adaptations to pregnancy: Hematologic changes".)
●(See "Evaluation of proteinuria in pregnancy and management of nephrotic
syndrome".)

RENAL CHANGES Pregnancy leads to an increase in kidney size, renal

plasma flow, and glomerular filtration rate (GFR) (table 1).

Size — Both kidneys increase 1 to 1.5 cm in length during pregnancy [1]. Kidney
volume increases by up to 30 percent [2], primarily due to an increase in renal vascular
and interstitial volume. There are no histologic changes or changes in number of
nephrons, but the GFR is also increased. (See 'Renal plasma flow and glomerular
filtration rate disconnect in late gestation' below.)
The renal pelvises and caliceal systems may be dilated as a result of progesterone
effects and mechanical compression of the ureters at the pelvic brim.
(See 'Ureters' below.)
Hemodynamic changes — Normal pregnancy is characterized by widespread
vasodilation, with increased arterial compliance, leading to decreased systemic vascular
resistance, increased cardiac output, and a small decrease in blood pressure (figure 1)
(see "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes").
These global hemodynamic changes include increased renal perfusion and GFR (table
2).
Glomerular filtration rate, renal plasma flow, and serum creatinine — Renal plasma
flow increases by up to 80 percent by 12 weeks of gestation [3], but then decreases in
the third trimester. (See 'Renal plasma flow and glomerular filtration rate disconnect in
late gestation' below.)
The increase in GFR is observed within one month of conception, peaks at
approximately 40 to 50 percent above baseline levels by the early second trimester, and
then declines slightly toward term [4]. Of note, in late gestation, left lateral positioning
increases GFR and sodium excretion [5].
The physiologic increase in GFR during pregnancy results in a decrease in serum
creatinine concentration in early pregnancy [6]. In a retrospective database study
including over 240,000 pregnancies in Canada, the mean serum creatinine
concentration dropped in the first trimester (beginning at four weeks of gestation),
leveled off in the second trimester, and then gradually rose again in the third trimester to
near prepregnancy levels [7]. The mean serum creatinine level was 0.68 mg/dL (60
micromol/L) prepregnancy, fell to 0.53 mg/dL (47 micromol/L) between 16 and 32 weeks
of gestation, and then increased to 0.72 mg/dL (64 micromol/L) at 18 weeks
postpartum. In midgestation (16 to 32 weeks), the 95th percentile (a reasonable estimate
of the upper limit of normal) for serum creatinine was >0.67 mg/dL (>59 micromol/L).

Thus, a serum creatinine of 0.8 mg/dL (70.7 micromol/L) or above, while normal in a
nonpregnant individual, usually reflects renal impairment in a pregnant woman. Blood
urea nitrogen levels fall to approximately 8 to 10 mg/dL (2.9 to 3.9 mmol/L) for the same
reason.

A small rise in serum creatinine usually reflects a marked reduction in renal function.
For example, in a physiologic study, women with preeclampsia had a 40 percent
reduction in GFR as compared with control pregnant women (89 versus 149
mL/min/1.73 m2 body surface area), but the serum creatinine levels remained within the
normal range (0.89 mg/dL in preeclampsia versus 0.60 mg/dL in control pregnancies)
[8]. Careful attention to small fluctuations in serum creatinine is required to detect renal
injury in pregnancy.
Mechanisms of increased glomerular filtration rate — Several mechanisms
contribute to decreased vascular resistance, increased renal plasma flow, and
increased GFR during pregnancy. Reduced vascular responsiveness to vasopressors
such as angiotensin 2, norepinephrine, and antidiuretic hormone (ADH) is well
documented [9]. This may be mediated, in part, by altered vascular receptor expression.
For example, vascular expression of the AT2 receptor, which produces vasodilation
rather than vasoconstriction in response to angiotensin II, is increased in pregnancy
[10]. Nitric oxide synthesis increases during normal pregnancy and may contribute to
the systemic and renal vasodilation and the fall in blood pressure [11,12].
Relaxin — Additionally, the ovarian hormone and vasodilator relaxin is a key mediator
of enhanced nitric oxide signaling in pregnancy. Relaxin is a peptide hormone in the
insulin family; it is normally produced in the corpus luteum and, in pregnancy, is
secreted in large amounts by the placenta and decidua in response to human chorionic
gonadotropin (hCG) (figure 2) [13]. Relaxin increases endothelin and nitric oxide
production in the renal circulation, leading to generalized renal vasodilation, decreased
renal afferent and efferent arteriolar resistance, and a subsequent increase in renal
blood flow and GFR. Chronic administration of relaxin in rats mimics the renal
hemodynamic changes of pregnancy (20 to 40 percent increase in GFR and renal
plasma flow); these changes can be abolished by the administration of a nitric oxide
synthase inhibitor [14]. In pregnant rats, increases in GFR and renal plasma flow can
also be abolished by the administration of antirelaxin antibodies or by oophorectomy
[15].
Relaxin has systemic hemodynamic effects which may be beneficial in human disease,
particularly heart failure. (See "Investigational and emerging strategies for management
of heart failure", section on 'Serelaxin'.)
Renal plasma flow and glomerular filtration rate disconnect in late
gestation — The gestational increase in GFR is primarily driven by increased renal
plasma flow [16]. In fact, through most of pregnancy, the rise in renal plasma flow
exceeds the increase in GFR, with a fall in the filtration fraction. Late in gestation, renal
plasma flow falls slightly, while GFR is maintained, resulting in an increased filtration
fraction [17]. However, not all studies support an increase in filtration fraction in the third
trimester [18-22]. The maintenance of a high GFR despite a fall in renal plasma flow in
late pregnancy may be due to decreased capillary oncotic pressure, increased
glomerular capillary pressure, and/or increased hydraulic permeability and surface area
of the glomerular filtration barrier.
Estimation of glomerular filtration rate — Endogenous creatinine clearance,
measured by 24-hour urine collection, remains the standard of care for estimation of
GFR in pregnancy [23,24]. Commonly used creatinine-based estimating formulas
should not be used in pregnant women [23-27]. All GFR formulas, including the
Modification of Diet in Renal Disease Study (MDRD) and Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) equations, consistently and significantly
underestimate true GFR in pregnancy.
However, 24-hour urine collection is cumbersome for the patient, and both over- and
under-collection are common [28]. Inaccurate collection may be due, in part, to urinary
stasis from dilation of the lower urinary tract in pregnancy: Several hundred milliliters of
urine can be trapped in the dilated ureters, resulting in a significant lapse between urine
formation and urine collection. For this reason, it is important to assess the adequacy of
the collection by measuring urine creatinine excretion. A complete 24-hour urine
collection will contain 10 to 15 mg of creatinine per kg body weight, using either
prepregnancy or current maternal weight [28]. (See "Assessment of kidney function",
section on 'Limitations of using creatinine clearance' and "Assessment of kidney
function", section on 'Estimation equations'.)
Laboratory tests — Changes in renal hemodynamics and solute handling during
pregnancy result in alterations in laboratory test results. Normal values vary slightly by
gestational age [29-31].
Hyponatremia — The plasma osmolality in normal pregnancy falls to a new set point of
approximately 270 mOsmol/kg (from a nonpregnancy level of 275 to 290 mOsmol/kg),
with a proportional decrease in plasma sodium concentration to 4 to 5 mEq/L below
nonpregnancy levels [32]. The physiologic responses to changes in osmolality above or
below the new set point (ie, thirst and release of ADH from the pituitary) are intact.
Hyponatremia of pregnancy appears to be mediated by hormonal factors. The fall in the
plasma sodium concentration during pregnancy correlates closely with increased
production of hCG [33,34]. Furthermore, the administration of hCG to normal women
during the luteal phase of the menstrual cycle can induce a similar resetting of the
thresholds for ADH release and thirst [33,35]. Rather than acting directly, hCG appears
to produce these changes via the release of relaxin [14]. As an example, hyponatremia
in pregnant rats can be corrected by the administration of antirelaxin antibodies or by
oophorectomy [15]. As noted above, relaxin also plays an important role in the
increased GFR in pregnancy. (See 'Hemodynamic changes' above.)
A serum sodium concentration below 130 mEq/L in pregnancy should prompt evaluation
for pathologic causes of hyponatremia, such as syndrome of inappropriate ADH
secretion. Evaluation of hyponatremia in such cases can be approached similarly to
nonpregnant individuals. Hypernatremia, particularly in the setting of polyuria, should
spur an evaluation for possible diabetes insipidus. (See "Polyuria and diabetes insipidus
of pregnancy".)
●(See "General principles of disorders of water balance (hyponatremia and
hypernatremia) and sodium balance (hypovolemia and edema)".)
●(See "Diagnostic evaluation of adults with hyponatremia".)
●(See "Manifestations of hyponatremia and hypernatremia in adults".)

Attempts to correct the physiologic hyponatremia of pregnancy are both unnecessary

(the change is mild and asymptomatic) and ineffective. Resetting of the osmostat
means that the plasma sodium concentration will be maintained at the new level despite
variations in water or sodium intake.

Proteinuria — Urinary protein excretion rises in normal pregnancy, from the

nonpregnant level of approximately 100 mg/day to approximately 150 to 200 mg/day in
the third trimester [36]. This may result in a positive dipstick result when a concentrated
urine sample is examined. Urinary protein excretion greater than 300 mg/day is
considered abnormal and should prompt further evaluation [37]. (See "Evaluation of
proteinuria in pregnancy and management of nephrotic syndrome".)
The mechanisms driving the physiologic increase in urinary protein excretion in
pregnancy are not well understood but may include increased GFR, increased
glomerular basement membrane pore size [38], increased protein transport across the
glomerular filtration barrier via the nondiscriminatory shunt pathway [39], and reduced
tubular reabsorption of filtered protein. Circulating antiangiogenic factors, which cause
glomerular endothelial dysfunction and proteinuria in preeclampsia, increase toward
term and may contribute to late gestational proteinuria even when preeclampsia is
absent [40].
Urine protein excretion is even higher in uncomplicated twin pregnancy, which can lead
to diagnostic confusion when evaluating a woman for preeclampsia because values
greater than 300 mg/day are considered abnormal [37]. In a prospective study of 50
twin pregnancies, 15 of 35 women (43 percent) who never developed hypertension had
urine protein excretion of at least 300 mg/day at 30 weeks of gestation [41]. If confirmed
in a larger study, these findings suggest that the definition of pathologic proteinuria in
singleton pregnancies should not be applied to twin pregnancies. (See "Preeclampsia:
Clinical features and diagnosis".)
Glucosuria — Glucosuria by dipstick testing is seen in approximately 50 percent of
pregnant women, and hence is not a useful screening tool for diabetes mellitus [42].
Glucosuria is primarily due to decreased proximal tubular glucose reabsorption [43].
(See 'Other changes' below.)
Other changes
●Chronic respiratory alkalosis – Minute ventilation rises in early pregnancy and
remains elevated until term, leading to a modest fall in the pCO2 (to 27 to 32
mmHg) and mild respiratory alkalosis. These changes are due to direct stimulation
of the central respiratory centers by progesterone [44]. The increase in minute
ventilation allows maintenance of a high-normal pO2 despite the 20 to 33 percent
increase in oxygen consumption in pregnancy. There is an appropriate metabolic
response to the respiratory alkalosis: plasma bicarbonate levels decrease in normal
pregnancy from 26 to approximately 22 mmol/L [45]. (See "Maternal adaptations to
pregnancy: Dyspnea and other physiologic respiratory changes", section on
'Physiologic cardiopulmonary changes in pregnancy'.)
●Hypouricemia – Serum uric acid declines in early pregnancy because of the rise
in GFR, reaching a nadir of 2.0 to 4.0 mg/dL (119 to 238 micromol/L) and remains
low until 22 to 24 weeks of gestation (table 3) [46]. Thereafter, the uric acid level
begins to rise, reaching nonpregnant levels by term. The late gestational rise in uric
acid is attributed to increased renal tubular absorption of urate.
●Decrease in serum anion gap and albumin – For reasons that are not well
understood, the serum albumin concentration falls in normal pregnancy (table 3).
The serum anion gap also falls, from 10.7 in the nonpregnant state to 8.5 during
pregnancy [47]. Since negatively charged albumin is a major component of the
anion gap, the physiologic hypoalbuminemia of pregnancy may account for the fall
in the anion gap. Low albumin levels in pregnancy can lead to increased free levels
of drugs which are highly protein-bound, such as digoxin, midazolam,
and phenytoin [48].
●Impaired tubular function – Pregnancy is associated with decreased fractional
reabsorption of amino acids and beta-microglobulin, in addition to glucose, which
results in higher rates of urinary excretion. Thus, pregnant patients may exhibit
glucosuria and aminoaciduria in the absence of hyperglycemia or renal disease
[49].

URINARY TRACT

Ureters — Dilation of the ureters and renal pelvis (hydroureter and hydronephrosis) is
more prominent on the right than the left and is seen in up to 80 percent of pregnant
women [50]. These changes can be visualized on ultrasound examination by the
second trimester and resolve by 6 to 12 weeks postpartum.
The dilated collecting system can hold 200 to 300 mL of urine. The resulting urinary
stasis can serve as a reservoir for bacteria, which may contribute to the increased risk
of pyelonephritis in pregnancy. (See "Urinary tract infections and asymptomatic
bacteriuria in pregnancy".)
Hydroureter and hydronephrosis in pregnancy have been attributed to hormonal effects,
external compression, and intrinsic changes in the ureteral wall [51]. The following
factors may contribute:
●High concentrations of progesterone reduce ureteral tone, peristalsis, and
contraction pressure.
●More prominent involvement of the right ureter may be due to dextrorotation of the
uterus by the sigmoid colon, kinking of the ureter as it crosses the right iliac artery,
and/or proximity to the right ovarian vein.
●The vessels in the suspensory ligament of the ovary enlarge and may compress
the ureter at the brim of the bony pelvis.
●Uterine enlargement may cause the ureters to become elongated, tortuous, and
displaced laterally as pregnancy advances. In rare cases, compression of the
ureters causes pain and true urinary obstruction, which resolves with placing the
mother on her side, insertion of stents, and/or delivery [52]. (See "Acute kidney
injury in pregnancy", section on 'Urinary tract obstruction'.)
●Hypertrophy of Waldeyer's sheath (the connective tissue that surrounds the
ureters within the true pelvis) may prevent hormone-induced dilation below the
pelvic brim [53].
Pathologic obstruction (ie, by nephrolithiasis or stricture) will also lead to ureteral
dilation. Pathologic hydronephrosis can usually be distinguished from physiologic
hydronephrosis by the presence of flank pain or radiographically or sonographically by
visualizing the cause of the obstruction. (See "Nephrolithiasis during pregnancy".)
Bladder — The bladder mucosa is edematous and hyperemic in pregnancy. Although
progesterone-induced bladder wall relaxation may lead to increased capacity, the
enlarging uterus displaces the bladder superiorly and anteriorly, and flattens it, which
can decrease capacity. Studies of bladder capacity during pregnancy have yielded
conflicting results [54,55].
Vesicoureteral reflux — Bladder flaccidity may cause incompetence of the
vesicoureteral valve. This change, combined with increased intravesical and decreased
intraureteral pressure, appears to result in intermittent vesicoureteral reflux [56,57].
Symptoms — Lower urinary tract symptoms of urinary frequency, nocturia, dysuria,
urgency, and stress incontinence are common during pregnancy [54].
●Frequency and nocturia – Urinary frequency (voiding >7 times per day) and
nocturia (voiding ≥2 times at night) are among the most common pregnancy-related
complaints, affecting 80 to 95 percent of women at some point during gestation [58-
60]. Frequency is caused by changes in bladder function and a small increase in
urine output. Urinary frequency typically begins in the first trimester; thus,
mechanical compression of the bladder by the enlarged uterus is not likely to be the
primary cause [58,61].
Nocturia is common and increases with advancing gestation. In a survey of 256
pregnant women, 86 percent reported nocturia by the third trimester, with 20
percent of women indicating they voided three or more times nightly [62]. In the
latter stages of pregnancy, nocturia may be partially attributable to nocturnal
mobilization of dependent edema when the woman is in the lateral position.
 The possibility of diabetes insipidus of pregnancy should be considered in pregnant
women with severe polyuria and nocturia. (See "Polyuria and diabetes insipidus of
pregnancy".)
●Urgency and incontinence – Urinary frequency, urgency, and incontinence are
common during pregnancy [60,61,63,64]. These symptoms may be due to uterine
pressure on the bladder, hormonal effects on the suspensory ligaments of the
urethra, and/or altered neuromuscular function of the urethral striated sphincter
[54,61,65,66]. Treatment includes pelvic floor muscle training. (See "Treatment of
urinary incontinence in females", section on 'Pelvic floor muscle (Kegel) exercises'.)
●Urinary retention – The bladder and urethra inevitably experience some trauma
during labor and delivery. The traumatic changes include mucosal congestion and
submucosal hemorrhage, which are most evident at the trigone [67]. Bladder
sensitivity/sensation is also decreased from trauma. As a result, detrusor atony,
increased postvoid residual urine, bladder overdistention, and urinary retention are
common in the first few days after delivery. These symptoms are typically mild and
transient. (See "Acute urinary retention" and "Postoperative urinary retention in
females".)

POSTPARTUM The pregnancy-induced physiologic changes described above

return to the nonpregnant state by four to six weeks following delivery [17,68]. However,
urinary incontinence may persist. Pregnancy- and delivery-related urinary incontinence
is reviewed elsewhere. (See "Effect of pregnancy and childbirth on urinary incontinence
and pelvic organ prolapse".)

SUMMARY AND RECOMMENDATIONS

●Kidney size increases by 1.0 to 1.5 cm during pregnancy. Kidney volume

increases by up to 30 percent, primarily due to an increase in renal vascular and
interstitial volume. (See 'Size' above.)
●Glomerular filtration rate (GFR) and renal blood flow rise markedly during
pregnancy, resulting in a physiologic fall in the serum creatinine concentration. A
serum creatinine of 1.0 mg/dL in a pregnant woman probably reflects significant
renal insufficiency. (See 'Glomerular filtration rate, renal plasma flow, and serum
creatinine' above.)
●Several mechanisms contribute to decreased vascular resistance, increased renal
plasma flow, and increased GFR during pregnancy. Reduced vascular
responsiveness to vasopressors such as angiotensin 2, norepinephrine, and
antidiuretic hormone is well documented. Additionally, the ovarian hormone and
vasodilator relaxin is a key mediator of enhanced nitric oxide signaling in
pregnancy. (See 'Mechanisms of increased glomerular filtration rate' above.)
●The best method to accurately estimate GFR in pregnancy is by 24-hour urine
collection for creatinine clearance. Completeness of the collection should be
confirmed by checking the 24-hour creatinine excretion (10 to 15 mg creatinine/day
per kg body weight is consistent with a complete collection). Estimating equations,
 such as the Modification of Diet in Renal Disease Study (MDRD) and Chronic
Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, are not accurate
in pregnancy. (See 'Estimation of glomerular filtration rate' above.)
●Other physiologic changes in pregnancy include respiratory alkalosis, mild
hyponatremia, glucosuria, and proteinuria up to 300 mg/day. (See 'Other
changes' above.)
●Physiologic ureteral dilation (hydronephrosis and hydroureter) is common during
pregnancy, and results from hormonal effects, external compression, and intrinsic
changes in the ureteral wall. (See 'Ureters' above.)
●Urinary frequency and nocturia are common, but usually require no specific
treatment. Urinary incontinence also can occur during pregnancy.
(See 'Symptoms' above.)
●The pregnancy-induced physiologic changes of the kidneys and urinary tract
return to the nonpregnant state by four to six weeks following delivery.
(See 'Postpartum' above.)

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