Oxford Handbook of Urology (3 edn)
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Physiological and anatomical changes in the urinary tract
Upper urinary tract
Renal size enlarges: by 1cm, secondary to increased interstitial volume and distended renal vasculature, with renal volume increasing up to 30%.
Dilatation of the collecting systems: producing physiological hydronephrosis and hydroureters (right > left side), which starts in the second month of pregnancy and is maximal by the middle of the second trimester. It is caused by mechanical obstruction by the growing uterus and ovarian venous plexus and smooth muscle relaxation due to progesterone.
Renal plasma flow (RPF) rate: goes up early in the first trimester, reaching an increase of ∼75% by 16 weeks’ gestation. This is maintained until 34 weeks’ gestation, followed by a decline of ∼25% towards term.
GFR: increases by 50% by the end of the first trimester, which is maintained until term. GFR has returned to normal levels by 3 months after delivery.
Renal function and biochemical parameters: are affected by changes in RPF and GFR. Creatinine clearance increases and serum levels of creatinine, urea, and urate fall in normal pregnancy due to glomerular hyperfiltration (Table 15.1). Raised GFR causes an increased glucose load at the renal tubules and results in glucose excretion (physiological glycosuria of pregnancy which tends to be intermittent). Of note, patients with persistent glycosuria should be screened for diabetes mellitus. Proteinuria is only increased in women with pre-existing proteinuria before pregnancy. Urine output is increased.
Salt and water handling: a reduction in serum sodium causes reduced plasma osmolality. The kidney compensates by increasing renal tubular reabsorption of sodium. Plasma renin activity is increased 10-fold and levels of angiotensinogen and angiotensin are increased 5-fold. Osmotic thresholds for ADH and thirst decrease.
Acid–base metabolism: serum bicarbonate is reduced. Increased progesterone stimulates the respiratory centre, resulting in reduced PCO2.
| Substance | Non-pregnant | Pregnant |
|---|---|---|
Sodium (mmol/L) | 135–145 | 132–141 |
Urea (mmol/L) | 2.5–6.7 | 2–4.2 |
Urate (μmol/L) | 150–390 | 100–270 |
Creatinine (μmol/L) | 70–150 | 24–68 |
Creatinine clearance (mL/min) | 90–110 | 150–200 |
Bicarbonate (mmol/L) | 24–30 | 20–25 |
| Substance | Non-pregnant | Pregnant |
|---|---|---|
Sodium (mmol/L) | 135–145 | 132–141 |
Urea (mmol/L) | 2.5–6.7 | 2–4.2 |
Urate (μmol/L) | 150–390 | 100–270 |
Creatinine (μmol/L) | 70–150 | 24–68 |
Creatinine clearance (mL/min) | 90–110 | 150–200 |
Bicarbonate (mmol/L) | 24–30 | 20–25 |
Lower urinary tract
Bladder: displacement occurs (superiorly and anteriorly) due to the enlarging uterus. The bladder becomes hyperaemic and raised oestrogen levels cause hyperplasia of muscle and connective tissues. Bladder pressures can increase over pregnancy (from 9 to 20cmH2O), with associated rises in absolute and functional urethral length and pressures.
Haematuria: there is an increased risk of non-visible haematuria due to elevation of the trigone and increased bladder vascularity. Persistent non-visible haematuria, patients with associated risk factors (i.e. smoking), or visible haematuria will need further investigation similar to non-gravid patients. Placenta precreta (placenta invades the bladder) can cause haematuria and should be excluded as a cause.
LUTS: urinary frequency (>7 voids during the day) and nocturia (≥1 void at night) increase over the duration of gestation (incidence of 80–90% in third trimester). Urgency is reported in up to 60% and urge incontinence may develop in 10–20%, predominantly in the third trimester. These effects are contributed to by pressure on the bladder from the enlarging uterus, causing reduced functional capacity. Nocturia is also exacerbated due to the increased excretion of water (whilst lying down) that tends to be retained during the day. Normal bladder function returns in the majority soon after delivery.
Acute urinary retention: is uncommon during pregnancy, but may occur at 12–14 weeks’ gestation in association with a retroverted uterus, which resolves by 16 weeks. Fibroids and other uterine anomalies may predispose to retention. Post-partum urinary retention occurs in up to 18%, associated with epidural use, assisted or first delivery, and long duration of labour.
Stress urinary incontinence: occurs in around 22% and increases with parity. It is partly caused by the placental production of peptide hormones (relaxin), which induces collagen remodelling and consequent softening of tissues of the birth canal. Infant weight, duration of first and second stages of labour (vaginal delivery), and instrumental delivery (ventouse extraction or forceps delivery) increase risks of post-partum stress incontinence.
Urinary tract infection (UTI)
Pregnancy does not alter the incidence of lower UTI. However, physiological and anatomical changes associated with pregnancy can alter the course of infection, causing an increased risk of recurrent UTI and progression to acute pyelonephritis.
Asymptomatic bacteriuria
An asymptomatic lower UTI which affects 5–10% of pregnant women, with a 20–40% risk of developing pyelonephritis during pregnancy. This risk is reduced if the bacteriuria is treated and, therefore, urine screening in pregnancy is advocated.
Symptomatic UTI
Cystitis: affects 1–3% and presents with urinary frequency, urgency, suprapubic pain, and dysuria.
Acute pyelonephritis: is more frequently seen than in non-pregnant women, affecting around 1–2%. It is most common in the third trimester and is most likely to affect the right side. Most are due to undiagnosed or inadequately treated lower UTI. It presents with fever, flank pain, nausea, and vomiting, often with an elevated WCC.
Risk factors for UTI
Previous history of recurrent UTIs, pre-existing anatomical or functional urinary tract abnormality (i.e. VUR), diabetes. Physiological changes in pregnancy include hydronephrosis with decreased ureteric peristalsis, causing urinary stasis. Up to 75% of pyelonephritis occurs in the third trimester when these changes are most prominent.
Pathogenesis
The most common causative organism is E. coli. An increased risk of gestational pyelonephritis is associated with E. coli containing the virulence factor ‘Dr adhesin’. Other common organisms include Klebsiella and Proteus.
Complications
UTI generally increases the risk of preterm delivery, low fetal birth weight, intrauterine growth retardation, and maternal anaemia. Acute pyelonephritis can be complicated by progression to septic shock, signs of preterm labour, and adult respiratory distress syndrome.
Screening tests
MSU: should be obtained at the first antenatal visit (week 10) and sent for urinalysis and culture to look for bacteria, protein, and blood. Repeated MSU investigation (urine dipstick ± culture) is recommended at later antenatal visits to examine for signs of bacteriuria (usually leukocyte esterase and nitrite-positive), protein, and glucose, particularly in high-risk patients with a history of urinary tract anomalies or recurrent UTI. (see 
p. 177; Table 6.2 for the recommended criteria for diagnosing UTI.)
Treatment
All proven episodes of UTI should be treated (asymptomatic or symptomatic), guided by urine culture sensitivities for 3–7 days, with follow-up cultures 1 week later and at one other point before delivery. Antibiotics that are safe to use during pregnancy include penicillins (i.e. ampicillin, amoxicillin, penicillin V) and cephalosporins (i.e. cefaclor, cefalexin, cefotaxime, ceftriaxone, cefuroxime) (Table 15.2). Moderate to severe pyelonephritis or women with pyelonephritis who develop signs of preterm labour require hospital admission for IV antibiotics (cephalosporin or aminopenicillin) until apyrexial. This is followed by oral antibiotics to complete a total of 10–14 days of therapy and repeated cultures for the duration of pregnancy.
| Trimester | Antibiotic | Potential risk to the fetus |
|---|---|---|
1,2,3 | Tetracyclines | Effects on skeletal development and dental discol-oration (maternal hepatotoxicity) |
1,2,3 | Quinolones | Arthropathy |
1,2,3 | Chloramphenicol | Neonatal ‘grey’ syndrome in third trimester |
1 | Trimethoprim | Teratogenic risk (folate antagonist) |
2,3 | Aminoglycosides | Auditory or vestibular nerve damage |
3 | Sulphonamides | Neonatal haemolysis; methaemoglobinaemia |
Avoid at term | Nitrofurantoin | Neonatal haemolysis |
| Trimester | Antibiotic | Potential risk to the fetus |
|---|---|---|
1,2,3 | Tetracyclines | Effects on skeletal development and dental discol-oration (maternal hepatotoxicity) |
1,2,3 | Quinolones | Arthropathy |
1,2,3 | Chloramphenicol | Neonatal ‘grey’ syndrome in third trimester |
1 | Trimethoprim | Teratogenic risk (folate antagonist) |
2,3 | Aminoglycosides | Auditory or vestibular nerve damage |
3 | Sulphonamides | Neonatal haemolysis; methaemoglobinaemia |
Avoid at term | Nitrofurantoin | Neonatal haemolysis |
See BNF for full details.
Of note, antibiotics which undergo excretion by glomerular filtration may need dose adjustment in pregnancy due to increased renal clearance of these drugs.
Hydronephrosis of pregnancy
Hydronephrosis is dilatation of the renal collecting system (pelvis and calyces). It can be associated with hydroureters (dilatation of the ureters) and represents a normal physiological event in pregnancy which is usually asymptomatic. Hydronephrosis develops from 6–10 weeks’ gestation. By 28 weeks’ gestation, 90% of pregnant women have hydronephrosis. The incidence appears to be higher in first pregnancies. It usually resolves within 2 months of delivery.
Anatomical causes
As the uterus enlarges, it rises out of the pelvis and rests upon the ureters, compressing them at the level of the pelvic brim. In addition, the ureters become elongation and mildly tortuous, with lateral displacement due to the gravid uterus. The right ureter is generally more dilated than the left due to extrinsic compression from the overlying congested right uterine vein and dextrorotation of the gravid uterus. The left ureter tends to be cushioned from compression by the colon. Ureteric dilatation tends to be from above the pelvic brim.
Physiological causes
Early onset of upper urinary tract dilatation is attributed to increased levels of progesterone, which causes smooth muscle relaxation. This mechanism, coupled with mechanical obstruction, contributes to the reduced peristalsis observed in the collecting system during pregnancy.
Diagnostic dilemmas
The hydronephrosis of pregnancy poses diagnostic difficulties in women presenting with flank pain thought to be due to a renal or ureteric calculi (see p. 488). To avoid using ionizing radiation in pregnant women, renal USS is often used as the initial imaging technique in those presenting with flank pain. In the non-pregnant patient, the presence of hydronephrosis is taken as surrogate evidence of ureteric obstruction. Because hydronephrosis is a normal finding in the majority of pregnancies, its presence cannot be taken as a sign of a possible ureteric stone. USS is an unreliable way of diagnosing the presence of stones in pregnant (and in non-pregnant) women. In a series of pregnant women, USS had a sensitivity of 34% (i.e. it ‘misses’ 66% of stones) and a specificity of 86% for detecting an abnormality in the presence of a stone (i.e. false positive rate of 14%).1 Measurement of resistive index (RI)* (derived from measuring the velocity of intrarenal blood flow using Doppler) improves the sensitivity and specificity of the diagnosis of ureteric obstruction, along with attempts to visualize ureteric jets. Pregnant women with obstruction secondary to stones have a higher difference in RI between affected and unaffected kidneys than women with non- obstructive hydronephrosis. Colour Doppler and transvaginal USS enhance the diagnostic accuracy further. MRU is a second-line investigation for evaluating painful hydronephrosis in the second and third trimesters.
Parity = pregnancies that resulted in delivery beyond 28 weeks’ gestation; post-partum = after delivery of the baby; gravid = pregnant.
