Renal changes during pregnancy include: 1. Structural changes such as increased kidney size and volume due to vascular and interstitial fluid changes. 2. Systemic changes including resetting of osmoregulation and volume regulation set points to accommodate increased plasma volume. Hormonal changes like increased progesterone, relaxin, and erythropoietin also impact renal function. 3. Renal hemodynamic changes with glomerular filtration rate increasing up to 50% in the first trimester due to reduced oncotic pressure and increased ultrafiltration capacity, remaining elevated through pregnancy.

1. Renal Changes
during Pregnancy
Waleed Elrefaey MD
Lecturer of Internal Medicine
Nephrology Division
Faculty of Medicine, Tanta University

2. AGENDA
• Structural Changes
• Systemic Changes:
 Osmoregulation
 Volume Regulation
 Endocrinal Changes
 Systemic Hemodynamics
 Electrolytes
• Renal Hemodynamics
• Renal Tubular Function
• Impact on Fetal Programming

3. • Substantial structural and functional changes take place as
a maternal adaptation to normal pregnancy.
• A state of new temporary norm, due to alterations in:
Renal Changes during Pregnancy
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• Distinguish normal from compromised pregnancies.

4. Structural Changes
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5. Structural Changes
• Increase in renal bipolar diameter.
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1st Trimester 2nd Trimester 3rd TrimesterNon pregnant Postpartum
1-1.5 cm
By 26th week
3-6 months

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Structural Changes
Kidney volume enlarges
by about 30% because
of increments in both
vascular and interstitial
fluid compartments.
Physiologic hydronephrosis
Smooth muscle–
relaxing effect of
progesterone
Mechanical
compression by the
enlarging uterus
Ogueh O, Clough A, Hancock M, Johnson MR. A longitudinal study of the control of renal and uterine hemodynamic changes of
pregnancy. Hypertens Pregnancy. 2011;30:243-259.
Rasmussen PE, Nielson FR. Hydronephrosis in pregnancy: a literature survey. Eur J Obstet Gynecol Reprod Biol. 1988; 27(3):249–259.
Urinary stasis predisposes pregnant
women with asymptomatic bacteriuria to
develop acute pyelonephritis.

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Structural Changes
The right ureter crosses the iliac and ovarian vessels at a more acute
angle than left ureter before entering the pelvis
Intravenous urogram at 36 weeks’ gestation

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Structural Changes
Threshold for development: 20 weeks
Maximal incidence: 28 weeks
Overall incidence: 63%

9. • Physiologic Proteinuria:
• Urine protein excretion increases during the course of normal
pregnancy, up to 250 mg/day.
• Gestational proteinuria has been attributed to:
1. Hyperfiltration.
2. Increase in glomerular membrane pore size and permeability in
the absence of a change in hydrostatic force.
3. As well as alterations in proximal tubular function.
• The threshold for pathological proteinuria in pregnancy has been
set at a protein excretion more than 300 mg/day or
(UPCR > 0.3 g/g).
Milne, J. E. C., Lindheimer, M. D. & Davison, J. M. Glomerular heteroporous membrane modeling in third trimester and postpartum before
and during amino acid infusion. Am. J. Physiol. Renal Physiol. 282, F170–F175 (2002).
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Structural Changes

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Structural Changes
an increase of 150 mg/g in singleton pregnancies and 220
mg/g in twin pregnancies at 34–38 weeks of gestation.

11. • In pre-eclampsia, studies have described the release of soluble
antiangiogenic factors from the ischemic placenta that are
injurious to the vascular endothelium, and disrupt the slit
diaphragm.
• The balance of angiogenic and antiangiogenic factors provides
further insights in protein excretion even in healthy pregnancy.
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Structural Changes

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Structural Changes
soluble fms-like tyrosine kinase 1
Placental growth factor VEGF
• The resultant maternal endothelial dysfunction is best
demonstrated at the level of the glomerulus in which GFR
depression and proteinuria are a direct result of glomerular
endotheliosis.
Maynard SE, et al: Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction,
hypertension, and proteinuria in preeclampsia. J Clin Invest 111: 649–658, 2003
Lafayette RA, Druzin M, Sibley R, Derby G, Malik T, Huie P, Polhemus C, Deen WM, Myers BD: Nature of glomerular
dysfunction in pre-eclampsia. Kidney Int 54: 1240–1249, 1998
VEC

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Structural Changes

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Structural Changes

15. Systemic Changes
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16. Systemic Changes
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Osmoregulation Volume Regulation
Endocrinal Changes Electrolytes
Systemic Hemodynamics

17.  Osmoregulation
• Early in pregnancy, plasma osmolality decreases
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Systemic Changes
10 mOsm/kg below the
nonpregnant norm because of
a reduction in serum sodium
and associated anions.
The osmotic threshold for
antidiuretic hormone
(ADH) release
The threshold
for thirst
to recognize the
reduced plasma
osmolality and
expanded plasma
volume as normal.
Plasma volume status
(a nonosmotic
determinant of ADH
release) is also reset

18.  Osmoregulation
• Human chorionic gonadotropin (which stimulates the release of
ovarian relaxin) may have a role in this reduction of the osmotic
threshold for ADH release.
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Systemic Changes
Lindheimer MD, Davison JM. Osmoregulation, the secretion of arginine vasopressin and its metabolism during pregnancy. Eur J
Endocrinol. 1995;132:133-143.
The metabolic clearance rate of
ADH has increased four times at
week 10 and through midpregnancy
because of the release of enzyme
vasopressinase from the placenta.
Plasma ADH
concentrations are
usually kept normal in
pregnancy because of
increased secretion.

19.  Volume Regulation
• The increase in plasma volume (1.2-1.6 liters) takes place
progressively up to 32 to 34 weeks, after which there is little
further change.
• The increase in plasma renin, angiotensin and aldosterone
concentrations of normal pregnancy suggests an underfill signal
• due to peripheral vasodilatation, that leads to renal sodium and
water retention.
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Systemic Changes
Schrier RW. Pathogenesis of sodium and water retention in high-output and low-output cardiac failure, nephrotic syndrome, cirrhosis and
pregnancy. Part 2. N Engl J Med. 1988;319:1127-1134.

20.  Volume Regulation
• The tubuloglomerular feedback system is suppressed by volume
expansion in the nonpregnant state.
• but in pregnancy, is reset to recognize the expanded volume and
increased GFR as normal.
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Systemic Changes

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Systemic Changes

22.  Endocrinal Changes:
Physiological changes strongly relate to the renal synthesis of or
renal response to several hormones.
Progesterone:
Early on, luteal phase progesterone plays a role in increasing the RPF
and GFR, and this role may continue during pregnancy.
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Systemic Changes

23.  Endocrinal Changes:
RAAS:
• Increased renin is produced by renal and extrarenal sources (the
ovaries and decidua).
• Angiotensinogen production by the liver increases under the
influence of estrogen.
• Aldosterone levels are higher during normal pregnancy.
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Systemic Changes
Chapman AB, Zamudio S, Woodmansee W, et al. Systemic and renal hemodynamic changes in the luteal phase of the menstrual cycle
mimic early pregnancy. Am J Physiol. 1997; 273(5 Pt 2):F777–F782.
Sibai BM, Ramadan MK. Acute renal failure in pregnancies complicated by hemolysis, elevated liver enzymes, and low platelets. Am J
Obstet Gynecol. 1993; 168(6 Pt 1):1682–1687.

24.  Endocrinal Changes:
RAAS:
• However, vasodilation takes place during pregnancy:
 Progesterone and vascular endothelial growth factor (VEGF)-
mediated prostacyclins increase refractoriness to angiotensin II.
 Angiotensin II type 1 (AT1) receptors are less responsive during
normal pregnancy as they exist in a monomeric state.
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Systemic Changes
Chapman AB, Zamudio S, Woodmansee W, et al. Systemic and renal hemodynamic changes in the luteal phase of the menstrual cycle
mimic early pregnancy. Am J Physiol. 1997; 273(5 Pt 2):F777–F782.
Sibai BM, Ramadan MK. Acute renal failure in pregnancies complicated by hemolysis, elevated liver enzymes, and low platelets. Am J
Obstet Gynecol. 1993; 168(6 Pt 1):1682–1687.

25.  Endocrinal Changes:
Relaxin:
• Relaxin, produced by the corpus luteum, decidua and placenta,
increases RPF, GFR and solute clearance by afferent and efferent
vasodilation.
• This is mediated through upregulation of nitric oxide-dependent
vasodilation.
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Systemic Changes
Jeyabalan A, Novak J, Danielson LA, et al. Essential role for vascular gelatinase activity in relaxin-induced renal vasodilation,
hyperfiltration, and reduced myogenic reactivity of small arteries. Circ Res. 2003; 93:1249–1257.

26.  Endocrinal Changes:
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Systemic Changes

27.  Endocrinal Changes:
Erythropoietin
• Gestational increases in plasma volume in pregnancy are
proportionally higher than the corresponding increase in red
blood cell mass,
• leading to haemodilution and a relative fall in haemoglobin
levels. (Normal Hb level= 10.5 – 11 mg/dl, hematocrit= 33%)
• Erythropoietin concentrations increase approximately 2 fold
during pregnancy.
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Systemic Changes
McMullin, M. F., White, R., Lappin, T., Reeves, J. & MacKenzie, G. Haemoglobin during pregnancy: relationship to erythropoietin and
haematinic status. Eur. J. Haematol. 71, 44–50 (2003).
Turner, M., Barré, P. E., Benjamin, A., Goltzman, D. & Gascon-Barré, M. Does the maternal kidney contribute to the increased circulating
1,25-dihydroxyvitamin D concentrations during pregnancy? Miner. Electrolyte Metab. 14, 246–252 (1988).

28.  Endocrinal Changes:
Vitamin D
• Serum calcitriol levels (1,25-dihydroxyvitamin D3) are
approximately 3 fold higher in the first trimester and 5-6 times
higher in the third trimester than those in nonpregnant women.
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Systemic Changes

29.  Systemic Hemodynamics
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Systemic Changes
Ogueh O, Brookes C, Johnson MR. A longitudinal study of the cardiovascular adaptation to spontaneous and assisted conception
pregnancies. Hypertens Pregnancy. 2009;28:273-289.
1st Trimester 2nd Trimester 3rd Trimester
50
40
30
20
10
5th 8th 26th
Heart
Rate
Stroke
Volume
Cardiac output significantly
increases by the 5th gestational week
% Increase

30.  Systemic Hemodynamics
• Pregnancy is a state of profound physiological vasodilatation with
mediators (including progesterone, nitric oxide and
prostaglandins) and reduction in systemic vascular resistance
• leading to a 5–10 mmHg reduction in blood pressure during
pregnancy.
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Systemic Changes
Magness RR, Gant NF. Normal vascular adaptations in pregnancy: Potential clues for understanding pregnancy induced hypertension.
In: Walker JJ, Gant NF, eds. Hypertension in Pregnancy. London: Chapman & Hall Medical; 1997:5-26.
Maynard SE, Min JY, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase (sFlt1) may contribute to endothelial
dysfunction, hypertension and proteinuria in preeclampsia. J Clin Invest. 2003;111:649-658.

31.  Systemic Hemodynamics
• Organ blood flow increases in pregnancy, with the most dramatic
changes occurring in
 the kidney and skin circulation throughout gestation and
 in the uterus in the second part of the pregnancy.
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Systemic Changes
Ogueh O, Clough A, Hancock M, Johnson MR. A longitudinal study of the control of renal and uterine hemodynamic changes of
pregnancy. Hypertens Pregnancy. 2011;30:243-259.

32.  Electrolytes
Pregnancy is characterized by increments in total body electrolyte
stores, albeit with decrements in serum levels because of greater
retention of water.
Sodium:
Total body sodium
 Increases on an average by 3–4 mEq/d,
 producing a net balance of 900-1000 mEq by the end of
gestation.
 serum level decrease by 4 mEq/L.
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Systemic Changes

33.  Electrolytes
Sodium:
Retention of sodium is a complex interplay of natriuretic and
antinatriuretic factors,
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Systemic Changes
Factors Influencing Sodium Excretion
During Pregnancy
Natriuretic Antinatriuretic
Increased GFR Aldosterone (+kaliuretic)
Atrial natriuretic peptide Angiotensin II
Progesterone (+Antikaliuretic) Estrogen
Nitric oxide Deoxycorticosterone
Prostaglandins Na+/K+ transporters

34.  Electrolytes
Sodium:
• Progesterone attenuates sodium reabsorption by competitively
inhibiting aldosterone at the tubular mineralocorticoid receptor.
• Other factors that may promote natriuresis include decrease in
serum albumin concentration and increase in prostaglandins and
melanocyte stimulating hormone.
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Systemic Changes
Davison JM, Lindheimer MD: Volume homeostasis and osmoregulation in human pregnancy. Baillieres Clin Endocrinol Metab
3: 451–472, 1989

35.  Electrolytes
Potassium:
• Total body potassium store increases by up to 320 mEq by the
end of gestation,
• but its serum level decreases by 0.25 mEq/L due to hemodilution.
• The decrease in potassium excretion occurs despite the high
aldosterone values of normal pregnancy, caused by the potent
antimineralocorticoid action of progesterone.
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Systemic Changes
Lindheimer MD, Richardson DA, Ehrlich EN, Katz AI. Potassium homeostasis in pregnancy. J Reprod Med. 1987;32:517-520.

36. Renal Hemodynamics
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37. Renal Hemodynamics
• The glomerular filtration rate (GFR) increases immediately after
conception, resulting in significant hyperfiltration.
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1st Trimester 2nd Trimester 3rd Trimester
50%
30%
80%
50%
% IncreaseIncreased GFR in pregnancy
is mainly influenced by
reduced average oncotic
pressure and increased
ultrafiltration capacity.
Renal plasma flow
increases, due to an
increase in COP and
increased renal vasodilation
of the afferent and arteriole
arterioles, however,
glomerular BP remains
normal.

38. • RPF falls toward nonpregnant levels in the third trimester,
whereas GFR continues to be elevated, resulting in an increased
filtration fraction.
• All these values normalize 4–6 weeks after delivery.
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Renal Hemodynamics
Odutayo A, Hladunewich M. Obstetric nephrology: renal hemodynamic and metabolic physiology in normal pregnancy. Clin J Am Soc
Nephrol. 2012; 7:2073–2080.

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Renal Hemodynamics
Glomerular filtration
dynamic determinants:
ΔP is the hydraulic pressure
gradient between the glomerular
capillary and Bowman’s capsule
πGC is the mean oncotic pressure
in the glomerular capillary
Kf is the glomerular ultrafiltration
coefficient, the product of the
surface area available for
filtration and the permeability of
the filtration membrane.

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Renal Hemodynamics
Tubuloglomerular Feedback
P

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Renal Hemodynamics
Tubuloglomerular Feedback
P
Increased ΔP and Kf, as well
as reduced πGC have all been
described to contribute, at
different stages and to
different degrees, to the high
GFR in pregnancy.
Oncotic pressure is
substantially decreased
because of expansion of the
plasma volume.
Kf may increase due to
changes in the surface area
for filtration and the
hydraulic permeability.
Deng A, Baylis C. Glomerular hemodynamic responses to pregnancy in rats with severe reduction of renal mass. Kidney Int. 1995;
48(1):39–44.

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Renal Hemodynamics
Tubuloglomerular Feedback
P
Sustained increase in GFR
postpartum is due to either a
rise in ΔP up to 16%, and 50%
increase in Kf.
On the other hand, several
studies were not able to find
evidence of increased ΔP.
Hladunewich MA, Lafayette RA, Gerby GC,
et al. The dynamics of glomerular filtration
in the puerperium. Am J Physiol Ren
Physiol. 2004; 286(3):F496–F503.
Baylis C. The mechanism of the increase in
glomerular filtration rate in the twelve-day
pregnant rat. J Physiol. 1980; 305(1):405–
414.

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Renal Hemodynamics
Tubuloglomerular Feedback
P
Increased RPF increases GFR
even without any changes to
ΔP or Kf, and contributes in
decreasing glomerular
oncotic pressure

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Renal Hemodynamics
Tubuloglomerular Feedback
P
Tubuloglomerular feedback,
(normally counteract the rise
in GFR) , is reset to allow for
higher GFR.
Baylis C. The mechanism of the increase in
glomerular filtration rate in the twelve-day
pregnant rat. J Physiol. 1980; 305(1):405–
414.

45. • This significant increase in GFR leads to decrease in serum
creatinine to 0.4 - 0.5 mg/dl,
• Blood urea nitrogen (BUN) falls to 8 - 10 mg/dl.
• MDRD and CKD-EPI formulae tend to underestimate GFR and
cannot be used in pregnancy.
• Assessment of renal function in pregnancy is therefore limited to
serial monitoring of serum creatinine level.
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Renal Hemodynamics
Smith, M. C., Moran, P., Ward, M. K. & Davison, J. M. Assessment of glomerular filtration rate during pregnancy using the MDRD formula.
BJOG 115, 109–112 (2008).
Alper, A. B. et al. Performance of estimated glomerular filtration rate prediction equations in preeclamptic patients. Am. J. Perinatol. 28,
425–430 (2010).

46. • Relaxin (released from the corpus luteum), nitric oxide (NO) and
progesterone mediate the renal vasodilation and glomerular
hyperfiltration.
• Relaxin mediates its effects via matrix metalloproteinase-2 and
endothelin receptor type B leading to NO-dependent
vasodilation.
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Renal Hemodynamics
Jeyabalan, A. et al. Essential role for vascular gelatinase activity in relaxin-induced renal vasodilation, hyperfiltration, and reduced
myogenic reactivity of small arteries. Circ. Res. 93, 1249–1257 (2003).

47. Relaxin administration to male and nonpregnant female rats
produced physiologic changes that mimicked normal pregnancy,
 Decrease in systemic vascular resistance
 Significant increases in effective RPF and GFR.
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Renal Hemodynamics

48. Elimination of relaxin, via administration of relaxin-specific
monoclonal antibodies or ovariectomy, prevented the characteristic
renal hemodynamic changes in pregnant rats.
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Renal Hemodynamics

49. • Pregnant rats received the nitric oxide synthase inhibitor,
nitro-L-arginine methyl ester (L-NAME),
• Acute or chronic inhibition of NO synthase, led to abolishment
of the glomerular hyperfiltration in pregnancy.
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Renal Hemodynamics

50. • Both relaxin and NO may also factor in the development of
glomerular hyperfiltration in human pregnancy, but the existing
data are less conclusive.
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Renal Hemodynamics
Irrespective of gender, short-term administration of recombinant
relaxin produced increase in RPF 47%, but no changes were noted
in GFR.

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Renal Hemodynamics

52. Renal Tubular Function
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53. Renal Tubular Function
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Glucose Calcium
Amino Acids
& Vitamins
Bicarbonate
Uric
Acid Protein
The renal handling
of a number of
solutes is altered in
normal pregnancy.
Increments in
excretion of some
substances, are
limited by
increases in tubular
reabsorption.

54.  Glucose:
• Glycosuria frequently occurs during pregnancy, and reflects
reduced tubular reabsorption without a metabolic disturbance.
• It is caused by:
 a decrease in The maximum transport capacity (Tmax) mostly in
the proximal tubule, and
 the inability of the renal tubules to cope with the increased
filtered glucose load.
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Renal Tubular Function
Baylis C, Davison JM. The renal system. In: Chamberlain G, Broughton Pipkin F, eds. Clinical Physiology in Obstetrics. 3rd
ed. Oxford: Blackwell Science; 1998:263-307.

55.  Calcium:
• Calcium excretion increases 2-3 times during pregnancy because
of the increased filtered load.
• Simultaneous increases in urinary acidic glycoproteins,
magnesium, citrate, and nephrocalcin serve to inhibit calcium
oxalate calculi formation.
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Renal Tubular Function
Gambaro, G. et al. Increased urinary excretion of glycosaminoglycans in pregnancy and in diabetes mellitus: a protective factor against
nephrolithiasis. Nephron 50, 62–63 (1988).
Butler, E. L., Cox, S. M., Eberts, E. G. & Cunningham, F. G. Symptomatic nephrolithiasis complicating pregnancy. Obstet. Gynecol. 96, 753–
756 (2000).

56.  Uric Acid:
• Reabsorption of uric acid is reduced in pregnancy.
• Serum uric acid is decreased in the first trimester by about 25%
(UA= 2-3 mg/dl), and then gradually increase as pregnancy
progresses.
• High renal clearance is necessary to clear the increased
production of fetal and placental growth.
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Renal Tubular Function
van Buul EJ, Steegers EA, Jongsma HW, Eskes TK, Thomas CM, Hein PR: Haematological and biochemical profile of uncomplicated
pregnancy in nulliparous women; a longitudinal study. Neth J Med 46: 73–85, 1995

57.  Uric Acid:
• Uric acid has been noted to be elevated in pregnancies
complicated by pre-eclampsia,
 due to decreased renal clearance secondary to glomerular
endotheliosis
 increased production caused by trophoblast breakdown.
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Renal Tubular Function

58.  Bicarbonate:
• Hyperventilation in pregnancy causes a mild chronic respiratory
alkalosis
• with secondary compensatory decrease in serum HCO3
concentration and increased its excretion.
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Renal Tubular Function

59.  Amino acids & Vitamins:
• Urinary excretion of most amino acids increases in pregnancy, as
a result of decreased tubular reabsorption.
• Nicotinic acid, ascorbic acid, and folic acid are all excreted in
increased amounts during pregnancy.
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Renal Tubular Function
Hytten FE, Cheyne GA. The aminoaciduria of pregnancy. J Obstet Gynaecol Br Commonw. 1972;79:424-432.
Lindheimer MD, Davison JM, Katz AI. The kidney and hypertension in pregnancy: Twenty exciting years. Semin Nephrol. 2001;21:173-189.

60.  Protein:
• Significant proteinuria should not only be attributed to the
hyperfiltration that occurs during normal pregnancy.
• Impaired tubular reabsorption also contributes to the generation
of proteinuria, which is notable after 20 weeks gestation.
• The protein content in urine is mostly Tamm-Horsfall, with a small
amount of albumin and other circulating proteins.
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Renal Tubular Function
Lindheimer MD, Kanter D: Interpreting abnormal proteinuria in pregnancy: The need for a more pathophysiological
approach. Obstet Gynecol 115: 365–375, 2010

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Renal Tubular Function

62. Impact on Fetal Programming
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63. Impact on Fetal Programming
• Women with normal pregnancy who have suboptimal increases
in plasma volume are more likely to have fetal growth restriction
and preterm delivery.
• This can program the offspring for adult life increased risk of
hypertension, other cardiovascular events, diabetes,
hypercholesterolemia, and chronic kidney disease caused by
reduction in nephron number.
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Zandi-Nejad K, Luyckx VA, Brenner BM. Adult hypertension and kidney disease: The role of fetal programming. Hypertension.
2006;47:502-508.

64. • The precise orchestration of hemodynamic changes and balance
of fluid and electrolytes are essential to the development and
maintenance of a successful pregnancy for mother and child.
• The volume sensing and regulatory systems are dramatically
readjusted throughout pregnancy to accommodate and maintain
the volume expansion.
• The sum effect of volume expansion, increases in COP and pulse
rate, reduced SVR, and blood pressure is renal vasodilation and
increased RPF and GFR.
Renal Changes during Pregnancy
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Take Home Message

65. Renal Changes during Pregnancy
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Take Home Message
Changes in Numbers
Kidney Size
Kidney volume
1 – 1.5 cm
30%
Osmolality 270 mosm/kg
Blood pressure 5 – 10 mmHg
RBF 80%
GFR 50%
S. Creatinine 0.4 – 0.5 mg/dl
BUN 8 – 10 mg/dl
Uric Acid 2 – 3 mg/dl
Hb 10.5 – 11 g/dl
Hct 33%
Sodium 4 – 5 mmol/l
Potassium 0.25 mmol/l
Bicarbonate 20 mmol/l
• Knowledge of the anatomical,
physiological and biochemical
values of these alterations
permits earlier detection and
facilitates management of renal
diseases and hypertension
during pregnancy.

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Thank You