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Pregnancy and the Kidney

Women with renal disease wishing to conceive or already pregnant seek our advice as to whether the pregnancy will be complicated, the baby will be healthy, and if gestation will further damage their kidneys. Similar queries come from renal allograft recipients. Most gestations succeed and there is little or no evidence that pregnancy adversely influences the natural history of the disease or transplant, provided that renal function is preserved, or but minimally decreased, and hypertension absent. The presentation which follows starts with a synopsis of changes in the urinary tract ocurrng in normal gestation, focusing on their relevance to clinical circumstance. The lecture then stresses gestation in women with chronic disease of the kidney including those receiving renal replacement therapy. There are also brief discussions of acute renal failure (ARF) and when to perform a renal biopsy during pregnancy

I. PHYSIOLOGICAL CHANGES IN NORMAL GESTATION (SEE TABLE 1)

A. Morphological changes

1. Kidney weight and size increase, mainly due to increments in interstitial and

vascular volumes. Kidney length, estimated radiologically or

Sonographically, increases by approximately I cm

2. The most striking morphological changes, however, occur in the collecting

system, where dilation of renal calyces, pelves, and ureters may be observed

in the initial trimester and persist to 3--4 months post partum

3. The causes of these alterations include both humoral and obstructive factors (eg, estrogens, progesterone, or compression of the ureters by the enlarging uterus and the iliac arteries where the latter cross the pelvic brim)

4. Relevance of these changes

a. Difficulty in obtaining reliable timed measurements of urinary volume

(which can be minimized by establishing high urine flow rates and

avoiding supine recumbency for 30 minutes before starting and ending

a collection period)

b. Urinary stasis may explain the propensity of gravidas with

asymptomatic bacteriuria to develop frank pyelonephritis

B. Glomerular filtration (GFR), effective renal plasma flow (ERPF), and the fractional clearance of urate each increase substantially during gestation

1. The basis for these increments is unknown, animal studies suggesting renal vasodilation leading to increased glomerular plasma flow is a contributing but not the sole factor. Studies in humans using the fractional clearance of neutral dextrans, and mathematical modelling, also suggest a primary rolefor renal vasodilation, and suggest changes in glomerular membrane porosity

2. The relevance of these changes is that concentrations of serum creatinine,

urea N, and uric acid of 0.9, 14, and 5.6 mg/dL (normal in nonpregnant

subjects) are already suspiciously high in gravid women. The increased

filtered loads, at any tiltrance, may be responsible for an approximate

doubling of urinary protein excretion, and contribute to the glycosuria and

aminoaciduria of normal pregnancy. (The fate of albumin excretion is more

complex and disputed)

C, Other physiological alterations

1. The decrease of renal bicarbonate threshold and Pco2 levels, the result being

a mild alkalemia with bicarbonate and Pco2 values 4 mEq/l and 10 tort

below those in nonpregnant women

2. The osmotic thresholds for thirst and AVP secretion decrease 10 mOsm/kg, resulting in mild hyponatremia and a Po~ 10 mOsm/kg below those in nongravid populations

3. Finally, there is a marked increment in the metabolic clearance of AVP, in

part due to the high circulating levels of vasopressinase, which may account

for a rare syndrome termed transient diabetes insipidus of pregnancy

II. Pregnancy in Women With Preexisting Disease (SEE

TABLES 2 AND 3)

A. Counselling and managing women with are based primarily

on retrospective studies of > 1,000 patients whose kidney disease was

diagnosed by renal biopsy. Most of the women surveyed had been normotensive

with only minimal renal dysfunction. The following concepts have emerged

1. Fertility and the ability to sustain an uncomplicated gestation generally

relate to the degree of functional impairment and whether hypertension

is present or absent, rather than the nature of the underlying disorder

2. Patients are arbitrarily considered in three categories

a. Preserved or only mildly impaired function (serum creatinine _< 1.4

mg/dL) and no hypertension

b. Moderate renal insufficiency (serum creatinine 1.5-3 mg/dL [some use

2.5 mg/dL as the cutoff])

c. Severe renal insufficiency (serum creatinine _> 3 mg/dL)

3. Women in the first category usually have successful obstetric outcomes and

gestation does not appear to adversely affect the underlying disease,

perinatal mortality now < 5 %, while evidence of irreversible functional loss

in the mother is even lower. This generalization, however, may not hold

true for certain specific diseases. For instance, patients with scleroderma

and periarteritis nodosum (disorders associated with hypertension)