Acute Kidney Failure in the Third Trimester of Pregnancy

Discussion 

In developed countries, the incidence of acute kidney injury during pregnancy has decreased significantly in the last 60 years from approximately 1 in 3,000 in the mid-20th century to approximately 1 in 20,000 today.1 Greater access to prenatal care with earlier detection of preeclampsia and other pregnancy-related complications accounts for much of this improvement.1 Nevertheless, managing these patients is a challenge because 2 patients, the mother and the child, are being treated simultaneously. The most common causes of pregnancy-associated kidney injury are pregnancy related, including preeclampsia/eclampsia, hyperemesis gravidarum, uterine hemorrhage, septic abortion, and coagulopathies, among others. However, as this case illustrates, it is important to recognize that the many pregnancy-related causes of acute kidney injury do not preclude pregnant patients from the kidney diseases that affect the general population (reviewed in2, 3).

Adaptations in kidney physiological states during pregnancy cause changes in kidney function that shift “normal” laboratory values. There is marked enlargement of the kidneys and dilation of the kidney collecting system. Renal plasma flow is increased by 50% to 85% and accompanied by a 40% to 65% increase in glomerular filtration rate. This increase in filtration rate results in a decrease in serum Cr and BUN levels to an average of 0.5 mg/dL (44.2 μmol/L) and 9 mg/dL (3.2 mmol/L), respectively. Thus, during pregnancy, serum Cr level greater than 0.9 mg/dL (>80 μmol/L) and BUN level greater than 14 mg/dL (>5 mmol/L) warrant further investigation. Other changes include an increase in protein excretion to an upper limit of 300 mg/24 h.1, 2 Last, approximately 20% of women in 1 study had microscopic hematuria on at least 2 occasions during pregnancy. The women with transient hematuria did not have increased risk over women without hematuria of the development of preeclampsia, gestational hypertension, or small-for-gestational-age infants.4

Poststreptococcal glomerulonephritis (PSGN) is a rare complication of pregnancy, with an incidence estimated at 1 in 40,000.5 Relatively few cases have been reported in the literature and, of these, our patient is only the ninth to have clinical, serological, and kidney biopsy confirmation. Reports of fetal death and poor recovery of maternal kidney function exist in earlier reports. However, in the cases with thorough documentation of the disease, including all 8 patients who previously underwent biopsy, fetal outcome was successful and maternal kidney function recovered completely.5, 6, 7, 8, 9, 10

PSGN is a disease that most commonly occurs in children 7 to 21 days after pharyngitic infections and 14 to 21 days after skin infections caused by group A streptococcus. It classically presents with abrupt onset of hypertension, azotemia, hematuria, and proteinuria, although severity can range from asymptomatic microscopic hematuria to acute kidney injury. However, the incidence of silent infection followed by mild or asymptomatic PSGN may not be uncommon.11 Although there is no specific treatment outside of supportive care, symptoms of PSGN typically resolve within 2 weeks (reviewed in12). The significance of large numbers of crescents in patients with PSGN is controversial. Clinical recovery is seen in approximately half the patients with 40% or less crescents,13 and in 1 small study of children, recovery was described even with 100% crescent formation.14

The laboratory diagnosis of PSGN is based on hematuria, a positive throat culture result, increased ASO titer, and decreased C3 and C4 levels. Subnephrotic-range proteinuria typically is present. Because ASO titers can be in the normal range in patients with streptococcal infections, the change in ASO titer over time is more useful for the diagnosis of recent streptococcal infection than an isolated increased value. Even if ASO titers remain unchanged, recent infection cannot be ruled out because certain strains of group A streptococci do not produce streptolysin O. Other streptococcal antibody titers, such as antistreptokinase, antihyaluronidase, and antideoxyribonuclease B, can be useful when PSGN is clinically suspected, but ASO titer is unchanged5 (reviewed in12).

Acute glomerulonephritis during pregnancy is easily confused with preeclampsia-related acute kidney injury. The distinction is of great importance because the only treatment for preeclampsia is prompt delivery. Identification of a cause for the kidney injury other than preeclampsia can minimize the risks related to iatrogenic preterm birth. Some key distinguishing characteristics include hematuria and decreased complement levels in patients with acute glomerulonephritis. ASO, antinuclear antibody, and other autoantibody titers should be normal in patients with preeclampsia. The finding of hematuria is rare in an otherwise typical patient with preeclampsia and suggests urinary tract infection, preexisting kidney disease, de novo glomerulonephritis, or a false-positive test result, among others.4, 15 A careful history of recent infection or signs of collagen vascular disease also raise the possibility of a cause other than preeclampsia. The difficulty diagnosing preeclampsia clinically is emphasized in the study by Fisher et al16 in which 176 women with gestations complicated by hypertension underwent kidney biopsy postpartum. They found that although most women had been considered “toxemic,” the characteristic lesion of preeclampsia, glomerular endotheliosis, was present in only 65% of specimens.16

Previous studies have shown the relative safety of kidney biopsy during pregnancy. Kuller et al17 looked at a case series of 18 kidney biopsies undertaken to differentiate preeclampsia from other kidney diseases. Seven patients developed kidney hematomas, 2 of whom required transfusion. Only 5 of 15 patients had histological evidence of preeclampsia, allowing two-thirds to continue the pregnancy.17 Packham and Fairley18 reported 111 kidney biopsies in 104 pregnant women in weeks 4 to 28 of gestation. Indications for the biopsy included hematuria, proteinuria, impaired kidney function, and/or hypertension. Only 1 patient had a perirenal hematoma requiring transfusion. In this series, 80% were found to have a primary glomerular disease.18 Overall, the literature suggests that the kidney biopsy provides significant diagnostic value, particularly in pregnant patients remote from term, who present with decreased kidney function.1, 17, 18, 19, 20

We present the case of a 31-week pregnant woman with a history of chronic hypertension presenting with acute kidney injury. Kidney biopsy showed acute proliferative glomerulonephritis that led to discovery of a history of recent contacts infected with streptococcus, increased ASO titer, and decreased C3 level, confirming the diagnosis of PSGN. This case emphasizes the importance of a broad differential diagnosis when examining pregnant patients with acute kidney injury and highlights a glomerular disease rarely seen in pregnancy.