Acute kidney injury (AKI) may complicate many medical conditions, although it usually arises in hospitalized patients. The term “acute kidney injury,” has generally replaced the term “acute renal failure” because it is a more accurate descriptor of kidney dysfunction that may lead to significant morbidity or mortality in the absence of complete renal failure. AKI is not a rare medical condition, with as many as 5% of hospitalized patients having some degree of it. With respect to obstetric patients, however, AKI has become an uncommon complication of pregnancy in developed countries, where it complicates approximately 1 per 10,000 pregnancies. In three successive 10-year periods between 1958 and 1987, Stratta et al. reported ongoing decreases in AKI requiring emergency renal dialysis, falling from a rate of 1 in 3000 gestations in 1958 to 1 in 15,000 in 1987. They documented 81 cases of AKI in pregnancy, of which 11.6% experienced irreversible renal damage, most of which resulted from complications of either severe preeclampsia or eclampsia. Possible explanations for this downward trend include ready availability of prenatal care and legalization of medical abortions. However, in underdeveloped countries, AKI remains a frequent complication of pregnancy, with attendant maternal mortality surpassing 50%. In these nations, AKI has a bimodal distribution, with peaks in the first and third trimesters, presumably reflective of the persistence of illegal abortions, the lack of access to quality prenatal care, as well as preeclampsia/eclampsia. A report of 569 cases of AKI in pregnancy in India showed that the most frequent gestational complication leading to AKI was septic abortion, accounting for 50% of cases.

An understanding of the changes that normally occur in renal architecture, function, and blood flow is essential for proper assessment and management of renal disease in the pregnant patient (Table 13-1).

Anatomic Changes

There is a marked increase in kidney size during pregnancy, primarily due to increases in renal vascular volume, as well as the capacity of the collecting system. Hormonal influence is the most likely cause of dilation. In addition, increased production of prostaglandin E₂ (PGE₂), which inhibits urethral peristalsis and progressive mechanical obstruction by the enlarging uterus and distended iliac vessels (particularly on the right side) produce changes evident as early as the first trimester, and continuing for as long as 12 weeks postpartum.

Changes in Renal Blood Flow, Glomerular Filtration Rate, and Renal Tubular Function

Substantial increases in renal blood flow begin early in the first trimester, wrought by increased renal blood flow due to both increased maternal cardiac output and halving of renal vascular resistance, the latter of which is believed to be the more important factor. The underlying cause of renal-vasodilation is thought to be secondary to the effects of maternal hormones, relaxin and prolactin. Increased concentrations of PGE₂ and prostacyclin (PGI₂) may also contribute to this effect. Estimation of renal plasma flow from clearance studies of p-aminohippuric acid indicate mean effective renal plasma flow of 809 mL/mm in the first trimester, 695 mL/mm in the last 10 weeks of pregnancy, and 482 mL/mm during the postpartum period. The most important consequence of this during pregnancy is a dramatic rise in maternal glomerular filtration rates (GFR).

Despite increased GFR, the renal tubules are not only able to preserve normal sodium balance, but are able to retain an additional 500 to 900 mEq of sodium over the course of pregnancy. Consequently, pregnant women maintain normal sodium balance, largely independent of sodium intake. Pregnant women also maintain normal water balance by retaining the ability to concentrate or dilute their urine despite significant alterations in thirst and vasopressin-release thresholds during pregnancy.

Maternal potassium homeostasis is unchanged in pregnancy. There is a physiologic requirement for retention of approximately 350 additional mEq of potassium for the developing fetal-placental unit and expansion of maternal erythrocyte volume, occurring despite elevated levels of aldosterone, a kaliuretic, and in maternal plasma.

Pregnancy produces mild respiratory alkalosis, decreasing maternal arterial PCO₂ by roughly 10 mm Hg. The maternal kidneys compensate via increased excretion of bicarbonate, thereby resulting in plasma bicarbonate levels down in the 18 to 20 mEq/L range.

The physiologic changes that occur in gravid patients’ renal systems have practical consequences. For example, dilated collecting systems make diagnosis of obstructive uropathy challenging. The increased GFR and tubular function result in changes of normal laboratory values for commonly used serum tests of renal function, including blood urea nitrogen (BUN) (~8.7 ± 1.5 mg/dL) and serum creatinine (~0.46 ± 0.13 mg/dL). Mild glucosuria is also common during normal pregnancy.

AKI is characterized by rapid (hours to weeks) declines in renal function, resulting in retention of nitrogenous waste products such as BUN and creatinine, in addition to inability to maintain normal fluid and electrolyte balances. Nonpregnant patients with AKI are often asymptomatic, but during pregnancy, AKI is rarely encountered in the absence of significant clinical findings. AKI may complicate a host of diseases that, for purposes of diagnoses and management, are divided into three categories (Table 13-2).

1. 
   

   Diseases characterized by renal hypoperfusion in which the integrity of renal parenchymal tissue is preserved (prerenal azotemia, prerenal AKI). This is the most common form of AKI and has the best prognosis.

   
   
2. 
   

   Diseases involving renal parenchymal tissue (intrarenal azotemia or intrinsic renal AKI).

   
   
3. 
   

   Diseases associated with acute obstruction of the urinary tract (postrenal azotemia, postrenal AKI).

In prerenal AKI (category 1), impaired renal perfusion is the problem; it may be secondary to intravascular volume depletion, decreased effective circulating volume to the kidneys secondary to impaired cardiac output, or due to agents that alter renal perfusion. Prerenal AKI may be rarely seen in the first trimester of pregnancy as a complication of severe hyperemesis gravidarum. In the second and third trimesters, severe blood loss as a complication of hemorrhage is an important and not uncommon cause of hypovolemia with subsequent AKI.

Most acute intrinsic renal azotemia (category 2) is caused by ischemia or nephrotoxins, and is classically associated with acute tubular necrosis (ATN). Thus, in clinical practice, the term ATN is commonly used to denote ischemic or nephrotoxic AKI.

Pregnancy is associated with a higher incidence of bladder infections and pyelonephritis. Increased incidents of upper and lower urinary tract infections, estimated to complicate approximately 2% of all pregnancies, are believed to result from hormonal and mechanical changes that result in stasis (category 3) within the urinary collecting system. Unlike their nonpregnant counterparts, pregnant women with pyelonephritis can manifest substantial decreases in creatinine clearance, and may even experience some degree of transient AKI. Moreover, aminoglycoside antibiotics, not infrequently used for treating pyelonephritis, may further compromise renal function. Pregnant patients with AKI attributable to pyelonephritis often have evidence of chronic renal parenchymal infection; as a result, recovery after appropriate antimicrobial therapy may be incomplete.

Preeclampsia and its variants (eg, eclampsia, HELLP [hemolysis, elevated liver transaminases, low platelets] syndrome, thrombotic thrombocytopenic purpura [TTP], hemolytic uremic syndrome [HUS], or acute fatty liver of pregnancy [AFLP]) are the most common causes of AKI unique to pregnancy. In most women with preeclampsia, there is only a modest (30%-40%) decrease in GFR, with resultant minor increases in serum creatinine. AKI is even more common in preeclamptic mothers with associated features of HELLP syndrome. Data suggests that AKI may occur in up to 15% of such women. Renal failure requiring renal replacement therapy is unusual, even with severe disease, unless there has also been significant blood loss with hemodynamic instability or severe disseminated intravascular coagulopathy. It can be difficult to determine which particular preeclampsia variant incites a given patient’s AKI in pregnancy, as these diagnoses carry significant clinical overlap. Accurate discernment requires careful attention to physical examination, timing of symptoms, and associated laboratory abnormalities.

Acute Tubular Necrosis

The clinical course of ATN can be divided into three phases, irrespective of the underlying disease process: an initiation phase, maintenance phase, and recovery phase. In the initiation phase, an inciting event (eg, ischemia, toxin[s], etc) occurs, at which time, renal parenchymal injury is not yet present. During the maintenance phase, renal parenchymal injury begins, and GFR falls to roughly 5 to 10 mL/min. Urine output is usually at its lowest during this phase, which typically lasts 1 to 2 weeks, although it may persist up to 11 months, depending on etiology. Uremic complications usually arise during this phase. The recovery phase is heralded by gradual restoration of urine output, as serum BUN and creatinine levels decline. The recovery phase is frequently accompanied by marked diuresis that results in profound electrolyte disturbances, unless closely monitored and corrected. Whereas some patients with preeclampsia/eclampsia-induced ATN may temporarily require dialytic support, even these patients usually experience complete recovery and have excellent long-term prognoses. In those patients with ATN secondary to preeclampsia in whom ATN persists, it appears that pregnancy and/or preeclampsia may have unmasked a chronic renal disorder or some degree of renal cortical necrosis has occurred. When AKI develops in patients with severe preeclampsia or eclampsia, consideration should be given to affecting delivery as safely and expeditiously as possible.