INTRODUCTION

Pregnancy is associated with structural, metabolic, synthetic, and functional changes in the kidney and renal tract that are central to successful pregnancy outcomes.

In women with compromised function, this can be associated with adverse pregnancy outcomes for both mother and baby. Pre-pregnancy counseling, good contraceptive education to avoid unwanted or ill-advised pregnancies, and management by a multidisciplinary team during pregnancy may help optimize outcomes, and alleviate anxiety, and dispel some of the myths surrounding pregnancy in women with more severe renal disorders. Acute renal failure in pregnancy has also been better recognized and managed over the last decade. This chapter discusses the normal physiological changes seen in pregnancy, management of pregnant women with acute and chronic kidney disease including dialysis and renal transplantation, and contraception for women with renal disease.

PHYSIOLOGY

Structural

Kidneys increase in size by 1–1.5 cm in pregnancy due to an increase in vascular and interstitial volume.^1,2,3 Physiological dilatation of the urinary system (pelvis, calyx, and ureter) is thought to be secondary to hormonal smooth muscle relaxation and compression from the gravid uterus. This dilatation is normally observed in the mid trimester and increases with increasing gestation. Iit is seen more commonly in primigravid and multiple pregnancies. Right- sided dilatation is more common than left, possiblythis may asbe a consequence of compression of the ureter by the right ovarian and iliac veins at the pelvic brim and dextra-rotation of the uterus, providing some protection to the left ureter.^4,5 In the third trimester it is uncommon for renal pelvis volume to exceed 15 mm.⁶ These structural changes may take up to 6–12 weeks to resolve postpartum.

Renal function and creatinine

Renal blood flow increases by 150% during pregnancy.⁷ There is a relaxation of both efferent and efferent arterioles and a resultant increase in glomerular filtration. These changes are most likely mediated via relaxin, progesterone, and nitric oxide.⁸ The increase in glomerular filtration reduces serum creatinine (sCr) compared to pre-pregnancy levels. Two recent systematic reviews have attempted to provide gestation-al specific measures of renal function. SCr levels >76 mmol/l (0.86 mg/dl) in the first trimester, >72 mmol/l (0.81 mg/dl) in the second trimester, and >77 mmol/l (0.87 mg/dl) in the third trimester are considered abnormal and a sign of renal impairment. In healthy women, sCr reaches a nadir in the 2nd trimester and starts to rise from 32 weeks onwards.^9,10

A pictorial summary of the renal structural, physiological, and hormonal changes in pregnancy is demonstrated in Figure 1.¹¹

Assessment of Renal Function in Pregnancy

Outside of pregnancy, formulae such as the Modification of Diet in Renal Disease (MDRD) or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation provide a better estimation of kidney function than sCr. These equations should not be used in pregnancy as they have been shown to underestimate renal function.^12,13 Cystatin C has also been shown to underestimate renal function in pregnancy. The Cockcroft–-Gault formula both overestimates and underestimates renal function depending what body weight is used (pre-pregnancy or pregnancy.⁸

Inulin clearance is accepted as the gold standard measurement of glomerular filtration rate in the nonpregnant and pregnant population. In practicse, inulin clearance measurements are complex and impractical and often reserved for use in research settings.^14,15 Twenty-four- hour urine collection for estimation of creatinine clearance has been shown to correlate with inulin clearance¹⁶ when collected accurately and using the recommended collection technique; in pregnancy this involves laying in the left lateral position before and after collection to minimize urine pooling in dilated ureters.¹⁷ Practically this is difficult to do in pregnancy, and accuracy is hampered by incomplete collections.^15,18 For the above reasons sCr is used for assessment of renal function. Reference ranges for creatinine levels in each trimester can be found in Table 1.

Proteinuria

Proteinuria increases in pregnancy to an upper limit of 300 mg/24 hours, whichthis is double the upper limit in the nonpregnant population (≤150 mg/24 hours). Factors that contribute to increase proteinuria in pregnancy include: increase in glomerular blood flow and, increase in glomerular permeability (Figure 2).²

The assessment of proteinuria in pregnancy is discussed in the accompanying cChapter: Screening for Hypertension and Proteinuria in pregnancy.

Proteinuria and renal disease in pregnancy

Acute and chronic kidney disease are discussed in detail in the following sections. All women with chronic kidney disease (non- proteinuric and proteinuric) should have baseline proteinuria assessment at the beginning of pregnancy; t. This information can be critical later in pregnancy. Proteinuria present before 20 weeks' gestation is consistent with underlying kidney disease and may often be the only manifestation of this. Increase in proteinuria after 20 weeks can have many differentials,; these includinge – worsening of underlying kidney disease, pre-eclampsia (PE), or physiological increase in proteinuria from baseline due to increase glomerular filtration and glomerular permeability (discussed in the previous section). Some studies in diabetic nephropathy have shown a 2– to 5 times increase in proteinuria in the 3rd trimester when compared to the 1st trimester or pre pregnancy values.^19,20 This situation poses a difficult diagnostic challenge an approach to this, and will be discussed in more detail in the sections on acute and chronic kidney disease.

Gestational proteinuria is defined as new- onset proteinuria in pregnancy that is not associated with features of pre-eclampsia, underlying renal disease, or urinary tract infection after 20 weeks of pregnancy. The true incidence of gestational proteinuria is unknown. Reports in the literature have varyied from 2 to –13.4%.^21,22 Some studies have shown an increase in the development of pre-eclampsia (30–50%),^23,24 while others have shown a relationship with the risk factors of pre-eclampsia (increase BMI, twin pregnancies, maternal age, and nulliparity).²² The underlying pathogenesis is not known; Holston showed a correlation with lower circulating angiogenic factors and gestational proteinuria.²⁵ Angiogenic factors are important for the integrity of the glomerular basement, and a reduction in these levels may offer an insight into the pathogenesis.²⁶ In women with gestational proteinuria, regular review for development of pre-eclampsia is advised. Women with gestational proteinuria should be followed up postpartum to ensure resolution of proteinuria. If this does not resolve by 6 months postpartum, or, if worsening of renal function and proteinuria occur, further investigation for underlying renal disease by a nephrologist is recommended.^24,27 Time to resolution of proteinuria has been shown to correlate with degree of proteinuria and, in some women, can take up to 48 months to completely resolve.²⁸

Electrolytes and Acid– Base Balance

Serum electrolytes

Pregnancy is associated with numerous changes in tubular function that impact volume regulation, electrolyte balance, acid– base equilibrium and serum osmolality. Normal ranges for serum electrolytes are altered in pregnancy; see: Table 1.^{9,10,29,30,31,32,33,34}

Volume regulation

An increase in plasma volume in pregnancy is driven by activation of the renin–-angiotensin–-aldosterone system (RAAS), whichthis increases sodium and water reabsorption and results in total body sodium increase of 1000 mmol.^2,35,36 This sodium balance is in response to regulated byunder a complex balance betweenof promoters of sodium wasting and promoters of sodium absorption. RaiIncreased GFR, progesterone, and atrial natriuretic peptide all increase sodium excretion^37,38 whilst aldosterone and deoxycorticosterone promote sodium reabsorption.^39,40 Progesterone is an antagonist of aldosterone; it competitively inhibits the binding of aldosterone to its receptor in the kidney,³⁸tand this decreases sodium reabsorption by the kidney. Progesterone also prevents potassium losses that would have occurred with the increase in sodium reabsorption;⁴¹ as with sodium there is a net increase inof potassium stores.² Aldosterone levels are significantly increased in pregnancy, despite a significant increase in plasma volume. The regulation of aldosterone production in pregnancy is not well understood. Estrogen increases hepatic synthesis, while vVascular eEndothelial gGrowth fFactor (VEGF) stimulates adrenal production of aldosterone. Despite this increase in total body sodium, serum levels of sodium and potassium fall in pregnancy—, sodium by 4 mmol/lL and potassium by 0.25 mmol (see Table 2). This decrease is due to increase in water retention. In pregnancy there is a resetting of the plasma osmostat and aAntidiuretic hormone (ADH) release occurs at lower serum osmolality.^42,43 The nett effect of this is water retention and reduction of serum osmolality, by 8–10 mmol/lL.

Acid–b Base balance

There is an increase in acid production in pregnancy due to increases in metabolic rate. Despite this, pH is higher as there is a respiratory alkalosis due to a progesterone- mediated increase in minute ventilation.⁴¹ Serum bicarbonate levels are lower due to mixed metabolic acidosis and respiratory alkalosis.³²

PREGNANCY- RELATED ACUTE KIDNEY INJURY (PRPRAKI)

Definition and diagnosis

The definition of AKI in pregnancy is controversial. RIFLE (Risk, Injury, Failure, Loss, End Stage) and AKIN (Acute Kidney Injury Network) criteria have been used outside the pregnancy setting to diagnose and grade the severity of AKI. The use of these criteria in pregnancy has not been validated. Consequently, there are less robust definitions used in pregnancy for the diagnosis of AKI. These include doubling of serum creatinine (often baseline creatinine is unknown), creatinine level >87–95 mmol/lL (0.67–1.0 mg/dl), or creatinine rise >26 mmol/lL (>0.3 mg/dl), or urine output <20 ml/hr for >12 hours.⁸

Incidence and outcomes

Worldwide the incidence of prAKI has fallen primarily due the reduction in septic abortions and puerperal sepsis related to improvements in antenatal care.^44,45 In low- and middle- income countries, the incidence of AKI is still high (0.2–1.8%),^44,45 but is falling with an incidence of 1/18,000 pregnancies in developed nations.⁴⁶ Recent data from Canada and the USA haves demonstrated increasing rates of AKI. In Canada rates increased from 1.6/10,000 deliveries in 2003 to 2.3/10,000 deliveries in 2007.⁴⁷ In the USA, prAKI rates increased over a 10- year period from 2.4/10,000 deliveries to 6.3/10,000 deliveries from 1999–2001 to 2010–2011.⁴⁸ Potential explanations for this include better recognition of prAKI, and an older maternal population with co-morbidities,^48,49,50 fluid restrictions in the management of women with pre-eclampsia, and increased numbers of women with underlying hypertension and chronic kidney disease. PrAKI most commonly presents in the 3rd trimester and postpartum period.⁸

PrAKI is associated with an increase in both maternal and fetal mortality and morbidity.^45,51 This is not surprising as AKI is often a reflection of the severity of the underlying clinical condition. Women may require dialysis support, inotropes for management of sepsis and hypotension, and regular monitoring of fluid electrolyte status. Many of these resources are not readily available in low- and middle- income countries. This contributes to poorer fetal and maternal outcomes with a higher risk of maternal deaths (odds ratio [OR]: 4.5), cesarean section (OR: 1.49), disseminated intravascular coagulation (OR: 3.41), placental abruption (OR: 3.13), and increase in the risks of hemorrhage and longer ICU stay. There was also an increase in fetal complications, with an increase in stillbirth and neonatal deaths (OR: 3.39) and increase in premature delivery and higher risk of intra uterine growth restriction.^51,52

Etiology

PrAKI can be due to obstetric orand non–obstetric causes and can be divided into pre-renal, renal, and post renal (Table 2). Pre-eclampsia (PE) and Hemolysis Elevated Liver enzymes and Low Platelets (HELLP) are the commonest cause of prAKI.^53,54 Sepsis and hemorrhage are also common causes worldwide.⁵²

History, examination, and investigations

A good clinical history and examination areis of utmost importance in determining the underlying etiology, and will help target investigations and identify and prioritize treatment. Septic abortions and hypovolemia secondary to hyperemesis are more common in the 1st trimester. PE, HELLP, and hemorrhage are more common in the 2nd and 3rd trimesters. Acute fatty liver of pregnancy (AFLP) and hemolytic-uremic ayndrome (p-aHUS) are rare cause of prAKI in late pregnancy or postpartum.⁵⁵ The presence of systemic symptoms such as arthralgias and rashes is an alert to underlying autoimmune diseases, whilst fevers may be an alert to underlying infection. A medication history may help identify potential nephrotoxic medications and family history, and may be important in the diagnosis of inherited renal diseases and pregnancy-associated atypical  (p-aHUS).

Physical examination can reveal important signs such as fever, hypertension or hypotension, rashes, and synovitis in autoimmune disease and volume status (hyper-volemia or hypovolemia). If available it is important and critical to compare current serum creatinine levels and, perform urine analysis and spot protein/creatinine ratio with pre-pregnancy or early pregnancy values. Fresh microscopy of a mid-stream urine specimen is important in ruling out infection and allows examination for the presence of red blood cells and casts, which may be a sign of underlying glomerulonephritis.⁵⁶ The presence of both hematuria and proteinuria in the absence of infection is suspicious of underlying primary glomerular disease.

Renal ultrasound is not always required, but is useful in excluding obstruction this is associated with dilatation of the ureters and renal pelvis,⁵⁷ and may also be helpful in identifying chronic kidney disease where the kidney size is small (<8 cm) and the renal cortex appears echogenic.⁵⁸ A renal biopsy may be required in women with significant prAKI where the diagnosis is unclear, to identify potential treatable causes such as interstitial nephritis or acute glomerulonephritis.

A summary of basic investigations (Table 3) and a practical approach to prAKI (Figure 3) can be found below.

Thrombotic microangiopathy (TMA)

TMA is a pathological definition;, it relates to the presence of anemia (Hb <10 g/dl) , fragmented red blood cells (schistocytes), and thrombocytopenia (<100 g/lL), undetected haptoglobins, and raised lactate dehydrogenase (LDH), with evidence of end organ damage such a AKI, neurological, or liver involvement.⁵⁵ In pregnancy, HELLP and PE are the commonest causes of TMA.⁵⁹ Thrombotic thrombocytopenic purpura (TTP) and pregnancy-associated atypical hemolytic-uremic syndrome (p-aHUS) are less common causes of TMA in pregnancy and the postpartum period. These disorders can be precipitated by pregnancy, and often this may be the first clinical presentation of these rare conditions.^60,61 The measurement of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) activity is a particularly useful investigation in TMA, becauseas activity (<10%) is consistent with the diagnosis of TTP.⁶² There are no specific diagnostic criteria for p-aHUS, which is a disorder of unregulated complement activation and is a diagnosis of exclusion when presenting for the first time in pregnancy.⁵⁵ Targeted therapies are now available for TTP (plasma exchange and steroids to remove and decrease production of inhibiting antibodies, and plasma infusion to replace the metalloproteinase),⁵⁵ and p-aHUS (eculizumab, a human monoclonal antibody, to complement 5 [(C5]) that has dramatically improved the prognosis of aHUS)⁶³. Early initiation of treatment may significantly impact both maternal and fetal outcomes. Often plasma exchange and plasma infusion may need to be initiated prior to confirmation of a diagnosis in the setting of severe or worsening end organ involvement⁵⁵ Catastrophic anti-phospholipid syndrome (CAPS) and severe systemic lupus erythematosus (SLE) can present as a TMA of pregnancy;,⁶⁴ a clinical history of autoimmune may help guide diagnosis.

Postpartum hemorrhage (PPH) can precipitate prAKI in the setting of hypovolemia and hypotension. A less common scenario is TMA following PPH.⁶⁵ If severe AKI I is present with significant oliguria, anuria, or dialysis dependence, then renal cortical necrosis (irreversible ischemia of the renal cortex) should be ruled out. A diagnosis of renal cortical necrosis avoids further unnecessary investigations and treatments such as plasma exchange.⁵⁵

A combination of clinical and laboratory features is used to guide and determine the underlying etiology of TMA (Table 4). It is important to remember that conditions can co-exist; both TTP and p- aHUS can be complicated by PE and HELLP.^66,67 In such complex cases it is always critical to involve multidisciplinary teams early in the management of these women.

Acute lupus nephritis and glomerulonephritis

Lupus nephritis can present acutely in pregnancy and, when the first presentation is in the second and third trimesters, can often be difficult to distinguish from PE as often many of the clinical features are similar.⁶⁸ A history of arthralgias, rashes, mouth ulcers, and alopecia may be helpful, and physical examination may reveal signs of synovitis and malar rash. Examination of the urine may reveal glomerular red blood cells and casts in addition to proteinuria;, antinuclear antibodyies and double- stranded DNA may be positive and titres increased;, complement levels thatwhich normally increase in pregnancy tend to fall in active lupus nephritis (complements 3 and complement 4 are consumed), and inflammatory markers are often raised (Table 5).

Antiangiogenic markers

Pre-eclampsia (PE)E is an imbalance between pro- (PlGF, placental growth factor) and anti- – angiogenic factors (sFlt-1 soluble fms-like tyrosine kinase-1),⁶⁹ which leads to vascular endothelial activation and inflammation.⁷⁰ sFlt-1/PlGF ratio and PlGF assay are useful tools in the prediction and diagnosis of PE.^71,72 Small studies have used the sFlt/PlGF ratio to differentiate PE from active lupus nephritis.^73,74 Larger studies are needed to determine the role of these assays and differentiation of underlying clinical conditions that may be misdiagnosed as PE.

Management

Management of prAKI requires a number of simultaneous steps to avoid worsening ofthe maternal, and potentially fetal, condition.

General principles of management include:

Recognition of AKI

• Early involvement of multidisciplinary team if available;, this may include maternal fetal medicine specialist, obstetric medical physician and nephrologist, intensive care physicians, and neonatologists
• Consideration of transfer to a tertiary referral center

Emergency management

Volume assessment and fluid resuscitation

Volume assessment is crucial in the acute management of prAKI. Hypovolemia is associated with a decrease in renal and placental perfusion. Volume depletion is commonly seen following obstetric hemorrhage, sepsis, and in severe hyperemesis. Clinical signs of hypovolemia include decreasing daily weight, hypotension, tachycardia, significant postural drop of >20 mmHg, and low jugular venous pressure (JVP).⁷⁵ More invasive monitoring is used in the intensive care setting:, measurement of central venous pressure and pulmonary capillary wedge pressure have been replaced by pulse pressure variation (PPV)⁷⁶ and stroke volume variation (SVV).⁷⁷ These and other dynamic assessments representare more accurate assessments of volume status and reserved for women that are critically ill. A recent small study used ultrasound to measure inferior vena cava to aortic diameter (IVC/Ao diameter) at the transhepatic level to assess volume status and guide fluid management in pregnant women.⁷⁸ This promising, simple, non- invasive, and inexpensive tool may increase the accuracy of bedside volume assessment and add to clinical assessment which can at times be difficult.

Recognition and correction of hypovolemia may prevent worsening of prAKI and improve placental perfusion. The aims of fluid replacement areis to achieve euvolemia, restore normotension, and maintain a urine output >30 ml/hour.⁷⁹ The choice of fluid replacement is determined by the clinical situation and includes blood, blood products, and crystalloid and colloid solutions. Crystalloids are preferred over colloids as they are cheaper and more readily available.⁸⁰ Albumin has been shown to have comparable safety to saline and can be used in combination with crystalloids.⁸¹ Colloids such as hydroxyethyl starch (HES) should be avoided as they have been associated with increased risk of renal failure.⁸² A large study in a critically ill non pregnant population demonstrated better renal outcomes and decrease mortality when balanced crystalloid solutions (lactated Ringer’s solution or Plasma-Lyte A) were used compared to nNormal saline. If available, balanced crystalloid solutions should be used in the critically ill.⁸³ The exact volume required will depend on many factors and should be assessed by response in blood pressure, urine output, and daily weight;, the more invasive measures discussed above may be used in the intensive care setting.

Volume overload is often associated with clinical signs of hypertension, peripheral edema, raised JVP, and often evidence of left ventricular failure. Oliguria may also be present. Fluid restriction and loop diuretics are the treatment of volume overload. Higher doses of diuretics may be required when there is significant renal impairment. Renal replacement therapy may need to be started if there is oliguria and worsening renal function.

In HELLP and PE, intravascular volume isf often reduced and vascular permeability increased.⁸⁴ Overzealous fluid resuscitation increases the risk of pulmonary edema, and isthis risk if further increased when oliguria is present. Hypoalbuminemia is also a contributorying factor. If significant intravascular depletion is suspected and oliguria is present in combination with renal impairment, a trial of 300 ml of crystalloid can be given followedd up by clinical assessment, if there is no response in urine output and no evidence of fluid overload, a further bolus of 300 ml of fluid can be given under close supervision.

Hyperkalemia

Hyperkalemia is commonly seen in prAKI. High potassium levels can be life threatening and may cause cardiac arrythmias, conduction defects, and muscle weakness. The rapidity of the increase, absolute level of potassium, and ECG changes of toxicity determine the urgency of treatment.⁸⁵ A practical approach to the management of hyperkalemia is summarized in Figure 4.

Management of pPotassium ≥6.0 mmol/l

• Stop medications associated with hyperkalemia – beta blockers, non steroidal inflammatory drugs (NSAIDs), potassium- retaining diuretics (spironolactone, amiloride).
• Establish IV access
• Continuous ECG monitoring⁸⁶
  • 12- lead ECG – ECG changes associated with hyperkalemia include peaked TT- waves, broadening of P-p waves, widening of the QRS complex, and broad sinusoidal complexes
• Identify high risk
  • Potassium ≥6.5 mmol/l
  • Rapid increase in potassium
  • Oliguria (unable to excrete potassium)
• If ECG changes are present, administer cCalcium gluconate iIntravenously  (IV) (10 ml 10% solution): onset of action 1–5 minutes and duration of action 30 minutes.⁸⁷
• Monitor potassium levels, 1, 2 , 4 , 6 hours then 24 hourly depending on severity.

Lowering of pPotassium ≥6.0 mmol/l

• Insulin/dDextrose
  IV iInsulin/dDextrose: 50 ml 50% dextrose with 5–10 units short- acting insulin given as a bolus over 5–10 minutes. This increases movement of potassium into cells.⁸⁸ Onset of action 15–30 minutes, duration of action 2–6 hours. Blood glucose levels should be monitored at 15 minutes and hourly for 6 hours.⁸⁹ The risk of hypoglycemia is greater when renal impairment exists, as the half life of insulin is prolonged.^89,90 Expected potassium decrease 0.5–1.5 mmol/l.
• Sodium bicarbonate
  Correction of acidosis when pH <7.2: – 100 ml of 8.4% sodium bicarbonate as an infusion over 30–60 minutes. Sodium bicarbonate delivers a high sodium load and should be used cautiously in the setting of volume overload and oliguria. Onset of action 1 hour.
• Salbutamol
  Nebulizsed salbutamol 10 mg (higher does than regular nebulizsed salbutamol used in asthma). Onset of action 15–30 minutes and duration 2–6 hours. Synergistic effect when combined with insulin/dextrose, but may not always be effective when used as a single agent.⁹¹ Expected potassium decrease 0.5–1 mmol/l. Intravenous salbutamol can be used: 500 mcgicrograms slow infusion over 30 minutes.⁸⁵ Salbutamol can cause reactive tachycardia, especially when given IV.
  

Treatment of mild hyperkalemia: potassium <6.0 mmol/l and no ECG changes

• Sodium polystyrene sulphonate (Resonium)
  15–30 g orally or 30–60 gm rectally as an enema (retain for 60 minutes) every 8 hours. Onset of action 2 hours with maximum effect 4–6 hours. Resonium is not a treatment for acute hyperkalemia⁹² due to its delayed onset and increase in gastrointestinal side effects.⁹³ Potassium is expected to decrease by 2 mmol/l. There is limited experience with new potassium- binding resins such as sSodium zirconium cyclosilicate and pPatiromer⁹⁴ in pregnancy.
• Loop DiureticsLoop diuretics
  A trial of loop diuretics in the setting of oliguria and volume overload may increase excretion of potassium.⁹⁵ Frusemide can be used at 20–40 mg IV;, higher doses can then be used if there is there has been no response at these low doses. Frusemide doses up to 120–250 mg can be trialed but, if there is no response in urine output, specialist input should be urgently sought. Potassium lowering is less predictable with loop diuretics.

Management of acidosis when pH <7.2

Acidosis can be treated with sodium bicarbonate, but this is only an interim measure.

• Sodium bicarbonate:
  100 ml of 8.4% sodium bicarbonate as an infusion over 30–60 minutes. Sodium bicarbonate delivers a high sodium load and should be used cautiously in the setting of volume overload and oliguria. Onset of action 1 hour.^96,97

Renal replacement therapy/dialysis

The main indications for renal replacement therapy are volume overload, refractory hyperkalemia or metabolic acidosis, or severe uraemic symptoms (pericarditis, neuropathy, or encephalopathy).⁹⁸ The threshold for initiation of dialysis needs to take into account the stage of pregnancy;, early initiation may potentially improve fetal outcomes although evidence is limited and most of the data haved been extrapolated fromorm the chronic kidney disease population.⁹⁹ In women whothat are hemodynamically unstable, continuous renal replacement therapy avoids hypotensive episodes that can occur with intermittent hemodialysis and may better mainta in utero placental perfusion.¹⁰⁰

Monitoring and optimization of fetal health

Fetal outcomes are intricately linked to underlying maternal health. Acute renal injury in pregnancy is often a reflection of a major pregnancy-related medical condition. Recognition of the severity of the condition and optimization of maternal health will optimize fetal outcomes. In general, maternal health takes priority. Because fFetal well-being is dependent on adequate uteroplacental blood flow, thus prompt treatment of hypotension, hypovolemia, and acidosis isare crucial.⁹⁹ Frequent monitoring of fetal heart rate once viability is reached, uteroplacental Ddopplers, and early delivery on obstetric grounds may be required.¹⁰¹ Magnesium sulfate for neonatal neuroprotection and corticosteroids, depending on the gestational age and clinical scenario, may be indicated prior to to delivery.¹⁰¹

Long- term follow- up following prAKI

Although renal recovery is generally good following prAKI, follow- up is often poor. In women requiring dialysis, 6–10% were still on dialysis 6 months postpartum. There also appears to be a risk of end- stage kidney disease requiring dialysis long term (2.4%),⁵¹ which is similar to non-pregnant AKI. PrAKI has been associated with an increased risk of PE and adverse fetal outcomes in subsequent pregnancies, despite return to normal creatinine levels.³ All women with prAKI should have long- term follow- up with annual review of blood pressure and urinalysis. Referral to a nephrologist should be considered if there is persistent proteinuria or renal impairment 6 months postpartum.¹⁰² In the non-pregnant population, AKI is also a risk factor for cardiovascular disease.¹⁰³ Future studies looking at long- term cardiovascular and renal outcomes will hopefully provide better insight into optimal postpartum management.

PRACTICE RECOMMENDATIONS