Chapter 44Renal Disorders David J. Williams, PhD, and John M. Davison, MDAmong the many physiologic changes that occur in normal pregnancy, Escherichia coli (70% to 80%), Klebsiella, Proteus, Enterobacter, andfew are as profound as those affecting the urinary system.1 These Staphylococcus saprophyticus.healthy alterations and various diagnostic pitfalls for the unwary clini- If urine from a symptomatic pregnant woman is cloudy and posi-cian are discussed in Chapter 7. Improvements in our knowledge about tive on dipstick testing for nitrite (produced by most uropathogens)gestational physiology in antenatal care generally, technology for fetal and leukocyte esterase (produced by white blood cells), a UTI is likelysurveillance, and neonatology services have meant better care and out- and empiric treatment can be started.9 These urine sticks are not sensi-comes for women with renal problems and their newborns.2,3 With this tive enough to be used for screening for asymptomatic bacteriuria inis mind, this chapter focuses on urinary tract infection (UTI), acute early pregnancy,10 and microscopy and culture of a clean catch mid-and chronic renal disease in pregnancy, and the management of preg- stream urine sample is necessary. Hematuria and proteinuria are unre-nant women on dialysis or with renal allografts. liable indicators of a UTI, but they are important signs of renal disease (discussed later).Urinary Tract Infection Asymptomatic BacteriuriaThe incidence of asymptomatic bacteriuria (i.e., signiﬁcant growth ofa uropathogen in the absence of symptoms) is 2% to 10%, which is Maternal and Fetal Risksthe same during pregnancy as it is in sexually active nonpregnant During pregnancy, untreated asymptomatic bacteriuria will developwomen.4 However, the structural and immunologic changes to the into acute pyelonephritis in up to 30% of women, but if treated, lessurothelium of the renal tracts during pregnancy5 make it more likely than 1% of pregnant women develop pyelonephritis.4,6,7 A systematicthat a lower UTI will ascend to cause acute pyelonephritis.4,5 During review of 14 studies conﬁrmed that antibiotic treatment of asymptom-pregnancy, 12.5% to 30% of women with untreated asymptomatic atic bacteriuria signiﬁcantly reduced the incidence of pyelonephritisbacteriuria develop acute pyelonephritis,4,6-8 a serious infection with compared with placebo or no treatment (odds ratio [OR], 0.25; 95%signiﬁcant morbidity for the mother and fetus. conﬁdence interval [CI], 0.14 to 0.48).11 After successful treatment of asymptomatic bacteriuria, monthly screening of midstream urine is necessary, because about 30% of women will have a relapse of bacte-Diagnosis of Urinary Tract Infections riuria, making them vulnerable to acute pyelonephritis again.4During pregnancy, symptoms suggesting a UTI are dysuria and offen- Asymptomatic bacteriuria has been associated with an increasedsive-smelling urine. Others usually associated with a UTI are urinary risk of preterm delivery and low birth weight.12 Treatment of asymp-frequency, nocturia, urge incontinence, and strangury (i.e., the urge to tomatic bacteriuria has been shown to reduce the incidence of low-pass urine having just done so), but these symptoms are also found in birth-weight infants (OR, 0.66; 95% CI, 0.49 to 0.89)11 but have nohealthy pregnant women. effect on preterm delivery.6 It has been suggested that the underlying Microscopy and culture of a freshly voided midstream urine sample renal pathology, which is commonly associated with bacteriuria, isallow quantiﬁcation of pyuria (i.e., leukocytes in the urine) and growth responsible for poor pregnancy outcomes.6 Additional good-qualityof a urinary pathogen. A bacterial UTI is the most common cause of studies are needed to settle this issue.pyuria and is considered signiﬁcant if microscopy of a sample ofunspun midstream urine reveals more than 10 leukocytes per micro- Management of Asymptomatic Bacteriurialiter. Urine culture is conventionally recognized as signiﬁcant if there Contrary to much published advice, not all pregnant women need tois growth of more than 105 colony-forming units per milliliter (CFU/ be screened for asymptomatic bacteriuria. There are two main reasons.mL) of a single recognized uropathogen, in association with pyuria.9 First, the prevalence of asymptomatic bacteriuria varies betweenLow counts of bacteriuria10 (24 to 104 CFU/mL) may still be signiﬁcant populations, and where it is low (<2.5%), it is hard to justify the cost-if symptomatic women have a high ﬂuid intake or are infected with a effectiveness of screening. In populations in which the prevalence ofslow-growing organism. If left untreated, most symptomatic women asymptomatic bacteriuria is more than 5%, the case for screening iswith low-count bacteriuria will have 105 CFU/mL 2 days later.9 During much stronger.7 Second, approximately 1% to 2% of the 90% to 98%pregnancy, the most common uropathogens are bowel commensals, of asymptomatic women who test negative for bacteriuria in the ﬁrst
906 CHAPTER 44 Renal Disorderstrimester will develop a symptomatic UTI.8,13 This means that one (>110 beats/min) at 20 weeks’ gestation or later and who have receivedthird of all women who develop a UTI in late pregnancy would have tocolytic agents and injudicious ﬂuid replacement.23been missed on ﬁrst-trimester screening.8,13 Women at increased riskfor pyelonephritis or renal impairment should be screened for asymp- Fetal Riskstomatic bacteriuria every 4 to 6 weeks throughout pregnancy. Acute pyelonephritis can trigger uterine contractions and preterm labor.24 Antibiotic treatment of pyelonephritis reduces uterine activity, but patients with recurrent infection or marked uterine activity are atTreatment of Urinary Tract Infections increased risk for preterm labor.24 Because uterine activity often occursThere is no consensus about the optimal treatment of asymptomatic in the absence of cervical change and because tocolysis with β-mimet-bacteriuria14 or the empiric treatment of symptomatic UTIs in preg- ics aggravates the cardiovascular response to endotoxemia,23 tocolyticnancy.15 Most urinary infections during pregnancy (approximately therapy should be used with care and only in those with cervical75%) are caused by E. coli, which is usually sensitive to nitrofurantoin changes.25(89%), trimethoprim with or without sulfamethoxazole (87%), ampi-cillin (72%), or cephalosporins.16,17 Until well-structured trials are Management of Acute Pyelonephritisdone, the most cost-effective treatment for asymptomatic bacteriuria Women suspected of acute pyelonephritis from their history, symp-or a ﬁrst episode of cystitis is nitrofurantoin monohydrate macrocrys- toms, and signs should be admitted to the hospital. Laboratory teststals (100 mg twice daily for 3 days) or trimethoprim (200 mg twice should include a full blood cell count, serum creatinine concentration,daily for 3 days).17 Nitrofurantoin should be avoided after the onset of levels of electrolytes, and urine culture. If there are systemic symptomslabor in patients with glucose-6-phosphate dehydrogenase deﬁciency, or septic shock, a blood culture may be useful. Pregnant womenalthough no well-documented cases of hemolysis in neonates have with pyelonephritis and septic shock need intensive care. For thesebeen recorded,18 and trimethoprim should be avoided in the ﬁrst tri- women, assessment of the state of hydration is critical and oftenmester because it is a folic acid antagonist associated with an increased requires invasive hemodynamic monitoring with a central venousrisk of neural tube defect.19 pressure line. This can optimize ﬂuid balance, aiming for a urine Screening for recurrent infections should begin 1 week after com- output greater than 30mL/hr to minimize renal impairment andpletion of initial treatment and then be done every 4 to 6 weeks for reduce the risk of pulmonary edema. Intravenous antibiotics shouldthe remainder of pregnancy. Recurrent infections or a ﬁrst infection in be started empirically (discussed later) until the sensitivities of blooda pregnant woman at high risk for pyelonephritis should be treated and urine cultures are known. These women often have transientwith a 7- to 10-day course of an antibiotic that reﬂects antibacterial renal impairment, thrombocytopenia, and hemolysis, suggesting thatsensitivities.17 Women who have had two episodes of asymptomatic the alveolar capillary endothelium is damaged by endotoxin.22 A bloodbacteriuria or cystitis should be considered for low-dose antibiotic ﬁlm and lactate dehydrogenase concentration can be used to diagnoseprophylaxis—guided by the sensitivities of the most recent infective hemolysis.organism—for the remainder of pregnancy and until 4 to 6 weeks after Trials investigating the outpatient management of pyelonephritisbirth.20 Suitable regimens for long-term antibiotic prophylaxis include in pregnancy have identiﬁed a group of women who can be managednitrofurantoin (50 to 100 mg each night), amoxicillin (250 mg each at home.25 These women should be less than 24 weeks’ gestation, benight), cephalexin (125 to 250 mg each night), or trimethoprim (100 relatively healthy, and understand the importance of compliance. Theyto 150 mg each night).20 These women should also be investigated for should have an initial period of observation in the hospital to demon-structural abnormalities of the renal tracts or renal calculus using strate an ability to take oral ﬂuids and receive intramuscular cefurox-ultrasonography. ime or ceftriaxone. After satisfactory laboratory tests, they can go home and are seen again within 24 hours for a second intramuscular dose of cephalosporin. They then start a 10-day course of oral cephalexinAcute Pyelonephritis (500 mg four times daily) or appropriate antibiotic with regular out-The same uropathogens that cause asymptomatic bacteriuria and patient follow-up.24 Following this regimen, 90% of women willcystitis are responsible for acute pyelonephritis.21 The prevalence of improve as outpatients, and 10% will require hospital admissionasymptomatic bacteriuria in a pregnant population dictates the inci- because of sepsis or recurrent pyelonephritis. Women with acutedence of acute pyelonephritis. Screening and treating a high-risk popu- pyelonephritis who are beyond 24 weeks’ gestation should be admittedlation for asymptomatic bacteriuria reduces the incidence of acute for at least 24 hours to observe the maternal condition as describedpyelonephritis to less than 1%.8,11 Unless acute pyelonephritis is treated earlier and to monitor uterine activity and the fetal heart rate.25promptly, there is considerable maternal and fetal morbidity.21 Gram-negative bacteria causing pyelonephritis in pregnancy are often resistant to ampicillin,26 and intravenous cefuroxime (750 mg toMaternal Symptoms and Signs 1.5 gm, depending on severity of condition, every 8 hours) is an effec-Most women with acute pyelonephritis present in the second or third tive ﬁrst choice until culture sensitivities are known.15 Women allergictrimester.21 More than 80% of women present with backache, fever, to β-lactam antibiotics can be given intravenous gentamicin (1.5 mg/rigors and costovertebral angle tenderness, and about one half have kg every 8 hours) for the initial treatment of acute pyelonephritis.lower urinary tract symptoms, nausea, and vomiting.21 Bacteremia A single-dose regimen (7 mg/kg every 24 hours) should be avoidedoccurs in 15% to 20% of pregnant women with acute pyelonephritis,21 during pregnancy to reduce the very small risk of cranial nerve VIIIand a small proportion of these women will develop septic shock and damage to the fetus.17 Serum concentrations of gentamicin should beincreased capillary leak, leading to pulmonary edema.22 It is important, measured and dose adjustments made according to identiﬁed levels.however, to differentiate the hypotension due to reduced intravascular Intravenous antibiotics should be continued until the patient has beenvolume (i.e., fever, nausea, and vomiting) from that caused by septic afebrile for 24 hours. Oral antibiotics should then be given for 7 to 10shock. Women with pyelonephritis at risk for serious complications days, according to bacterial sensitivities, or if not available, as if forare those who present with the highest fever (>39.4 °C) and tachycardia symptomatic lower UTI.17
CHAPTER 44 Renal Disorders 907 Failure of these measures to improve the maternal clinical conditionwithin 48 to 72 hours suggests an underlying structural abnormality. PreeclampsiaUltrasonography is an easy but inconclusive way of excluding stones. Ifclinical suspicion is high, a plain abdominal radiograph can identify 90% Preeclampsia and the Kidneyof renal stones, and a one-shot intravenous urogram (IVU) at 20 to 30 Preeclampsia rarely causes acute renal failure severe enough to requireminutes can identify the remainder.25 The risk to the fetus from radiation dialysis.32 In a cohort of South African women with severe preeclamp-of one or two radiographs is minimal, especially when compared with sia and renal impairment, 7 (10%) of 72 required temporary dialysis,the clinical beneﬁt of identifying an obstructed, nonfunctioning kidney. and none developed chronic renal failure.32 All women with severeUrinary tract obstruction can also be detected using magnetic resonance preeclampsia who needed dialysis had hemorrhage, which often wasurography, especially during the second and third trimesters.27 caused by abruptio placentae.32 Preeclampsia causing mild transient After one episode of pyelonephritis, pregnant women should have renal impairment (serum creatinine up to 125 μmol/L or 1.41 mg/dL)monthly urine cultures to screen for a recurrence.25 The risk of recur- is common, but with appropriate management, there should be com-rent pyelonephritis can be reduced with antimicrobial prophylaxis plete recovery of renal function.chosen according to the sensitivities of initial bacterial infection20,28 or Women with preexisting renal disease are more vulnerable to pre-with nitrofurantoin (100 mg every night) continued until 4 to 6 weeks eclampsia, especially when it is associated with chronic hypertension33after delivery.25 (see Chapter 35). A meta-analysis of trials investigating the effective- ness of low-dose aspirin (50 to 150 mg/day) in pregnant women with moderate to severe renal disease revealed a signiﬁcant reduction in the risk of preeclampsia and perinatal death.34Acute Renal Failure Conversely, 2% to 5% of women with preeclampsia are later foundin Pregnancy to have underlying renal disease,35 but if preeclampsia is severe, up to 20% of women will have chronic kidney disease (CKD).36 Women whoAcute renal failure has become a rare but serious complication of have had preeclampsia should therefore be checked for persistentpregnancy. In early pregnancy, acute renal failure is associated with postpartum hypertension and proteinuria. Gestational hypertensionseptic abortion (a complication largely conﬁned to the developing usually resolves within 3 months of delivery, but severe proteinuria dueworld) and dehydration related to hyperemesis gravidarum. Around to preeclampsia can take up to 12 months to disappear. Women whothe time of delivery, acute renal failure is most commonly caused by have had preeclampsia are more likely to have persistent microalbu-gestational syndromes such as preeclampsia and abruptio placentae minuria compatible with microvascular disease and are at increased(Table 44-1). However, pregnancy is a prothrombotic state that is asso- risk for cardiovascular disease in later life.37,38ciated with heightened inﬂammation29 and major changes to the vas- Women who develop high levels of proteinuria (>10 g/24 hr) tendcular endothelium,30 particularly the glomerular capillary endothelium.31 to have earlier-onset preeclampsia and deliver at an earlier gestationalThese physiologic changes predispose pregnant women to acute glo- age compared with preeclamptic women who have less marked pro-merular capillary thrombosis. Whereas nonpregnant patients who teinuria (<5 g/24 hr).39 After correction for prematurity, however,suffer an acute prerenal insult (e.g., hemorrhage, dehydration, septic massive proteinuria (>10 g/24 hr) has no signiﬁcant effect on neonatalshock) may develop transient acute tubular necrosis if inadequately outcome.39 Increasing proteinuria is not therefore an indication fortreated, the same prerenal insult in pregnancy is more likely to develop delivery. We suggest that pregnant women who develop a proteinuriainto renal cortical necrosis with permanent renal impairment. This is level of more than 1 to 3 g in 24 hours accompanied by other maternaleven more likely to occur if a prerenal insult coexists with a pregnancy- risk factors for thrombosis should be considered for thromboprophy-related condition that induces a consumptive coagulopathy or endo- laxis with enoxaparin (40 mg SC each day) or Fragmin (5000 units SCthelial damage (e.g., preeclampsia). each day). Management is aimed at identiﬁcation and correction of the pre- The diagnosis of preeclampsia is difﬁcult if there is chronic hyper-cipitating insult and optimal ﬂuid resuscitation, which is best guided tension and preexisting proteinuria, especially because these twoby monitoring the central venous pressure and pulmonary artery parameters become increasingly marked in late pregnancy. Hyperuri-wedge pressure. If oliguria persists despite euvolemia with deteriorat- cemia and intrauterine growth restriction are common features ofing renal function or ﬂuid overload, ﬂuid restriction followed by renal preeclampsia and chronic renal impairment, but the presence ofreplacement therapy is indicated. increased levels of hepatic transaminases and thrombocytopenia support a diagnosis of preeclampsia.40 TABLE 44-1 CAUSES OF ACUTE RENAL Preeclampsia: Management of Renal FAILURE IN PREGNANCY Impairment and Fluid Balance Most common causes Severe preeclampsia The cure for severe preeclampsia is delivery of the infant and placenta. Placental abruption Delivery may halt the general progression of preeclampsia, but post- Causes in early pregnancy Septic abortion partum maternal renal function usually deteriorates before improv- Hyperemesis gravidarum ing.32 It is advisable to recommend delivery for women who have Ovarian hyperstimulation syndrome preeclampsia and an increase in the serum creatinine concentration Rare causes Amniotic ﬂuid embolus from about 70 μmol/L (0.79 mg/dL) to more than 120 μmol/L Hemolytic uremic syndrome/ thrombotic thrombocytopenic (1.36 mg/dL) to prevent ongoing renal impairment. purpura Fluid balance is critical to the management of acute renal failure Acute fatty liver of pregnancy during pregnancy. Too little intravascular ﬂuid leads to prerenal failure, Acute obstruction of renal tracts which is especially damaging to chronically impaired kidneys, whereas too much ﬂuid risks pulmonary edema, adult respiratory distress syn-
908 CHAPTER 44 Renal Disordersdrome, and maternal death.41 Transient oliguria (<100 mL over 4 hours) They are characterized by microangiopathic hemolytic anemia andis a common observation in the ﬁrst 24 hours after a healthy pregnancy. thrombocytopenia. The congenital and acquired forms of HUS/TTPIf a preeclamptic woman is not obviously hypovolemic and has a serum are more common in late pregnancy.46 Women with HUS/TTP developurea level of 5 mmol/L or less and serum creatinine level of 90 μmol/L platelet thrombi attached to von Willebrand factor multimers in end-or less, repeated ﬂuid challenges to increase urine output are unneces- organ microvessels. This typically results in a multiorgan disorder withsary and increase the maternal risk of pulmonary edema. Women with abdominal ischemia and renal or neurologic impairment.47 A plasmasevere preeclampsia and renal impairment (i.e., serum creatinine level metalloprotease (ADAMTS13), which normally cleaves von Willebrandof more than 120 μmol/L or 1.36 mg/dL) should have their ﬂuid balance factor multimers to prevent microthrombi, is deﬁcient in some womenguided by a central venous pressure catheter or, when available, a pul- with congenital HUS/TTP,48 and antibodies that neutralize ADAMTS13monary artery ﬂotation catheter on a high-dependency unit familiar have been found in women with acquired HUS/TTP.49with this equipment.42 The rate of ﬂuid replacement should take account HUS/TTP is more common in women (approximately 70% ofof central venous ﬁlling pressure, pulmonary wedge pressure, hourly cases) and more common in association with pregnancy (approxi-urine output, and insensible loses. After the patient is euvolemic, the mately 13% of cases).46 During pregnancy, the levels of ADAMTS13rate of intravenous ﬂuid replacement should equal the previous hours’ fall progressively.50 This may explain why women with a congenitalurine output plus insensible losses; this is usually 30 mL/hr if the patient deﬁciency of ADAMTS13 or with other risk factors for thrombosisis afebrile. The amount of intravenous ﬂuid replacement can be reduced (e.g., obesity, thrombophilia) are predisposed to peripartumafter the mother can take oral ﬂuid and her renal impairment starts to HUS/TTP.improve. Intravenous ﬂuid regimens that stick to a ﬁxed hourly replace-ment can lead to ﬂuid overload in oliguric women and to reduced Hemolytic Uremic Syndrome, Thromboticintravascular volume in those having a diuresis. Fluid replacement Thrombocytopenic Purpura, and Preeclampsiashould include blood to replace blood loses and then isotonic sodium Preeclampsia shares many similarities with HUS/TTP. Both syndromeschloride or compound sodium lactate (i.e., Hartmann’s solution). Dex- occur most frequently in the third trimester or immediately aftertrose solutions are hypotonic and lead to maternal hyponatremia (5% delivery. It is, however, important to differentiate them, becausedextrose contains only 30 mmol/L of NaCl, compared with 150 mmol/L management is different. Women with HUS/TTP often present withof NaCl in a 0.9% sodium chloride solution). gastrointestinal or neurologic abnormalities,46 and they are more likely Low-dose “renal” dopamine infusion (3 μg/kg/min) was previously to have severe renal impairment, hemolysis, and thrombocytopeniaused to increase renal blood ﬂow in people with acute renal failure, but compared with women who have preeclampsia. Because disseminatedit is no longer thought to be beneﬁcial. It is recommended that once intravascular coagulation (DIC) is rare in HUS/TTP, the prothrombinhypovolemia has been corrected, as judged by the central venous pres- time and kaolin clotting time are usually normal.47 Women withsure or pulmonary wedge pressure, preeclamptic women with oliguria preeclampsia are also more likely to have elevated levels of hepatic(<200 mL/12 hr) and a serum urea level higher than 14 mmol/L transaminases, heavy proteinuria, and abnormal clotting compared(39 mg/dL) and serum creatinine level higher than 500 mmol/L with women with HUS/TTP.40 However, in many women, the(5.65 mg/dL) may beneﬁt from a furosemide infusion (5 mg/hr) in an distinction between preeclampsia and HUS/TTP can be determinedeffort to prevent ﬂuid overload and hemodialysis.43 only by the course of the illness after delivery,51 but acute renal failure After acute tubular necrosis is established with oliguria and a rising due to preeclampsia usually becomes transiently worse beforeserum creatinine level despite adequate intravascular volume and improving.32blood pressure, ﬂuid intake should be restricted to avoid ﬂuid over-load. In these circumstances, dialysis is indicated. There are no good Management of Hemolytic Uremic Syndromestudies that have followed up women with acute renal failure related and Thrombotic Thrombocytopenic Purpurato preeclampsia, but those with the most severe renal impairment will Maternal survival from HUS/TTP greatly improved since treatmentundoubtedly be left with a degree of permanent renal impairment that with plasmapheresis (i.e., infusion of fresh plasma and removal of oldmay not manifest until later life.32 plasma).52 Until recently, it was unclear why plasmapheresis worked, Hypertension due to preeclampsia is caused by vasoconstriction but the discovery of antibodies to ADAMTS13 (removed with oldaround a reduced plasma volume.40 For this reason and despite the lack plasma) and a congenital deﬁciency of ADAMTS13 (replenished withof evidence from randomized trials, women with severe preeclampsia infusion of fresh plasma) gives reason to this process. However, severeoften receive plasma volume expansion before therapeutic vasodila- deﬁciency of ADAMTS13, which is not a routine laboratory measure-tion. Unless there are signs of pulmonary edema (i.e., basal crackles ment, is not present in all cases of HUS/TTP, and plasmapheresisand PO2 < 95% on air), 500 mL of colloid or crystalloid given over 30 is effective in pregnant women who have milder deﬁciencies ofto 60 minutes or 250 mL per hour until the pulmonary wedge pressure ADAMTS13.53is 10 to 12 mm Hg can improve maternal and fetal well-being in cases Steroids are often added to the plasma exchange regimen and are aof severe preeclampsia.45,46 A vasodilator given alone can cause pro- rationale choice for acquired HUS/TTP with an autoimmune pathol-found hypotension that may threaten maternal renal, cerebral, and ogy, but there are no randomized, controlled trials of their use. Anti-uteroplacental blood ﬂow. platelet regimens with aspirin and dipyridamole may also be beneﬁcial in conjunction with plasma exchange.54 Conversely, administration of platelets to thrombocytopenic patients with HUS/TTP can result in aHemolytic Uremic Syndrome precipitous decline in clinical status.and ThromboticThrombocytopenic Purpura Acute Renal Cortical NecrosisHemolytic uremic syndrome (HUS) and thrombotic thrombocytope- In the developed world, acute renal cortical necrosis (ARCN) hasnic purpura (TTP) are similar syndromes (designated HUS/TTP). become a rare complication of pregnancy. The reduced incidence of
CHAPTER 44 Renal Disorders 909septic abortion and improved management of peripartum obstetricemergencies have prevented prerenal impairment developing into Nephrotoxic Drugs during Pregnancyacute tubular necrosis and then renal cortical necrosis. In the develop- Nonsteroidal anti-inﬂammatory drugs (NSAIDs), including the moreing world, however, obstetric emergencies are still responsible for most selective cyclooxygenase-2 (COX-2) inhibitors, when given to thecases of ARCN.55 Acute renal failure after septic abortion or peripar- mother in the peripartum period, reduce renal blood ﬂow and havetum obstetric emergencies developed into ARCN in 20% of women been associated with acute renal impairment in the mother and fetus.61after a prolonged period of acute tubular necrosis.56 Women with reduced intravascular volume, especially with preexisting ARCN is most commonly caused by abruption of the placenta with renal impairment, are particularly vulnerable and should be prescribedhemorrhage, amniotic ﬂuid embolus, and sepsis associated with DIC.57 NSAIDs with caution. Aminoglycosides are also nephrotoxic andAfter hemorrhage or sepsis with hypotension, prerenal failure without should be prescribed with care and attention to drug plasma levels inadequate resuscitation leads to acute tubular necrosis. If anuria persists women with mild renal impairment.for longer than a week, ARCN should be suspected. A deﬁnitive diag-nosis can be made with renal biopsy, but it is often missed because ofthe patchy nature of cortical necrosis. Selective renal angiography canconﬁrm the diagnosis, but it introduces another nephrotoxic agent and Acute Renal Obstruction in Pregnancyis usually unnecessary. Because of the serious nature of the precipitat- The renal tracts may be obstructed during pregnancy by renal calculiing illness and the limited availability of renal replacement therapy in (discussed later), congenital renal tract abnormalities, or a gestationalthe developing world, the maternal mortality rate is still high.56 overdistention syndrome. Women born with congenital obstructive For women who survive the acute illness, renal function usually uropathies at the pelviureteral junction (PUJ) or vesicoureteric junc-returns slowly over the next 6 to 24 months. Long-term renal function tion (VUJ) are at increased risk of urine outﬂow obstruction in thedepends on the extent of cortical necrosis, which is often incomplete. second half of pregnancy, even if they have had surgical correction inHyperﬁltration through remnant glomeruli usually leads to a subse- childhood.62 Congenital abnormalities of the lower urinary tracts,quent progressive decline in renal function. including the bladder and urethra, are varied and usually require extensive surgical correction in childhood. During pregnancy, these women are at increased risk for recurrent urine infections and, lessAcute Fatty Liver of Pregnancy commonly, for outﬂow obstruction requiring temporary nephrostomyAcute fatty liver of pregnancy (AFLP) causes reversible peripartum or a ureteric stent.63liver and renal impairment in 1 of 5000 to 10,000 pregnancies.58 The Women with a single kidney and urologic abnormalities are par-diagnosis is based on clinical and laboratory ﬁndings of impaired liver, ticularly vulnerable to develop post-renal failure in relation to gesta-renal function, and clotting function, rather than on histologic or tional obstruction of their solitary kidney. An incomplete obstructionradiologic evidence of a fatty liver.58 Women with AFLP usually present can cause renal impairment with an apparently good urine output.with nausea, vomiting, and abdominal cramps. Impaired renal func- High backpressures compress and damage the renal medulla, leadingtion and reduced plasma antithrombin levels are early ﬁndings of to a loss of renal concentrating ability and production of dilute urineAFLP that may precede liver dysfunction.58 In established cases of that is passed through an incomplete obstruction. It is also importantAFLP, depressed function of the liver with prolonged prothrombin for the obstetrician to remember that a congenitally single kidney istime, hypoglycemia, and DIC are more markedly abnormal than levels often associated with other abnormalities of the genital tracts, such asof liver transaminases, which may only be moderately elevated.58 In a a unicornuate uterus.64series of 28 women with AFLP, other ubiquitous laboratory ﬁndings at During pregnancy, the renal tracts can rarely and spontaneouslythe time of delivery were elevated levels of serum total bilirubin (mean, become grossly overdistended. If untreated, overdistention occasion-7.5 mg/dL), serum creatinine (mean, 205 mmol/L or 2.3 mg/dL), and ally can lead to rupture of the kidney or renal tracts.65 Women withuric acid (mean, 11 mg/dL).58 overdistention of the renal tracts initially present with severe loin pain, A recessively inherited fetal inborn error of mitochondrial fatty acid most commonly on the right side and radiating to the lower abdomen.oxidation may explain up to 20% of AFLP cases.59 Mitochondrial fatty The pain is positional and inconstant; it is characteristically relievedacid oxidation is important for normal renal and liver function and by lying on the opposite side and tucking the knees up to the chest. Amay therefore explain the dual vulnerability of these organs in women palpable tender ﬂank mass may suggest renal tract rupture.65 Rupturewith AFLP. of the kidney almost always occurs in a previously diseased kidney, In women with AFLP, maternal renal impairment is aggravated by usually in association with a benign hamartoma or renal abscess.65hypotension from hemorrhage, which is most likely to follow an emer- Urinalysis can reveal gross or microscopic hematuria. A renal ultra-gency operative delivery.58,60 The combination of renal dysfunction, sound can detect a hydronephrotic kidney with a grossly dilatedhemorrhage, and DIC resulting from liver failure during pregnancy or pelvicaliceal system. Occasionally, a urinoma is evident around theafter delivery requires intensive care with a multidisciplinary team of kidney, indicating rupture of the renal pelvis that can sometimes sealhepatologists, nephrologists, intensive care specialists, and obstetri- spontaneously.cians. Management is supportive and aimed at maintaining adequate The pain from the overdistention syndrome varies from mildﬂuid balance for renal perfusion, replacing blood, correcting the coag- to very severe. Women with mild symptoms can usually be managedulopathy with fresh frozen plasma and possibly with antithrombin with advice on positional relief and regular analgesia. Women withconcentrate and fresh platelets. Hypoglycemia should be corrected severe unremitting pain, hematuria, and grossly distended renal tractswith 10% dextrose solutions. Temporary dialysis may be necessary, but on ultrasound in the absence of structural or infected masses usuallywith good supportive care, recovery of normal renal and liver function have immediate pain relief after decompression of the system withis usual.58 Perinatal survival in association with AFLP is improving, but a ureteric stent or nephrostomy. Rupture of the kidney necessi-it depends on the early recognition of the maternal condition, close tates immediate surgery and almost invariably an emergencyfetal surveillance, timely delivery, and excellent neonatal care. nephrectomy.65
910 CHAPTER 44 Renal Disorders TABLE 44-2 STAGES OF CHRONIC KIDNEYChronic Kidney Disease DISEASENormal Pregnancy and Stage Description GFR*Renal Assessment 1 Kidney damage with normal or ≥90 increased GFRThe glomerular ﬁltration rate (GFR), measured as 24-hour creatinine 2 Kidney damage with mildly 60-89clearance, increases by more than 50% shortly after conception. decreased GFRSerum creatinine (and urea nitrogen levels, which average 70 μmol/L 3 Moderately decreased GFR 30-59(0.8 mg/dL) and 5 mmol/L (13 mg/dL), respectively, in nonpregnant 4 Severely decreased GFR 15-29women, decrease to mean values of 50 μmol/L (0.6 mg/dL) and 5 Kidney failure <15 or dialysis3 mmol/L (9 mg/dL) in pregnant women. Near term, a 15% to 20% *Glomerular ﬁltration rate (GFR) reported as mL/min/1.73 m2.decrement in GFR occurs, which affects serum creatinine levels From the National Kidney Foundation: K/DOQI clinical practiceminimally. guidelines for chronic kidney disease: Evaluation, classiﬁcation and Serum creatinine values of 80 μmol/L (0.9 mg/dL) and urea nitro- stratiﬁcation. Am J Kidney Dis 39(Suppl 1):S1-S266, 2002.gen of 6 mmol/L (14 mg/dL), which are acceptable in nonpregnantsubjects, are suspect in pregnant women. However, the physicianshould use caution in assessing renal function by serum creatinine Women with CKD are less able to make the renal adaptationslevels alone, because the creatinine is ﬁltered and secreted by the characteristic of and essential to healthy pregnancy. Their inability tokidney, and the ratio of creatinine to inulin clearance normally falls to boost renal hormones often leads to normochromic normocyticbetween 1.1 and 1.2. As renal disease progresses, a greater portion of anemia, reduced plasma volume expansion, and vitamin D deﬁ-urinary creatinine is formed as a result of secretion (clearance ratios ciency.75,76 The gestational rise in GFR is impaired in women withrise to between 1.4 and 1.6 when the serum creatinine level is 1.4). The moderate renal impairment and usually absent in those with a serumGFR may be overestimated by 50%. creatinine level higher than 200 μmol/L (2.26 mg/dL).68,77,78 If pre- Formulas (e.g., the Cockroft-Gault formula) that use serum creati- eclampsia develops there is often a mild deterioration in renal func-nine in relation to age, height, and weight to calculate GFR should not tion, but the addition of a prerenal insult, such as signiﬁcant peripartumbe used in pregnancy because weight or body size does not reﬂect hemorrhage, can seriously threaten maternal renal function.kidney size. The use of estimated GFR (eGFR) from the Modiﬁcationof Diet in Renal Disease (MDRD) formula, whereby the serum creati-nine value is adjusted for age, gender, and race, cannot be recom- Renal Dysfunction and the Impactmended for use in pregnancy because it signiﬁcantly underestimates of Pregnancythe GFR.66 Ideally, evaluation of renal function in pregnancy should bebased on the clearance of creatinine rather than its serum concentra- Mild Renal Impairment: Chronic Kidney Diseasetion. Creatinine levels may increase by up to 12 μmol/L (0.15 mg/dL) Stages 1 and 2shortly after ingestion of cooked meat (because cooking converts pre-formed creatine into creatinine), and the timing of the blood sample Most women with CKD who become pregnant have mild renal dys-during a clearance period must take into account meals and their function, and pregnancy usually succeeds without affecting renal prog-content. nosis. However, complications such as preeclampsia, intrauterine fetal growth restriction, and preterm birth are more common (Table 44-3).69,68Renal Dysfunction and A case-controlled study of 360 women with primary glomerulone-Preconception Counseling phritis and only mild pre-pregnancy renal dysfunction (serum creati-CKD is often clinically and biochemically silent until renal impair- nine level less than 110 μmol/L), minimal proteinuria (<1 g/24 hr),ment is advanced. Symptoms are unusual until GFR declines to less and absent or well-controlled hypertension, showed that pregnancythan 25% of normal, and more than 50% of renal function can be lost had little or no adverse effect on long-term (up to 25 years) maternalbefore the serum creatinine level rises above 120 μmol/L (1.36 mg/dL). renal function.79 The situation is quite different for women who haveHowever, women who become pregnant with a serum creatinine level moderate to severe renal impairment (CKD stages 3, 4, or 5).above 125 μmol/L (1.4 mg/dL) are at increased risk for an accelerateddecline in renal function and poor pregnancy outcome.67-70 Moderate to Severe Renal Impairment: Chronic CKD is universally classiﬁed into ﬁve stages according to the level Kidney Disease Stages 3 through 5of renal function (i.e., GFR) (Table 44-2). CKD stages 3 through 5 Small, mainly uncontrolled, retrospective studies have shown that(GFR < 60 mL/min) affect approximately 1 in 250 women of child- women with the worst pre-pregnancy renal function are at greatest riskbearing age (20 to 39 years),71 but due to reduced fertility and an for an accelerated decline in renal function caused by pregnancy (seeincreased rate of early miscarriage, pregnancy in these women is less Table 44-3). Proteinuria and hypertension add to this risk.68,70,77,80,81common. Studies of CKD in pregnancy have mostly classiﬁed women One retrospective series of women with CKD (87 pregnancies) foundon the basis of serum creatinine values, but we estimate that approxi- that those with initially moderate renal impairment (serum creatininemately 1 of 750 pregnancies are complicated by CKD stages 3, 4, or level of 124 to 168 mmol/L or 1.4 to 1.9 mg/dL) had a 40% risk of a5.72,73 Some women are discovered to have CKD for the ﬁrst time pregnancy-related decline in renal function, which persisted afterduring pregnancy. Approximately 20% of women who develop early delivery in about one half of those affected, whereas 13 (65%) of 20preeclampsia (≤30 weeks’ gestation), especially those with heavy pro- women with severe renal impairment (i.e., serum creatinine levelteinuria, have previously unrecognized CKD.74 higher than 177 mmol/L or 2.0 mg/dL) had a decline in renal function
CHAPTER 44 Renal Disorders 911 TABLE 44-3 PRE-PREGNANCY RENAL FUNCTION IN CHRONIC RENAL DISEASE WITH ESTIMATES FOR PREGNANCY OUTCOME (>24 WEEKS) AND IMPACT ON MATERNAL RENAL FUNCTION Loss of Renal Function* Serum Creatinine Level IUGR Preterm Delivery Preeclampsia Perinatal Deaths Pregnancy Persists after Delivery ESRF in 1 Year mmol/L (mg/dL) (%) (%) (%) (%) (%) (%) (%) <125 (<1.4) 25 30 22 1 2 — — 125-180 (1.4-2.0) 40 60 40 5 40 20 2 >180 (>2.0) 65 >95 60 10 70 50 35 *Estimates are based on literature from 1985 to 2007, with all pregnancies attaining at least 24 weeks’ gestation. ESRF, end-stage renal function; IUGR, intrauterine growth restriction. Data from references 67-70, 72, 77, 78, 83, 165-169.during the third trimester that persisted in almost all and deteriorated and infection increase the risk of complications at all levels of renalto end-stage renal failure in 7 (35%) of 20.67,82 impairment. The ﬁrst prospective study to assess the rate of decline of maternal A question should be asked: Is pregnancy advisable? If a womanrenal function before and after pregnancy in 49 women with pre-preg- with chronic renal disease wishes to have a family, the sooner she starts,nancy CKD stages 3 to 5 conﬁrmed these earlier observations.70 Spe- the better. In some of these patients, renal function continues to declineciﬁcally, women with a pre-pregnancy eGFR less than 40 mL/min/1.73 m2 with time. Women are not always counseled before conception. Aand proteinuria level of more than 1 g in 24 hours, but not either factor patient with suspected or known renal disease may present alreadyalone, showed an accelerated decline in renal function after their preg- pregnant, and the question then becomes whether to continue thenancy compared with before pregnancy. Chronic hypertension, which pregnancy.predisposes women to preeclampsia, may explain why those with Ideally, all women with CKD should be made aware of the risksmilder renal dysfunction also have a gestational decline in renal func- pregnancy may have on their own long-term renal function and preg-tion. This risk is reduced when hypertension is controlled. nancy outcome before they conceive. Folic acid (400 mg daily) should be given as usual around conception until at least 12 weeks’ gestation. Low-dose aspirin (50 to 150 mg/day) should be started in early preg-Impact of Chronic Kidney Disease on nancy to reduce risk of preeclampsia and improve perinatal outcome.34Perinatal Outcome Regular drugs should be reviewed so that fetotoxic drugs (e.g., angio-Maternal hypertension, proteinuria, and recurrent urinary infection tensin-converting enzyme [ACE] inhibitors, angiotensin II receptoroften coexist in women with CKD, and it is difﬁcult to apportion the blockers) can be stopped as soon as pregnancy is conﬁrmed.85contribution that each factor makes to a poor pregnancy outcome. It There are reports of women with severe chronic renal failure havingappears, however, that each factor is individually and cumulatively successful pregnancies managed without dialysis.86 In one woman, thedetrimental to fetal outcome.67,70,76,77 Although women with severe serum creatinine level was 700 μmol/L (8 mg/dL) at the time of spon-renal impairment have the greatest difﬁculty conceiving, the highest taneous delivery.87 Dialysis has also been instituted prophylacticallyrate of miscarriage, and poorest fetal outcome, there is a spectrum during pregnancy to increase the chances of a successful outcome.88of poor outcomes, including preeclampsia, fetal growth restriction, Nevertheless, we believe that these women should not take additionalpreterm delivery, and perinatal death, correlating with the level of renal health risks. The aim should be to preserve what little renal functiondysfunction.68,69,70,78,83 remains and to achieve renal rehabilitation by dialysis and transplanta- tion, after which the question of pregnancy can be considered if appropriate.Preconception Counseling The literature that forms the basis of our views is primarily retro-Initiating and sustaining pregnancy are related to the degree of func- spective. Most patients described had only mild dysfunction, andtional impairment. Fertility is diminished as renal function falls. When women with greater dysfunctional disease were limited in number.the preconception serum creatinine level exceeds 280 μmol/L (3 mg/ Conﬁrmation of any preconception guidelines requires deﬁnitiveL), corresponding to a GFR of less than 25 mL/min, normal pregnancy observational trials that must be prospective.is unusual; however, successes have been documented in women withmoderate to severe disease, including some treated with dialysis becauseof accelerated maternal renal deterioration.84 Antenatal Strategy and Ideally, pregnancy is probably best restricted to women with pre- Decision Makingconception serum creatinine levels below 180 μmol/L (2 mg/dL) anda diastolic blood pressure of 90 mm Hg or less. If the patient has Patients should be seen at least at 2-week intervals or less until 32hypertension requiring more than one drug for control, prognosis weeks’ gestation, after which assessment should be weekly. Routinebecomes substantially poorer. Some clinicians extend this limit serial antenatal observations should be supplemented with theto 250 μmol/L (2.8 mg/dL), whereas others believe it should be following:no higher than 140 μmol/L (1.5 mg/dL). Whatever level is used, wereiterate that degrees of impairment not causing symptoms or disrupt- 1. Assessment of renal function using serum creatinine levels anding homeostasis in nonpregnant individuals can still jeopardize preg- protein excretion using the protein to creatinine ratio on a spotnancy. Clinical complications such as hypertension, proteinuria, urine sample on approximately a monthly basis
912 CHAPTER 44 Renal Disorders2. Careful monitoring of blood pressure for early detection of hyper- of ﬂuid balance, renal function, and blood pressure and a further tension and treatment to keep blood pressure at 140/90 mm Hg or review of drug therapy are necessary. Breastfeeding should be encour- less aged in women with CKD, but is sometimes not possible for those with3. Early detection of superimposed preeclampsia, with checks of blood severe CKD. Information is still lacking on whether some immunosup- urea nitrogen, full blood cell count, liver function tests, blood pres- pressive drugs appear in breast milk, but prednisolone, azathioprine, sure, and proteinuria and ACE inhibitors are barely detectable in breast milk. Women who4. Biophysical assessment of fetal size, development, and well-being have heavy proteinuria associated with preeclampsia should be fol-5. Early detection of asymptomatic bacteriuria or conﬁrmation of lowed until the proteinuria disappears or a diagnosis of renal disease UTI every month is made.Renal FunctionIf renal function deteriorates, reversible causes should be sought, suchas a UTI, subtle dehydration, or electrolyte imbalance, which is occa- Problems Associated withsionally precipitated by inadvertent diuretic therapy. Near term, a 15%to 20% decrement in function, which affects serum creatinine levels Speciﬁc Kidney Diseasesminimally, is permissible. Failure to detect a reversible cause of a sig- In 1991, Imbasciati and Ponticelli90 reviewed outcomes for more thanniﬁcant decrement is reason to end the pregnancy by elective delivery. 1000 patients with a variety of speciﬁc disorders, which were usuallyWhen proteinuria occurs and persists but blood pressure is normal and documented by kidney biopsy. In this review and in other editorials,3renal function is preserved, the pregnancy can be allowed to continue. therapeutic abortions were excluded from calculation of pregnancy success rates and the discussion of the underlying factors.Blood PressureMost of the speciﬁc risks of hypertension appear to be mediatedthrough superimposed preeclampsia. There is still controversy about Acute and Chronic Glomerulonephritisthe incidence of preeclampsia in women with preexisting renal disease. The acute form of glomerulonephritis is a rare complication of preg-The diagnosis cannot be made with certainty on clinical grounds alone nancy, and it can be mistaken for preeclampsia. For patients withbecause hypertension and proteinuria may be manifestations of the chronic glomerulonephritis, one view warns of aggravation because ofunderlying renal disease. Treatment of hypertension in pregnancy is the hypercoagulable state accompanying pregnancy, with patientsconsidered in Chapter 35. more prone to superimposed preeclampsia or hypertensive crises High blood pressure in the presence of an underlying kidney dis- earlier in pregnancy. The consensus, however, is that if renal func-order is treated more aggressively than are other hypertensive compli- tion is stable and hypertension is absent, most pregnancies are suc-cations of pregnancy. This is done because such actions preserve cessful.76 In a review of 906 pregnancies in 557 women, thesefunction longer. Although diastolic levels of 100 mm Hg or less may generalizations were endorsed90 and several speciﬁc issues werebe permissible in many pregnant women with underlying essential highlighted:hypertension, a diastolic goal of 90 mm Hg or less should be set forpatients with renal disease. Complications developed more frequently in women who already had some dysfunction or hypertension in earlyFetal Surveillance and Timing of Delivery pregnancy.Serial assessment of fetal well-being is essential because renal disease De novo hypertension or worsening of preexistingcan be associated with intrauterine growth restriction, and when com- hypertension occurred in 25% of pregnancies but usuallyplications do arise, the judicious moment for intervention is inﬂuenced reverted after delivery, suggesting superimposed preeclampsia,by fetal status. Current technology should minimize the risk of intra- a diagnosis that is not easy to conﬁrm in this group of patients.uterine fetal death and neonatal morbidity and mortality. Regardless In 10% of pregnancies, hypertension persisted after delivery,of gestational age, most infants weighing 1500 g or more are better off especially in patients with focal and segmentalin a special care nursery than in a hostile intrauterine environment. glomerulosclerosis, membranoproliferative glomerulonephritis,Deliberate preterm delivery may be necessary if renal function deterio- and IgA nephropathy.rates substantially or for the usual maternal and fetal causes, such as Higher rates of fetal loss observed in these women can beuncontrollable hypertension, and signs adduced by monitoring of fetal accounted for by the greater prevalence of severe hypertensionjeopardy. and renal insufﬁciency.Renal Biopsy Other, smaller series have endorsed these points. For example, preg-Percutaneous renal biopsy is usually avoided in pregnancy because the nancy is well tolerated without effect on the course of the disease ifplethoric kidney appears to be more prone to bleeding, especially in blood pressure is normal and the GFR is higher than 70 mL/minutehypertensive pregnant women.89 Renal biopsy, although not usually before conception.76,91 With hypertension, the rate of live births isrequired for the diagnosis and management of preeclampsia, may be reduced if hypertension exists before pregnancy or is not well con-indicated if there is reason to suspect a renal lesion that could be suc- trolled during gestation.cessfully treated, especially in early pregnancy and up to 32 weeks’ Hereditary nephritis, an uncommon disorder, may ﬁrst manifest orgestation, whilst permitting the pregnancy to continue. become exacerbated during pregnancy, but most gestations succeed. One variant of hereditary nephritis involves disordered platelet mor-Postpartum Care phology and function. In these cases, pregnancy has been successfulIt can take up to 3 months (occasionally longer) for the physiologic but was sometimes complicated by bleeding problems, especially atchanges of pregnancy to disappear. During that time, close monitoring delivery.
CHAPTER 44 Renal Disorders 913 pain or fever, and when the pregnancy is over, the usual x-ray evalua-Chronic Pyelonephritis tion is obtained and standard management resumed.97Chronic pyelonephritis (i.e., tubulointerstitial disease) in pregnancy Sonographically guided percutaneous nephrostomy is anothermay be infectious or noninfectious. The prognosis in pregnancy is effective and safe method of treating gravidas with ureteric colic orsimilar to that for patients with glomerular disease; the outcome is best symptomatic obstructive hydronephrosis. The procedure is rapid,for patients with adequate renal function and normal blood pressure. requires minimal anesthesia, and is preferable to retrograde stentingCompared with nonpregnant women, pregnant women have a higher or more invasive surgery.frequency of symptomatic infections, but these patients may have In patients with cystinuria, assiduous maintenance of high ﬂuida more benign antenatal course than do women with glomerular intake is the mainstay of management. Although D-penicillaminedisease. appears relatively safe, it should be used only for severe cases, such as when urinary cystine excretion is known to be very high.98Reﬂux Nephropathy Autosomal Dominant PolycysticThe term reﬂux nephropathy is used to describe renal morphologic andfunctional changes that relate to past (and usually present) vesicoure- Kidney Diseaseteric reﬂux, which often is complicated by recurrent infection. Opin- Autosomal dominant polycystic kidney disease (ADPKD) is the mostions were once controversial, but with preserved renal function and no common genetic renal disorder, but it may remain undetected duringhypertension, fetal and maternal outcomes appear to be excellent.77 For pregnancy. Careful questioning for a history of familial problemsthese patients, vigilance is still necessary to detect and treat UTIs (28% and the use of ultrasonography may lead to earlier detection. Patientsto 65%), with many physicians advocating prophylactic antibiotics. do well when functional impairment is minimal and hypertensionUnfortunately, reﬂux nephropathy is often associated with hyperten- is absent, as is often the case in childbearing years.99 They do,sion and moderate or severe renal dysfunction by the time these however, have an increased incidence of hypertension late in preg-patients reach childbearing age, and such a scenario adversely affects nancy and a higher rate of perinatal mortality compared with thatpregnancy outcome. Speciﬁc obstetric concerns about affected patients in pregnancies of sisters unaffected by this autosomal dominantinclude severe intrauterine growth restriction and the risk of sudden, disease.rapid worsening of hypertension and renal function with accelerated Women with advanced renal failure are best advised against preg-progression to renal failure.92 nancy, although use of prophylactic dialysis has been advocated, despite lack of controlled studies, for this type of patient.100 If one or the other prospective parent has evidence of polycystic renal disease, the coupleUrolithiasis may seek genetic counseling. There is a 50% chance of transmittingThe prevalence of urolithiasis in pregnancy is 0.03% to 0.35%.93 Renal the disease to the offspring, which is caused by two identiﬁed genes:and ureteric calculi cause nonuterine abdominal pain severe enough PKD1 (85%) and PKD2 (15%). DNA probe techniques can make theto necessitate hospital admission during pregnancy. Most calculi are diagnosis of ADPKD, but a signiﬁcant number of ADPKD mutationscalcium oxalate (the more benign type), but occasionally, the more are caused by multiple amino acid substitutions, which need to bemalicious struvite stones (e.g., staghorn) are seen. Uric acid and cystine interpreted with caution.101are much less common. Management should be conservative initially, with adequate hydra-tion, appropriate antibiotic therapy, and pain relief with systemic anal- Diabetic Nephropathygesics. Most women pass their stones spontaneously. The use of Because many patients have had diabetes since childhood, theycontinuous segmental (T11 to L2) epidural block has been advocated, probably already have microscopic changes in the kidneys.102 Duringas in nonpregnant patients with ureteric colic, and it may favorably pregnancy, diabetic women have an increased prevalence of covertinﬂuence spontaneous passage of the stones. With good pain relief, bacteriuria (and may be more susceptible to symptomatic UTI),patients micturate without difﬁculty, move without assistance, and are peripheral edema, and preeclampsia.84less at risk for thromboembolic problems than if they are drowsy, Most women with diabetic nephropathy who become pregnant stillnauseated, and bedridden with pain. have good renal function and demonstrate normal GFR increments When there are complications that may require surgical interven- (with perhaps signiﬁcant proteinuria), and pregnancy does not accel-tion, pregnancy should not be a deterrent to limited IVU, even though erate renal deterioration.103 There is, however, a report of diabeticthe clinician may be reluctant to consider radiologic investigation. women with moderate renal dysfunction (serum creatinine level aboveSpeciﬁc clinical criteria should be met before a limited IVU is under- 125 μmol/L or ≤1.4 mg/dL) whose renal function permanently deteri-taken: microscopic hematuria, recurrent urinary tract symptoms, and orated in pregnancy compared with the changes before and after-sterile urine culture when pyelonephritis is suspected. The presence ward.104 Such changes occurred despite good metabolic control andof two of these criteria indicates a diagnosis of calculi in 60% of might have been related to hypertension, which often accelerates in thewomen.94 third trimester regardless of intensiﬁed treatment.105 However, there Magnetic resonance urography can be used to avoid radiation were no controls for this study. The condition of diabetic patients withexposure.95 Another approach involves the cystoscopic placement of an creatinine levels above 1.4 mg/dL who do not become pregnant oftenintraureteral tube, or stent, between the bladder and kidney under local progresses rapidly to further renal failure.anesthesia.96 The stent retains its position because it has a pigtail or J- Hypertension should be treated more intensively in diabetics. Aslike curve at each end (double-J), and it can be changed every 8 weeks with other renal disorders during pregnancy, we believe that moreto prevent encrustation. Early empiric use for presumed stone obstruc- aggressive antihypertensive therapy is a reasonable objective. Thesetion in pregnant women with ﬂank pain is recommended by some, patients often are treated with “renoprotecting” ACE inhibitors orespecially when hydration, analgesia, and antibiotics do not resolve angiotensin receptor blockers prescribed before conception, but
914 CHAPTER 44 Renal Disordersthese drugs should be stopped as soon as possible after conceptionto avoid teratogenic effects that become evident after 6 weeks’ Systemic Sclerosisgestation.85 Scleroderma is a term that includes a heterogeneous group of limited and systemic conditions causing hardening of the skin. Systemic scle- rosis implies involvement of skin and other sites, particularly certainSystemic Lupus Erythematosus internal organs. Renal involvement is thought to occur in about 60%Systemic lupus erythematosus (SLE) is a relatively common disease of these patients, usually within 3 to 4 years of diagnosis. Manifestationand has a predilection for women of childbearing age. Its coincidence may take one of three forms: sudden onset of malignant hypertension,with pregnancy poses complex clinical problems because of the pro- rapidly progressive renal failure, or slowly increasing azotemia.110found disturbance of the immunologic system, multiorgan involve- The combination of systemic sclerosis and pregnancy is unusualment, and complicated immunology of pregnancy itself.84 The outcome because the disease occurs most often in the fourth and ﬁfth decades,of pregnancy for women with SLE is variable and to some extent and affected patients are usually infertile. When it has its onset inunpredictable, so careful monitoring, especially for those women with pregnancy, there is a greater tendency for deterioration. Patients withlupus nephritis, is required (see Chapter 51). scleroderma and no evidence of renal involvement before conception Decisions regarding the status of the disease and the importance of have developed severe kidney disease during gestation. There arehaving a child to the patient and her partner should be made on an also instances in which pregnancy has been uneventful and successful,individual basis. Most pregnancies succeed, especially when the mater- but marked reactivation occurred unexpectedly in the puerperium.nal disease has been in complete clinical remission for 6 months before Most maternal deaths involve rapidly progressive scleroderma withconception, even if there were marked pathologic changes in the origi- severe pulmonary complications, infections, hypertension, and renalnal renal biopsy and heavy proteinuria in the early stages of the failure.disease.106 Continued signs of disease activity or increasing renal dys- The extent of systemic involvement is probably more importantfunction reduces the likelihood of an uncomplicated pregnancy and than the duration of the disease, and limited, mild disease carries athe clinical course thereafter. better prognosis. Sclerosis usually spares the abdominal wall skin, but The effects of gestation on SLE activity and on the course of lupus there is one report of hydronephrosis, presumed to have been causednephritis have long been debated. Taking into account extrarenal man- by thickened skin and decreased abdominal wall compliance, in a twinifestations and renal changes, at least 50% of women show some pregnancy complicated by polyhydramnios.111change in clinical status, often called a lupus ﬂare.107 Some incrementsin proteinuria or blood pressure may result from preeclampsia. Womenwith lupus nephritis and renal insufﬁciency (serum creatinine level Wegener Granulomatosishigher than 125 μmol/L or 1.4 mg/dL) that antedates pregnancy have Information on the outcome of pregnancy in women with Wegenerworse outcomes. granulomatosis is scarce. Proteinuria (with or without hypertension) Lupus nephritis may sometimes become manifest during preg- is common, and reports have described complicated and uneventfulnancy, and when accompanied by hypertension and renal dysfunction, pregnancies.112 Experience with cyclophosphamide (Cytoxan) in preg-it may be mistaken for preeclampsia. Some patients experience relapse, nancy is limited, and the risks to the embryo and fetus must be weighedoccasionally severely in the puerperium; therefore, some clinicians in relation to the course of the disease if such therapy were to be with-prescribe or increase immunosuppression at this time.108 It is our prac- held from the mother.tice to increase immunosuppression only if there are signs of increaseddisease activity. SLE serum contains an array of autoantibodies (i.e., lupus serum Previous Urinary Tract Surgeryfactor) against nucleic acids, nucleoproteins, cell-surface antigens, and Permanent urinary diversion is still used in the management of patientsphospholipids. Antiphospholipid antibodies exert a complicated effect with congenital lower urinary tract defects, but its use for neurogenicon the coagulation system.109 This led to the deﬁnition of a lupus bladder has declined since the introduction of self-catheterization.anticoagulant, which is found in 5% to 10% of patients with SLE (see The most common complication of pregnancy is urinary infection.Chapter 40). Because treatment with low-molecular-weight heparin Premature labor occurs in 20%, and the use of prophylactic antibioticsand aspirin may lead to successful pregnancies, it is important to screen throughout pregnancy may reduce its incidence. Decline in renal func-for lupus anticoagulant in women with SLE and especially in those tion may occur, invariably related to infection or intermittent obstruc-with a history of recurrent intrauterine death or thrombotic episodes tion, or both. With an ileal conduit, elevation and compression by theto identify this particular cohort. expanding uterus can cause outﬂow obstruction, whereas with a ure- terosigmoid anastomosis, actual ureteral obstruction may occur. The changes usually reverse after delivery.Periarteritis Nodosa The mode of delivery is dictated by obstetric factors. AbnormalIn contrast to lupus nephritis, the outcome of pregnancy in women presentation accounts for a cesarean section rate of 25%. Vaginal deliv-with renal involvement as a result of periarteritis nodosa is very poor, ery is safe, but because the continence of a ureterosigmoid anastomosislargely because of the associated hypertension, which frequently is depends on an intact anal sphincter, this area must be protected withmalignant. Many cases in the literature have involved maternal demise. a mediolateral episiotomy.However, this dismal prognosis is based primarily on selected anec- During the past decade, urinary tract reconstruction by means ofdotal studies, and a few successful pregnancies have been reported. augmentation cystoplasty, with or without artiﬁcial genitourinaryStill, until more data are available (perhaps through a registry), con- sphincter, has become more common. Deterioration of renal functionsideration of early therapeutic termination must be made in the best and urinary tract obstruction or infection can occur at any time ininterests of maternal health. pregnancy. Delivery by cesarean section is recommended for these
CHAPTER 44 Renal Disorders 915gravidas because of the potential for disruption of the continence incidence of this HIV-associated nephropathy appears to be increas-mechanism. ing, particularly in the African-American population and in cases of intravenous drug abuse. Although few cases of this nephropathy have been reported in pregnant women, with the rising incidenceSolitary Kidney of acquired immunodeﬁciency syndrome (AIDS), especiallySome patients have a congenital absence of one kidney or marked among black African women, this form of renal disease shouldunilateral renal hypoplasia. Most, however, have had a previous be considered in HIV-infected patients presenting with severenephrectomy because of pyelonephritis (with abscess or hydronephro- proteinuria.sis), unilateral tuberculosis, congenital abnormalities, or a tumor. It isimportant to know the indication for and the time elapsed since thenephrectomy. In patients with an infectious or a structural renal Factors Affecting Prognosisproblem, sequential pre-pregnancy investigation is needed to detectany persistent infection. Effects of Speciﬁc Disorders on Fetal Outcome It makes no difference whether the right or left kidney remains, as The problems associated with the speciﬁc disorders discussed in thislong as it is located in the normal anatomic position. If function is section are summarized in Table 44-4. In general, we suggest that pre-normal and stable, women with this problem seem to tolerate preg- served renal function and the absence of hypertension before concep-nancy well despite the superimposition of GFR increments on already tion predict successful fetal outcome and few maternal complications,hyperﬁltering nephrons. Single kidneys are most often associated with regardless of the nature of the disorder. These conclusions often arethe rare instances of acute renal failure as a result of obstruction during based on poorly controlled, retrospective data, underscoring the needpregnancy. for registries and for prospectively acquired data; there is only one such Ectopic kidneys (usually pelvic) are more vulnerable to infection study.70and are associated with decreased fetal salvage, probably because ofassociated malformations of the urogenital tract. If infection occurs in Effect of Pregnancy on Renal Disease/a solitary kidney during pregnancy and does not quickly respond to Remote Prognosisantibiotics, termination may have to be considered for preservation of Pregnancy does not adversely affect the natural history of the renalrenal function. lesion if kidney dysfunction is minimal and hypertension is absent at conception, with the exception of certain collagen disorders. An impor- tant factor in remote prognosis is the sclerotic effect that hyperﬁltra-Nephrotic Syndrome tion might already have had in the residual (intact) glomeruli ofThe most common cause of nephrotic syndrome in late pregnancy is kidneys of patients with renal insufﬁciency. Further progressive losspreeclampsia. Other causes include proliferative or membranoprolif- of renal function can ensue in pregnancy, but this is not the caseerative glomerulonephritis, lipid nephrosis, lupus nephritis, hereditary in animals when pregnancy is superimposed on experimentalnephritis, diabetic nephropathy, renal vein thrombosis, and amyloido- glomerulonephritis.115sis. Some of these conditions do not respond to steroids and may even The superimposition of pregnancy hyperﬁltration on the com-be aggravated by them; this emphasizes the importance of a tissue pensatory changes already present in a single kidney may lessen thediagnosis before steroid therapy is begun.113 lifespan of the kidney. The crux of this hypothesis is the implication If renal function is adequate and hypertension is absent, there that increases in glomerular pressure or glomerular plasma ﬂowshould be few complications during pregnancy and good fetal outcome. cause sclerosis within the glomerulus and that in pregnancy furtherHowever, physiologic changes occurring during gestation may mimic physiologic hyperﬁltration augments the damage. In health, itaggravation or exacerbation of disease. Increments in renal hemody- seems unlikely that there are long-term renal sequelae.115 More humannamics and increases in renal vein pressure may enhance protein and animal research is needed because patients with renal diseaseexcretion during pregnancy. Serum albumin levels usually decrease can have unpredicted, accelerated, and irreversible renal declineby 0.5 to 1.0 g/dL during normal pregnancy, and further decreases in pregnancy or immediately afterward, and the mechanisms aredue to nephrotic syndrome may enhance the tendency toward ﬂuid unknown.retention. Care must be taken with the use of diuretics to treat edemabecause reduced intravascular volume may reduce uteroplacentalperfusion or aggravate the increased tendency to thromboticepisodes. Hemodialysis Patients and PregnancyHuman Immunodeﬁciency Virus— It has been several decades since the ﬁrst description of conception andAssociated Nephropathy successful delivery in a patient on chronic hemodialysis, and additionalDuring the past 25 years, there have been increasing numbers of case reports and registry data have been published since then.116-119 Anyreports about a nephrotic syndrome and severe renal impairment in optimism must be tempered by the thought that clinicians are reluc-patients infected with the human immunodeﬁciency virus (HIV).114 tant to publish failures or disasters, and consequently, the true inci-The condition is characterized by severe proteinuria, by bright dence of unsuccessful pregnancies in women on dialysis cannot beechogenic kidneys, and often by rapid progression to end-stage determined. The high surgical abortion rate in these patients, althoughrenal disease. The distinctive features seen on histologic evaluation decreased from 40% in 1989 to 18% today, still indicates that thoseof renal biopsy are a collapsing glomerulosclerosis, visceral epithelial who become pregnant do so accidentally, probably because they arecell hypertrophy, and cystic tubular degenerative changes.114 The unaware that pregnancy is a possibility.
916 CHAPTER 44 Renal Disorders TABLE 44-4 CHRONIC RENAL DISEASE AND PREGNANCY Renal Disease Effects Chronic glomerulonephritis and Incidence of high blood pressure late in gestation is increased, but there usually is no adverse effect if focal glomerular sclerosis (FGS) renal function is preserved and hypertension is absent before gestation. Some disagree, believing coagulation changes in pregnancy exacerbate disease, especially immunoglobulin A (IgA) nephropathy, membranoproliferative glomerulonephritis, and FGS. IgA nephropathy Some cite risks of sudden escalating or uncontrolled hypertension and renal deterioration. Most ﬁnd good outcomes when renal function is preserved. Chronic pyelonephritis (infectious Bacteriuria occurs in pregnancy and may lead to exacerbation. tubulointerstitial disease) Reﬂux nephropathy In the past, some emphasized risks of sudden escalating hypertension and worsening of renal function. Consensus now is that results are satisfactory when preconception function is only mildly affected and hypertension is absent. Vigilant screening for urinary tract infections is necessary. Urolithiasis Ureteral dilatation and stasis do not seem to affect natural history, but infections can become more frequent. Stents have been successfully placed, and sonographically controlled ureterostomy has been performed during gestation. Polycystic kidney disease Functional impairment and hypertension are usually minimal in childbearing years. Diabetic nephropathy There are no adverse effects of the renal lesion. Frequencies of infections, edema, and preeclampsia increase. Systemic lupus erythematosus Prognosis is most favorable if disease is in remission 6 or more months before conception. Some authorities increase steroid dosage in the immediate postpartum period. Periarteritis nodosa Fetal prognosis is poor. Disease is associated with maternal death. Therapeutic abortion should be considered. Scleroderma For onset during pregnancy, there can be rapid overall deterioration. Reactivation of quiescent scleroderma can occur during pregnancy and after delivery. Previous urologic surgery Depending on the original reason for surgery, there may be other malformations of the urogenital tract. Urinary tract infection is common during pregnancy, and renal function may undergo reversible decrease. No signiﬁcant obstructive problem, but cesarean section may be necessary in case of abnormal presentation or to avoid disruption of the continence mechanism if artiﬁcial sphincters or neourethras are present. After nephrectomy, solitary and Pregnancy is well tolerated. Condition may be associated with other malformations of the urogenital pelvic kidney tract. Dystocia rarely occurs with a pelvic kidney.Counseling and Early TABLE 44-5 ESTIMATES FOR PREGNANCYPregnancy Assessment COMPLICATIONS AND OUTCOMESDespite irregular or absent menstruation and impaired infertility, IN DIALYSIS PATIENTSwomen on dialysis should use contraception if they wish to avoid Complication or Outcome Incidence or Timing*pregnancy.120 The introduction of recombinant human erythro-poietin (rHuEPO) for the treatment of women with renal failure Polyhydramnios 40%appears to be associated in some cases with return of normal Intrauterine growth restriction 90% Preterm delivery 85%menses (and ovulation), probably because of improved overall Average gestational age at delivery 33 wkhealth.121 Hypertension/preeclampsia 70% There are substantial arguments against pregnancy, not least of (Severe) 15%which are the risks to the patient (e.g., severe hypertension, cardiac Surviving infantfailure, maternal death) and the fact that even when therapeutic ter- Conceived on dialysis 50%mination of pregnancy is excluded, there is at the very best only a 40% Conceived before dialysis 75%to 50% likelihood of a successful outcome.122 If only data since the late1990s are considered, fetal survival seems to be improving, although *Estimates are based on literature from 1992 to 2007, with all pregnancies attaining at least 24 weeks’ gestation.maternal risk remains formidable (Table 44-5).116 Data from references 2, 88, 121, 123-127, 163, 164. Early diagnosis of pregnancy is difﬁcult. A missed period isusually ignored. The mistake the clinician may make is failure toconsider the possibility of pregnancy, and many of these patients have Antenatal Strategy andnot been given contraception counseling. Resistance to rHuEPO orprogression of anemia (i.e., hematocrit decrease by 8% of pre- Decision Makingpregnancy levels) can be a useful clue to early diagnosis of pregnancy. For a successful outcome, scrupulous attention must be paid to bloodUrine pregnancy tests are unreliable, and deﬁnitive diagnosis and pressure control, ﬂuid balance, increased hours of dialysis, and provi-estimation of gestational age are best accomplished by sonar sion of good nutrition. Excellent publications should be consulted fortechnology. more details.116,123-127