Renal parenchymal disease consists of two general groups of disorders, glomerulopathies and tubulointerstitial disease . Glomerulopathies are further subdivided into disorders that involve inflammatory or necrotizing lesions—the nephritic syndromes —and disorders that involve abnormal permeability to protein and other macromolecules—the nephrotic syndromes . More than 20 specific glomerulopathies exist. The nomenclature for these glomerulopathies is complex, and specific diseases are not discussed in detail here.

Tubulointerstitial diseases are characterized by abnormal tubular function. They result in abnormal urine composition and concentration but are not characterized by decreased GFR until late in the disease course. The disorders in this category include interstitial nephritis, acute tubular necrosis, multiple myeloma of the kidney, and functional tubular defects such as renal tubular acidosis.

Patients with renal parenchymal disorders may remain asymptomatic for years, and they may exhibit only proteinuria and microscopic hematuria, with little if any evidence of reduced renal function. Spontaneous recovery or improvement with treatment occurs with many glomerulopathies. However, other patients exhibit progressive nephropathy, hypertension, and renal insufficiency. The incidence of chronic kidney disease (CKD) in pregnancy is as high as 3%, a stark increase from prior estimates as fertility rates in the patient population have increased. In two-thirds of these patients, the disorder results from glomerulopathy, and in one-third, from tubulointerstitial disease.

Ideally, the severity of renal disease should be assessed by preconception GFR as classified by the National Kidney Foundation/Kidney Disease: Improving Global Outcomes organization’s definition and guidelines on improving outcome, as standard GFR equations are inaccurate in pregnancy. Creatinine clearance and the level of proteinuria should be determined. Urinalysis yields information about the presence of renal casts and bacteriuria. The determination of serum creatinine and BUN concentrations defines the extent of renal insufficiency. A serum creatinine concentration > 0.87 mg/dL (77 µmol/L), which may be normal in the nonpregnant woman, may represent significant renal insufficiency during pregnancy. Alternatively, the obstetric provider may first detect renal dysfunction through routine prenatal screening tests as patients may otherwise be asymptomatic, because symptoms rarely develop until GFR decreases by 25%. If proteinuria, hematuria, or azotemia is detected, further evaluation should be performed.

Both preeclampsia and renal disease may manifest as hypertension, proteinuria, and edema. Differentiating the two entities is complex, especially after 20 weeks’ gestation. Serial blood pressure measurements define the severity of hypertension and the efficacy of current antihypertensive therapy. In cases where CKD needs to be differentiated from preeclampsia, biomarkers such as placental growth factor (PIGF) and FMS-like tyrosine kinase-1 (sFlt-1) can be obtained; in preeclampsia the sFlt-1:PIGF ratio is elevated and in CKD it is not.

Although renal tissue biopsy is often used to establish a diagnosis in nonpregnant patients, it is rarely required to manage kidney disease in pregnancy, and may be associated with procedural complications. A systematic review by Piccoli et al. compared complication rates from 243 renal biopsies performed during pregnancy with 1236 performed in the postpartum period. Significant complications occurred in 7% of biopsies performed before delivery compared with 1% in the postpartum period. Most complications were minor and included groin pain as well as hematuria. The authors did report, however, that more serious complications (e.g., bleeding and loin pain) occurred the further along in pregnancy the biopsy was performed and seemed to peak around 25 weeks’ gestation. It should be noted that in 23 of the studies in the metaanalysis, kidney biopsies were performed to characterize morphologies in preeclampsia, a practice that is no longer recommended and may have influenced the subject pool substantially. Given the increased risk associated with biopsy during pregnancy, it should only be performed in patients with a high likelihood of severe glomerular disease and when a definitive diagnosis is critical to guide treatment.

In addition to clinical information, urinalysis and inflammatory and biomarker data have also supplanted the need for renal biopsy in some cases. For example, when a diagnosis is obtained through antineutrophil cytoplasmic antibodies or through double-stranded DNA antibodies, empiric treatment may begin with corticosteroids, azathioprine, or calcineurin inhibitors in lieu of a kidney biopsy. Novel biomarkers at the genetic and epigenetic levels have been investigated, many of which are found in the urine and plasma/serum. The list is too extensive for the purposes of this chapter; however, one of the most robust biomarkers in kidney disease, the M-type phospholipase A2 receptor antibody, is commonly used to diagnose membranous nephropathy. It has recently gained approval from the US Food and Drug Administration for the diagnosis and monitoring of membranous nephropathy.

The extent to which pregnancy affects preexisting renal disease depends on the level of renal insufficiency before pregnancy. Among women with mild antenatal renal insufficiency with well-controlled blood pressure and proteinuria < 1 g/day, pregnancy does not appear to substantially alter the natural course of renal disease. Jungers et al. evaluated the effect of pregnancy on renal function among 360 women with primary glomerulonephritis. During the study period, 171 (48%) women became pregnant. All study subjects had normal renal function at the time of entry into the study and all patients who became pregnant had normal renal function at conception. In the case-control analysis of the study, pregnancy was not identified as a risk factor for progression to end-stage renal failure. Limardo et al. evaluated 223 women with biopsy-documented IgA nephropathy who had a serum creatinine level > 1.2 mg/dL (106 µmol/L), 136 of whom became pregnant. Women were observed for a minimum of 5 years (median, 10 years), and pregnancy did not seem to affect the long-term outcome of kidney disease or the onset of proteinuria or hypertension.

In contrast, Jones and Hayslett analyzed the outcome of 82 pregnancies in 67 women with preexisting moderate or severe renal insufficiency (i.e., serum creatinine level > 1.4 mg/dL [124 µmol/L] before pregnancy or at the first antepartum visit). The mean ± standard deviation serum creatinine concentration increased from 1.9 ± 0.8 mg/dL (168 ± 71 µmol/L) in early pregnancy to 2.5 ± 1.3 mg/dL (221 ± 115 µmol/L) in the third trimester. The prevalence of hypertension rose from 28% at baseline to 48% during late pregnancy. Pregnancy-related deterioration of maternal renal function occurred in 43% of cases. Purdy et al. also found that more than 40% of women with moderate to severe kidney disease had deterioration in renal function caused by pregnancy. Women with a serum creatinine concentration > 2.0 mg/dL (177 µmol/L) who became pregnant had a one-in-three chance of developing dialysis-dependent end-stage renal disease during or shortly after pregnancy. In summary, the preponderance of evidence demonstrates that while pregnancy exacerbates renal disease, it has a greater effect on those who present with moderate to severe levels of renal dysfunction before pregnancy or in those in whom blood pressure control is difficult or there is significant proteinuria.

The pathophysiology by which pregnancy exacerbates renal disease is unknown. One hypothesis is that increased glomerular perfusion paradoxically causes further injury to the kidneys in patients with preexisting impairment of function. However, this hypothesis is unsupported by published data, which do not demonstrate evidence of hyperfiltration (i.e., an initial decline in serum creatinine concentration) during early pregnancy in patients with renal disease. An alternative hypothesis is that preexisting renal disease may induce a cascade of platelet aggregation, microvascular fibrin thrombus formation, and endothelial dysfunction that leads to microvascular injury in the already tenuous kidneys. In addition to general changes to renal mechanics discussed earlier, exacerbation or improvement of the initial disease process during pregnancy could also alter the long-term course of renal dysfunction.

Pregnant women with CKD are at an increased risk for maternal and fetal complications. Al Khalaf et al. systematically reviewed all published studies of women with CKD that included a control group for comparison. They identified 31 studies between 1988 and 2021. Of these, 17 studies compared outcomes in women with and without CKD; 10 studies compared early with late stages of CKD, and 4 studies had both comparisons. Several adverse outcomes were associated with CKD, including preeclampsia, cesarean delivery, preterm birth, low birthweight, and neonatal intensive care unit (NICU) admission ( Fig. 50.1 ). A prespecified subgroup analysis comparing early- versus late-stage CKD demonstrated similar findings, with late-stage CKD demonstrating an association with preeclampsia and very preterm birth. Other outcomes were associated as well; however, the model was not robust enough to provide risk-adjusted estimates for factors such as maternal age, smoking, body mass index, race, income, educational level, parity, and other comorbidities. Additional analyses demonstrated risk differences by the type of kidney disease, with elevated risk profiles in cases of diabetic CKD and glomerulonephritis compared with polycystic kidney disease.

Forest plots of studies of the association between CKD and fetal or neonatal outcomes. The colored rectangles represent the OR for each study, and the lateral black lines represent the 95% CI for each study. The diamond represents the overall OR, and the lateral tips of the diamond represent the 95% CI for the combined estimates. Panel A shows adjusted OR for preeclampsia, Panel B shows adjusted OR for cesarean delivery, Panel C shows adjusted OR for preterm birth, and Panel D shows adjusted OR for small for gestational age. CI , Confidence interval; CKD , chronic kidney disease; OR , odds ratio; IV , inverse variance.

Modified from Al Khalaf S, Bodunde E, Maher GM, et al. Chronic kidney disease and adverse pregnancy outcomes: a systematic review and meta-analysis. Am J Obstet Gynecol . 2022;226:656–670.e32.

During pregnancy, the nephrologist and the obstetric provider should monitor maternal renal function, blood pressure, and fetal development at frequent intervals. Monthly determination of serum creatinine concentration, creatinine clearance, and proteinuria allows the recognition of renal deterioration and establishes a baseline for the patient, which may be useful in diagnosing superimposed preeclampsia if it occurs. An antepartum consultation with the anesthesia provider should also be considered to address issues such as peripartum medication and fluid management, and to perform an overall risk assessment to discuss and develop potential plans for anesthetic technique and monitoring. Blood pressure control is important to mitigate further renal damage, and the American College of Obstetricians and Gynecologists recommends treatment for systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg.

Some glomerulopathies respond to corticosteroids, and corticosteroid therapy should be continued during pregnancy. Rapid deterioration of renal function that occurs before 28 weeks’ gestation may require renal biopsy to exclude rapidly progressive glomerulopathies that require treatment (see earlier discussion). Up to 68% of pregnant women with CKD will have anemia. These women may be treated with iron supplementation (oral or IV) or erythropoietin-stimulating agents (ESAs) . Because of its large molecular weight, recombinant erythropoietin does not appear to cross the placenta or have an adverse impact on the fetus. There is no standardized regimen; however, it should be noted that doses may need to be changed during varying stages of the pregnancy to maintain the hemoglobin target within the range of 11 to 12 g/dL, as recommended by the National Kidney Foundation for pregnant patients.

There may be a benefit to administering both iron and ESA. In a retrospective study at a single Australian institution over a 15-year period, Morton et al. analyzed the impact of both iron supplementation (oral and IV) and ESA use in pregnant patients with CKD. They identified 63 pregnancies in 52 women with CKD and found that oral iron supplementation resulted in a hemoglobin higher than 10 g/dL in 9/30 (30%) of pregnancies after 12 weeks of therapy. IV iron resulted in an average increase in hemoglobin from 8.6 to 11.6 g/dL over 5 weeks. In patients receiving ESA alone, hemoglobin increased from 8.1 to 10.5 g/dL on average; when IV iron and ESA were both used, 16/18 (89%) of women had resolution of their anemia. Protein restriction places the fetus at risk for growth restriction and is not advised. Deterioration of maternal renal function, the onset of preeclampsia, or evidence of fetal compromise may necessitate urgent delivery.

When renal disease has progressed to end-stage renal failure (i.e., GFR < 5 mL/min), fertility is suppressed. Less than 10% of premenopausal patients undergoing dialysis have regular menses. Luteinizing hormone and follicle-stimulating hormone concentrations assume an anovulatory pattern, which causes 70% of affected women to be either oligo- or amenorrheic. Half of all female patients undergoing dialysis exhibit hyperprolactinemia because of reduced clearance and hypothalamic disturbances. Rates of conception for women on dialysis are about 1/100th of the general population.

When pregnancy does occur, there are several important management considerations necessary to maximize the probability of a successful outcome. Hemodialysis necessitates vascular access and the need for anticoagulation of the extracorporeal circuit and may be complicated by cardiovascular instability, and large fluid and electrolyte shifts. Hypotension may compromise uteroplacental perfusion and cause fetal compromise. Even when hypotension and major fluid shifts are avoided, Doppler ultrasonographic examination of uterine and umbilical artery flow during hemodialysis suggests the occurrence of a redistribution of arterial flow away from the uteroplacental vascular bed. Fetal heart rate monitoring should be considered during dialysis. Rapid removal of maternal solutes and reduced oncotic pressure with attendant free-water diffusion into the amniotic cavity may lead to polyhydramnios. Live birth rates correlate positively with dialysis time, leading to changes in dialysis scheduling to shorter but more frequent runs. Long-term ambulatory peritoneal dialysis allows less hemodynamic trespass, and the freedom to undergo dialysis at home. Complications of this modality include peritonitis and catheter difficulties. With the increase in fetal survival with newer enhanced hemodialysis regimens and retrospective evidence suggesting potentially worse outcomes with peritoneal dialysis, current guidelines recommend changing from peritoneal dialysis to hemodialysis prior to conception or in the first trimester.

Fetal outcomes for women on newer dialysis regimens have improved with live birth rates > 80%. In a metaanalysis and systematic review of almost 550 pregnancies in patients undergoing both hemodialysis and peritoneal dialysis, Piccoli et al. reported a low maternal perinatal mortality rate (0.4%), with a malformation rate of approximately 2%, which aligns with the risk in the general population. Fetal complications are most often seen in the form of respiratory distress, sepsis, and retinopathy and are likely a result of the higher incidence of preterm birth rather than related directly to dialysis. BUN levels should be kept less than 50 mg/dL (urea < 17.9 mmol/L) before dialysis and less than 30 mg/dL (urea < 10.7 mmol/L) after dialysis. At birth, azotemia in the newborn is similar to that in the mother, but this quickly corrects because the newborn has normal kidney function. The long-term effects of intrauterine azotemia on newborn cognitive development are unknown; however, it appears that if the neonate survives the complications from preterm delivery, further development may be normal.

Patients undergoing hemodialysis have a high rate of viral hepatitis ; a greater frequency of active tuberculosis ; and a higher rate of infection with vancomycin-resistant enterococci , human immunodeficiency virus (HIV) , and methicillin-resistant Staphylococcus aureus . The risk for hepatitis C virus (HCV) infection is particularly of concern, with reported rates as high as 36%. However, with improvement in aseptic technique and more attention to handwashing, the decline in the reuse of dialysis equipment, and the use of dedicated isolated dialysis machines for HCV-seropositive patients, the rates of infection and seroconversion can be markedly reduced.

Anesthetic management is influenced by the extent of renal dysfunction and hypertension. The parturient with stable renal disease, mild to moderate renal insufficiency, well-controlled hypertension, and euvolemia requires minimal special consideration. In contrast, the dialysis patient with end-stage renal failure presents many anesthetic challenges because renal disease may affect almost every organ system ( Box 50.1 ). Poorly controlled hypertension may lead to left ventricular hypertrophy and dysfunction. Symptoms of cardiovascular compromise should prompt echocardiography to evaluate ventricular function. An intraarterial catheter also may aid the management of the parturient with poorly controlled hypertension, or when the continuous infusion of antihypertensive agents is required. Uremic pericarditis, cardiomyopathy, and accelerated atherosclerosis are rarely seen until advanced uremia has been present for several years.

Uremic toxins may cause functional platelet defects; these abnormalities are reversed by dialysis. Thrombocytopenia may also occur because of increased peripheral destruction of platelets. Generalized coagulopathy may result from the anticoagulation used during the dialysis process. A full coagulation profile and careful bleeding history should be performed in patients on hemodialysis, especially before the initiation of neuraxial anesthesia. Hemodialysis fistulas should be padded carefully to prevent thrombosis. Blood pressure cuffs should not be placed on these extremities.

Acute kidney injury (AKI) is a serious potential complication that can develop in pregnancy. The inciting disorders previously varied throughout the world; however, hypertensive disorders in pregnancy are now the leading cause of pregnancy-related acute kidney injury (PR-AKI) worldwide, followed by hemorrhage and sepsis. Rapid deterioration of renal function leads to an accumulation of fluid and nitrogenous waste products with impaired electrolyte regulation. Definitions for renal dysfunction in the general population vary and have changed over time. What was previously called acute renal failure (ARF) is now included among a greater spectrum of disorders, including varying levels of kidney dysfunction, and is now termed AKI. Guidelines and recommendations (including definitions) have been maintained by the Kidney Disease: Improving Global Outcomes consortium of the International Society of Nephrologists ( Table 50.1 ). The most recent version of the recommendations are from 2012 and they are in the process of being updated. These definitions and recommendations are based on the RIFLE (risk, injury, failure, loss, and end-stage renal failure) and Acute Kidney Injury Network criteria, which have been applied to the pregnant population because no similar guidance exists for pregnant patients.

During the past five decades, the incidence of PR-AKI has decreased worldwide from 1:3000 to 1:15,000. This progress has resulted from improved obstetric care and fewer septic abortions. Although the overall incidence of PR-AKI is declining worldwide, it has been increasing in incidence in the United States and Canada. Shah et al. reported that the incidence of AKI-related admission during pregnancy increased from 0.04% in 2006 to 0.12% in 2015. Factors associated with the increased hospitalization included older age, Black and Native American race, and diabetes mellitus. They also found that those hospitalized had a higher rate of inpatient mortality and cardiovascular events.

AKI is defined by one of the following criteria: (1) increase in serum creatinine by greater than or equal to 0.3 mg/dL (26.5 µmol/L) within 48 hours, (2) increase in serum creatinine to greater than or equal to 1.5 times baseline within the last 7 days, or (3) urine volume ≤ 0.5 mL/kg/h for 6 hours. Once the diagnosis is made, staging the level of severity of AKI is recommended. This is an important component of management because the risk for death and renal replacement therapy increases significantly with each stage (see Table 50.1 ). AKI is subdivided according to underlying cause (i.e., prerenal, intrarenal, and postrenal) ( Box 50.2 ). One study examined the kidney injury molecule-1 (KIM-1) as a biomarker for the diagnosis and prediction of AKI complications in pregnancy ; the cohort of patients with elevated KIM-1 and endothelin-1 suffered from greater degrees of kidney injury.

Although maternal prognosis has improved significantly in developed countries, mortality ranges between 20% and 30% in low-income countries, likely because of the lack of availability of renal replacement therapy. Although mortality in high-income countries is very low, up to one-third of mothers do not have complete recovery and suffer long-term sequelae from their AKI episode. There is also evidence that women with recovered PR-AKI have increased rates of preeclampsia and other complications in future pregnancies even in cases where prepregnancy serum creatinine is similar. The prognosis for the fetus is worse as well, with significant increases in stillbirth, perinatal death, NICU stay, lower birth weight, lower gestational age at delivery, and higher odds of cesarean delivery.

Management is directed toward rapid recognition of the underlying abnormality. Reversible disorders such as hypovolemia, concealed uterine hemorrhage, urinary tract infection, ureteral obstruction, and drug-induced AKI must be excluded. Urine osmolality (>500 mOsm/kg) is a useful laboratory test to identify reversible prerenal causes. Intravascular volume should be optimized. Electrolyte and acid-base status should be monitored carefully. Hypertension and preeclampsia must be managed aggressively. Many obstetric causes of AKI also may cause disseminated intravascular coagulation; therefore, coagulation abnormalities should be excluded in pregnant women with AKI.

Because urea and other metabolic products cross the placenta, hemodialysis or peritoneal dialysis should be directed toward maintaining the postdialysis BUN concentration ≤ 30 mg/dL (urea 10.7 mmol/L). Fluid shifts during hemodialysis should be minimized by short but frequent periods of dialysis. If the fetus is mature, delivery should be accomplished when the maternal condition is stabilized. The pediatrician must be alerted to the presence of high fetal BUN levels, which may lead to an osmotic diuresis and neonatal dehydration. Ertürk et al. reported the first known delivery of a healthy infant during a hemodialysis session. All nephrotoxic drugs should be discontinued and avoided if possible. Renal dosing of medications (e.g., muscle relaxants, antibiotics, magnesium) should be considered in these patients. A flow diagram to aid in the diagnosis and management of suspected AKI is shown in Fig. 50.2

Approach to acute kidney injury in pregnancy.

AFLP , Acute fatty liver of pregnancy; aHUS , atypical hemolytic-uremic syndrome; AKI , acute kidney injury; ATN , acute tubular necrosis; CKD , chronic kidney disease; KUB , kidney, ureter, and bladder; TTP , thrombotic thrombocytopenic purpura; US , ultrasound.

Modified from Hall DR, Conti-Ramsden F. Acute kidney injury in pregnancy including renal disease diagnosed in pregnancy. Best Pract Res Clin Obstet Gynaecol . 2019;57:47–59.

A multidisciplinary approach involving anesthesia providers, obstetric providers, and nephrologists should be employed to optimize the maternal condition before delivery in a woman with AKI. The level of azotemia, electrolyte balance, and hematologic status should be assessed. If the BUN level is greater than 80 mg/dL (urea > 28.6 mmol/L) or if the serum potassium concentration is greater than 5.5 mEq/L, dialysis should be performed before vaginal or cesarean delivery. Neuraxial anesthesia may be administered in the absence of coagulopathy, thrombocytopenia, and severe hypovolemia. Volume status may be difficult to assess, and transthoracic echocardiography may be useful.

Both spinal and epidural analgesia/anesthesia are safe and preferred to general anesthesia. As the sympathetic blockade dissipates, the mother should be monitored for evidence of volume overload and pulmonary edema. General anesthesia may be required for urgent cesarean delivery or in patients with coagulopathy or hemorrhage.