INTRODUCTION/DEFINITION — In nonpregnant individuals without kidney disease, normal urinary protein excretion is less than 150 mg daily. In pregnancy, urinary protein excretion normally increases substantially; hence, urinary protein excretion is considered abnormal in pregnant people when it exceeds 300 mg daily [1]. In many pregnant people, proteinuria appears to increase further at the time of labor and delivery [2]. Although pregnant people with uncomplicated twin pregnancies have greater increases in urinary protein excretion than those with singleton pregnancies, abnormal proteinuria is similarly defined for singleton and multiple gestations [3,4].
Proteinuria is one of the cardinal features of preeclampsia (table 1), a common and potentially severe complication of pregnancy. Proteinuria in pregnancy can also indicate primary kidney disease or kidney disease secondary to systemic disorders, such as diabetes mellitus or primary hypertension. Adding to the complexity, 20 to 25 percent of pregnant people with chronic hypertension, diabetes mellitus, or chronic kidney disease develop superimposed preeclampsia [5,6].
It is important for clinicians caring for pregnant people to understand how to identify proteinuria, and how to determine whether preeclampsia or kidney disease (or both) is the cause. This topic will discuss the approach to the evaluation of pregnant people with proteinuria and management of nephrotic syndrome in pregnancy. The evaluation of proteinuria in nonpregnant individuals and measurement of protein excretion are discussed in detail separately. (See "Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults".)
PROTEINURIA IN NORMAL PREGNANCY — Glomerular filtration rate (GFR) and renal blood flow rise markedly during pregnancy, resulting in a physiologic fall in the serum creatinine concentration. Urinary protein excretion increases substantially due to a combination of increased GFR and increased permeability of the glomerular basement membrane [7]. Additionally, tubular reabsorption of filtered protein is reduced in pregnancy, along with other nonelectrolytes, such as amino acids, glucose, and beta-microglobulin. (See "Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults".)
Additional information on pregnancy-related changes in kidney function and the urinary tract can be found separately. (See "Maternal adaptations to pregnancy: Renal and urinary tract physiology".)
ASSESSMENT OF PROTEINURIA — Initial assessment of a pregnant person with proteinuria should include determination of the time of onset and quantity of proteinuria. If the onset is after 20 weeks gestation, preeclampsia is likely (table 1) (see "Preeclampsia: Clinical features and diagnosis"). If the onset is before 20 weeks gestation, primary or secondary kidney disease is likely. In pregnant people with chronic kidney disease, proteinuria >1 g/day is associated with increased risk of adverse pregnancy and neonatal outcomes (odds ratio 3.69, 95% CI 1.63-8.36), including preterm delivery, small for gestational age infants, and need for neonatal intensive care [8]. In pregnant people with chronic hypertension, even mild proteinuria (50 to 300 mg/day) is associated with adverse pregnancy outcomes [9] (see "Pregnancy in women with nondialysis chronic kidney disease", section on 'Pregnancy outcomes'). Urinary protein excretion >3 g/day can be seen in preeclampsia but can also signify nephrotic syndrome due to other primary or secondary glomerular disease. (See 'Management of nephrotic syndrome in pregnancy' below.)
Semiquantitative — The urinary dipstick may be used to screen for proteinuria.
Standard urine dipstick testing should be performed on a fresh, clean voided, midstream urine specimen, obtained before pelvic examination to minimize the chance of contamination from vaginal secretions. The urinary dipstick for protein is a semi-quantitative colorimetric test that primarily detects albumin. Results range from negative to 4+, corresponding to the following estimates of protein excretion:
●Negative
●Trace – between 15 and 30 mg/dL
●1+ – between 30 and 100 mg/dL
●2+ – between 100 and 300 mg/dL
●3+ – between 300 and 1000 mg/dL
●4+ – >1000 mg/dL
A positive reaction (1+) for protein develops at the threshold concentration of 30 mg/dL, which crudely corresponds to a 24-hour urinary protein excretion of 300 mg/day, depending on urine volume.
Although inexpensive and commonly used, the urinary dipstick has a high false positive and false negative rate when used to screen for abnormal proteinuria in pregnancy, especially at the 1+ level [10,11]. This is due primarily to variability in urine concentration (osmolality), which can substantially affect random urine protein concentration (ie, the dipstick result).
False positive tests may occur in the presence of gross (macroscopic) blood in the urine, semen, very alkaline urine (pH >7), quaternary ammonium compounds, detergents and disinfectants, drugs, radio-contrast agents, and concentrated urine (specific gravity >1.030). Positive tests for protein due to blood in the urine seldom exceed 1+ by dipstick.
False negatives may occur with dilute urine (specific gravity <1.010), high salt concentration, highly acidic urine, or nonalbumin proteinuria. False negative urine dipstick proteinuria testing is most common in the third trimester of pregnancy, when the clinical findings of preeclampsia are most likely to manifest [12].
Because the urinary dipstick has low diagnostic accuracy for the detection of proteinuria in pregnancy, it is not recommended as a routine screening test for preeclampsia by the United States Preventive Services Task Force [13]. However, it is commonly performed and the detection of proteinuria at the level of 2+ or greater by urine dipstick may be used for the diagnosis of preeclampsia if quantitative methods are unavailable [14]. (See "Preeclampsia: Clinical features and diagnosis", section on 'Screening and risk reduction'.)
Quantitative — Urinary protein can be measured as either albumin or total protein. Nonpregnant people normally excrete less than 30 mg of albumin [15] and less than 150 mg of total protein daily. In normal pregnancy, total protein excretion increases to 150 to 250 mg daily [1], and may be higher than 300 mg in twin pregnancies [3,4].
There are three methods to quantify proteinuria: 24-hour urine collection, spot urine protein-to-creatinine ratio, and spot urine albumin-to-creatinine ratio.
24-hour urine collection — The traditional method to quantify proteinuria requires a 24-hour urine collection to directly measure the daily total protein or albumin excretion. If urine and serum creatinine are also measured, the 24-hour urine collection creatinine clearance can provide an estimate of the glomerular filtration rate.
The 24-hour collection is begun at the usual time the patient awakens. At that time, the first void is discarded and the exact time noted. Subsequently, all urine voids are collected with the last void timed to finish the collection at exactly the same time the next morning. The time of the final urine specimen should vary by no more than 5 or 10 minutes from the time of starting the collection the previous morning.
An inexpensive basin urinal that fits into the toilet bowl facilitates collection for pouring into a bottle. The bottle(s) may be kept at normal room temperature for a day or two, but should be kept cool or refrigerated for longer periods of time. No preservatives are needed. (See "Patient education: Collection of a 24-hour urine specimen (Beyond the Basics)".)
Although generally considered the "gold standard" for diagnosis of proteinuria in both preeclampsia and kidney disease, the 24-hour urine protein excretion in pregnant people is frequently inaccurate due to under-collection or over-collection [16]. Thus, when interpreting the results of a 24-hour urine collection, it is critical to assess the adequacy of collection by quantifying the 24-hour urine creatinine excretion, which depends on muscle mass. In a complete collection, the 24-hour urine creatinine excretion will be between 15 and 20 mg/kg body weight, calculated using prepregnancy weight. Values substantially above or below this estimate suggest over- and under-collection, respectively, and should call into question the accuracy of the 24-hour urine protein result.
In addition to the high rate of inaccurate/incomplete collection, the 24-hour urine sample is cumbersome for ambulatory patients, and the laboratory result is not available for at least 24 hours while the collection is being completed and analyzed [16].
Urine protein-to-creatinine ratio — The spot urine protein-to-creatinine ratio (UPCR) has become the preferred method for the quantification of proteinuria in the nonpregnant population because of its high accuracy, reproducibility, and convenience when compared with timed urine collection [17]. (See "Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults".)
Most international organizations endorse the use of the spot UPCR ≥0.26 to 0.3 mg protein/mg creatinine for the diagnosis of preeclampsia [14,18,19]. Some laboratories and international guidelines use UPCR in units of mg protein per mmol creatinine (mg/mmol). To convert mg/mmol to mg/mg, divide by 113.6. An UpToDate calculator is available for calculating the UPCR using spot urine protein and spot urine creatinine values (calculator 1).
The majority of studies evaluating the UPCR in pregnant people were performed in patients with suspected preeclampsia. In these studies, the UPCR was highly correlated with the 24-hour urine protein measurement [20-34], as it is in nonpregnant adults. Use of the UPCR has also been validated for baseline proteinuria quantification in early pregnancy [35].
Two systematic reviews have evaluated this literature and came to similar conclusions [36]:
●In a 2012 meta-analysis including 2978 pregnant participants from 20 studies, spot urine ratio had a pooled sensitivity of 83.6 percent (95% CI 77.5-89.7) and specificity of 76.3 percent (95% CI 72.6-80) using a cut-off of 0.26 mg protein/mg creatinine to predict proteinuria >300 mg/day by 24-hour urine collection [37]. The authors concluded that a low spot UPCR is a reasonable "rule-out" test for excluding proteinuria >300 mg/day in hypertensive pregnancy.
●Another 2012 meta-analysis, including 2790 pregnant participants from 15 studies, had similar findings. A single diagnostic threshold of approximately 0.30 mg protein/mg creatinine had sensitivity and specificity of 81 and 76 percent, respectively, for the detection of >300 mg/day proteinuria by 24-hour urine collection [38]. A lower cut-off (0.13 mg/mg) had better (89 percent) sensitivity for the exclusion of proteinuria.
Taken together, these data suggest that a UPCR above 0.3 mg protein/mg creatinine predicts abnormal proteinuria (>300 mg/24 hours) in pregnancy. A UPCR less than 0.15 mg protein/mg creatinine can be considered normal (predictive of less than 300 mg/24 hours). Pregnant people with UPCR results between 0.15 and 0.3 mg protein/mg creatinine should have a 24-hour urine collection to accurately determine if abnormal proteinuria is present, especially if a diagnosis of preeclampsia is being considered. In addition, many obstetricians still prefer to measure proteinuria by 24-hour urine collection in all pregnant people with abnormal UPCR (>0.3 mg protein/mg creatinine).
Urine albumin-to-creatinine ratio — The urine albumin-to-creatinine ratio (UACR), like the UPCR, is measured using a random "spot" urine specimen. (See "Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults".)
The UACR can be performed using an automated analyzer, allowing immediate point-of-care testing that could be utilized in an antenatal clinic. Like the UPCR, the UACR (using a threshold between 20 and 60 mg albumin/g creatinine) is strongly predictive of significant proteinuria (>300 mg protein/day by 24-hour urine collection) in a high-risk obstetric antenatal clinic [32,39] and in patients with hypertensive pregnancies [40,41]. In one study, pregnant people with a spot UACR >312 mg albumin/g creatinine measured at 17 to 20 weeks of gestation were at almost eightfold higher risk of subsequently developing preeclampsia (relative risk [RR] 7.8) compared with those with UACR <312 mg albumin/g creatinine [42]. The UACR performs similarly to the UPCR with regard to prediction of adverse pregnancy outcomes [43]. Although more data are needed, the spot UACR has the potential to supplant urinary dipstick as a rapid and accurate screening method for proteinuria in routine obstetric care.
Some laboratories report UACR in units of mg albumin per mmol creatinine (mg/mmol). To convert mg/mmol to mg/g, divide by 0.1136.
8- or 12-hour collection — Although not commonly used, measurement of protein in an 8-hour [44] or 12-hour [45] urine collection is a reasonable alternative to the 24-hour urine collection for quantification of proteinuria. In a systematic review including seven studies, >150 mg of protein in a 12-hour collection was highly predictive of >300 mg protein in a 24-hour collection (pooled sensitivity 92 percent [95% CI 86-96], specificity 99 percent [75-100]) [45].
DIFFERENTIAL DIAGNOSIS OF PROTEINURIA — The differential diagnosis for the combination of hypertension and proteinuria in pregnancy is discussed in detail separately. (See "Hypertensive disorders in pregnancy: Approach to differential diagnosis".)
In patients in whom the proteinuria is the prominent finding, distinguishing between new onset or worsening kidney disease and preeclampsia or superimposed preeclampsia can be challenging.
●Renal disease versus preeclampsia – In the evaluation of a pregnant patient with proteinuria, first determine whether the proteinuria is due to preeclampsia (diagnostic criteria are described in the table (table 1)) or some other kidney disease, whether preexisting or de novo (table 2). (See "Preeclampsia: Clinical features and diagnosis".)
The distinction between renal disease and preeclampsia is important because it affects management. Primary or secondary kidney disease may require diagnostic testing (including kidney biopsy in some cases) and disease-specific therapy. In these patients, the usual aim is term delivery. The definitive treatment for preeclampsia is delivery, which sometimes must be done preterm when there are severe maternal features or fetal complications. In instances where the distinction between renal disease and preeclampsia cannot be resolved, it is prudent to assume preeclampsia as the working diagnosis, as it has the potential for rapid development of serious maternal and fetal complications. (See "Pregnancy in women with nondialysis chronic kidney disease" and "Preeclampsia: Antepartum management and timing of delivery".)
In patients with established kidney disease before conception or in whom proteinuria is documented before the 20th week of gestation, the diagnosis of underlying renal disease can be readily made because preeclampsia rarely occurs before that time. Conversely, new-onset proteinuria after 20 weeks of gestation suggests preeclampsia. Approximately one-third of pregnant people who present with new proteinuria after 20 weeks of gestation eventually progress to preeclampsia [46,47], which may have severe features [48], and 25 percent of pregnant people with preeclampsia have proteinuria as their initial presenting sign [49]. In such cases, adverse pregnancy and neonatal outcomes are more common as compared with patients in whom hypertension was the first presenting sign of preeclampsia [49,50].
The degree of proteinuria is only weakly associated with adverse maternal and neonatal outcomes, and heavy proteinuria is not considered a severe feature in preeclampsia [51-55], although some studies report heavy proteinuria (>3 to 5 g/day) is associated with earlier gestational age at preeclampsia onset, earlier gestational age at delivery, and a higher incidence of fetal growth restriction as compared with milder degrees of proteinuria [56,57]. It is also important to note that proteinuria may be absent in preeclampsia: up to 10 percent of patients with preeclampsia and 20 percent of those with eclampsia have no proteinuria at the time of initial presentation [58,59]. Proteinuria is no longer required for the diagnosis of preeclampsia, according to American College of Obstetricians and Gynecologists guidelines, if severe features of the disease are present (table 1) [14]. (See "Preeclampsia: Clinical features and diagnosis".)
Of course, de novo kidney disease (for example, lupus nephritis) can also occur later in pregnancy. Distinguishing between kidney disease and preeclampsia can be difficult in these cases, especially when information on protein excretion (and hypertension) in early pregnancy is unavailable. For this reason, it is useful to quantify protein excretion in early pregnancy in patients at risk for kidney disease (ie, patients with chronic hypertension, diabetes mellitus, and systemic lupus erythematosus).
The following algorithms and UpToDate topics are useful for evaluating patients suspected of having renal disease (algorithm 1 and algorithm 2). Of note, urinary tract dilation (eg, >3 cm) on kidney ultrasound has been associated with proteinuria in pregnancy [60]. (See "Glomerular disease: Evaluation and differential diagnosis in adults" and "Chronic kidney disease (newly identified): Clinical presentation and diagnostic approach in adults".)
Measurement of soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) may be helpful for the diagnosis of preeclampsia [61,62]. sFlt1 and PlGF are angiogenic factors secreted by the placenta and implicated in the pathogenesis of preeclampsia (see "Preeclampsia: Pathogenesis", section on 'sFlt-1, VEGF, PlGF'). The sFlt1:PlGF maternal serum assay is available in Europe (Roche Diagnostics, Rotkreuz, Switzerland, and Thermo Fisher/Brahms, Hennigsdorf, Germany) [63,64] but is not yet approved for use in the United States. Although more studies are needed to validate its use, this blood test may prove useful and cost-effective in distinguishing preeclampsia from other causes of proteinuria in pregnancy [65,66] and appears to be predictive of preeclampsia with severe features, adverse maternal outcomes, and adverse neonatal outcomes in patients with clinical suspicion of preeclampsia [67-69]. The sFlt1:PlGF ratio may be particularly helpful in distinguishing chronic kidney disease and preeclampsia [70].
In some cases, the distinction between renal disease and preeclampsia can only be made in retrospect, as clinical signs of preeclampsia generally resolve within 12 weeks after delivery [71], while proteinuria due to underlying kidney disease does not. However, resolution of proteinuria after preeclampsia, especially when severe features are present, can sometimes take much longer. In one cohort study of 205 pregnant people with preeclampsia, 14 percent had persistent proteinuria at 12 weeks after delivery, which resolved by two years postpartum in all but 2 percent of participants [72]. In another study of 202 pregnant people with preeclampsia, 33 percent had persistent proteinuria at six months postpartum [73]. Nevertheless, proteinuria (or hypertension) that persists longer than three months after delivery should prompt close follow-up and consideration of further evaluation and appropriate referral so that underlying renal disease or chronic hypertension is detected and treated expeditiously.
●Worsening kidney disease versus superimposed preeclampsia – When preeclampsia develops in pregnant people with preexisting kidney disease and/or hypertension, it often occurs in the late second or early third trimester and may be particularly severe. In such cases, preeclampsia typically manifests as new or worsening hypertension, often with worsening proteinuria. When a substantial (twofold or greater) increase in proteinuria occurs in a pregnant person with preexisting proteinuria, it is usually in the context of a clinical diagnosis of preeclampsia [74]. Other clues to the diagnosis of superimposed preeclampsia can be provided by the hematologic, neurologic, and hepatic manifestations of the disorder (table 3), if present, and/or evidence of fetal compromise (including intrauterine growth restriction).
Alternatively, worsening hypertension and proteinuria in a pregnant patient with kidney disease may represent an exacerbation of the underlying disease. Most pregnant people with glomerular disease have increasing proteinuria as gestation progresses, and some may progress to the nephrotic syndrome in the third trimester [75,76].
●Nephrotic syndrome versus preeclampsia – Nephrotic-range proteinuria (>3 g/24 hours) is a sign of glomerular injury. Pathology limited to the renal tubules and interstitium typically results in protein excretion rates less than 2 g/24 hours unless glomerular disease is also present. Patients with protein excretion less than 3 g/24 hours are usually asymptomatic. In contrast, rates greater than 3 g/24 hours may cause the nephrotic syndrome, which consists of nephrotic-range proteinuria together with edema, hypoalbuminemia, and hyperlipidemia.
Preeclampsia is the most common cause of de novo nephrotic-range proteinuria in pregnancy. In a retrospective study of 104 patients with nephrotic-range proteinuria during pregnancy who were evaluated postnatally, the postnatal diagnosis was preeclampsia alone in 60 percent, superimposed preeclampsia in 9 percent, newly diagnosed kidney disease in 9 percent, worsening proteinuria due to renal disease in 6 percent (no hypertension), isolated gestational proteinuria in 1 percent, and unclear in the remainder [77]. (See "Overview of heavy proteinuria and the nephrotic syndrome".)
Nephrotic range proteinuria during pregnancy due to primary glomerular disease is associated with a high risk of several adverse outcomes, including superimposed preeclampsia, acute kidney injury, preterm birth, low birth weight, and the need for neonatal intensive care [78]. Nevertheless, conservative management until delivery, particularly in patients who present in the third trimester, is often a reasonable management approach. When nephrotic syndrome presents early in pregnancy, and/or there is progressive decline in kidney function, timely treatment of the underlying kidney disease is often indicated. In such cases, the potential benefits of kidney biopsy may outweigh the risks. (See 'Role of kidney biopsy in pregnancy' below.)
Role of kidney biopsy in pregnancy — Once it has been determined that the patient has heavy proteinuria, the etiology may be suggested from the history and physical examination. This is particularly true for patients who have preeclampsia or another systemic disease such as diabetes mellitus, systemic lupus erythematosus, HIV infection, or use of a medication known to cause nephrotic syndrome (nonsteroidal anti-inflammatory drug, pamidronate, lithium, interferon-alpha). Serologic testing for lupus nephritis (ie, antinuclear antibodies and anti-double stranded DNA antibody titers and complement levels), primary membranous nephropathy (anti-PLA2R antibody titers), and infections associated with glomerular diseases (eg, HIV and hepatitis C virus) may be useful. Kidney biopsy is sometimes appropriate to establish the diagnosis. The decision to perform renal biopsy during pregnancy, or to defer until after delivery, is based on several factors, including the stage of pregnancy, the severity of the kidney disease, and the suspected underlying diagnosis.
Data on the safety of renal biopsy during pregnancy are limited. The major complication of kidney biopsy is bleeding. In a systematic review of reports of kidney biopsies performed during pregnancy or postpartum, the risk of bleeding was higher when the biopsy was performed during pregnancy as compared with postpartum (7 percent [16/197] versus 1 percent [3/268]) [79]. All observed cases of major bleeding (ie, requiring blood transfusion) occurred in biopsies performed between 23 to 26 weeks of gestation, suggesting patients in this gestational age range may be particularly vulnerable to complications. Early in pregnancy, the benefit of a biopsy (accurate diagnosis and subsequent tailored management) is more likely to outweigh its risks. Later in gestation, the gravid uterus makes the standard prone position for biopsy difficult. In such cases, renal biopsy can be performed with the patient in the lateral decubitus position or deferred until the patient has stabilized postpartum. If the patient is taking aspirin, it should be held for at least one week prior and for one to two weeks following kidney biopsy, to minimize the risk of bleeding. (See "The kidney biopsy".)
MANAGEMENT OF NEPHROTIC SYNDROME IN PREGNANCY — The management of nephrotic syndrome in pregnancy is based on expert opinion, as minimal data are available to support evidence-based practice. In nonpregnant patients with nephrotic syndrome, inhibitors of the renin-angiotensin aldosterone system (ie, angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists) are routinely used as nonspecific therapy to reduce proteinuria. These agents are contraindicated in pregnancy, due to well-documented teratogenicity, particularly in the second and third trimesters of pregnancy. (See "Adverse effects of angiotensin converting enzyme inhibitors and receptor blockers in pregnancy".)
Immunosuppressive drugs — First-line therapy for nephrotic syndrome caused by glomerular disease frequently includes immunosuppressive agents. Immunosuppressive drugs generally considered safe for use in pregnancy include azathioprine, glucocorticoids, and calcineurin inhibitors (eg, tacrolimus and cyclosporine). Mycophenolate mofetil and cyclophosphamide are teratogenic and should be avoided in pregnancy. There are limited data on the safety of rituximab in pregnancy, so this agent should also be avoided in pregnancy unless benefits are felt to outweigh the potential risks. (See "Safety of rheumatic disease medication use during pregnancy and lactation".)
Low dose aspirin — In pregnant patients with chronic kidney disease, initiation of low dose aspirin beginning at 12 to 16 weeks of gestation is recommended to reduce the risk of developing preeclampsia later in gestation. The use of aspirin for preeclampsia prevention is reviewed in detail separately. (See "Preeclampsia: Prevention" and "Preeclampsia: Prevention", section on 'Low-dose aspirin'.)
Management of edema — A major goal in the management of nephrotic syndrome is to reduce edema to a level that allows comfort during ambulation. The dietary intake of sodium may be limited to 1.5 g (approximately 60 mEq) of sodium per day, provided normal blood pressure is maintained. Graduated compression stockings and leg elevation are safe and often effective methods to facilitate resolution of edema.
Historically, the use of diuretics has been discouraged because of the theoretical risk that they will impair the normal pregnancy-associated expansion of plasma volume, possibly decreasing placental perfusion. However, there is no clear evidence of adverse fetal effects, and loop diuretics are appropriate in pregnant people with severe, refractory edema [80]. In such cases, therapy should aim to reduce excessive edema at a slow rate of no more than 1 to 2 pounds per day with a loop diuretic, while a low sodium diet is maintained. A written record of daily weights, taken by the patient, is highly recommended.
Diuretics should not be used in patients with preeclampsia because plasma volume is already reduced.
Anticoagulation — Nephrotic syndrome is associated with an increased risk of deep venous thrombosis (DVT). Patients with severe nephrotic syndrome (particularly those with membranous nephropathy) and very low serum albumin levels who are not at high risk for bleeding may benefit from prophylactic anticoagulation. However, there is no high quality evidence to guide the optimal approach to prophylactic anticoagulation in this patient population. A suggested approach to prophylactic anticoagulation in pregnant people is presented in more detail elsewhere. (See "Hypercoagulability in nephrotic syndrome" and "Hypercoagulability in nephrotic syndrome", section on 'Pregnant patients'.)
Management of hyperlipidemia — Statins are generally discontinued in pregnancy because of limited and contradictory data suggesting an increased risk of congenital anomalies with first-trimester exposure. We suggest discontinuing statins in females who are planning pregnancy and resuming these drugs after delivery/breast feeding. However, individual decisions need to be made about benefit versus risk in patients at very high risk of a myocardial infarction or stroke, such as those with homozygous familial hypercholesterolemia or established cardiovascular disease [81]. (See "Statins: Actions, side effects, and administration", section on 'Risks in pregnancy and breastfeeding'.)
Bile acid sequestrants and fibrates have no established teratogenic effects and can be safely used in pregnancy to treat severe hyperlipidemia due to nephrotic syndrome.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Glomerular disease in adults" and "Society guideline links: Hypertensive disorders of pregnancy".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topic (see "Patient education: Protein in the urine (proteinuria) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Urine dipstick is routinely used to screen for proteinuria in pregnancy, but false positive and false negative results are common. It is most predictive of abnormal 24-hour proteinuria if +2 or greater. Positive urine dipsticks should be followed up with a quantitative test. (See 'Assessment of proteinuria' above.)
●The spot urine protein-to-creatinine ratio (UPCR; mg protein/mg creatinine) is an accurate, convenient, and relatively rapid method to quantify proteinuria in pregnancy. A UPCR less than 0.15 mg/mg may be considered normal (predictive of less than 300 mg protein in a 24-hour collection), and values above 0.7 mg/mg are very likely to indicate significant proteinuria (more than 300 mg protein in a 24-hour collection). A UPCR greater than 0.3 mg/mg after 20 weeks gestation is one of the diagnostic criteria for preeclampsia (table 1). (See 'Quantitative' above.)
●The gestational age at which proteinuria is first documented is important in establishing the likelihood of preeclampsia versus other kidney disease. Proteinuria documented before 20 weeks of gestation suggests preexisting renal disease. Proteinuria beginning after 20 weeks gestation is usually due to preeclampsia, especially in the presence of hypertension or other features of severe preeclampsia (table 3). (See 'Differential diagnosis of proteinuria' above.)
●Preeclampsia is the most common cause of proteinuria in pregnancy and is the most likely diagnosis in all pregnant patients with proteinuria first identified after 20 weeks of gestation. If hypertension is absent, then the presence of primary or secondary kidney disease should be considered. (See 'Differential diagnosis of proteinuria' above.)
●In nephrotic syndrome, severe leg edema can be managed with sodium restriction, graduated compression stockings, and leg elevation. If edema persists despite these measures, loop diuretics may be used with caution. (See 'Management of nephrotic syndrome in pregnancy' above.)
●Nephrotic syndrome is associated with an increased risk of deep venous thrombosis (DVT). Patients with severe nephrotic syndrome (particularly those with membranous nephropathy) and very low serum albumin levels who are not at high risk for bleeding may benefit from prophylactic anticoagulation. However, there is no high quality evidence to guide the optimal approach to prophylactic anticoagulation in this patient population. (See "Hypercoagulability in nephrotic syndrome", section on 'Pregnant patients'.)
●Bile acid sequestrants and fibrates can be safely used in pregnancy to treat severe hyperlipidemia due to nephrotic syndrome; statins should be avoided. (See 'Management of nephrotic syndrome in pregnancy' above.)
