Contributor: Bill Mabie, MD
Last Update: 5/1/2011
A large number of insults or disorders may damage the function of the kidneys. The clinical presentation is frequently subtle. The differential diagnosis of chronic kidney disease (CKD) is as follows:
Diabetic kidney disease – Microalbuminuria, proteinuria, hypertension, and retinopathy.
Nondiabetic kidney disease
Nephritic syndrome – hematuria, RBC casts, proteinuria, and hypertension.
• Poststreptococcal glomerulonephritis, IgA nephropathy, membranoproliferative disease
Nephrotic syndrome- bland urinalysis, proteinuria, hypoalbuminemia, hyperlipidemia, and edema.
• Minimal change disease, Focal Segmental Glomerulosclerosis (FSGS), and membranous
Lupus – nephritic or nephrotic
Analgesic nephropathy, chronic pyelonephritis, obstructive, and reflux
Hypertension, sickle cell, TTP/ HUS, renal artery stenosis
Simple cysts, autosomal dominant polycystic kidney disease
Chronic rejection, drug toxicity, recurrence of native kidney disease
Glomerular Filtration Rate (GFR )
The serum creatinine has been the most widely used test of kidney function and reasonably accurately reflects GFR. The serum creatinine tends to overestimate GFR. Moreover, serum creatinine levels are a function not only of creatinine clearance (which reflects kidney function) but also of creatinine production, which is a reflection of muscle mass. This is particularly relevant for women who may have reduced muscle mass. It is now customary to estimate GFR using two equations endorsed by the National Kidney Foundation – the Cockcroft Gault equation and the Modification of Diet in Renal Disease equation. The estimated GFR is now routinely reported by the GHS lab using the MDRD equation. The estimated GFR has limitations also. For example, the equations are not accurate when the GFR is rapidly changing. In addition, the GFR estimating equations have not been validated for use in pregnancy. Timed urine collections, such as 24-hour urine for creatinine clearance and total protein, are still recommended by the National Kidney Foundation to assess renal function and proteinuria in pregnant women.
Chronic kidney disease is classified by the National Kidney Foundation clinical practice guidelines into 5 stages.
Stage Description GFRa (mL/min/1.73 m2)
1 Kidney damage with normal GFR ≥90
2 Kidney damage with mildly decreased GFR 60-89
3 Moderately decreased GFR 30-59
4 Severely decreased GFR 15-29
5 Kidney failure <15 (or dialysis)
The literature on CKD in pregnancy is primarily uncontrolled and retrospective, classifications vary, most patients have mild renal dysfunction, and the number with severe disease is small. Most of the literature does not use the National Kidney Foundation CKD classification. Much of our prepregnancy counseling is based on the serum creatinine values.
The degree of renal dysfunction in pregnancy can be classified according to the serum creatinine as follows:
• Mild: serum creatinine <1.5 mg/dL and minimal hypertension
• Moderate: serum creatinine 1.5 mg/dL – 3.0 mg/dL
• Severe: serum creatinine >3.0 mg/dL
General Initial Laboratory Evaluation
Should be ordered with microscopic for detailed urine sediment examination.
2. Serum creatinine
A creatinine >0.9 mg/dl is abnormal in a pregnant woman. Values above this threshold should be repeated each trimester or more frequently as dictated by the clinical situation. In the absence of an apparent explanation (e.g., long-standing diabetes), renal ultrasound to assess renal size and rule out obstruction should be considered if the creatinine is > 1.3 mg/dL.
3. Random urine protein/creatinine ratio
A spot urine protein/creatinine ratio is highly correlated with a 24-hour urine collection in chronic renal disease, as well as in the assessment of proteinuria in patients with gestational hypertension. Values from a cath specimen ³0.3 are indicative of significant proteinuria (>300 mg/d) and should be further assessed. A P/C ratio of <0.14 is not associated with significant proteinuria. Intermediate values may need further evaluation and depending on the clinical situation consideration given to obtaining a 24 hour urine collection.
4. Additional testing may include (depending on history and previous work-up): urine culture, CBC, CMP (lytes, glucose, calcium, phosphorus), ANA, serum complement, HIV, and Hepatitis B and C serologies.
5. Increasing proteinuria by dipstick should prompt repeat P/C ratio.
Complications and counseling
During normal pregnancy, the GFR increases about 50% due to an increase in renal plasma flow. This occurs normally in patients with mild impairment, but in patients with moderate impairment this response is blunted and in patients with severe dysfunction the response is essentially nil. The red cell and plasma volume expansion that occurs during pregnancy may be attenuated in patients with chronic renal disease. The degree of volume and red cell expansion is inversely proportional to the serum creatinine, such that patients with creatinine >3.0 mg/dL may have only a minimal blood volume expansion. Patients with uncontrolled hypertension and/or nephrotic range proteinuria have the least favorable prognosis.
Whether pregnancy causes an irreversible accelerated decline in renal function in women with CKD has been controversial for years, with most obstetricians and nephrologists agreeing that pregnancy does not accelerate renal dysfunction. Recent evidence, however, shows that patients with both a GFR <40ml/min/1.73m2 and proteinuria > 1g/24 hrs before pregnancy have accelerated decline in renal function and a shorter time to dialysis.
Mild Renal Insufficiency (Stages 1 & 2)
Pregnancy outcome is usually favorable in these patients and pregnancy does not seem to accelerate the process of renal deterioration. However, 50% of patients may develop increasing proteinuria, 25% may develop IUGR, and up to 25% may deliver preterm, usually due to the development of hypertension.
Moderate and Severe Renal Insufficiency (Stages 3 – 5)
The prognosis for pregnancy is more guarded. Maternal and fetal complications are approximately twice as common, with a marked increase in the development/exacerbation of hypertension and proteinuria (approximately 50% develop these complications), the acceleration of the underlying disease process, and the occurrence of preterm birth and IUGR. Overall, however, neonatal survival is approximately 90%. In patients with a serum creatinine 1.5 – 3.0 mg/dL, approximately 60% deliver preterm and 40% have IUGR. In those with creatinine >3.0 mg/dL, 75% deliver preterm and nearly 60% have IUGR. In patients with a creatinine >2.0 mg/dL, 50% of patients will have a pregnancy related decline in renal function measurable at 6 months post-partum. Based on the potential for significant maternal and obstetric complications, termination of pregnancy should be discussed with women who have this degree of renal impairment.
Due to the frequent coexistence of hypertension or diabetes, patients should be managed according to the guidelines of their primary disease process. Isolated renal disease, as might occur with minimal change disease, is not an indication for antenatal testing or early delivery unless the clinical scenario dictates otherwise (e.g., IUGR, preeclampsia). In all patients with renal disease, vigilance for the development of preeclampsia and IUGR is imperative. Hypertension should be treated per our usual protocol. Often these patients require more than one agent. The degree of anemia should be assessed. Iron supplementation can be provided for women with documented iron deficiency, and erythropoietin can be considered for patients with profound anemia due to renal insufficiency and normal iron stores.
Even in cases in which the etiology of the renal disease is uncertain, renal biopsy is usually not indicated antepartum because of an associated complication rate of 5-10%. However, in certain situations, the results of renal biopsy may substantially alter management and should not be arbitrarily avoided.
Nephrotic range proteinuria is defined as the excretion of more than 5 gm of protein per day (roughly equivalent to P/C ³ 3). In addition to renal disease, these patients may have hypoalbuminemia, hyperlipidemia, and a diminished ability to excrete sodium. Because of the low albumin and sodium retention, these patients can develop massive edema, in which case they should be managed with a 2.0 gm Na diet and careful use of diuretics, with close attention to electrolytes. Nephrotic syndrome is a hypercoagulable state, and thromboprophylaxis should be considered. Fortunately, the prognosis does not correlate with the amount of proteinuria, but rather with the creatinine and degree of hypertension.
End Stage Renal Disease/Dialysis
Possible maternal complications are accelerated hypertension, CVA, and mortality. Although pregnancy outcomes for patients on dialysis have improved over the last 20 years, from a livebirth rate of < 50% to approximately 75% (after exclusion of first trimester losses), the occurrence of other complications remains exceedingly high. Overall, patients with some residual renal function have better outcomes than those who are completely anuric. There is no evidence that patients on peritoneal dialysis fare better or worse than those on hemodialysis. Most patients are on the latter. In pregnancy, the requirements for dialysis typically increase by 50%. In order to avoid hypotension and large volume shifts, this demand is best met by increasing weekly hours of dialysis from 12 hours to more than 20, minimal weight gain between dialyses, and aggressive management of anemia. More intensive hemodialysis (e.g., 5X/week) has been associated with longer pregnancy, higher birthweight, and better survival. Despite optimum care, approximately 80-90% of pregnancies will deliver preterm; Hypertension will worsen or develop in more than 50%. Increased BUN levels may cause fetal osmotic diuresis and polyhydramnios in up to 25%.
There have been no rigorous clinical trials examining the need for fetal monitoring during hemodialysis following viability. Due to the potential for hypotensive episodes from large volume shifts, some have advocated continuous fetal monitoring during and for a few hours following each hemodialysis session. In the absence of hypotension and with attention paid to the avoidance of large volume shifts, it is unlikely that fetal compromise would develop during a hemodialysis session. Therefore, in the absence of other signs of potential uteroplacental insufficiency (e.g., IUGR, oligohydramnios, abnormal UA Doppler), continuous fetal monitoring during hemodialysis is not routinely necessary.
Post Renal Transplant
Following renal transplant, many previously amenorrheic women, resume normal ovarian function. Although the spontaneous loss rate is estimated to be 40%, pregnancy outcome is more favorable than for women with ESRD with approximately 90% of continuing pregnancies having a successful pregnancy. Patients with stable graft function typically have the normal physiologic renal responses to pregnancy, although 10-15% may develop evidence of renal functional impairment during pregnancy and up to 40% develop proteinuria, which is usually reversible. Approximately 50% of women will deliver preterm and 20% of pregnancies will be complicated by IUGR. Preeclampsia develops in approximately 30% of patients and must be distinguished from graft rejection, which develops in up to 10% of patients. Impaired glucose tolerance, increased risk of infection, ectopic pregnancy, and uterine rupture are other complications. Immunsuppressive medication should be continued during pregnancy. Corticosteroids, azathioprine, and calcineurin inhibitors (cyclosporine, tacrolimus) are considered reasonably safe. Although calcineurin inhibitor blood levels may decrease during pregnancy because of alterations in plasma volume and increased CYP3A enzyme activity; it is not clear whether dose adjustment is required, particularly because dose adjustment in stable transplant patients several years after kidney transplant has not proved to be associated with a better outcome. Calcineurin inhibitors are associated with an increased incidence of hypertension, preterm delivery, and slightly smaller infants. Mycophenolate mofetil and rapamycin are associated with fetal malformations and are contraindicated in pregnancy. Prognosticators associated with the most favorable outcomes in post transplant patients include:
• > 2 years from transplant
• Stable renal function with Cr <2.0 mg/dL
• BP £140/90 mmHg
• Proteinuria <500 mg
• Prednisone £15 mg/d
• Azathioprine £2mg/kg/d
• Cyclosporine £5mg/kg/d
• No evidence of graft rejection
Obstetricians should be aware of the pelvic location of the kidney, particularly if cesarean delivery is planned.
Criteria for Nephrology Consultation
• Serum creatinine >1.3 mg/dL
• Spot protein/creatinine ratio > 3.0 (>5 gm/d protein)
• Spot protein/creatinine ratio ³ 0.3 and positive ANA
• Patients followed at OB Center for a P/C ratio ³0.3 unrelated to pre-eclampsia or a serum creatinine >0.9 mg/dL may need referral to an internist or a nephrologist by 4-6 weeks post-partum.
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