Saudi Journal of Kidney Diseases and Transplantation

: 2016  |  Volume : 27  |  Issue : 5  |  Page : 1029--1032

Triple confusion: An interesting case of proteinuria in pregnancy

Pramod K Guru1, Devon M Ramaeker2, Arundhathi Jeybalan2, Nirav A Shah3, Sheldon Bastacky4, Kelly V Liang3,  
1 Division of Critical Care Medicine, Mayo Clinic, Florida, FL, USA
2 Maternal-Fetal Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
3 Division of Renal-Electrolyte, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
4 Anatomic Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Correspondence Address:
Pramod K Guru
Department of Critical Care Medicine, Mayo Clinic, Florida, FL


Pregnancy-related renal diseases are unique and need special attention, both for diagnosis and management. The major confounding factors for diagnosis are the physiological multiorgan changes that occur throughout the gestational period. Proper diagnosis of the renal disease is also important, given the impact of varied management options both on the maternal and fetal health. A young middle-aged female with a long-standing history of diabetes presented to the hospital with worsening proteinuria in her second trimester of pregnancy. Clinical history, examinations, and laboratory analysis did not give any clues for diagnosis of a specific disease entity. This led us to take the risk of renal biopsy for a tissue diagnosis. The odds of renal biopsy favored the management decision in her case, thereby avoiding the confusions prior to biopsy. The pathological diagnosis is a surprise though not a unique entity on its own (minimal change disease in pregnancy). The case illustrates the disparity of clinical presentations and the pathology in patients, and the importance of renal biopsy in pregnant patients in particular.

How to cite this article:
Guru PK, Ramaeker DM, Jeybalan A, Shah NA, Bastacky S, Liang KV. Triple confusion: An interesting case of proteinuria in pregnancy.Saudi J Kidney Dis Transpl 2016;27:1029-1032

How to cite this URL:
Guru PK, Ramaeker DM, Jeybalan A, Shah NA, Bastacky S, Liang KV. Triple confusion: An interesting case of proteinuria in pregnancy. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2021 Oct 21 ];27:1029-1032
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Full Text


The evaluation of pregnant patient with proteinuria is a challenge to both obstetricians and nephrologists. The physiological renal changes of pregnancy can lead to increased excretion of protein, which is often benign in nature as it subsides after delivery. However, pregnant patients with worsening proteinuria (considered pathological) need extra vigilance because of the potential associated adverse maternal and fetal consequences. It is often difficult to differentiate between preeclampsia and de novo or worsening of preexisting renal disease, though it is critically important for implementation of management strategies. Kidney biopsy as a diagnostic tool for the management of renal disease in pregnancy is weighed for case by case, given the heightened risk of complications. We came across one such patient with long-standing diabetes and worsening proteinuria in her second trimester of pregnancy.

 Case Report

A 40-year-old gravida 3, para 0111 Caucasian female was admitted for evaluation of accelerated hypertension and nephrotic range proteinuria at 18 weeks' gestation. She reported worsening pedal edema and new facial edema for two weeks prior to admission. She did not have neurologic symptoms, abdominal pain, chest pain, shortness of breath, fever, cough, and bowel or bladder disturbance. She also denied having jaundice, rash, joint pain, or anorexia. History was negative for recent trauma, surgery, intravenous drugs, or nonsteroidal anti-inflammatory drug use. Her medical history was significant for Type 1 diabetes mellitus (DM) diagnosed at 10 years of age, with documented diabetic retinopathy, hypertension for 15 years, and dyslipidemia. She had been on an insulin pump (for five years), and prior to pregnancy was on a statin and angiotensin-converting enzyme inhibitor. Her obstetrical history included first pregnancy at the age of 24, complicated by a preterm delivery at 34 weeks gestation by cesarean section due to preeclampsia, and a first trimester termination. She was a teacher by profession and was actively smoking one pack/day with a 50-pack year history. She admitted previous alcohol and marijuana abuse but was sober for five years. Her family history was significant for diabetes in her mother and negative for hypertension, renal disease, malignancy, autoimmune disease, or preeclampsia.

On physical examination, she was healthy looking, afebrile, and vital signs were notable for hypertension with blood pressure (BP) of 180/82 mm Hg. She had a systolic flow murmur at the precordium, a palpable uterus corresponding to her gestational age, and 1-2+ bilateral lower extremity edema. The rest of her general physical examinations were unremarkable.

On laboratory assessment, her 24 h urinary total protein was 5771 mg in comparison to 251 mg at 14 weeks of gestation. Urinary microscopy revealed pH 7.5, specific gravity 1.010, 3+ protein, 2-3 red blood cells/hpf, and no casts. The rest of her laboratory studies including blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, hemoglobin, platelets, and uric acid were normal. Serological markers for hepatitis B virus (HBV) and hepatitis C virus (HCV), HIV, ANA, serum complements, serum and urine protein electrophoresis, and lactate dehydrogenase were normal. A pelvic and renal ultrasound revealed a viable fetus and unremarkable kidneys.

After controlling her BP with medications and thorough discussion with the patient regarding the risks versus benefits of renal biopsy, she underwent an ultrasound-guided renal biopsy without procedure-related complications at 21 weeks of pregnancy.

The renal biopsy showed normal cellularity of the glomerulus, minimal focal mesangial expansion [Figure 1], and interstitial fibrosis with global glomerulosclerosis involving 2/10 glomeruli on light microscopy. Immunofluorescence was negative for immune deposits of immunoglobulin or complement either in the glomerular or tubular basement membrane or the mesangium. There was no glomerular endotheliosis to suggest preeclampsia or any features of nodular glomerulosclerosis (Kimmelstiel-Wilson nodules) to suggest diabetic nephropathy. Given the electron microscopic evidence of extensive foot process effacement and no immune complex deposits [Figure 2], a diagnosis of minimal change disease versus unsampled focal segmental glomerulosclerosis was made.{Figure 1}{Figure 2}

Conservative management was instituted with tight BP control with diltiazem and labetalol. Steroids were not initiated as there was little evidence that this therapy would improve outcome, and due to the potential risk for hyperglycemia and worsening of diabetic control. In addition, she was encouraged to quit smoking. She was discharged from the hospital with close outpatient follow-up.


Our differential diagnosis of new-onset nephrotic range proteinuria in this young patient with long-standing diabetes and hypertension in her second trimester of pregnancy included superimposed preeclampsia, diabetic or hypertension-related renal disease, systemic immunologic disease, and other primary glomerular diseases. Superimposed preeclampsia must be strongly considered if a pregnant patient develops proteinuria for the first time or has worsening proteinuria, with or without associated worsening hypertension, after the 20 th week of gestation. [1] Superimposed preeclampsia in the setting of chronic hypertension can be clinically challenging to diagnose, given the benign increase in BP that may occur in the third trimester. Proteinuria diagnosed prior to or early in pregnancy can also make the diagnosis of preeclampsia difficult, since urinary protein excretion increases over the course of gestation. Preeclampsia is the most frequent cause of nephrotic syndrome in pregnancy. [2] This patient had an unclear clinical picture with worsening proteinuria at 18 weeks gestation in the setting of both long-standing diabetes and hypertension. Moreover, she did not have any classic symptoms (headaches, visual changes, and right upper quadrant abdominal pain), or laboratory abnormalities (elevated liver transaminases and low platelets) to support the diagnosis of superimposed preeclampsia. We ruled out molar pregnancy by ultrasound, which has been reported to present as nephrotic syndrome prior to 20 weeks of gestation. [3] She did not have any systemic features suggestive of lupus or other autoimmune diseases, had no history of NSAID abuse or other drug and heavy metal exposures, and had negative serology for HIV, HBV, and HCV.

Diabetic nephropathy is a progressively worsening disease characterized by proteinuria, hypertension, and reduced glomerular filtration leading to renal failure. About 20-30% of patients develop microalbuminuria after a mean of 15 years of Type 1 DM. [4] Without any preventive strategy, macroalbuminuria develops in 30-45% of patients after 40 years of disease. [5] The prevalence of diabetic nephropathy is around 6% in pregnant women with Type 1 DM and is a well-known risk factor for worsening proteinuria or development of preeclampsia. [6] A long history (30 years) of DM and evidence of target organ damage (retinopathy and hypertension) in our patient led us to consider diabetes as the principal cause of her nephrotic syndrome. However, the rapid worsening in her proteinuria within a span of four weeks is unusual for diabetic nephropathy and therefore widened our differential. A de novo glomerulonephritis could not be ruled out and would alter management, so a renal biopsy was considered as a potential tool to guide our diagnosis.

Renal biopsies in pregnancy carry definite risks to both the patient and the fetus. The data on renal biopsy in pregnancy are not robust, limited by small sample sizes, and reporting bias. Potential complications of renal biopsy in pregnancy include the risk of pain, bleeding, and perirenal hematoma either requiring transfusion or nephrectomy. The risk of bleeding is exponentially increased secondary to the physiologic increase in renal blood flow. In addition, there is the added risk of intrauterine fetal demise and maternal death. The reported incidence of complications ranges from 1.6% to 4.4% from data in the 1960s. [7] However, recent studies have shown improved success and decreased complication rates. [8],[9],[10],[11],[12] It has been advocated that if indicated, biopsy should be performed prior to the 30 th week of gestation. [11],[12]

The results of the biopsy, in our patient, added significantly in the management decision for the patient's nephrotic syndrome and for the rest of her pregnancy. In conclusion, although proteinuria and hypertension are hallmark findings of preeclampsia when presenting during the third trimester, the etiology is less clear before 20 weeks gestation. Despite the inherent significant risks associated with a renal biopsy performed during pregnancy, it may provide critical information for the management. A multidisciplinary approach to patient care is recommended in such cases.


There are no financial conflicts of interest or relevant disclosures with respect to any of the authors. We affirm that all authors had access to the data and a role in writing the manuscript and that the manuscript is entirely original.


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