5 Pearls on Nephrotic Syndrome

Core IM

There are current knowledge gaps in the evaluation of patients with nephrotic syndrome. Physicians often feel overwhelmed by the myriad of causes of nephrotic syndrome and unempowered to send first-pass workup for the syndrome. Similarly, clear indications for a kidney biopsy can appear elusive at times. In this episode of Core IM, the team discusses this challenge and explores the many management strategies for nephrotic syndrome that may appear to be anecdotal and based on presumed mechanism rather than proven by evidence-based medicine.

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Welcome to Core IM, a virtual medical community! Core IM strives to empower its colleagues of all levels and backgrounds with clinically applicable information as well as inspire curiosity and critical thinking. Core IM promotes its mission through podcasts and other multimodal dialogues. ACP has teamed up with Core IM to offer continuing medical education, available exclusively to ACP members by completing the CME/MOC quiz.

  1. Pearl 1: Don’t be fooled by the UA!
    1. Review of urine dipstick vs. UA
      1. urine dipstick: done at bedside, not looked at under microscope but rough sense of protein, blood, pH, spec grav, LE/nitrites, ketones, glucose, bili
      2. UA: done in lab, microscopic exam of WBCs, RBCs, casts, crystals
    2. Don’t brush off +1 protein or “few” RBCs
      1. despite some evidence for the contrary, anecdotally, nephrologists and primary care physicians alike have been fooled by the dipstick before
    3. Don’t ignore the specific gravity
      1. concentrated urine may falsely elevate proteinuria and vice versa
    4. Follow-up with a UPCR
      1. UPCR most inclusive and includes non-albumin proteins, such as myeloma proteins
      2. however, UACR may be a little more sensitive than the UPCR
  2. Pearl 2: Key questions to ask a patient with new nephrotic syndrome/1.73m2 body surface area
    1. Defining nephrotic syndrome:
      1. nephrotic-range proteinuria: ≥3.5 g/d proteinuria
      2. nephrotic syndrome: nephrotic-range proteinuria with low albumin and edema/anasarca ± hyperlipidemia, thromboses
    2. Framework: can approach questioning from different subtypes, which is defined by extent and pattern of injury to the podocyte
      1. minimal change disease (MCD): so “minimal” that podocyte effacement can only be seen on electron microscopy
      2. focal segmental glomerulosclerosis (FSGS): focal and segmental scarring, can be thought of as more severe MCD (on a spectrum)
      3. membranous nephropathy: circulating antibody or other unidentified toxin causes epithelial and surrounding podocyte damage
      4. other: amyloidosis, preeclampsia, diabetes (arguably most common cause of nephrotic range proteinuria)
    3. Summary: ask about chronic illnesses, cancer screening, viral infections and STIs, drugs, and family history
  3. Pearl 3: What a generalist needs to know about a kidney biopsy
    1. Who should we biopsy?
      1. most patients with nephrotic syndrome and no clear cause; specifically, experts cite proteinuria >1 g/d on multiple visits without clear comorbidities and >3 g/d without diabetes as two specific scenarios, with a third scenario being…
      2. diabetes that appears atypical
      3. minimal change disease refractory to treatment
    2. Are kidney biopsies safe?
      1. kidney biopsies are relatively safe, with bleeding observed in <1% of biopsies
      2. biopsies may be made safer by controlling blood pressure, holding anticoagulants, holding pressure, pre-biopsy dialysis to lower “uremic” platelet dysfunction
      3. expert comment: let the proceduralists talk about the risks!
  4. Pearl 4: Practical management of the edematous state
    1. use higher doses of diuretics
      1. higher doses of loop diuretics are needed given hypoalbuminemia
    2. oral Lasix least bioavailable, so can start with an IV agent to bypass gut edema
    3. hearing loss appears to be rare and is reversible
    4. do not need to routine give with albumin; there are some short-term effects that do not affect long-term outcomes
    5. recommend a food diary to help with food restriction
    6. this practical handout can help patients choose which foods to eat
  5. Pearl 5: Nephrotic Syndrome and risk of thrombosis
    1. Patients with membranous nephropathy have been shown to be at increased risk for thrombotic events
    2. Prophylactic anticoagulation is recommended in pts with membranous nephropathy and severe hypoalbuminemia (albumin <2.5)
      1. Current use of warfarin and heparin, not DOAC given lack of studies
    3. Of note, no RCTs that have studied if patients with nephrotic syndrome benefit from anticoagulation


Shreya Trivedi, MD - Author, Producer

Martin Fried, MD - Author, Producer

Clem Lee, MD - Author, Producer

Samira Farouk, MD - Guest Expert

Matthew Sparks, MD - Guest Expert


Swapnil Hiremath, MD, MPH

Gerren Hobby, MD

Tejas Patel, MD, FACP, FASN

Those named above unless otherwise indicated have no relationships with any entity producing, marketing, reselling, or distributing health care goods or services consumed by, or used on, patients.

Release Date: September 2, 2020

Expiration Date: September 2, 2023

CME Credit

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the American College of Physicians and the Core IM.  The American College of Physicians is accredited by the ACCME to provide continuing medical education for physicians.

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Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 0.75 medical knowledge MOC Point in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program.  Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

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