5 Pearls on Nephrotic Syndrome

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
         • Common causes: Idiopathic, NSAIDs, Hodgkin lymphoma
      2. focal segmental glomerulosclerosis (FSGS): focal and segmental scarring, can be thought of as more severe MCD (on a spectrum)
         • causes: chronic illnesses (obesity, DM, HTN), viruses (HIV, parvovirus, SARS-CoV-2), hereditary, drugs (bisphosphonates, heroin)
           • in many of the chronic illnesses, there is hyperfiltration-related injury leading to FSGS
      3. membranous nephropathy: circulating antibody or other unidentified toxin causes epithelial and surrounding podocyte damage
         • causes: PLA2R antibody, HBV, syphilis, lupus, cancers
      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
         • rapid increase in proteinuria
         • diabetic nephropathy without retinopathy
         • diabetic nephropathy seemingly out of proportion to diabetic control and/or duration.
      3. minimal change disease refractory to treatment
         • could represent missed FSGS
         • generally, 10-20 glomeruli on biopsy is adequate for FSGS diagnosis, but occasionally will be missed if all 20 of those happen to miss sclerotic lesions
   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

Contributors

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

Reviewers

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

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