Nephrotic vs Nephritic Syndrome: How to Spot the Difference

Matthew F. Watto, MD; Paul N. Williams, MD; Stuart K. Brigham, MD


March 08, 2021

This transcript has been edited for clarity.

Matthew F. Watto, MD: I'm Dr Matthew Frank Watto, here with my two good friends and co-hosts, fellow internists Dr Stuart Kent Brigham and Dr Paul Nelson Williams.

Paul N. Williams, MD: We are the internal medicine podcast. We use expert interviews to bring you clinical pearls and practice-changing knowledge. In this short video, we will highlight our favorite pearls from show favorite Dr Joel Topf (aka @kidney_boy), who talked us through what had previously been the bewildering topic of predicting nephrotic syndrome. And now he made it crystal clear and I feel like I'm practically a nephrologist.

We'll go through the pearls that we garnered from this particular episode. Stuart, what do you take away that now has you a master of the kidney?

Stuart K. Brigham, MD: I love the idea of approaching nephrotic syndrome as either a primary or secondary diagnosis. To me, it just makes sense. It helps to put it in the framework that cognitively helps me to understand why it's important to treat the underlying cause for secondary nephrotic syndrome. And it's also interesting talking about the antiphospholipase A2 receptor (antiPLA2R) titer. Potentially in the future, getting an antiPLA2R may reduce the need for a biopsy because it identifies primary nephrotic syndrome.

Watto: I was embarrassed to know that this was around. He mentioned 2009 and it's now 2021. I've seen it ordered but I never bothered to look it up.

Brigham: It's like cystatin C for AKI.

Watto: He mentioned the antiPLA2R antibodies. They tend to be present in primary membranous nephropathy. That means that if you have a positive antiPLA2R antibody, there will probably be some point in the future where they just forgo a biopsy and treat this as primary membranous nephropathy. The other good thing about it was that you can follow the response to treatment with antiPLA2R antibody titers.

Brigham: But until then, you're going to get a biopsy.

Watto: Yes. And Stuart will do it without too much guidance. Paul, what was your pearl for this one?

Williams: My pearl is more prosaic. I feel like every time nephrotic syndrome comes up, it's always an afterthought about anticoagulation. The vestiges of your brain remind you that this is actually a prothrombotic state, especially as the patient becomes progressively hypoalbuminemic. And so the discussion around prophylactic anticoagulation came up and we got a little bit clearer guidance.

The KDIGO guidelines from 2012 recommend considering prophylactic anticoagulation if the patient's albumin level is < 2.5 mg/dL with heavy proteinuria (> 10 g/day), a BMI > 35 kg/m2, a family history of genetic venous thromboembolism, class III-IV heart failure, or even prolonged immobilization or surgery. The word "consider" always trips me up a little because I just need someone to tell me what to do.

Dr Topf gave us the GNTools calculator as a possible resource. If you've not had a chance to look at it, it's a really nice tool. You plug in the patient's age and serum albumin level and a bunch of other factors, including how risk-averse you are. How willing are you to risk a bleed using anticoagulation? You can actually plug in 1 in 2 chance, 1 in 5 chance, 1 in 10 chance, etc. Based on that, it will tell you whether there would be benefit to anticoagulation in this patient, and whether the benefits outweigh the risk. I thought that was a really nice tool to help when you're considering anticoagulation and no one's actually telling you what to do.

Nephrotic or Nephritic?

Watto: Speaking of the features of nephrotic syndrome, we have a great infographic from this episode.

It shows nephrotic vs nephritic syndrome and which labs you would order for each. It's really useful to refer back to it. Paul's already mentioned hypercoagulability, one of the features of nephrotic syndrome. Edema is the other clinical feature. Labs show nephrotic-range proteinuria. We had a good discussion about how you measure that. You also see hyperlipidemia and a low albumin level.

In nephritic syndrome, you'd expect urine sediment with red cells, white cells, and protein, but not to the same level as you see with nephrotic syndrome. The patient usually has a more prominent creatinine elevation and hypertension as well. That's how you can remember the difference between nephrotic and nephritic.

The labs differ also. For nephritic syndrome, you will be getting complement levels and antineutrophil cytoplasmic autoantibodies (ANCAs).

For nephrotic syndrome, you will get the antiPLA2R, but also hepatitis B and C, and HIV. What am I forgetting? SPEP and UPEP — we just did an episode on MGUS.

Brigham: If you want to enjoy more kidney pearls, stay dehydrated and take a listen to episode #250, Nephrotic Syndrome vs Glomerulonephritis with Kidney Boy, Dr Joel Topf. We talk about all of these fascinating topics and more.

Watto: You can also join our mailing list and get a PDF copy of our show notes every week. Thank you for watching.

The Curbsiders are a national network of students, residents, and clinician educators from across the country, representing 15 different institutions. They "curbside" experts to deconstruct various topics in the world of medicine to provide listeners with clinical pearls, practice-changing knowledge, and bad puns. Learn more about their contributors and follow them on Twitter.

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