Membranous nephropathy and pregnancy

I promised a full examination of the renal biopsy in pregnancy.

This is the longest post I have ever done and so I have segmented it into two parts:

1. My conclusions along with  discussion of the survey of clinical decision making
2. The supporting data, which is structured as a detailed annotated bibliography.

My conclusions:

The renal biopsy is as safe in pregnancy as it is outside of pregnancy. Ultrasound guidance and modern understanding of coagulopathy paired with aggressive use of antihypertensives makes this an acceptable risk in pregnancy.  This is a field of medicine that accepts risk to the fetus to in the name of better diagnostic data, see amniocentesis.

As long as the blood pressure is controlled, and the patient is not coagulopathic, if you need the biopsy, get the biopsy.

However, I have not been fully satisfied that the diagnostic data is that useful in most situations. The therapeutic options in pregnancy seem pretty narrow:

• IV methylprednisolone with or without azathioprine
• Therapeutic abortion
• Delivery of the infant prematurely
• Symptomatic therapy

Given those options, a biopsy will not make a difference in many situations.

Timing becomes critical as a therapeutic abortion and delivery of the infant both have narrow windows of opportunity. The decision to use symptomatic treatment will not be influenced by histologic findings.

That leaves IV methylprednisolone. In every case report I read where methylprednisolone +/– azathioprine was used I thought the decision to use it coud have been made solely from the patient's symptoms and that the biopsy results didn't really influence that decision. In every case the mother had increasing blood pressure, creatinine and proteinuria 20+ weeks into the pregnancy. It was too early to deliver the baby and steroids were used to buy time for the fetus to grow prior to delivery.

Here are the situations I would recommend doing a biopsy:

• First trimester with early signs that the patient may be in for a rocky pregnancy due to renal disease. There are three risk factors: nephrotic range proteinuria, renal failure with a creatinine over 1.5 and hypertension. Getting a pathologic diagnosis at this point could allow termination of the pregnancy if any frightening diagnosis are made, i.e. lupus nephritis, scleroderma, crescentic GN, possibly MPGN. Outside of those findings I doubt the biopsy will actually change your therapy. I am sympathetic to the argument that each of these diagnosis has pretty good serologic tests that could decrease the need for the biopsy. That said the decisions are weighty enough that I would prefere a tissue diagnosis.
• The only other situation would be a patient with symptoms suggestive of scleroderma presenting late in pregnancy, 20+ weeks with high blood pressure. The right choice here is probably terminating the pregnancy. The mother's life is in danger and the condition will not respond to steroids, the only therapeutic option available. I would like to get a tissue diagnosis to confirm prior to proceeding down that road.

In the survey I presented I had 6 different clinical scenarios, they are summarized below:

1. Gestational age 12 weeks, nephrotic syndrome, normal BP, normal Cr
2. Gestational age 24 weeks, nephrotic syndrome, normal BP, normal Cr
3. Gestational age 12 weeks, nephrotic syndrome, normal BP, elevated Cr
4. Gestational age 24 weeks, nephrotic syndrome, normal BP, elevated Cr
5. Gestational age 12 weeks, nephrotic syndrome, elevated BP, elevated Cr
6. Gestational age 24 weeks, nephrotic syndrome, elevated BP, elevated Cr

So I would recommend a biopsy in case 3 and 5, and think long and hard about case 1. I wouldn't biopsy 2, 4 or 6. I would start steroids in case 6 and consider it in case 4. I didn't vote this way, as my opinions have changed the more I learned and thought about this. Of note, the only maternal-fetal medicine doctor voted exactly as I just described. 

As of Sunday April 3rd we had 53 votes:

81% are nephrologists. I guess we know who reads PBFluids.

And 76% are from North America. And that compares favorably to the overall traffic to the blog:

from Google Analytics

Mexico represents 0.8% of blog traffic but showed up big time for 4% of the sample.

Here is how the community voted:

1. Gestational age 12 weeks, nephrotic syndrome, normal BP, normal Cr.
   I voted BIOPSY, the community:
   
   
   
   
   
2. Gestational age 24 weeks, nephrotic syndrome, normal BP, normal Cr.
   I voted NO biopsy, the community:
   
   
   
   
3. Gestational age 12 weeks, nephrotic syndrome, normal BP, elevated Cr.
   I voted BIOPSY, the community:
   
   
   
   
4. Gestational age 24 weeks, nephrotic syndrome, normal BP, elevated Cr.
   I voted NO biopsy, the community:
   
   
   
   
5. Gestational age 12 weeks, nephrotic syndrome, elevated BP, elevated Cr.
   I voted BIOPSY, the community:
   
   
   
   
6. Gestational age 24 weeks, nephrotic syndrome, normal BP, elevated Cr.
   I voted NO biopsy, the community:
   
   
   

The thing that confuses me is why the percent of people that want a biopsy at 12 weeks seems to fall as the patient gets sicker: 49% in case 1 to 34% in cases 3 and 5. What happened to 8 of the pro-biopsy doctors?

The same puzzling trend held for the 24 week gestational age with the biopsy rate being highest, 81%, in the healthiest and as the patient developed decreased renal function and hypertension it fell to 64% and 57%.

I broke down the data for attendings versus fellows:

And now you can see where those missing biopsies for the patient at 12 weeks went. Over half the fellows were willing to biopsy the asymptomatic nephrotic syndrome at 12 weeks. But the bravado disappeared if you added a bit of hypertension (scenario 3) with the biopsy rate falling below 20%.

The attendings were more likely to biopsy the patient in just about every scenario with an overall biopsy rate of 59% versus 49% for fellows.

In the U.S. versus the world:

It looks like a general trend for doctors outside of the US to be less likely to biopsy patients, at least in the first trimester.

Here is a link to the raw data in case anyone is interested. And yes I did see the fellow from Lebanon double voted, but given the importance of Chicago in the study of both renal disease in pregnancy and glomerular disease, I figured a vote early, vote often policy was appropriate.

Look here for the link to the second post with the annotated bibliography.