If you are anything like me and have worked in renal nutrition care for a long time, you are likely familiar with celiac disease, but perhaps not necessarily comfortable with knowing all the ins and outs of the diet.
I will admit that I also wasn’t aware of a potential connection between IgA nephropathy and celiac disease until it was brought to my attention by my colleague! Thank goodness for good colleagues!
The key reference for today’s post can be found here: https://pmc.ncbi.nlm.nih.gov/articles/PMC10117010/
What is IgA nephropathy?
IgA nephropathy occurs when clumps of immunoglobulin A (IgA) are deposited in the glomerular mesangium (parts of the kidneys). Over time, this can lead to inflammation and kidney damage.
What is known about celiac disease and IgA nephropathy?
According to the National Kidney Foundation, celiac disease is a known risk factor for IgA nephropathy. However, what hasn’t been well established is whether the relationship is casual (meaning the two conditions just happen to occur together) or causal (meaning celiac disease causes IgA nephropathy).
Why might the distinction between a casual and causal relationship matter?
It is well established that for people diagnosed with celiac disease, following a gluten-free diet is essential for preventing negative health outcomes, including bowel cancer. However, to date, we don’t know whether we should also be telling people living with celiac disease that they need to follow a gluten-free diet to prevent kidney damage.
What did this study do?
In the study noted above, the authors’ goal was to assess whether there could be a causal relationship between celiac disease and IgA nephropathy.
To do this, chart records were reviewed to identify people who had biopsy-proven IgA nephropathy. These people were then invited to have blood testing for celiac disease using anti-tTG antibodies.
From there, the goal was to offer people who had elevated tTG levels an endoscopic duodenal biopsy to assess the extent of intestinal villous damage.
In addition, kidney biopsy samples from health records were investigated for evidence of celiac-disease-associated tTG deposits/damage (IgA anti-TG2 deposits).
Who participated in the study?
Of the original 151 people who had kidney biopsies, unfortunately, only 32 consented to tTG testing. Interestingly, five of these people (15.6%) had elevated tTG levels. Of these five people, two consented to duodenal biopsies, and both were found to have confirmed celiac disease and were put on a gluten-free diet.
Of the five people who had tTG testing, four had kidney biopsies that showed evidence of TG deposits. None of the 27 people who had normal tTG levels had TG deposits in their kidneys.
Of the remaining 105 kidney biopsy tissues available from people who did not consent to tTG testing, only one of the 105 (<1%) showed TG deposits in the kidney.
Overall, 5 of the 137 kidney biopsies reviewed showed evidence of celiac disease-associated TG deposits (3.6%).
What does this study tell us?
Unfortunately, the sample size of this study was small, so we need to be cautious when interpreting the results.
However, this study certainly points to a potential causal relationship, such that untreated celiac disease may contribute to tTG-associated IgA deposits in the kidney, potentially leading to IgA nephropathy.
However, because the people who were confirmed to have celiac disease were lost to follow-up—and there were only two of them—this study can’t tell us for sure whether people who have both IgA nephropathy and celiac disease and start following a gluten-free diet will experience complete remission.
That being said, the authors highlighted three other studies that suggest it might:
- One study used a mouse model and demonstrated that following a gluten-free diet resulted in remission of IgA nephropathy.
- Two case reports have been published reporting remission of IgA nephropathy in people who had celiac disease and started following a gluten-free diet.
Taken together, these studies provide some hope, but they should be interpreted cautiously.
Should all people with IgA nephropathy be screened for celiac disease?
There are no clear guidelines that recommend screening people presenting with IgA nephropathy for celiac disease.
However, a 2021 case report of an adolescent boy who presented with IgA nephropathy without GI symptoms and experienced complete remission after five years on a gluten-free diet prompted the authors of that article to recommend routine screening for everyone with IgA nephropathy.
That being said, the authors of the Dutta et al. study highlighted that only a small percentage of IgA nephropathy cases had IgA anti-TG2 deposits, which makes a blanket recommendation for celiac screening challenging.
Takeaways
- For people living with celiac disease, it appears possible that consuming gluten may contribute to IgA nephropathy and that following a gluten-free diet, particularly before reaching end-stage kidney disease, may result in remission.
- Current guidelines don’t address whether all people with IgA nephropathy should be offered celiac disease screening, although authors of one case report have recommended routine screening.
