Individuals with a genetic predisposition to celiac disease have an increased risk for nephropathy and chronic glomerulonephritis, as well as a reduced level of estimated glomerular filtration rate (eGFR), according to a new study.
Previous observational studies have linked celiac disease to kidney conditions including elevated risk of end-stage renal disease and immunoglobulin A nephropathy (IgAN). However, to combat potential biases associated with observational studies, researchers led by Ya-mei Ge, of Hubei University of Chinese Medicine, Wuhan, China, used Mendelian randomization using nonoverlapping European population data to examine the link between celiac disease and 10 kidney traits in whole-genome association studies.
“The study has enhanced our understanding of the mechanisms underlying the development of kidney diseases in individuals with celiac disease and lays the groundwork for evaluating the risk of kidney diseases in celiac disease patients and reducing the incidence of kidney diseases in a clinical setting,” the researchers wrote in Medicine.
Findings Clarify Increased Risk of Kidney Diseases
An inverse variance weighting method showed that a genetic susceptibility of celiac disease was associated with a 44% increased odds of IgAN (odds ratio [OR]=1.44; 95% CI, 1.17-1.78) and a 15% increased odds for chronic glomerulonephritis (OR=1.15; 95% CI, 1.08-1.22). A decline in eGFR was also identified.
A similar method of analysis was recently used by another group of researchers in China to look at a potential link between celiac disease and chronic kidney disease. The team, led by Zhimin Chen, of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China, used a two-sample Mendelian randomization approach to study data from three genome-association studies of individuals of European ancestry. According to the researchers, this method design allowed for the “reduction of confounding factors and the avoidance of reverse causation.” Chen and colleagues also found a potential causal relationship between celiac disease and increased risk for chronic kidney disease.
These two studies are only the most recent in what appears to be mounting evidence showing associations between celiac disease and renal disease.
Kidney Disease Risk Doubled in Individuals with Celiac Disease
In 2016, a meta-analysis looked at eight studies– six cohort studies and two cross-sectional studies – of kidney diseases among patients with and without celiac disease. Patients with celiac disease had double the risk of overall kidney diseases compared with those without (pooled risk ratio [RR]=2.01; 95% CI, 1.44-2.81). This risk remained after adjusting for potential confounders. In addition, patients with celiac disease also had an increased risk for end-stage renal disease (RR=2.57), diabetic nephropathy (RR=1.49), and IgAN (RR=2.62).
The meta-analysis researchers acknowledged potential limitations of the work. However, they wrote that “although the majority of celiac disease patients have no clinical manifestation of kidney diseases, physicians should be aware of this association.”
Does Celiac Disease Phenotype Impact Renal Risk?
More recently, Rakel Nurmi, of the Celiac Disease Research Center, Tampere University, Finland, and colleagues published work indicating that the risk for kidney disease might vary by the phenotype of celiac disease. Looking at more than 40 years of data, their study also showed that individuals with celiac disease had an increased risk for kidney diseases – particularly IgAN– but this risk was not seen in individuals with dermatitis herpetiformis, a cutaneous manifestation of celiac disease.
According to the researchers, the reason that patients with dermatitis herpetiformis had a different risk for renal disorders was unclear.
“Increased intestinal permeability and mucosal inflammation have been suggested to link bowel diseases and glomerulonephritis, and because celiac‐type enteropathy is milder in dermatitis herpetiformis than in celiac disease, the bowel pathology may affect the different risk of renal involvement,” they wrote.
Nurmi and colleagues again wrote that “awareness of possible associated renal diseases, especially glomerulonephritis, is necessary when treating patients with celiac disease. At least an easily accessible urine dipstick test and serum creatinine measurements could be used to exclude these renal comorbidities in celiac disease.”
The researchers involved in these studies were contacted for comment but did not respond in time for publication.