Celiac Disease and Renal Comorbidities

Celiac disease is an autoimmune disorder caused by gluten and presents with classic gastrointestinal symptoms or a wide range of extraintestinal manifestations. Individuals with celiac disease may be asymptomatic or suffer from very mild symptoms. An association with various other autoimmune disorders, such as type 1 diabetes and autoimmune thyroidal disease, has been detected in celiac disease. The prevalence of celiac disease is increasing due to improved diagnostic methods and also to a true increase in prevalence rates.

The prevalence of chronic kidney disease is moreover increasing worldwide. The link between celiac disease and renal disorders has been recognized but the results are still somewhat contradictory. In celiac disease, an association especially with glomerulonephritis, diabetic nephropathy and end-stage renal disease has been shown. The possible connection between celiac disease and IgA nephropathy (IgAN), the most common chronic glomerulonephritis, has aroused increased interest in this field of study.

This dissertation investigated the prevalence of celiac disease in patients suffering from nephrological disorders, especially IgAN. The risk of various kidney comorbidities in celiac disease patients was also studied. The dissertation consists of four sub-studies. In Study I, the prevalence of celiac disease autoimmunity (previous diagnosis of celiac disease or positive celiac disease-specific autoantibody levels) was investigated in 827 patients undergoing kidney biopsy. The possible influence of such autoimmunity on the clinical picture of IgAN was also studied. Study II observed the prevalence of diagnosed celiac disease, screen-detected celiac disease autoimmunity (positive celiac disease-specific autoantibody levels), and another common chronic bowel disorder, inflammatory bowel disease (IBD) in 629 patients with IgAN in recent decades. The aim of Study III was to ascertain whether celiac disease-type tissue transglutaminase-specific autoantibody deposits are found in the kidney biopsies of IgAN patients with or without celiac disease. The register-based Study IV compared the risk of glomerulonephritis, such as IgAN, diabetic nephropathy, interstitial nephritis, and end-stage renal disease between patients (1,072 celiac disease and 368 dermatitis herpetiformis patients) and age- and sex-matched reference subjects.

According to Study I, the prevalence of celiac disease autoimmunity was 5.4% in patients undergoing kidney biopsies and in IgAN even higher, 8.2%. Such autoimmunity may have an effect on worse clinical outcome of IgAN as the patients with autoimmunity had higher levels of creatinine than the group without autoimmunity. It was observed in Study II that the prevalence of celiac disease decreased over time in IgAN while the opposite was detected for the prevalence of IBD. Study III showed that celiac disease-type autoantibody deposits can be found in kidney biopsies of gluten-consuming IgAN patients with celiac disease but also among some of the IgAN patients without celiac disease. Interestingly, these deposits may already present prior to clinical diagnosis of celiac disease. In Study IV an elevated risk of kidney disorders, especially IgAN, was detected in celiac disease. The celiac disease phenotype had an effect on the risk of renal comorbidities as no similar risk was seen among patients with dermatitis herpetiformis.

The findings of this dissertation show that patients with kidney disorders, especially with IgAN, may have an increased risk of celiac disease. Furthermore, celiac disease patients are at higher risk for renal comorbidities, especially for glomerulonephritis. No official global guidelines concerning the screening of these diseases have so far been published. The association between the diseases is important to remember, and an easily available urine dipstick test and serum creatinine test for the investigation of renal function in celiac disease patients and a tissue transglutaminase antibody test for screening for celiac disease in individuals with renal disorders may be considered for clinical practice when treating these patient groups. However, this study area still needs further investigation. Further studies are likewise called for to investigate the exact common mechanisms in the association between celiac disease and renal disorders. In addition, new knowledge is needed of the influence of various celiac disease phenotypes on the risk of renal comorbidities.