5-aminosalicylic acids and the risk of renal disease: A large British epidemiologic study

doi:10.1053/j.gastro.2004.03.016

Gastroenterology

Volume 126, Issue 7, June 2004, Pages 1733-1739

https://doi.org/10.1053/j.gastro.2004.03.016 Get rights and content

Abstract

$Background & Aims:$ This study was performed to quantify the risk of renal disease in patients using aminosalicylates (5-ASA). $Methods:$ Data from the United Kingdom General Practice Research Database were used to estimate the incidence of renal disease in adult patients with inflammatory bowel disease (IBD) or prescription for 5-ASA and in patients without IBD. In a nested case-control analysis, each case of renal disease was matched to 5 controls. $Results:$ Among the 19,025 5-ASA users with IBD, 130 patients developed renal disease (incidence rate of 0.17 cases per 100 patients per year). The incidence among patients with IBD but without 5-ASA use was 0.25 and among patients without IBD was 0.08. In the case-control analysis, the crude odds ratio (OR) for renal disease in current 5-ASA users was 1.60 (95% confidence interval [95% CI]: 1.14–2.26); the adjusted OR was 0.86 (95% CI: 0.53–1.41). For recent users, the crude OR was 4.18 (95% CI: 2.59–6.76) and adjusted OR 2.48 (95% CI: 1.33–4.61); for past users (last prescription more than 12 months before), 1.71 (95% CI: 1.09–2.70) and 0.99 (95% CI: 0.55–1.76), respectively. Although the numbers were small, mesalazine and sulfasalazine users had comparable risks (crude OR for current and recent users of OR 2.08 [95% CI: 1.44–3.01] and 1.84 [95% CI: 1.20–2.82], respectively). In only a few records was renal disease attributed to interstitial nephritis or 5-ASA use. $Conclusions:$ Users of 5-ASA have an increased risk of renal disease that may be partly attributable to the underlying disease. Although renal disease is a recognized adverse effect of 5-ASA, the incidence appears to be low and does not appear to be related to either the dose or type of 5-ASA used.

Section snippets

Data source

In the United Kingdom, health care delivery is centered on general practitioners (GPs) whose responsibilities include primary health care and specialist referrals. The information for this study was obtained from the General Practice Research Database (GPRD), which contains the computerized medical records of general practices across the United Kingdom.24 Approximately 6% of the total registered population of England and Wales is represented in the database, and it includes a cumulative total

Results

A total of 37,984 patients in the GPRD population had a record of IBD or a prescription for 5-ASA; 19,025 were assigned to the 5-ASA/IBD cohort. The mean age of these patients was 48 years, and 53.0% were women. They were followed for an average of 6 years. Their mean number of 5-ASA prescriptions during follow-up was 19.4 (median 10): The mean duration of each prescription was 1 month. The distribution of the type of prescribed 5-ASA in the 5-ASA/IBD cohort was as follows in these patients:

Discussion

This study found that IBD patients who were 5-ASA users had an increased risk of renal disease. However, after adjustment, the risks of 5-ASA users were comparable with controls. In only a few records was renal disease attributed to interstitial nephritis or 5-ASA use. These findings indicate that the incidence of 5-ASA-induced renal disease is rare.

We also found that both IBD patients not using 5-ASA drugs and past 5-ASA users had increased risks of renal disease. Risk of renal disease was

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An anti-inflammatory medication termed Mesalazine (MLZ) is generally recommended to prevent inflammatory bowel diseases (IBD). However, its prolonged usage has been associated with the risk of kidney failure. Therefore, there is a pressing need for the development of effective electrocatalysts to enable rapid detection of MLZ in the environment. Layered double hydroxides (LDHs) have emerged as promising candidates in the realm of sensor technology due to their adjustable interlayer spacing and large surface area. In this study, we utilized the hydrothermal method to synthesize cobalt aluminum-layered double hydroxide (CoAl-LDH) and evaluated its suitability as an active electrocatalyst for MLZ detection. The prepared CoAl-LDH was characterized for its physicochemical attributes employing XRD, FT-IR, XPS, FESEM, and TEM analysis. Subsequent examination of its electrochemical properties via voltammetric techniques revealed that the CoAl-LDH-modified glassy carbon electrode (GCE) exhibited enhanced electrocatalytic activity. Notably, the CoAl-LDH/GCE demonstrated a lower detection limit of 0.029 µM and a linear detection range spanning from 0.049 to 665.1 µM. Furthermore, the modified electrode demonstrated favorable attributes such as good repeatability, reproducibility, and stability. Real-time application of the modified electrode in the spiked water and urine samples yielded satisfactory recovery results, indicating its potential for practical use in environmental monitoring.
Inflammatory Bowel Disease With Chronic Kidney Disease and Acute Kidney Injury
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It remains unclear whether inflammatory bowel disease is associated with long-term risk of chronic kidney disease (CKD) and acute kidney injury (AKI) in the general population.
A total of 417,302 participants, including 2,940 patients with ulcerative colitis and 1,261 patients with Crohn's disease, without previous CKD and AKI at baseline (2006–2010) from the UK Biobank were included. The study outcomes included incident CKD and AKI, ascertained by self-report data and data linkage with primary care, hospital admissions, and death registry records. Analysis was conducted in 2022.
During a median follow-up of 12.5 years, 13,564 and 14,331 participants developed CKD and AKI, respectively. Compared with the hazard ratio for non-inflammatory bowel diseases, the hazard ratios for CKD and AKI related to inflammatory bowel diseases were 1.57 (95% CI=1.37, 1.79) and 1.96 (95% CI=1.74, 2.20) after adjustments for age, sex, and race and were 1.32 (95% CI=1.15, 1.51) and 1.70 (95% CI=1.51, 1.91) after further adjustments for biological, behavioral, and socioeconomic factors in addition to mental health and self-rated health. Similar results were found for patients with Crohn's disease (adjusted hazard ratio=1.38 (95% CI=1.09, 1.75) for CKD and 1.62 [95% CI=1.30, 2.02] for AKI) and those with ulcerative colitis (adjusted hazard ratio=1.29 (95% CI=1.09, 1.51) for CKD and 1.71 [95% CI=1.49, 1.97] for AKI) in the fully adjusted models. Genetic risks of kidney diseases did not significantly affect the association of inflammatory bowel disease with incident CKD and AKI (both p-interactions>0.05). The association between inflammatory bowel disease and the risk of incident CKD (p-interaction=0.010) and AKI (p-interaction<0.001) were stronger in younger participants than in older participants.
Inflammatory bowel disease was associated with higher risks for CKD and AKI, independent of genetic risks of kidney diseases.
Glomerulonephritis and inflammatory bowel disease: A tale of gut-kidney axis dysfunction
2023, Autoimmunity Reviews
The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased over the past decades, imposing a growing socioeconomic burden on healthcare systems globally. Most of the morbidity and mortality related to IBD is typically attributed to gut inflammation and its complications; yet the disease is characterized by various extraintestinal manifestations that can be severe. Glomerulonephritis (GN) is of particular interest since a significant proportion of patients evolve into end-stage kidney disease, requiring kidney replacement therapy and associated with high morbidity and mortality.
Herein, we review the GN landscape in IBD and define the clinical and pathogenic associations reported to date in the literature. Underlying pathogenic mechanisms suggest either the initiation of antigen-specific immune responses in the inflamed gut that cross react with non-intestinal sites, such as the glomerulus, or that extraintestinal manifestations are gut-independent events that occur due to an interaction between common genetic and environmental risk factors. We present data associating GN with IBD either as a bona fide extraintestinal manifestation or reporting it as an extraneous co-existing entity, involving various histological subtypes, such as focal segmental glomerulosclerosis, proliferative GN, minimal change disease, crescentic GN, but most emphatically IgA nephropathy. Supporting the pathogenic interplay between gut inflammation and intrinsic glomerular processes, enteric targeting the intestinal mucosa with budesonide reduced IgA nephropathy-mediated proteinuria. Elucidating the mechanisms at play would provide insight not only into IBD pathogenesis but also into the gut's role in the development of extraintestinal diseases, such as glomerular diseases.
Crohn's Disease of the Elderly: Unique Biology and Therapeutic Efficacy and Safety
2022, Gastroenterology Clinics of North America
Kidney function monitoring to prevent 5-aminosalicylic acid nephrotoxicity: What the gastroenterologist should know
2021, Digestive and Liver Disease
Citation Excerpt :
In the first one, 59 news cases of nephrotoxicity were identified by the British Society of Gastroenterology (BSG) during a two-years prospective study [32]. In the second study, 130 out of 19,025 IBD patients using 5-ASA developed renal disease from the United Kingdom General Practice Research Database [16]. In addition, the prevalence of deterioration of kidney function after 5-ASA treatment is of 0.06% according to the safety data from 18 clinical trials assessing the efficacy of 5-ASA in 1638 IBD patients [33]; this prevalence rate is low, but the follow-up was only of 6 to 12 months, thus underestimating it.
The kidney function monitoring is recommended in routine practice to detect 5-aminosalicylic acid (5-ASA) related nephrotoxicity, although is not standardized. The optimal monitoring is unknown, especially the best timing and which tests to perform. We summarized why, how, and when to perform the monitoring for patients treated with 5-ASA and provided an overview of the current guidelines on this topic.
Relevant studies on this topic were searched in PubMed, Embase, and Web of Science databases from July to August 2020.
Serum creatinine, the estimated glomerular filtration rate, and 24-h proteinuria are the 3 main tests used for the monitoring in daily practice. Regarding the timing, several monitoring strategies have been proposed and guidelines are available too, but they provide conflicting information. To date, there is no medical evidence-based that one strategy is better than another. Comorbidities, chronic renal disease, use of nephrotoxic drugs or concomitant steroid therapy also impact the nephrotoxicity risk. Based on the literature review we proposed a kidney function monitoring strategy to guide physicians in clinical practice.
A baseline assessment should be performed in all patients treated with 5-ASA. The monitoring should be carried out according to the other nephrotoxic factors. A tight monitoring may reduce morbidity and mortality of drug nephrotoxicity.
Inflammatory Bowel Diseases Are Associated With an Increased Risk for Chronic Kidney Disease, Which Decreases With Age
2020, Clinical Gastroenterology and Hepatology
It is not clear what factors affect risk of chronic kidney disease (CKD) in patients with inflammatory bowel disease (IBD); increased risk has been inconsistently associated with use of 5-aminosalicylates (5-ASAs). We aimed to calculate the relative hazard of CKD among patients with IBD, adjusted for CKD risk factors, and to determine whether IBD medications are associated with change in estimated glomerular filtration rate (eGFR).
We performed a retrospective cohort study of data from The Health Improvement Network. Patients with IBD (n = 17,807) were matched for age, sex, and practice to individuals without IBD (n = 63,466). The relative hazard of CKD, stages 3 through 5D, in patients with IBD was calculated using a Cox proportional hazards model adjusted for common CKD risk factors. We also evaluated the association of 5-ASAs, azathioprine, and methotrexate with change in eGFR using a longitudinal model.
After we controlled for risk factors associated with CKD, we found IBD to be associated with development of CKD in patients 16–77 years old. As patient age increased, the adjusted hazard ratio for CKD decreased monotonically, from 7.88 (95% CI, 2.56–24.19) at age 16 to 1.13 (95% CI, 1.01–1.25) at age 77. In the longitudinal analysis, exposure to 5-ASAs or methotrexate was not associated with change in eGFR, whereas azathioprine was associated with a slightly higher eGFR (0.32 mL/min/1.73 m²; 95% CI, 0.16–0.48).
In a retrospective study of more than 80,000 persons, we found that IBD is associated with increased risk of CKD, and the hazard ratio is highest among younger patients. Commonly used non-biologic therapeutic agents were not associated with lower eGFR.

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^☆: Supported by Procter & Gamble Pharmaceuticals.

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Clinical-alimentary tract5-aminosalicylic acids and the risk of renal disease: A large British epidemiologic study☆

Abstract

Section snippets

Data source

Results

Discussion

Am J Kidney Dis

Lancet

Gastroenterology

Gastroenterology

Sulphasalazine induced renal failure

Gut

Nephrotic syndrome associated with sulfasalazine

Br Med J

Sulphasalazine and nephrotic syndrome

Am J Gastroenterol

Mesalazine associated nephrogenic diabetes insipidus presenting as weight loss

Gut

Acute interstitial nephritis due to 5-aminosalicylic acid

Can Med Assoc J

Mesalazine induced interstitial nephritis

Gut

Mesalazine-associated tubulo-interstitial nephritis in inflammatory bowel disease

Clin Nephrol

Late onset interstitial nephritis

Br Med J

Interstitial nephritis in patients with inflammatory bowel disease treated with mesalamine

Clin Gastroenterol

Early renal failure after mesalazine (case report)

Acta Univ Palacki Olumuc Fac Med

Acute interstitial nephritis due to 5-aminosalicylic acid

Internist

Nephritis due to 5-aminosalicylic acid

Deutsche Med Wschr

Side effects of medicinestubulointerstitial nephritis by mesalazine (5-ASA) drugs

Ned Tijdschr Geneesk

Chronic interstitial nephritis after treatment with 5-aminosalicylic acid

Deutsche Med Wschr

Nephrotic syndrome after treatment with 5-aminosalicylic acid

Br Med J

Mesalazine-induced interstitial nephritis

Neprol Dial Transplant

Nephrotic syndrome from 5-ASA for ulcerative colitis

J Clin Gastroenterol

Clinical-alimentary tract
5-aminosalicylic acids and the risk of renal disease: A large British epidemiologic study☆