Renal tubular injury is present in acute inflammatory bowel disease prior to the introduction of drug therapy

Abstract

Background : 5‐aminosalicylic acid (5‐ASA) has been associated with renal complications in inflammatory bowel disease. Renal function is typically monitored using serum creatinine; however, significant disease may predate increases in creatinine. Aims : To identify whether markers of early renal disease (urinary albumin, α‐1‐microglobulin [α‐1‐M] and N‐acetyl‐β‐D‐glucosaminidase [NAG], and serum cystatin C) are useful in the assessment of renal function in inflammatory bowel disease patients receiving 5‐ASA. Methods : Twenty‐one patients with a new diagnosis of inflammatory bowel disease were investigated. Samples were taken at diagnosis, and at 3‐monthly intervals after the commencement of 5‐ASA, for 1 year. Results : Mean creatinine clearance was 100 mL/min and did not change following treatment. Inflammatory bowel disease was not associated with albuminuria. Urinary N‐acetyl‐β‐D‐glucosaminidase and α‐1‐microglobulin at diagnosis were increased in 10 (48%) and 11 (52%) patients, respectively: treatment was not associated with consistent changes in urinary protein excretion. There was a significant correlation between cystatin C and creatinine clearance both at diagnosis (r=–0.533, P=0.0275) and combining the initial and follow‐up data (r=–0.601, P < 0.01), but not between creatinine and creatinine clearance (P > 0.05). Conclusions : Tubular proteinuria is an extra‐intestinal manifestation of inflammatory bowel disease irrespective of 5‐ASA treatment. Tubular proteins are not useful predictors of an adverse renal response to 5‐ASA. Serum cystatin C may be an improved marker of glomerular filtration rate in this setting.

The Histopathologic Spectrum of Kidney Biopsies in Patients with Inflammatory Bowel Disease

“…However, kidney tubular damage, in the form of proteinuria and enzymuria, has been frequently observed in IBD and is more strongly correlated with disease activity than therapy (41)(42)(43). There have also been several case reports of interstitial nephritis in therapy-naive patients to include the development of kidney failure before or concurrently with the diagnosis of bowel inflammation (44)(45)(46)(47)(48)(49)).…”

Current application of proteomics in biomarker discovery for inflammatory bowel disease

“…Schreiber et al [47] reported the possible link between high dose 5aminosalicylic acid (5ASA) and modulated urinary protein concentrations. However, other groups have suggested that these urinary pro teins reflect renal extraintestinal manifestations rather than 5ASA toxicity [48,49] . Derici et al [50] identified an association between similar urinary proteins and disease activity in UC, however none of these have been conclusive.…”

Netrin-1 regulates colon-kidney cross talk through suppression of IL-6 function in a mouse model of DSS-colitis

“…This noncalculus obstruction (NCO) is on the right in the great majority of patients. Renal tubular injury was also seen in many IBD patients (7). A recent study also showed the presence of an anti-brush border antibody in these IBD patients that cross-reacts with a kidney proximal tubular brush-border membrane antigen.…”

“…A description of tubulointerstitial disease unrelated to the consumption of nephrotoxic agents in such patients is not extensive. However, the presence of tubular injury in IBD patients is increasingly appreciated even before the start of nephrotoxic drugs such as aminosalicylate (7,10,16,18). Moreover, it is now even recommended for the clinicians to look for the presence of tubulointerstitial disease and renal failure in IBD patients (16).…”