Renal Involvement in Inflammatory Bowel Disease Patients

Inflammatory bowel disease (IBD) is a chronic, relapsing and remitting inflammatory condition predominantly affecting the gastrointestinal (GI) tract that results from complex interplay of the individual's genetic makeup, the environment, the gut microbiota and the host immune response .

IBD is an umbrella disorder that covers Crohn's disease, ulcerative colitis and IBD unclassified . Crohn's disease is characterised by transmural inflammation that can affect any part of the GIT with characteristic skip lesions of healthy tissues, while ulcerative colitis is a continuous mucosal inflammation largely confined to the colon. 'IBD unclassified' is a term used when the endoscopic and histological features are not sufficient to favour one of the other diagnoses.

The prevalence of extraintestinal manifestations (EIMs) in inflammatory bowel diseases (IBDs) varies from 6%-46%.

The mechanisms that have been suggested include contributions of genetic factors, infectious agents, circulating bacterial endotoxins and immune-complex deposition.

EIMs can involve almost every organ system. It is not always possible to identify the pathophysiological mechanism underlying an organ's involvement in IBD; it may originate from the same pathophysiological mechanism as intestinal disease, or as a secondary complication of IBDs, Renal involvement has been considered as an EIM and has been described both in Crohn's disease (CD) and in ulcerative colitis (UC).

Renal EIMs and IBD-related therapy are potential risk factors for the development of renal insufficiency (both acute and chronic) in patients with CD and UC.

Chronic kidney disease (CKD) is a type of kidney disease in which there is gradual loss of kidney function over a period of months to years.

CKD is defined as kidney damage or glomerular filtration rate (GFR) <60 ml /min/1.73 m2 for 3 months or more .

GFR can be estimated from calibrated serum creatinine and estimating equations ,such as the Modification of Diet in Renal Disease (MDRD) study equation or the Cockcroft -Gault formula .

Kidney disease severity is classified into five stages according to the level of GFR.

1. Stage 1: Slightly diminished function; kidney damage with normal or relatively high GFR (≥90 ml/min/1.73 m2)
2. Stage 2: Mild reduction in GFR (60-89 ml/min/1.73 m2) with kidney damage
3. Stage 3: Moderate reduction in GFR (30-59 ml/min/1.73 m2)
4. Stage 4: Severe reduction in GFR (15-29 ml/min/1.73 m2)
5. Stage 5: Established kidney failure (GFR <15 ml/min/1.73 m2)

The most frequent renal diseases in patients with IBD are: nephrolithiasis, tubulointerstitial nephritis, glomerulonephritis and amyloidosis .

As in other EIMs, renal manifestations can be considered as dependent on the same immunological mechanism that determines intestinal inflammatory diseases, directly related to intestinal activity. Another hypothesis to be considered is that renal involvement is an independent of bowel disease, due to its autoimmune mechanism of action; otherwise, it could be related to metabolic disorders that develop in IBD. Finally, kidney pathologies in IBD have been associated with side e!ects of drugs Aminosalicylates, azathioprine, cyclosporin and TNFα inhibitors may be involved in renal impairment. However, it is not always possible to clarify the mechanism of these drugs in kidney damage. In many cases it remains unclear whether renal impairment is an EIM or a drug adverse effect