Diabetic kidney disease (DKD) is a progressive disorder, which is increasing globally in prevalence due to the increased incidence of obesity and diabetes mellitus. Despite optimal clinical management, a significant number of patients with diabetes develop DKD. Hence, hitherto unrecognized factors are likely to be involved in the initiation and progression of DKD. An extensive number of studies have demonstrated the role of microbiota in health and disease. Dysregulation in the microbiota resulting in a deficiency of short chain fatty acids (SCFAs) such as propionate, acetate, and butyrate, by-products of healthy gut microbiota metabolism, have been demonstrated in obesity, type 1 and type 2 diabetes. However, it is not clear to date whether such changes in the microbiota are causative or merely associated with the diseases. It is also not clear which microbiota have protective effects on humans. Few studies have investigated the centrality of reduced SCFA in DKD development and progression or the potential therapeutic effects of supplemental SCFAs on insulin resistance, inflammation, and metabolic changes. SCFA receptors are expressed in the kidneys, and emerging data have demonstrated that intestinal dysbiosis activates the renal renin-angiotensin system, which contributes to the development of DKD. In this review, we will summarize the complex relationship between the gut microbiota and the kidney, examine the evidence for the role of gut dysbiosis in diabetes and obesity-related kidney disease, and explore the mechanisms involved. In addition, we will describe the role of potential therapies that modulate the gut microbiota to prevent or reduce kidney disease progression.

Constipation is both a symptom and a disorder, seen in both functional constipation and irritable bowel syndrome with constipation predominance (IBS‐C). Despite the Rome IV criteria distinguishing between these conditions, they share many therapeutic approaches. This review aims to explore the relationship between constipation and abdominal pain and assess the evidence surrounding whether laxation improves abdominal pain and whether such a response to laxation differs between IBS‐C and functional constipation. In patients with functional constipation, increasing frequency of bowel motions by laxatives regardless of mechanism of action is associated with reductions in the severity of abdominal pain, supporting the role of constipation as a contributor to abdominal discomfort. In patients with IBS‐C, evidence from systematic reviews indicates that abdominal pain is driven by factors additional to constipation alone and that visceral analgesic modulation is also needed to optimize pain. Changing definitions of IBS‐C and heterogeneity in clinical trial design including endpoints have raised uncertainty about the comparative ability of older laxatives without known neuromodulatory effects to improve chronic abdominal pain compared with new secretagogues and prokinetics for the management of IBS‐C. While it is known that abdominal pain is associated with constipation and laxation contributes to relief of that pain, it remains unproven whether proposed visceral analgesic properties of new laxatives provide greater pain relief than laxation alone. However, it is likely that the response to laxation in IBS‐C is only part of the puzzle.

Benign biliary strictures can be difficult to manage. Untreated biliary strictures can lead to complications, such as chronic cholestasis, jaundice, recurrent sepsis, and secondary biliary cirrhosis, which can have severe ramifications. The management landscape is constantly evolving, with the development of modifiable self-expandable metal stents and biodegradable stents. This review critically appraises current endoscopic treatment strategies, in particular focusing on the shortfalls, such as stent migration and stricture recurrence. It also proposes a treatment algorithm based on aetiologias and the location of the strictures.

With better understanding of the molecular mechanisms underpinning chronic kidney disease, the roles of inflammation and fibrosis are becoming increasingly inseparable. The progression of renal disease is characterized by pathomorphological changes that consist of early inflammatory responses followed by tubulointerstitial fibrosis, tubular atrophy, and glomerular and vascular sclerosis. Currently available therapies that reduce hypertension, proteinuria, hyperglycemia, and interruption of the renin-angiotensin-aldosterone system are at best only partially effective. Hence, there remains a need to explore agents targeting nonrenin-angiotensin-aldosterone system pathways. In this review, we discuss mechanistic aspects in the physiological and pathological role of semicarbazide-sensitive amine oxidase, a protein enzyme involved in cellular trafficking and inflammation, with respect to the kidney. We explore the evidence for the use of semicarbazide-sensitive amine oxidase inhibitors as potential agents in renal fibrosis to delay the onset and progression of chronic kidney disease.

Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme with a unique dual function in controlling inflammation as well as reactive oxygen species (ROS) generation. We have demonstrated benefit of SSAO inhibition in acute kidney fibrosis. However the function of SSAO in chronic kidney disease (CKD) and diabetic kidney disease (DKD) is yet to be determined. We aimed to assess the effectiveness of a SSAO inhibitor (SSAOi; PXS-4728A) as an antifibrotic agent using a diabetic model of CKD. Diabetic mice were treated with SSAOi for 24 weeks and outcomes compared with untreated diabetic mice and telmisartan treated animals as a standard of care comparator. Extracellular matrix markers, fibronectin and oxidative stress, were downregulated in diabetic mice treated with SSAOi compared with untreated diabetic mice. Expression of the pan-leukocyte marker CD45 was also supressed by SSAOi. SSAO inhibition in diabetic mice resulted in a significant reduction in glomerulosclerosis and associated albuminuria compared to untreated diabetic mice. However, the effect of SSAO inhibition was less obvious in the tubulointerstitial compartment than in the glomeruli. Therefore, SSAO may be a potential target for diabetic glomerulosclerosis.