John A. Oates, M.D., Editor Alastair J.J. Wood, M.D., Associate Editor THE nonsteroidal antiinflammatory drugs (NSAIDs) are very commonly prescribed. This fact reflects the high prevalence of rheumatic diseases; approximately 8 percent of people have a rheumatic symptom at any one time. In 1984, it was estimated that nearly one in seven Americans was treated with an NSAID,1 and in 1986 100 million prescriptions were written for these drugs.2 During the past 30 years, there has been a substantial increase in the number of NSAIDs, but their availability varies markedly between countries.3 In the United States, at least until recently, . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199106133242407?listPDF=true

Nonsteroidal antiinflammatory drugs--differences and similarities.

https://www.amjmed.com/article/S0002-9343(99)00113-8/pdf

Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications

The British Society of Gastroenterology in collaboration with British Association for the Study of the Liver has prepared this document. The aim of this guideline is to review and summarise the evidence that guides clinical diagnosis and management of ascites in patients with cirrhosis. Substantial advances have been made in this area since the publication of the last guideline in 2007. These guidelines are based on a comprehensive literature search and comprise systematic reviews in the key areas, including the diagnostic tests, diuretic use, therapeutic paracentesis, use of albumin, transjugular intrahepatic portosystemic stent shunt, spontaneous bacterial peritonitis and beta-blockers in patients with ascites. Where recent systematic reviews and meta-analysis are available, these have been updated with additional studies. In addition, the results of prospective and retrospective studies, evidence obtained from expert committee reports and, in some instances, reports from case series have been included. Where possible, judgement has been made on the quality of information used to generate the guidelines and the specific recommendations have been made according to the ‘Grading of Recommendations Assessment, Development and Evaluation (GRADE)’ system. These guidelines are intended to inform practising clinicians, and it is expected that these guidelines will be revised in 3 years’ time.

https://gut.bmj.com/content/gutjnl/early/2020/10/15/gutjnl-2020-321790.full.pdf

Guidelines on the management of ascites in cirrhosis.

A decade ago, it was proposed that peripheral arterial vasodilation was an important event in the pathophysiology of ascites formation in patients with cirrhosis.1 At the same time, nitric oxide was demonstrated to be a potent vasodilator with a major role in the regulation of vascular tone,2 and it was hypothesized that nitric oxide could be the cause of the hyperdynamic circulation of patients with cirrhosis.3 Since then, studies in animals and humans with portal hypertension have provided evidence suggesting that nitric oxide has an important role in the hemodynamic abnormalities that characterize cirrhosis and the associated sodium and water . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199808203390807?listPDF=true

Nitric Oxide as a Mediator of Hemodynamic Abnormalities and Sodium and Water Retention in Cirrhosis

Nonsteroidal anti-inflammatory drugs (NSAIDs) are capable of inducing a variety of renal function abnormalities, particularly in high-risk patients with decreased renal blood perfusion who depend on prostaglandin synthesis to maintain normal renal function. Fluid retention is the most common NSAID-related renal complication, occurring to some degree in virtually all exposed individuals; however, clinically detectable edema occurs in less than 5% of patients and is readily reversible on discontinuation of the NSAID. Other electrolyte complications, notably hyperkalemia, are seen infrequently and occur in specific at-risk patients. The next most worrisome complication is acute deterioration of renal function, which occurs in high-risk patients and is also reversible. Nephrotic syndrome with interstitial nephritis is a rare problem of NSAID use and is reversible. Papillary necrosis is the only permanent complication of NSAIDs and is very rare. Altogether, these renal function abnormalities, with the exception of mild fluid retention, are clinically detectable in approximately 1% of exposed patients. Given the number of patients who take NSAIDs on a prescription or over-the-counter basis, the absolute number of at-risk patients is relatively large. Consequently, an appreciation for the risk factors and pathophysiology of NSAID-induced renal function abnormalities is required for optimal use of these drugs.

Nonsteroidal anti-inflammatory drugs: Effects on kidney function

Much progress has been made in the recognition of factors involved in the pathogenesis of the abnormal regulation of extracellular fluid volume in cirrhosis. It is now well established that cirrhosis induces modifications in the activity of several systemic vasoactive factors which then play a major role in the development of renal dysfunction and the formation of ascites and edema. It is also evident that intrarenal factors participate in the pathogenesis of these abnormalities. Nevertheless, the available information is still limited. The link between the diseased liver and the disturbances in the vasoactive systems is not completely known but much evidence suggests that it consists of a circulatory dysfunction that affects mainly the arterial circulation and is characterized by an inability to maintain an effective arterial blood volume within normal limits. Research on the mechanisms of this circulatory dysfunction may yield clues that will help in the design of more pathophysiologically oriented therapeutic approaches to the management of ascites.

Pathogenesis of ascites in cirrhosis

During the first 18 months of liver transplantation program for adult patients we evaluated 98 potential candidates for this treatment. Forty five patients were refused for transplantation and 53 were accepted. Forty six out of these 53 cases were transplanted. Ten (22%) out of the 46 patients undergoing transplantation had chronic hepatic cholestasis, 31 (67%) chronic hepatic diseases of non biliary origin (3 patients had an associated hepatocarcinoma), and 5 patients (11%) suffered an acute hepatic failure. All transplanted patients with previous chronic hepatic diseases had clinical and biological signs of advanced hepatic failure. There were no operative deaths. During the follow-up period 6 transplanted patients (13%) died. The survival probability among the 46 operated patients was about 84% at 12 months after the transplant. This survival was theoretically higher than that expected to occur without transplantation. The survival probability among the 46 transplanted patients was significantly higher (p = 0.0001) than that recorded in 36 patients with comparable hepatic diseases who were evaluated during the same study period and who were not considered for transplantation due to several reasons. The survival probability at the first year in the later group of 36 patients was 20%.

[Liver transplantation: candidate selection and results of a program for adult patients].

Short-term treatment with losartan targeted to activated stellate cells reduces advanced liver fibrogenesis : A new strategy to treat liver fibrosis

To investigate the influence of blood extraction conditions on the renin-angiotensin system in rats, plasma renin activity (PRA) and plasma renin concentration (PRC) were measured in blood samples obtained by different methods. PRA and PRC in samples obtained by chronic catheterization, cardiac puncture without anesthesia, and decapitation immediately following light ether anesthesia were not significantly different from those obtained by simple decapitation (control group). In contrast, PRA and PRC in samples obtained by cardiac puncture and cavernous sinus puncture after light ether anesthesia were significantly (p less than 0.01) higher than those obtained in the control group. There was a significant direct correlationship between PRA and PRC in all samples studied (r = 0.87, p less than 0.001). The present results suggest that light ether anesthesia increases renin levels, except when blood samples are taken by decapitation, and that chronic catheterization and cardiac puncture are the choice blood extraction methods to evaluate the renin-angiotensin system in rats.

Effect of the method of blood extraction on plasma levels of renin in the Wistar rat

Acute-on Chronic Liver Failure (ACLF): A distinct clinical syndrome

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