Prevention of Renal Complications Induced by Non- Steroidal Anti-Inflammatory Drugs

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for the treatment of pain, inflamation and fever. They are usually well tolerated in healthy persons, but in patients with risk factors (advanced age, renal impairment, heart failure, liver disease, concurrent medications with antihypertensive drugs), NSAIDs can induce serious renal adverse effects. They include sodium and water retention with edema, worsening of heart failure, hypertension, hyponatremia, hyperkalemia, acute kidney injury, chronic kidney disease, renal papillary necrosis and acute interstitial nephritis. The majority of these adverse effects are due to the inhibition of prostaglandins synthesis and they are dose and duration-dependent. Acute forms of kidney injuries are transient and often reversible upon drug withdrawal. Chronic use of NSAIDs in some patients may result in chronic kidney disease. It is recommended that patients at risk should have preventative strategies in place, including the use of the "lowest effective dose" of NSAID for the "shortest possible time" and monitoring renal function, fluid retention and electrolyte abnormalities. Patients who are taking antihypertensive medications should be monitored for high blood pressure and the doses of antihypertensive medications should be adjusted if needed. In general, the combination of NSAIDs and angiotensin inhibitors should be avoided. Some other preventive measures are dietary salt restriction, use of topical NSAIDs/non-pharmacological therapies and use of calcium channel blockers for treating hypertension.

Therapeutic potential of mesenchymal stem cell based therapy for osteoarthritis

“…Non-steroidal anti-inflammatory drugs (NSAIDs) Analgesic effects; reduction in pain, stiffness, swelling Often inadequate symptom relief; potential for liver damage in overdose; potential for ulcer and kidney disease; potential for bleeding and vascular events; can cause allergies; effectiveness is dependent upon patient compliance; will not reverse cartilage damage [4][5][6][7][8] Physical activity/therapy Can improve flexibility, range of motion, and function of joint; can provide pain relief; strengthens muscles around the joint; targets obesity, the most important modifiable risk factor for OA Often poor patient compliance; pain/symptom relief is often not enough for patient to adhere to the regiment; will not reverse cartilage damage [9][10][11][12] Opioids Provide pain relief Usefulness in the long-term is limited; Increased risk of adverse events (fractures, cardiovascular events, depression, addiction, overdose, mortality); numerous side effects; will not reverse cartilage damage [9,[13][14][15] Intra-articular injections Hyaluronic acid injections can provide pain relief and improved function that can last over 8 weeks; corticosteroid injections can provide effective short-term pain relief and improved function Injections must be performed in a doctor's office; injections done more than once every 4 months can result in cartilage and joint damage and increase the risk of infection; hyaluronic acid injections show varying efficacy; neither type of injections will reverse cartilage damage [9,[15][16][17] Surgery Total joint arthroplasty can potentially provide permanent pain relief and improved mobility; arthroscopic irrigation and debridement can offer pain relief Many joints do not respond well to total joint arthroplasty; surgery is expensive for patients; increased risk of infection and invasive trauma; arthroscopic procedures do not provide long-term benefits [9,15,17,18] Embryonic stem cells (ESCs) Can undergo self-renewal and are pluripotent; can differentiate into chondrocytes; unlimited proliferative potential; induce cartilage repair in animal models Risk for teratoma formation, tumorgenicity, and immunogenicity; often require mouse fibroblasts to support cell growth, limiting human application; ESCs will likely never be used due to their ethically controversial nature; possibility of heterogeneous population of cells upon injection in patient;…”

Cannabinoids and Pain: New Insights From Old Molecules

“…Acute pain is usually successfully managed with non-steroidal anti-inflammatory drugs (NSAIDs) and/or opioids ( Vučković S. et al, 2006 ; Vučković S.M. et al, 2006 ; Vučković et al, 2009 , Vučković et al, 2016 ), but chronic pain is often difficult to treat and can be very disabling ( Gatchel et al, 2014 ). An adjuvant is a drug that is not primarily intended to be an analgesic but can be used to reduce pain either alone or in combination with other pain medications ( Bair and Sanderson, 2011 ).…”

<p>Practice Advisory on the Appropriate Use of NSAIDs in Primary Care</p>

“…[78][79][80][81][82][83][84] Renal side effects which include sodium and water retention with edema, hyponatremia, hyperkalemia, and acute kidney injury may precipitate renal failure resulting in acute dialysis. 62,85 Risk factors include older age, renal impairment, heart failure, liver disease, diabetes mellitus (DM), and concurrent prescription with antihypertensive drugs (eg, diuretics, renin-angiotensin system inhibitors). 62,86,87 Again, mechanisms of NSAID-induced kidney damage relate to inhibition of prostaglandin synthesis and are dose-and duration-dependent.…”

“…91 It is recommended that patients with risk factors for renal impairment have preventative strategies in place that include using the lowest effective NSAID dose for the shortest possible time, as well as monitoring renal function, fluid retention and electrolyte abnormalities. 62,92 The concomitant use of NSAIDs and angiotensin converting enzyme (ACE) inhibitors should be avoided.…”

“… 58 , 61 COX-dependent inhibition of prostaglandin synthesis may also contribute to sodium and water retention, worsening heart failure, hypertension, and effects on the renal system. 21 , 62 At a mechanistic level, there are differences among NSAIDs. For example, celecoxib but not rofecoxib reduces endothelial tissue-factor expression, a key initiator of the coagulation cascade, and may thus have a lower prothrombotic potential.…”