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The management of pain in patients with chronic kidney disease (CKD) is challenging for many reasons. These patients have increased susceptibility to adverse drug effects due to altered drug metabolism and excretion, and there are limited safety data for use in this population despite a high pain burden. Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been regarded as dangerous for use in patients with CKD because of their risk for nephrotoxicity and thus alternative classes of analgesics, including opioids, have become more commonly used for pain control in this population. Given the well-established risks that opioids and other analgesics pose, further characterization of the risk posed by NSAIDs in patients with CKD is warranted. NSAID use has been associated with acute kidney injury, progressive loss of glomerular filtration rate in CKD, electrolyte derangements, and hypervolemia with worsening of heart failure and hypertension. The risk for these nephrotoxicity syndromes is modified by many comorbid conditions, risk factors, and characteristics of use, and in patients with CKD, the risk differs between levels of glomerular filtration rate. In this review, we offer recommendations for the cautious use of NSAIDs in the CKD population after careful consideration of these risk factors on an individualized basis.

The debate in this issue of Kidney360 addresses the quandary that exists regarding the safety of nonsteroidal anti-inflammatory drug (NSAID) use in patients with CKD. This is an important issue because pain syndromes are common in patients with CKD. Whereas NSAIDs are a widely used and effective analgesic, they can be associated with several adverse clinical kidney syndromes (Table 1), particularly in patients with underlying CKD (1,2). Clinicians struggle to achieve adequate analgesia while also avoiding toxicity in this group. However, is avoiding NSAIDs in patients with CKD too restrictive and unnecessary? Our two expert debaters Erin Baretto and Bruce Guthrie tackle the conundrum of whether NSAIDs can be safely used in patients with nondialysis CKD. They will present the PRO and CON sides of the debate. We provide background on NSAID therapy in patients with CKD to set the stage for the debate. View this table: Table 1. Clinical kidney syndromes of nonsteroidal anti-inflammatory drugs Pain management in patients with CKD is limited by a number of analgesic drug-related adverse effects (3). Reduced GFR and impaired tubular secretion put patients with AKI or CKD at increased risk of drug-related nephrotoxicity because of increased accumulation of parent drugs, and their metabolites, from impaired metabolism and excretion (4). A significant number of drugs with potential toxicity are concomitantly prescribed to patients with advanced CKD (5). As such, NSAIDs are considered a class of drugs that should be avoided in patients with CKD, particularly those with advanced CKD (6,7). This approach has led to increased opioid administration and …

Sodium-glucose co-transporter-2 (SGLT2) inhibitor drugs are effective for treatment of type-2 diabetes mellitus. These medications target the SGLT2 transporter in the proximal convoluted tubule to prevent reabsorption of filtered glucose, resulting in glucosuria. Other clinically meaningful benefits beyond glycemic control include reductions in blood pressure, weight, and albuminuria. Three large clinical trials and subsequent meta-analyses studying SGLT2 inhibitors demonstrated significant cardiovascular benefits including reductions in heart failure hospitalizations, as well as reduced risk of myocardial infarction, stroke, or cardiovascular death in patients with established atherosclerotic cardiovascular disease. In addition, these agents produced kidney benefits including significant reductions in worsening estimated glomerular filtration rate, progression to end-stage kidney disease, and progression of chronic kidney disease in patients with type-2 diabetes mellitus and albuminuric chronic kidney disease. However, despite these beneficial cardiovascular and kidney effects, numerous reports of acute kidney injury, including need for dialysis and death, have been reported to the FDA adverse events reporting system raising concern among providers and a warning announcement from the FDA. This review will examine the clinical effects of the SGLT2 inhibitor drugs, mechanisms behind both kidney protection and harm, and clinical recommendations for their use.