Gastrointestinal Bleeding in Patients with CKD

Abstract

Gastrointestinal bleeding (GIB) remains a significant cause of hospitalization, morbidity, and mortality among patients with CKD.1 In this issue, Lin et al.2 examined GIB-related hospitalizations in patients with advanced CKD (ACKD) and ESKD, comparing their outcomes with those of non-CKD patients (study results are summarized in Table 1). Their findings revealed not only higher rates of morbidity and in-hospital mortality, but also highlighted the often-overlooked phenomenon of renalism. Renalism refers to the hesitation or reluctance to provide optimal, standard care to patients with kidney disease because of concerns about their renal condition.3 Table 1 - Summary of the findings of Lin et al. and the disparities faced by patients with CKD Parameter Non-CKD ACKD ESKD KT Renalism GIB hospitalization rate (%) 2.2 3.2a 3.4a 2.1 Delayed recognition of high-risk populations aOR for GIB hospitalization (95% CI) Reference 1.12 (1.1 to 1.14)a 1.37 (1.35 to 1.39)a 0.88 (0.83 to 0.92) aOR for early endoscopy (95% CI) Reference 0.91 (0.87 to 0.94)a 0.83 (0.80 to 0.85)a 0.94 (0.85 to 1.04) Delayed diagnostic and therapeutic procedures aOR for late endoscopy (95% CI) Reference 1.11 (1.07 to 1.15)a 1.2 (1.16 to 1.23)a 1 (0.91 to 1.11) aOR arterial embolization (95% CI) Reference 0.6 (0.51 to 0.70)a 1.06 (0.96 to 1.17) 1.18 (0.86 to 1.63) Hesitancy in pursuing invasive procedures aOR surgical intervention (95% CI) Reference 0.72 (0.58 to 0.89)a 0.71 (0.60 to 0.84)a 0.74 (0.43 to 1.28) In-hospital mortality rate (%) 1.7 3a 3.1a 2a Higher mortality from delayed interventions aOR for mortality (95% CI) Reference 1.33 (1.19 to 1.48)a 1.94 (1.78 to 2.13)a 1.73 (1.22 to 2.46)a ACKD, advanced CKD; aOR, adjusted odds ratio; CI, confidence interval; GIB, gastrointestinal bleeding; KT, kidney transplant.aDenotes statistically significant difference. GIB in Patients with CKD The association between ACKD, as well as ESKD with GIB, has long been recognized4 and may be exacerbated by kidney disease–related factors. Uremia itself may cause gastritis and bleeding tendency. Anticoagulants are routinely administered in most patients during dialysis sessions and may increase risk of GIB.5 The findings of Lin et al. confirm this elevated risk, reporting higher hospitalization and mortality rates for patients with CKD presenting with GIB. Using a national inpatient database from 2016 to 2019, Lin et al. analyzed over 2 million hospitalizations to compare GIB outcomes in patients with ACKD, ESKD, or kidney transplant (KT) with non-CKD patients. GIB hospitalization rates were higher in patients with ACKD (3.2%) and ESKD (3.4%) compared with non-CKD patients (2.2%), with increased in-hospital mortality in patients with ACKD (3.0%), ESKD (3.1%), and KT (2.0%) versus non-CKD patients (1.7%). Nevertheless, comorbidities emerged in this study as a major predictor of GIB hospitalization and in-hospital mortality, as also reported in previous research.6 The study highlighted a novel independent predictor of mortality, which is a lower rate of early endoscopy (<24 hours) and higher rate of delayed endoscopy (>48 hours) among patients with kidney disease. These findings underscore the challenges faced by patients with CKD, many of which are exacerbated by renalism. Renalism in Clinical Practice: A Historical Perspective First described in 2004 by Chertow et al., renalism manifests as delayed or withheld diagnostic procedures, invasive treatments, or therapies deemed risky for patients with CKD. In their landmark study, patients with CKD hospitalized for acute myocardial infarction were significantly less likely to receive coronary angiography compared with non-CKD patients, despite meeting clinical criteria (25.2% versus 46.8%; P < 0.0001).3 After adjusting for predictors of angiography, the adjusted odds ratio (aOR) for patients with CKD undergoing angiography was 0.47 (95% confidence interval [CI], 0.40 to 0.52). This disparity, renalism, worsened with advancing CKD, as only 28.1% of 7783 patients with GFR <30 ml/min per 1.73 m2 underwent angiography. Notably, patients with CKD who received angiography had lower 1-year adjusted mortality (aOR, 0.54; 95% CI, 0.49 to 0.60), suggesting that withholding the procedure may inadvertently harm patients. Although the risk of contrast-associated AKI may partially justify this caution in coronary angiography, other manifestations of renalism are less defensible. For example, patients with CKD are often excluded from anticancer trials, delaying their access to novel therapies.7,8 This pattern of care denial persists in other domains like GIB, as evidenced by the findings of Lin et al. The Cost of Delayed Endoscopy in GIB The delays in care Lin et al. report, specifically the reduced rates of early endoscopy and definitive interventions, highlight renalism impact on GIB outcomes. Early endoscopy is critical for managing acute upper GIB, with guidelines recommending endoscopy within 12 hours for variceal and 24 hours for nonvariceal GIB to enable timely diagnosis and intervention.9,10 Yet, patients with ACKD and ESKD in this study experienced unacceptably high delays in endoscopy. Delayed endoscopy worsened outcomes, increasing the risk of prolonged hospital stays, blood transfusions, and in-hospital mortality. These delays exemplify renalism, driven by unfounded fears of exacerbating kidney injury or complications. Renalism in Therapeutic Interventions Renalism extended to therapy as well. Patients with ACKD were significantly less likely to receive arterial embolization or surgical interventions for GIB (aOR, 0.6; 95% CI, 0.51 to 0.70, for embolization; aOR, 0.72; 95% CI, 0.58 to 0.89, for surgery) and patients with ESKD faced similar reluctance for surgical intervention (aOR, 0.71; 95% CI, 0.60 to 0.84; P < 0.001), which may have further contributed to their poor outcomes. The observed disparity in the use of contrast-based interventions for patients with ESKD and KT, but not ACKD, underscores the persistence of renalism among practitioners, perpetuating poorer outcomes for patients with kidney disease. Clinical Implications: Addressing Renalism and Improving Outcomes To address the disparities revealed in the study by Lin et al., systemic changes are necessary: Prioritized early endoscopy: Health care systems must ensure patients with CKD receive timely diagnostic procedures. Screening for GIB: Active screening for GIB in high risk patients with CKD, such as those with comorbidities, those with erythropoietin stimulating agents-resistant anemia, or those taking anticoagulants or antiplatelets, can facilitate earlier detection and intervention. Indications for these treatments should also be continuously revised because they were independent risk factors of GIB hospitalizations but not for mortality. Risk mitigation: Limiting nonsteroidal anti-inflammatory drug (NSAID) use, alcohol, and gastric irritants should be emphasized in CKD patient care. The role of corticosteroids in KT-related GIB also warrants scrutiny. This study did not explore the use of NSAIDs and corticosteroids, both known to play a role in GIB, among the studied group.11 NSAIDs are usually avoided in patients with ACKD, but may be easily accessible over the counter and may be a major cause of both GIB and kidney disease. They are also sometimes taken by patients with ESKD. Corticosteroids may have played a role in patients with KT, who are not on a steroid-free regimen. Multidisciplinary care: Collaboration among nephrologists, gastroenterologists, and intensivists can ensure tailored, evidence-based interventions. Future Directions and Research Priorities The findings of Lin et al. underscore the need for targeted research to: Evaluate the benefits of GIB screening in CKD populations. Develop evidence-based guidelines for the timing and safety of interventions, to ensure that optimum care is not withheld out of an irrational fear of potential complications. Explore the effect of multidisciplinary care models on outcomes and the reduction of renalism. Shifting the Mindset: Overcoming Renalism Renalism is not simply a care gap; it is a mindset. Changing this mindset requires advocacy from nephrologists to ensure patients with CKD receive evidence-based, timely, and appropriate care. Denying necessary interventions for unrealistic concerns about potential complications must be abandoned. Education and awareness initiatives can help combat renalism by empowering clinicians to act decisively and collaboratively. By addressing delays in care, improving guideline adherence, and fostering multidisciplinary collaboration, we can overcome renalism in GIB and improve outcomes for those high-risk CKD population. Together, clinicians and health care systems must strive to eliminate renalism and ensure equitable care for patients with CKD.