Impact of proton pump inhibitor and non-steroidal anti-inflammatory drug use on renal function and chronic kidney disease progression

INTRODUCTION

Chronic kidney disease (CKD) is a major public health concern with an estimated global prevalence of 9.1%.¹ CKD progression can result in end-stage renal disease (ESRD), which calls for renal replacement therapy and places a significant financial strain on the individual patients and their family members, as well as the healthcare system at large. Finding the variables that adversely affect kidney function is therefore crucial from a clinical and financial standpoint. Proton pump inhibitors (PPIs) and nonsteroidal anti-inflammatory drugs (NSAIDs) have proven to be beneficial in treating a range of gastrointestinal and painful conditions, although they may have negative effects on renal function.

Proton pump inhibitors are frequently used to treat a variety of gastrointestinal conditions, the most common being gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD). For preventive purposes, they are also often given in combination with NSAIDs. Conversely, chronic pain is a common symptom among CKD patients; reports indicate that one-half or more of this vulnerable group experience pain.^2-5 Poorly managed pain in patients with CKD is linked to high rates of mood disorders, maladaptive coping measures, and impaired quality of life.⁵ As such, effective pain management is still a challenge and a crucial component of total care for these patients. Also, there are growing worries about the possible negative effects of NSAIDs and PPIs on renal function as well as their roles in CKD development and progression.

A previous study reported a link between PPI use and an increased risk of CKD progression.⁶ Comparably, it is well known that NSAIDs are nephrotoxic to individuals with CKD. Sudden kidney damage, gradual loss of kidney function, imbalance of essential minerals, volume overload in comorbid hypertension, have all been linked to NSAID use.^7-9 There is a paucity of data of African origin on the relationship between PPIs, NSAIDs, and renal function and CKD progression. The objectives of the study were to determine the prevalence and use rates of PPIs, NSAIDs, and the combination of both drugs in the CKD population, examine their indications and prescribing patterns, and ascertain their impact on renal function and CKD progression. The findings of this study will help determine areas for targeted interventions and direct future quality improvement in renal care.

MATERIAL AND METHODS

RESULTS

Prevalence of and indications for PPI or NSAID use

The analysis of the study data revealed that 15.3% (n = 61/400), 14.0% (n = 56/400), and 11.0% (n = 44/400) of patients with CKD were prescribed PPI only, NSAID only, and a combination of both drugs, respectively. Peptic ulcer disease (PUD) (81.9%, n = 86/105) and epigastric pain (16.2%, n = 17/105) were the most common indications for PPI prescriptions in the study population. Various forms of body (neck, waist, back, flank, muscle, and joint) pains were the most common indication for NSAID prescriptions (88.0%, n = 88/100) in the study population [Figure 1].

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Figure 1: Indications for PPIs or NSAIDs use. PPI: Proton pump inhibitors, NSAID: Nonsteroidal anti-inflammatory drugs, PUD: Peptic ulcer disease.

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The prescription patterns of PPIs and NSAIDs

The analysis of the prescriptions for individual PPIs revealed omeprazole (82.7%) followed by rabeprazole (11.5%) as the most frequently prescribed [Figure 2].

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Figure 2: PPI prescription patterns. PPI: Proton pump inhibitors.

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The analysis of the prescriptions for individual NSAIDs revealed diclofenac (40.0%) followed by aceclofenac (29.0%) as the most frequently prescribed [Figure 3].

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Figure 3: NSAID prescription patterns. NSAID: Nonsteroidal anti-inflammatory drugs.

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DISCUSSION

The present study found that considerable proportions of patients with CKD were prescribed PPIs and NSAIDs, respectively. PPI and NSAID prescriptions were mainly for the management of PUD and pains, respectively, with omeprazole and diclofenac being the most frequently prescribed PPI and NSAID, respectively. Also, this study demonstrates that both NSAIDs and PPIs, independently and in combination, significantly impair renal function over 3 months period, as evidenced by increased serum creatinine and decreased eGFR. The effect was most pronounced in the combination group, indicating a potential synergistic nephrotoxic interaction.

The point prevalence of total NSAID use of 25.0% noted in the present study is comparable to 27.0% (n = 46055/170574) reported in Alberta, Canada.¹⁵ In CKD, the use of NSAIDs is recommended only when necessary.^9,16,17 If used, treatment should last no longer than five days,⁹ with close monitoring to enable early detection of adverse effects. Despite these recommendations, it has been found that the use of NSAIDs for a brief duration can also have deleterious effects, especially the risk for AKI in the CKD population.¹⁸ Moreover, patients with CKD are already at an increased risk for AKI, and a large number of these patients also take other medications such as diuretics and renin-angiotensin-aldosterone system-blockers, which may potentiate the kidney-damaging properties of NSAIDs.^19,20 The high use of NSAIDs despite their renal adverse effects may be a reflection of physicians’ reluctance to use opioids for pain relief due to the attendant risks of addiction and dependence. Therefore, the dilemma of pain management in CKD calls for global attention and renewed strategies to ensure rational prescribing and optimal pain management in the CKD population. In the present study, diclofenac ranked first among the individual NSAIDs prescribed, contrary to ibuprofen and meloxicam, respectively reported in previous studies conducted in the US²¹ and Indonesia.²² These results may reflect differences in the study population, prescribing cultures, formularies, and cost, among others.

On the other hand, a considerable point prevalence of total PPI use, mainly due to PUD, was recorded in the current study. In contrast, an earlier study conducted in Korea reported a lower prevalence rate mainly due to reflux esophagitis,²³ while a Japanese study among patients undergoing hemodialysis reported a much higher prevalence.²⁴ It is worth noting that gastrointestinal disorders, such as gastrointestinal bleeding or GERD, are more frequently seen in patients on dialysis than in patients with non-dialysis CKD.²⁵ The analysis of individual PPIs prescribed revealed omeprazole as the most frequently prescribed. This pattern may be cost-driven. In Nigeria, omeprazole remains the cheapest PPI and is within the purchasing power of most citizens due to a lack of or inadequate health insurance coverage.²⁶ The findings of a previous study in Maiduguri corroborate this result.²⁷ Inconsistent with the findings of the present study, Korean and Indian studies found lansoprazole and pantoprazole, respectively, as the most prescribed PPIs to patients with CKD.^23,28 The plausible reasons for these observations could be differences in formularies, prescribing cultures, acid-related disease burden, and health insurance coverage.

In the present study, the within-group analysis supports existing literature showing the nephrotoxic potential of NSAIDs due to their inhibition of renal prostaglandin synthesis, especially in patients with compromised renal function.²⁹ PPIs, although generally considered safer, have also been implicated in adverse renal outcomes, including acute interstitial nephritis and progression to CKD.^30-34 The combination therapy group not only started with a higher baseline creatinine but also demonstrated the greatest deterioration in creatinine and eGFR, highlighting the compounded risk of co-prescribing these medications.

Between-group comparisons further reinforced these findings, with significant differences in renal function parameters across the groups at both time points. However, despite these findings, logistic regression did not show a statistically significant association between drug exposure and CKD progression, possibly due to the short follow-up duration or sample size limitations.

These findings underscore the need for cautious prescribing of PPIs or NSAIDs, or both drugs concurrently, particularly in at-risk populations. Monitoring of renal parameters should be prioritized, and the concurrent use of both drug classes should be minimized where possible.

CONCLUSION

This study demonstrates that the use of PPI only, NSAID only, and the combination of both drugs, is common in the CKD population primarily for the treatment of gastrointestinal disorders and body pains, respectively despite emerging concerns and current recommendations. Furthermore, it was found that PPIs or NSAIDs were significantly associated with an increase in median creatinine level and a decrease in median eGFR, respectively, although exposure to the combination of the two drugs had the highest significant impact on these parameters. These findings highlight the importance of cautious prescribing of PPIs or NSAIDs or both in patients with CKD. Regular monitoring of renal function should be prioritized, and the concurrent use of both drug classes should be minimized whenever possible to reduce the risk of further renal impairment.