Can a Glucagon-like peptide-1 (GLP-1) receptor agonist cause interstitial nephritis?

GLP-1 Receptor Agonists and Interstitial Nephritis

Based on current evidence, GLP-1 receptor agonists do not cause interstitial nephritis and are generally considered safe for kidney function, with some even showing nephroprotective effects.

Kidney Safety Profile of GLP-1 Receptor Agonists

GLP-1 receptor agonists have been extensively studied in patients with diabetes and chronic kidney disease (CKD), with evidence supporting their safety and potential benefits for kidney function:

• GLP-1 receptor agonists have been studied with eGFR as low as 15 ml/min/1.73 m² and retain glucose-lowering potency across the range of eGFR and among dialysis patients 1
• Rather than causing kidney damage, GLP-1 receptor agonists have been shown to reduce albuminuria and slow eGFR decline 1
• In a meta-analysis of 8 cardiovascular outcome trials, GLP-1 receptor agonists significantly reduced risk for a composite kidney disease outcome compared with placebo 1

Documented Adverse Effects

The most common adverse effects of GLP-1 receptor agonists are:

• Gastrointestinal symptoms: nausea, vomiting, and diarrhea (occurring in 15-20% of patients with moderate-to-severe CKD) 1
• These symptoms usually abate over several weeks to months with dose titration 1
• Other reported effects include:
  • Increased heart rate (typically by ~5 bpm) 1
  • Injection site reactions (rare, <1%) 1

Notably, interstitial nephritis is not listed among the known adverse effects in any of the major guidelines or clinical trials.

Use in Patients with Kidney Disease

GLP-1 receptor agonists are actually recommended for patients with diabetes and CKD:

• The American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) consensus report recommends GLP-1 receptor agonists for patients with T2D and CKD who do not meet glycemic targets with metformin and/or SGLT2 inhibitors 1
• KDOQI guidelines also support this recommendation with a 1B evidence rating 1
• Most GLP-1 RAs can be used without dose adjustment in reduced renal function, even with eGFR down to 15 ml/min/1.73 m² 2

Nephroprotective Effects

Rather than causing kidney damage, evidence suggests GLP-1 receptor agonists may protect kidney function:

• In cardiovascular outcome trials, GLP-1 receptor agonists reduced risk for a composite kidney disease outcome by 21% (HR 0.79 [95% CI 0.73-0.87]; p<0.0001) 3
• Dulaglutide produced similar glycemic control to insulin glargine but resulted in significantly slower GFR decline in patients with moderate-to-severe CKD 1
• These kidney protective effects are not fully explained by reductions in glycemia, blood pressure, and weight, suggesting direct protective effects on the kidney 1

Monitoring Recommendations

While interstitial nephritis is not a documented concern, monitoring kidney function is still recommended:

• Regular assessment of kidney function (eGFR) is crucial for patients with renal impairment 2
• Baseline assessments should include renal function (eGFR) and other parameters 2

Conclusion

GLP-1 receptor agonists have not been associated with interstitial nephritis in major clinical trials or guidelines. Instead, they appear to have nephroprotective effects, reducing albuminuria and slowing eGFR decline. They are recommended for use in patients with diabetes and CKD, with evidence supporting their safety down to eGFR levels of 15 ml/min/1.73 m².

If kidney function deteriorates unexpectedly in a patient on a GLP-1 receptor agonist, other causes should be investigated rather than assuming the medication is responsible.