From the Guidelines
Interstitial nephritis is a form of kidney inflammation characterized by immune-related renal toxicities, including nephritis or acute kidney injury (AKI), which can present with symptoms such as urinary frequency, dark cloudy urine, and fluid retention, as noted in the context of immune checkpoint inhibitor therapy 1.
Definition and Causes
Interstitial nephritis is an inflammatory condition affecting the interstitial tissue of the kidneys, which can be acute or chronic. According to the study by 1, immune-related renal toxicities, including nephritis or AKI, can occur in patients treated with immune checkpoint inhibitor therapy, with a median time to onset of 14 weeks. The condition can be caused by various factors, including medication reactions, infections, autoimmune disorders, and systemic diseases.
Symptoms and Diagnosis
Patients with interstitial nephritis may experience symptoms such as fever, rash, kidney pain, changes in urination patterns, and sometimes blood in urine. As mentioned in the study 1, presenting symptoms related to immune therapy–induced renal toxicities may include urinary frequency, dark cloudy urine, fluid retention, sudden weight gain, abdominal or pelvic pain, nausea or vomiting, high blood pressure, and/or change in mental status. Diagnosis typically involves blood and urine tests, kidney imaging, and sometimes kidney biopsy.
Treatment and Management
Treatment of interstitial nephritis focuses on removing the underlying cause, providing supportive care, and sometimes using corticosteroids to reduce inflammation. As recommended in the study 1, patients with new elevations in creatinine should be considered for holding therapy while other potential causes are evaluated, and those without other obvious causes or who do not respond to alternative treatment measures should be presumed to have immune-related renal toxicity and treated empirically. Renal biopsy is typically not necessary or recommended unless the AKI is refractory to steroids and other immunosuppressant agents.
Key Considerations
It is essential to recognize and treat interstitial nephritis early to prevent permanent kidney damage, as chronic interstitial nephritis can progress to irreversible kidney failure requiring dialysis or transplantation. The study by 1 highlights the importance of monitoring serum creatinine levels before every dose of checkpoint inhibitor therapy and considering the risk of renal allograft rejection in patients with a renal transplant.
From the Research
Definition of Interstitial Nephritis
Interstitial nephritis is an immune-mediated form of tubulointerstitial kidney injury that may occur secondary to drugs, autoimmune disease, infections, and hematologic disorders or as a reactive process 2. It is characterized by inflammation of the tubules and interstitial tissue of the kidneys.
Causes of Interstitial Nephritis
The causes of interstitial nephritis include:
- Drugs such as antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), and proton pump inhibitors 3, 2, 4, 5
- Infections 3, 2
- Systemic diseases 3
- Autoimmune diseases 2
- Hematologic disorders 2
Clinical Outcome and Symptoms
The clinical outcome of interstitial nephritis varies from asymptomatic progression to acute kidney injury 3. The symptoms of interstitial nephritis are variable and often not specific, and may include:
- Tubular proteinuria (alpha(1)-microglobulin) 3
- Phosphaturia with hypophosphatemia 3
- Aminoaciduria 3
- Diminished H(+) secretion with metabolic acidosis with inadequate high urinary pH 3
- Glucosuria 3
- Salt loss 3
Treatment and Prognosis
The main principle of treatment is avoidance of the inducing agent 3. Corticosteroids have been proven usable after exclusion of an infection, and a good prognosis can be expected for acute nephritis in the majority of cases 3. In chronic forms, interstitial nephritis involves the glomeruli as well as potentially resulting in end-stage renal failure in the long run, and supportive therapies are required to prevent further functional loss up to end-stage renal disease 3.