Case 2: Diagnosis & Conclusions

Diagnosis: Acute Interstitial Nephritis (AIN)

Case Summary:

Great work! This case relies heavily on time course to determine the diagnosis. Our patient is a man with hypertension that seems to be well-controlled, without other clear risk factors for chronic kidney disease. He was admitted 10 days ago for an upper gastrointestinal (GI) bleed in the setting of non-steroidal anti-inflammatory drug (NSAID) use. Of note, his kidney function was normal at that time.  Therefore, we are dealing with an acute process, making isolated progression of hypertensive nephropathy less likely – though an acute kidney injury in the setting of hypertensive emergency would be possible if the vital signs fit. We also see that he was started on a new medication, a proton pump inhibitor (PPI).

With our thorough history, our differential diagnosis would include rapidly progressive glomerulonephritis (RPGN, given the rapid rise in creatinine), analgesic nephropathy (given the recent ibuprofen use, though less likely as the patient stopped his NSAID use prior to the onset of kidney dysfunction), acute tubular necrosis (ATN, particularly if the patient had experienced prolonged hypotension during the GI bleed), and acute interstitial nephritis (AIN, with the introduction of a proton pump inhibitor).

There are MANY medications that have been implicated in acute interstitial nephritis, and the list will likely continue to grow.
Some of the most clinically significant that have been identified include:
*Antibiotics: Penicillins, Cephalosporins, Sulfonamides, Isoniazid, Rifampin
*Diuretics & Anti-Hypertensives: Furosemide, Thiazides, Triamterene, Amlodipine, Diltiazem
*Miscellaneous: Allopurinol, Famotidine, Omeprazole, Ranitidine, Phenytoin, Carbamazepine, Immune Checkpoint Inhibitors (i.e. PD-L1 inhibitors)

Given the wide differential diagnosis for this patient’s acute kidney failure, the laboratory data will prove to be extremely helpful! The urinalysis shows us many white blood cells and white blood cell casts along with sub-nephrotic range proteinuria. White blood cell casts may be indicative of pyelonephritis (inflammation of the kidney, usually due to a bacterial infection), of which this patient has no signs or symptoms, or acute interstitial nephritis. Don’t let the absence of urine eosinophils fool you. Hansel’s stain for urine eosinophils has a low sensitivity and a positive predictive value for AIN of only about 40% – you might be better off flipping a coin! Other notable laboratory abnormalities include a hyperchloremic metabolic acidosis, which is characteristic of tubulointerstitial injury. Kidney ultrasound is often normal (as in this case) or shows mild increased echogenicity.

With the findings above in the setting of new omeprazole therapy, our leading diagnosis is likely acute interstitial nephritis. Imaging studies such as a Gallium 67 scan (nuclear medicine test in which gallium salts are taken up by inflammation, tumors, and infection) may also be suggestive of AIN, but the gold standard for diagnosis is kidney biopsy. If our diagnosis is correct, histology on the H&E should show us interstitial inflammation with prominent eosinophils and tubulitis (the presence of inflammatory cells within the tubular wall). This is exactly what we see!

AIN Labeled

The presentation of acute interstitial nephritis is often non-specific and may only present as a rapid deterioration in kidney function. The classically described findings of rash, fever, and eosinophilia are seen in only 5 – 10% of patients. In fact, our patient did not exhibit any of these! History is crucial, and may reveal a recent medication exposure, most often within 10 days to a month, but occasionally longer. AIN may also be associated with certain infections as well as neoplastic or immune disorders (think sarcoidosis or autoimmune diseases like Sjögren’s syndrome!). Look out for AIN – acute kidney injury (AKI) without an obvious cause can end up being biopsy-proven AIN in anywhere from 10 to 27% of cases.

How do we treat? For drug-induced AIN, the most important step is removal of the offending agent! There may be a role for corticosteroids, but data is limited and may not improve outcomes significantly over supportive care alone.

For a closer look, please see the references below:

  1. Kodner CM, Kudrimoti A: Diagnosis and management of acute interstitial nephritis. Am. Fam. Physician 67: 2527–2534, 2003
  2. Raghavan R, Eknoyan G: Acute interstitial nephritis – a reappraisal and update. Clin. Nephrol. 82: 149–162, 2014
  3. Moledina DG, Perazella MA: PPIs and kidney disease: from AIN to CKD. J. Nephrol. 29: 611–616, 2016
  4. Muriithi AK, Nasr SH, Leung N: Utility of Urine Eosinophils in the Diagnosis of Acute Interstitial Nephritis. Clin. J. Am. Soc. Nephrol. CJN.01330213, 2013
  5. Perazella MA: Diagnosing drug-induced AIN in the hospitalized patient: A challenge for the clinician. Clin. Nephrol. 81: 381–388, 2014

Case 2 Index
Case 2 Introduction
Case 2 Physical Exam
Case 2 Diagnostic Testing
Case 2 Pathology
Case 2 Additional Pathology