Diagnosis: Sarcoidosis, granulomatous interstitial nephritis
Case Summary: Great work! Let’s review this case.
In this case, we’re presented with a patient with an asymptomatic patient with a history of diabetes mellitus for 8 years with an acute kidney injury (AKI) – with a rise in serum creatinine to 2.4 mg/dL from previously normal baseline. As always, step 1 in the evaluation of AKI is the urinalysis and urine microscopy. What do we see? Pyuria, followed by a negative urine culture = sterile pyuria. The differential diagnosis for sterile pyuria is broad, though the absence of infectious signs and symptoms along with the presence of AKI and normal kidney ultrasound narrows our differential diagnosis here towards interstitial nephritis – though urinalysis findings can be variable. We don’t see any obvious offending medications here that are associated with acute interstitial nephritis (AIN), so we’ll have to dig a little deeper. Oral valganciclovir is not typically associated with crystal nephropathy or acute interstitial nephritis – if this patient was treated with intravenous acyclovir, crystal nephropathy might make it onto our differential diagnosis.
A closer review of the labs reveals hypercalcemia – let’s take a look at the pathophysiology of calcium homeostasis to choose our next steps:
We find that the intact parathyroid hormone (iPTH) in this patient is suppressed, with an elevated calcitriol level (vitamin D 1,25 OH). Here’s a pretty differential diagnosis for hypercalcemia from The New England Journal of Medicine:
With an elevated calcitriol level and hypercalcemia…granulomatous interstitial nephritis rises to the top of our differential diagnosis. Remember that in patients with granulomatous disorders, there is inappropriate calcitriol overproduction by activated macrophages. Potential etiologies might include sarcoidosis, tuberculosis, fungal infections, granulomatosis with polyangitis, or lymphoma. The chest x-ray reveals bilateral hilar lymphadenopathy. Add the elevated angiotensin converting enzyme level and we can put our money on sarcoidosis as the most likely diagnosis here.
A kidney biopsy may be helpful here to guide treatment and confirm our suspicion for sarcoidosis given the chest x-ray findings, as our patient does not have pulmonary symptoms. The light microscopy (H&E) slide below confirm our suspicion – we find granuloma formation with interstitial inflammation (the small blue cells in the interstiaal space are likely lymphocytes).
What’s a granuloma? Here’s a nice definition from Nathan Hellman on the Renal Fellow Network: “Granulomas are essentially an organized collection of macrophages–they are often recognized by the presence of multinucleated giant cells, which are multiple macrophages which fuse together, and they can be broadly categorized as being either caseating (that is, containing a necrotizing core) or non-caseating granulomas.” In short, they are balls of inflammatory cells.
Finally, what about that angiotensin converting enzyme (ACE) level? In this patient – it was high, though this is not always the case in patients with sarcoidosis. Though ACE levels are elevated in the majority of patients with untreated sarcoidosis, poor sensitivity as well as specificity have been described.
A brief word on treatment – as with many inflammatory conditions, first line here is glucocoricoids which are followed by biologic agents for patients with relapsing or refractory disease.
Case Published: August 2020