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posted Jun 18, 2013, 5:04 AM by Eliany Mejia   [ updated Jul 10, 2013, 4:15 AM by Purnema Madahar ]

Acute Interstitial Nephritis 6/18/13

Yesterday, we discussed a case of 71 yo male who presented with ARF and eosinophilia in the setting of NSAIDs use, who ultimately received the diagnosis of AIN. The etiology of the new infiltrates wasn't completely clear (drug reaction vs parasitic infection vs malignancy). So, I'd thought I'd take this opportunity to talk about AIN.

·         How can it present clinically?

·         How is it diagnosed?

·         What are the treatment options?

·         What’s the prognosis?


 The term AIN was first used by Councilman in 1898 when he noted the histopathologic changes in autopsy specimens of patients with diphtheria and scarlet fever. Although the term acute interstitial nephritis is more commonly used, acute tubulointerstitial nephritis more accurately describes this disease, because the renal tubules, as well as the interstitium, are involved. It is characterized by an inflammatory infiltrate in the kidney interstitium.


The most frequent causes of AIN can be found in one of three general categories:


Drug Induced:

The clinical presentation of AIN is variable and in part dependent on the underlying medication. Development of drug-induced AIN is NOT dose-related. AIN may become clinically evident an average of two weeks or longer after starting a medication. (See list of medication in the article attached and the list continues to expand).



AIN is associated with acute bacterial (pyelo) and viral infections ( CMV, EBV, Hep C ) and also have been associated with other infections like TB and fungal organisms. Systemic infections can cause direct injury to the kidney or can be associated with indirect injury caused by medications used in the Rx of infections.

Associated with immune or neoplastic disorders:

Autoimmune disorders such as SLE, Sarcoid and Sjögren's syndrome have been associated with AIN, possibly due to antibodies or immune complex-mediated disease. (See tables in the article attached).


·         How can it present clinically, and how is it diagnosed?

The clinical presentation of AIN is variable. The classic presentation is fevers, rash and eosinophilia in a patient with an elevated creatinine, but this presentation is found in only 10% of pts. Our patient presented with eosinphilia and elevated creatinine levels from baseline.

Diagnosis is often made by a history of exposure to a drug with a high likelihood of causing AIN ( NSAID, in the case presented). AIN usually occurs after 7-10 days of drug exposure; however prior exposure to a drug may results in a more sudden onset.


The urine may show leucocytes with negative cultures, in other words, sterile pyuria. About 23% of patients have eosinophilia. Eosinophiluria has a sensitivity of 67% and specificity of 83%.  The sensitivity is higher in patients with interstitial nephritis induced by methicillin or when the Hansel's stain is used.

Isosthenuria (what it means? It’s all about specific gravity, concentration is neither greater (more concentrated) nor less (more dilute) than that of protein-free plasma, typically 1.008-1.012. Isothenuria reflects renal tubular damage of renal medullary function. And hematuria may be also present.


·         What are the treatment options? What’s the prognosis?

The mainstay of AIN treatment is discontinuation of the drug. Recovery may sometimes be prolonged. The evidence of corticorsteroid Rx is limited, and there is conflicting evidence.

Some retrospectives studies demonstrate no benefit of corticosteroid therapy. I have attached a nice paper from Nephrol Dial Transplant. This paper included 42 cases of biopsy-proven AIN (44%, 33%, and 7% due to NSAIDs, antibiotics, and PPIs, respectively). 26 pts were treated with IV methylprednisolone for 3 days followed by oral prednisone (initial dose 0.75 mg/kg per day tapered over three to six weeks), and the remaining 16 were not treated. Baseline creatinine was somewhat higher in the glucocorticoid group (7.9 versus 6.2 mg/dL. There was no difference in serum creatinine between the two groups at 1, 6, and 12 months (at one year, the mean serum creatinine was 1.60 mg/dL in both groups).

On the other hand, improvement in kidney function following glucocorticoid therapy for AIN has been suggested by several uncontrolled reports. There are several possible explanations for a lack of effect from glucocorticoids in the negative studies: the patients treated with steroids had more severe disease as manifested by higher maximum serum creatinine concentrations; a significant proportion of the patients had NSAID-associated AIN, which is less likely to respond to glucocorticoid therapy.


Given the potential for benefit and the relative safety of short-term therapy, it seems reasonable to treat patients with corticosteroids if they do not have significant improvement in the serum creatinine within three to seven days after discontinuation of the offending agent.


Most patients with AIN in whom offending medications are withdrawn early can be expected to recover normal or near-normal renal function within a few weeks.


Adverse prognostic factors in AIN recovery include diffuse (versus patchy) inflammation on biopsy; excess number of neutrophils (1 to 6 percent); and extent or severity of interstitial fibrosis, which was noted to correlate most closely with the final glomerular filtration rate.


Our patient was started on prednisone 60 mg, so far no evidence of renal recovery, now getting HD. I have attached a decent review article and a paper from Nephrol Dial Transplant which evaluated the effects of treatment with corticosteroid in this patient population. Enjoy the reading!! I'll keep you updated with the final diagnosis of the lung infiltrates.


Purnema Madahar,
Jun 18, 2013, 5:04 AM
Purnema Madahar,
Jun 18, 2013, 5:04 AM