Original Investigation
Pathogenesis and Treatment of Kidney Disease
Biopsy-Proven Acute Interstitial Nephritis, 1993-2011: A Case Series

https://doi.org/10.1053/j.ajkd.2014.04.027Get rights and content

Background

Acute interstitial nephritis (AIN) is an important cause of acute kidney injury, especially in hospitalized patients. The cause and outcome of AIN, particularly that due to drugs, is changing with prevalent medication use. The effectiveness of steroids for treatment of AIN is debated.

Study Design

Case series.

Setting & Participants

133 patients with biopsy-proven AIN from 1993 through 2011 at a single center.

Outcomes

Recovery of kidney function by 6 months, either complete, partial, or none. Complete recovery was defined as improvement in serum creatinine level to within 25% of baseline (or <1.4 mg/dL), and partial recovery, as a ≥50% decrease in serum creatinine level from its peak value but not reaching within 25% of its baseline value.

Results

Causes of AIN included drugs (70%), autoimmune diseases (20%), and infections (4%). Drug-induced AIN was due to antibiotics in 49%, proton pump inhibitors (PPIs) in 14%, and nonsteroidal anti-inflammatory drugs (NSAIDs) in 11%. Overall, the top 3 drug causes were omeprazole (12%), amoxicillin (8%), and ciprofloxacin (8%).  Patients with drug-induced compared to non-drug-induced AIN were older and had higher baseline kidney function, but more severe acute kidney injury. Patients with PPI-induced AIN were older, were less symptomatic, and had longer durations of drug exposure and longer delays in getting kidney biopsy and steroids than for antibiotic-induced or NSAID-induced AIN. At 6 months postbiopsy, 49% of patients with drug-induced AIN treated with steroids achieved complete recovery; 39%, partial recovery; and 12%, no recovery. Correlates of poor recovery included a longer duration of drug exposure (15 vs 30 vs 130 days for complete, partial, and no recovery, respectively; P = 0.04) and longer delay in starting steroid therapy (8 vs 11 vs 35 days, respectively; P = 0.05).

Limitations

Retrospective study, selection bias in patients who had kidney biopsy, single-center experience.

Conclusions

The cause of AIN may be shifting; PPIs are emerging as an important contributor to this disease. Delays in discontinuation of the culprit drug and in initiating steroid treatment adversely affect recovery of kidney function.

Section snippets

Study Population

Retrospective review of all native kidney biopsies evaluated in the Renal Pathology Laboratory at Mayo Clinic, Rochester, from 1993 through 2011 identified 133 Mayo Clinic patients with AIN without concurrent glomerulonephritis. We excluded patients younger than 18 years, patients with glomerulonephritis or primary vascular disease, and those with transplant biopsies, as well as outside institution referrals.

Pathologic Studies

A pathologic diagnosis of AIN required the presence of prominent interstitial

Baseline Clinical and Demographic Data

Table 1 lists demographic and clinical characteristics of all 133 patients with AIN and compares drug-induced AIN to AIN from other causes. Most patients (58%) were hospitalized and developed AKI during the course of this hospitalization. Baseline serum creatinine levels (median, 1.1 mg/dL) were available for 109 patients, and 48 (44%) patients had CKD as defined by baseline eGFR < 60 mL/min/1.73 m2. Prior to biopsy, AIN was suspected in only 55% of cases. Close to half the patients had pyuria and

Discussion

A main cause of AKI, especially in hospitalized patients, AIN accounts for 15%-27% of cases; the incidence of AIN may be increasing, possibly due to more detection.21, 22, 23, 24 Over time, since AIN was first described,2, 3 when infections were by far the most common culprit, the cause of AIN has changed. Currently, drugs are responsible for most cases.7, 8, 9, 10 Two studies published in 2000 and 2004 that included a total of 124 patients with AIN found NSAIDs to be the most common culprit

Acknowledgements

Support: None.

Financial Disclosure: The authors declare that they have no relevant financial interests.

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