ESSENTIALS OF DIAGNOSIS
Clinical suspicion of tubulointerstitial nephritis is raised by acute to subacute rise in serum creatinine, presence of sterile pyuria, and exposure to offending medications.
Diagnosis of tubulointerstitial nephritis requires a kidney biopsy.
On histology, tubulointerstitial nephritis is characterized by presence of lymphocytes in the interstitium, presence of lymphocytes infiltrating into the tubular space (“tubulitis”), and varying degree of interstitial eosinophils. The glomeruli are usually spared except in nonsteroidal anti-inflammatory drug-induced tubulointerstitial nephritis, which may show global foot process effacement.
Medications are the most common cause of tubulointerstitial nephritis in the United States; autoimmune diseases are an uncommon etiology of tubulointerstitial nephritis in the elderly, but may be seen in the young.
Antibiotics, proton pump inhibitors and nonsteroidal anti-inflammatory drugs are the most common causes of tubulointerstitial nephritis in the United States. Immune checkpoint inhibitors are the newest class of drugs implicated in the tubulointerstitial nephritis.
Acute tubulointerstitial nephritis (ATIN) is a common histological diagnosis characterized by presence of inflammatory cells in the renal interstitial space, varying degree of interstitial eosinophils, and infiltration of these inflammatory cells into the tubular space (“tubulitis”). ATIN suspicion is raised clinically by an acute or subacute decrease in glomerular filtration rate (GFR) indicated by a rise in serum creatinine, or by an abnormal urinalysis and urinary sediment examination in a patient with clinical scenario suspicious for ATIN. This is usually followed by a kidney biopsy to establish the diagnosis as there is as yet no reliable noninvasive test for ATIN. Most biopsy series report that 2–3% of all kidney biopsies carry a diagnosis of ATIN. In patients with acute kidney injury (AKI), however, the reported proportion of this diagnosis increases to 13–20%. Thus, ATIN is a relatively common cause of AKI cases that require a biopsy. ATIN incidence is also on the rise, particularly in the elderly population.
A number of causes of ATIN have been described (Table 37–1). The following describes those that are most common and of highest interest for clinicians.
Table 37–1.Typical features and therapy of various forms of acute tubulointerstitial nephritis. ||Download (.pdf) Table 37–1. Typical features and therapy of various forms of acute tubulointerstitial nephritis.
|Etiology of ATIN ||Clinical and Laboratory Features ||Typical Histopathologic Features ||Therapy |
|Drug-induced ||Most common etiology (over 70% in developed countries) ||Lymphocytic infiltrate with eosinophils || |
Discontinue offending agent;
Consider trial of glucocorticoids
| Proton pump inhibitors ||Long latent period; few typical clinical features. || || |
| Nonsteroidal anti-inflammatory drugs ||ATIN is often associated with massive proteinuria; long latent period; rarely present with typical allergic manifestations. ||Interstitial eosinophilia may be absent. Glomerular lesions are sometimes present. ||Questionable benefit of corticosteroids. |
| Antibiotics ||More likely to present with systemic allergic manifestations of rash, eosinophilia, and fever (particularly with methicillin and penicillin). Short latent period. ||Interstitial eosinophilia is ...|