eMedicine Specialties > Nephrology > Tubulointerstitial Diseases of the Kidney
Nephritis, Interstitial: Differential Diagnoses & Workup
Updated: Nov 11, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Acute Renal Failure
Glomerulonephritis, Acute
Urinary Tract Obstruction
Other Problems to Be Considered
Radiation nephritis
Toxic nephropathies
Workup
Laboratory Studies
- Complete blood cell count with differential: Eosinophilia, when present, can be very helpful. However, this is neither specific nor sensitive enough to establish the diagnosis. Although the true incidence of eosinophilia in acute tubulointerstitial nephritis is unknown, it is estimated to be present in approximately half of patients. Unfortunately, the absence of eosinophiluria does not rule out the diagnosis, and it can be observed in other diseases, including cholesterol microembolism, urinary tract infections, parasitic disorders, and glomerulonephritis. Typically, eosinophilia is absent in AIN-induced by NSAIDs.
- Blood chemistry: A complete set of chemistries, including BUN and serum creatinine, provides information on whether renal insufficiency exists. A low bicarbonate level (total carbon dioxide <24-23 mEq/L) may indicate acidosis. Low serum potassium levels may indicate a proximal tubular disorder, and elevated serum potassium levels with a low bicarbonate level may indicate type 4 renal tubular acidosis, which can be observed with lead nephropathy and NSAID-induced analgesic nephropathy, among other conditions.
- Urinalysis: Urinalysis may reveal proteinuria, hematuria, and the presence of white cells, with or without bacteria. A microscopic analysis of urine sediment may reveal casts, white cells, eosinophils, and crystals. If allergic interstitial nephritis is suspected, send a cytospin specimen to determine if eosinophils are in the urine. In NSAID-induced AIN, eosinophiluria is usually absent.
Imaging Studies
- Ultrasonography: This noninvasive technique is extremely helpful in identifying hydronephrosis in obstructive disease, as well as calculi in stone disease. Both radiolucent and radiopaque stones can be visualized using ultrasonography. A combination of ultrasonography and flat plate kidney, ureter, and bladder (KUB) radiography is helpful in workup and identification of radiopaque versus radiolucent stones. Normal kidney size by ultrasonographic examination generally favors but does not prove a diagnosis of acute (thus potentially reversible) kidney disease. In contrast, small (shrunken) kidneys with increased echogenicity indicate chronic and irreversible kidney disease.
- Computer-assisted tomography (CT) scanning: This technique provides information similar to ultrasonographic scanning in the workup of kidney disease, generally with greater resolution. However, an ultrasonographic examination is sufficient in most kidney diseases. A high-resolution scan showing microcalcifications in renal papillary tips can be very helpful in diagnosis of analgesic nephropathy. The kidneys may be very small in Balkan endemic nephropathy and aristolochic acid nephropathy.
- Intravenous pyelography: Once widely used, this technique seldom plays a role in the workup of kidney diseases in modern medicine. In many instances, similar information can be obtained by ultrasonography without exposing the patient to potentially nephrotoxic contrast dye.
- Gallium scanning: Findings on gallium scanning have been reported to be confirmatory in the diagnosis of acute interstitial nephritis. Thus, a negative finding helps to rule out this diagnosis. However, findings on this test have proved to be too nonspecific, except as a confirmatory tool in suspected cases.
Other Tests
- EDTA lead mobilization test
- Consider the possibility of lead nephropathy in patients presenting with chronic renal insufficiency, hypertension, and gout. In the absence of documented episodes of acute symptomatic lead poisoning, medical history is not reliable in ascertaining the lead etiology in patients presenting with chronic tubulointerstitial nephritis.
- Diagnosis of lead nephropathy requires estimation of cumulative body stores of lead by either EDTA lead mobilization test or by determination of bone lead content by radiographic fluorescence. EDTA lead mobilization test is performed by measuring 24-hour urine lead excretion after intravenous or intramuscular administration of 2 g EDTA (calcium disodium versenate). Excretion of more than 0.6 g of lead per 24 hours is considered an abnormal finding.
- Blood lead levels, although elevated during acute or recent exposure, are not very helpful in the evaluation of chronic lead poisoning. During acute exposure, lead is concentrated in the red blood cells and later extracted to tissues and bone as the red cells senesce. Kidney biopsy is not diagnostic of lead etiology either and shows nonspecific changes such as interstitial fibrosis, tubular atrophy, and vascular sclerosis, findings common to tubulointerstitial nephritides of other etiologies. Body burden of lead and bone lead concentration can be reduced by extended chelation treatment using EDTA (versenate).
- Quantitative determination of urine protein may be helpful. Low-molecular weight proteins, such as beta-2 microglobulin, retinol binding protein (RBP), alpha-1 microglobulin, and immunoglobulin light chains, are increased in chronic tubulointerstitial nephritides. Beta-2 microglobulinuria has been found helpful in the diagnosis of Balkan endemic nephropathy and cadmium nephropathy.
Procedures
- Kidney biopsy: Kidney biopsy is the definitive test for diagnosing acute allergic interstitial nephritis, particularly in cases where clinical diagnosis is difficult. The differential diagnosis of acute tubulointerstitial nephritis encompasses multiple etiologies, including acute tubular necrosis, acute glomerulonephritis (shown first image below and Image 2), vasculitis, and atheroembolic disease. Therefore, consider kidney biopsy when diagnosis is not obvious. Kidney biopsy shows mononuclear and often eosinophilic cellular infiltration of the renal parenchyma with sparing of the glomeruli (see second and third images below and Images 5-6). Sometimes, interstitial changes such as fibrosis and atrophy are also present (Image 2).
Kidney biopsy. Shown here is an example of acute interstitial nephritis. The diagnosis is based on the active inflammatory infiltrate on the right with unaffected glomeruli. Interstitial edema and fibrosis are present on the left side of the field, where some tubules show thickened basement membrane (hematoxylin and eosin, 20 X).
Kidney biopsy. This image shows acute interstitial nephritis. The mononuclear inflammatory infiltrate contains abundant eosinophils, suggesting an allergic etiology. Severe tubular damage is observed (hematoxylin and eosin, 40 X).
Kidney biopsy. This image shows acute interstitial nephritis. The inflammatory infiltrate forms an ill-defined granuloma, suggesting allergic or infectious etiologies. A partially destroyed tubule is present (periodic acid-Schiff, 40 X).
Histologic Findings
Acute cellular infiltration, particularly with eosinophilia, can be diagnostic of acute allergic interstitial nephritis (see first five images below and Images 1-5). In cholesterol microembolism in the kidney, the finding of a characteristic needle-shaped cleft in medium- or small-sized renal arterioles is diagnostic (see sixth and seventh images below and Images 8-9). Chronic tubulointerstitial nephritis is characterized by tubular atrophy, fibrosis, and patchy infiltrate of mononuclear cells (see eighth image below and Image 7).
Kidney biopsy. This is an example of acute interstitial nephritis. The renal cortex shows a diffuse interstitial, predominantly mononuclear, inflammatory infiltrate with no changes to the glomerulus. Tubules in the center of the field are separated by inflammation and edema, as compared with the more normal architecture in the right lower area (periodic acid-Schiff, 40 X).
Kidney biopsy. Shown here is an example of acute interstitial nephritis. The diagnosis is based on the active inflammatory infiltrate on the right with unaffected glomeruli. Interstitial edema and fibrosis are present on the left side of the field, where some tubules show thickened basement membrane (hematoxylin and eosin, 20 X).
Kidney biopsy. This image shows acute interstitial nephritis. The interstitium is expanded by mononuclear inflammatory infiltrate and edema. Acute tubular damage is present; some tubules are distended and contain granular casts (hematoxylin and eosin, 40 X).
Kidney biopsy in interstitial nephritis. Acute crescentic glomerulonephritis. The glomerular tuft is compressed by the proliferation of epithelial cells, forming a crescent. The interstitium shows mononuclear inflammatory infiltrate and edema (periodic acid-Schiff, 40 X).
Kidney biopsy. This image shows acute interstitial nephritis. The mononuclear inflammatory infiltrate contains abundant eosinophils, suggesting an allergic etiology. Severe tubular damage is observed (hematoxylin and eosin, 40 X).
Kidney biopsy in interstitial nephritis. This image shows a cholesterol microembolism. The 2 arterioles in the center are occluded by elongated crystals (hematoxylin and eosin, 20 X).
Kidney biopsy in interstitial nephritis. This image shows a cholesterol microembolism. The arteriole in the center of the field has a thickened wall. The lumen is occluded by elongated spaces, corresponding to dissolved crystals surrounded by cellular reaction. The 2 glomeruli flanking the arteriole are sclerotic and hardly recognizable (hematoxylin and eosin, 40 X).
Kidney biopsy. This image shows chronic tubulointerstitial nephritis. The interstitium is expanded by fibrosis, with distortion of tubules and periglomerular fibrosis. Glomeruli do not show pathologic changes (hematoxylin and eosin, 20 X).
More on Nephritis, Interstitial |
| Overview: Nephritis, Interstitial |
 Differential Diagnoses & Workup: Nephritis, Interstitial |
| Treatment & Medication: Nephritis, Interstitial |
| Follow-up: Nephritis, Interstitial |
| Multimedia: Nephritis, Interstitial |
| References |
| Further Reading |
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References
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Further Reading
Related eMedicine topics:
Acute Renal Failure
Alport Syndrome [Nephrology]
Alport Syndrome [Pediatrics: General Medicine]
Goodpasture Syndrome [Nephrology]
Goodpasture Syndrome [Pediatrics: General Medicine]
Hypersensitivity Nephropathy
Lead Nephropathy
Nephritis
Nephritis, Lupus
Papillary Necrosis [Radiology]
Papillary Necrosis [Urology]
Renal Failure, Acute
Clinical guidelines:
ACR Appropriateness Criteria® renal failure. American College of Radiology - Medical Specialty Society. 1995 (revised 2008). 10 pages. NGC:007019
K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. National Kidney Foundation - Disease Specific Society. 2004 May. 290 pages. NGC:003985
Clinical trials:
Abatacept and Cyclophosphamide Combination Therapy for Lupus Nephritis (ACCESS)
Etanercept for the Treatment of Lupus Nephritis
Immune System Related Kidney Disease
Study of Systemic Lupus Erythematosus
Keywords
interstitial nephritis, nephritis, kidney disease, obstructive uropathy, acute interstitial nephritis, nephritis lupus, analgesic nephropathy, end-stage renal disease, tubulointerstitial diseases, tubulointerstitial nephritis, acute tubulointerstitial nephritis, chronic tubulointerstitial nephritis, lithium nephropathy, cyclosporine-induced nephropathy, tacrolimus-induced nephropathy, lead nephropathy, atherosclerotic kidney disease, cholesterol microembolic disease, Balkan endemic nephropathy, Chinese herb nephropathy
