Diagnosis: Acute tubulointerstitial
Tubulointerstitial nephritis encompass diverse etiologies and pathophysiologic processes, and the patient can present with acute or chronic disease. Many forms of tubulointerstitial injury involve exposure to drugs or other nephrotoxic agents such as heavy metals and infection. By far the most common form of tubulointerstitial inflammation is immunologic.
The term primary tubulointerstitial nephritis refers to cases where the inflammation is limited to the tubules and intertitium; glomeruli and vessels are uninvolved or show minor changes. Secondary tubulointerstitial nephritis implies tubulointerstitial inflammation associated with a primary glomerular, vascular or systemic disease. Idiopathic tubulointerstitial nephritis is a primary tubulointerstitial nephritis whose etiologic agent or cause is unknown (Jennette JC et al. Heptinstall's Pathology of the kidney. 6th edition, Lippincitt Williams & Wilkins, Philadelphia, 2007, p.1084).
In acute interstitial nephritis, the tubular damage leads to renal tubular dysfunction, with or without renal failure. The renal dysfunction is generally reversible, possibly reflecting the regenerative capacity of tubules with preserved basement membrane. Conversely, chronic tubulointerstitial nephritis is characterized by interstitial scarring, fibrosis, and tubule atrophy, resulting in progressive chronic renal insufficiency.
The principal mechanism in acute tubulointerstitial nephritis is hypersensitivity reaction to drugs such as penicillins, NSAIDs, and sulfa drugs. Another mechanism is acute cellular injury caused by infection, viral or bacterial, often associated with obstruction or reflux (Batuman V, Meleg-Smith S. Nephritis, Interstitial. In: E-Medicine. Consulted: December 26th, 2007.[Link]).
Typically, acute tubulointerstitial nephritis begins abruptly, manifesting as acute renal failure. In most instances, acute tubulointerstitial nephritis occurs within days of exposure to the offending drug. In some instances (particularly with NSAIDs), acute tubulointerstitial nephritis begins after several months of exposure. With the exceptions of acute tubulointerstitial nephritis induced by rifampin and NSAIDs, patients commonly present with rash, fever, eosinophilia, eosinophiluria, and elevated immunoglobulin E levels. In mild cases, clinical presentation may consist of subtle tubular function abnormalities, such as Fanconi syndrome (ie, aminoaciduria, glycosuria, renal tubular acidosis). Patients may present with rash and hematuria (Batuman V, Meleg-Smith S. Nephritis, Interstitial. In: E-Medicine. Consulted: December 26th, 2007.[Link]).
Proteinuria is usually absent or modest. Urinalysis may show microscopic hematuria and/or sterile pyuria (with or without eosinophils). Although the clinical presentation is often sufficient to make the diagnosis, renal biopsy is required to make a definitive diagnosis (Batuman V, Meleg-Smith S. Nephritis, Interstitial. In: E-Medicine. Consulted: December 26th, 2007.[Link]).
In systemic lupus erythematosus (SLE) tubulointerstitial lesions are often associated with severe glomerular lesions; predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities in SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only few cases are reported in the English literature. In these patients there is acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy shows diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study usually reveal positive staining for immunoglobulins and/or complement along the renal tubular basement membrane (TBM). Electron microscopy can also show electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection must be ruled out.
Tubulointerstitial nephritis mediated by immunologic mechanisms may be due to antibodies (anti-TBM), immune complexes, or T cells. Anti-tubular basement membrane antibody nephritis may be primary or secondary (in patients with primary glomerulonephritis or with allograft nephropathy); in these cases there is immunoglobulins (Igs) and/or complement deposition along the TBM. In tubulointerstitial nephritis by immune complexes there is also Igs and/or complement deposition. Tubulointerstitial nephritis with T-cell mechanisms also include primary and secondary forms; in these cases there are not immune complexes detected by immunofluorescence; in this category tubulointerstitial nephritis associated to drug reactions, secondary to some systemic diseases, reactions to various microorganisms, sarcoidosis, and most forms of progressive renal disease are included.
In the present case is not possible determine the etiology of the disease. Absence of immune complexes detected by immunofluorescence suggest a T-cell mechanism, but if primary (primary T-cell mediated tubulointerstitial nephritis without uveitis, sarcoidosis, or granulomatous disease in non-transplanted kidneys is not described in many renal pathology texts) or secondary is not possible to know at the present. Follow-up will give us very important information to determine the etiology of the disease in this patient; if there is any additional information in the future for a more precise diagnosis I will inform in this same page.
See the chapter Tubulointerstitial nephritis of our Tutorial (At present only there is a Spanish version).