The term tubulointerstitial is used to broadly refer to kidney diseases that involve structures in the kidney outside the glomerulus. These diseases generally involve tubules and/or the interstitium of the kidney and spare the glomeruli, as shown in the image below.
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Kidney biopsy. This is an example of acute interstitial nephritis. The renal cortex shows a diffuse interstitial, predominantly mononuclear, inflammat....
Although primary glomerular diseases are often associated with prominent tubulointerstitial changes (see the following image), the clinical presentation is dominated by the consequences of glomerular injury; hence, they are not considered in this article.
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Kidney biopsy in interstitial nephritis. Acute crescentic glomerulonephritis. The glomerular tuft is compressed by the proliferation of epithelial cel....
The authors suggest the reader see the Mayo Clinic - Kidney Transplant Information Website for further information.
For patient information, see Chronic Kidney Disease, and Kidney Transplant.
See also Glomerulonephritis, Membranoproliferative Glomerulonephritis, Pediatric Nephritis, and Radiation Nephritis.
Tubulointerstitial nephritis involves the immune-mediated infiltration of the kidney interstitium by inflammatory cells.[1] Lethal or sublethal injury to renal cells leads to expression of new local antigens, inflammatory cell infiltration, and activation of proinflammatory and chemoattractant cytokines. These cytokines are produced by inflammatory cells (ie, macrophages, lymphocytes) and also by the renal cells (ie, proximal tubule, vascular endothelial cells, interstitial cells, fibroblasts). The outcome can be acute or chronic nephritis.
In acute interstitial nephritis, the tubular damage leads to renal tubular dysfunction, with or without renal failure. Regardless of the severity of the damage to the tubular epithelium, 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.[2, 3]
The principal mechanism in acute tubulointerstitial nephritis is hypersensitivity reaction to drugs such as penicillins, nonsteroidal anti-inflammatory drugs (NSAIDs), and sulfa drugs. Another mechanism is acute cellular injury caused by infection, viral or bacterial, often associated with obstruction or reflux. The kidney is remarkably resistant to structural damage in bacterial infections, and, in the absence of obstruction, damage from bacterial infection in the kidney parenchyma is extremely unlikely to occur.
Studies have revealed transforming growth factor–beta (TGF-β) as a major participant in fibrogenesis. TGF-β favors accumulation of collagen and noncollagen basement membrane components by direct stimulation of production and by inhibiting matrix degradation enzymes such as collagenases and metalloproteinases. Activation of nuclear transcription factors, such as nuclear factor kappa B (NFκB) in injured kidney cells,[4] with consequent transcription and release of proinflammatory cytokines into the interstitium, appears to be a major mechanism of chronic tubulointerstitial inflammation accompanying proteinuric kidney diseases.
Tubulointerstitial diseases of the kidney encompass diverse etiologies and pathophysiologic processes, and the patient can present with acute or chronic conditions. Many forms of tubulointerstitial injury involve exposure to drugs or other nephrotoxic agents such as heavy metals and, rarely, infection. By far the most common form of tubulointerstitial inflammation is hypersensitivity reaction to medications, termed allergic interstitial nephritis.
The following are causes of acute tubulointerstitial nephritis:
Hypersensitivity reactions: Any drug can cause an acute allergic reaction involving the kidneys (eg, penicillins, sulfa drugs, nonsteroidal anti-inflammatory drugs [NSAIDs] most common) (See Clinical.)
Immunologic diseases (eg, associated with lupus, Goodpasture syndrome)
Acute transplant rejection
Infections, including bacterial (must be accompanied by obstruction or reflux), viral (eg, cytomegalovirus [CMV], hantavirus, human immunodeficiency virus [HIV], hepatitis B [HBV]), fungal (eg, histoplasmosis), and parasitic (eg, Leishmania, Toxoplasma)
The following are causes of chronic tubulointerstitial nephritis:
Atherosclerotic kidney disease (ischemic) - Underlying atherosclerotic disease, dyslipidemia, and smoking are conditions commonly associated with cholesterol microembolism; catheter manipulations above the level of the renal arteries or anticoagulation in a patient with atherosclerosis can trigger cholesterol microembolic disease
Miscellaneous (eg, Balkan endemic nephropathy, Chinese herb/aristolochic acid nephropathy)[6, 7]
Lead nephropathy
Environmental and occupational exposure to lead can cause chronic tubulointerstitial nephritis. Occupations in welding, smelting, the battery industry, and mining have all been responsible for lead nephropathy cases. Environmental exposure from leaded gasoline is decreasing, because the use of leaded gasoline has ceased in the United States; however, sporadic exposure is still observed, particularly among children living in deteriorating housing in urban areas. Rarely, lead poisoning can be observed among individuals who consume moonshine whiskey and those who drink beverages from imported ceramics painted with leaded glaze.
Obstructive uropathy
A variety of causes contribute to obstructive uropathy, including prostate disease in elderly males; pelvic or colonic tumors involving both ureters in both sexes; nephrolithiasis, with or without urinary tract infection; and radiation to the pelvic area as well as some drugs, such as methysergide, can cause retroperitoneal fibrosis and obstruction.
Sjögren syndrome
A study by Maripuri et al found that of 24 patients with primary Sjögren syndrome who also had renal impairment, biopsies revealed that 17 individuals had tubulointerstitial nephritis as the primary lesion behind their kidney dysfunction,[8] and 11 of the 17 patients had the chronic form of this nephritis. The investigators suggested these results support the notion that in patients with primary Sjögren syndrome, chronic tubulointerstitial nephritis is the most frequent cause of renal impairment found through kidney biopsy.
Similarly, a prospective study by Jain et al of renal involvement in 70 patients with primary Sjögren syndrome reported that tubulointerstitial nephritis was the most common disorder found on kidney biopsy. Tubulointerstitial nephritis was identified in nine of 17 biopsies in this study.[9]
Balkan endemic nephropathy
Epidemiology and natural history clearly implicate environmental factors in the pathophysiology of Balkan endemic nephropathy. Lead contamination of food has been considered but ruled out as a cause of this disease. Some studies have implicated a fungal toxin, called "ochratoxin," which can grow in moist grains in storage and which has been shown to cause a similar kidney disease in pigs in several central European countries. However, most experts agree that the evidence for its role in this endemic nephropathy is weak. More recent studies have linked aristolochic acid, the underlying factor in Chinese herb nephropathy (see below), as a causative agent.[10]
Chinese herb/aristolochic acid nephropathy
In the early 1990s, aristolochic acid was recognized as a potent nephrotoxin that can cause rapidly progressive interstitial fibrosis and end-stage renal disease (ESRD) in young women using a Chinese herb as part of a slimming regimen in Belgium. Since then, many other cases of so-called Chinese herb (CH) nephropathy have been reported from around the world.
Chinese herb nephropathy may not be an appropriate name for the disease, however, because aristolochic acid can be present in herbal medicines from any country. The term aristolochic acid nephropathy (AAN) more accurately characterizes this form of toxic nephropathy.
Another interesting feature of term aristolochic acid nephropathy is its association with uroepithelial cancers reminiscent of Balkan nephropathy. Aristolochic acid not only can trigger severe renal fibrosis, but it also can cause oncogene mutations that can explain the high incidence of renal cancer with this type of interstitial nephritis. Patients have also been found to have abnormal function of TP53, a known tumor suppressor gene.[6]
A recently recognized cause of interstitial kidney disease is immunoglobulin G (IgG)-4–related disease.[11] This multiorgan disorder, characterized by high serum levels of IgG and IgG4, is associated with a tubulointerstitial nephritis with an abundant IgG4-positive plasma cell interstitial infiltration and has a good response to steroids.[12] However, there have been reports of high relapse rates after treatment with corticosteroids.[13, 14]
Primary tubulointerstitial diseases (ie, diseases of the renal tubules and interstitium sparing the glomeruli) constitute 10-15% of all kidney diseases both in the United States and around the world. In certain regions, such as the Balkans (ie, Yugoslavia, Bosnia, Croatia, Romania, Bulgaria), where endemic nephropathy is common, interstitial diseases may be more prevalent.[6, 7]
Neither acute nor chronic tubulointerstitial diseases of the kidney demonstrate racial predilections. However, lead nephropathy may be more common in black people because of socioeconomic factors.
Analgesic nephropathy is 5-6 times more common in women. This is generally attributed to women taking more analgesics than men. However, a greater sensitivity to the toxic effects of analgesics or differences in analgesic metabolism in women cannot be ruled out.
All toxic nephropathies are related to the cumulative effects of toxic substances, particularly lead, and consequently are likely to be observed more frequently with advancing age. However, this is highly variable. For example, people with severe lead poisoning during childhood may present with chronic tubulointerstitial nephritis in early adult life. Atherosclerotic and/or ischemic kidney disease is increasingly more common in elderly individuals. Metabolic disorders, such as cystinosis, oxalosis, and hypercalcemia, can occur in younger individuals.
Tubulointerstitial disease may progress to end-stage renal disease (ESRD) and thus require dialysis or transplantation. Electrolyte and acid-base disorders may also be observed, and an increased incidence of uroepithelial cancers is found among patients with analgesic nephropathy, aristolochic acid nephropathy, and Balkan endemic nephropathy.[6, 7]
Hypertension may also complicate any renal disease, but not all cases of interstitial renal disease are associated with hypertension (ie, Balkan endemic nephropathy, acute allergic interstitial nephritides).
Most patients with allergic interstitial nephritis recover renal function upon cessation of the offending agent.
Patients with cholesterol microembolic kidney disease often have some spontaneous improvement in renal function after the embolic event. Complete resolution of renal insufficiency is rare, however.
Although the natural history of chronic tubulointerstitial nephritides varies depending on the etiology, most chronic tubulointerstitial renal disease eventually progresses to ESRD. However, the rate of progression is generally believed to be much slower in tubulointerstitial nephritis compared to glomerular diseases.
The history of patients with tubulointerstitial nephritis depends on whether the disease is acute or chronic. A thorough physical examination may provide clues to the diagnosis (eg, fever, rash in acute tubulointerstitial nephritis, livido reticularis and Hollenhorst plaques in the optic fundi in atheroembolic disease), but, in most patients, no characteristic findings exist. Some patients present with hypertension, although others may be normotensive or hypotensive (eg, Balkan endemic nephropathy).[15]
Typically, acute tubulointerstitial nephritis begins abruptly, manifesting as acute kidney injury. In most instances, acute tubulointerstitial nephritis occurs within days of exposure to the offending drug. In some instances (particularly with nonsteroidal anti-inflammatory drugs [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 (IgE) levels. In mild cases, the 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.
Almost all acute tubulointerstitial nephritides are caused by hypersensitivity reactions to drugs and are not mediated by direct toxicity. Although any drug can potentially cause a hypersensitivity reaction involving the kidney, the following agents are the most frequently implicated:
Anticoagulant-related tubulointerstitial nephritis is most often reported with warfarin. However, case reports involving novel oral anticoagulants such as dabigatran are beginning to appear.[16]
Although the presence of rash can be supportive evidence of an allergic etiology of an acute renal insufficiency, its absence is not useful in ruling out acute allergic interstitial nephritis.
Acute tubulointerstitial nephritis caused by NSAIDs
Acute tubulointerstitial nephritis due to NSAIDs is more common in elderly people, perhaps because of the higher incidence of arthritic disorders in this population. Acute allergic interstitial nephritis should not be confused with the acute vasomotor renal insufficiency that can occur in patients with preexisting underperfusion of the kidney.
A unique feature of allergic interstitial nephritis caused by NSAIDs is that patients may present with nephrotic syndrome. In such patients, massive proteinuria with hypoalbuminemia and edema are present in addition to the typical features of acute interstitial nephritis. Findings on kidney biopsy show features of minimal change nephrosis in addition to the characteristic findings of interstitial nephritis.
Antibiotic-induced acute tubulointerstitial nephritis is usually observed in the hospital setting during treatment of serious infections, within several days to weeks of initiation of antibiotic therapy. Rash, eosinophilia, and eosinophiluria, as well as pyuria (sterile), hematuria, and modest proteinuria (usually < 1 g/d), are common. However, unlike in NSAID-induced allergic interstitial nephritis, nephrotic-range proteinuria is very rare. If a renal biopsy is performed, eosinophils can be a component of the interstitial nephritis. Occasionally, ill-defined granulomas are present.
Among antibiotics, rifampin is unique in that the interstitial nephritis generally occurs when the antibiotic is reintroduced after an interval. Furthermore, the interstitial nephritis associated with it does not manifest with eosinophilia. In some cases, rifampin-associated interstitial nephritis has been reported to show casts containing immunoglobulin light chains in tubular lumens without any evidence of myeloma in the patient. Flulike symptoms, flank pain, hypertension, and oliguric acute renal failure are common. In some patients, circulating antirifampin antibodies and immunoglobulin G (IgG) deposits along the tubular basement membranes have been reported.
Acute tubulointerstitial nephritis caused by miscellaneous agents
Infections with viral agents, bacteria, and fungi are occasionally associated with acute interstitial nephritis. Hantavirus, cytomegalovirus (CMV), and human immunodeficiency virus (HIV) are common among the infectious agents associated with acute interstitial nephritis.
In HIV disease, acute interstitial nephritis is usually observed in conjunction with glomerular disease (ie, focal segmental glomerulosclerosis). Parenchymal invasion by the virus is not always present, and other characteristic features, such as eosinophilia and fever, are usually absent.
Bacterial infection with renal parenchymal invasion is sometimes responsible for acute interstitial nephritis, but this is exceedingly rare in the absence of obstruction. Other infections such as tuberculosis and histoplasmosis are also among the rare causes of acute tubulointerstitial nephritis and may be diagnostic challenges.
The chronic form of tubulointerstitial nephritis is an insidious disease and most probably represents the common final response pattern of the kidney to a variety of insults and agents (see Etiology ). Important causes include drugs (eg, analgesics, cyclosporine, cisplatin, and lithium); lead; and metabolic disorders, notably hypercalcemia, potassium depletion, and hyperoxaluria.
Because of its insidious nature, chronic tubulointerstitial nephritis is often diagnosed incidentally on routine laboratory screening or evaluation of hypertension. Patients are usually asymptomatic. Hypertension is common but not universal, and it is conspicuously absent in Balkan endemic nephropathy.
Analgesic nephropathy
Analgesic nephropathy is the most common category of chronic interstitial nephritis worldwide.[5] This disorder occurs with long-term ingestion of combinations of phenacetin, aspirin, and caffeine or phenacetin-acetaminophen or NSAIDs and acetaminophen. In its most severe form, analgesic nephropathy is associated with papillary necrosis.
The amount of phenacetin-acetaminophen combination required to cause chronic interstitial nephritis has been estimated to be at least 2-3 kg over many years. Although initially thought to be exclusively associated with phenacetin-containing combinations, all analgesics, including acetaminophen, aspirin, and NSAIDs, can cause analgesic-induced chronic tubulointerstitial nephritis.
Analgesic nephropathy is most common in women in the sixth and seventh decades of life who have a history of low back pain, migraine headaches, or other chronic musculoskeletal pain. In some patients, a history can be elicited of episodes of papillary necrosis (ie, gross hematuria with flank pain occasionally accompanied by obstruction and infection). Clinically, patients with analgesic nephropathy present with renal insufficiency, modest proteinuria, sterile pyuria, and anemia. Diagnosis of this condition can be supported by a history of heavy analgesic use, and computed tomography (CT) scans may reveal microcalcifications at the papillary tips.
Lithium nephropathy
Distal tubular dysfunction (ie, polyuria, concentrating defect, downregulation of aquaporin-2) occurs in up to 50% of patients receiving lithium. Chronic interstitial nephritis occurs in a small subset of patients receiving long-term lithium therapy who have had repeated episodes of lithium toxicity with high serum levels.
Cyclosporine- and tacrolimus-induced nephropathy
Although indispensable in the management of solid organ transplantation, cyclosporine and tacrolimus can cause acute and chronic nephrotoxicity. The mechanism appears to be dependent largely on the potent vasoconstrictive effects of these drugs. Chronic tubulointerstitial nephritis induced by cyclosporine or tacrolimus is common among patients receiving kidney, heart, liver, and pancreas transplants. However, this condition is rare in bone marrow transplant recipients, because these individuals receive the drugs for a short time and generally at lower doses. In renal transplant recipients, cyclosporine- or tacrolimus-induced chronic interstitial nephritis is similar to chronic rejection.
Because the pathophysiology of both is poorly understood, these conditions tend to be included under the generic term of chronic transplant nephropathy. Most kidney transplant patients have a stable course with mild impairment of renal function. However, up to 10% of heart transplant recipients develop progressive renal insufficiency and eventually require dialysis.
Both cyclosporine and tacrolimus frequently cause hypertension and hyperkalemia. Hypomagnesemia caused by renal magnesium wasting is also common in cyclosporine-treated patients. Concomitant use of calcium channel blockers reduces nephrotoxicity. Long-term use of cyclosporine has been associated with patchy interstitial fibrosis, usually in a striped pattern and with tubular atrophy. Thrombotic microangiopathy might further contribute to both acute and chronic nephrotoxicity.
Lead nephropathy
Since antiquity, lead has been known to cause kidney disease and gout. In the modern industrialized world, lead is a ubiquitous environmental and occupational toxin and is an important cause of chronic tubulointerstitial nephritis and hypertension, mainly in urban poor communities and particularly among black people.
Children with severe lead poisoning can present with encephalopathy and acute renal failure with Fanconi syndrome. Because lead has a biologic half-life of several decades, if untreated by chelation, both intermittent acute poisoning and low-level environmental exposure result in chronic cumulative lead poisoning. The major consequence of chronic lead poisoning is chronic tubulointerstitial disease, usually in the third to fourth decades of life.
A common source of lead poisoning is leaded paint chipping in old urban tenements. Young children attracted to the sweet taste of the leaded paint may ingest or inhale dust particles containing lead and are at particular risk. In the industrial setting, welders, smelters, battery workers, painters, and restorers of old buildings, especially in poorly ventilated work environments, can be exposed to toxic amounts of lead.
Hypertension is almost always present, and, in the absence of appropriate testing or careful exposure history, lead nephropathy is often misdiagnosed as so-called hypertensive kidney disease. Patients with lead nephropathy tend to have disproportionately worse hyperuricemia compared to patients with other kidney diseases because of the unique effects of lead on urate metabolism, and, consequently, gout is common.
In retrospect, after careful investigation including the ethylenediaminetetraacetic acid (EDTA) lead mobilization test (see Workup), many patients presumed to have either gouty nephropathy or hypertensive nephrosclerosis are discovered to have lead nephropathy. Identification of the lead etiology in patients presumed to have gout nephropathy has cast doubt on the existence of this entity.
Obstructive uropathy
Obstruction of urinary outflow as observed in prostate disease, stone disease, neoplasm, and retroperitoneal fibrosis, among others, can cause chronic tubulointerstitial disease. Modest proteinuria and hyperkalemic renal tubular acidosis are common. Vesicoureteral reflux disease, usually congenital, characteristically results in focal glomerulosclerosis with nephrotic syndrome and a prominent tubulointerstitial component in adult life even if the reflux has been corrected early. Superimposed infection and pyelonephritis often complicate obstruction.
Recurrent urinary tract infection itself can cause ammonium magnesium phosphate stones, further aggravating tubulointerstitial disease and perpetuating infection. Similarly, papillary necrosis and infection may complicate the course and may lead to acute pyelonephritis with fever, flank pain, hematuria, and, especially in elderly patients, urosepsis.
Atherosclerotic kidney disease
As life expectancy increases, atherosclerotic disease of the kidney is emerging as a major category of chronic tubulointerstitial nephropathy. Unfortunately, no unanimity on nomenclature exists among experts, and kidney disease in this category is variably termed ischemic nephropathy, renovascular disease, and nephrosclerosis.
In all likelihood, cases of so-called hypertensive kidney disease or hypertensive nephrosclerosis belong in the category of atherosclerotic kidney disease. Lack of appropriate diagnosis can explain the discrepancy in the incidence of kidney disease in hypertensive populations in Europe and the United States. In Europe, kidney disease is found in only about 1% of hypertensive populations, whereas in the United States, 30% of all end-stage disease requiring dialysis is attributed to hypertensive kidney disease.
Atherosclerotic kidney disease is typically observed in elderly white males who smoke, but it is by no means confined to this population. Many individuals with dyslipidemia and other atherosclerotic phenomena, such as coronary artery disease, carotid artery disease, and peripheral arterial disease, are prone to involvement of renal arteries, regardless of age.
Often, these patients have hypertension, not necessarily severe, with elevated serum creatinine and urea nitrogen and proteinuria, 1-2 g/d. The course of progression of the kidney disease is usually slower than in patients with glomerular diseases such as diabetic nephropathy.
Cholesterol microembolic disease and nephropathy
Cholesterol microembolic disease is a unique syndrome that has been recognized in the setting of catheter procedures involving vasculature above the renal arteries, such as coronary angiography, although it can occur in patients on anticoagulation, and it can even occur spontaneously. The pathophysiology is destabilization of atheroma plaques, either during catheter manipulation or spontaneously, resulting in showering of cholesterol crystals downstream and eventual lodging of needle-shaped cholesterol crystals in small arterioles within the kidney vessels.
Microemboli can also occur in the central nervous system (CNS) and retinal arteries (Hollenhorst plaques). In the extremities, distal vessel emboli may result in small superficial skin infarcts (scabs). More extensive cholesterol microembolization to the extremities can result in the characteristic livedo reticularis appearance in the lower extremities. Oddly, some patients have other systemic signs and symptoms, such as low-grade fever, leukocytosis, eosinophilia, elevated sedimentation rate, and hypocomplementemia.
Cholesterol microembolism usually causes acute renal failure of varying degrees, with some spontaneous improvement in renal function but often with permanent residual renal damage.
The presence of small skin infarcts or scabs, especially on or between the toes or fingers, is a helpful clue to cholesterol microembolism.
Sometimes, particularly after displacement of a large aortic plaque, marked ischemia of the lower extremities yields a bluish-purplish discoloration (ie, livedo reticularis) of the feet or lower portions of legs. Evidence for other atherosclerotic disease, such as carotid or inguinal bruits, may be clues to so-called atherosclerotic kidney disease, particularly in elderly white males who smoke.
Metabolic disorders and nephropathy
Hypercalcemia, chronic potassium depletion, and cystinosis can lead to chronic tubulointerstitial nephritis. Hypercalcemia is the most common cause. Chronic hypercalcemia can occur in primary hyperparathyroidism, sarcoidosis, multiple myeloma, and other neoplasms (particularly with bone metastases) and in vitamin D intoxication. Even transient hypercalcemia can lead to chronic renal insufficiency; renal involvement is mostly confined to the distal tubular structures.
Clinically, polyuria and concentrating defect are common. During acute hypercalcemia, urinary concentrating defect can lead to dehydration and may aggravate acute renal failure. Radiologic examinations may reveal nephrocalcinosis, and renal stone formation can be a complicating factor in hypercalcemia.
Balkan endemic nephropathy
Balkan endemic nephropathy is an endemic kidney disease confined to well-defined discrete settlements located along the Danube River and its tributaries. The caseload of patients is particularly heavy in the Balkans (eg, Croatia, Bosnia & Herzegovina, Serbia, Romania, Bulgaria). The disease occurs in individuals, autochthonous or immigrant, who have resided in the endemic regions for at least 15-20 years and does not occur among residents who move to nonendemic areas. Thus, the evidence implicates environmental factor(s), but no definitive agent or factor has been identified yet. Typically, patients are nonhypertensive and have disproportionately profound anemia.
Because a major criterion to identify Balkan endemic nephropathy is residency in the endemic region, whether similar kidney diseases occur in other parts of the world is not known. Most patients eventually develop end-stage renal disease and require dialysis. Up to 40% of patients develop upper urinary tract uroepithelial tumors.
In general, proteinuria is usually absent or modest in acute tubulointerstitial nephritis. 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.
Patients with acute tubulointerstitial nephritis caused by nonsteroidal anti-inflammatory drugs (NSAIDs) typically present with heavy proteinuria, often in the nephrotic range. Findings on gallium scanning have been reported to be confirmatory in the diagnosis of acute interstitial nephritis.[19, 20] 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.
Clinical investigations in chronic tubulointerstitial nephritis may show modest elevation in serum creatinine, evidence of tubular dysfunction (ie, renal tubular acidosis), or Fanconi syndrome (ie, aminoaciduria, glycosuria, hypophosphatemia, hypouricemia). Proteinuria is usually mild, often less than 1 g/d. In contrast to glomerular disease, a significant fraction of the protein is low molecular weight (eg, immunoglobulin light chains, beta2 microglobulin, lysozyme, peptide hormones). These proteins are normally taken up by the proximal tubules and broken down there. Thus, in diseases predominantly involving tubular structures, decreased endocytosis of filtered proteins leads to the characteristic tubular proteinuria.
In patients with suspected lead exposure, an ethylenediaminetetraacetic acid (EDTA) lead mobilization test or determination of tibial bone lead by radiographic fluorescence can confirm lead etiology.
The diagnosis of atherosclerotic kidney disease can usually be made clinically, and radiologic investigations, such as duplex scanning of the renal arteries, digital subtraction angiography, or magnetic resonance imaging (MRI), reveal atherosclerotic stenosis of the renal arteries. Kidney biopsy is seldom necessary and, if performed, shows nonspecific changes of chronic tubulointerstitial nephritis (ie, tubular atrophy, fibrosis, and arterial or arteriolar sclerosis with paucity of cellular infiltration). Because these patients tend to have atherosclerotic complications, they are likely to experience multiple contrast procedures and hence are at risk for acute recurrent contrast nephropathy, which can accelerate progression to end-stage renal disease.
Patients with Balkan endemic nephropathy are identified easily in endemic regions by checking for tubular proteinuria. Beta2 microglobulinuria has proved particularly useful in identifying cases and has been proposed and used as a marker of the disease.
Eosinophilia, when present, can be very helpful in the evaluation of tubulointerstitial nephritis. However, this finding 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. Typically, eosinophilia is absent in acute tubulointerstitial nephritis that is induced by nonsteroidal anti-inflammatory drugs (NSAIDs).
A complete set of chemistries, including blood urea nitrogen (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 nonsteroidal anti-inflammatory drug (NSAID)–induced analgesic nephropathy, among other conditions.
Urinalysis may reveal proteinuria, hematuria, and the presence of white blood cells (WBCs), with or without bacteria. A microscopic analysis of urine sediment may reveal casts, WBCs, eosinophils, and crystals. If allergic interstitial nephritis is suspected, send a cytospin specimen to determine if eosinophils are in the urine. 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. In nonsteroidal anti-inflammatory drug (NSAID)–induced acute tubulointerstitial nephritis, eosinophiluria is usually absent.
Quantitative determination of urine protein may also 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.
Hettinga and colleagues, in a prospective cohort study of 45 young patients with uveitis, found that urinary β2-microglobulin (β2M), urinary protein, and serum creatinine had predictive value for detecting tubulointerstitial nephritis and uveitis (TINU) syndrome. The positive predictive value of increased β2M levels combined with increased serum creatinine was 100% for detecting patients with definitive and/or probable TINU syndrome.[21]
Urinary N-acetyl-β-D-glucosaminidase (NAG) and matrix metalloproteinases (MMPs) 2 and 9 were significantly inversely correlated with the rate of decline in estimated glomerular filtration rate (GFR) over a period of 11 to 54 months in a study of 54 patients with drug-induced chronic tubulointerstitial nephritis, 10 patients with IgA nephropathy, and 20 healthy controls. These biomarkers may be able to predict deterioration in drug-induced chronic tubulointerstitial nephritis. The areas under the receiver operating characteristic curve for urinary NAG, MMP-9, MMP-2 and α1-microglobulin for predicting decline in estimated GFR were 0.879, 0.867, 0.735 and 0.709, respectively (all P< 0.05).[22]
Ultrasonography is noninvasive imaging technique that is extremely helpful in identifying hydronephrosis in obstructive disease as well as calculi in stone disease. Both radiolucent and radiopaque stones can be visualized with this modality. A combination of ultrasonography and flat plate kidney, ureter, and bladder (KUB) radiography is helpful in the 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.
Once widely used, intravenous pyelography 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.
Computed tomography (CT) scanning 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.
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, the medical history is not reliable in ascertaining the lead etiology in patients presenting with chronic tubulointerstitial nephritis.
Diagnosis of lead nephropathy requires an estimation of the cumulative body stores of lead by either ethylenediaminetetraacetic acid (EDTA) lead mobilization test or by determination of bone lead content by radiographic fluorescence.
The 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 (RBCs) and later extracted to tissues and bone as the RBCs senesce.
Kidney biopsy is the definitive test for diagnosing acute allergic interstitial nephritis, particularly in cases in which the clinical diagnosis is difficult. Because the differential diagnosis of acute tubulointerstitial nephritis encompasses multiple etiologies, consider kidney biopsy when the diagnosis is not obvious.
Kidney biopsy shows mononuclear and often eosinophilic cellular infiltration of the renal parenchyma with sparing of the glomeruli (see the following images). Sometimes, interstitial changes such as fibrosis and atrophy are also present (eg, Renal biopsies have shown severe interstitial fibrosis in patients with Chinese herb/aristolochic acid nephropathy).
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Kidney biopsy. This is an example of acute interstitial nephritis. The renal cortex shows a diffuse interstitial, predominantly mononuclear, inflammat....
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Kidney biopsy. Shown here is an example of acute interstitial nephritis. The diagnosis is based on the active inflammatory infiltrate on the right wit....
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Kidney biopsy. This image shows acute interstitial nephritis. The mononuclear inflammatory infiltrate contains abundant eosinophils, suggesting an all....
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Kidney biopsy. This image shows acute interstitial nephritis. The inflammatory infiltrate forms an ill-defined granuloma, suggesting allergic or infec....
Findings on kidney biopsy in chronic tubulointerstitial nephritis usually show varying degrees of interstitial fibrosis, tubular atrophy, fibrosis, arteriolar sclerosis, and, occasionally, patchy mononuclear cell infiltration (see the image below). Often, the findings are nonspecific and the etiology is not discernible from the biopsy; some diseases, such as sarcoidosis, show noncaseating granulomas, and, in viral diseases, immunostaining can yield clues to the cause.
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Kidney biopsy. This image shows chronic tubulointerstitial nephritis. The interstitium is expanded by fibrosis, with distortion of tubules and periglo....
Kidney biopsy during the acute phase of cholesterol microembolism shows the characteristic needle-shaped clefts caused by the cholesterol crystals within the small- and medium-sized arterioles accompanied by patchy tubulointerstitial nephritis with mild mononuclear cellular infiltration. (Eyeground examination may also reveal the characteristic cholesterol crystals, also termed Hollenhorst plaques, in retinal vessels, which can support the diagnosis.)
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Kidney biopsy in interstitial nephritis. This image shows a cholesterol microembolism. The 2 arterioles in the center are occluded by elongated crysta....
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Kidney biopsy in interstitial nephritis. This image shows a cholesterol microembolism. The arteriole in the center of the field has a thickened wall. ....
Kidney biopsy is not diagnostic of lead etiology for chronic lead poisoning and shows nonspecific changes such as interstitial fibrosis, tubular atrophy, and vascular sclerosis, findings common to tubulointerstitial nephritides of other etiologies.
Corticosteroids have been a mainstay of therapy for tubulointerstitial nephritis, but mycophenolate mofetil may also have a role. Ultimately, however, treatment depends on the underlying etiology.[1]
Most patients presenting with renal insufficiency, proteinuria, and/or acid-base electrolyte disorders require consultation with a nephrologist. These patients may require inpatient care until stabilization or resolution.
Hypertensive patients should be on a low-sodium diet. For all patients with early renal disease, recommend general guidelines for a healthy diet (ie, low-fat [low-cholesterol] diet rich in fresh fruits and vegetables such as the Dietary Approaches to Stop Hypertension [DASH] diet).
Provide patients with acute interstitial nephritis with follow-up care until resolution. Patients who do not recover renal function and those with chronic tubulointerstitial nephritis should receive long-term follow-up care to ensure that optimal control of blood pressure is achieved and to protect kidneys from further potentially nephrotoxic therapies and/or interventions.
In cases of acute tubulointerstitial nephritis due to hypersensitivity reactions (allergic interstitial nephritis), early recognition and prompt discontinuation of the offending drug are helpful; cessation of the offending agent usually, but not always, results in complete recovery in patients. However, the rate of recovery is variable, and, in some patients, renal failure persists for many weeks before renal function improves. Some patients may progress to chronic renal insufficiency.
Obtain a thorough history of previously documented drug allergies before prescribing a new drug.
If no sign of improvement is observed within a few days of discontinuation of the offending agent, consider therapy with steroids. Although controlled trials are lacking, many authors suggest using prednisone at relatively high doses (eg, 1 mg/kg for 4-6 wks with rapid tapering of the dose). This intervention may improve the outcome, speeding renal recovery and reducing the requirement for dialysis.
A systematic review concluded that limited evidence does not support the use of corticosteroids in the treatment of drug-induced cases. The review included eight studies with 430 patients (300 of whom received corticosteroids and 130 of whom did not): four studies showed no difference in serum creatinine levels between the corticosteroid and comparator arms, while four studies found a benefit.[23]
Treatment of chronic tubulointerstitial nephritis depends on the etiology and generally consists of supportive measures, such as adequate blood pressure control and management of anemia.
Analgesic nephropathy
Treatment of analgesic nephropathy is supportive and also includes discontinuation of analgesic use. Long-term follow-up studies have shown progression to end-stage renal disease (ESRD) requiring dialysis, and increased incidence of uroepithelial cancers is also observed in patients with analgesic nephropathy.
Cyclosporine/tacrolimus–induced renal failure
Reduce the cyclosporine/tacrolimus doses and target trough levels. Discontinuing these medications and/or switching to other immunosuppressives (eg, rapamycin), especially in those with more advanced renal failure, should also be considered.
Lead nephropathy
Body burden of lead and bone lead concentration can be reduced by extended chelation treatment using ethylenediaminetetraacetic acid (EDTA) (versenate). Chelation therapy is of proven value and must be implemented in acute lead poisoning. Although the oral chelating agent succimer (Chemet) has proved highly successful in treating children, it has not been widely used in adults. Nevertheless, it appears effective in reducing body lead stores.
Chelation therapy with EDTA may slow progressive renal insufficiency in patients with mild lead intoxication. Several studies from Taiwan have shown that chelation therapy in patients with modest increases in body lead burden (ie, 80-600 µg of lead) significantly slowed and/or reversed the rate of decline in the glomerular filtration rate (GFR) compared with placebo.[24, 25] This was found in both diabetics and nondiabetics.[24, 25] However, given that these studies took place in Taiwan, it is difficult to generalize these results. Further study is needed before this treatment can be recommended.
Because no effective therapy reverses the long-term consequences of lead poisoning, the best therapy is prevention and awareness of potential environmental and occupational sources for lead exposure. Therefore, implement environmental measures, such as removal of lead from indoor paint and gasoline, and eliminate other sources of exposure. Use caution with imported ceramics, particularly if glazed.
In patients with established lead nephropathy, treatment consists of management of hypertension, gout, and chronic renal insufficiency. Many patients with lead nephropathy progress to end-stage kidney failure and require dialysis.
Atherosclerotic kidney disease and cholesterol microembolic disease
No specific therapy is available for atherosclerotic kidney disease, but good control of hypertension, cessation of smoking, and vigorous control of dyslipidemia with diet and with statins are expected to result in improved outcomes. There is also no effective treatment available for cholesterol microembolic disease.
Immunoglobulin G (IgG)-4–related disease
McMahon and colleagues reported a case of a 58-year-old man initially misdiagnosed with chronic interstitial nephritis secondary to renal sarcoid and treated with repeated doses of prednisone. After his third relapse, a repeat renal biopsy confirmed a diagnosis of IgG4-tubulointerstitial nephritis. The patient had become refractory to treatment with prednisone but achieved sustained improvement in renal function after receiving rituximab. At 1 year post-treatment, serum creatinine remained at baseline and a reduction in his kidney size was observed with imaging.[13]
For acute allergic interstitial nephritis, if no spontaneous recovery in renal function is observed after cessation of the offending agent, implementing a short course of steroid therapy is generally recommended. No controlled studies exist on the effect of corticosteroids; therefore, no well-defined dosage and duration exist. Most practitioners recommend a relatively high dose (eg, 1 mg/kg prednisone) with a rapidly tapering regimen within several weeks.
Clinical Context:
Prednisone has anti-inflammatory properties and causes profound and varied metabolic effects by modifying the body's immune response to diverse stimuli. This agent may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear lymphocyte (PMN) activity. Prednisone also stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.
Clinical Context:
Succimer is a metal chelator, an analogue of dimercaprol that is used in lead poisoning. This agent is particularly useful in children with lead blood levels > 45 mcg/dL. Succimer is approved for chelation therapy in children for lead poisoning. However, its value in chronic lead nephropathy is not established.
Clinical Context:
Edetate is used for lead chelation; only the calcium disodium preparation should be used. In the context of this article, use of this medication is confined to testing (ie, to perform the ethylenediaminetetraacetic acid [EDTA] lead mobilization test for diagnosing lead as the etiology of chronic tubulointerstitial nephritis). Extended therapy with this agent to reduce body lead stores may be of possible benefit.
What is tubulointerstitial nephritis?What is the pathophysiology of tubulointerstitial nephritis?What causes tubulointerstitial nephritis?What causes acute tubulointerstitial nephritis?What causes chronic tubulointerstitial nephritis?What is the role of lead in the etiology of tubulointerstitial nephritis?What causes obstructive uropathy in tubulointerstitial nephritis?What is the role of Sjögren syndrome in the etiology of tubulointerstitial nephritis?What is the role of Balkan endemic nephropathy, in the etiology of tubulointerstitial nephritis?What is the role of aristolochic acid in the etiology of tubulointerstitial nephritis?What is the prevalence of tubulointerstitial nephritis?What is the prognosis of tubulointerstitial nephritis?Which clinical history findings are characteristic of tubulointerstitial nephritis?What are the signs and symptoms of acute tubulointerstitial nephritis?Which drugs may induce acute tubulointerstitial nephritis?What are the signs and symptoms of NSAID-related acute tubulointerstitial nephritis?What are the signs and symptoms of antibiotic-induced acute tubulointerstitial nephritis?What are the infectious causes of acute tubulointerstitial nephritis?What are the signs and symptoms of chronic tubulointerstitial nephritis?What is analgesic nephropathy?What is lithium nephropathy?What are cyclosporine- and tacrolimus-induced nephropathy?What are the signs and symptoms of lead nephropathy in tubulointerstitial nephritis?What are the signs and symptoms of obstructive uropathy in tubulointerstitial nephritis?What are atherosclerotic kidney diseases in patients with tubulointerstitial nephritis?What is cholesterol microembolic disease in tubulointerstitial nephritis?Which metabolic disorders are associated with tubulointerstitial nephritis?What is Balkan endemic nephropathy?Which conditions should be included in the differential diagnoses of tubulointerstitial nephritis?What are the differential diagnoses for Tubulointerstitial Nephritis?How is tubulointerstitial nephritis diagnosed?What is the role of a complete blood count (CBC) with differential in the workup of tubulointerstitial nephritis?What is the role of a chemistry panel in the workup of tubulointerstitial nephritis?What is the role of urine studies in the workup of tubulointerstitial nephritis?What is the role of ultrasonography in the workup of tubulointerstitial nephritis?What is the role of IV pyelography in the workup of tubulointerstitial nephritis?What is the role of CT scanning in the workup of tubulointerstitial nephritis?What is the role of an EDTA lead mobilization test in the workup of tubulointerstitial nephritis?What is the role of kidney biopsy in the workup of tubulointerstitial nephritis?Which histologic findings are characteristic of tubulointerstitial nephritis?How is tubulointerstitial nephritis treated?How is acute tubulointerstitial nephritis treated?How is chronic tubulointerstitial nephritis treated?How is analgesic nephropathy treated in tubulointerstitial nephritis?How is cyclosporine/tacrolimus–induced renal failure treated in tubulointerstitial nephritis?How is lead nephropathy treated in tubulointerstitial nephritis?How are atherosclerotic kidney disease and cholesterol microembolic disease treated in patients with tubulointerstitial nephritis?How is immunoglobulin G (IgG)-4–related disease treated in patients with tubulointerstitial nephritis?What is the role of steroid therapy in the treatment of tubulointerstitial nephritis?Which medications in the drug class Chelating agents are used in the treatment of Tubulointerstitial Nephritis?Which medications in the drug class Glucocorticoids are used in the treatment of Tubulointerstitial Nephritis?
A Brent Alper, Jr, MD, MPH, Associate Professor of Medicine, Section of Nephrology and Hypertension, Department of Medicine, Tulane University School of Medicine
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Ajay K Singh, MB, MRCP, MBA, Associate Professor of Medicine, Harvard Medical School; Director of Dialysis, Renal Division, Brigham and Women's Hospital; Director, Brigham/Falkner Dialysis Unit, Faulkner Hospital
Disclosure: Nothing to disclose.
Chief Editor
Vecihi Batuman, MD, FASN, Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System
Disclosure: Nothing to disclose.
Additional Contributors
F John Gennari, MD, Associate Chair for Academic Affairs, Robert F and Genevieve B Patrick Professor, Department of Medicine, University of Vermont College of Medicine
Disclosure: Nothing to disclose.
Acknowledgements
We wish to thank Suzanne Meleg-Smith, MD, for her previous contributions to this article.
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 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 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 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).
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).
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 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. 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).
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).
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).
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