eMedicine Specialties > Nephrology > Tubulointerstitial Diseases of the Kidney

Nephritis, Interstitial

A Brent Alper Jr, MD, MPH, Associate Professor of Medicine, Section of Nephrology and Hypertension, Department of Medicine, Tulane University School of Medicine

Updated: Sep 21, 2009

Introduction

Background

Kidney diseases that involve structures in the kidney outside the glomerulus are broadly referred to as tubulointerstitial. These diseases generally involve tubules and/or the interstitium of the kidney and spare the glomeruli, as shown in the first 3 images below and in Images 1-3. Although primary glomerular diseases are often associated with prominent tubulointerstitial changes (see fourth image below and Image 4), the clinical presentation is dominated by the consequences of glomerular injury; hence, they are not considered in 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. 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).

Tubulointerstitial diseases

• Acute tubulointerstitial nephritis:
  • Hypersensitivity reactions (eg, drugs, penicillins, sulfa drugs, nonsteroidal anti-inflammatory drugs [NSAIDs] most common)
  • Immunologic diseases (eg, associated with lupus, Goodpasture syndrome)
  • Acute transplant rejection
  • Infections:
    • Bacterial (must be accompanied by obstruction or reflux)
    • Viral (eg, cytomegalovirus [CMV], hantavirus, HIV, hepatitis B)
    • Fungal (eg, histoplasmosis)
    • Parasitic (eg, Leishmania, Toxoplasma)
• Chronic tubulointerstitial nephritis:
  • Drugs (eg, analgesics, lithium, cyclosporine, tacrolimus)¹
  • Heavy metals (eg, lead, cadmium, mercury)
  • Obstructive uropathy, nephrolithiasis, reflux disease
  • Immunologic diseases:
    • Lupus, Sjögren syndrome, primary glomerulopathies, sarcoidosis - A study by Maripuri et al found that out 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.² Eleven of the 17 patients had the chronic form of this nephritis. The results, according to the investigators, 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.
    • Vasculitis, antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides, Wegener granulomatosis
    • Chronic transplant nephropathy
  • Neoplasia (eg, myeloma, leukemia, amyloidosis)
  • Atherosclerotic kidney disease (ischemic) - Cholesterol microembolism
  • Metabolic diseases (eg, hypercalcemia, cystinosis, potassium depletion, nephropathy, hyperoxaluria)
  • Genetics (eg, Alport syndrome, medullary cystic disease)
  • Miscellaneous (eg, Balkan endemic nephropathy, Chinese herb/aristolochic acid nephropathy)^3,4

Pathophysiology

At the structural level in acute and chronic tubulointerstitial diseases, clinical presentations are the result of the interplay of renal cells and inflammatory cells and their products. 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.

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. 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 (NF- κ B) in injured kidney cells, 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.

Frequency

United States

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.

International

In certain regions, such as the Balkans (ie, Yugoslavia, Bosnia, Croatia, Romania, Bulgaria), where endemic nephropathy is common, interstitial diseases may be more prevalent.^3,4

Mortality/Morbidity

• Tubulointerstitial disease may progress to end-stage renal disease.
• An increased incidence of uroepithelial cancers is found among patients with analgesic nephropathy, aristolochic acid nephropathy, and Balkan endemic nephropathy.^3,4

Race

Neither acute nor chronic tubulointerstitial diseases of the kidney demonstrate racial predilections. Lead nephropathy may be more common in black people because of socioeconomic factors.

Sex

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.

Age

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.

Clinical

History

History depends on whether the tubulointerstitial nephritis is acute or chronic.

Acute tubulointerstitial nephritis (general features)

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 (IgE) 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.

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 (see image below and Image 1). Patients with acute tubulointerstitial nephritis caused by NSAIDs typically present with heavy proteinuria, often in the nephrotic range (see below). Cessation of the offending agent (see list below) usually, but not always, results in complete recovery. However, the rate of recovery is variable, and, in some patients, renal failure persists for many weeks before renal function improves.

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).

• Antibiotics (eg, penicillins, cephalosporins, sulfa drugs, quinolones)
• NSAIDs
• Diuretics (eg, thiazides, furosemide)
• Allopurinol
• Phenytoin
• Rifampin
• Interferon alfa
• Proton pump inhibitors

Acute tubulointerstitial nephritis caused by NSAIDs

This condition 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 (see images below and Images 1-3).

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).

This form of 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. 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 (see first image below and Image 5). Occasionally, ill-defined granulomas are present (see second image below and Image 6).

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).

Acute tubulointerstitial nephritis caused by miscellaneous agents

Infections with viral agents, bacteria, and fungi are occasionally associated with acute interstitial nephritis. Hantavirus, CMV, and 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.

Chronic tubulointerstitial nephritis (general features)

The chronic form is an insidious disease and most probably represents the common final response pattern of the kidney to a variety of insults and agents (see Background). Important causes include analgesics; lead; drugs, including cyclosporine, cisplatin, and lithium; 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.

Clinical investigations 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.

Findings on kidney biopsy in chronic tubulointerstitial nephritis usually show varying degrees of interstitial fibrosis, tubular atrophy, arteriolar sclerosis, and, occasionally, mononuclear cell infiltration (see image below and Image 7). 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. 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.

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).

Analgesic nephropathy is the most common category of chronic interstitial nephritis worldwide. 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, it 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 can be supported by history of heavy analgesic use, and computer-assisted tomograms may reveal microcalcifications at the papillary tips.

Treatment is supportive and includes discontinuation of analgesic use. Long-term follow-up studies have shown progression to end-stage renal disease requiring dialysis, and increased incidence of uroepithelial cancers is also observed in patients with analgesic nephropathy.

Lithium nephropathy

Distal tubular dysfunction (ie, polyuria, concentrating defect, down-regulation 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

These agents, although indispensable in the management of solid organ transplantation, 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, it is rare in bone marrow transplant recipients because they 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 EDTA lead mobilization test, 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, while 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. Diagnosis can usually be made clinically, and radiologic investigations, such as duplex scanning of the renal arteries, digital subtraction angiography, or magnetic resonance imaging, 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.

No specific therapy is available, but good control of hypertension, cessation of smoking, and vigorous control of dyslipidemia with diet and with hepatic 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are expected to result in improved outcomes.

Cholesterol microembolic disease and nephropathy

This 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; it can even 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 (see images below and Images 8-9).

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).

Cholesterol microembolism usually causes acute renal failure of varying degrees, with some spontaneous improvement in renal function but often with permanent residual renal damage. Kidney biopsy during the acute phase shows the characteristic needle-shaped clefts caused by the cholesterol crystals within the small- and medium-sized arterioles (see Images 8-9) accompanied by patchy tubulointerstitial nephritis with mild mononuclear cellular infiltration. No effective treatment for this disorder is available.

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^3,4

This 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 (ie, Bosnia, Croatia, Yugoslavia, 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.

Patients are identified easily in the 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. Because a major criterion to identify the disease 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.

Chinese herb/aristolochic acid nephropathy

Chronic progressive tubulointerstitial nephritis has been observed in many countries among patients using Chinese herbal medicines for weight reduction. Most of these cases have been attributed to herbs containing aristolochic acid. The pathophysiology of nephrotoxicity is not well understood. Renal biopsies have shown severe interstitial fibrosis.

Physical

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).⁵

• Acute allergic tubulointerstitial nephritis: Physical examination in acute tubulointerstitial nephritis may show a rash accompanying renal findings. However, rash is highly variable. 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.
• Cholesterol microembolic disease: In cholesterol microembolic disease, eyeground examination may reveal the characteristic cholesterol crystals, also termed Hollenhorst plaques, in retinal vessels, which can support the diagnosis. Similarly, 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.
• Atherosclerotic (ischemic) kidney disease: 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.

Causes

• Acute allergic interstitial nephritis: Any drug can cause an acute allergic reaction involving the kidneys. Drugs most commonly associated with acute allergic nephritides are listed in History. 
• Cholesterol microembolic disease: Underlying atherosclerotic disease, dyslipidemia, and smoking are conditions commonly associated with this disorder. Catheter manipulations above the level of the renal arteries or anticoagulation in a patient with atherosclerosis can trigger cholesterol microembolic disease.
• Balkan endemic nephropathy: Epidemiology and natural history clearly implicate environmental factors in the pathophysiology of this disease. Lead contamination of food has been considered but ruled out as a cause. 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.
• 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. 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. Prostate disease in elderly males and pelvic or colonic tumors involving both ureters in both sexes can cause obstructive uropathy. Nephrolithiasis, with or without urinary tract infection, may also cause obstructive uropathy. Radiation to the pelvic area and some drugs, such as methysergide, can cause retroperitoneal fibrosis and obstruction.
• Chinese herb/aristolochic acid nephropathy 
  • Aristolochic acid was recognized as a potent nephrotoxin that can cause rapidly progressive interstitial fibrosis and end-stage renal disease in young women using a Chinese herb as part of a slimming regimen in Belgium in early 1990s.
  • Since then, many other cases of so-called Chinese herb (CH) nephropathy have been reported from around the world. CH 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 AAN is its association with uroepithelial cancers reminiscent of Balkan nephropathy. Aristolochic acid not only can trigger severe renal fibrosis but 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 p53, a known tumor suppressor gene.

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).

Treatment

Medical Care

• Treatment of acute tubulointerstitial nephritis 
• In most cases, cessation of the offending agent results in quick recovery and complete resolution of the renal disorder, although some patients progress to chronic renal insufficiency.
• 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 weeks, with rapid tapering of the dose. This intervention may improve the outcome, speeding renal recovery and reducing the requirement for dialysis.
• Treatment of chronic tubulointerstitial disease: Treatment depends on the etiology and generally consists of supportive measures, such as adequate blood pressure control and management of anemia.
• Treatment of lead nephropathy
• 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 to placebo. This was found in both diabetics and nondiabetics.^6,7 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.
• 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.
• Treatment of cyclosporine/tacrolimus induced renal failure: Treatment includes reducing 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.

Consultations

Most patients presenting with renal insufficiency, proteinuria, and/or acid-base electrolyte disorders require consultation with a nephrologist.

Diet

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.

Medication

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.

Glucocorticoids

Immunosuppressants for treatment of autoimmune disorders.

Prednisone (Sterapred)

Has anti-inflammatory properties and causes profound and varied metabolic effects. Modifies the body's immune response to diverse stimuli. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.

Dosing

Adult

0.5-2 mg/kg/d PO, taper as condition improves; single am dose safer for long-term use, but divided doses have greater anti-inflammatory effect

Pediatric

Not established

Interactions

Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Chelating agents

These agents promote the excretion of lead.

Succimer (Chemet)

Metal chelator, analog of dimercaprol. Used in lead poisoning. Particularly useful in children with lead blood levels >45 mcg/dL. Approved for chelation therapy in children for lead poisoning. Its value in chronic lead nephropathy is not established.

Dosing

Adult

10 mg/kg PO q8h for 5 d, followed by 10 mg/kg PO q12h for 14 d; repeat dosing may be necessary

Pediatric

Administer as in adults

Interactions

Not to be administered concomitantly with edetate calcium disodium or penicillamine

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Renal or hepatic impairment; to prevent toxicity, patients should be well hydrated

Edetate calcium disodium (Calcium Disodium Versenate)

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 EDTA lead mobilization test for diagnosing lead etiology of chronic tubulointerstitial nephritis. Extended therapy to reduce body lead stores may possibly be beneficial.

Dosing

Adult

EDTA lead mobilization test: 2 g IV/IM; for IV, dilute with 500 mL of D5W or 0.9% NaCl and infuse over 8-12 h; if IM used, mix with 5 mL of 2% lidocaine to avoid pain at injection site

Pediatric

Administer as in adults; not to exceed 1 g/d

Interactions

EDTA enhances hypoglycemic effects of insulin in diabetic patients; not to be used with other chelating agents

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Patients should be well hydrated; EDTA may worsen CNS toxicity if administered prior to BAL therapy; use only calcium disodium preparation to avoid hypocalcemia; do not confuse with the similarly named product edetate disodium (Endrate), which is indicated for hypercalcemia and ventricular arrhythmia secondary to digitalis toxicity; each of these 2 products are commonly referred to as EDTA, and, as a result, the 2 products are easily mistaken for each other when prescribing, dispensing, and administering; deaths in patients when mistakenly given edetate disodium instead of edetate calcium disodium or when edetate disodium was used for chelation therapy; for more information, see the FDA MedWatch Safety Information

Follow-up

Further Inpatient Care

• Patients with acute renal failure or with serious electrolyte or acid-base disorders may require inpatient care until stabilization or resolution.

Further Outpatient Care

• 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.

Deterrence/Prevention

• Allergic interstitial nephritis: Early recognition and prompt discontinuation of the offending drug are helpful.
• Lead nephropathy: 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.

Complications

• Hypertension may complicate any renal disease, but not all cases of interstitial renal disease are associated with hypertension (ie, Balkan endemic nephropathy, acute allergic interstitial nephritides).
• Electrolyte and acid-base disorders may be observed.
• Chronic tubulointerstitial disease may progress to end-stage renal disease, requiring dialysis or transplantation.

Prognosis

• Allergic interstitial nephritis: Most patients recover renal function upon cessation of the offending agent.
• Cholesterol microembolic kidney disease: Often, some spontaneous improvement in renal function occurs after the embolic event. Complete resolution of renal insufficiency is rare, however.
• Chronic tubulointerstitial nephritides: Although the natural history of these diseases varies depending on the etiology, most chronic tubulointerstitial renal disease eventually progresses to end-stage renal disease. However, the rate of progression is generally believed to be much slower in tubulointerstitial nephritis compared to glomerular diseases.

Patient Education

• For excellent patient education resources, visit eMedicine's Diabetes Center and Cholesterol Center. Also, see eMedicine's patient education articles Acute Kidney Failure, High Cholesterol, and Cholesterol FAQs.
• For further information, see Mayo Clinic - Kidney Transplant.

Miscellaneous

Medicolegal Pitfalls

• Allergic interstitial nephritis: Make sure to obtain a thorough history of previously documented drug allergies before prescribing a new drug.

Multimedia

Media file 1: 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).

Media file 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).

Media file 3: 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).

Media file 4: 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).

Media file 5: 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).

Media file 6: 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).

Media file 7: 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).

Media file 8: 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).

Media file 9: 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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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

Contributor Information and Disclosures

Author

A Brent Alper Jr, MD, MPH, Associate Professor of Medicine, Section of Nephrology and Hypertension, Department of Medicine, Tulane University School of Medicine
A Brent Alper Jr, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Hypertension, American Society of Nephrology, National Kidney Foundation, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Medical Editor

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
F John Gennari, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Federation for Medical Research, American Heart Association, American Physiological Society, American Society for Clinical Investigation, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Ajay K Singh, MB, MRCP, MBA, Associate Professor of Medicine, Harvard Medical School; Clinical Chief, Renal Division, Director of Dialysis, Brigham and Women's Hospital; Consulting Staff, Faulkner Hospital
Disclosure: Nothing to disclose.

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

We wish to thank Suzanne Meleg-Smith, MD, for her previous contributions to this article.

Related eMedicine topics:
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Nephritis, Lupus
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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

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