Introduction
Background
Nephritis is an older term used to clinically denote a child with hypertension, decreased renal function, hematuria, and edema. Technically, nephritis suggests a noninfectious inflammatory process that involves the nephron; glomerulonephritis (GN) generally is a more precise term.
Diseases that produce GN are usually classified as primary (ie, diseases in which the kidney is the primarily affected organ) and secondary (ie, systemic disorders that involve the kidneys in addition to other organs, such as systemic lupus erythematosus [SLE]).
Currently, most children with hematuria and decreased renal function who do not have a presentation consistent with postinfectious GN receive a renal biopsy, leading to a specific pathologic diagnosis. The general terms GN and nephritis are not specific enough to be very useful for treatment or prognosis.
For a more complete discussion of poststreptococcal GN, see Acute Poststreptococcal Glomerulonephritis.
A second use of the term nephritis is to describe tubulointerstitial nephritis (TIN). TIN is a group of unrelated inflammatory disorders that initially affect mainly the interstitium and renal tubules.
Pathophysiology
In general, nephritis (ie, nonsuppurative) is produced by antigen-antibody complexes (or some other unknown mechanism) trapped in the renal parenchyma. A process of inflammation and cell proliferation (ie, endothelial, mesangial, or epithelial cells are stimulated to proliferate in varying degrees) is initiated, which damages normal renal tissue. If the inflammatory process is turned off, such as in acute poststreptococcal GN, recovery occurs. If the inflammatory process continues unabated, progressive loss of glomeruli and nephrons occurs (eg, in membranoproliferative GN).
In children with TIN, some stimulus (eg, infection, drug, metabolic abnormality) initiates a tubulointerstitial inflammatory process, leading to a mononuclear cell infiltrate. TIN is often clinically classified as acute or chronic based on the rapidity with which decreased renal clearance function develops. With acute TIN, treatment or removal of the stimulus leads to resolution. In chronic TIN, differing rates of progressive renal damage persist.
Frequency
United States
Incidence and prevalence of nephritis in the pediatric population is unknown. Acute postinfectious (most often poststreptococcal) GN has diminished in recent years but is still the most frequent. Other conditions sometimes presenting with nephritis, such as membranoproliferative GN, mesangial proliferative GN, Henoch-Schönlein purpura, immunoglobulin A (IgA) nephropathy, Alport syndrome, and SLE are infrequent.
Acute TIN may account for 5-10% of acute renal failure, and chronic TIN may account for 20% of chronic renal failure in children. TIN is purely a biopsy diagnosis, thus the previous estimates of TIN may be underrepresentations. Most cases of acute TIN in children are virus or medication related. Most cases of chronic TIN in children are related to chronic infection, vesicoureteral reflux, or metabolic disease (eg, oxalosis, Crohn disease1 ).
International
Incidence and prevalence of nephritis and TIN on a worldwide basis is unknown. Industrialized countries tend to produce more reports.
Mortality/Morbidity
A child with nephritis might die of potential complications of severe hypertension (eg, cerebral hemorrhage) or complications of renal failure (eg, hyperkalemia). Generally, fatal outcome in the United States is rare. Children with postinfectious GN usually have complete recovery. Children with chronic GN may develop morbidity secondary to hypertension, chronic renal failure, complications of end-stage renal disease, or complications of the primary disease (eg, SLE).
Over the last 3 decades, an important increase in the survival of children with SLE has been observed, especially in those patients with renal involvement. Management with immunosuppressive drugs (eg, intravenous cyclophosphamide, azathioprine) has changed the prognosis in these children. Children with SLE have increased life expectancy but are now faced with new types of morbidity because of the sequelae related to the disease.
When TIN leads to acute or chronic renal failure, associated morbidity may occur. TIN is an unusual cause of death in children. The prognosis for complete recovery of acute renal failure in TIN is excellent. The prognosis for recovery with chronic TIN depends on the primary disease.
Race
Nephritic syndrome may occur in people of all races. The race of the child is not generally helpful in determining the primary etiology of GN. No racial differences have been reported for the incidence of TIN in children.
Sex
Acute poststreptococcal GN and IgA nephropathy occur more frequently in males than in females. SLE is more frequent in females. TIN occurs with equal frequency in both sexes.
Age
Acute postinfectious GN usually occurs in children older than 2 years. IgA nephropathy is rare before adolescence. Henoch-Schönlein purpura and membranoproliferative GN tend to occur in children older than 8 years. SLE can occur in people of any age but is more frequent in adolescents. Age is not usually very helpful in determining the pathobiology of nephritis.
TIN is very rare in children younger than 5 years. Acute TIN can potentially occur in people of any age. Chronic TIN tends to occur late in childhood or adolescence with obstructive uropathy or reflux. Chronic TIN may occur in younger patients with inherited metabolic diseases.
Clinical
History
- When considering Alport syndrome, family history is important, especially to identify other family members with nephritis or renal failure. When considering poststreptococcal glomerulonephritis (GN), elicit an antecedent history of streptococcal throat or skin infection. Inquire about symptoms of swelling and facial, perioral, or pedal edema or ascites. Symptoms of pulmonary edema or congestive heart failure (eg, dyspnea with exertion, orthopnea, shortness of breath) may be present. Gross hematuria (eg, dark, rust colored, coke colored, tea colored) may be present. With severe hypertension, identify nosebleed, headache, or encephalopathy. The parent may note decreased urine frequency. Nonspecific symptoms, such as malaise, fever, anorexia, or weakness, may be present.
- For children with tubulointerstitial nephritis (TIN) who present with allergic manifestations, most have fever (80-100%) and many have maculopapular rash (25-50%). These symptoms often occur with arthralgias and malaise.
- When considering the diagnosis of TIN, attempt to obtain a history of a known etiology (eg, bacterial, viral, drug-related, metabolic, other).
- In patients with TIN, a history of polyuria rather than oliguria is obtained.
Physical
- Elevated blood pressure is an important physical finding. Look for edema. The child may have a pale appearance because of dilutional anemia. Tachypnea, dyspnea, hepatic congestion, and gallop rhythm suggest fluid overload with congestive heart failure. If a secondary form of GN is suspected, seek physical findings of the condition (eg, vasculitis in SLE).
- With TIN, physical findings include maculopapular rash, joint pain (with flexion and extension), and fever. Rarely, the patient may present with uveitis as part of tubulointerstitial nephritis and uveitis syndrome (TINU).
Causes
- In general, nephritis (nonsuppurative) is produced by the trapping of antigen-antibody complexes (or some other unknown mechanism) in the renal parenchyma. A process of inflammation and cell proliferation (ie, endothelial, mesangial, or epithelial cells are stimulated to proliferate in varying degrees) is initiated, which damages normal renal tissue. If the inflammatory process is ended, such as in acute poststreptococcal GN, recovery occurs. If the inflammatory process continues unabated, progressive loss of glomeruli and nephrons occurs (eg, in membranoproliferative GN).
- TIN probably occurs as a result of humoral and cell-mediated immune reactions against a haptin-protein complex. Cytokines are released and recruitment/dysregulation of inflammatory cells continues, leading to injury out of proportion to the initial insult. Mononuclear cell infiltrates in tubulointerstitial areas is the principal pathogenic process. Tubular dysfunction is out of proportion to glomerular dysfunction. With acute TIN, removal of the stimulus usually results in resolution of the inflammatory process.
More on Nephritis |
 Overview: Nephritis |
| Differential Diagnoses & Workup: Nephritis |
| Treatment & Medication: Nephritis |
| Follow-up: Nephritis |
| References |
| Next Page » |
References
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Eknoyan G. Tubulointerstial nephritis. In: Massry SG, Glassock RJ, eds. Massry and Glassock's Textbook of Nephrology. Philadelphia, PA: Lippincott Williams & Wilkins; 2001:746-58.
Flanc RS, Roberts MA, Strippoli GF, et al. Treatment of diffuse proliferative lupus nephritis: a meta-analysis of randomized controlled trials. Am J Kidney Dis. Feb 2004;43(2):197-208. [Medline].
Glassock RJ, Cohen AH, Adler SG. Primary glomerular diseases. In: Brenner BM, ed. The Kidney. 5th ed. Philadelphia, PA: WB Saunders Co; 1996:1392-1497.
Goda C, Kotake S, Ichiishi A, et al. Clinical features in tubulointerstitial nephritis and uveitis (TINU) syndrome. Am J Ophthalmol. 2005;140(4):637-41. [Medline].
Gonzalez B, Hernandez P, Olguin H, et al. Changes in the survival of patients with systemic lupus erythematosus in childhood: 30 years experience in Chile. Lupus. 2005;14(11):918-23. [Medline].
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Further Reading
Keywords
nephritis, glomerulonephritis, GN, Bright disease, interstitial nephritis, tubulointerstitial disease, tubulointerstitial nephritis, TIN, hypertension, hematuria, edema, systemic lupus erythematosus, SLE, membranoproliferative glomerulonephritis, membranoproliferative GN, mesangial proliferative GN, Henoch-Schönlein purpura, immunoglobulin A nephropathy, Alport syndrome, vesicoureteral reflux, oxalosis, Crohn disease, cerebral hemorrhage, hyperkalemia, pulmonary edema, heart failure, ascites, encephalopathy, polyuria
