eMedicine Specialties > Pediatrics: General Medicine > Nephrology

Nephritis

Sahar Fathallah-Shaykh, MD, Assistant Professor in Pediatric Nephrology, Northwestern University Feinberg School of Medicine; Consulting Staff, Division of Kidney Diseases, Children's Memorial Hospital
Richard Neiberger, MD, PhD, Director of Pediatric Renal Stone Disease Clinic, Associate Professor, Department of Pediatrics, Division of Nephrology, University of Florida College of Medicine and Shands Hospital

Updated: Jul 18, 2008

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.

Differential Diagnoses

Other Problems to Be Considered

Glomerulonephritis (GN)
Takayasu disease
Membranoproliferative GN
Other: Conditions that produce hematuria, decreased clearance, and, sometimes, hypertension include all specific types of GN, anatomic abnormalities of the kidneys, renal stones, tumors, drugs, and infection.

Workup

Laboratory Studies

• The most helpful laboratory studies include assessment of electrolyte, creatinine, and BUN levels; CBC count; urinalysis; urine culture; lupus serologies; measurement of complement components (ie, C3, C4); antistreptolysin-O (ASO) titer; anti-DNAase B, perinuclear antineutrophil cytoplasmic antibody (P-ANCA) measurement; cellular antineutrophil cytoplasmic antibody (C-ANCA) assessment; and serum IgA measurement.
  • If the child has a history consistent with acute poststreptococcal glomerulonephritis (GN), such as low C3, positive ASO, and anti-DNAase B, a provisional diagnosis of acute poststreptococcal GN can be made. Supportive care and observation for improvement within 10-14 days is reasonable.
  • If a diagnosis of acute poststreptococcal GN seems unlikely, a percutaneous renal biopsy is the single most effective mechanism to arrive at a pathologic diagnosis.
  • Laboratory findings with tubulointerstitial nephritis (TIN) include hematuria, eosinophilia, sterile pyuria, low-grade proteinuria, eosinophiluria, and urinary white blood cell casts.
  • A percutaneous renal biopsy is the criterion standard for diagnosing TIN.
• With TIN, the hallmarks of GN (ie, edema, hypertension, sodium chloride retention) are not present. Tubular dysfunction is the predominant feature.
• The pattern of tubular dysfunction that develops depends on the tubular segment(s) involved. Proximal tubular lesions result in aminoaciduria, glucosuria, phosphaturia, uricosuria, beta2 microglobinuria, and bicarbonaturia, often producing proximal renal tubular acidosis. Lesions involving the distal tubule result in inability to acidify the urine (distal renal tubular acidosis), to regulate sodium balance, and to secrete potassium. Lesions affecting the medulla and papilla result in inability to concentrate the urine.
• These tubular functions may be tested by calculating the fractional excretion of phosphate or bicarbonate, measuring the urinary glucose excretion, and measuring the urine pH and osmolality with fasting.

Imaging Studies

• Renal ultrasonography is usually performed to exclude other causes of hypertension and hematuria, such as renal artery stenosis (ie, small abnormal kidney on one side), anatomic abnormalities, tumor, and stones. The kidneys are frequently echodense when GN is present. The kidneys may be abnormally large or small.
• No imaging tests are sensitive or specific for TIN. Renal ultrasonography may show large kidneys with normal echogenicity. Gallium scanning may reveal increased uptake.

Procedures

• If a specific diagnosis is needed for a child with hematuria, proteinuria, edema, and hypertension (ie, nephritis), a percutaneous renal biopsy usually is the criterion standard for identifying a specific pathology.
• The kidney biopsy findings are diagnostic for TIN.

Histologic Findings

• In GN, light microscopy usually reveals infiltration of the kidney by lymphocytes, polymorphonuclear leukocytes, or both. Immunofluorescence microscopy may reveal immunoglobulin G (IgG), IgA, immunoglobulin M (IgM), or complement in mesangial or vascular distribution, depending on the type of nephritis. Electron microscopy may reveal deposits in mesangial, subendothelial, subepithelial, or a combination of tissues, depending on the type of nephritis present. Replacement of renal tissue by scar tissue (tubular atrophy and interstitial fibrosis) is the final common pathway for several types of GN.
• For TIN, light microscopy reveals focal interstitial infiltrates of edema that contains lymphocytes and eosinophils. Tubular injury is usually greater than glomerular or vascular injury.

Treatment

Medical Care

Medical care for glomerulonephritis (GN) is usually divided into 2 major components: treatment of primary pathology and supportive care. In renal diseases, supportive care involves managing hypertension and fluid and electrolyte abnormalities and managing decreased renal function.

Treatment of primary pathology ranges from watchful waiting, as in postinfectious GN, to treatment with immunosuppressive medication, such as steroids or cyclophosphamide in lupus or tubulointerstitial nephritis (TIN). To discuss the primary treatment of all forms of nephritis is beyond the scope of this article. In some causes, for example IgM nephropathy, no definitive therapy is known.

Hypertension can be managed with antihypertensives, such as calcium channel–blocking agents, ACE inhibitors, angiotensin receptor–blocking agents, peripheral vasodilators, and diuretics. The most common fluid abnormality is hypervolemia managed with fluid restriction and diuretics or dialysis if renal function is too poor to respond to diuretics. Hyponatremia is usually dilutional and responds, at least partially, to removal of excess fluid. Hypocalcemia may respond to oral or intravenous calcium, depending on severity. Mild metabolic acidosis may be present but rarely requires primary treatment. For dosages of the above medications see Medication.

The primary treatment for TIN is to stop the offending agent.

Surgical Care

If dialysis access is necessary, consultation with a surgeon may be required.

Consultations

Primary care physicians can usually manage children with poststreptococcal GN unless dialysis is imminent. Refer children with other forms of GN or TIN to a pediatric nephrologist.

Diet

In children with acute renal failure secondary to GN who have lost the ability to excrete a water load, fluid restriction may prevent fluid overload. TIN usually produces nonoliguric ARF. Fluid restriction of 300 mL/m²/d plus losses may allow management of acute renal failure for 2-3 days without dialysis. In patients with hypertension, sodium restriction to recommended daily allowances (RDA) of 2-4 mEq/kg/d may aid in management. In children with renal failure, potassium restriction is justified to prevent hyperkalemia. A short-term high-carbohydrate diet may prevent catabolism of body protein as an energy source. Calcium supplementation is useful to maintain normal serum calcium.

Activity

In patients with hypertension and renal failure, discourage strenuous activity; however, walking, playing, and other activities are acceptable.

Medication

Medications used to treat patients with glomerulonephritis (GN) generally fall into 3 categories: antihypertensives, diuretics, and anti-inflammatory or immunosuppressives.

Some recommend a short course of steroids or cyclophosphamide for tubulointerstitial nephritis. These drugs are usually not necessary. Most often, stopping the offending agent leads to recovery.

Pharmacotherapy may include numerous drug classes that have antihypertensive effects. They possess different pharmacological actions. Thiazide diuretics and beta-blockers have been the mainstay of drug therapy for hypertension. Recently, the availability of other drugs (eg, calcium-channel blockers, ACE inhibitors, alpha-blockers, angiotensin II receptor antagonists) allows regimens to be customized to the population treated and allows enhanced compliance and improved ability to tolerate treatment. For complete information, see the following pediatric topics Hypertension and Neonatal Hypertension.

Diuretic agents

These agents are used to remove excess fluid in children with edema secondary to renal disease and as an adjunct to manage hypertension.

Furosemide (Lasix)

A loop diuretic. Often effective in removing fluid even when GFR is reduced secondary to nephritis.
Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule.

Dosing

Adult

20-80 mg/d PO/IV/IM; titrate up to 600 mg/d for severe edematous states

Pediatric

1-2 mg/kg PO/IV up to 6 mg/kg/d

Interactions

Metformin decreases furosemide concentrations; furosemide interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides and furosemide; hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently with this medication; increased plasma lithium levels and toxicity are possible when taken concurrently with this medication

Contraindications

Documented hypersensitivity; hepatic coma; anuria; state of severe electrolyte depletion

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

Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter

Follow-up

Further Inpatient Care

• Inpatient care is usually necessary only to manage severe hypertension or complications of acute or chronic renal failure (eg, dialysis access, uremic syndrome, congestive heart failure, electrolyte abnormalities such as hyperkalemia and pericardial effusion). These problems are infrequent in the general pediatric population.

Further Outpatient Care

• Outpatient care is an extension of inpatient care.
• Outpatient care may be as simple as observation in a child with tubulointerstitial nephritis or resolving poststreptococcal glomerulonephritis (GN) or may involve antihypertensives, diuretics, and diet modification as in a child with IgA nephropathy or membranoproliferative GN and preserved renal function.
• Outpatient care may involve dialysis and transplantation in a child who develops end-stage renal disease.

Inpatient & Outpatient Medications

• No specific change in medications is necessary for transition from inpatient to outpatient care.

Transfer

• A physician who has experience in managing renal failure in children should care for children with renal failure. In the United States, this is frequently at a tertiary facility.

Deterrence/Prevention

• No effective methods of deterrence or prevention are known.

Complications

• Primary complications associated with hypertension
  • Seizure
  • Encephalopathy
  • Stroke
  • End-organ damage
• Primary complications associated with kidney failure
  • Fluid overload
  • Electrolyte abnormality
  • Uremic symptoms
  • Anemia
  • Abnormal bone mineralization
  • Sexual dysfunction
  • Poor growth
  • Anorexia
  • Endocrine abnormalities

Prognosis

• The overall prognosis for survival in children with all forms of nephritis is good.

Patient Education

• Education about the specific nephritis is helpful.
• Encourage medication compliance and a healthy lifestyle (eg, ideal body weight, no smoking, exercise, avoidance of risk behaviors).
• For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also, see eMedicine's patient education article Blood in the Urine.

Miscellaneous

Medicolegal Pitfalls

• Failure to consider the diagnosis in a child with nephritis may delay diagnosis and treatment, which may allow progression to end-stage renal disease and allow complications, such as hypertensive seizures, to occur. A provider might be held responsible.

References

1. Marcus SB, Brown JB, Melin-Aldana H, Strople JA. Tubulointerstitial nephritis: an extraintestinal manifestation of Crohn disease in children. J Pediatr Gastroenterol Nutr. Mar 2008;46(3):338-41. [Medline].

2. Adler SG, Cohen AH, Glassock RJ. Secondary glomerular diseases. In: Brenner BM, ed. The Kidney. 5^th ed. Philadelphia, PA: WB Saunders Co; 1996:1498-1596.

3. Balow JE, Austin HA. Treatment of proliferative lupus nephritis. Am J Kidney Dis. Feb 2004;43(2):383-5. [Medline].

4. Bargman JM. Management of minimal lesion glomerulonephritis: evidence-based recommendations. Kidney Int Suppl. Jun 1999;70:S3-16. [Medline].

5. Cattran DC. Evidence-based recommendations for the management of glomerulonephritis. Introduction. Kidney Int Suppl. Jun 1999;70:S1-2. [Medline].

6. Eddy AA. Mechanisms of immune glomerular injury. In: Barrett TM, Avener EV, Harmon H, eds. Pediatric Nephrology. 4^th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999:641-68.

7. 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.

8. 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].

9. Glassock RJ, Cohen AH, Adler SG. Primary glomerular diseases. In: Brenner BM, ed. The Kidney. 5^th ed. Philadelphia, PA: WB Saunders Co; 1996:1392-1497.

10. 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].

11. 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].

12. Lee JW, Kim HJ, Sung SH, Lee SJ. A case of tubulointerstitial nephritis and uveitis syndrome with severe immunologic dysregulation. Pediatr Nephrol. 2005;20(12):1805-8. [Medline].

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

Contributor Information and Disclosures

Author

Sahar Fathallah-Shaykh, MD, Assistant Professor in Pediatric Nephrology, Northwestern University Feinberg School of Medicine; Consulting Staff, Division of Kidney Diseases, Children's Memorial Hospital
Sahar Fathallah-Shaykh, MD is a member of the following medical societies: American Society of Nephrology
Disclosure: emedecine Honoraria Other

Coauthor(s)

Richard Neiberger, MD, PhD, Director of Pediatric Renal Stone Disease Clinic, Associate Professor, Department of Pediatrics, Division of Nephrology, University of Florida College of Medicine and Shands Hospital
Richard Neiberger, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Medical Association, American Society of Nephrology, American Society of Pediatric Nephrology, Christian Medical & Dental Society, Florida Medical Association, International Society for Peritoneal Dialysis, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Shock Society, Sigma Xi, Southern Medical Association, Southern Society for Pediatric Research, and Southwest Pediatric Nephrology Study Group
Disclosure: Nothing to disclose.

Medical Editor

Uri S Alon, MD, Director of Research and Education, Department of Pediatrics, Division of Pediatric Nephrology, Children's Mercy Hospital of Kansas City; Professor, University of Missouri at Kansas City
Uri S Alon, MD is a member of the following medical societies: American Federation for Medical Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Frederick J Kaskel, MD, PhD, Director of the Division and Training Program in Pediatric Nephrology, Vice Chair, Department of Pediatrics, Montefiore Medical Center and Albert Einstein School of Medicine
Frederick J Kaskel, MD, PhD is a member of the following medical societies: Academy of Medical Royal Colleges, American Academy of Pediatrics, American Association for the Advancement of Science, American Heart Association, American Pediatric Society, American Physiological Society, American Society of Nephrology, American Society of Pediatric Nephrology, American Society of Transplantation, Eastern Society for Pediatric Research, Federation of American Societies for Experimental Biology, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Renal Physicians Association, Sigma Xi, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Howard Trachtman, MD, Program Director, Pediatrics Research, Schneider Children's Hospital, Department of Pediatrics, Division of Nephrology, Professor, Albert Einstein College of Medicine
Howard Trachtman, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD, The Isaac A Abt, MD, Professor of Kidney Diseases, Feinberg School of Medicine, Northwestern University; Division Head of Kidney Diseases, Children's Memorial Hospital, Chicago
Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology
Disclosure: Amgen Grant/research funds None; Abbott Honoraria Speaking and teaching; Altus Pharmaceuticals Grant/research funds None; Genzyme Grant/research funds None; Merck Grant/research funds None; NIH Grant/research funds None

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