Glomerulonephritis is a spectrum of inflammatory disorders characterized by hematuria and proteinuria. Signs of glomerulonephritis vary from asymptomatic proteinuria and microscopic hematuria to gross hematuria, nephrotic syndrome, hypertension, and impaired renal functioning requiring renal replacement therapy.2 Glomerulonephritis is caused by several disorders, all of which cause inflammation leading to glomerular injury. Examples of hereditary glomerular diseases include systemic lupus erythematosus nephritis, thin glomerular basement membrane disease, and Alport's syndrome.2,7 Poststreptococcal glomerulonephritis, immunoglobulin A (IgA) nephropathy, and Henoch-Schönlein purpura will be discussed in this section.
Glomerulonephritis is an inflammatory process affecting the glomerulus. It can be caused by immune-mediated disorders, inherited disorders, or postinfection sequelae. Glomerulonephritis usually results from deposition of immune complexes within the glomeruli. These immune complexes activate a number of processes including complement activation, leukocyte recruitment, and release of growth factors and cytokines. This leads to inflammation and injury. Sclerosis occurs within the glomeruli, and fibrosis occurs in the tubulointerstitial cells.2,7
Glomerulonephritis may be classified as primary (isolated to the kidney) or secondary (a result of a systemic disorder). There are four main presentations: acute glomerulonephritis, rapidly progressive glomerulonephritis, recurrent macroscopic hematuria, and chronic glomerulonephritis. Although glomerulonephritis caused by streptococcal disease or Henoch-Schönlein purpura usually resolves completely and without sequelae, glomerulonephritis from other causes can progress to renal damage and ultimately end-stage renal failure.2
Glomerulonephritis is often associated with hypertension, which may cause headaches when severe. Symptoms related to hypertension may be the chief complaint of a child with undiagnosed glomerulonephritis.2,7 Patients may complain of bloody or foamy urine (a result of proteinuria), oliguria, fatigue, and lethargy.2,7 In glomerulonephritis, the urinalysis demonstrates macroscopic or microscopic hematuria, RBC casts, and proteinuria. Microscopic examination of urinary sediment shows dysmorphic RBCs and RBC casts. The physical examination is often normal. The blood pressure may be elevated. Other examination findings depend on the underlying disorder.
The microscopic urinalysis demonstrates dysmorphic RBCs and RBC casts. Send urine for culture, because proteinuria and hematuria may represent urinary tract infection, although RBC casts are not typical of infection.7 Other useful studies include a CBC, creatinine level, and electrolytes. Serum albumin level is often reduced. Send serum complement levels (C3 and C4), because complement proteins (C3) are decreased in >90% of patients with poststreptococcal glomerulonephritis, whereas levels are usually normal in patients with IgA nephropathy. Consider streptococcal serologic tests (antistreptolysin-I and streptozyme).7 More specific tests may be needed to make a clear diagnosis in illnesses with systemic manifestations such as Henoch-Schönlein purpura and systemic lupus erythematosus. A renal biopsy is often required for definitive diagnosis in glomerulonephritic disorders.7
Poststreptococcal glomerulonephritis is caused by prior infection with group A β-hemolytic streptococci. Only certain strains of this group are "nephritogenic," and infection of the pharynx is the most common type of infection leading to acute glomerulonephritis, which occurs on average 7 to 14 days after infection. Group A β-hemolytic streptococci stimulate immune complex formation secondary to deposition of streptococcal nephritogenic antigens within the glomerulus. Other infections such as Staphylococcus aureus and S. epidermidis may also lead to renal disease, usually with a longer latency period.
Clinically, poststreptococcal glomerulonephritis consists of microscopic or gross hematuria, proteinuria, hypertension, and edema. Children may give a history of a recent upper respiratory tract or skin infection or have tea-colored urine. The most common serologic markers include an anti-streptolysin O titer, which is typically elevated, and a serum C3 level, which is typically decreased.8 The recovery phase, where proteinuria and gross hematuria begin to resolve, starts after resolution of the patient's fluid overload.8
Treatment is largely supportive. Symptoms of poststreptococcal glomerulonephritis usually resolve in a few weeks. Hypertension rarely requires long-term treatment and tends to resolve within 1 to 2 weeks.8 Renal biopsy is not indicated for diagnosis, unless atypical clinical features are present.8 Asymptomatic patients with probable poststreptococcal disease and normal vital signs are eligible for discharge after consultation, and arrangement for follow-up, with a nephrologist.
IgA nephropathy, also known as Berger's disease, is an autoimmune disease that is responsible for up to 10% of acute glomerulonephritis in the United States. Initially, IgA is deposited on the mesangial cells of the kidney. This alone is not enough to cause IgA nephropathy. In addition, there needs to be reduced IgA clearance, development of glomerular injury, and complement activation, all resulting from dysregulation of mucosal-type IgA immune responses. The cause is unknown.
Clinically, IgA nephropathy may present one of three ways: macroscopic hematuria, microscopic hematuria with mild proteinuria, or acute rapidly progressive glomerulonephritis with edema, hypertension, and renal insufficiency. Macroscopic hematuria is often concurrent with an upper respiratory tract infection and is called synpharyngitic hematuria. The diagnosis is typically based on the clinical history and laboratory data (including urinalysis). Renal biopsy is confirmatory.
Treatment is symptomatic. Immunosuppressant therapy may be initiated to treat underlying inflammation, depending on disease severity. ACE inhibitors or angiotensin receptor blockers may be used to control blood pressure, particularly in patients with proteinuria.9 IgA nephropathy can either completely resolve or progress to end-stage renal disease.9 Concern for a IgA nephropathy in the ED warrants an outpatient referral to nephrology. Rapidly progressive glomerulonephritis requires admission.
Henoch-Schönlein purpura, also known as IgA vasculitis, is a form of systemic vasculitis associated with IgA deposition in the small vessels of the body. Palpable purpura, arthritis/arthralgias, abdominal pain, and renal disease make up the classic presentation tetrad. Henoch-Schönlein purpura nephritis is often asymptomatic, and it is extremely important to follow up to detect persistent renal inflammation.10 Full discussion of Henoch-Schönlein purpura is in chapter 130, "Acute Abdominal Pain in Infants and Children," and we focus on the renal manifestations here.
Renal complications occur in 20% to 54% of patients with Henoch-Schönlein purpura and include gross or microscopic hematuria, proteinuria, or nephritic syndrome.11 Of the children diagnosed with Henoch-Schönlein purpura, 40% have mild nephritis, manifested only by microscopic hematuria or low-grade proteinuria.12 Renal complications may develop any time over a period of 28 days, and 2% of children may develop long-term renal impairment.13 Obtain a urinalysis to identify RBCs, casts, and protein. Treatment focuses on hydration, rest, and analgesics. Treatment with corticosteroids in Henoch-Schönlein purpura with renal involvement is controversial and may lead to increased recurrence of disease. Nephrology consultation is recommended.
Hemolytic-uremic syndrome is a multisystem disorder resulting in acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia. Hemolytic-uremic syndrome is one of the most common causes of AKI in children and typically occurs in those <10 years old. It is classified as typical (diarrhea associated) or atypical. In children, Shiga toxin–producing Escherichia coli causes 90% of hemolytic-uremic syndrome cases, presenting with a prodrome of diarrhea.14 Other causes of hemolytic-uremic syndrome are S. pneumoniae infection, genetic disorders, oral contraceptive use, pregnancy, and malignancy.
Epidemic hemolytic-uremic syndrome is usually caused by infection with E. coli O157:H7, an organism associated with ingestion of undercooked meat, unpasteurized milk, and contaminated fruits and vegetables. E. coli O157:H7 produces a Shiga toxin, which is absorbed from the intestines into the circulation, causing microangiopathic intravascular thrombosis, RBC hemolysis, thrombocytopenia (due to platelet consumption), and decreased glomerular perfusion.14 Microthrombi are deposited in kidney parenchyma, causing hypertension, oliguria, and anuria.15 Renal involvement ranges from mild renal insufficiency to acute renal failure requiring dialysis.
In atypical hemolytic-uremic syndrome associated with S. pneumoniae, pathogenesis is initiated by the pneumococcal enzyme neuraminidase. This enzyme cleaves N-acetylneuraminic acid from the surface of RBCs and endothelial cells, uncovering the T antigen on the surface of endothelial cells. This in turn leads to an immune response, initiating the cascade leading to hemolytic-uremic syndrome.16
The majority of hemolytic-uremic syndrome is associated with E. coli enteritis, and the disease starts with nausea, vomiting, and bloody diarrhea with or without fever. Within a week, anemia, oliguria, and seizures or encephalopathy develop. Other complications include hypertension, heart failure, intussusception, diabetes mellitus, acidosis, and colitis.15 A careful dietary and travel history may identify a potential source of infection to aid public health officials assess epidemic outbreaks.
The differential diagnosis of diarrhea-associated hemolytic-uremic syndrome includes acute gastroenteritis, appendicitis, colitis, intussusception, inflammatory bowel disease, and perforation. Petechiae, hemolysis, and thrombocytopenia are seen in disseminated intravascular coagulation, thrombotic thrombocytopenia purpura, and systemic lupus erythematosus. Some of the symptoms of hemolytic-uremic syndrome may also be seen in malignant hypertension and renal vein thrombosis.
Microangiopathic hemolytic anemia, one of the cardinal features of hemolytic-uremic syndrome, may be profound with a hemoglobin level between 5 and 9 grams/dL. A peripheral smear demonstrates schistocytes, helmet cells, and burr cells. The Coombs test is negative. The platelet count is <150 000/mm3. The WBC count may be elevated.
Hyponatremia and hyperkalemia develop as a result of metabolic acidosis from renal failure, and hyperbilirubinemia results from acute hemolysis.
Obtain a stool specimen to test for Shiga toxin, and specifically test for E. coli O157:H7. Urinalysis demonstrates gross or microscopic hematuria with granular and hyaline casts and variable proteinuria and leukocyturia.
ED management is supportive. Correct life-threatening electrolyte disturbances, and treat hypovolemia with IV fluid boluses (10 to 20 mL/kg normal saline). Exercise cautious use of fluids to prevent fluid overload, particularly in patients with oliguria/anuria.14 Antibiotics are contraindicated in pediatric diarrheal illness and may increase the risk hemolytic-uremic syndrome.15 Antiperistaltic agents increase the risk for systemic complications associated with E. coli infection and are also contraindicated.14 Blood transfusions may be needed for severe anemia. Platelet transfusion is not recommended because it could worsen the thrombotic process. For atypical hemolytic-uremic syndrome, consult with hematology for possible plasma exchange therapy.
All patients with hemolytic-uremic syndrome require hospitalization. Patients with neurologic symptoms and oliguric renal failure should be admitted to the intensive care unit.15 Renal replacement therapy is required in 15% to 70% of cases of acute hemolytic-uremic syndrome.14 Most children (90%) survive the acute phase of the illness, and most regain normal renal function.