para>Urgent investigation and treatment are required to avoid irreversible loss of kidney function.
EPIDEMIOLOGY
- Postinfectious GN
- Most commonly follows group A β-hemolytic Streptococcus infection but can occur as a result of other bacterial infections or less commonly in the setting of viral or parasitic infections
- Accounts for 80% of acute GN in children
- May also occur in the setting of infective endocarditis
- IgA nephropathy
- Most common form of primary acute GN
- Occurs mainly in the 2nd and 3rd decades
- Male > female (2:1)
- Incidence differs geographically: Asia > United States
- HSP typically childhood illness, usually <10 years old
- Anti-GBM disease
- A notable cause of the pulmonary-renal syndrome known as Goodpasture disease
- Peak distribution in 3rd and 6th decades
- ANCA-associated GN
- Often has a relapsing and remitting course
- Four disease presentations:
- Granulomatosis with polyangiitis (GPA) formerly Wegener granulomatosis
- Microscopic polyangiitis (MPA)
- Isolated Pauci-immune GN-when isolated to kidneys
- Eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss disease-GN relatively common but renal involvement rarely severe
- Older patients are more commonly affected, although this GN can affect any age group.
- MPGN
- May be primary or secondary
- May present in the setting of a systemic viral (hepatitis B or hepatitis C) or rheumatologic illness
- Classification by immunofluorescence: immune complex mediated or complement mediated (dense deposit disease [DDD] and C3 glomerulonephritis [C3GN])
- Classification by electron microscopy: MPGN types I-III
- Lupus nephritis
- 30-70% of systemic lupus patients will have renal involvement.
- Several histologic variants but diffuse proliferative GN most severe and requires urgent treatment
- Cryoglobulin-associated vasculitis
- 80% of cases are associated with hepatitis C infection.
ETIOLOGY AND PATHOPHYSIOLOGY
- In general, an immunologic mechanism triggers inflammation and proliferation of glomerular tissue.
- Postinfectious GN: immune complex disease with host immune reaction to nephritogenic strains of streptococci as a trigger
- IgA nephropathy: relates to an abnormal glycosylation of IgA
- Anti-GBM disease: caused by autoantibodies that target type IV collagen of basement membranes
- ANCA-associated GN: Autoantibodies against neutrophil granules are involved in the pathogenesis.
- MPGN: An immune or genetic etiology is presumed, which triggers glomerular deposits and inflammation.
- Lupus nephritis: an immune complex-mediated glomerular disease
- Cryoglobulin-associated GN: An immune etiology is presumed but not clearly defined.
Genetics
Genetic factors are likely to play a role in susceptibility to many of the acute GNs, although these have not been sufficiently defined to be clinically useful in most circumstances.
RISK FACTORS
- Epidemics of nephritogenic strains of streptococci are triggers for postinfectious GN.
- Hepatic cirrhosis, celiac disease, and HIV infection place patients at risk for IgA nephropathy.
- Anti-GBM disease has been associated with influenza A infection and inhaled hydrocarbon solvent exposure.
- ANCA-associated GN is increased in settings where there is increased silica exposure (i.e., earthquakes and farming).
- Infection with hepatitis B or C is known to be associated with MPGN.
- Infection with hepatitis C is a risk factor for developing cryoglobulinemic GN.
- Mutations in alternate complement pathway genes are associated with complement-mediated MPGN.
GENERAL PREVENTION
Early detection is paramount.
DIAGNOSIS
HISTORY
- Patients may report cola- or tea-colored urine and decreased urine volume.
- Edema occurs in many patients, typically in face and lower extremities.
- Shortness of breath may occur with significant fluid overload.
- Generalized malaise
- Timing
- Postinfectious GN typically occurs 1to 3 weeks after pharyngitis or 2 to 6 weeks after skin infection.
- IgA nephropathy may present within several days after an acute infection.
- Patients may also present with complaints more specific to the associated disease:
- Joint pain or rash in lupus nephritis
- Hemoptysis in pulmonary-renal syndromes (see "Physical Exam")
- Sinusitis, pulmonary infiltrates, arthralgias in ANCA-associated GN
- Abdominal or joint pain and purpura in IgA-HSP
- Purpura and skin vasculitis in cryoglobulinemia-associated GN
PHYSICAL EXAM
- A complete physical exam may discover clues to systemic disease as a potential cause.
- Sinus disease: ANCA-associated GN, most commonly GPA
- Pharyngitis or impetigo: postinfectious GN or IgA nephropathy
- Pulmonary hemorrhage (pulmonary-renal syndrome): anti-GBM disease/Goodpasture, ANCA-associated GN, or lupus nephritis
- Hepatomegaly or liver tenderness could point to cryoglobulinemia-associated GN or IgA nephropathy.
- Purpura may point to ANCA-associated GN or HSP/IgA nephropathy.
DIFFERENTIAL DIAGNOSIS
Nonglomerular hematuria: trauma, prostate diseases, urologic cancer, cystitis, nephrolithiasis, renal cysts
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Urinalysis with examination of sediment
- Dysmorphic RBCs or RBC casts on urine microscopy indicate glomerular hematuria and strongly suggest the diagnosis of an acute GN.
- Pyuria and white blood cell casts may also be present.
- Electrolytes, BUN, creatinine, CBC
- Antistreptolysin O titer, streptozyme: often positive in poststreptococcal GN
- Complement levels (C3, C4)
- C3 complement levels are low in postinfectious GN.
- C3 and C4 are abnormal in lupus nephritis and MPGN.
- C4 can be low in cryoglobulinemia.
- Proteinuria: 24-hour collection or random urine protein/creatinine ratio
- Typically mild to moderate proteinuria, sometimes nephrotic range
- Antinuclear antibody (ANA) to rule out lupus nephritis
- ANCA antibody screen: MPO and PR3 antibodies
- Anti-GBM antibody
- Hepatitis B surface antigen and antibody
- Hepatitis C antibody
- HIV testing
- A chest x-ray may be useful in the setting of hemoptysis or a suspected infiltrate on exam.
Test Interpretation
- Renal biopsy
- If clinical picture is consistent with postinfectious GN in a child, a biopsy may not be required.
- If there is clinical suspicion for other causes of acute GN, renal biopsy should be done.
- Light microscopy
- Diffuse hypercellularity suggests a proliferative disease such as IgA nephropathy, lupus nephritis, or postinfectious GN.
- Presence of glomerular crescents correlates with RPGN and disease severity.
- Immunofluorescence
- Isolated mesangial IgA staining is pathognomonic for IgA nephropathy, with the absence of immune complex staining suggesting ANCA-associated GN.
- Pattern of IgG, IgM, C3, and C4 staining may also aid in characterizing the GN.
- Lupus nephritis typically positive for all immunoglobulins and complements ("full house")
- Electron microscopy: The location of immunoglobulin deposits is useful in pointing to a particular diagnosis.
TREATMENT
Supportive in postinfectious GN
MEDICATION
First Line
- Hypertension
- Diuretics are useful for management of salt retention and edema.
- Calcium channel blockers
- Avoid angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) if acute renal dysfunction is present.
- Peripheral edema: Loop diuretics are often required due to the degree of edema.
- Pulmonary edema: oxygen and diuretics
Second Line
- Each of the glomerular diseases often requires a specific treatment plan based on renal biopsy results; therefore, a nephrologist is often the guiding care at this point.
- Empiric pulse methylprednisolone prior to kidney biopsy may be indicated in cases of RPGN (1)[C].
- Crescents on renal biopsy may be an indication for steroids in postinfectious GN and in other cases, are often an indication for potent immunosuppressive medications in addition to steroids (2)[C].
- Steroids plus either cyclophosphamide, rituximab, or mycophenolate may be used to treat ANCA-associated renal disease and proliferative forms of lupus nephritis (2, 3, 4, 5, 6)[A].
- Plasmapheresis may also be considered in some cases for RPGN or anti-GBM disease or ANCA-associated renal disease with diffuse pulmonary hemorrhage (2)[C],(4,7)[A].
- Dialysis may be needed for uremia, hyperkalemia refractory to medical management, intractable acidosis, and diuretic-resistant pulmonary edema.
- IgA nephropathy: ACE-Is or ARBs recommended for patients with proteinuria (1,2)[C], selected patients may benefit from immunosuppression.
ISSUES FOR REFERRAL
Consultation with a nephrologist is usually required to assist with renal biopsy to confirm diagnosis and assist with management.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Consider admission for patients with no urine output, rapidly deteriorating renal function, significant hypertension, and suspicion of pulmonary hemorrhage or fluid overload that is compromising heart or respiratory function.
Discharge Criteria
Hemodynamically stable patients without complications may be managed as outpatients.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Depends on type of GN
- Regular BP checks and urinalysis to detect recurrence, assessment of renal function to detect acute or follow chronic renal disease as a result of the primary event, and regular clinical assessment to detect suspicious symptoms that may herald a recurrence (i.e., rash, joint complaint, hemoptysis)
- Periodic reassessment of serology tests to detect asymptomatic individuals
DIET
- No-added-salt diet and fluid restriction until edema and hypertension clear
- Avoid high-potassium foods if significant renal dysfunction is present.
PATIENT EDUCATION
- National Kidney Foundation, http://www.kidney.org/atoz/content/glomerul
PROGNOSIS
- In general, the prognosis depends on the cause of the GN.
- The GN may be self-limited (as often is the case in postinfectious GN) or part of a chronic disease that makes the possibility of recurrence of acute disease likely, with the potential for progressive loss of renal function over time.
- Some forms of acute GN (including ANCA associated and severe lupus) require long-term immunosuppression to prevent recurrence.
COMPLICATIONS
- Hypertensive retinopathy and encephalopathy
- RPGN
- Microscopic hematuria may persist for years.
- Chronic kidney disease
- Nephrotic syndrome (~10%)
REFERENCES
11 Chadban SJ, Atkins RC. Glomerulonephritis. Lancet. 2005;365(9473):1797-1806.22 Beck L, Bomback AS, Choi MJ, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for glomerulonephritis. Am J Kidney Dis. 2013;62(3):403-441. doi:10.1053/j.ajkd.2013.06.002.33 Hahn BH, McMahon MA, Wilkinson A, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012;64(6):797-808. doi:10.1002/acr.21664.44 Walters G, Willis NS, Craig JC. Interventions for renal vasculitis in adults. Cochrane Database Syst Rev. 2008;(3):CD003232. doi:10.1002/14651858.CD003232.pub2.55 Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221-232. doi:10.1056/NEJMoa0909905.66 Bomback AS, Appel GB. Updates on the treatment of lupus nephritis. J Am Soc Nephrol. 2010;21(12):2028-2035. doi:10.1681/ASN.2010050472.77 Jayne DR, Gaskin G, Rasmussen N, et al. European Vasculitis Study Group. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol. 2007;18(7):2180-2188.
SEE ALSO
- Acute Kidney Injury (Acute Renal Failure); Glomerulonephritis, Postinfectious; Henoch-Sch ¶nlein Purpura; Hyperkalemia; Hypertensive Emergencies; IgA Nephropathy; Nephrotic Syndrome; Vasculitis
- Algorithm: Hematuria
CODES
ICD10
- N00.9 Acute nephritic syndrome with unsp morphologic changes
- N00.2 Acute nephritic syndrome w diffuse membranous glomrlneph
- N00.8 Acute nephritic syndrome with other morphologic changes
- N00.3 Acute neph syndrome w diffuse mesangial prolif glomrlneph
- N00.5 Acute nephritic syndrome w diffuse mesangiocap glomrlneph
- N00.1 Acute neph syndrome w focal and segmental glomerular lesions
- N00.4 Acute neph syndrome w diffuse endocaplry prolif glomrlneph
ICD9
- 580.9 Acute glomerulonephritis with unspecified pathological lesion in kidney
- 580.0 Acute glomerulonephritis with lesion of proliferative glomerulonephritis
- 580.89 Acute glomerulonephritis with other specified pathological lesion in kidney
- 580.4 Acute glomerulonephritis with lesion of rapidly progressive glomerulonephritis
- 580.81 Acute glomerulonephritis in diseases classified elsewhere
SNOMED
- 19351000 Acute glomerulonephritis (disorder)
- 197579006 Acute proliferative glomerulonephritis (disorder)
- 197582001 Acute glomerulonephritis associated with another disorder (disorder)
- 35546006 Mesangial proliferative glomerulonephritis (disorder)
CLINICAL PEARLS
- Dysmorphic RBCs and RBC casts are a key component of the urinalysis in GN.
- Postinfectious GN in children is typically a self-limited disease.
- Searching for other organ involvement is useful in establishing a definitive diagnosis.
- With the discovery of a GN, monitor the initial renal function labs frequently to identify a RPGN.