eMedicine Specialties > Pediatrics: General Medicine > Nephrology
IgA Nephropathy
Updated: Dec 15, 2008
Introduction
Background
Idiopathic immunoglobulin A (IgA) nephropathy, often termed Berger nephropathy, was first described by Berger and Hinglais in 1968, based on the finding of predominant IgA deposition in the mesangium with a mesangial proliferation and clinical features that spanned the spectrum from asymptomatic hematuria to rapidly progressive glomerulonephritis.
IgA nephropathy is the most common cause of primary glomerulonephritis throughout the world. Although it can present at any time, the peak incidence of disease is in the second and third decades of life. A male-to-female ratio of 2:1 is observed in North American and Western European populations, although this difference is not observed among populations in the Pacific.
IgA nephropathy occurs with greatest frequency in Asians and whites and is relatively rare in blacks. In a Chinese study, IgA nephropathy constituted 45% of all cases of primary glomerulonephritis. However, IgA deposits may also be seen on kidney biopsy findings in individuals with no evidence of renal disease. The reported incidence rate of mesangial IgA deposition in apparently healthy individuals is 3-16%. These cases had no clinical features of nephritis, but their renal biopsy findings were consistent with IgA nephropathy.
Spontaneous remission has been reported in children and adults. Secondary IgA nephropathy is also associated with various underlying disease processes. It was initially considered a benign condition, but extended follow-up indicates that IgA nephropathy does lead to significant kidney damage and progressive disease develops in 20–30% of children 15–20 years after disease onset. Advanced age, hypertension, proteinuria, and impaired renal function at presentation are poor prognostic indicators.
Pathophysiology
Forty years after its first description, the pathogenesis of IgA nephropathy is now becoming more clear. The pathogenesis of IgA nephropathy is the mesangial deposition of IgA, which is predominantly polymeric IgA of the IgA1 subclass (polymeric IgA1-containing J chain). Co-deposits of immunoglobulin G (IgG) and complement C3 are also commonly observed and may contribute to disease severity. The characteristic pathologic findings on immunofluorescence microscopy are granular deposits of IgA and C3 in the glomerular mesangium. The detection of IgA immune complexes from circulation suggests that this disease is the result of the deposition of circulating immune complexes.
The key elements that contribute to IgA nephropathy include the following:
- Synthesis and release of IgA immune complexes into the circulation with chemical and biological characteristics that favor mesangial deposition
- The ability of the reticuloendothelial system to effectively remove potentially pathogenic IgA immune complexes
- The mesangial cell affinity and reaction to mesangial IgA accumulation
- Inherent tendency of the kidney to respond to injury by mounting a response favoring progressive renal injury with glomerulosclerosis and interstitial fibrosis, rather than resolution of inflammation without these sequelae
IgA is a major serum immunoglobulin and the predominant antibody class in the external secretions that bathe mucosal surfaces. This plays a key role in immune protection. Indeed, the body expends considerable energy in producing IgA, such that the daily production of IgA exceeds that of all the other antibody classes combined.
IgA, at concentrations of about 2-3 mg/mL, is the second most prevalent antibody in serum after IgG, which is normally present at about 12 mg/mL. Because serum IgA is metabolized 5 times faster than IgG, the production rates of serum IgA and IgG must be similar. Serum IgA is predominantly monomeric in nature; the secretory IgA (S-IgA) is chiefly polymeric, comprising mainly dimeric forms of IgA containing the J (joining) chain. S-IgA serves various functions to protect the vast surface area (approximately 400 m2) occupied by mucosal surfaces, such as the linings of the respiratory, GI , and genitourinary tracts. As the major class of antibody present at these sites, S-IgA can be considered an important first line of defense against many invading pathogens.
In humans, 2 subclasses of IgA (termed IgA1 and IgA2) are recognized, from a separate gene origin. Numerous sequence differences are found in their heavy chain constant regions (ie, C1, hinge, C2, and C3). A major difference between the subclasses lies in the hinge region, which is greatly extended in IgA1. Two allotypic variants of IgA2, named IgA2m(1) and IgA2m(2), have been well characterized. Their heavy chain constant region sequences differ at numerous points along their length. The most notable difference is that although IgA2m(2) has the disulphide bridges linking light and heavy chains typical of most immunoglobulins, these are generally lacking in IgA2m(1). Instead, the light chains bond to each other, and the association with the heavy chains is stabilized through noncovalent interactions.
Early electron microscopy studies provided the first insights into the shape and size of the different forms of IgA. More recently, molecular models for human IgA1 and IgA2m(1) based on radiographic and neutron scattering data have been generated. IgA1 may have a more extended reach
S-IgA
The IgA patterns of external secretions are characterized by secretory IgA in saliva, tears, bile, and urine. IgA is also found in nasal, tracheobronchial, intestinal, and cervical fluids. Most IgA molecules in external secretions are present as dimers composed of 2 7S IgA monomers plus two other non-Ig proteins, the J chain and secretory component (molecular weight, 71,000).
IgA is the most abundant immunoglobulin in the body; it is chiefly concerned with mucosal defense. IgA is produced by plasma cells in the mucosa and by bone marrow cells. The mucosal immune system synthesizes polymer IgA (pIgA) and transports it into mucosal fluid. The secretory component remains attached to the pIgA. Plasma cells only assemble pIgA. Both subclasses of IgA (ie, IgA1, IgA2) are present in mucosa.
The process begins with the accumulation of IgA, predominantly IgA1, in renal mesangial cells. Glycosylation and the size of IgA1 are essential for the interaction with mesangial receptors in IgA nephropathy. IgA1 contains a J chain but no secretory component. IgA nephropathy is often assumed to be an immune complex disease because similar patterns of mesangial immunoglobulin deposition can be induced by the infusion of preformed antigen-antibody complexes. Deposition of IgA immunoglobulin leads to cytokine release, mesangial cell proliferation, and the activation of the complement system via the alternative pathway. Ultimately, the glomerular filtering surface is damaged and reduced, and renal failure ensues.
The fact that polymeric IgA1 is usually derived from the mucosal immune system, is associated with IgA nephropathy, and affects the respiratory or GI tract suggests that IgA nephropathy is a disease of the mucosal immune system. This concept was supported by the finding of immunoglobulin antibodies in dietary antigens or various infectious agents, both viral and bacterial, in some patients with IgA nephropathy. Additionally, it was supported by the clinical observation that some patients with IgA nephropathy, the hematuria increases acutely at the time of upper respiratory tract or gastrointestinal infection.
Regardless of the mechanism that leads to the increased deposition of IgA or IgA-containing immune complexes in the glomeruli, the mechanisms responsible for the glomerular injury remain poorly understood. Despite the demonstration of a specific IgA receptor on mesangial cells and in the glomerulus of patients with IgA nephropathy, studies of the expression of Fc alpha R on peripheral blood mononuclear cells and granulocytes led to conflicting results. IgA nephropathy may be linked to the expression of an IgA nephropathy specific variant of Fc alpha R (receptor) on monocytes. The role, if any, of Fc alpha R in the pathogenesis of IgA nephropathy remains to be elucidated.
IgA nephropathy and Henoch-Schönlein purpura (HSP)
IgA nephropathy and HSP share many morphologic and immunopathologic features. The most striking similarities between IgA nephropathy and HSP nephropathy (HSN) are mesangial IgA deposition, elevated serum IgA level, and IgA circulating immune complexes. The glomerular changes (diffuse or focal mesangial proliferation) in HSN are essentially the same as those in IgA nephropathy. An infective episode precedes HSN in 30-50% of patients, and presence of Haemophilus influenza antigen in the glomerular mesangium and the presence of IgA antibody against H Influenza in sera has been reported in the patient with HSN.
The presence of antineutrophil cytoplasm antibodies (ANCA) was proposed as a marker of HSN to distinguish HSN from IgA nephropathy. Both have broadly similar geographic distributions and are rare in black persons. Coexistence in different members of the same family have been reported. Despite these similarities, the 2 conditions are clinically different, and the pathogenesis is not clear. HSN is an acute condition, with a glomerular lesion, and mostly nonprogressive after the onset. Meanwhile, IgAN is a chronic progressive lesion, which may eventually lead to renal failure. IgAN has a male predominance. HSP occurs mostly in young children and is rare in adults, whereas IgA nephropathy mainly occurs in older children and young adults.
Frequency
United States
IgA nephropathy accounts for 5-10% of all primary glomerular diseases occurring in the United States. The prevalence of IgA nephropathy in the general population has been estimated to be about 25-50 cases per 100,000 population. Almost 5% of all biopsied patients have at least some IgA deposits in their glomeruli. The incidence of end-stage renal disease (ESRD) due to IgA nephropathy was 5.5 cases per million population per year; about 8.4 cases for males and 2.7 cases for females.
International
IgA nephropathy has been diagnosed worldwide, but its prevalence in different countries varies. In Pacific countries, particularly in Japan, it accounts for approximately 50% of all primary glomerular diseases. In Europe, it is responsible for 20-30%. The explanation of this apparent variability is uncertain but may be related, in part, to differing indications for renal biopsy in different centers. High incidence rates are reported in Asia, France, Italy, Finland, and southern Europe. Genetic and environmental factors may contribute to geographic differences in prevalence. Population studies in Germany and France have calculated an incidence of 2 cases per 10,000, although autopsy studies performed in Singapore suggest that 2-4.8% of the population may have IgA deposition in their glomeruli.
Mortality/Morbidity
Although IgA nephropathy was thought to carry a relatively benign prognosis, an estimated 1-2% of all patients with IgA nephropathy develop end-stage renal failure each year from the time of diagnosis. In a study of 1900 patients derived from 11 separate series, the long-term renal survival was estimated to be 78-87% within a decade of presentation. Similarly, European studies have suggested that renal insufficiency may occur in 20-30% of patients within 2 decades of the original presentation.
In a study from Hong Kong, patients with mild IgA nephropathy were prospectively followed.1 Significant proteinuria or renal insufficiency was found in numerous patients, suggesting that a significant risk of progression is present, even in patients who present with milder forms of disease.
Several studies have assessed features that predict a poor prognosis. Sustained hypertension, persistent proteinuria (especially proteinuria >1 g), impaired renal function, and the nephrotic syndrome constitute poor prognostic markers.
Typically, mortality associated with IgA nephropathy is secondary to renal failure or its complications. Morbidity may be subsequent to hypertension, electrolyte abnormalities, or other consequences of reduced renal function.
Familial IgA nephropathy has an increased risk of end-stage renal disease.
Race
The distribution of IgA nephropathy varies in different geographic regions throughout the world. It is the most common form of primary glomerular disease in Asia, accounting for as much as 30-40% of all biopsy findings, for 20% of biopsies in Europe, and for 10% of all biopsies performed for glomerular disease in North America. The reason for this wide variance in incidence is partly attributable to indications for renal biopsy in Asia compared to those in North America. In the United States, incidence of IgA nephropathy is increased in children who are Asian or white; incidence is lowest in blacks.
Sex
Incidence is higher in males than in females. Male-to-female ratios of 2:1 and 6:1 have been reported.
Age
IgA nephropathy occurs in persons of all ages but is still most common in the second and third decades of life and is much more common in males than females. IgA nephropathy is uncommon in children younger than 10 years. In fact, 80% of patients are between the ages of 16-35 years at the time of renal biopsy.
Clinical
History
Immunoglobulin A (IgA) nephropathy (IgAN) is characterized by recurrent episodes of macroscopic hematuria accompanied by upper respiratory tract infections or persistent asymptomatic microscopic hematuria with or without proteinuria. IgA nephropathy is frequently classified as primary (idiopathic) or secondary (associated with some other known condition).
- Although the clinical presentation of IgA nephropathy varies from asymptomatic urinary abnormalities to acute renal failure, 5 different clinical syndromes are generally recognized.
- The most common presentation (approximately 60-80%) of IgA nephropathy is asymptomatic microscopic urinary abnormalities with one or more episodes of intermittent gross hematuria. The recurrent macroscopic hematuria often associated with upper respiratory infection (pharyngitis) is traditionally regarded as the hallmark of childhood IgA nephropathy, compared with poststreptococcal glomerulonephritis (PSGN), in which hematuria usually occurs 1-2 weeks after infection. The hematuria is usually painless, but loin pain has been reported. Blood pressure may be within the reference range or elevated. Renal clearance function is within the reference range or reduced.
- The second most common presentation (approximately 26%) is asymptomatic microscopic hematuria with or without mild proteinuria, hypertension, or reduced renal clearance function.
- Acute nephritic presentation (approximately 12%) with heavy proteinuria, normal or low clearance function, and normal or high blood pressure is the third most common presentation.
- Nephrotic syndrome may be the initial presentation in as many as 10% of patients.
- Rarely, IgA nephrology may present as an acute crescentic glomerulonephritis with oliguria, edema, and hypertension.
- When renal mesangial IgA deposition occurs because of another specific clinical condition (secondary IgA nephrology), the history of that disease or signs and symptoms related to the primary condition may be present.
Physical
In the early stages of primary IgA nephropathy, no physical signs may be observed. However, early diagnosis might be suggested by a urinalysis that reveals microscopic hematuria with or without proteinuria.
- Hypertension is infrequent, is mild to moderate, and is usually a late presentation of disease.
- Edema due to nephrosis is reported in approximately 10% of patients.
- If renal function is compromised at presentation, the patients may have signs of uremic syndrome, anemia, pallor, and lethargy.
- If IgA nephrology is secondary to underlying disease, such Henoch-Schönlein purpura (HSP)or systemic lupus erythematosus (SLE), the signs and symptoms of that specific primary disease may be apparent.
Causes
The cause of primary IgA nephropathy is unknown. The conditions producing secondary mesangial IgA deposition include the following:
- HSP
- Celiac disease
- Chronic ulcerative colitis
- Crohn disease
- Dermatitis herpetiformis
- Psoriasis
- Cystic fibrosis
- Sarcoidosis
- Lung cancer
- Colon cancer
- Monoclonal IgA gammopathy
- Non-Hodgkin lymphoma
- Pancreatic cancer
- Human immunodeficiency virus (HIV)
- Mycoplasma infection
- Toxoplasmosis
- Cirrhosis
- Pulmonary hemosiderosis
- Cryoglobulinemia
- Polycythemia
- Hepatitis B
- Systemic lupus erythematosus
- Sjögren syndrome
- Rheumatoid arthritis
Differential Diagnoses
| Acute Poststreptococcal
Glomerulonephritis | Medullary Sponge Kidney |
| Alport Syndrome | Minimal-Change Disease |
| Anti-GBM Antibody Disease | Nephritis |
| Antiphospholipid Antibody Syndrome | Nephritis, Interstitial |
| Diabetic Nephropathy | Nephrotic Syndrome |
| Glomerulonephritis, Acute | Polyarteritis Nodosa |
| Glomerulonephritis, Chronic | Polycystic Kidney Disease |
| Glomerulonephritis, Crescentic | Pyelonephritis |
| Glomerulonephritis, Diffuse
Proliferative | Sickle Cell Anemia |
| Glomerulonephritis, Nonstreptococcal Associated
With Infection | Systemic Lupus Erythematosus |
| Glomerulonephritis, Poststreptococcal | Uric Acid Stones |
| Glomerulonephritis, Rapidly Progressive | Urinary Tract Infection |
| Goodpasture Syndrome | Urolithiasis |
| Hematuria | Wegener Granulomatosis |
| Henoch-Schoenlein Purpura | |
| Hypercalciuria | |
| Medullary Cystic Disease |
Workup
Laboratory Studies
Upon initial evaluation, the studies below are directed at identifying immunoglobulin A (IgA) nephropathy. Evaluation from a renal standpoint should include consideration of any condition causing hematuria, proteinuria, hypertension, and/or reduced renal function.
- Urinalysis (UA): These results should reveal hematuria, proteinuria, and leukocytes. Microscopic examination reveals dysmorphic RBCs and RBC casts suggestive of glomerular origin of RBC but not specific for IgA nephropathy, whereas normal RBC morphology indicates lower urinary tract involvement.
- CBC count with differential count
- A 24-hour urine collection: This is used is to estimate creatinine clearance (CrCl) and protein excretion. Proteinuria is associated with histologic lesion and a risk for progression.
- Urine calcium (Ca) to creatinine (Cr) ratio: This is performed to measure hypercalciuria (normal is <0.2) and the protein (Pr) to Cr ratio to measure proteinuria (normal is <0.2).
- Serum electrolyte levels
- BUN and Cr levels: These estimate renal function.
- Serum C3 levels: These levels are usually normal. C3 is routinely measured to eliminate the diagnosis of postinfectious glomerulonephritis or membranoproliferative glomerulonephritis.
- Antistreptolysin-O (ASO) titer or streptozyme test
- Serum IgA level: These are elevated in approximately 30-50% in adults but in only 8-16% of children with IgA nephropathy.
Imaging Studies
- Renal ultrasonography is an excellent diagnostic tool to detect structural abnormalities leading to hematuria, such as renal stone, neoplasm, cystic lesion, hydronephrosis, dilated urinary tract, and bladder abnormalities. However, it cannot be used to confirm, support, or reject the diagnosis of IgA nephropathy.
Procedures
- The diagnosis of IgA nephropathy is based on the presence of IgA immunoglobulin in the glomerular mesangium.
- Percutaneous renal biopsy is essential for the confirmation of IgA nephropathy. The indications for biopsy include the following:
- Macroscopic hematuria
- Microscopic hematuria with significant proteinuria (>2 mg/kg/d)
- Acute nephritic syndrome (hematuria with hypertension or renal insufficiency)
- Nephrotic syndrome
Histologic Findings
The diagnostic histopathologic hallmark of IgA nephropathy by light, immunofluorescence, and electron microscopy is the presence of IgA in the glomerular mesangium. With light microscopy, the most characteristic abnormality is mesangial enlargement produced by hypercellularity and mesangial matrix increase. The severity of renal involvement can be graded based on mesangial cell proliferation.
- Minimal lesion: The glomeruli appear normal. The number of mesangial cells per peripheral mesangial area does not exceed 3. Small foci of tubular atrophy and interstitial lymphocyte infiltration may be present.
- Focal mesangial proliferation: The glomeruli show moderate to severe mesangial cell proliferation (ie, >3 mesangial cells per peripheral mesangial area). The proliferation may be associated with increased matrix, small crescent, capsular adhesions and prolapsed.
- Diffuse mesangial proliferative and crescentic glomerulonephritis can occur. A small number of patients may have global sclerosis, tubular atrophy, interstitial fibrosis, and interstitial lymphocyte infiltrate.
Treatment
Medical Care
Immunoglobulin A (IgA) nephropathy (IgAN) posses a therapeutic challenge to both the patient and physician. Medical treatment must address the primary disease, if a secondary form of IgA nephropathy is encountered. Because spontaneous remission may occur, aggressive therapies that may introduce additional risk are probably not indicated in children with mild disease.
Risk factors for progressive renal disease include heavy proteinuria (protein excretion >2 mg/kg/d), reduced renal clearance (estimated glomerular filtration rate [GFR] or measured creatinine clearance [CrCl] <75% of normal), hypertension, renal biopsy revealing proliferative glomerulonephritis, crescents, or advanced chronic disease. For children with progressive disease, several treatment options are available. No treatment has been shown to cure IgA nephropathy. Treatments tend to delay progression in patients with above listed risk factors.
The following treatment options are available:
- Children with the highest risk of progressive disease are most likely to benefit from therapy. The most appropriate treatment is unknown. The agents most often reported to be effective for IgA nephropathy treatment include corticosteroids (2 mg/kg), ACE inhibitors, angiotensin receptor blockers (ARB) and omega-3 polyunsaturated fatty acids (fish oil).
- The dosage and length of treatment for maximal benefit in children with IgA nephropathy are unknown for these agents. In each case, the effectiveness of these therapies should be initially assessed and periodically reassessed to determine that treatment is beneficial and that benefits outweigh the risks.
- Several investigators have reported that corticosteroids and/or fish oil have slowed the deterioration of renal function.2,3,4,5 However, a meta-analysis showed only 75% probability that fish oil was beneficial.
- Some studies have indicated that ACE inhibitors and ARB agents are useful in reducing proteinuria, controlling blood pressure, and preserving renal function in IgA nephropathy.
- High-dose pulse methylprednisolone has shown to delay the development of renal failure.
- The primary focus of treatments for IgA nephropathy is to direct therapy at reducing inflammatory mediated renal injury, controlling hypertension, decreasing proteinuria, and managing sequelae of reduced renal function, if present.
- The Japanese Pediatric IgA Study Group reported that in children with severe IgA nephropathy, treatment with the combination of azathioprine, prednisolone, heparin-warfarin, and dipyridamole might ameliorate renal immunologic injury and delays progression.4
- Hotta et al reported that complete regression of IgA nephropathy was apparent in a group of patients treated with a combination of tonsillectomy, methylprednisolone, warfarin, alternate-day prednisolone, and dipyridamole.6
- Other treatments reported to provide benefit include the following:
- Prophylactic antibiotic and tonsillectomy may reduce the episodes and frequency of gross hematuria. Beneficial effect remains questionable.
- Glucocorticoids may benefit the few patients with minimal change disease, but long-term effects do not confirm any benefit. Alternate day steroid therapy reduces long-term complications.
- Plasmapheresis combined with an immunosuppressive drug is probably of value in patients with rapidly progressive crescentic diseases, but full recovery remains unlikely.
- Phenytoin, danazol, azathioprine, dipyridamole, and heparin-warfarin have been tried but failed to influence the clinical and histological course.
- Children with reduced renal function may need treatment for growth failure, bone mineralization, and reduced RBC production.
- Patients with end-stage renal disease require dialysis or transplantation.
- After renal transplantation, recurrent IgA nephropathy may result in graft loss. Current immunosuppressive regimens do not prevent the recurrence of IgA nephropathy.
- The recurrence of IgA nephropathy in renal allograft was initially considered as benign, with a low incidence of graft failure. However, newer reports in adults show graft failure rates of 30% and 60%.7,8,9 No studies have been performed in children, but IgA nephropathy recurrence may become a concern for long-term graft survival in children.
Surgical Care
Generally, surgical care is not necessary except for dialysis access or renal transplantation.
Consultations
Because IgA nephropathy has the potential to progress to end-stage renal disease, consultation with a pediatric nephrologist is necessary.
Diet
An American Heart Association step I diet is recommended for all children older than 2 years. Patients may require consultation with a dietitian to determine a renal diet if renal insufficiency develops.
Activity
Typically, no activity restriction is necessary.
Medication
The risks and benefits of immunoglobulin A (IgA) nephropathy (IgAN) treatment with steroids, fish oil, or ACE inhibitors should be discussed with patients and parents. These agents theoretically may protect the kidney and prolong the interval between onset and renal failure.
Anti-inflammatory and immunosuppressive agents
These agents elicit anti-inflammatory and immunosuppressive properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli and reduce immune-mediated renal injury resulting from IgA deposition in the kidney.
Prednisone (Deltasone) or methylprednisolone (Solu-Medrol)
Potent anti-inflammatory and immunosuppressive therapy with corticosteroids has been reported to reduce the rate of progression of IgAN.
Dosing
Adult
Methylprednisolone: 1 g IV
Prednisone: 0.5 mg/kg/d PO
Pediatric
Prednisone: 2 mg/kg (up to 80 mg/d) for 4 wk, then 1-2 mg/kg on alternate days as one of several possible reduction schedules; total treatment lasts 2 y
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
Coadministration with anticoagulants or antiplatelet agents may increase risk of bleeding; may antagonize neuromuscular blockers; high-dose or long-term glucocorticoid therapy may inhibit the thyroid-stimulating hormone (TSH), thereby interfering with thyroid medication regulation
Increases blood glucose in diabetes mellitus, and higher doses of insulin may be required
Contraindications
Documented hypersensitivity; Cushing syndrome; fungal infection, measles, varicella
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in diabetes mellitus, abdominal pain, fever, increased intracranial pressure, pancreatitis, or infection
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
Fish oil
Several investigators have suggested that fish oil delays the progression of renal disease. The precise mechanism is not fully understood.
Omega-3 polyunsaturated fatty acid (Promega, Lovaza)
May be beneficial by decreasing mediators of glomerular injury and decreasing platelet aggregation. Omega-3 fatty acids may be used as nondrug dietary supplements in early high-risk coronary disease and IgAN.
Dosing
Adult
4-8 g/d PO
Pediatric
Not established; not to exceed 4 g/d PO
Interactions
May increase insulin requirements; may increase effects of antiplatelet or anticoagulant drugs; concomitant use of other oils (eg, olive oil) may reduce effects
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
May cause fishy odor, diarrhea, hyperglycemia, and bleeding due to decreased platelet aggregation; caution in bleeding disorders or diabetes mellitus
Angiotensin-converting enzyme (ACE) inhibitors
In 1980, captopril became the first ACE inhibitor approved by the US Food and Drug Administration. Subsequently, at least 40 compounds have been identified. ACE inhibitors reduce the production of angiotensin II, thereby, lowering intraglomerular filtration pressure, reducing proteinuria, and slowing the decline of glomerular function in several chronic renal diseases. All ACE inhibitors probably have similar renal protective effects.
Enalapril (Vasotec)
Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
Dosing
Adult
2.5-5 mg/d PO qd or divided bid; not to exceed 40 mg/d
Pediatric
0.1 mg/kg/d PO qd or divided bid; not to exceed 0.5 mg/kg/d
Interactions
NSAIDs may reduce hypotensive effects of enalapril; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases enalapril levels; probenecid may increase enalapril levels; the hypotensive effects of ACE inhibitors may be enhanced when given concurrently with diuretics; additive risk of hyperkalemia with potassium sparing diuretics or potassium supplements; may decrease insulin resistance (adjust dose of antidiabetic agents)
Contraindications
Documented hypersensitivity; angioedema; hyperkalemia; bilateral renal artery stenosis
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
Caution in renal impairment, valvular stenosis, severe congestive heart failure, hypotension, hypoglycemia, angina, asthma, or neutropenia
Angiotensin Receptor Antagonist
Angiotensin II receptor antagonists may be considered if ACE inhibitors are not tolerated.
Losartan (Cozaar)
Angiotensin II receptor antagonist that blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. May induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors, does not affect the response to bradykinin, and is less likely to be associated with cough and angioedema. For patients unable to tolerate ACE inhibitors.
Angiotensin II receptor blockers reduce blood pressure and proteinuria, protecting renal function, and delaying onset of end-stage renal disease.
Dosing
Adult
25-100 mg PO qd or divided bid
Pediatric
Not established
Interactions
May increase digoxin, lithium, and allopurinol levels; probenecid may increase losartan levels; coadministration with diuretics, increase hypotensive effects; NSAIDs may reduce hypotensive effects of losartan; may increase risk of hyperkalemia if taken concurrently with potassium supplements or other potassium-sparing diuretics
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
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in patients with unilateral or bilateral renal artery stenosis
Follow-up
Further Inpatient Care
- Inpatient care is not necessary in patients with immunoglobulin A (IgA) nephropathy (IgAN), except for complications of renal failure, hypertension, dialysis, or renal transplantation.
Further Outpatient Care
- Routine follow up is important for monitoring the progression of disease.
- Medications must be taken as prescribed.
- A healthy diet and lifestyle is important.
- Patients should avoid obesity, smoking, and other activities that negatively influence the cardiovascular system.
Inpatient & Outpatient Medications
- No specific change of medication is necessary to transition from inpatient to outpatient therapy.
Transfer
- No transfer is necessary.
Deterrence/Prevention
- No methods for deterrence or prevention of IgA nephropathy are known.
Complications
- Primary complications include those related to uncontrolled hypertension (eg, seizure, stroke, end-organ damage), renal insufficiency (eg, growth failure, bone demineralization, anemia), and adverse reactions to one of the prescribed medications.
Prognosis
- IgA nephropathy may follow a variable course, ranging from benign throughout childhood to rapidly progressive renal failure.
- Children with renal failure require dialysis and/or transplantation, but the prognosis for long-term survival is very good.
Patient Education
- Inform patients about specific disease processes when possible.
- Encourage patients to avoid risk factors, such as smoking, drugs, obesity, and poor medication compliance.
- 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
- Immunoglobulin A (IgA) nephropathy (IgAN) may progress to end-stage kidney disease. No well-established therapy has been established to prevent progression. Currently, few treatment trials are in progress. Failure to make the diagnosis precludes offering the patient an opportunity to participate in a study that might be beneficial.
Special Concerns
- Careful management of hypertension is essential. If reduced renal function occurs, referral to a nephrologist is appropriate.
Multimedia
Media file 1: Glomerulus with mesangial hypercellularity and intact capillary loops. Trichrome Stain, original magnification 400x. Image courtesy of Patrick D Walker, MD.
Media file 2: Mesangial deposits of immunoglobulin A (IgA). Fluoresceinated Anti-IgA Antibody, Immunofluorescence microscopy, original magnification 400x. Image courtesy of Patrick D Walker, MD.
Media file 3: Electron photomicrograph showing mesangial electron dense deposits (arrow). Uranyl acetate and lead citrate stain, original magnification 12,000x. Image courtesy of Patrick D Walker, MD.
References
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Keywords
IgA nephropathy, IgAN, immunoglobulin A nephropathy, glomerulonephritis, focal glomerulonephritis, Berger focal glomerulonephritis, Berger's focal glomerulonephritis, Berger nephropathy, Berger's nephropathy, hypertension, proteinuria, Henoch-Schönlein purpura, HSP, Henoch-Schönlein nephropathy, HSN, end-stage renal disease, renal insufficiency, pharyngitis, poststreptococcal glomerulonephritis, PSGN, nephrotic syndrome, systemic lupus erythematosus, SLE, celiac disease, chronic ulcerative colitis, Crohn disease, dermatitis herpetiformis, psoriasis, cystic fibrosis, sarcoidosis, lung cancer, colon cancer, monoclonal IgA gammopathy, non-Hodgkin lymphoma, pancreatic cancer, human immunodeficiency virus, HIV, mycoplasma infection, toxoplasmosis, cirrhosis, pulmonary hemosiderosis, cryoglobulinemia, polycythemia, hepatitis B, systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis
Contributor Information and Disclosures
Author
Mohammad Ilyas, MD, FAAP, Assistant Professor of Pediatrics, University of Florida College of Medicine; Consulting Staff, Department of Pediatrics, Section of Nephrology, Wolfson Children Hospital and Shands Hospital Jacksonville
Mohammad Ilyas, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics and American Society of Nephrology
Disclosure: Nothing to disclose.
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: The Osler Institute Honoraria Speaking and teaching
Medical Editor
Deogracias Pena, MD, Medical Director of Dialysis, Department of Pediatrics, Cook Children's Medical Center; Clinical Associate Professor, Texas Tech University School of Medicine
Deogracias Pena, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and American Society of Pediatric Nephrology
Disclosure: Nothing to disclose.
Pharmacy Editor
Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner
Managing Editor
Adrian Spitzer, MD, Professor, Department of Pediatrics, Albert Einstein College of Medicine; Director of NIH Training Program, Children's Hospital at Montefiore Medical Center
Adrian Spitzer, MD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Pediatric Society, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, 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; 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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