IgA nephropathy
Encyclopedia
IgA nephropathy is a form of glomerulonephritis
(inflammation
of the glomeruli
of the kidney
). This should not be confused with Buerger's disease
, an unrelated condition.
IgA nephropathy is the most common glomerulonephritis throughout the world Primary IgA nephropathy is characterized by deposition of the IgA
antibody
in the glomerulus. There are other diseases associated with glomerular IgA deposits, the most common being Henoch-Schönlein purpura
(HSP), which is considered by many to be a systemic form of IgA nephropathy. HSP presents with a characteristic purpuric skin rash, arthritis
, and abdominal pain and occurs more commonly in young adults (16-35 yrs old). HSP is associated with a more benign prognosis than IgA nephropathy. In IgA nephropathy there is a slow progression to chronic renal failure in 25-30% of cases during a period of 20 years.
which usually starts within a day or two of a non-specific upper respiratory tract infection
(hence synpharyngitic) as opposed to post-streptococcal glomerulonephritis which occurs some time (weeks) after initial infection. Less commonly gastrointestinal or urinary infection can be the inciting agent. All of these infections have in common the activation of mucosal defenses and hence IgA antibody production. Loin pain can also occur. The gross hematuria resolves after a few days, though microscopic hematuria
may persist. These episodes occur on an irregular basis every few months and in most patients eventually subsides (although it can take many years). Renal function usually remains normal, though rarely, acute renal failure
may occur (see below). This presentation is more common in younger adults.
A smaller proportion (20-30%), usually the older population, have microscopic hematuria and proteinuria
(less than 2 g
ram/day). These patients may not have any symptoms and are only clinically found if a doctor decides to take a urine sample. Hence, the disease is more commonly diagnosed in situations where screening of urine is compulsory, e.g. schoolchildren in Japan
.
Very rarely (5% each), the presenting history is:
A variety of systemic diseases are associated with IgA nephropathy such as liver failure
, celiac disease, rheumatoid arthritis
, Reiter's disease, ankylosing spondylitis
and HIV
. Diagnosis of IgA Nephropathy and a search for any associated disease occasionally reveals such an underlying serious systemic disease. Occasionally, there are simultaneous symptoms of Henoch-Schönlein purpura
; see below for more details on the association. Some HLA alleles have been suspected along with complement phenotypes as being genetic factors.
, tests such as ultrasound
of the kidney and cystoscopy
are usually done first to pinpoint the source of the bleeding
. These tests would rule out kidney stones and bladder cancer
, two other common urological
causes of hematuria. In children and younger adults, the history and association with respiratory infection can raise the suspicion of IgA nephropathy. A kidney biopsy
is necessary to confirm the diagnosis. The biopsy specimen shows proliferation of the mesangium
, with IgA deposits on immunofluorescence
and electron microscopy. However, all patients with isolated microscopic hematuria
(i.e. without associated proteinuria and with normal kidney function) are not usually biopsied since this is associated with an excellent prognosis
. A urinalysis
will show red blood cells, usually as red cell urinary casts
. Proteinuria
, usually less than 2 grams per day, also may be present. Other renal causes of isolated hematuria include thin basement membrane disease
and Alport syndrome
, the latter being a hereditary disease associated with hearing impairment
and eye problems.
Other blood test
s done to aid in the diagnosis include CRP
or ESR
, complement
levels, ANA
, and LDH
. Protein electrophoresis
and immunoglobulin
levels can show increased IgA in 50% of all patients.
and smaller amounts of other immunoglobulins (IgG or IgM
). Early components of the classical complement pathway
(C1q or C4
) are usually not seen. Electron microscopy confirms electron-dense deposits in the mesangium that may extend to the subendothelial area of adjacent capillary walls in a small subset of cases, usually those with focal proliferation.
The disease derives its name from deposits of Immunoglobulin A
(IgA) in a granular pattern in the mesangium (by immunofluorescence
), a region of the renal glomerulus
. The mesangium by light microscopy may be hypercellular and show increased deposition of extracellular matrix
proteins.
There is no clear known explanation for the accumulation of the IgA. Exogenous antigen
s for IgA have not been identified in the kidney, but it is possible that this antigen has been cleared before the disease manifests itself. It has also been proposed that IgA itself may be the antigen.
A recently advanced theory focuses on abnormalities of the IgA1 molecule. IgA1 is one of the two immunoglobulin subclasses (the other is IgD) that is O-glycosylated
on a number of serine
and threonine
residues in a special proline
-rich hinge region. Deficiency of these sugars appears to lead to polymer
isation of the IgA molecule in tissues, especially the glomerular mesangium. A similar mechanism has been claimed to underlie Henoch-Schönlein purpura
(HSP), a vasculitis
that mainly affects children and can feature renal involvement that is almost indistinguishable from IgA nephritis. However, human studies have found that degalactosylation of IgA1 occurs in patients with IgA nephropathy in response only to gut antigen exposures (not systemic), and occurs in healthy people to a lesser extent. This strongly suggests degalactosylation of IgA1 is a result of an underlying phenomenon (abnormal mucosal antigen handling) and not the ultimate cause of IgA nephropathy.
From the fact that IgAN can recur after renal transplant it can be postulated that the disease is caused by a problem in the immune system
rather than the kidney itself. Remarkably, the IgA1 that accumulates in the kidney does not appear to originate from the mucosa-associated lymphoid tissue (MALT), which is the site of most upper respiratory tract infections, but from the bone marrow
. This, too, suggests an immune pathology rather than direct interference by outside agents.
, there is considerable possibility for variation in any population studied depending upon the screening
policy. Similarly, the local policy for performing kidney biopsy
assumes a critical role; if it is a policy to simply observe patients with isolated hematuria
, a group with a generally favourable prognosis
will be excluded. If, in contrast, all such patients are biopsied, then the group with isolated microscopic hematuria
and isolated mesangial IgA will be included and ‘improve’ the prognosis of that particular series.
Nevertheless, IgA nephropathy, which was initially thought to be a benign disease, has been shown to have not-so-benign long term outcomes. Though most reports describe IgA nephropathy as having an indolent evolution towards either healing or renal damage, a more aggressive course is occasionally seen associated with extensive crescents, and presenting as acute renal failure
. In general, the entry into chronic renal failure
is slow as compared to most other glomerulonephritides – occurring over a time scale of 30 years or more (in contrast to the 5 to 15 years in other glomerulonephritides). This may reflect the earlier diagnosis made due to frank hematuria.
Complete remission, i.e. a normal urinalysis, occurs rarely in adults, in about 5% of cases. Thus, even in those with normal renal function
after a decade or two, urinary abnormalities persist in the great majority. In contrast, 30 – 50% of children may have a normal urinalysis at the end of 10 years. However, given the very slow evolution of this disease, the longer term (20 – 30 years) outcome of such patients is not yet established.
Overall, though the renal survival is 80 – 90% after 10 years, at least 25% and maybe up to 45% of adult patients will eventually develop end stage renal disease.
up to a rapid progression to chronic renal failure
. Hence the decision on which patients to treat should be based on the prognostic factors and the risk of progression. Also, IgA nephropathy recurs in transplant
s despite the use of ciclosporin
, azathioprine
or mycophenolate mofetil
and steroid
s in these patients. There are persisting uncertainties, due to the limited number of patients included in the few controlled randomized studies performed to date, which hardly produce statistically significant evidence regarding the heterogeneity of IgA nephropathy patients, the diversity of study treatment protocols, and the length of follow-up.
Patients with isolated hematuria, proteinuria
< 1 g/day and normal renal function
have a benign course and are generally just followed up annually. In cases where tonsillitis
is the precipitating factor for episodic hematuria, tonsillectomy
has been claimed to reduce the frequency of those episodes. However, it does not reduce the incidence of progressive renal failure
. Also, the natural history of the disease is such that episodes of frank hematuria
reduce over time, independent of any specific treatment. Similarly, prophylactic antibiotic
s have not been proven to be beneficial. Dietary gluten
restriction, used to reduce mucosal antigen
challenge, also has not been shown to preserve renal function
. Phenytoin
has also been tried without any benefit
A subset of IgA nephropathy patients, who have minimal change disease
on light microscopy
and clinically have nephrotic syndrome
, show an exquisite response to steroid
s, behaving more or less like minimal change disease
. In other patients, the evidence for steroids is not compelling. Short courses of high dose steroids have been proven to lack benefit. However, in patients with preserved renal function
and proteinuria (1-3.5 g/day), a recent prospective study has shown that 6 months regimen of steroids may lessen proteinuria and preserve renal function. However, the risks of long-term steroid use have to be weighed in such cases. It should be noted that the study had 10 years of patient follow-up data, and did show a benefit for steroid therapy; there was a lower chance of reaching end-stage renal disease (renal function so poor that dialysis was required) in the steroid group. Importantly, angiotensin-converting enzyme inhibitors were used in both groups equally.
Cyclophosphamide
had been used in combination with anti-platelet
/anticoagulant
s in unselected IgA nephropathy patients with conflicting results. Also, the side effect profile of this drug, including long term risk of malignancy and sterility
, made it an unfavorable choice for use in young adults. However, one recent study, in a carefully selected high risk population of patients with declining GFR, showed that a combination of steroids and cyclophosphamide
for the initial 3 months followed by azathioprine
for a minimum of 2 years resulted in a significant preservation of renal function. Other agents such as mycophenolate mofetil
, ciclosporin
and mizoribine
have also been tried with varying results.
A study from Mayo Clinic did show that long term treatment with omega-3 fatty acids results in reduction of progression to renal failure
, without, however, reducing proteinuria
in a subset of patients with high risk of worsening kidney function. However, these results have not been reproduced by other study groups and in two subsequent meta-analyses. However, fish oil therapy does not have the drawbacks of immunosuppressive therapy. Also, apart from its unpleasant taste and abdominal discomfort, it is relatively safe to consume.
The events that tend to progressive renal failure are not unique to IgA nephropathy and non-specific measures to reduce the same would be equally useful. These include low-protein diet and optimal control of blood pressure
. The choice of the antihypertensive
agent is open as long as the blood pressure is controlled to desired level. However, Angiotensin converting enzyme inhibitors and Angiotensin II receptor antagonist
s are favoured due to their anti-proteinuric effect.
polymorphism
(D allele) is associated with progression of renal failure, similar to its association with other causes of chronic renal failure
. However, more than 90% of cases of IgA nephropathy are sporadic, with a few large pedigrees described from Kentucky
and Italy
.
(especially > 2 g/day), hypertension
, smoking
, hyperlipidemia
, older age, familial disease and elevated creatinine
concentrations are markers of a poor outcome. Frank hematuria
has shown discordant results with most studies showing a better prognosis, perhaps related to the early diagnosis, except for one group which reported a poorer prognosis. Proteinuria
and hypertension
are the most powerful prognostic factors in this group.
There are certain other features on kidney biopsy
such as interstitial scarring which are associated with a poor prognosis. ACE gene polymorphism
has been recently shown to have an impact with the DD genotype
associated more commonly with progression to renal failure
.
and Southeast Asia
, comprising almost half of all the patients with glomerular disease. However, it comprises only about 25% of the proportion in European and about 10% among North Americans, with African–Americans having a very low prevalence of about 2%. A confounding factor in this analysis is the existing policy of screening
and use of kidney biopsy
as an investigative tool. School children in Japan
undergo routine urinalysis
(as do Army recruits in Singapore
) and any suspicious abnormality is pursued with a kidney biopsy, which might partly explain the high incidence
of IgA nephropathy in those countries.
, hematochezia
, and purpura of the legs. In 1837, Johann Schönlein described a syndrome of purpura associated with joint pain and urinary precipitates in children. Eduard Henoch, a student of Schönlein's, further associated abdominal pain and renal involvement with the syndrome. Jean Berger and Hinglais, in 1968, were the first to describe IgA deposition in this form of glomerulonephritis
(hence, Berger’s disease).
Glomerulonephritis
Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...
(inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
of the glomeruli
Glomerulus
A glomerulus is a capillary tuft that is involved in the first step of filtering blood to form urine.A glomerulus is surrounded by Bowman's capsule, the beginning component of nephrons in the vertebrate kidney. A glomerulus receives its blood supply from an afferent arteriole of the renal...
of the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
). This should not be confused with Buerger's disease
Buerger's disease
Thromboangiitis obliterans is a recurring progressive inflammation and thrombosis of small and medium arteries and veins of the hands and feet...
, an unrelated condition.
IgA nephropathy is the most common glomerulonephritis throughout the world Primary IgA nephropathy is characterized by deposition of the IgA
IGA
Iga or IGA may stand for:-Given name:* a female given name of Polish origin. The name originates from the female given name Jadwiga and stands for gia,or gina in the USA....
antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
in the glomerulus. There are other diseases associated with glomerular IgA deposits, the most common being Henoch-Schönlein purpura
Henoch-Schönlein purpura
Henoch–Schönlein purpura is a disease of the skin and other organs that most commonly affects children. In the skin, the disease causes palpable purpura ; often with joint and abdominal pain...
(HSP), which is considered by many to be a systemic form of IgA nephropathy. HSP presents with a characteristic purpuric skin rash, arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
, and abdominal pain and occurs more commonly in young adults (16-35 yrs old). HSP is associated with a more benign prognosis than IgA nephropathy. In IgA nephropathy there is a slow progression to chronic renal failure in 25-30% of cases during a period of 20 years.
Signs and symptoms
The classic presentation (in 40-50% of the cases) is episodic frank hematuriaHematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
which usually starts within a day or two of a non-specific upper respiratory tract infection
Upper respiratory tract infection
Upper respiratory tract infections are the illnesses caused by an acute infection which involves the upper respiratory tract: nose, sinuses, pharynx or larynx...
(hence synpharyngitic) as opposed to post-streptococcal glomerulonephritis which occurs some time (weeks) after initial infection. Less commonly gastrointestinal or urinary infection can be the inciting agent. All of these infections have in common the activation of mucosal defenses and hence IgA antibody production. Loin pain can also occur. The gross hematuria resolves after a few days, though microscopic hematuria
Microscopic hematuria
Microscopic hematuria is a medical condition in which urine contains small amounts of blood. Blood quantity is too low to change the color of the urine...
may persist. These episodes occur on an irregular basis every few months and in most patients eventually subsides (although it can take many years). Renal function usually remains normal, though rarely, acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
may occur (see below). This presentation is more common in younger adults.
A smaller proportion (20-30%), usually the older population, have microscopic hematuria and proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
(less than 2 g
G
G is the seventh letter in the basic modern Latin alphabet.-History:The letter 'G' was introduced in the Old Latin period as a variant of ⟨c⟩ to distinguish voiced, from voiceless, . The recorded originator of ⟨g⟩ is freedman Spurius Carvilius Ruga, the first Roman to open a fee-paying school,...
ram/day). These patients may not have any symptoms and are only clinically found if a doctor decides to take a urine sample. Hence, the disease is more commonly diagnosed in situations where screening of urine is compulsory, e.g. schoolchildren in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
.
Very rarely (5% each), the presenting history is:
- Nephrotic syndromeNephrotic syndromeNephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
(3-3.5 grams of protein loss in the urine, associated with a poorer prognosis) - Acute renal failureAcute renal failureAcute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
(either as a complication of the frank hematuria, when it usually recovers, or due to rapidly progressive glomerulonephritisRapidly progressive glomerulonephritisRapidly progressive glomerulonephritis is a syndrome of the kidney that is characterized by a rapid loss of renal function, with glomerular crescent formation seen in at least 50% or 75% of glomeruli seen on kidney biopsies...
which often leads to chronic renal failureChronic renal failureChronic kidney disease , also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite...
) - Chronic renal failureChronic renal failureChronic kidney disease , also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite...
(no previous symptoms, presents with anemiaAnemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, hypertensionHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
and other symptoms of renal failure, in people who probably had longstanding undetected microscopic hematuria and/or proteinuria)
A variety of systemic diseases are associated with IgA nephropathy such as liver failure
Liver failure
Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease , and indicates that the liver has sustained severe damage . The complications are hepatic encephalopathy and impaired protein synthesis...
, celiac disease, rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
, Reiter's disease, ankylosing spondylitis
Ankylosing spondylitis
Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...
and HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
. Diagnosis of IgA Nephropathy and a search for any associated disease occasionally reveals such an underlying serious systemic disease. Occasionally, there are simultaneous symptoms of Henoch-Schönlein purpura
Henoch-Schönlein purpura
Henoch–Schönlein purpura is a disease of the skin and other organs that most commonly affects children. In the skin, the disease causes palpable purpura ; often with joint and abdominal pain...
; see below for more details on the association. Some HLA alleles have been suspected along with complement phenotypes as being genetic factors.
Diagnosis
For an adult patient with isolated hematuriaHematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
, tests such as ultrasound
Medical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...
of the kidney and cystoscopy
Cystoscopy
Cystoscopy is endoscopy of the urinary bladder via the urethra. It is carried out with a cystoscope.Diagnostic cystoscopy is usually carried out with local anaesthesia...
are usually done first to pinpoint the source of the bleeding
Bleeding
Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...
. These tests would rule out kidney stones and bladder cancer
Bladder cancer
Bladder cancer is any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis...
, two other common urological
Urology
Urology is the medical and surgical specialty that focuses on the urinary tracts of males and females, and on the reproductive system of males. Medical professionals specializing in the field of urology are called urologists and are trained to diagnose, treat, and manage patients with urological...
causes of hematuria. In children and younger adults, the history and association with respiratory infection can raise the suspicion of IgA nephropathy. A kidney biopsy
Needle aspiration biopsy
Needle aspiration biopsy , may refer to fine needle aspiration cytology , fine needle aspiration biopsy and fine needle aspiration , is a diagnostic procedure sometimes used to investigate superficial lumps or masses...
is necessary to confirm the diagnosis. The biopsy specimen shows proliferation of the mesangium
Mesangium
The mesangium is an inner layer of the glomerulus, within the basement membrane surrounding the glomerular capillaries. This term is often used interchangeably with mesangial cell, but in this context refers specifically to the intraglomerular mesangial cells. These cells are phagocytic and secrete...
, with IgA deposits on immunofluorescence
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
and electron microscopy. However, all patients with isolated microscopic hematuria
Microscopic hematuria
Microscopic hematuria is a medical condition in which urine contains small amounts of blood. Blood quantity is too low to change the color of the urine...
(i.e. without associated proteinuria and with normal kidney function) are not usually biopsied since this is associated with an excellent prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
. A urinalysis
Urinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
will show red blood cells, usually as red cell urinary casts
Urinary casts
Urinary casts are cylindrical structures produced by the kidney and present in the urine in certain disease states. They form in the distal convoluted tubule and collecting ducts of nephrons, then dislodge and pass into the urine, where they can be detected by microscopy.They form via precipitation...
. Proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
, usually less than 2 grams per day, also may be present. Other renal causes of isolated hematuria include thin basement membrane disease
Thin basement membrane disease
Thin basement membrane disease is, along with IgA nephropathy, the most common cause of asymptomatic hematuria. The only abnormal finding in this disease is a thinning of the basement membrane of the glomeruli in the kidneys...
and Alport syndrome
Alport syndrome
Alport syndrome or hereditary nephritis is a genetic disorder characterized by glomerulonephritis, endstage kidney disease, and hearing loss. Alport syndrome can also affect the eyes . The presence of blood in the urine is almost always found in this condition.It was first identified in a British...
, the latter being a hereditary disease associated with hearing impairment
Hearing impairment
-Definition:Deafness is the inability for the ear to interpret certain or all frequencies of sound.-Environmental Situations:Deafness can be caused by environmental situations such as noise, trauma, or other ear defections...
and eye problems.
Other blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s done to aid in the diagnosis include CRP
C-reactive protein
C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
or ESR
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
, complement
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
levels, ANA
Anti-nuclear antibody
Anti-nuclear antibodies are autoantibodies directed against contents of the cell nucleus....
, and LDH
Lactate dehydrogenase
Lactate dehydrogenase is an enzyme present in a wide variety of organisms, including plants and animals.Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes, each acting on either D-lactate or L-lactate...
. Protein electrophoresis
Protein electrophoresis
Protein electrophoresis is a method for analysing the proteins in a fluid or an extract. The electrophoresis may be performed with a small volume of sample in a number of alternative ways with or without a supporting medium: SDS polyacrylamide gel electrophoresis Protein electrophoresis is a method...
and immunoglobulin
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
levels can show increased IgA in 50% of all patients.
Morphology
Histologically, IgA nephropathy may show mesangial widening and focal and segmental inflammation. Diffuse mesangial proliferation or crescentic glomerulonephritis may also be present. Immunoflourescence shows mesangial deposition of IgA often with C3 and properdinProperdin
Properdin or factor P is a globulin protein found in the blood serum of more complex animals. In the complement system, an innate-immunity series of proenzymes dissolved in the circulation, it is also called "Factor P".-Function:...
and smaller amounts of other immunoglobulins (IgG or IgM
IGM
IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
). Early components of the classical complement pathway
Classical complement pathway
The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. The main activators of the Classical Pathway are antigen-antibody complexes.-Initiation:...
(C1q or C4
C4
C4, C04, C.IV or C-4 may refer to:* C-4 , a type of plastic explosive* Hafdasa C-4, an Argentine submachine gunIn biology:* C4 carbon fixation, a pathway for carbon fixation in photosynthesis...
) are usually not seen. Electron microscopy confirms electron-dense deposits in the mesangium that may extend to the subendothelial area of adjacent capillary walls in a small subset of cases, usually those with focal proliferation.
Pathophysiology
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
(IgA) in a granular pattern in the mesangium (by immunofluorescence
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
), a region of the renal glomerulus
Glomerulus
A glomerulus is a capillary tuft that is involved in the first step of filtering blood to form urine.A glomerulus is surrounded by Bowman's capsule, the beginning component of nephrons in the vertebrate kidney. A glomerulus receives its blood supply from an afferent arteriole of the renal...
. The mesangium by light microscopy may be hypercellular and show increased deposition of extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
proteins.
There is no clear known explanation for the accumulation of the IgA. Exogenous antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s for IgA have not been identified in the kidney, but it is possible that this antigen has been cleared before the disease manifests itself. It has also been proposed that IgA itself may be the antigen.
A recently advanced theory focuses on abnormalities of the IgA1 molecule. IgA1 is one of the two immunoglobulin subclasses (the other is IgD) that is O-glycosylated
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
on a number of serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
and threonine
Threonine
Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
residues in a special proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
-rich hinge region. Deficiency of these sugars appears to lead to polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
isation of the IgA molecule in tissues, especially the glomerular mesangium. A similar mechanism has been claimed to underlie Henoch-Schönlein purpura
Henoch-Schönlein purpura
Henoch–Schönlein purpura is a disease of the skin and other organs that most commonly affects children. In the skin, the disease causes palpable purpura ; often with joint and abdominal pain...
(HSP), a vasculitis
Vasculitis
Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...
that mainly affects children and can feature renal involvement that is almost indistinguishable from IgA nephritis. However, human studies have found that degalactosylation of IgA1 occurs in patients with IgA nephropathy in response only to gut antigen exposures (not systemic), and occurs in healthy people to a lesser extent. This strongly suggests degalactosylation of IgA1 is a result of an underlying phenomenon (abnormal mucosal antigen handling) and not the ultimate cause of IgA nephropathy.
From the fact that IgAN can recur after renal transplant it can be postulated that the disease is caused by a problem in the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
rather than the kidney itself. Remarkably, the IgA1 that accumulates in the kidney does not appear to originate from the mucosa-associated lymphoid tissue (MALT), which is the site of most upper respiratory tract infections, but from the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
. This, too, suggests an immune pathology rather than direct interference by outside agents.
Natural history
Since IgA nephropathy commonly presents without symptoms through abnormal findings on urinalysisUrinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
, there is considerable possibility for variation in any population studied depending upon the screening
Screening (medicine)
Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....
policy. Similarly, the local policy for performing kidney biopsy
Needle aspiration biopsy
Needle aspiration biopsy , may refer to fine needle aspiration cytology , fine needle aspiration biopsy and fine needle aspiration , is a diagnostic procedure sometimes used to investigate superficial lumps or masses...
assumes a critical role; if it is a policy to simply observe patients with isolated hematuria
Hematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
, a group with a generally favourable prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
will be excluded. If, in contrast, all such patients are biopsied, then the group with isolated microscopic hematuria
Microscopic hematuria
Microscopic hematuria is a medical condition in which urine contains small amounts of blood. Blood quantity is too low to change the color of the urine...
and isolated mesangial IgA will be included and ‘improve’ the prognosis of that particular series.
Nevertheless, IgA nephropathy, which was initially thought to be a benign disease, has been shown to have not-so-benign long term outcomes. Though most reports describe IgA nephropathy as having an indolent evolution towards either healing or renal damage, a more aggressive course is occasionally seen associated with extensive crescents, and presenting as acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
. In general, the entry into chronic renal failure
Chronic renal failure
Chronic kidney disease , also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite...
is slow as compared to most other glomerulonephritides – occurring over a time scale of 30 years or more (in contrast to the 5 to 15 years in other glomerulonephritides). This may reflect the earlier diagnosis made due to frank hematuria.
Complete remission, i.e. a normal urinalysis, occurs rarely in adults, in about 5% of cases. Thus, even in those with normal renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
after a decade or two, urinary abnormalities persist in the great majority. In contrast, 30 – 50% of children may have a normal urinalysis at the end of 10 years. However, given the very slow evolution of this disease, the longer term (20 – 30 years) outcome of such patients is not yet established.
Overall, though the renal survival is 80 – 90% after 10 years, at least 25% and maybe up to 45% of adult patients will eventually develop end stage renal disease.
Therapy
The ideal treatment for IgAN would remove IgA from the glomerulus and prevent further IgA deposition. This goal still remains a remote prospect. There are a few additional caveats that have to be considered while treating IgA nephropathy. IgA nephropathy has a very variable course, ranging from a benign recurrent hematuriaHematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
up to a rapid progression to chronic renal failure
Chronic renal failure
Chronic kidney disease , also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite...
. Hence the decision on which patients to treat should be based on the prognostic factors and the risk of progression. Also, IgA nephropathy recurs in transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
s despite the use of ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
, azathioprine
Azathioprine
Azathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
or mycophenolate mofetil
Mycophenolate mofetil
Mycophenolate mofetil is an immunosuppressant and prodrug of mycophenolic acid, used extensively in transplant medicine. It is a reversible inhibitor of inosine monophosphate dehydrogenase in purine biosynthesis, which is necessary for the growth of T cells and B cells...
and steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
s in these patients. There are persisting uncertainties, due to the limited number of patients included in the few controlled randomized studies performed to date, which hardly produce statistically significant evidence regarding the heterogeneity of IgA nephropathy patients, the diversity of study treatment protocols, and the length of follow-up.
Patients with isolated hematuria, proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
< 1 g/day and normal renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
have a benign course and are generally just followed up annually. In cases where tonsillitis
Tonsillitis
Tonsillitis is an inflammation of the tonsils most commonly caused by viral or bacterial infection. Symptoms of tonsillitis include sore throat and fever. While no treatment has been found to shorten the duration of viral tonsillitis, bacterial causes are treatable with antibiotics...
is the precipitating factor for episodic hematuria, tonsillectomy
Tonsillectomy
A tonsillectomy is a 3,000-year-old surgical procedure in which the tonsils are removed from either side of the throat. The procedure is performed in response to cases of repeated occurrence of acute tonsillitis or adenoiditis, obstructive sleep apnea, nasal airway obstruction, snoring, or...
has been claimed to reduce the frequency of those episodes. However, it does not reduce the incidence of progressive renal failure
Chronic renal failure
Chronic kidney disease , also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite...
. Also, the natural history of the disease is such that episodes of frank hematuria
Hematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
reduce over time, independent of any specific treatment. Similarly, prophylactic antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s have not been proven to be beneficial. Dietary gluten
Gluten
Gluten is a protein composite found in foods processed from wheat and related grain species, including barley and rye...
restriction, used to reduce mucosal antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
challenge, also has not been shown to preserve renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
. Phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
has also been tried without any benefit
A subset of IgA nephropathy patients, who have minimal change disease
Minimal change disease
Minimal Change Disease is a disease of the kidney that causes nephrotic syndrome and usually affects children .-Epidemiology:...
on light microscopy
Microscopy
Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye...
and clinically have nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
, show an exquisite response to steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
s, behaving more or less like minimal change disease
Minimal change disease
Minimal Change Disease is a disease of the kidney that causes nephrotic syndrome and usually affects children .-Epidemiology:...
. In other patients, the evidence for steroids is not compelling. Short courses of high dose steroids have been proven to lack benefit. However, in patients with preserved renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
and proteinuria (1-3.5 g/day), a recent prospective study has shown that 6 months regimen of steroids may lessen proteinuria and preserve renal function. However, the risks of long-term steroid use have to be weighed in such cases. It should be noted that the study had 10 years of patient follow-up data, and did show a benefit for steroid therapy; there was a lower chance of reaching end-stage renal disease (renal function so poor that dialysis was required) in the steroid group. Importantly, angiotensin-converting enzyme inhibitors were used in both groups equally.
Cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
had been used in combination with anti-platelet
Antiplatelet drug
An antiplatelet drug is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation...
/anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
s in unselected IgA nephropathy patients with conflicting results. Also, the side effect profile of this drug, including long term risk of malignancy and sterility
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
, made it an unfavorable choice for use in young adults. However, one recent study, in a carefully selected high risk population of patients with declining GFR, showed that a combination of steroids and cyclophosphamide
Cyclophosphamide
Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....
for the initial 3 months followed by azathioprine
Azathioprine
Azathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
for a minimum of 2 years resulted in a significant preservation of renal function. Other agents such as mycophenolate mofetil
Mycophenolate mofetil
Mycophenolate mofetil is an immunosuppressant and prodrug of mycophenolic acid, used extensively in transplant medicine. It is a reversible inhibitor of inosine monophosphate dehydrogenase in purine biosynthesis, which is necessary for the growth of T cells and B cells...
, ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
and mizoribine
Mizoribine
Mizoribine is an immunosuppresive drug. The compound was first observed in Tokyo, Japan, in 1971. It is a natural product, first isolated from the mould Eupenicillium brefeldianum....
have also been tried with varying results.
A study from Mayo Clinic did show that long term treatment with omega-3 fatty acids results in reduction of progression to renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
, without, however, reducing proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
in a subset of patients with high risk of worsening kidney function. However, these results have not been reproduced by other study groups and in two subsequent meta-analyses. However, fish oil therapy does not have the drawbacks of immunosuppressive therapy. Also, apart from its unpleasant taste and abdominal discomfort, it is relatively safe to consume.
The events that tend to progressive renal failure are not unique to IgA nephropathy and non-specific measures to reduce the same would be equally useful. These include low-protein diet and optimal control of blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
. The choice of the antihypertensive
Antihypertensive
The antihypertensives are a class of drugs that are used to treat hypertension . Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from...
agent is open as long as the blood pressure is controlled to desired level. However, Angiotensin converting enzyme inhibitors and Angiotensin II receptor antagonist
Angiotensin II receptor antagonist
Angiotensin II receptor antagonists, also known as angiotensin receptor blockers , AT1-receptor antagonists or sartans, are a group of pharmaceuticals which modulate the renin-angiotensin-aldosterone system...
s are favoured due to their anti-proteinuric effect.
Genetics
Though various associations have been described, no consistent pattern pointing to a single susceptible gene has been yet identified. Associations described include those with C4 null allele, factor B Bf alleles, MHC antigens and IgA isotypes. ACE geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
polymorphism
Polymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
(D allele) is associated with progression of renal failure, similar to its association with other causes of chronic renal failure
Chronic renal failure
Chronic kidney disease , also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite...
. However, more than 90% of cases of IgA nephropathy are sporadic, with a few large pedigrees described from Kentucky
Kentucky
The Commonwealth of Kentucky is a state located in the East Central United States of America. As classified by the United States Census Bureau, Kentucky is a Southern state, more specifically in the East South Central region. Kentucky is one of four U.S. states constituted as a commonwealth...
and Italy
Italy
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
.
Prognosis
Male gender, proteinuriaProteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
(especially > 2 g/day), hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, smoking
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
, hyperlipidemia
Hyperlipidemia
Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood...
, older age, familial disease and elevated creatinine
Creatinine
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...
concentrations are markers of a poor outcome. Frank hematuria
Hematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
has shown discordant results with most studies showing a better prognosis, perhaps related to the early diagnosis, except for one group which reported a poorer prognosis. Proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
are the most powerful prognostic factors in this group.
There are certain other features on kidney biopsy
Needle aspiration biopsy
Needle aspiration biopsy , may refer to fine needle aspiration cytology , fine needle aspiration biopsy and fine needle aspiration , is a diagnostic procedure sometimes used to investigate superficial lumps or masses...
such as interstitial scarring which are associated with a poor prognosis. ACE gene polymorphism
Polymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
has been recently shown to have an impact with the DD genotype
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
associated more commonly with progression to renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
.
Epidemiology
Men are affected three times as often as women. There is also a striking geographic variation in the prevalence of IgA nephropathy throughout the world. It is the most common glomerular disease in the Far EastFar East
The Far East is an English term mostly describing East Asia and Southeast Asia, with South Asia sometimes also included for economic and cultural reasons.The term came into use in European geopolitical discourse in the 19th century,...
and Southeast Asia
Southeast Asia
Southeast Asia, South-East Asia, South East Asia or Southeastern Asia is a subregion of Asia, consisting of the countries that are geographically south of China, east of India, west of New Guinea and north of Australia. The region lies on the intersection of geological plates, with heavy seismic...
, comprising almost half of all the patients with glomerular disease. However, it comprises only about 25% of the proportion in European and about 10% among North Americans, with African–Americans having a very low prevalence of about 2%. A confounding factor in this analysis is the existing policy of screening
Screening (medicine)
Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....
and use of kidney biopsy
Needle aspiration biopsy
Needle aspiration biopsy , may refer to fine needle aspiration cytology , fine needle aspiration biopsy and fine needle aspiration , is a diagnostic procedure sometimes used to investigate superficial lumps or masses...
as an investigative tool. School children in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
undergo routine urinalysis
Urinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
(as do Army recruits in Singapore
Singapore
Singapore , officially the Republic of Singapore, is a Southeast Asian city-state off the southern tip of the Malay Peninsula, north of the equator. An island country made up of 63 islands, it is separated from Malaysia by the Straits of Johor to its north and from Indonesia's Riau Islands by the...
) and any suspicious abnormality is pursued with a kidney biopsy, which might partly explain the high incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
of IgA nephropathy in those countries.
History
Heberden first described the disease in 1801 in a 5-year-old child with abdominal pain, hematuriaHematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
, hematochezia
Hematochezia
Hematochezia is the passage of fresh blood per anus, usually in or with stools . Hematochezia is commonly associated with lower gastrointestinal bleeding, but may also occur from a brisk upper GI bleed...
, and purpura of the legs. In 1837, Johann Schönlein described a syndrome of purpura associated with joint pain and urinary precipitates in children. Eduard Henoch, a student of Schönlein's, further associated abdominal pain and renal involvement with the syndrome. Jean Berger and Hinglais, in 1968, were the first to describe IgA deposition in this form of glomerulonephritis
Glomerulonephritis
Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...
(hence, Berger’s disease).