Acute proliferative glomerulonephritis
The post-infectious glomerulonephritis (post- streptococcal glomerulonephritis ) is an acute inflammation of the glomeruli ( glomerulonephritis ), which can occur up to four weeks after an infection with group A streptococcus betahämolysierenden. In recent years, the disease is becoming increasingly caused by other pathogens (bacteria, viruses, fungi, parasites). The cause of the renal injury is the deposition of immune complexes in the capillaries of the renal corpuscle with activation of the complement system. Symptoms include dark urine due to excretion of red blood cells ( hematuria ), increased protein excretion ( proteinuria), decreased kidney function, decreased urine production ( oliguria ), water retention (edema ) and high blood pressure. The course can not be influenced by drug treatment. In epidemics and for household contacts antibiotic prophylaxis is recommended. The prognosis is generally good. Rare, especially in the elderly or the presence of additional risk factors may lead to a permanent kidney damage. In developed countries, the disease goes back, in underdeveloped regions, it is still common.
- 4.1 Acute nephritic syndrome
- 4.2 Rapidly progressive nephritic syndrome
- 4.3 Subclinical or asymptomatic glomerulonephritis
- 5.1 IgA nephritis
- 5.2 Membranoproliferative glomerulonephritis
- 5.3 membranous glomerulonephritis
- 5.4 ANCA -associated glomerulonephritis
- 5.5 hemolytic uremic syndrome
- 5.6 renal infarction and abscess
- 5.7 Renal amyloidosis
- 6.1 Light Microscopy
- 6.2 Immunhistolochemie
- 6.3 electron
- 8.1 skin infections
- 8.2 throat infections
- 8.3 Epidemic Post streptococcal glomerulonephritis
- 9.1 Short-term forecast
- 9.2 Long -term prognosis
History
The post-infectious glomerulonephritis is one of the oldest known renal diseases.
Two hundred years ago watched C. D. Wells that during the recovery phase after scarlatina dropsy could occur, accompanied with dark discolored urine and decrease or cessation of urine production. In the second half of the 19th century was found in the histological examination in the kidneys of patients who had died of kidney failure after scarlet fever, inflammation of the glomeruli.
1903 Clemens von Pirquet suspected based on clinical observations of a pathological, antibody-mediated immune response as the cause of the disease. The altered immune response he described as foreign reaction, Greek allergy.
When it was discovered that scarlet caused by beta -haemolytic streptococci, the term post- streptococcal glomerulonephritis, has been introduced. In the first half of the 20th century it was discovered that it could cause acute glomerulonephritis after infection of the upper respiratory tract and skin and wound infections, in the vast majority were found streptococci as the causative agent. As a result, it could be shown that not all streptococcal strains were able to induce an acute nephritis. It was possible to isolate nephritogene ( nephritis - inducing ) streptococcal strains and to distinguish streptococcal strains that were responsible for rheumatic fever.
Epidemiology
In developed countries, the post-infectious glomerulonephritis ( adults 6 cases per 100,000 persons per year, 0.3 children cases) has become rare in recent decades and there occurs mainly in older people, particularly if additional predisposing factors are present such as alcoholism or drug addiction. In up to one half of cases of the disease is based on this infection with gram- negative bacteria based. In Central Europe, Chile and the disease has virtually disappeared, in Italy, China, Singapore, Mexico and the United States is a significant reduction of new cases observed (incidence). In underdeveloped regions, the disease is far more common, per year for adults 24.3 cases per 100,000 people, for children reported 2 cases. High incidences are reported in rural areas of Australia. In Valencia, Venezuela, the disease is based in pediatric nephrology in 70% of hospital admissions. In India there is a post - streptococcal glomerulonephritis in 73 % of acute glomerulonephritis older people. In underprivileged countries, the post - streptococcal glomerulonephritis is an important cause of acute renal failure ( 30% of cases in Istanbul, 52 % in Casablanca, 27 % in Mumbai, 25% in Nigeria). Large epidemic outbreaks, with 103-760 cases of disease have been reported since 1950 in the United States ( 1951-1952, were affected recruits ), Venezuela, Trinidad, Cuba, Armenia, Costa Rica, Lithuania, Brazil and Peru. Smaller outbreaks with case numbers below 100 were also observed in industrialized nations. The underreporting of the disease is very likely to be very high, because subclinical courses are about 4-19 times more common than symptomatic disease.
Pathogenesis
Skin and throat infections ( S. pyogenes, S. equi, S. constellatus )
Bacterial endocarditis ( Staph aureus, S. viridans)
Pneumonia ( S. pneumoniae, Mycoplasma pneumoniae)
Abscesses ( tooth abscess, deep abscesses, osteomyelitis)
Shunt nephritis ( Staph epidermidis, Propionibacterium acnes )
Gram-positive pathogens ( streptococci, staphylococci,
Pneumococci, enterococci, Listeria monocytogenes )
Gram-negative cocci ( meningococci, N. gonorrhoeae )
Gram-Negative Kokkobazillen ( Haemophilus )
Gram-negative bacilli (Salmonella, Klebsiella, Serratia,
Yersinia, Proteus, Pseudomonas )
Legionnaires' disease, brucellosis, bartonellosis
Tuberculosis, mycobacteriosis atyptische
Syphilis ( Treponema pallidum )
Leptospirosis ( Leptospira interrogans )
Rickettsial ( Coxiella burnetii )
Mycoplasma pneumoniae
Chlamydia pneumoniae
Histoplasmosis ( Histoplasma capsulatum )
Coccidioidomycosis ( Coccidioides immitis )
DNA viruses
Hepadnaviridae ( Hepatitis B virus)
Herpesviridae ( varicella- zoster virus,
Epstein -Barr virus, cytomegalovirus )
Parvoviridae ( parvovirus B19)
Adenoviridae ( adenovirus)
RNA viruses
Retroviridae (HIV)
Picornaviridae ( coxsackievirus, echovirus, hepatitis A virus )
Flaviviridae ( Dengue virus, Hepatitis C virus )
Paramyxoviridae ( mumps virus, measles virus)
Bunyaviridae ( Hantavirus )
Reoviridae ( Rotavirus )
Malaria ( Plasmodium falciparum, Plasmodium malariae )
Schistosomiasis ( Schistosoma hematobium, Schistosoma mansoni )
Toxoplasmosis ( Toxoplasma gondii )
Filariasis ( Wuchereria bancrofti )
Trichinosis ( Trichinella spiralis )
Cystic echinococcosis ( Echinococcus granulosus )
Amebiasis ( Entamoeba histolytica )
The realization that a variety of pathogens ( staphylococci, gram-negative bacteria, mycobacteria, parasites, fungi and viruses) can cause glomerulonephritis, led to the coining of the term "post -infectious glomerulonephritis ." Today, the term post - streptococcal glomerulonephritis and post-infectious glomerulonephritis can be used side by side.
It was assumed previously that group A streptococci are the only tribe that is able to induce glomerulonephritis. In recent times, but epidemics of post- streptococcal glomerulonephritis were observed, which was caused by streptococcus group C, especially S. zooepidemicus. Maybe nephritogene antigens occur in streptococci of different groups.
It is believed that the basic pathological mechanism of postinfectious glomerulonephritis is the deposition of immune complexes in the area of the glomerular capillary loops.
At the molecular level, two streptococcal antigens are present mainly investigated which are used as triggers of post - streptococcal glomerulonephritis in question: nephritis -associated plasmin receptor ( NAPR ) and streptococcal pyrogenic exotoxin B ( SPEB ).
Nephritis -associated plasmin receptor ( NAPR )
The nephritis -associated plasmin receptor is a glyceraldehyde -3- phosphate dehydrogenase. Deposits ( deposits) of this antigen can be detected early in tissue samples (kidney biopsies ) from patients with post- streptococcal glomerulonephritis, antibodies against this antigen can be found in Japan in the serum of 92 % of patients with post- streptococcal glomerulonephritis and 60% of patients with uncomplicated streptococcal infections. NAPR deposited in the glomeruli together with plasmin, but not with immunoglobulin G or components of the complement system.
Fumed streptococcal exotoxin B ( SPEB )
Streptococcal pyrogenic exotoxin B ( streptococcal pyrogenic exotoxin B, SPEB ) is a cationic cysteine proteinase by proteolysis of a precursor enzyme ( zymogen ) which is referred to as zSPBE arises. Both SPEB and zSPBE activate the alternative pathway of the complement system. SPBE is produced by group A streptococci, deposits of this antigen are detectable in kidney biopsies of patients with acute post- streptococcal glomerulonephritis. In Latin America, antibodies against SPEB found in the serum of most patients with post- streptococcal glomerulonephritis. In the renal SPEB is detectable along with components of the complement system in the electron-dense immune deposits.
References to other nephritogene antigens
Pathogenic strains of S. zooepidemicus lacking the gene for SPEB, there must be additional antigens which are able to initiate a post - streptococcal glomerulonephritis. One possible candidate is a protein called Szp5058 M protein having phagocytic inflammatory properties.
Pathomechanism
Inflammation
SPEB and NAPI can trigger an inflammatory reaction in the glomeruli. When mesangial cells of the renal corpuscle with SPEB and NAPI come into contact, they produce proinflammatory cytokines ( monocyte chemoattractant protein 1 and interleukin 6) and expressing increased adhesion molecules, monocytes are attracted and collide in the glomeruli of an inflammatory reaction. Also, peripheral blood leukocytes unleashed proinflammatory cytokines when they come in contact with SPEB: IL- 6, TNF - α, IL -8, and TGF- β.
Plasmin
Both NAPI and SPEB are to bind plasmin able. This points to a possible role of Plasminablagerungen in the pathogenesis of post- streptococcal glomerulonephritis.
Symptoms
The post - streptococcal glomerulonephritis can occur sporadically or in the context of an epidemic. During an epidemic occurs approximately in 5-10% of children with throat infections ( pharyngitis), glomerulonephritis and in about 25% of children with skin infections (impetigo ). The time ( latency ) between infection and the onset of the post- streptococcal glomerulonephritis is at revenge infections about 10 days for skin infections for about three weeks.
The symptoms may vary from asymptomatic microscopic hematuria up to an acute nephritic syndrome with haematuria by red to brown colored urine, proteinuria and nephrotic syndrome, decreased urine production ( oliguria ), water retention ( edema ), high blood pressure and acute renal failure.
Acute nephritic syndrome
Acute nephritic syndrome is characterized by hematuria (blood in urine), proteinuria (protein in urine) and edema ( water retention in the tissue) is often also hypertension and mild renal impairment. Acute nephritic syndrome is the classic progressive form of post- streptococcal glomerulonephritis. In the typical case occurred in a child about 10 days after a skin or throat infection suddenly swollen eyelids and water retention on, the urine is cloudy, urine production decreases, the blood pressure rises. 4 to 7 days after onset of disease, the urine production increases again, the edema disappear quickly, the blood pressure returns to normal. Red blood cells are detectable in the urine for months up to one year after the illness. Typical triggers a nephritic syndrome are tonsillitis, impetigo and scarlet fever. A nephritic syndrome can also be caused by protozoa or viruses even after other bacterial infections (eg, endocarditis, pneumococcal pneumonia) or occur.
Rapidly progressive nephritic syndrome
In about 5 % of cases, the course of post-infectious glomerulonephritis is complicated by a rapid decline in renal function. The trigger for the rapidly progressive course form streptococci, Staphylococcus aureus, gram-negative bacilli, mycoplasma and Mycobacterium leprae were detected. In the majority of cases, the peak of serum creatinine is reached within the first days of the disease.
Subclinical or asymptomatic glomerulonephritis
If in individuals who suffer from bacterial, viral or parasitic infections, the urine examined closely, proteinuria below 1 g / d, a leukocyturia or hematuria is not uncommon temporarily detectable. The incidence of asymptomatic courses can be a multiple of the courses that are associated with disease symptoms.
Differential Diagnosis
There is a variety of other pathological mechanisms known about an infectious disease can lead to kidney damage:
IgA nephritis
Bloody urine following an infection of the upper airways may indicate both a post- streptococcal glomerulonephritis as well as IgA nephritis. In general, the diseases can be distinguished by the clinical picture so that a kidney biopsy is only required in exceptional circumstances:
- A post- streptococcal glomerulonephritis occurs on average 10 days after the revenge infections and three weeks after skin infection on IgA nephritis within 5 days.
- In IgA nephritis repeated episodes of bloody urine ( hematuria ) are often at the post streptococcal glomerulonephritis, however, rare.
- For throat infections saith the detection of group A streptococci in throat swab or an elevated antistreptolysin O titer for a post streptococcal glomerulonephritis. Negative results, in particular for skin infections, but do not rule out a strep infection.
- The Postspreptokokken glomerulonephritis improves after annealing of the inciting infection, renal function begins to improve after 1-2 weeks, the previously lowered complement levels in serum to normal within 6 weeks, the excretion of red blood cells in the urine ( hematuria ) vanishes within 6 months. Persistent microscopic hematuria indicates an IgA nephritis, permanently lowered complement levels in membranoproliferative glomerulonephritis a.
Membranoproliferative glomerulonephritis
A membranoproliferative glomerulonephritis can be caused by an infected CSF drainage (shunt nephritis), infective endocarditis, osteomyelitis, chronic abscesses, infected vascular prostheses, schistosomiasis ( Schistosoma mansoni ) or river blindness ( Onchocerca volvulus ). The symptoms corresponds to the nephritic syndrome with microscopic hematuria, proteinuria, and renal function loss.
Membranous glomerulonephritis
Malaria, syphilis, and Loa loa - infections can lead to membranous glomerulonephritis with nephrotic syndrome.
ANCA -associated glomerulonephritis
Certain pathogens, such as Staphylococcus aureus, an ANCA -associated glomerulonephritis can trigger with a rapid loss of renal function.
Haemolytic uraemic syndrome
Following diarrheal diseases by Shigella dysenteriae or Escherichia coli ( O157: H7) caused a hemolytic uremic syndrome may be caused by bacterial verotoxin, which is characterized by hemolytic anemia, and acute renal failure.
Renal infarction and abscess
Fungal infections and endocarditis caused by Streptococcus agalactiae or Haemophilus influenzae, can by embolization of blood clots (thrombi ) or infected material lead to renal infarction or Nierenabszessen. Symptoms are flank pain and hematuria.
Renal amyloidosis
Chronic activation of the immune system by a long-lasting infections can lead to renal amyloidosis with nephrotic syndrome and chronic renal failure.
Histology
Light microscopy
- In the early stages it comes in the capillary loops of the glomeruli to the accumulation of granulocytes and monocytes, as well as for multiplication (proliferation ) of the capillary endothelial cells ( Endokapilläre glomerulonephritis, and Fig ).
- In the course of a multiplication (proliferation ) of mesangial cells and an increase of the extracellular matrix is observed ( mesangial proliferative glomerulonephritis, Fig.)
- Rare deposits of immune complexes between the glomerular basement membrane and the glomerular surface cells ( podocytes ) can already be seen in the light microscope ( Subepithelial Humps, Fig.)
- In a very severe damage to the glomerular capillaries may occur exudation of fibrin into the capsular space of the glomeruli, the result is a crescent-shaped proliferation of Kapselepithelzellen ( extracapillary crescent formation, and Fig ). The extracapillary crescent formation is the histological correlate of the rapidly progressive nephritic syndrome. In patients with crescent formation in less than 50 % of glomeruli annealing of the disease is probably more effective in the treatment of the triggering infection.
In crescent formation in more than 75 % of glomeruli and initial oligo- anuria, the prognosis for renal function is very poor.
Immunhistolochemie
In the immunohistochemical study are found in the capillary loops of the renal glomerular basement membrane and between podocytes ( = subepithelial ) located deposits of Ig G and C3. The deposits can form irregular patterns (Fig.), scalloped (Fig.) or graining celled (Fig.). Garlands shaped immune deposits indicate a worse prognosis of the disease.
Electron
Electron microscopic examination shows hump-shaped immune complex deposits ( humps ) between basement membrane and podocytes (Fig.).
Therapy
In general, the acute postinfectious glomerulonephritis heals without treatment of the underlying infection. The treatment is therefore supportive with bed rest, physical protection, sodium and water deprivation, and treatment of hypertension. For more severe gradients also corticosteroids, immunosuppressive and anticoagulant substances were used, but are lacking controlled studies.
Prophylaxis
An acute post- streptococcal glomerulonephritis can be prevented by early antibiotic treatment of streptococcal infection. A spreading nephritogener ( = nephritis -inducing ) streptococci can be prevented by preventive administration of antibiotics ( antibiotic prophylaxis ) to contacts. The problem, however, is the safe diagnosis of streptococcal infection, in order to avoid an unnecessary ( and problematic because of the risk of resistance development ) antibiotic treatment.
Skin infections
Active skin infections (impetigo ) caused usually by staphylococci or streptococci should be treated with penicillin, except for increased incidence of multidrug-resistant staphylococci in the affected population.
Throat infections
Only in 10-20 % of cases of streptococcal pharyngitis can be detected as the causative agent. Evidence of streptococcal infection are fever over 38 ° C, lack of cough, painful enlarged lymph nodes, tonsillitis (tonsillitis ) and between the ages of 3 and 14 years. In unclear cases, the diagnosis of streptococcal rapid test or bacterial culture can be secured from a throat swab. Antibiotic treatment should be done only if the four clinical criteria are met or the excitation could be secured.
Epidemic Post streptococcal glomerulonephritis
During an epidemic with nephritogenic streptococci antibiotic prophylaxis is recommended for household members of patients.
Forecast
Short-term forecast
In children, the short-term prognosis of acute post- streptococcal glomerulonephritis is very good. In contrast, in older patients are often serious comorbidities before, such as malnutrition ( malnutrition ), alcoholism, diabetes or other chronic diseases. In addition, the progression of the disease in elderly patients are more difficult with uremia, heart failure and proteinuria in the nephrotic range; Mortality may be up to 20-25%.
Long -term prognosis
In long-term observations of 10-20 years can be found in approximately 20% of children who have undergone a post- streptococcal glomerulonephritis, abnormalities in the urinalysis as proteinuria or microscopic hematuria, approximately 3 % will develop high blood pressure, but less than 1% of uremia.
In certain populations, however, the long-term prognosis can be much worse. After an epidemic in Minas Gerais, Brazil, 8% of patients developed within five years of a chronic renal failure. In communities of Aborigines in Australia, where risk factors such as low birth weight, diabetes and metabolic syndrome are common, the long-term prognosis of post- streptococcal glomerulonephritis is also worse with an increased incidence of microscopic hematuria and albuminuria as well as one in comparison to the non-indigenous population several times increased risk of uremia.