Post-infectious glomerulonephritis
The postinfectious glomerulonephritis (poststreptococcal glomerulonephritis) is an acute inflammation of the glomeruli ( glomerulonephritis ), one to four weeks after infection with a betahämolysierenden streptococci can occur in group A. In recent years, the disease has increasingly been caused by other pathogens ( bacteria , viruses , fungi , parasites ). The cause of kidney damage is the deposition of immune complexes in the capillaries of the kidney corpuscle with activation of the complement system . Symptoms include dark urine due to erythrocyte excretion ( hematuria ), increased protein excretion ( proteinuria ), decline in kidney function , decrease in urine production (oliguria) , water retention (edema), and high blood pressure . The course cannot be influenced by drug treatment. In epidemics and for household contacts is an antibiotic - prophylaxis recommended. The prognosis is generally good. In rare cases, particularly in older patients or in the presence of additional risk factors, permanent kidney damage can occur. The disease is on the decline in industrialized nations, but is still common in underdeveloped regions.
history
Post-infectious glomerulonephritis is one of the oldest known kidney diseases .
Observed two centuries ago C. D. Wells that during the recovery period after scarlet fever a dropsy could occur, which was accompanied by dark discolored urine and decrease or cessation of urine production . In the second half of the 19th century, histological examination of the kidneys of patients who had died of kidney failure after scarlet fever found inflammation of the kidney corpuscles .
In 1903, on the basis of clinical observations , Clemens von Pirquet suspected a pathological , antibody-mediated immune reaction as the cause of the disease. He described the changed immune response as a foreign reaction, in Greek allergy .
When it was discovered that scarlet fever is caused by beta hemolytic streptococci , the term post-streptococcal glomerulonephritis was introduced. In the first half of the 20th century it was discovered that acute glomerulonephritis could also occur after infections of the upper respiratory tract and skin as well as wound infections . Streptococci were the pathogen in the vast majority. As a result, it could be shown that not all streptococcal strains were able to cause acute nephritis . It became possible to isolate nephritogenic (nephritis-causing) streptococcal strains and to distinguish them from streptococcal strains that were responsible for rheumatic fever .
Epidemiology
In the industrialized nations, post-infectious glomerulonephritis has become rare in the last few decades (adults 6 cases per 100,000 people per year, children 0.3 cases) and occurs predominantly in older people, especially if there are additional predisposing factors such as alcoholism or drug addiction . In up to half of the cases, the disease is based on an infection with gram-negative pathogens. In Central Europe and Chile the clinical picture has practically disappeared, in Italy, China, Singapore, Mexico and the USA a considerable decrease in new cases ( incidence ) can be observed. The disease is far more common in underdeveloped regions, with 24.3 cases per 100,000 people reported per year for adults and 2 cases for children. High incidences are reported in rural areas of Australia. In Valencia, Venezuela, the disease underlies 70% of inpatient admissions in pediatric nephrology . In India, 73% of acute glomerulonephritis in the elderly is post-streptococcal glomerulonephritis. In underprivileged countries, post-streptococcal glomerulonephritis is a major cause of acute kidney failure (30% of cases in Istanbul, 52% in Casablanca, 27% in Bombay, 25% in Nigeria). Large epidemic outbreaks, with 103 to 760 cases, have been reported since 1950 from the USA (1951–1952, affected recruits), Venezuela, Trinidad, Cuba, Armenia, Costa Rica, Lithuania, Brazil and Peru. Smaller outbreaks with case numbers below 100 have also been observed in industrialized nations. The number of unreported cases of the disease is very likely very high, also because subclinical courses are around 4–19 times more common than symptomatic diseases.
Pathogenesis
The knowledge that a large number 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 terms post-streptococcal glomerulonephritis and post-infectious glomerulonephritis are used side by side.
It was previously believed that group A streptococci were the only strain capable of causing glomerulonephritis. Recently, however, epidemics of post-streptococcal glomerulonephritis caused by group C streptococci, particularly S. zooepidemicus, have been observed. It is possible that nephritogenic antigens are found in streptococci of different groups.
It is believed that the basic pathological mechanism of post-infectious glomerulonephritis is the deposition of immune complexes in the area of the glomerular capillary loops.
At the molecular level, two streptococcal antigens are currently being investigated that can trigger post-streptococcal glomerulonephritis: 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 (depots) of this antigen can be detected early in tissue samples (kidney biopsies) from patients with post-streptococcal glomerulonephritis.In Japan, antibodies against this antigen are found in the serum of 92% of patients with post-streptococcal glomerulonephritis and 60% of patients with uncomplicated streptococcal infections . NAPR is deposited in the kidney corpuscle together with plasmin, but not with immunoglobulin G or components of the complement system .
Pyrogenic Streptococcal Exotoxin B (SPEB)
Pyrogenic streptococcal exotoxin B (streptococcal pyrogenic exotoxin B; SPEB) is a cationic cysteine proteinase that is produced by proteolysis of an enzyme precursor (zymogen) called zSPBE. Both SPEB and zSPBE activate the alternative path of the complement system . SPBE is produced by group A streptococci; deposits of this antigen can be detected in kidney biopsies from patients with acute post-streptococcal glomerulonephritis. In Latin America, antibodies to SPEB are found in the serum of most patients with post-streptococcal glomerulonephritis. In the kidney corpuscles, SPEB can be detected together with components of the complement system in the electron-dense immune depots.
Evidence of other nephritogenic antigens
Pathogenic strains of S. zooepidemicus lack the gene for SPEB, so there must be other antigens that are able to trigger post-streptococcal glomerulonephritis. A possible candidate is a protein called Szp5058 M protein, which has anti- phagocytosis properties.
Pathomechanism
inflammation
SPEB and NAPI can trigger an inflammatory reaction in the kidney corpuscle. When mesangium cells of the kidney corpuscle come into contact with SPEB and NAPI, they produce proinflammatory cytokines ( monocyte chemoattractant protein 1 and interleukin 6 ) and increasingly express adhesion molecules , monocytes are attracted and trigger an inflammatory reaction in the kidney corpuscle . Peripheral blood leukocytes also release proinflammatory cytokines when they come into contact with SPEB: IL-6 , TNF-α , IL-8 , and TGF-β .
Plasmin binding
Both NAPI and SPEB are able to bind plasmin. This suggests a possible role of plasmin deposits in the pathogenesis of post-streptococcal glomerulonephritis.
Symptoms
Post-streptococcal glomerulonephritis can occur sporadically or as part of an epidemic . During an epidemic, around 5–10% of children with throat infections (pharyngitis) develop glomerulonephritis and around 25% of children with skin infections (impetigo) . The period of time (latency) between infection and onset of post-streptococcal glomerulonephritis is around 10 days for throat infections and around three weeks for skin infections.
The symptoms can vary from asymptomatic microhematuria to acute nephritic syndrome with urine colored red to brown due to macrohematuria , proteinuria and nephrotic syndrome , decreased urine production (oliguria) , water retention (edema) , high blood pressure and acute kidney failure .
Acute Nephritic Syndrome
The acute nephritic syndrome is characterized by hematuria (blood in the urine) , proteinuria (protein in the urine) and edema (water retention in the tissue) ; there is also often high blood pressure and a mild impairment of kidney function . Acute nephritic syndrome is the classic form of post-streptococcal glomerulonephritis. Typically around 10 days after a skin or throat infection, a child will suddenly experience swollen eyelids and water retention, the urine becomes cloudy, the urine production decreases, and the blood pressure rises. 4 to 7 days after the onset of the disease, urine production increases again, the edema disappears quickly, and blood pressure returns to normal. Red blood cells can be found in the urine for months to a year after the disease. Typical triggers of nephritic syndrome are tonsillitis , impetigo contagiosa, and scarlet fever . But a nephritic syndrome can also search for other bacterial infections (. Eg endocarditis , pneumococcal - pneumonia ) occur or by protozoa or viruses are triggered.
Rapidly progressive nephritic syndrome
In about 5% of cases, the course of post-infectious glomerulonephritis is complicated by a rapid decline in kidney function. Streptococci , Staphylococcus aureus , gram-negative bacilli , mycoplasma and Mycobacterium leprae have been shown to cause the rapidly progressive form . In the majority of cases the summit of is serum - creatinine reached within the first days of the disease.
Subclinical or asymptomatic glomerulonephritis
If the urine of individuals suffering from bacterial, viral or parasitic infections is closely examined, it is not uncommon for temporary proteinuria below 1 g / d, leukocyturia or microhematuria to be detectable. The frequency of asymptomatic courses can be a multiple of the courses associated with the symptoms of the disease.
Differential diagnosis
A large number of other pathomechanisms are known by which an infectious disease can damage the kidneys:
IgA nephritis
Bloody urine following an upper respiratory infection can indicate both post-streptococcal glomerulonephritis and IgA nephritis . As a rule, the clinical pictures can be differentiated on the basis of the clinical picture, so that a kidney biopsy is only required in exceptional cases:
- Post-streptococcal glomerulonephritis occurs on average 10 days after throat infections and three weeks after skin infections , and IgA nephritis occurs within 5 days.
- Repeated episodes of bloody urine (macrohematuria) are common in IgA nephritis, but rare in post-streptococcal glomerulonephritis.
- In the detection of Streptococcal throat infections speaks the group A in throat swab or increased Antistreptolysin O - titer for a post-streptococcal glomerulonephritis. However, negative results, especially in the case of skin infections, do not rule out a streptococcal infection.
- Post-spreptococcal glomerulonephritis improves after the offending infection has healed, kidney function begins to improve after 1–2 weeks, the previously lowered complement levels in the serum normalize within 6 weeks, and the excretion of red blood cells in the urine ( microhematuria ) disappears within 6 months. Persistent microhematuria indicates IgA nephritis, long-term decreased complement levels indicate membranoproliferative glomerulonephritis .
Membranoproliferative glomerulonephritis
A membranoproliferative glomerulonephritis can be triggered by an infected CSF drainage (shunt nephritis) , infectious endocarditis , an osteomyelitis , chronic abscess , infected vascular prostheses , schistosomiasis ( Schistosoma mansoni ), or river blindness ( Onchocerca volvulus ). The symptoms correspond to the nephritic syndrome with microhematuria , proteinuria and loss of renal function .
Membranous glomerulonephritis
Malaria , syphilis, and loa loa infections can lead to membranous glomerulonephritis with nephrotic syndrome .
ANCA Associated Glomerulonephritis
Certain pathogens, e.g. B. Staphylococcus aureus can cause ANCA-associated glomerulonephritis with rapid loss of renal function .
Hemolytic uremic syndrome
Following diarrhea caused by Shigella dysenteriae or Escherichia coli (O157: H7) , bacterial verotoxin can trigger a hemolytic-uremic syndrome , which is characterized by hemolytic anemia and acute kidney failure .
Kidney infarction and abscess
Fungal infections and endocarditis caused by Streptococcus agalactiae or Haemophilus influenzae can lead to kidney infarcts or kidney abscesses through embolization of blood clots (thrombi) or infected material . Symptoms are flank pain and hematuria .
Renal amyloidosis
Chronic activation of the immune system from long-term infections can lead to amyloidosis of the kidneys with nephrotic syndrome and chronic kidney failure .
histology
Black: Immune complexes
Dark violet: Basement membrane
Pink: Endothelium
Green: Visceral epithelium
Light violet: Mesangium
Light microscopy
- In the early stages it comes in the capillary loops of the glomeruli to the accumulation of granulocytes and monocytes and for proliferation (proliferation) of the capillary ( endocapillary glomerulonephritis , Fig. And).
- In the further course, an increase (proliferation) of the mesangium cells and an increase in the extracellular matrix can be observed ( mesangioproliferative glomerulonephritis , Fig.).
- Deposits of immune complexes between the glomerular basement membrane and the glomerular cover cells (podocytes) can rarely be seen under the light microscope ( subepithelial humps , Fig.).
- Very severe damage to the glomerular capillaries can lead to exudation of fibrin into the capsular space of the renal corpuscle, resulting in a sickle-shaped proliferation of capsular epithelial cells ( extracapillary crescent formation , Fig. And). The extracapillary crescent formation is the histological correlate of the rapidly progressive nephritic syndrome. In patients with crescent formation in less than 50% of the kidney corpuscles, the disease is likely to heal if the causative infection is effectively treated.
In crescent formation in more than 75% of renal and initial oligo - anuria renal function is the prognosis for very bad.
Immunohistochemistry
During the immunohistochemical examination , deposits of Ig G and C3 are found in the capillary loops of the kidney corpuscles between the glomerular basement membrane and podocytes (= subepithelial) . The deposits can form irregular (Fig.), Garland-shaped (Fig.) Or granular (Fig.) Patterns. Garland-shaped immune complex deposits indicate a poorer prognosis for the disease.
Electron microscopy
The electron microscopic examination shows hump-shaped immune complex deposits (humps) between the basement membrane and podocytes (Fig.).
therapy
Usually, acute post-infectious glomerulonephritis heals without treatment for the underlying infection. Therapy is therefore supportive with bed rest, physical rest, sodium and water withdrawal, and treatment of hypertension . In more severe cases, corticosteroids , immunosuppressants, and anticoagulant substances were also used, but there are no controlled studies on this .
prophylaxis
Acute post-streptococcal glomerulonephritis can be prevented by early antibiotic therapy of a streptococcal infection. The spread of nephritogenic (= nephritis-causing) streptococci can be prevented by the preventive administration of antibiotics (antibiotic prophylaxis ) to contact persons. However, a reliable diagnosis of a streptococcal infection is problematic in order to avoid unnecessary (and problematic because of the risk of developing resistance ) antibiotic treatment.
Skin infections
Active skin infections (impetigo) , which are usually caused by staphylococci or streptococci, should be treated with penicillin, unless there is an increased occurrence of multi-resistant staphylococci in the affected population group.
Throat infections
Streptococci can only be detected as a pathogen in 10–20% of cases of sore throat . Indications of a streptococcal infection are fever over 38 ° C, lack of cough , painfully enlarged lymph nodes , tonsillitis and age between 3 and 14 years. In unclear cases, the diagnosis can be confirmed by a rapid streptococcal test or a bacterial culture from a throat swab . Antibiotic treatment should only be given if four of the clinical criteria are met or the pathogen has been confirmed.
Post-streptococcal epidemic glomerulonephritis
During an epidemic of streptococcal nephritogenic one is for household members of patients antibiotics - prophylaxis recommended.
forecast
Short term forecast
In children, the short-term prognosis for acute post-streptococcal glomerulonephritis is very good. In contrast, older patients often have serious comorbidities such as malnutrition (malnutrition) , alcoholism , diabetes or other chronic diseases. In addition, the disease progression in older patients is more severe with uremia , heart failure and proteinuria in the nephrotic range; the mortality can be up to 20-25%.
Long-term prognosis
In long-term observations over 10–20 years, about 20% of children who have suffered post-streptococcal glomerulonephritis have abnormalities in the urine examination such as proteinuria or microhematuria , about 3% develop high blood pressure , but less than 1% develop uremia .
In certain populations, however, the long-term prognosis can be significantly worse. Following an epidemic in Minas Gerais , Brazil , 8% of patients developed chronic kidney failure within five years . In communities of Aborigines in Australia , where risk factors such as low birth weight , diabetes and metabolic syndrome are frequent, long-term prognosis of post streptococcal glomerulonephritis is also worse with an increased incidence of microscopic hematuria and albuminuria as well as a multi-fold increased compared to the non-indigenous population risk of uremia .
literature
- Talerngsak Kanjanabuch, Wipawee Kittikowit, Somchai Eiam-Ong: An update on acute postinfectious glomerulonephritis worldwide . In: Nature Reviews Nephrology . 5, No. 5, May 2009, ISSN 1759-507X , pp. 259-269. doi : 10.1038 / nrneph.2009.44 . PMID 19384327 .
- Bernardo Rodriguez-Iturbe, James M. Musser: The Current State of Poststreptococcal Glomerulonephritis . In: J Am Soc Nephrol . 19, No. 10, October 1, 2008, pp. 1855-1864. doi : 10.1681 / ASN.2008010092 . PMID 18667731 .
- Bernardo Rodríguez-Iturbe, S Batsford: Pathogenesis of poststreptococcal glomerulonephritis a century after Clemens von Pirquet . In: Kidney International . 71, No. 11, June 2007, ISSN 0085-2538 , pp. 1094-104. doi : 10.1038 / sj.ki.5002169 . PMID 17342179 .
- Bernardo Rodriguez-Iturbe: Epidemic poststreptococcal glomerulonephritis . (PDF) In: Kidney Int . 25, No. 1, January 1984, ISSN 0085-2538 , pp. 129-136. doi : 10.1038 / ki.1984.19 . Retrieved November 19, 2008.
Web links
- Poststreptococcal Glomerulonephritis Pathology - Pathopic image database of the University of Basel; Instructions: PathoPic (PDF; 2.2 MB)
- Postinfectious glomerulonephritis . From: Agnes Fogo et al .: Atlas of Renal Pathology. In: Am J Kidney Dis , 31 (5): E1, 1998 (English)
Individual evidence
- ↑ Gabriella Moroni: Long-term prognosis of diffuse proliferative glomerulonephritis associated with infection in adults . In: Nephrology Dialysis Transplantation . 17, No. 7, July 2002, ISSN 0931-0509 , pp. 1204-1211. PMID 12105242 .
- ↑ Jonathan R Carapetis, Andrew C Steer, E Kim Mulholland, Martin Weber: The global burden of group A streptococcal diseases . In: The Lancet Infectious Diseases . 5, No. 11, November 2005, ISSN 1473-3099 , pp. 685-694. doi : 10.1016 / S1473-3099 (05) 70267-X . PMID 16253886 .
- ↑ a b c d Talerngsak Kanjanabuch, Wipawee Kittikowit, Somchai Eiam-Ong: An update on acute postinfectious glomerulonephritis worldwide . In: Nature Reviews. Nephrology . 5, No. 5, May 2009, ISSN 1759-507X , pp. 259-269. doi : 10.1038 / nrneph.2009.44 . PMID 19384327 .
- ↑ Ximena Berríos, et al .: Post-streptococcal acute glomerulonephritis in Chile - 20 years of experience . In: Pediatric Nephrology . 19, No. 3, March 2004, ISSN 0931-041X , pp. 306-312. doi : 10.1007 / s00467-003-1340-9 . PMID 14689289 .
- ^ A Sarkissian, M Papazian, G Azatian, N Arikiants, A Babloyan, E Leumann: An epidemic of acute postinfectious glomerulonephritis in Armenia . In: Archives of Disease in Childhood . 77, No. 4, October 1997, ISSN 1468-2044 , pp. 342-344. PMID 9389241 .
- ↑ Amr A El-Husseini, Hussein A Sheashaa, Alaa A Sabry, Fatma E Moustafa, Mohamed A Sobh: Acute postinfectious crescentic glomerulonephritis: clinicopathologic presentation and risk factors . In: International Urology and Nephrology . 37, No. 3, 2005, ISSN 0301-1623 , pp. 603-609. doi : 10.1007 / s11255-005-0399-6 . PMID 16307349 .
- ↑ RN Srivastava, A Moudgil, A Bagga, AS Vasudev, UN Bhuyan, KR Sundraem: Crescentic glomerulonephritis in children: a review of 43 cases . In: American Journal of Nephrology . 12, No. 3, 1992, ISSN 0250-8095 , pp. 155-161. PMID 1415376 .
- ↑ B Rodríguez-Iturbe, et al .: Attack rate of poststreptococcal nephritis in families. A prospective study . In: Lancet . 1, No. 8217, February 21, 1981, ISSN 0140-6736 , pp. 401-403. PMID 6110037 .
- ↑ Endocapillary glomerulonephritis . Pathology image database Pathopic of the University of Basel
- ↑ Endocapillary proliferation . ( Memento of the original from June 27, 2003 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. From: Agnes Fogo et al .: Atlas of Renal Pathology. In: Am J Kidney Dis 31 (5): E1, 1998
- ↑ Mesangioproliferative Glomerulonephritis Pathology Image database Pathopic of the University of Basel.
- ↑ hump in the English-language Wiktionary.
- ↑ Subepithelial Humps, light microscopy pathology image database Pathopic of the University of Basel.
- ↑ Extracapillary stressed glomerulonephritis: segmental crescent pathology Image database Pathopic of the University of Basel.
- ↑ Extracapillary stressed glomerulonephritis: global crescent pathology image database Pathopic of the University of Basel.
- ↑ A clinico-pathologic study of crescentic glomerulonephritis in 50 children. A report of the Southwest Pediatric Nephrology Study Group . In: Kidney International . 27, No. 2, February 1985, ISSN 0085-2538 , pp. 450-458. doi : 10.1038 / ki.1985.30 . PMID 3887000 .
- ↑ Irregular immune complex deposits, immunofluorescence . ( Memento of the original from June 27, 2003 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. From: Agnes Fogo et al .: Atlas of Renal Pathology. In: Am J Kidney Dis , 31 (5): E1, 1998.
- ↑ Garland-shaped immune complex deposits, immunofluorescence . ( Memento of the original from June 27, 2003 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. From: Agnes Fogo et al .: Atlas of Renal Pathology. In: Am J Kidney Dis , 31 (5): E1, 1998.
- ↑ Granular immune complex deposits, immunofluorescence . ( Memento of the original from June 27, 2003 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. From: Agnes Fogo et al .: Atlas of Renal Pathology. In: Am J Kidney Dis , 31 (5): E1, 1998.
- ↑ Subepithelial humps, electron microscopy . ( Memento of the original from June 27, 2003 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. From: Agnes Fogo et al .: Atlas of Renal Pathology. In: Am J Kidney Dis , 31 (5): E1, 1998.
