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Post-Streptococcal Glomerulonephritis

Glomerulonephritis Streptococcal Acute

Post-streptococcal glomerulonephritis is a renal disease that may be detected in individuals who were infected with certain strains of Streptococcus. Immune complexes produced in the course of immune defense then bind to glomeruli and trigger inflammation.


Presentation

PG may not be diagnosed in patients who do not have a medical history of streptococcal infection, i.e., of tonsillitis, pharyngitis, laryngitis or pyodermitis. Such infection usually occurred several weeks ago. Acute PG may develop one or two weeks after infections of the upper respiratory tract, three to six weeks often pass between skin infection and first signs of glomerulonephritis. PG does not develop at the same time as the aforementioned infections. If PG-like symptoms are observed, immunoglobulin A nephropathy is a more likely diagnosis.

In PG, erythrocytes may pass through the damaged glomerular basement membrane and will subsequently undergo hemolysis. Degradation products account for the dark color of urine that is often the first sign of PG. Hematuria is present in all PG patients. It may be accompanied by symptoms indicating a reduced general condition. Malaise, anorexia and overall weakness are registered in about half of all PG patients. Some experience nausea and vomitus, but these symptoms are less common.

Further symptoms of PG account for severe water and electrolyte imbalances. They result from water and salt retention that, in turn, are caused by reduced renal blood flow and decreased glomerular filtration rates. Hypertension and edema are the second most common symptoms of PG. Hypertension is more often detected in the elderly than in pediatric patients and is associated with low plasma renin levels. Acute periorbital edema that are more prominent after periods of rest are characteristic for PG. Generalized edema and symptoms pointing at circulatory congestion, e.g., left ventricular dysfunction, reduced resistance to exercise and dyspnea, may be observed. A small share of patients suffering from PG develops hypertensive encephalopathy. It has been suggested that the severity of edema development increases proportionally to renal function impairment. 

The symptom complex of hematuria, hypertension, edema and possibly oliguria is known as the acute nephritic syndrome. It has been estimated that 95% of all PG patients present at least two of the aforementioned symptoms, 40% present all of them.

Rapidly Progressive Glomerulonephritis
  • We report a patient with rapidly progressive glomerulonephritis and nephrotic-range proteinuria following acute pharyngitis, in whom serologic and kidney biopsy findings led to a diagnosis of PSGN.[ncbi.nlm.nih.gov]
  • On exploration, a sterile perirenal hematoma was found and a wedge renal biopsy revealed crescentic rapidly progressive glomerulonephritis of the post infectious type. Deterioration to end stage renal failure occurred within a few months.[ncbi.nlm.nih.gov]
  • The clinical concept of rapidly progressive glomerulonephritis includes various renal diseases that cause renal function to deteriorate over a subacute course.[clinicaltrials.gov]
  • Rapidly progressive glomerulonephritis (RPGN): it is possible for PSGN to develop rapidly to RPGN (a nephritic syndrome that progresses to renal failure rapidly) especially in adults.[stepwards.com]
  • ., hematuria and RBC casts , mild proteinuria ) Ultrasound : enlarged kidneys Renal biopsy (not performed in most cases) Indication: suspected rapidly progressive glomerulonephritis Findings Light microscopy: glomeruli appear enlarged and hypercellular[amboss.com]
Congestive Heart Failure
  • Severe hypertension was closely associated with either symptoms of an acute encephalopathy or congestive heart failure.[ncbi.nlm.nih.gov]
  • This is secondary to congestive heart failure and azotemia. Congestive heart failure is more common in adults (43%) than in children ( 5%). Nephrotic-range proteinuria is also more common in adults (20%) than in children (4-10%).[emedicine.medscape.com]
  • heart failure or pulmonary edema End-stage renal disease Hyperkalemia High blood pressure (hypertension) Nephrotic syndrome Source:[theiyafoundation.org]
  • heart failure (raised JVP, enlarged liver, crepitations in lung bases).[bpac.org.nz]
Fatigue
  • […] edema Rapidly progressive glomerulonephritis Microhematuria (persisting for years) Chronic renal failure (rare) Nephrotic syndrome Untreated respiratory streptococcal infection or impetigo within the last 1 to 3 weeks Abdominal pain Anorexia Back pain Fatigue[quizlet.com]
  • Issues Symptoms of PSGN can include: Dark, reddish-brown urine Swelling (edema), especially in the face, around the eyes, and in the hands and feet Decreased need to pee or decreased amount of urine Feeling tired due to low iron levels in the blood (fatigue[cdc.gov]
  • Many will also experience decreased alertness, drowsiness, fatigue and confusion. In some cases, acute nephritis can progress to chronic glomerulonephritis, a serious condition characterized by a worsening of the glomeruli of the kidneys.[livestrong.com]
Hypertension
  • Adults may have a higher incidence of hypertension and chronic renal failure as a result of post-streptococcal glomerulonephritis.[ncbi.nlm.nih.gov]
  • He later developed severe hypertension with evidence of glomerulonephritis, which was diagnosed as acute post-streptococcal glomerulonephritis.[ncbi.nlm.nih.gov]
  • Severe hypertension was closely associated with either symptoms of an acute encephalopathy or congestive heart failure.[ncbi.nlm.nih.gov]
  • Acute post streptococcal glomerulo-nephritis (APSGN) is a form of acute nephritic syndrome characterized by edema, hematuria, proteinuria, and hypertension.[ncbi.nlm.nih.gov]
  • Immediate control of hypertension resulted in rapid and complete neurological recovery.[ncbi.nlm.nih.gov]
Facial Edema
  • Case summary Initial presentation A 7-year-old male presented with 2 weeks of progressive facial edema, oligoanuria and ‘iced-tea’ colored urine.[ckj.oxfordjournals.org]
Hematuria
  • Among children with normal GFR, eight (23.5%) had microalbuminuria plus hematuria and four (11.7%) had hematuria.[ncbi.nlm.nih.gov]
  • The proteinuria and hematuria resolved completely in eight weeks. Our case demonstrates that APSGN should be considered in evaluating hematuria and nephrotic syndrome in infants and children below two years of age.[ncbi.nlm.nih.gov]
  • A high ASO titer, high urine specific gravity, severe hematuria and pyuria early in the illness were suggestive of a higher risk for an atypical presentation.[ncbi.nlm.nih.gov]
  • Post-streptococcal glomerulonephritis (PSGN) classically presents with hypertension, edema, macroscopic hematuria, acute renal failure, proteinuria, and an active urine sediment with red blood cells and red blood cell casts.[ncbi.nlm.nih.gov]
  • This case illustrates that APSGN needs to be considered in the evaluation of both gross and microscopic hematuria in this age group.[ncbi.nlm.nih.gov]
Oliguria
  • A 14-year-old boy presented with 3 days of hematuria and oliguria following impetigo. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis with subendothelial electron dense deposits but no crescents.[ncbi.nlm.nih.gov]
  • We herein report the case of a 17-year-old man who developed an increased plasma creatinine level (11.1 mg/dL) and oliguria with massive proteinuria (27.3 g/day) four weeks after an abraded wound to his right knee.[ncbi.nlm.nih.gov]
  • Anti-C1q positive patients had significantly higher proteinuria and serum creatinine as well as more often oliguria, hypertension and delayed resolution of the disease than patients without anti-C1q.[ncbi.nlm.nih.gov]
  • A 59-yr-old woman was admitted with oliguria and hemoptysis two weeks after pharyngitis. Renal insufficiency rapidly progressed, and respiratory distress developed. Chest radiography showed acute progressive bilateral pulmonary infiltrates.[ncbi.nlm.nih.gov]
  • Symptoms of APSGN include: fluid accumulation and tissue swelling ( edema ) initially in the face and around the eyes, later in the legs low urine output (oliguria) blood in the urine (hematuria) protein in the urine (proteinuria) high blood pressure[medical-dictionary.thefreedictionary.com]
Dark Urine
  • urine, typical of the condition, may not be noticed by children.[bpac.org.nz]
  • Diagnosis Acute onset Symptoms: edema, oliguria, dark urine, hypertension Urinalysis: RBCs, protein, casts Evidences of streptococcal infection: Prodromes Elavated serum titers of Abs to streptozymes(ASO) Serum C3 - Reduced 39.[slideshare.net]
  • The damage may cause dark urine, swelling, high blood pressure, or even kidney failure. Some patients get kidney damage from strep, but it is so mild they never know. Other infections can cause GN, although less commonly than strep.[pascalelane.wordpress.com]
Macroscopic Hematuria
  • Post-streptococcal glomerulonephritis (PSGN) classically presents with hypertension, edema, macroscopic hematuria, acute renal failure, proteinuria, and an active urine sediment with red blood cells and red blood cell casts.[ncbi.nlm.nih.gov]
  • Laboratory Investigations Urinalysis Macroscopic hematuria: Rusty or tea-color. 18. Microscopy: leukocytes, red blood cell casts (pathognomonic), and granular casts. 19. Proteinuria 2 . (Nephrotic-range proteinuria occurs in 20. Pyuria.[slideshare.net]
Smoky Urine
  • Patients with overt disease demonstrate gross hematuria characterized by red or smoky urine, headache, and generalized symptoms such as anorexia, nausea, vomiting, and malaise. 32 Swelling of the renal capsule can cause flank or back pain.[aafp.org]

Workup

It is of utmost importance to obtain a detailed medical history, since patients usually do not relate earlier infections of the upper respiratory tract or skin to their current renal problems.

Diagnostic measures aim at verifying Streptococcus involvement in earlier infections and assessing renal function. Serologic tests may be of great value to achieve the former and elevated antibody titers can be detected in as much as 95% and 80% of PG patients after upper respiratory tract and skin infections, respectively. Titers for anti-streptolysin and anti-nicotinamide adenine dinucleotidase are often elevated after throat infections with β-hemolytic Streptococcus. Levels of anti-hyaluronidase and anti-DNAse B may serve in both cases. All the aforementioned antibody titers are checked in a streptozyme screen. Anti-zymogen titers have been proposed as an alternative parameter to evaluate involvement of Streptococcus in past infections. In general, elevated antibody titers are detectable after one week; they peak one month after infection and decrease slowly afterwards.

Relevant information regarding renal function may be deduced from blood urea nitrogen and serum creatinine values. These parameters reliably reflect alterations of the glomerular filtration rate. They usually normalize within weeks or few months at most. Rapid deterioration of renal function and gross increases in the above mentioned parameters may indicate more severe forms of PG in which patients less frequently regain complete renal function.

Serum analyses may further reveal decreased complement levels that result from activation of the classic and alternative pathways of the complement system. As is the case with blood urea nitrogen and serum creatinine, these parameters usually return to physiological values in between weeks or few months.

Circulating immune complexes, cryoglobulins and rheumatoid factor may be detected in a significant share of PG patients. More recently, N-terminal pro-brain natriuretic peptide has been proposed as an alternative parameter to evaluate circulatory congestion in PG patients [10].

Urine samples, ideally obtained in the early morning, should be analyzed. All PG patients show hematuria and proteinuria, but the severity of these pathologic conditions varies greatly. In up to 10% of PG patients, these parameters justify diagnosis of nephrotic syndrome. According to the aforementioned findings, erythrocytes as well as leukocytes are found in the sediment of the urine. If phase-contrast microscopy of the urine sediment can be performed, it may help to detect dysmorphic erythrocytes - a finding that indicates glomerular hematuria. Hematuria usually resolves in between three months, proteinuria in between six months. Even if clinical symptoms ceased, microscopic examinations may still reveal altered urine properties.

Imaging techniques are not usually applied to support diagnosis of PG. They may, however, help to assess the severity of the disease, particularly by informing about heart function and kidney condition.

If these diagnostic measures do not allow for confirmation of PG, if certain parameters develop uncharacteristically, do not normalize over the course of the expected time frames, or if the patient's condition rapidly deteriorates, tissue samples may be required and subsequent analysis of renal biopsies.

Bilateral Pulmonary Infiltrate
  • Chest radiography showed acute progressive bilateral pulmonary infiltrates. The clinical presentation suggested DAH with PSGN. Three days after treatment with high-dose steroids, the respiratory distress and pulmonary infiltrates resolved.[ncbi.nlm.nih.gov]
Abnormal Renal Function
  • Children typically have a good prognosis with normalization of creatinine, while adults may have residual effects of hypertension, recurrent proteinuria, and abnormal renal function.[visualdx.com]

Treatment

Patients suffering from acute PG should receive symptomatic treatment. Therapy aims at controlling hypertension and edema in order to gain time for recovery. Initially, restriction of water and salt intake is recommended. Diuretics, particularly loop diuretics such as furosemid, may be administered if hypertension and edema persist. In severe cases that do not respond to such treatment, circulation may be improved with calcium channel blockers or angiotensin-converting enzyme inhibitors [11]. Parenteral administration of compounds like nitroprusside poses another option to decrease blood pressure if non of the aforementioned drugs has been able to regulate hypertension. Physical activity should be limited as long as cardiovascular parameters are not normalized.

In patients showing signs of renal failure like uremia or life-threatening alterations of electrolyte levels, dialysis may be indicated.

Of note, immunosuppressive therapy is generally not recommended to treat PG. Steroid therapy has been applied to support treatment of severe cases, but corresponding data obtained in controlled clinical trials is not available.

Prognosis

Prognosis depends on the overall condition of the patient and is generally good in pediatric patients but less favorable in geriatric patients that present with one or more comorbidities. With regards to geriatric patients, symptoms of renal failure are often observed and mortality may be as high as 25% [8].

There is certain disagreement regarding the long-term prognosis for children that suffered from PG. According to different studies, urine alterations persist in some patients. However, data regarding the share of patients suffering long-term consequences differ between 3.5% and 60% [9].

Etiology

Streptococcus strains capable of inducing PG are classified as nephritogenic Streptococcus. The vast majority of nephritogenic Streptococcus belongs to Lancefield group A.

These bacteria initially cause infections of the respiratory tract and the skin, stimulate antibody production and evoke secondary PG. In detail, Streptococcus M serotypes 1, 2, 3, 4, 12, 25 and 49 may trigger PG after respiratory tract infection; Streptococcus M serotypes 2, 47, 49, 55, 57 and 60 may provoke dermatitis and subsequent PG.

Epidemiology

The annual worldwide incidence of PG is estimated to reach nearly half a million. With regards to national incidences, there is a strong correlation between development status and number of PG cases. Highest incidences, i.e., up to 3 per 10,000 inhabitants, have been reported from underdeveloped, poor countries. In general, 97% of all PG cases occur in the developing world [3]. Elsewhere, incidences are decreasing. An Italian study realized in the early 90's of the last century determined the local PG incidence to be 0.03 per 10,000 inhabitants [4].

There are two age peaks in the incidence of PG, one in children aged 5 to 12 and another in geriatric patients aged 60 years and older. PG is the most common cause of nephritis in pediatric patients but is rarely observed in children aged 3 years and less.

PG may occur sporadically or during an epidemic of group A Streptococcus infections. The incidence of PG in children that contracted Streptococcus during epidemics is higher after skin infections than after those affecting the respiratory tract (25% and 10%, respectively) [5].

Sex distribution
Age distribution

Pathophysiology

The most widely accepted hypothesis regarding PG pathogenesis is that of the disease being triggered by immune complexes that deposit at the glomerular basement membrane. These immune complexes presumably consist of Streptococcus antigens and antibodies against these antigens. According to current knowledge, Streptococcus antigens capable of inducing long-lasting immune responses, immune complexes and finally PG may be the streptococcal pyrogenic exotoxin B, which corresponds to a cationic cysteine protease, and the nephritis-associated streptococcal plasmin receptor, a plasmin-binding protein with glycolytic activity [6]. Studies conducted with serum and tissue samples of PG patients have shown that exotoxin B has an even higher potential of triggering PG than the plasmin receptor, but if serological test for the corresponding antibodies are carried out, serum concentrations will be elevated for both in the majority of PG patients. PG may be provoked by injection of such antibodies, as has been shown in animal studies.

Also, there seems to be a correlation between basement membrane pore size and immune complex diameter. The former is about 3 nm in children and 4.5 nm in adults, the latter has been estimated to be about 15 nm. It has been speculated that these proportions somehow predispose children for PG, which may serve as an explanation for the observed age peak in PG incidence.

Apart from age, the genetic background of the individual patient may affect their susceptibility to PG. In this line, the HLA-DRB1*03011 allele seems to be more frequently carried by PG patients [7]. It is to be expected that genome-wide sequencing approaches will reveal further genetic factors affecting susceptibility to PG.

Prevention

In order to detect possibly persisting Streptococcus, throat cultures should be prepared for the patient themselves, family members and close personal contacts. Positive results justify preventive treatment with penicillin G (250 mg, qid, up to 10 days) or erythromycin (250 mg, qid, up to 10 days) [12]. Erythromycin may be applied if the person to be treated is allergic to penicillin. These measures help to prevent PG in the respective individual, but also to avoid the spread of nephritogenic Streptococcus. Similar measures may be taken to protect individuals with a high personal risk during epidemics.

In general, adequate hygiene measures are recommended when treating with people suffering from respiratory tract or skin infections.

Summary

Post-streptococcal glomerulonephritis (PG) is a renal disease triggered by infections with group A β-hemolytic Streptococcus.

The association between Streptococcus infection and renal disease has been made centuries ago. It has been observed that patients suffering from "dropsy that follows scarlet fever" excrete reduced quantities of urine that does, however, adopt a dark color [1].

Many years passed until an explanation for this phenomenon could be found. Nowadays, it is known that antibodies produced in the course of Streptococcus infection react with antigens and form immune complexes that bind to glomeruli and provoke glomerulonephritis [2]. Streptococcus strains capable of inducing PG are termed nephritogenic Streptococcus.

Indeed recent research revealed that other microorganisms may also trigger PG. For this reason, the disease may sometimes also be referred to as post-infectious glomerulonephritis. Nevertheless, this article will focus on Streptococcus-induced glomerulonephritis.

Patient Information

Post-streptococcal glomerulonephritis (PG) is a renal disease that may develop weeks after upper respiratory tract or skin infections with determined strains of bacteria of the genus Streptococcus. The majority of PG patients are children aged 5 to 12 years.

Causes

In order to fight bacterial throat or skin infection, immune cells of the patient's body produce antibodies. These antibodies bind to foreign structures, so called antigens, such as those presented by Streptococcus. Antibodies and antigens form immune complexes that circulate through the body and eventually reach the kidneys. They deposit here and cause inflammation. Thus, Streptococcus strains do not directly damage the patient's kidneys, which is why PG symptoms may not occur until weeks after the initial infection. Up to two weeks may pass after throat infection, up to six weeks after skin infection.

Symptoms

PG symptoms result from renal function impairment. Often, the first symptom noted is dark urine. The color of the urine changes because red blood cells that physiologically cannot pass the kidney's urine filter may be lost through the damaged kidney.

Due to the kidneys' important function in maintaining water and electrolyte balance, cardiovascular symptoms such as hypertension and generalized edema may also be experienced in PG. Edema may first be noted in close proximity to the eyes but may also affect other parts of the body.

The overall quantity of urine may be reduced.

Diagnosis

PG diagnosis is based on clinical examination and laboratory tests. It is necessary to verify involvement of Streptococcus in past infections and to assess kidney function. The physician will draw blood samples in order to do so. Antibody titers will be measured as well as blood urea nitrogen and serum creatinine, reliable renal parameters. Also, urine samples will be examined to evaluate the functionality of the kidneys' filter.

If there are still doubts after these diagnostic measures have been taken, a kidney biopsy may need to be performed.

Treatment

Therapy aims at controlling blood pressure and edema. In mild cases, restriction of water and salt intake may be sufficient to achieve this. Otherwise, diuretics, calcium channel blockers and ACE inhibitors may be administered to promote fluid excretion and to improve cardiac function.

Prognosis is generally good in pediatric patients but less favorable in geriatric patients presenting with several other diseases.

References

Article

  1. Wells CD. Observations on the dropsy that succeeds scarlet fever. Trans Soc Imp Med Cir Knowledge. 1812; 3:167 –186.
  2. Rodriguez-Iturbe B, Batsford S. Pathogenesis of poststreptococcal glomerulonephritis a century after Clemens von Pirquet. Kidney Int. 2007; 71(11):1094-1104.
  3. Carapetis JR, Steer AC, Mulholland EK, Weber M. The global burden of group A streptococcal diseases. Lancet Infect Dis. 2005; 5(11):685-694.
  4. Coppo R, Gianoglio B, Porcellini MG, Maringhini S. Frequency of renal diseases and clinical indications for renal biopsy in children (report of the Italian National Registry of Renal Biopsies in Children). Group of Renal Immunopathology of the Italian Society of Pediatric Nephrology and Group of Renal Immunopathology of the Italian Society of Nephrology. Nephrol Dial Transplant. 1998; 13(2):293-297.
  5. Stetson CA, Rammelkamp CH, Jr., Krause RM, Kohen RJ, Perry WD. Epidemic acute nephritis: studies on etiology, natural history and prevention. Medicine (Baltimore). 1955; 34(4):431-450.
  6. Oda T, Tamura K, Yoshizawa N, et al. Elevated urinary plasmin activity resistant to alpha2-antiplasmin in acute poststreptococcal glomerulonephritis. Nephrol Dial Transplant. 2008; 23(7):2254-2259.
  7. Bakr A, Mahmoud LA, Al-Chenawi F, Salah A. HLA-DRB1* alleles in Egyptian children with post-streptococcal acute glomerulonephritis. Pediatr Nephrol. 2007; 22(3):376-379.
  8. Melby PC, Musick WD, Luger AM, Khanna R. Poststreptococcal glomerulonephritis in the elderly. Report of a case and review of the literature. Am J Nephrol. 1987; 7(3):235-240.
  9. Baldwin DS, Gluck MC, Schacht RG, Gallo G. The long-term course of poststreptococcal glomerulonephritis. Ann Intern Med. 1974; 80(3):342-358.
  10. Taskesen M, Taskesen T, Katar S, Karadede A, Tas MA. Elevated plasma levels of N-terminal pro-brain natriuretic peptide in children with acute poststreptococcal glomerulonephritis. Tohoku J Exp Med. 2009; 217(4):295-298.
  11. Parra G, Rodriguez-Iturbe B, Batsford S, et al. Antibody to streptococcal zymogen in the serum of patients with acute glomerulonephritis: a multicentric study. Kidney Int. 1998; 54(2):509-517.
  12. Johnston F, Carapetis J, Patel MS, Wallace T, Spillane P. Evaluating the use of penicillin to control outbreaks of acute poststreptococcal glomerulonephritis. Pediatr Infect Dis J. 1999; 18(4):327-332.

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Last updated: 2018-06-21 17:27