​Kembara Xtra - Medicine - Post infectious Glomerulonephritis

​Kembara Xtra - Medicine - Post infectious  Glomerulonephritis 
An immunological complex disease known as post infectious glomerulonephritis (PIGN) is linked to nonrenal bacterial infections, most frequently caused by the bacterial strains Streptococcus and Staphylococcus. Streptococcus spp. infection precedes the most prevalent type of PIGN, poststreptococcal glomerulonephritis (PSGN), which primarily affects youngsters. Acute nephritic syndrome, which includes gross hematuria, proteinuria, edema, hypertension (HTN), and acute kidney injury, may be apparent clinically or it may be asymptomatic.

Epidemiology 

Globally and in industrialized nations in particular, PIGN is on the decline, largely as a result of improved hygiene and a decline in the frequency of streptococcal skin infections. With 97% of cases occurring in developing nations, PSGN continues to be the most common cause of acute nephritis in children worldwide, with an estimated 470,000 new cases per year. Although nonstreptococcal GN in adults has recently witnessed a rise in incidence, PSGN is largely a juvenile illness.

Incidence
In poor nations, there are 9.5 to 28.5 new cases of PSGN for per 100,000 people annually.
Pediatrics: 6 cases per 100,000 people per year in industrialized countries, compared to 24.3 cases per 100,000 people per year in underdeveloped countries.
Adults: 0.3 cases per 100,000 in industrialized nations; 2 cases per 100,000 in poor countries each year.

With a global burden of 68,000 cases per year, 34% of cases are now seen in adults. Estimated incidence is 470,000 cases and 5,000 deaths per year.
Male:female ratio is 2:1.

Pathophysiology and Etiology 

 Glomerular immune complex illness brought on by particular nephritogenic bacterial strains:
- Group A beta-hemolytic Streptococcus (GAS) is responsible for more than 95% of cases (1).
- Staphylococcus, primarily Staphylococcus aureus, rarely coagulase-negative Staphylococcus, and more frequently methicillin-resistant S. aureus (MRSA).
- Gram-negative bacteria such as Haemophilus influenzae, Yersinia pestis, and Escherichia coli 
- Viral, fungal, helminthic, and protozoal causes can occur sporadically.
● Mechanisms for the glomerular damage have been proposed:
- The buildup of circulating immune complexes containing streptococcal or staphylococcal antigens; while these complexes can be found in patients with GN caused by streptococci or staphylococci, they are unrelated to the progression of the disease.
IgG is the most prevalent immunoglobulin in PSGN, as noted.
- In situ immunological complex development following antibody binding and antigen deposition within the glomerular basement membrane (GBM)
- Antibodies to streptococcal or staphylococcal antigens increase the development of in situ glomerular immune complexes.
- Modification of a normal renal antigen that results in molecular mimicry and an autoimmune response Glomerular immune complex that activates complement and causes inflammation
The alternative complement pathway is activated by the nephrotic-associated plasmin receptor (NAPlr), which also activates plasmin.
Streptococcal pyrogenic exotoxin B (SPE B): stimulates the release of inflammatory mediators by binding to plasmin and acting as a protease. Activation of the alternative complement pathway results in early glomerular damage as seen by C3 deposition and lower serum C3 levels. Recently, glomerular damage has also been linked to the lectin pathway of complement activation.


Children aged 5 to 12 and older patients (those who are over 65) are at risk.
- Patients with co-occurring diseases that compromise immunity
Diabetes and alcoholism

Improved hand hygiene and respiratory etiquette, early antibiotic treatment for streptococcal and staphylococcal infections, prophylactic penicillin treatment for closed communities and household contacts of index cases in areas where PIGN is common. However, the effectiveness of these measures in preventing GN is unknown.


Accompanying Conditions 

infection with staphylococcus or streptococcus

Patients with acute nephritic syndrome, marked by the abrupt development of hematuria coupled with edema and HTN for 1 to 2 weeks following an infection, are diagnosed by a history of a preceding GAS skin/throat infection.
A traditional but not always observed trifecta of edema (often widespread), extensive hematuria, and HTN.
The description of urine as "tea-colored" or "cola-colored"
Depending on the site of infection, there is a latent interval between GAS infection and PIGN of 1 to 3 weeks after GAS pharyngitis and 3 to 6 weeks after GAS skin infection.
Adult PIGN most frequently occurs after staphylococcal infections of the upper respiratory tract, skin, heart, lung, bone, or urinary tract (3 times more prevalent than streptococcal infections). According to studies, 7–16% of adult PIGN patients have no prior signs of infection, and in 2–59% of cases, the causative bacterium cannot be determined.


clinical assessment 
Constitutional: 40–50% of patients have fever.

Cardiovascular: Edema is more uncommon in children and occurs in about 2 out of 3 adult patients as a result of sodium and water retention.
- HTN: owing to fluid retention, it is present in 80–90% of patients and ranges in severity from mild to severe. Uncommon but severe, hypertensive encephalopathy is a complication.
Pulmonary: (rare) Respiratory discomfort brought on by pulmonary edema
• Genitourinary
- Gross hematuria: 25–60% of patients have it.
- Microscopic hematuria: PIGN patients that are not yet symptomatic
- 18-51% of patients have oliguria.
- 44–70% of individuals have azotemia or decreased renal function.
- 90% of patients have proteinuria
Neuro: Rare cases of encephalopathy and seizures

Multiple Diagnoses 

Once acute nephritis has been diagnosed, the diagnosis of PIGN is typically made by history, with proof of a recent infection and nephritis starting to resolve 1–2 weeks following presentation. However, the differential diagnosis of GN must be taken into consideration and a renal biopsy must be conducted in cases of progressive disease (>2 weeks, persistent hematuria/HTN >4 to 6 weeks, or lack of appropriate documentation of a GAS or other infection):

MPGN, or membrane-proliferative glomerulonephritis
Patients with MPGN have hypocomplementemia and chronic nephritis that lasts longer than 4 to 6 weeks. Within 2 to 4 weeks, patients with PIGN typically see a remission of their illness and a return to normal C3 and CH50 levels.
Secondary causes of GN include Henoch- Schönlein purpura nephritis and lupus nephritis, both of which share characteristics with PIGN.
Henoch- Schönlein purpura does not exhibit hypocomplementemia, and the hypocomplementemia that occurs in lupus nephritis typically causes decreases in both C3 and C4, whereas C4 levels are normal in PIGN.
The onset of IgA nephropathy frequently follows an upper respiratory infection. Given the rarity of PIGN recurrence, it can be recognized from PIGN by a shorter interval between the upper respiratory infection and the development of hematuria as well as a history of gross hematuria. IgA nephropathy is a chronic condition that will come back. The C3/C4 levels in patients with IgA nephropathy are normal.
IgA-dominant acute PIGN is a newly identified kind of PIGN that develops in poststaphylococcal GN. These patients do not have a history of renal illness, which makes this condition distinct from primary IgA nephropathy.

Antineutrophil cytoplasmic antibody (ANCA) tests should be done in order to diagnose pauci-immune crescentic GN, which is significantly more common in older patients with severe renal failure and active urine sediment.


Laboratory Results 

Initial examinations (lab, imaging)
Proteinuria (nephrotic range proteinuria is uncommon in children) - Hematuria (perhaps dysmorphic red cells), with/without RBC casts, and pyuria
Renal function: Adults (83%) are more likely than adolescents (25%) to have decreased glomerular filtration rate (GFR) and increased creatinine to the point of renal insufficiency.

Tests in the Future & Special Considerations
A positive throat or skin culture will only be present in about 25% of individuals with PSGN, which often manifests weeks after a GAS infection.
Complement: In the first two weeks of the disease, C3 and CH50 levels will be decreased in 90% of pediatric patients (and somewhat fewer adult patients), but C2 and C4 levels stay normal. Within 4 to 8 weeks following presentation, the levels of C3 and CH50 revert to normal.
Serology: Increased antibody titers support the presence of recent GAS infection. Antistreptolysin O (ASO), antihyaluronidase (AHase), antistreptokinase (ASKase), anti-nicotinamide-adenine dinucleotidase (anti-NAD), and anti-DNAse B antibodies were detected positively by the streptozyme test in >95% of patients with PSGN caused by pharyngitis and 80% of patients with cutaneous infections. ASO, anti-DNAse B, anti-NAD, and AHase titers are increased in pharyngeal infection. Only the anti-DNAse and AHase titers are frequently raised in skin infections.
Other/Diagnostic Procedures
Most adults are advised to have a renal biopsy to confirm the diagnosis and rule out other glomerulopathies with comparable clinical symptoms. Renal biopsy is uncommon in children.


Interpretation of Tests
Light microscopy reveals diffuse proliferative glomerulonephritis, which is accompanied by noticeable endocapillary proliferation and a profusion of neutrophils within the capillary lumen. Additionally, deposits can be discovered in mesangium (the "starry sky"). Variable and correlated with clinical findings is the severity of involvement.
Crescent development is unusual and is indicative of a disastrous outcome.
In immunofluorescence microscopy, C3 and IgG deposits are spread in a diffuse granular pattern. In electron microscopy, "humps" are dome-shaped subepithelial electrondense deposits. These deposits, which are immunological complexes, are equivalent to the IgG and C3 deposits seen on immunofluorescence.
Recovery time depends on how quickly these deposits are cleared.

Medication There is no known treatment for PIGN, and there is no evidence from randomized controlled trials to support the use of intensive immunosuppressive medication in individuals with rapidly progressing crescentic disease.
In spite of this, steroids are frequently administered to patients whose renal biopsy showed >30% crescents.

To treat problems of heart failure (HF) brought on by volume overload, older individuals frequently need to be admitted to the hospital. With a focus on addressing the clinical symptoms of PIGN (HTN; pulmonary edema), management is mostly supportive:
- Patients with evidence of chronic bacterial infection should get a course of antibiotic therapy. - Salt and water restriction and loop diuretics may be utilized in situations of severe HTN. - Calcium channel blockers/angiotensin-converting enzyme (ACE) inhibitors may also be employed.

Surgical Techniques 

Approximately 50% of elderly patients need acute dialysis.

Admission

Particularly for senior individuals who are more vulnerable to problems including the start or worsening of preexisting congestive HF, admission may be required.


Patient Follow-Up Monitoring
Repeat urinalysis to ensure that proteinuria and/or hematuria have been cleared up.
If there is no improvement within 2 weeks, think about another diagnosis.
DIET If you need to use dialysis, follow a renal diet.


The majority of children with PIGN have excellent prognoses, with >90% of cases seeing complete recovery of renal function. Elderly patients, especially adults, develop HTN, recurrent proteinuria, and renal insufficiency years after the first sickness. Complete remission in adult PIGN is only 26-56%, and adults with several comorbid variables had the lowest prognosis and highest incidence of chronic kidney damage following PIGN. This has decreased since the 1990s, indicating that the prognosis is getting worse.
● Risk factors for developing end-stage renal disease include diabetes, elevated creatinine levels, and more severe glomerular disease (such as crescents on biopsy).