About

➀ Read and Learn

The following course content

Introduction   

Glomerulonephritis, often referred to as glomerular disease, is a variation of conditions that cause inflammation of the glomerulus in the kidneys due to an immune-mediated response by the human body [4]. Glomerulonephritis can result from an infection, inflammatory disease processes like lupus, from taking certain medications or other diseases [2].  

The main function of the glomerulus is to filter toxins and excess fluids from the blood which are excreted as urine. When there is damage to the glomerulus, the kidneys cannot perform their function effectively. Glomerulonephritis can occur as an acute or chronic condition.  In this course, our focus will be on Acute glomerulonephritis.  

Definition  

Acute glomerulonephritis (AGN) is a specific set of diseases that manifests suddenly due to inflammation following damage to the glomerulus in the kidneys [3]. Acute Glomerulonephritis can develop due to a primary cause that originates in the kidneys such as Immunoglobulin A (IgA) or a secondary cause such as Acute Poststreptococcal Glomerulonephritis (PSGN) secondary to a streptococcal infection. PSGN is considered the most common form of AGN with most cases being in children [1, 2, 9] 

However, due to the growing age population, there has been an increase in older adults with AGN related to endocarditis due to intravenous drug use and cardiovascular disease [3]. AGN often presents as a nephritic syndrome that induces hematuria, mild to moderate amounts of proteinuria (protein in the urine), hypertension, and oliguria (decreased amount in urine output).  

Fifty percent of people who have AGN may not show any symptoms [9]. The prognosis of AGN is dependent on the underlying cause and severity [3]. AGN occurs suddenly from days to weeks and can resolve with early diagnosis and treatment, unlike chronic glomerulonephritis which develops slowly over time and can lead to kidney failure as it is reversible [1]. 

Epidemiology/Statistical Evidence 

Glomerulonephritis is the leading cause of End Stage Renal Disease (ESRD) in the United States by 10% – 15% following diabetes and hypertension [1]. Acute Glomerulonephritis (AGN) is a form of glomerulonephritis. If left untreated, AGN can progress to a chronic condition which could lead to ESRD and eventually to morbidity.  

Fifty percent of patients who have AGN have no symptoms. AGN progresses to chronic glomerulonephritis in about 30% of the adult population [3]. Acute Poststreptococcal Glomerulonephritis (PSGN) is one of the most common forms of AGN. The incidences of PSGN have reduced significantly in developing countries like the United States of America (USA).  

Staphylococcal infections contribute to the increase in glomerulonephritis due to the rising number of antibiotic-resistant staphylococcus aureus [4, 6]. Acute Poststreptococcal Glomerulonephritis (ASPG) is commonly found in the pediatric patient population between ages 3 – 12 years. Only 10% of cases occur in patients over 40 years and above. ASPG is more common in males than females. AGN can occur 1 to 12 weeks after infection. PSGN has a better prognosis. Studies indicated that 95% of children recover from illness. IgA nephropathy is the most common cause of glomerulonephritis worldwide [5].  

Kidney Function  

The functional and structural units of the kidneys are called nephrons. Each kidney contains millions of nephrons. The nephrons are made up of glomerulus which are clusters of small blood vessels enclosed in a cup-shaped structure called the Bowman’s capsule which extends with a renal tubule [4, 10].  

The glomerulus contains multiple layers that form a filter with fenestrated endothelium, glomerular basement membrane and the podocyte foot processes which are cells that line the capsule. The main function of the glomerulus is to filter toxins and excess fluids from the blood. In healthy working kidneys, toxins, and excess fluids are excreted from the bloodstream in the form of urine while retaining red blood cells and protein [4, 6].  

Pathophysiology of Acute Glomerulonephritis  

In AGN, the glomerulus becomes permeable to protein and sometimes red blood cells can leak into the urine. This leads to the deposition of antibodies and immune complexes that trigger inflammation in the glomeruli causing injury or lesions that could involve both structural and functional changes [4]. The kidneys may appear enlarged by 50% on gross appearance from an ultrasound imaging. 

The microscopic examination of the kidneys may indicate changes such as swelling of the glomerular tufts and infiltration with polymorphonucleocytes. Immunofluorescence, which is used to accurately diagnose glomerulonephritis by visualizing components of the biopsy tissue, reveals deposition of immunoglobulins and complement. AGN involves both structural and functional changes [8].  

Functional changes would include proteinuria, hematuria (micro and macro presentation) decrease in Glomerular Filtration Rate (GFR) which would be manifested as oliguria, edema, and impaired kidney function which could lead to retaining of sodium and water in the distal nephrons, edema and systemic hypertension [5]. Structural changes could result in hyalinization or sclerotic tissue which would indicate irreversible injury in the glomerulus [4].  

Etiology 

Although the etiology of glomerulonephritis is not fully understood, with increased research there has been a better approach in the classification of glomerulonephritis that can be made based on clinical presentation [4]. The classifications of AGN are divided between infectious-related and noninfectious-related diseases.   

Infection-Related Diseases 

Infection-related causes can be classified as post-streptococcal and non-post-streptococcal GN. These are due to the immune response to pathogens. The most common infectious diseases that cause AGN are from post-streptococcal immune pathogens which are usually group A or beta-hemolytic streptococcal infections whose antigens attach to the glomerular endothelial cells [9]. Typically, the strep infections are from upper respiratory infections or skin infections.  

About 5%-10% precede pharyngitis infection and 24% precede skin infections. Poststreptococcal glomerulonephritis is often diagnosed in children with upper respiratory infections. It affects children between the ages of 2 – 10 years and is more common in male than female patients [5].  

Non-poststreptococcal infections may include:  

• Viral: Epstein-Barr virus (EBV), hepatitis B virus (HBV), Human immunodeficiency Virus (HIV).  

• Parasitic infections: Plasmodium malariae.  

• Bacterial: mycobacteria, staphylococci, salmonenal thyphosa (typhoid fever), treponema pallidum (syphyllis) [2][5] 

Noninfectious-Related Disease 

Noninfectious infections comprise of primary kidney diseases, systemic diseases, and miscellaneous conditions [5, 6] 

Primary Kidney Diseases: 

• Immunoglobulin A (IgA) nephropathy, also known as Berger disease, progresses slowly from the acute phase: The most common form of AGN worldwide. It occurs when there is too much protein deposited in the glomeruli. It affects mostly males between their teenage years to the age of 30 [3, 4].   

• Lupus nephritis: Systemic Lupus Erythematosus (SLE) is a disease process caused by a group of autoimmune responses to nuclear antigens.  There are 50% of patients that are diagnosed with SLE. It is known to cause kidney disease which includes AGN. Immune complexes containing anti-DNA antibodies form and deposit in the GBM, subendothelial, intramembranous, subepithelial and mesangial of the glomerulus [7].  

• Membranous Glomerulonephritis (MPGN): caused by an abnormal immune response that leads to deposition of antibodies that build up in the membrane of the glomerular basement which could develop into lesions. Common causes are cancer (i.e. Leukemia or lymphoma), and autoimmune diseases like Systemic Lupus Erythematosus (SLE), scleroderma, and sarcoidosis [3, 6].  

Systemic Diseases: 

• Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN): This is a rare condition worldwide. RPGN is the most serious form of AGN that can develop into necrotizing damage to the kidneys and lead to the rapid loss of kidney function that may require dialysis. The prognosis is poor because it affects 50% of the glomeruli. It can happen between days to weeks to months. RPGN is characterized by the presence of crescent cells that form in the glomeruli [5, 6]. Three types have been distinguished: Type I is an anti-glomerular basement membrane disease, type II is mediated by immune complexes, and type III is identified by antineutrophil cytoplasmic antibody (ANCA). It’s mostly seen in Caucasians. The hallmark is a positive anti-neutrophil cytoplasmic antibody (ANCA) or anti-GBM antibodies [9].  

• IgA Vasculitis: Also known as Henoch Schonlen pupura, involves different systems in the body which includes the skin, joints, gastrointestinal tract and glomerulonephritis. Affects children mostly male children between the ages of 3 to 15 years old. It precedes an upper respiratory infection. They present with purple spots called purpura and a rash on the lower extremities i.e. legs and elbows, hives and angioedema, and diarrhea which is sometimes bloody [5].  

• Anti Glomerular Basement Membrane disease (Anti GBM): Formerly known as Goodpasture syndrome, Anti GBM disease is a life-threatening autoimmune disorder that attacks the lungs and the glomeruli in the kidneys. This causes circulating antibodies to type IV collagen and often results in a rapidly progressive oliguric renal failure that can occur in weeks to months [4, 5]. 

• Granulomatosis with Polyangiitis: This condition requires a prompt diagnosis is critical as it may lead to rapidly progressive [5] 

• Miscellaneous: These include some diseases and vaccines. Guillain Barre, irradiation of Wilms Tumor, Covid -19 Vaccine and Diphtheria-Pertussis-Tetanus Vaccine [5]. 

Clinical Presentation  

AGN often presents with what’s known as the nephritic syndrome which is associated with the following: [3, 7, 8]  

• History of an infection streptococcus and viral infections such as Epstein Barr and Hepatitis B. Renal involvement manifests 8 – 14 days following an upper respiratory infection and 14 – 21 days after skin infection caused by streptococci.  

• Hypertension and dark urine 1 to 12 weeks following pharyngitis or skin infection with peri orbital edema. Hypertension can be unexplained, especially with SLE.   

• Hematuria (microscopic or macroscopic): due to red blood cells leaking into the urine caused by inflammation in the glomerular. 

• Impaired kidney function: a result of decreased glomerular filtration rate (GFR) These can manifest as hypertension, edema (usually periorbital), oliguria, shortness of breath due to fluid overload, hematuria (microscopic or macroscopic), Red blood cell casts (clusters of RBCs), and moderate proteinuria as protein leaks through urine causing fluid to go into the interstitial spaces. 

• Tea-colored or cola-colored urine: caused  red blood cells leaking in the urine. 

• Puffiness of the face and periorbital edema: more prominent in the morning; edema of the extremities due to low protein because it is excreted in the urine.  

• Fatigue, anemia, hypertension. 

• Azotemia decreases in GFR. 

• Anorexia, abdominal or flank pain can be present.  

• Rare cases can cause convulsions may be present due to high sodium levels from impaired kidney function.  

• Confusion is common in mild to subclinical cases.  

Diagnosis  

The following tests may be used to assist with diagnosing AGN: [5, 8] 

• Kidney biopsy: the “gold standard” for diagnosing glomerulonephritis. is vital to help to reveal obstruction of glomerular capillaries from proliferation of endothelial cells. 

• Imaging: renal ultrasound to view the size of the kidney; chest x-ray to test for fluid overload and pulmonary hemorrhage if present. 

• Urinalysis: includes test for the following: hematuria, proteinuria, cellular elements. 

• Serum levels: increased antistreptolysin O titer (ASOT), dysmorphic RBC casts in urine, blood cultures, hepatitis serology, immunoglobulins (reaction from streptococcal organism), serum electrolytes to check for increased potassium and sodium, creatinine levels and Complete Blood Count (CBC) to test for decrease in hematocrit and other blood levels such as white blood cell count. C3 Levels – Low C3 levels can be present with (PSGN).  

• Blood cultures: to rule out any infection.   

• Kidney function tests: BUN and creatinine, GRF are tested to help to outline the degree of renal function, 24-hour urine is used to check for protein.   

Treatment and Management of AGN  

Depending on the disease process, treating the underlying cause is often associated with systemic disease [5]. Emphasis should be placed on supportive treatments and lifestyle modifications [9]. Some of the following medications are used to treat AGN:  

• Angiotensin-converting-enzyme inhibitors to control blood pressure. The goal is to have a systolic blood pressure parameter of less than 120 mmHg.  

• Antibiotics to treat infections such as streptococcal, for example Cephalexin (Keflex) and erythromycin.  

• Loop diuretics to treat fluid overload and control blood pressure. 

• Immunosuppression, high-dose corticosteroids, or plasma exchange for suppression of the immune system in RPGN and sometimes used to treat Lupus Nephritis. 

• Phosphate binders to reduce phosphate and high calcium levels.

Complications  

The following are complications manifested in patients with AGN: 

• Acute kidney injury (AKI) due to inflammation in the glomerulus. This could be related to rapidly progressive glomerulonephritis with crescent formation.  

• Chronic renal disease 

• Progression of chronic renal failure – can be caused by late diagnosis or late treatment of AKI.  

• Pulmonary edema and heart failure.  

• Generalized anasarca 

• Hypertension and hypertensive encephalopathy 

• Nephrotic syndrome 

• Seizures related to increased sodium levels and malnutrition (due to less intake to reduce complications in the glomerulus) 

Patient Education  

• Educate the patient on the importance of following up on blood pressure evaluations, lab work, and urinary protein.  

• Counsel the patient on dietary modifications and exercise: reduce intake of sodium to less than 2 grams/day and limit protein intake until the patient recovers 

• For patients who smoke, counsel on the importance of smoking cessation (helps decrease renal aggression).  

• Encourage the patient to report any signs of decreased kidney function by paying close attention to their urine output.  

Conclusion

AGN can lead to chronic glomerulonephritis or morbidity unless early diagnosis and treatment are initiated. AGN that is commonly caused by PSGN has decreased in the United States and globally with good prognosis when resources are available to treat the underlying cause.  

➁ Complete Survey

Give us your thoughts and feedback

➂ Click Complete

To receive your certificate