Glomerulonephritis

What is Glomerulonephritis?

The kidney is made up of tiny structures called ‘nephrons,’ and each adult kidney has about 1 million of these. Nephrons are comprised of a part called the ‘renal corpuscle’ (a tiny structure known as ‘glomerulus’ surrounded by a capsule) and a tube called the ‘renal tubule.’ These nephrons work together to filter the blood in our bodies.

Glomerulonephritis refers to a group of kidney diseases that result from a reaction of the immune system, causing damage to the kidneys. This damage might lead to blood in the urine, protein in the urine, and an increase in waste products in the blood, a condition called ‘azotemia.’

This disease can be due to an issue that directly affects the kidneys, or it can be a secondary effect of other illnesses; like after being affected by strep throat or a staph infection. In recent years, cases of glomerulonephritis due to staph infections have become more common, while those due to strep throat have become less common, especially in the USA and other developed countries.

Many variations of glomerulonephritis worsen over time if not treated promptly. This progressive damage to the glomeruli (the tiny filtering units) in the kidneys and resulting scarring can lead to a decrease in the kidney’s ability to filter blood efficiently. As a result, waste products can accumulate in the body, leading to chronic kidney disease and potentially, end-stage kidney disease, along with associated heart conditions.

What Causes Glomerulonephritis?

Glomerulonephritis, a form of kidney disease, can be classified in different ways based on the symptoms you’re experiencing. This disease can range from cases where the main symptom is a high amount of protein in your urine (more than 3.5 grams a day) and swelling in different parts of your body, to cases where blood in the urine and high blood pressure are the main symptoms, while protein in the urine is less noticeable.

The types of Glomerulonephritis include:

— Nephrotic, which includes Minimal change disease, Focal segmental glomerulosclerosis, Membranoproliferative glomerulonephritis, Membranous nephropathy, HIV associated nephropathy, Diabetic nephropathy, and Amyloidosis.

— Nephritic, which includes IgA nephropathy, Henoch Schonlein purpura, Post streptococcal glomerulonephritis, Anti-glomerular basement membrane disease, Rapidly progressive glomerulonephritis, Granulomatosis with polyangiitis, Eosinophilic granulomatosis with polyangiitis, Polyarteritis nodosa, Idiopathic crescentic glomerulonephritis, Goodpasture syndrome, Lupus nephritis, and Hepatitis C infection.

A more recent and broadly accepted way to categorize glomerulonephritis is by splitting it into five types based on the immune processes going on in your body. These types are:

1. Immune-complex GN which include IgA nephropathy, IgA vasculitis, infection-related GN, lupus nephritis, and fibrillary GN with polyclonal Ig deposits.

2. Pauci-immune GN which include PR3-ANCA GN, MPO-ANCA GN, and ANCA-negative GN.

3. Anti-glomerular basement membrane (GBM) GN which include Anti-GBM GN.

4. Monoclonal Ig GN which include Proliferative GN with monoclonal Ig deposits, monoclonal Ig deposition disease, fibrillary GN with monoclonal Ig deposits, and immunotactoid glomerulopathy.

5. C3 glomerulopathy which include C3 glomerulonephritis and dense deposit disease.

Risk Factors and Frequency for Glomerulonephritis

Glomerulonephritis, or GN, is a leading cause of kidney damage and can result in severe kidney disease. In fact, it accounts for 10% to 15% of all severe kidney disease cases in the United States. If it isn’t treated quickly, the disease can worsen and cause serious health problems. This has made chronic glomerulonephritis the third most common cause of severe kidney disease in the United States, following diabetes and high blood pressure, and affects 10% of dialysis patients.

About a quarter of all severe kidney disease cases are due to glomerulonephritis. Many of these patients show symptoms of a condition known as nephritic syndrome. This usually happens quite speedily and severe kidney disease can happen within weeks or months of the start of the syndrome.

One type of glomerulonephritis, called IgA nephropathy, is the most common kind worldwide. But another type, post-streptococcal glomerulonephritis, has become less common in most developed countries. The number of cases of post-streptococcal glomerulonephritis in Japan reached its peak in the 90s and has since dropped to about 40-50% of all post-infection GN cases. At the same time, the number of Staphylococcus aureus-related nephritis and hepatitis C virus-associated glomerulonephritis cases has been rising.

However, post-streptococcal glomerulonephritis is still quite common in regions such as the Caribbean, Africa, India, Pakistan, Papua New Guinea, South America, and Malaysia. For example, in Nigeria, acute glomerulonephritis in children aged 3-16 years occurred at a rate of 15.5 cases per year, with an equal number of boys and girls affected.

An Ethiopian study found that acute glomerulonephritis was the second most common cause of acute kidney failure requiring dialysis, accounting for about 22% of such cases. Interestingly, the occurrence of post-streptococcal glomerulonephritis tends to change depending on the geographical location and season.

Acute nephritis can affect people of any age, including babies. Post-streptococcal glomerulonephritis tends to develop in children aged 5-15 years. Only 10% of cases occur in people 40 years old or above, and outbreaks are common in children around six years old. Acute glomerulonephritis affects boys more than girls, with twice as many boys affected. Post-infectious glomerulonephritis affects all racial or ethnic groups equally.

Signs and Symptoms of Glomerulonephritis

Glomerulonephritis is a type of kidney inflammation, and certain symptoms or activities can indicate its presence. Often, children between 2-14 years of age develop symptoms like facial swelling and puffiness around the eyes, following a streptococcal infection. Their urine may appear dark and frothy or reduced in amount. Other symptoms could include high blood pressure, weakness, mild fever, discomfort in the abdomen and a general feeling of being unwell.

When it comes to glomerulonephritis that’s linked with a staphylococcal infection, it’s more common in middle-aged men and older, especially those diagnosed with diabetes. The onset typically happens alongside a concurrent infection, such as pneumonia, endocarditis, osteomyelitis or a skin infection caused by methicillin-resistant Staphylococcus aureus. Blood in urine is a common symptom in these cases.

The onset and duration of the disease provide crucial information. For instance, in post-infectious glomerulonephritis, symptoms usually appear up to three weeks after the original infection. But this can vary. For example, after a throat infection, symptoms may start one to two weeks later; after a skin infection, it might be two to four weeks. If kidney inflammation occurs within one to four days of a streptoccal infection, this usually indicates that there was a pre-existing kidney condition.

It’s important to pin down a possible cause. This could be anything from a recent fever or sore throat, to joint pains, hepatitis, or possible exposure due to travel or use of intravenous drugs. Symptoms like loss of appetite, itching, fatigue, nausea, swelling of the face, build-up of fluid in the legs or shortness of breath could also indicate the progress of the disease. As the disease progresses and the kidneys’ filtration capacity decreases, symptoms like swelling and high blood pressure can occur, primarily due to the body retaining more salt and water.

The symptoms fall under two categories:

• Hypertension
• Swelling (either peripheral or around the eyes)
• Abnormal urinary sedimentation
• Blood in urine (either visible or under microscopic examination)
• Reduced urine output
• Azotemia (high levels of nitrogen-containing compounds in urine)
• Shortness of breath or difficulty breathing upon exertion
• Headache caused by high blood pressure
• Confusion due to very high blood pressure
• Potential pain in the flanks (sides of the body between the upper abdomen and back)

Or symptoms can be specifically tied to an underlying systemic disease:

• A combination of sinusitis, lung infiltration and nephritis could point to granulomatosis with polyangiitis.
• Nausea, vomiting, abdominal pain, and purpura (small purple spots on skin) could indicate Henoch-Schönlein purpura.
• Joint pains could be a sign of systemic lupus erythematosus (SLE).
• Presence of blood in sputum may be due to Goodpasture syndrome or idiopathic progressive glomerulonephritis.
• Skin rashes could be seen in hypersensitivity vasculitis, SLE, cryoglobulinemia or Henoch-Schönlein purpura.

Typically, a physical examination may not reveal much. Yet, patients could present with a triad of symptoms: swelling, high blood pressure and reduced urine output. Signs of excess fluid in the body can include, swelling around the eyes or in the limbs, high blood pressure, crackles in the chest on inhaling due to fluid in the lungs, distention of neck veins, accumulation of fluid in the abdomen (ascites) and fluid in the lungs (pleural effusion). On the other hand, skin rashes due to vasculitis (as seen in Henoch-Schönlein purpura or lupus nephritis), pallor, fullness or tenderness at the kidney area (renal angle), abnormal neurological examination, and arthritis are also potential signs of this condition.

Testing for Glomerulonephritis

When trying to identify the cause and measure the extent of damage in certain medical conditions, your doctor will run several investigations or tests. Here is what goes on behind the scenes:

Blood tests

These tests can hint at issues like anemia or infections. For example, a decrease in red blood cells might suggest anemia, while an increase in white blood cells could point to an infection. Blood tests also measure electrolyte levels, such as potassium. Increased potassium could point to severe kidney problems. Other tests look at substances like BUN (blood urea nitrogen), creatinine and glomerular filtration rate (GFR) levels, which are used to measure kidney function. An increase in BUN and creatinine, and decrease in GFR suggest a problem with the kidneys. Liver function tests are used to find possible causes of the issue.

Blood tests also look for proteins or antibodies in the blood. Certain proteins, such as C-reactive protein (CRP), increase when your body is fighting an infection. Autoantibodies like ANA (antinuclear antibodies), ANCA (anti-neutrophil cytoplasmic antibodies), or anti-ds-DNA, are tested to find out if a specific type of disease called collagenopathy is the cause of the problem.

The doctor will also test blood culture if you have fever, weakened immune system, are using intravenous drugs or have devices like catheters or shunts inside your body.

In certain cases, the doctor will also look for evidence of infections like Hepatitis and post-strep complications. To do that, they check for levels of Antistreptolysin O titer (ASOT), a substance that increases after a staph or strep infection. ASOT increases in 60-80% cases and usually returns to normal levels in about six months.

Urine tests

In addition to blood tests, your doctor may also ask for a urine sample. Dark urine or urine with an elevated specific gravity (usually more than 1.020) could suggest infection or other issues. The presence of red blood cell casts (clumps of red blood cells that have leaked into your urine from your kidneys) is usually a strong indicator of certain types of kidney disease.

Imaging

Imaging, such as a chest X-ray or renal ultrasound, is also often used. Chest X-rays can be used to detect any signs of lung hemorrhage, while a renal ultrasound is used to assess the size and anatomy of your kidneys.

Renal Biopsy

A renal biopsy is a procedure where a small piece of kidney tissue is removed and examined under a microscope. It helps to answer important questions like how many glomeruli (the tiny blood vessels in your kidney which filter your blood) are damaged and to what extent, whether there is increased cell activity, presence of any scarring, deposits of certain substances, or signs of other related diseases.

Overall, these tests help your doctor confirm a diagnosis, determine the severity of the disease and plan a treatment strategy.

Treatment Options for Glomerulonephritis

Glomerulonephritis is a condition related to a systemic disease, which means it’s connected to an overall illness in your body. The best way to treat glomerulonephritis is typically to cure the underlying disease that caused it. If not treated on time, glomerulonephritis can lead to chronic kidney disease, increase the risk of heart disease, and eventually result in end-stage renal disease that damages the kidneys so badly they stop working.

The treatment usually involves two methods:

The first one, specific management, is based on reducing your immune system’s response since it’s often the immune system that’s causing damage to the kidneys. The options for this type of treatment are dependent on your diagnosis, the severity and progression of your disease, and any other health conditions you may have. There are several options for this including:

– High-dose steroids that reduce inflammation
– Rituximab, a drug that helps to control your immune system
– The use of strong drugs (cytotoxic agents) such as cyclophosphamide with steroids; these are often useful in severe cases
– Plasma exchange, a procedure that replaces your blood plasma, and is used in certain types of glomerulonephritis

The second method applies to situations where the disease has progressed to a chronic condition, similar to chronic kidney disease. This involves:

1. Regularly monitoring your kidney function through tests and tracking protein levels in your urine.
2. Controlling your blood pressure and preventing an overactive kidney hormone system. Medications, such as Loop diuretics for removing excess fluids and correcting hypertension, are common in these cases.
3. If your hypertension is severe and hard-to-treat, vasodilators, which relax and widen your blood vessels, might be added.

Doctors will also work with you to manage complications caused by chronic kidney disease, such as anemia, bone diseases, heart disease, and restless leg symptoms. Diet recommendations may be given, and in severe cases, there may be preparations for renal replacement therapy, or kidney treatment, if needed.

Some specific forms of glomerulonephritis, like IgA nephropathy and Henoch Schonlein purpura, might be treated with blood pressure medications that also reduce protein in urine. If protein levels remain high, steroids and fish oil can be considered.

Post streptococcal glomerulonephritis would be treated with supportive care and antibiotics to eliminate the harmful bacteria causing the condition. Other forms, like anti-GBM disease and rapidly progressive glomerulonephritis, could also be treated with plasma exchange, steroids, rituximab, or cyclophosphamide.

For lupus nephritis, another form of glomerulonephritis, the treatment can involve special antibodies, cyclophosphamide, mycophenolate mofetil (a medication that suppresses the immune system), and corticosteroids to control inflammation.

In nephrotic glomerulonephritis, a variety that leads to high amounts of protein in the urine, different treatment strategies might be employed based on the subtype. Prednisolone is commonly used for minimal change disease, while for focal segmental glomerulosclerosis, treatment may start with blood pressure medications and then other drugs might be considered based on your condition.

Overall, managing glomerulonephritis often involves a mix of these strategies to help care for your kidney health.

What else can Glomerulonephritis be?

When diagnosing kidney-related diseases, doctors need to decide if the condition is more like nephrotic syndrome or nephritic syndrome, which are two broad types of kidney illness. This decision assists them in determining the specific disease that might be causing the kidney damage. In addition, they also need to distinguish between diseases that originate in the kidney and those that are secondary to other illnesses, which might vary depending on the patient’s age and symptoms.

For instance, if a young patient presents with nephrotic syndrome, the condition is likely to be minimal change disease. In adults, however, a similar presentation may suggest membranous glomerulonephritis. The presence of diabetes is also to be ruled out. If the main symptoms align more with nephritic syndrome, in children, it may be due to a recent infection, while in adults, IgA nephropathy could be the cause. Depending on the patient’s age, different diseases can cause systemic vasculitis involving the kidney’s filtering units, such as Henoch Schonlein purpura in children and granulomatosis with polyangiitis in adults. Lupus nephritis is a condition that often occurs in younger women, between the ages of 20 to 30.

Other conditions that need to be considered when diagnosing glomerulonephritis (a type of kidney disease) include:

• Acute kidney injury
• Crescentic glomerulonephritis
• Diffuse proliferative glomerulonephritis
• Focal segmental glomerulonephritis
• Glomerulonephritis associated with non-streptococcal infection
• Goodpasture syndrome
• Lupus nephritis
• Membranoproliferative glomerulonephritis
• Post-streptococcal glomerulonephritis
• Rapidly progressive glomerulonephritis

Also, it’s important to note that the following kidney-related conditions can often appear like the early stages of acute glomerulonephritis:

• Idiopathic hematuria
• Chronic glomerulonephritis with an acute exacerbation
• Anaphylactoid purpura with nephritis
• Familial nephritis

What to expect with Glomerulonephritis

Several diseases fall under the category of Nephritic Spectrum Diseases, which are basically different types of kidney ailments:

* Post-streptococcal glomerulonephritis (PSGN) usually has a positive outcome, especially in kids, who mostly recover fully within around 6-8 weeks. However, for adults, approximately half may continually experience decreased kidney function, high blood pressure, or persistent protein leakage in urine.

* Often, IgA nephropathy (a kidney illness) develops with little to no serious issues. But for some, it might gradually worsen to end-stage renal disease (ESRD, severe kidney failure, the last stage of chronic kidney disease). This likeliness tends to increase with age. The Oxford classification can predict the potential outcome. Moreover, at the onset, if a large amount of protein leaks into the urine, high blood pressure, high creatinine level in blood (a sign of poor kidney function), and extensive kidney fibrosis (scarring of tissue), then these could suggest a potential negative outcome.

Henoch-Schönlein purpura is normally a self-limited illness (a disease with a finite course) that shows a high recovery rate in patients without kidney implication. The majority of patients recover fully in around a month. The long-term effects of this disease depend on the degree of kidney influence. Roughly 1% of patients might develop ESRD and need a kidney transplant. With proper and immediate treatment, the lightest form of glomerulonephritis (a type of kidney disease) usually improves (in 75% of cases). If untreated, the disease outcome could be severe. Unfortunately, membranoproliferative glomerulonephritis, another type of kidney ailment, inevitably progresses to ESRD despite therapy. Moreover, the likelihood of this disease returning, even after a kidney transplant, is high.

The following are Nephrotic Spectrum Diseases, another category of kidney diseases:

* Minimal change disease has a very good prognosis at all ages if there is a response to corticosteroid therapy (a class of drug that reduces inflammation). The main health issue deals with the negative side effects of the medications.

* About one-third of patients with membranous nephropathy (a disorder causing kidney damage) who have moderate protein leakage respond well to conservative management. Even in cases with severe protein leakage, spontaneous recovery has been observed. Yet, for others with symptoms of nephrotic syndrome (a type of kidney disorder), remission might take up to half a year with appropriate treatment.

* Suitable treatment can slow HIV-associated nephropathy’s progression (a kidney disease related to HIV), but with an unfortunate progression into ESRD, a kidney transplant could be required.

Amyloid light-chain (AL) amyloidosis (a disorder that causes abnormal protein buildup) takes 2 to 3 years to progress towards ESRD. On the other hand, for those with Amyloid A (AA) amyloidosis, remission can be achieved by identifying and managing the root cause of the disease.

Possible Complications When Diagnosed with Glomerulonephritis

Glomerulonephritis can cause serious kidney problems. In some cases, it can lead to sudden kidney damage, known as acute kidney injury (AKI). This is often how rapidly progressing glomerulonephritis, a condition that forms abnormal shapes in your kidneys, first reveals itself. Other conditions, like vasculitis (an inflammation of your blood vessels) and Goodpasture syndrome, can also be linked to an AKI. Many times, however, glomerulonephritis gradually worsens over time. This leads to long-term kidney damage, known as chronic kidney disease (CKD), and eventually to end-stage renal disease (ESRD), where your kidneys have almost completely failed and you would need dialysis, a treatment to replace the function of the kidneys.

Healthcare providers should be mindful of the following potential complications:

• Pulmonary edema (fluid accumulation in the lungs)
• High blood pressure
• Swelling all over the body (generalized anasarca)
• Low levels of albumin in the blood (hypoalbuminemia)
• Eye damage due to high blood pressure (hypertensive retinopathy)
• Brain damage due to high blood pressure (hypertensive encephalopathy)
• Quickly worsening glomerulonephritis (rapidly progressive glomerulonephritis)
• Long-term kidney failure (chronic renal failure)
• Nephrotic syndrome, a kidney disorder causing your body to excrete too much protein in your urine

Preventing Glomerulonephritis

During a sudden or acute illness, it’s crucial to reduce the amount of salt in your diet. For ongoing or progressive diseases, limiting the amount of sodium, potassium, and protein you eat each day (2 grams of sodium and potassium, and 40-60 grams of protein) can help decrease the buildup of waste in your body and prevent overloading your body with fluids.

Quitting smoking is extremely important to lessen the worsening of kidney diseases. It’s also crucial to manage diabetes and high blood pressure through a healthy lifestyle and prescribed medications. Doctors will also provide advice on controlling high cholesterol levels.

Patients suffering from kidney diseases, especially men, often face sexual health issues such as a decrease in sexual desire. Thus, patients should receive proper guidance on how to manage these issues.

People with a kidney condition called nephrotic syndrome, particularly those progress into a long-term renal disease known as chronic kidney disease (CKD), are more prone to infections. Therefore, getting a seasonal flu shot and a pneumococcal vaccine can offer them additional protection.