What is Diffuse Proliferative Glomerulonephritis?
Glomerulonephritis describes a type of damage to the parts of the kidneys that help filter waste and fluids. It usually involves inflammation and an increase in cell growth, affecting more than half of these filtering units, technically known as glomeruli. When this happens, it’s called Diffuse Proliferative Glomerulonephritis (DPGN). People with DPGN can show different symptoms including protein loss in the urine and blood in the urine. This condition is often linked to immune system disorders that can affect the kidneys either by depositing immune system components, or directly producing harmful antibodies. These processes can harm the kidneys by causing hardening, scarring, tube shrinkage, and cell death, which can be seen in kidney tissue samples.
What Causes Diffuse Proliferative Glomerulonephritis?
Diffuse proliferative glomerulonephritis is a kidney condition that can be caused by various diseases, as seen from kidney biopsy results. The most common one is systemic lupus erythematosus (SLE). Lupus nephritis Class IV, a type of kidney disease caused by SLE, is known to have a widespread pattern when studied under a microscope.
Other diseases showing similar patterns in the kidneys include IgA nephropathy, a condition where your body’s immune system attacks your kidneys, as well as anti-glomerular basement membrane (anti-GBM) antibody disease, and specific types of vasculitis like granulomatosis with polyangiitis, microscopic polyangiitis, and Henoch-Schonlein purpura.
Post-infectious glomerulonephritis, a condition that develops after certain infections like endocarditis, hepatitis B and C, can also cause diffuse damage to the glomeruli (tiny filters in the kidney) along with an increase in cell growth.
Risk Factors and Frequency for Diffuse Proliferative Glomerulonephritis
Diffuse proliferative glomerulonephritis is mostly linked with SLE (Systemic Lupus Erythematosus) or IgA nephropathy. Almost 38% of those living with SLE may progress to end-stage kidney disease. Research has found that 8.6% of individuals diagnosed with lupus nephritis died, while 95% survived for at least five years post-diagnosis.
Similarly, about 4.8% of those diagnosed with IgA nephropathy have been found to have widespread granular deposits within a part of their kidney known as the mesangium. Japanese research points to roughly 16.1% of those having kidney transplants showed mesangial IgA deposits.
However, nephritis associated with anti-GBM disease is a rare event. Studies from Australia and New Zealand indicate that only 0.8% of all patients with end-stage kidney disease could trace the cause back to it.
Signs and Symptoms of Diffuse Proliferative Glomerulonephritis
Patients with kidney problems may display a variety of symptoms. Some people may experience general symptoms like feeling sick, throwing up, and feeling tired, which suggest the presence of increased waste products in the blood, also known as uremia. Some individuals may show signs of high blood pressure, a decrease in the amount of urine they produce, foamy urine due to the presence of protein, swelling throughout the body, swelling in the legs, and the presence of microscopic or visible blood in their urine.
Patients with a specific type of kidney disease called IgA nephropathy (Berger disease) may present with the classical symptoms of side pain and visible blood in their urine following upper respiratory infections. Patients with autoimmune diseases that result in another type of kidney problem called DPGN, may experience sensitivity to light, skin rash, joint pains, inflammation of body tissue linings, and mouth sores. On the other hand, those suffering from a disease affecting the filters in their kidneys (anti-GBM disease) may experience symptoms affecting their lungs and respiratory system, including internal bleeding in the lungs.
- Feeling sick
- Throwing up
- Feeling tired
- High blood pressure
- Decrease in the amount of urine
- Foamy urine
- Swelling throughout the body
- Leg swelling
- Presence of microscopic or visible blood in urine
- Side pain (in IgA nephropathy)
- Sensitivity to light, skin rash, joint pains, inflammation of body tissue linings, mouth sores (in DPGN)
- Internal bleeding in the lungs (in anti-GBM disease)
Testing for Diffuse Proliferative Glomerulonephritis
If your doctor suspects you have a problem with your kidneys, they will start with a full blood test. This test can indicate anemia (low red blood cell count) or a low platelet count. They will also check for kidney function by looking at your serum creatinine levels, which, if high, could suggest your kidneys are not working properly. Blood urea nitrogen levels will also be checked, along with a urine test to look for things like red and white blood cells, which can be a sign of kidney disease.
Further tests can be done to confirm if there’s a problem with your kidneys. This includes measuring the amount of protein in your urine over a 24-hour period. If the protein levels are more than 3.5 g per day, this could suggest a serious kidney condition which is linked to a poorer outcome. Your doctor may also use a 24-hour urine sample to calculate your eGFR (estimated glomerular filtration rate) – a measure of how well your kidneys are working.
An ultrasound of your kidneys can help check their size, make sure you have two kidneys, and check for any blockages that might be causing a build-up of fluid in the kidneys.
Additionally, your doctor may want to check your serum complement (C3 and C4) levels, as low levels can be an indicator of conditions like Lupus, cryoglobulinemia, or infectious diseases.
However, the most accurate test for diagnosing kidney disease is a renal biopsy. This involves taking a small sample of kidney tissue, which is then examined under a microscope. The biopsy can give important information about the severity and how long-term the disease is.
Your doctor may also want to check for any autoantibodies (these can attack the body’s own tissues and organs causing damage) in your blood. Plus, they may do tests for Hepatitis B, Hepatitis C, and HIV to rule out these as possible causes of kidney disease.
Treatment Options for Diffuse Proliferative Glomerulonephritis
Treatment approaches depend on how severe the disease is. For those with a milder form of the disease, showing small amounts of protein in urine, normal creatinine levels, and a healthy kidney filter rate, they may only need treatment with drugs called ACE inhibitors and regular check-ups every 3 to 6 months to monitor disease progression. Statins are also prescribed since the risk of heart disease is higher for people with chronic kidney issues.
People with a worse degree of kidney damage, blood in their urine, high blood pressure, increased creatinine, and a lower kidney filter rate get treatment with corticosteroids for 12 to 16 weeks, which are gradually reduced. If the corticosteroids don’t work or if the patient can’t tolerate them, other drugs like tacrolimus can be used.
In the case of Lupus nephritis, when it’s in an active phase, treatment is divided into start-up and maintenance stages. Some studies suggest that combining methotrexate and a drug given in pulses called intravenous cyclophosphamide can improve outcomes for stubborn cases of proliferative lupus nephritis. In certain severe situations, cyclophosphamide can be added to steroids and then gradually reduced. Another drug called mycophenolate mofetil has also proven effective in some cases. Some studies suggest that lupus nephritis can be treated with a mixture of double-filtration plasmapheresis and methylprednisolone, leading to a faster recovery, lower chances of it returning, and normal levels of complements. Fortunately, no side effects related to plasmapheresis have been found.
Anti-GBM disease has shown a great response to treatment involving a combination of pulse methylprednisolone, two weeks of plasmapheresis, and then two months of corticosteroids with cyclophosphamide. The effectiveness of treatment suppressing the immune system can be checked by measuring a urinary marker called macrophage migration inhibitory factor (MIF). High levels in urine is a sign of a good outlook. This substance activates immune cells called macrophages and is linked to inflammation.
What else can Diffuse Proliferative Glomerulonephritis be?
All forms of glomerulonephritis, a type of kidney inflammation, present the same symptoms. The specific type can only be identified by examining a sample of the kidney. If a patient comes in with blood in their urine, this is classified as a type of kidney disease called nephritic syndrome. This syndrome can encompass various types of glomerulonephritis, including acute, diffuse proliferative, focal proliferative, or membranoproliferative.
To diagnose the precise form of glomerulonephritis, doctors look at how many clusters of tiny blood vessels in the kidneys (glomeruli) are affected. If more than half of the glomeruli are involved, the condition is called ‘diffuse.’ If less than 50% are affected, it’s known as ‘focal.’ The presence of a thicker-than-normal basement membrane in the kidneys reveals a ‘membranous’ type, while a higher cell count suggests a ‘proliferative’ type.
If the cellular damage is severe, leading to a high level of protein in the urine (greater than 3.5 grams per day), the condition is then reclassified as nephrotic syndrome, another group of kidney disorders.
What to expect with Diffuse Proliferative Glomerulonephritis
The prognosis of a disease called diffuse proliferative glomerulonephritis primarily depends on how early it is detected. Severity indicators include extensive tubule-interstitial injury with inflammation and scarring, as well as the occurrence of ‘crescents’, structures associated with worse outcomes. Several factors can influence the disease’s survival rate, including the amount of excess protein in urine, serum creatinine levels, blood urea nitrogen levels, and glomerular filtration rate (eGFR) at the time of the initial medical consultation.
Accelerated blood vessel inflammation (hematuria), high blood pressure (hypertension), and low protein levels in the blood (hypoalbuminemia) are also considered negative signs for disease progression. Also, it should be noted that men tend to have worse outcomes compared to women.
Some studies suggest that among the various types of this kidney disease, IgA nephropathy has the best prognosis, while lupus nephritis is associated with high death and disease rates in patients with Systemic Lupus Erythematosus (SLE). Moreover, 10% of patients with lupus nephritis eventually develop a condition called end-stage renal disease, which is the final stage of chronic kidney disease.
A low level of substances known as ‘complements’ in the blood is considered a poor indicator of disease prognosis.
Possible Complications When Diagnosed with Diffuse Proliferative Glomerulonephritis
Delays in diagnosing and treating kidney disease can lead to severe complications. An untreated disease can damage the microscopic structures in your kidneys that filter your blood, causing you to have an abnormal amount of protein in your urine, low proteins in your blood, high lipid levels, and a risk of developing blood clots. If the disease progresses rapidly, it can lead to further kidney damage. Moreover, complications may arise following a kidney biopsy, which include excessive bleeding, abnormal connections between arteries and veins, infection around the kidney area, and long-lasting pain.
A late diagnosis can also lead to chronic kidney disease and eventually to a very severe form, known as end-stage renal disease. This is when your kidneys can no longer function on their own, and you would need lifelong sessions of a treatment called hemodialysis, which uses a machine to filter your blood outside your body.
Key issues that may arise due to delayed diagnosis and treatment include:
- Disease progression causing an abnormal amount of protein in urine
- Low proteins in blood
- High lipid levels
- Risk of developing blood clots
- Complications following a kidney biopsy such as excessive bleeding and infections
- Progression to chronic kidney disease
- Progression to end-stage renal disease, requiring lifelong hemodialysis
Preventing Diffuse Proliferative Glomerulonephritis
If you have an autoimmune disease, it’s crucial to understand the symptoms of potential kidney problems. Being aware can help in early identification and managing the disease better. It’s also recommended to make some lifestyle changes like losing weight, reducing the amount of salt in your diet, and consuming more fiber. These changes can decrease the chances of developing high blood pressure, which can affect the kidneys.
If kidney disease is diagnosed, it’s important to start treatment as soon as possible and keep up with regular health checks. Early detection and sticking to your treatment plan can prevent you from needing life-long dialysis, a treatment that artificially filters your blood like healthy kidneys would.
