Chronic glomerulonephritis:
Glomerulonephritis is an immune-mediated inflammatory disease affecting both kidneys, primarily involving the glomeruli – the kidney’s filtering units.
Chronic glomerulonephritis encompasses a variety of kidney diseases, differing in their causes, morphological structure, and treatment approach, but united by primary damage to the glomeruli.
The incidence rate of chronic glomerulonephritis ranges from 13-50 cases per 10,000 population. This condition is more common in males and can occur at any age, but it’s more prevalent among children aged 3-7 years and adults aged 20-40 years.
Incidence rates of glomerulonephritis are influenced by demographic, climatic, social, and economic factors. For example, focal segmental glomerulosclerosis is more common among African Americans, IgA nephropathy is more prevalent in Asia, and infection-related glomerulonephritis occurs more frequently in tropical regions and developing countries.
Often, the causes of chronic glomerulonephritis are unknown. The role of bacterial and viral infections in the development of some diseases, including hepatitis B and C viruses, HIV infection, measles virus, and Epstein-Barr virus, has been identified. Essentially, each rare and new infection can cause glomerulonephritis. Additionally, medications, tumors, and other external and internal factors can contribute to the onset of chronic glomerulonephritis.
What’s the difference between glomerulonephritis and pyelonephritis?
In pyelonephritis, the kidney tissues and pelvis are inflamed instead of the glomeruli, and this inflammation is often associated with bacterial infection, whereas glomerulonephritis occurs due to immune system dysfunction.
What is lupus nephritis?
Lupus nephritis is kidney inflammation resulting from systemic lupus erythematosus. It manifests with blood and protein in the urine, and in later stages, there’s an increase in nitrogenous compounds in the blood. The disease is diagnosed in nearly half of patients with systemic lupus erythematosus.
Symptoms of Chronic Glomerulonephritis:
The initial clinical symptoms of chronic glomerulonephritis may be few, so the disease often progresses silently. In such cases, the disease may only be suspected through changes in urine composition: the appearance of protein in the urine (proteinuria) and changes in urine sediment – the presence of red and white blood cells in the urine.
Sometimes the disease begins as acute glomerulonephritis. In this case, some symptoms may appear:
- Nephrotic Syndrome – Associated with kidney inflammation and characterized by the presence of blood in the urine, proteinuria exceeding 3 grams per day, elevated blood pressure due to sodium retention, decreased urine output, and reduced glomerular filtration rate.
- Nephritic Syndrome – These symptoms include significantly increased proteinuria exceeding 3.5 grams per day, swelling, lipid disorders in the blood, decreased blood protein, and decreased albumin.
- Urinary Syndrome – Involves changes in urine tests that do not correspond to the main syndromes. The combination of nephrotic and nephritic syndromes is the most inappropriate.
In addition to these phenomena, the following symptoms are characteristic of chronic glomerulonephritis: - Lower back pain;
- High blood pressure;
- Swelling;
- Joint pain;
- Fatigue;
- Skin rash.
All forms of chronic glomerulonephritis can exacerbate periodically, in which case the clinical picture corresponds exactly to or repeats the symptoms of the acute form of the disease. In the case of subacute or rapidly progressive glomerulonephritis, kidney function is reduced by 50% or more within three months.
Characteristics of Chronic Glomerulonephritis in Children:
The disease may persist for a long time in children without any symptoms. It usually appears after the age of twenty and is accompanied by kidney function disorder.
Chronic Glomerulonephritis During Pregnancy:
Pregnancy with chronic glomerulonephritis is not prohibited. The course of pregnancy depends on the degree of kidney dysfunction and blood pressure monitoring.
Mechanism of Chronic Glomerulonephritis:
Aggressive stimuli and others contribute to an immune response by forming and depositing antibodies and/or immune complexes in the renal glomeruli (or directly forming them in the glomeruli), in addition to enhancing a cellular immune response. In response to immune disturbances in the renal glomeruli, changes evolve through a series of stages. It is currently reasonable to confidently assert only certain mechanisms among them.
The onset of immune inflammation is linked to the activation of tissue damage mediators, primarily activation of chemotactic factors that promote lymphocyte migration. At the same time, coagulation factors are activated, leading to the formation of fibrin deposits and the release of growth factors and cytokines – hormone-like substances secreted by immune cells.
In the early stages of the disease, immune inflammation is the predominant feature. Therefore, the earlier immune suppressive treatments start, the better the disease prognosis. With the fading of the inflammatory process, other growth mechanisms come forward to advance the disease:
- Excessive renal filtration – non-changing glomeruli operate under overload.
- Elevated intra-renal and arterial blood pressure.
- Disorders of lipid metabolism and blood clotting.
- Increased uric acid in the blood.
As the disease progresses, secondary changes occur: the process spreads to other kidney structures – renal tubules and interstitial spaces (a type of connective tissue).
End of Inflammation – Followed by fibrosis and sclerosis of kidney tissue, meaning loss of kidney function.
Classification and Stages of Chronic Glomerulonephritis:
Glomerulonephritis is classified according to its causes into two groups:
- Primary (idiopathic) – When the causes are unknown.
- Secondary – When the disease progression is related to:
- Systemic autoimmune diseases (such as systemic lupus erythematosus, vasculitis associated with anti-neutrophil cytoplasmic antibodies, hemorrhagic vasculitis, and rheumatoid arthritis).
- Kidney diseases within the framework of secondary granulomatous cell tumor syndrome (tumors and lymphomas) – These kidney inflammations are resistant to standard treatment, so prognosis may improve (even complete recovery) after complete tumor removal.
- Infections (internal inflammations, hepatitis B and C viruses, human immunodeficiency virus, Epstein-Barr virus, and others).
- Drug-related diseases (autoimmune response to pharmacological and biological drugs).
To differentiate clinical symptoms, five forms of the disease are identified:
- Nephrotic (renal) – More common and characterized by prominent swelling, heavy proteinuria (more than 5 grams per liter for adults and 3 grams per liter for children), sedimentation of cylinders, decreased blood protein, and lipid disorders in the blood.
- Hypertensive – Quantitative and qualitative changes in urine are less pronounced compared to continuous hypertension, with blood pressure reaching 180/100-200/120 mmHg.
- Hematuric (Berger’s disease or IgA nephropathy) – The presence of blood in the urine predominates among other symptoms of the disease, whether visible (visible to the eye) or laboratory, with large or continuous amounts of red blood cells observed in urine sediment. This type is more common in young men.
- Latent – Occurs very frequently. Due to unclear symptoms, it can continue for 10-20 years or more, but ultimately always leads to kidney failure. Usually, the person feels comfortable, there may be weak urinary syndrome, no swelling or elevated blood pressure. Protein in the urine can be detected (not exceeding 1-2 grams per day), small amounts of red blood cells and cylinders in the urine, yellow thin fibrin interlacing threads, and normal urine density.
- Mixed – Includes a mixed presentation of nephrotic and hypertensive symptoms.
As for morphological changes, three chronic glomerulonephritis are distinguished:
- Minimal – Microscopically, there are almost no changes, only the convexity of the podocyte-covered glomerular vessels can be distinguished.
- Focal – Under the microscope, the convexity of the podocyte-covered glomerular vessels can be seen, in addition to sclerosis and deterioration in some loops of the renal capsule.
- Diffuse – There is an increase in the number of cells in the renal vessels, whether:
- Mesangial proliferation.
- Or mesangiocapillary. This synthetic condition attacking the kidney is usually accompanied by a variety of symptoms and physiological changes, requiring multiple treatment methods to deal with its effects on the urinary system and the patient’s overall health.
Complications of Chronic Glomerulonephritis
Kidney inflammation can be complicated by infections, including pyelonephritis and tuberculosis, especially in cases of immunosuppressive therapy. Imbalance in phosphorus and calcium levels and osteoporosis can also occur, caused by acute inflammation or complications of immunosuppressive therapy.
Nephrotic (renal) manifestations of chronic glomerulonephritis complications include:
- Nephrotic crisis: the most severe complication
- Blood clotting within blood vessels (DIC syndrome)
- Venous thrombosis, including renal veins
- Skin changes resembling tumors, accompanied by fever and worsening toxic symptoms.
Nephrotic crisis (renal) can occur suddenly and may be caused by active diuretic therapy. Typical symptoms include severe abdominal pain, peritonitis, and fever. This complication can later lead to shock and death.
One scenario for the progression of the constrictive form of chronic kidney inflammation is left ventricular hypertrophy (cardiac asthma, pulmonary edema). Acute heart failure can also occur.
Key aspects of diagnosing glomerulonephritis include: - Changes in urine analysis, primarily proteinuria, hematuria, and renal casts.
- Chemical blood analysis, including decreased blood protein and albumin, protein disorders, elevated alpha-2-globulin and gamma-globulin, creatinine, urea nitrogen, sugar and lipid levels, increased cholesterol, lipid disorders, and elevated uric acid.
- Ultrasound examination of the kidneys, assessing changes in kidney size, parenchymal thinning and distortion, and cortical-medullary differentiation violation.
- CT and MRI with contrast to rule out urinary problems. Diagnosing many glomerular diseases is impossible without kidney biopsy.
Indications for biopsy include: - Presence of steroid-resistant nephrotic syndrome
- Signs of acute infection with kidney failure
- Suspicion of rapidly progressive glomerulonephritis or chronic intermediate nephritis
- Diseases involving disorders in various body systems, including the kidneys (such as systemic lupus erythematosus, hemorrhagic vasculitis)
- Isolated kidney protein or blood in the urine for a long period.
Contraindications to biopsy include: - Frequently recurrent nephrotic protein syndrome (except for excluding cyclosporine-associated kidney toxicity)
- Nearly solitary kidney (not critical contraindications)
- Blood clotting disorders
- Unmonitored hypertension
- Advanced kidney formation stages
- End-stage kidney failure. Kidney specialists or experienced surgeons perform kidney biopsies in hospital settings. The procedure takes about 15-20 minutes. Complications during kidney biopsy are rare, and bleeding can occur in about 5-10% of cases.
Treatment of Chronic Glomerulonephritis
The importance of treating chronic glomerulonephritis lies in three main objectives:
- Suppressing immune reactions.
- Reducing disease progression rate.
- Preventing the development of chronic kidney failure.
Causative-directed therapy is only done when identifying the cause of chronic glomerulonephritis, such as leptospirosis, viral infections, viral hepatitis, human immunodeficiency virus (HIV) infection, among others. In such cases, antibiotics and antiviral medications are used.
Immunotherapy includes the use of the following medications: - Corticosteroids (steroids): One of the initial evidence for their use was in childhood nephrotic syndrome with minimal change disease. These drugs have a potent anti-inflammatory effect, suppress the immune system, and are also used in treating autoimmune kidney diseases.
- Steroids cause many side effects, so they are preferably given in high doses for a short period, then gradually transitioned to lower maintenance doses.
- Immunosuppressive agents: Currently, such immunosuppressive agents like cyclosporine are recognized methods for treating subtypes of glomerulonephritis, which primarily involve damage to basement membrane cells. In cases of minimal change disease, focal segmental glomerulosclerosis, and membranous glomerulonephritis, this medication is used more frequently concurrently with steroids.
- Monoclonal antibodies: Medications based on this approach are considered a new direction in the treatment of chronic glomerulonephritis. For example, rituximab is an effective drug with fewer toxic side effects that allow symptom relief in some forms of the disease.
One method for treating forms resistant to standard therapy is “pulse therapy,” where medications are given in high doses for a short period. This method effectively limits the exacerbation of chronic glomerulonephritis and is relatively well tolerated by patients.
In general, pulse therapy is conducted using methylprednisolone or cyclophosphamide: - Methylprednisolone pulse therapy is given for 2-3 days, then the cycle is repeated 3-4 times with a rest period lasting 10 days.
- Cyclophosphamide pulse therapy is given once every four weeks, with repetition ranging from 6 to 12-14 times.
In recent decades, renal protective therapy has been used to slow the progression of chronic glomerulonephritis. This therapy works to restore the integrated renal microcirculation cycle and has anti-inflammatory and cell-protective effects. These drugs are used to treat all forms of chronic glomerulonephritis and slow disease progression. In cases of some non-glomerular forms, such as gout and gouty arthritis, when immunotherapy does not show improvement, such drugs are considered the first choice.
Additionally, treatment is directed towards monitoring and managing blood pressure and regulating blood sugar and lipid levels to prevent further kidney damage. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are used as part of this therapeutic strategy.
Advanced and complicated cases of glomerulonephritis require regular evaluation and monitoring by a specialized medical team and may sometimes necessitate intensive therapeutic procedures such as kidney dialysis or even kidney transplantation in cases of end-stage kidney failure.
Dealing with Chronic Glomerulonephritis requires a set of important treatments and procedures:
Medicinal Treatment:
- Cause-directed Therapy: Treatment is directed towards addressing the main cause of chronic glomerulonephritis if known, such as infection or autoimmune-related diseases.
- Immunotherapy: This includes the use of corticosteroids to control inflammation and immunosuppressive agents like cyclophosphamide.
- Biological Therapy: Such as rituximab, a novel treatment based on antibodies directed against white blood cells, which can be effective in some cases of glomerulonephritis.
Procedural Treatment:
- Plasma Exchange: Used to treat rapidly progressive glomerulonephritis and kidney inflammation arising from systemic diseases.
- Plasmapheresis and Kidney Dialysis: Considered alternative kidney treatment methods used during acute kidney failure.
Symptom-Induced Treatment:
- Diuretics, anti-coagulants, anti-inflammatories, blood pressure-lowering medications, statins, and other medications are used as needed.
- Attention is also given to treating chronic infections and preventing viral infections, which often exacerbate the disease.
Nutrition:
- Dietary advice includes reducing sodium intake, increasing water consumption, reducing protein intake if there is no kidney failure, and increasing potassium intake.
- A dietary plan should focus on healthy foods containing moderate amounts of protein, vitamins, and minerals.
- Foods rich in salt, fats, and added sugars should be avoided.
Treatment Monitoring:
- Continuous treatment and regular monitoring by a specialized medical team are required to ensure the patient’s response and disease progression monitoring.
Sources:
Kozina O., Blagoveshchenskaya N., Zaitseva L., Ramazina N., Frolova M. Experience with the use of cyclosporine in the treatment of nephrotic syndrome / IX All-Russian Conference of the Russian Dialysis Society. Theses of reports // Nephrology and Dialysis. — 2015. — No. 3. — P. 294.