What Is Glomerular Disease?

The kidneys, a pair of symmetrical bean-shaped organs, are integral parts of the urinary system alongside the ureters, bladder, and urethra. Their primary roles include filtering the blood and producing urine. Specifically, the renal glomerulus, which consists of numerous capillary loops enveloped by epithelial cells called podocytes, serves as the specialised region within the kidneys responsible for blood filtration. These podocytes form the glomerular filtration barrier, through which blood is processed.

Glomerular diseases comprise a broad range of conditions that affect the glomeruli, which are the filtering units in the kidneys. These diseases can result from various factors, including genetic abnormalities, immune system disorders, infections, and certain medications. Glomerular diseases can cause damage to the glomeruli, leading to impaired kidney function and potential complications such as proteinuria (presence of excess protein in the urine), haematuria (presence of blood in the urine), and reduced filtration of waste products.

This article aims to explore various types of glomerular diseases, their underlying causes, available treatment options, and diagnostic methods. By understanding these aspects, readers can gain insights into the diverse nature of glomerular diseases and how they are approached in clinical settings.

Overview

Chronic kidney disease (CKD) represents a significant global health concern that continues to rise in prevalence.¹ CKD involves a gradual decline in kidney function, with many underlying diseases manifesting as proteinuria, which is the presence of plasma proteins in the urine.² Proteinuric kidney diseases can be categorised as glomerular or non-glomerular. Glomerular diseases involve the leakage of proteins across the glomerular filtration barrier, while non-glomerular conditions are characterised by inadequate reabsorption of filtered protein by the proximal tubule.³ This article will focus specifically on glomerular diseases.

Here are some common glomerular diseases:

1. IgA nephropathy - characterised by the accumulation of immunoglobulin A (IgA) in the glomeruli, leading to inflammation and kidney damage⁴
2. Membranous nephropathy - characterised by the thickening and dysfunction of the glomerular basement membrane, which affects the filtration process⁵
3. Focal segmental glomerulosclerosis (FSGS) - which involves scarring (sclerosis) of certain segments of the glomeruli, resulting in impaired kidney function⁶
4. Minimal change disease - primarily seen in children and characterised by minimal changes in the glomeruli under a microscope. It is often associated with nephrotic syndrome, causing proteinuria and oedema⁷
5. Lupus nephritis - a kidney complication of systemic lupus erythematosus (SLE), an autoimmune disease. It involves inflammation of the glomeruli, leading to kidney damage⁸
6. Alport syndrome - a genetic disorder characterised by mutations in genes encoding type IV collagen, a component of the glomerular basement membrane. It can lead to progressive kidney damage and hearing loss⁹
7. Goodpasture syndrome - a rare autoimmune disease characterised by the presence of autoantibodies that attack the glomerular basement membrane and the lungs¹⁰
8. Membranoproliferative glomerulonephritis (MPGN) - a rare condition characterised by thickening of the glomerular basement membrane and increased cellularity within the glomeruli¹¹

Causes of glomerular disease

Glomerular diseases are mainly caused by damage or dysfunction of podocytes. Podocytes play a central role in the progression of glomerular damage, and as a result, all glomerular diseases can be classified within the spectrum of podocytopathies. 

The various clinical syndromes associated with glomerular diseases can be directly linked to different aspects of altered podocyte biology, including developmental abnormalities, defective podocyte products, phenotypic changes, podocyte loss, dedifferentiation, and proliferation. Podocytes can be damaged by a range of mechanisms, including non-mechanical factors such as immune reactions, toxicity, viral infections, as well as mechanical stress and genetic mutations.

Due to their terminal differentiation and inability to replicate, podocytes that are lost cannot be replaced by new podocytes. While the loss of some podocytes is a normal part of the ageing process, an accelerated loss can contribute to the development of kidney diseases.¹²

Glomerular diseases can arise from various causes, including:

1. Immunologic causes - such as abnormal immune system responses. Examples include IgA nephropathy and Lupus nephritis
2. Genetic causes - such as in the case of Alport syndrome and Fabry disease
3. Infections - both viral or bacterial. Some examples are the post-infectious glomerulonephritis and HIV-associated nephropathy
4. Drug-induced - some medications or toxins can cause glomerular damage,  such as nonsteroidal anti-inflammatory drugs as well as certain antibiotics and chemotherapeutic agents
5. Systemic diseases - diabetes mellitus and amyloidosis can be a common cause of glomerular disease
6. Unknown causes - in some cases, the exact cause of glomerular diseases remains unknown, as in the case of idiopathic membranous nephropathy or focal segmental glomerulosclerosis (FSGS)

Signs and symptoms of glomerular disease

Glomerular diseases can present with a variety of signs and symptoms, many of which are related to impaired kidney function and the presence of proteinuria and haematuria. Proteinuria is the presence of excess protein in the urine while haematuria is the presence of blood in the urine that can occur due to damage to the glomeruli.¹³ 

Oedema, especially around the eyes, hands, and feet, can occur as a result of fluid retention and decreased kidney function.

Another symptom of glomerular diseases, as the kidneys play a vital role in blood pressure regulation, is hypertension.

Glomerular diseases can lead to a decrease in urine production and changes in urinary frequency and anaemia resulting from reduced kidney function that can cause fatigue and weakness.

Management and treatment for glomerular disease

Despite significant advancements in scientific research and medical knowledge, the current approach to treating glomerular diseases primarily focuses on managing symptoms rather than providing a definitive cure. Unfortunately, there is currently no therapy available that can completely reverse the renal damage caused by glomerular impairment. The treatment strategies employed in managing glomerular diseases aim to alleviate symptoms, slow down disease progression, and preserve kidney function as much as possible. These may include medication regimens, lifestyle modifications, and supportive therapies.

Medications prescribed to manage symptoms and slow the progression of glomerular diseases may include angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs), drugs which help control blood pressure and reduce proteinuria.¹⁴

In cases of immune-mediated glomerular diseases, medications such as corticosteroids, immunosuppressants and biological agents may be prescribed to suppress the immune system and reduce inflammation.¹⁵ 

Since two symptoms of glomerular diseases are water retention and the presence of oedema, diuretics may help control fluid retention and reduce oedema.

Diet and lifestyle modifications are very important in the management of this type of kidney disease; reducing salt intake, maintaining a healthy weight, and managing underlying conditions such as diabetes or high blood pressure play a crucial role in the management of glomerular disease.

In advanced stages of glomerular disease, where renal function is severely impaired, renal replacement therapies, such as dialysis or renal transplantation, are necessary. 

Diagnosis

The initial diagnosis of glomerular diseases relies on clinical symptoms and manifestations. 

Urinalysis is a diagnostic test that assesses kidney damage by measuring protein and red blood cell levels in the urine. Blood tests, such as measuring creatinine and urea nitrogen levels, are performed to assess renal function and determine if filtration capacity is impaired.

However, since glomerular disease affects the cellular level, a kidney biopsy is often recommended. This procedure involves extracting small tissue samples using a needle for examination under various types of microscopes, each providing different insights into the tissue. A kidney biopsy can help confirm the presence of glomerular disease and identify its underlying cause.

The traditional histopathological evaluation of glomerular diseases involves the examination of renal biopsies using staining techniques such as Haematoxylin/Eosin, Periodic acid–Schiff, Silver stain, and Trichrome stain. However, due to the small size of the glomerular filtration barrier, this structure cannot be adequately visualised using conventional light microscopy.¹⁶  Therefore, electron microscopy (EM) has been crucial in identifying glomerular diseases, but this technique is difficult and expensive. In recent years, various super-resolution (SR) microscopy techniques, such as stochastic optical reconstruction microscopy (STORM), stimulated emission depletion microscopy (STED), and three-dimensional structured illumination microscopy (3D-SIM), have been developed to overcome the resolution limit and have shown promise in enhancing the visualisation of podocyte structures.¹⁷

FAQs

How can I prevent glomerular disease?

Preventing glomerular diseases involves adopting a healthy lifestyle and managing underlying conditions that can contribute to kidney damage. Maintaining blood pressure in the range, managing diabetes, staying hydrated, following a healthy diet, and avoiding smoking are some of the key measures in preventing glomerular diseases.

How common is glomerular disease?

Approximately 850 million people are affected by chronic kidney disease (CKD) worldwide.

Who is at risk of glomerular disease?

People of every age and race could be affected by glomerular disease; however, some conditions, such as hypertension and diabetes, may increase the risk of getting sick, as may 

having a family history of glomerular diseases or kidney disease and belonging to specific ethnic groups.

When should I see a doctor?

It is advisable to see a doctor if you experience any signs or symptoms that could be related to glomerular disease or if you have specific risk factors for kidney problems.

Summary

Glomerular diseases encompass a range of conditions characterised by damage to the glomeruli. These diseases can lead to the development of nephrotic syndrome, a condition characterised by excessive protein loss in the urine. Unfortunately, there are no curative therapies available for glomerular diseases, and treatment primarily focuses on managing symptoms. Therefore, the emphasis is on prevention by addressing potential risk factors such as hypertension and diabetes. Adopting a healthy lifestyle, including regular exercise and a nutritious diet, can play a significant role in preventing the onset of glomerular diseases. By managing these factors, individuals can promote kidney health and reduce the risk of developing glomerular diseases.