Glomerular Diseases

Chapter: Glomerular Diseases
McMaster Section Editor(s): Christine M. Ribic, Karen C.Y. To
Section Editor(s) in Interna Szczeklika: Franciszek Kokot, Robert Drabczyk
McMaster Author(s): Matthew Miller
Author(s) in Interna Szczeklika: Marian Klinger, Ilona Dziemianko, Krzysztof Kazimierczak, Robert Drabczyk
Additional Information

Definition and ClassificationTop

Glomerular diseases, or glomerulopathies, belong to a heterogeneous group of kidney diseases that affect mainly the glomeruli, causing structural and functional abnormalities. They have a varied presentation and course, ranging from asymptomatic and benign to rapidly life-threatening. The diseases can be limited to the glomeruli or be part of a systemic disease affecting multiple organ systems. The term glomerulonephritis is often used to reflect the involvement of inflammation in many of the diseases that affect the glomerulus.

Classification, etiologies, and clinical features of glomerulopathies: Table 9.2-1.

The classification and diagnosis of glomerular diseases are primarily based on histologic patterns seen on renal biopsy, although specific histologic patterns can have multiple causes, requiring interpretation based on other presenting factors and laboratory investigations. Diagnosis is therefore further classified by etiology. Primary diseases are idiopathic in nature and lack a known associated secondary cause. Ongoing research is increasingly isolating specific markers and antibodies associated with some of the primary glomerular diseases. Multiple secondary causes exist, depending on the underlying histologic lesion. Distinguishing between primary and secondary causes of a glomerular disease is important, as the pathophysiology and subsequent management of the disease can differ substantially. Primary diseases are mostly immune-mediated and often require immunosuppression, whereas secondary diseases require treating the underlying inciting cause. Lastly, glomerular diseases can be congenital, and in such cases they are almost always evident prior to adulthood.

While diagnosis is dependent on the histologic pattern and renal biopsy may be necessary in case of diagnostic uncertainty, not all patients require or benefit from biopsy. The decision to biopsy a patient requires careful consideration of the risks and benefits and a clear understanding of how the information provided would change management. For example, a biopsy is often required in patients with adult-onset nephrotic syndrome or rapidly progressive glomerulonephritis to assist with the diagnosis and management, whereas in individuals with microscopic hematuria and normal renal function it is not necessary because of the usually benign nature of presentation. Similarly, individuals with a classic presentation for diabetic nephropathy without concern for other pathologies usually do not require a biopsy despite potentially severe proteinuria.

Glomerular diseases are relatively uncommon, and there is significant geographic variation in the incidence of the various diseases. Worldwide incidence: Table 9.2-2.

Clinical FeaturesTop

Glomerular diseases can be asymptomatic and only identifiable on blood or urine tests. However, many can be associated with systemic signs and symptoms, which may assist in providing evidence for an underlying diagnosis. Additionally, in the setting of secondary glomerular diseases, past medical history and medications may strongly suggest a diagnosis. In the majority of patients with a glomerular disease, one of the following clinical forms is often present, although significant overlap can exist and individual diseases can have different clinical presentations:

1) Nephrotic syndrome.

2) Nephritic syndrome: Characterized by hypertension, oliguria, and edema (which is usually mild to moderate). Proteinuria is <3.5 g/d and urine microscopy shows active or nephritic urine sediment (dysmorphic erythrocytes, red blood cell casts, or both). Glomerular filtration rate (GFR) is often reduced at presentation.

3) Asymptomatic microscopic hematuria with or without proteinuria: Persistent or recurrent microscopic hematuria, or gross hematuria during exacerbations, with varying degrees of proteinuria that do not exceed the nephrotic range. Often no other clinical manifestations of glomerular disease are present. With time, chronic kidney disease (CKD) may develop.

4) Chronic glomerulonephritis: Progressive CKD caused by occult glomerulonephritis lasting several years. The progression of CKD is a result of long-term damage affecting a significant number of glomeruli and of progressive secondary fibrosis of the interstitium with tubular atrophy. The disease is often undiagnosed, as patients can be asymptomatic and do not present until CKD is advanced or discovered incidentally. Clinical features are typical of chronic kidney disease and depend on its stage. Urinalysis reveals proteinuria and microscopic hematuria.

5) Rapidly progressive glomerulonephritis: Nephritic syndrome accompanied by rapidly progressive renal failure.

TablesTop

Table 9.2-1. Classification, etiologies, and clinical features of glomerulopathies

Glomerulopathy

Etiology/secondary causes

Clinical features

Postinfectious GN

– Primarily streptococcal and staphylococcal infections

– Less commonly gram-negative bacteria, viral, fungal, or protozoal

Nephritic syndrome ~1-3 weeks after streptococcal infection, 4 weeks after staphylococcal infection

IgA nephropathy

– Seen with Henoch-Schönlein purpura

– Associated with cirrhosis, celiac disease, inflammatory bowel disease, HIV, and seronegative arthritis

Microscopic hematuria, “synpharyngitic” gross hematuria, hypertension, proteinuria

Membranoproliferative GN

 

Immune complex–mediated

Hepatitis C with cryoglobulinemia, hepatitis B, HIV, endocarditis, shunt nephritis, malaria, schistosomiasis, autoimmune disorders (SLE, Sjögren syndrome), malignancies (dysproteinemias, rarely lymphomas, carcinomas)

Varied presentation: microscopic hematuria and nonnephrotic proteinuria, nephrotic syndrome, occasionally rapidly progressive renal failure, commonly hypertension

Complement-mediated

C3 nephritic factor, factor H deficiency (inherited or autoimmune)

Minimal change disease

– Most commonly primary/idiopathic

– Secondary causes include NSAIDs, interferon, lithium, gold, lymphoproliferative disorders (Hodgkin lymphoma)

Nephrotic syndrome

Membranous nephropathy

– Most commonly primary/idiopathic

– Secondary causes include autoimmune conditions (primarily SLE), infections (hepatitis B and C), medications (NSAIDs, gold, penicillamine), malignancies

Nephrotic syndrome

FSGS

– Primary/idiopathic

– Secondary causes include HIV, parvovirus B19, CMV, EBV, pamidronate, heroin, lithium, obesity, reflux, sickle cell disease

Hypertension, proteinuria, and microscopic hematuria; nephrotic syndrome and abrupt development more common in primary/idiopathic FSGS

CMV, cytomegalovirus; EBV, Epstein-Barr virus; FSGS, focal segmental glomerulosclerosis; GN, glomerulonephritis; NSAID, nonsteroidal anti-inflammatory drug; SLE, systemic lupus erythematosus.

Table 9.2-2. Worldwide incidence of various primary glomerular diseases

Glomerular disease

Incidence (per 100,000 people)

IgA nephropathy

0.2-2.9

Membranous nephropathy

0.3-1.4

Focal segmental glomerulosclerosis

0.2-1.1

Minimal change disease (in adults)

0.2-0.8

Membranoproliferative disease

0.1-0.9

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