Chronic glomerulonephritis (CGN) is characterized by proteinuria, hematuria, hypertension, and edema as its primary clinical manifestations. The onset varies, and the disease progresses insidiously and slowly, often leading to varying degrees of renal dysfunction. Some patients eventually develop end-stage renal failure.
Etiology and Pathogenesis
Chronic glomerulonephritis is primarily the result of progression from various primary glomerular diseases, with only a small proportion arising from acute glomerulonephritis (either through direct progression or recurrence years after clinical recovery). The causes, pathogenesis, and pathological types of CGN vary, but the initiating factors are often immune-mediated inflammation. Additionally, non-immune and non-inflammatory factors such as hypertension, heavy proteinuria, hyperlipidemia, and hyperuricemia play significant roles.
Pathology
Chronic glomerulonephritis encompasses a range of renal pathological types, including mesangial proliferative glomerulonephritis (both IgA and non-IgA types), mesangiocapillary glomerulonephritis, membranous nephropathy, and focal segmental glomerulosclerosis. As the disease progresses to later stages, all pathological types may lead to varying degrees of glomerular sclerosis, accompanied by tubular atrophy and interstitial fibrosis in the affected renal units. The kidneys may become smaller, with thinning of the renal cortex.
Clinical Manifestations and Laboratory Findings
Chronic glomerulonephritis can occur at any age but is more common in young and middle-aged individuals, with a higher prevalence in males. The onset is often slow and insidious. Clinical manifestations are diverse and vary significantly between individuals. In the early stages, patients may have no specific symptoms but may experience loss of appetite, fatigue, tiredness, and lower back pain. Mild to moderate edema may be present, and some patients may develop hypertension. Renal function may be normal or exhibit varying degrees of impairment. When renal function is moderately to severely impaired, patients may present with anemia, electrolyte disturbances, metabolic acidosis, and other related clinical features.
In cases where certain clinical manifestations are prominent, misdiagnosis can occur. For example, some patients may present with significantly elevated blood pressure, with persistent moderate to severe diastolic hypertension. Severe cases may involve fundus hemorrhage, exudates, or even papilledema, which may lead to misdiagnosis as primary hypertension. Proliferative glomerulonephritis (e.g., mesangiocapillary glomerulonephritis or IgA nephropathy) may present with acute exacerbations following infections, which can be mistaken for acute glomerulonephritis. Differentiation is crucial in such cases.
The progression of chronic glomerulonephritis-related renal dysfunction is gradual, with the rate of progression influenced by the pathological type and severity (e.g., mesangiocapillary glomerulonephritis progresses more rapidly, while membranous nephropathy progresses more slowly). Progression is also affected by the adequacy of treatment. Factors such as high-protein diets, poorly controlled hypertension, hypotension, severe anemia, infections, overexertion, hyperuricemia, and nephrotoxic drugs can accelerate renal function decline in the short term. Removal of these triggers and appropriate treatment may temporarily alleviate the condition, but irreversible chronic renal failure may still develop in some cases.
Laboratory findings typically reveal mild urinary abnormalities. Proteinuria is usually in the range of 1–3 g/day and may be accompanied by microscopic hematuria and urinary casts. Phase-contrast microscopy of urinary red blood cells or red blood cell volume distribution curve analysis can confirm the glomerular origin of hematuria. Renal function may initially be normal or mildly impaired (with a decline in creatinine clearance), often persisting for years before gradually deteriorating and eventually progressing to end-stage renal failure.
Ultrasound findings show normal kidney size in the early stages, but in advanced stages, symmetrical reduction in kidney size and cortical thinning may be observed. Renal biopsy can provide a definitive diagnosis of the underlying pathological type, which is valuable for guiding treatment and assessing prognosis.
Diagnosis and Differential Diagnosis
Patients with abnormal urinalysis findings (proteinuria, hematuria), with or without edema and hypertension, and a disease course of over three months, should be considered for a diagnosis of chronic glomerulonephritis (CGN). This diagnosis can be established clinically after excluding secondary glomerulonephritis and hereditary glomerular diseases, regardless of whether renal dysfunction is present.
Chronic glomerulonephritis should primarily be differentiated from the following conditions:
Secondary Glomerular Diseases
Conditions such as lupus nephritis, Henoch-Schönlein purpura nephritis, and diabetic nephropathy can usually be distinguished based on specific medical histories, clinical manifestations, and specialized laboratory tests.
Alport Syndrome
This condition often manifests in adolescence and is frequently associated with a family history (commonly X-linked dominant inheritance). Patients may present with abnormalities in the eyes (e.g., lenticonus), ears (sensorineural hearing loss), and kidneys (hematuria, mild to moderate proteinuria, and progressive renal dysfunction).
Other Primary Glomerular Diseases
Asymptomatic hematuria and/or proteinuria
Mild CGN should be differentiated from asymptomatic hematuria and/or proteinuria, which are not accompanied by edema, hypertension, or renal dysfunction.
Post-infectious acute glomerulonephritis
Chronic glomerulonephritis with acute onset following a preceding infection should be differentiated from this condition. Differences in the latency period and dynamic changes in serum C3 levels can aid in differentiation. Additionally, the clinical course varies, as CGN tends to progress chronically without spontaneous resolution.
Hypertensive Nephropathy
Chronic glomerulonephritis with significant hypertension should be distinguished from secondary renal damage caused by primary hypertension (benign arteriolar nephrosclerosis). In hypertensive nephropathy, there is typically a long-standing history of hypertension preceding the onset of renal dysfunction. Tubular dysfunction (e.g., impaired urine concentration and nocturia) often manifests earlier than glomerular dysfunction. Urinary abnormalities are generally mild (microalbuminuria to mild proteinuria <2.0 g/day, predominantly small- and medium-sized proteins, with possible microscopic hematuria). Other target organ complications of hypertension (e.g., heart, brain) and fundus changes are often present.
Chronic Pyelonephritis and Obstructive Nephropathy
Chronic pyelonephritis is often associated with recurrent urinary tract infections and imaging or renal function abnormalities. Urine sediment typically shows leukocytes, and positive urine cultures can assist in differentiation. Obstructive nephropathy is often associated with a history of urinary tract obstruction, and imaging commonly reveals findings such as multiple renal calculi, renal pelvic dilation with hydronephrosis, and renal atrophy in chronic cases.
Treatment
The treatment of chronic glomerulonephritis primarily aims to slow the progression of renal dysfunction, improve clinical symptoms, and prevent or manage cardiovascular and cerebrovascular complications.
Control of Hypertension and Reduction of Proteinuria
Hypertension and proteinuria are key factors that accelerate glomerular sclerosis and promote the deterioration of renal function. Effective management of hypertension and reduction of proteinuria are essential.
Blood pressure goals: For most adult patients, the target systolic blood pressure should be <120 mmHg.
Proteinuria goals: The aim is to reduce proteinuria to <1 g/day.
Patients with hypertension should follow a low-sodium diet (NaCl <5 g/day). In cases of water and sodium retention, thiazide diuretics or loop diuretics may be used. When creatinine clearance (Ccr) falls below 30 ml/min, thiazide diuretics become ineffective and should be replaced with loop diuretics. If diuretic effects are inadequate, combination therapy with loop diuretics and other diuretics with different mechanisms of action, such as aldosterone antagonists or vasopressin V2 receptor antagonists, may be considered. Diuretics should generally be used cautiously and not for prolonged periods to avoid electrolyte imbalances.
Other antihypertensive agents, such as angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers, alpha-blockers, and calcium channel blockers, may also be used. When blood pressure control is suboptimal, a combination of multiple antihypertensive drugs may be required to achieve target levels. In the absence of contraindications, ACEIs or ARBs, which have renal protective effects, are often preferred as first-line treatments.
Long-term studies have confirmed that ACEIs and ARBs not only lower blood pressure but also reduce proteinuria and delay the progression of renal dysfunction. These renal protective effects are achieved through specific hemodynamic mechanisms (e.g., dilation of both afferent and efferent arterioles, with a greater effect on efferent arterioles), which reduce intraglomerular hypertension, hyperperfusion, and hyperfiltration. Additionally, they exert non-hemodynamic effects (e.g., inhibition of cytokines and reduction of extracellular matrix accumulation) that slow glomerular sclerosis. These drugs are considered first-line options for treating hypertension and/or proteinuria in CGN.
To reduce proteinuria, doses of ACEIs or ARBs are often higher than standard antihypertensive doses, and the dosage is gradually increased to the maximum tolerable level. In patients with renal dysfunction, the use of ACEIs or ARBs requires monitoring for hyperkalemia and acute kidney injury. When serum creatinine exceeds 264 μmol/L (3 mg/dL), these drugs should be used under close supervision, with regular monitoring of serum potassium and renal function. Potassium-binding agents or potassium-wasting diuretics may be co-administered if necessary. If hypovolemia is present or if serum creatinine rises by more than 30% from baseline shortly after initiating ACEI or ARB therapy, discontinuation of the drug may be required.
SGLT2 inhibitors have been increasingly used in recent years for patients with chronic kidney disease (CKD) accompanied by proteinuria. Regardless of whether diabetes is present, the use of these drugs can improve glomerular hyperfiltration and alleviate renal hypoxia, thereby reducing proteinuria and slowing the progression of renal dysfunction.
Restriction of Dietary Protein and Phosphorus Intake
Based on the patient's renal function, a high-quality, low-protein diet [0.6–1.0 g/(kg·d)] is recommended, along with controlled phosphorus intake. Adequate caloric intake is ensured to prevent negative nitrogen balance. After two weeks on a low-protein diet, essential amino acids or alpha-keto acids [0.1–0.2 g/(kg·d)] may be administered.
Glucocorticoids and Cytotoxic Drugs
Aggressive use is generally not recommended. However, for patients with normal or mildly impaired renal function, who have a pathological type responsive to immunotherapy, significant proteinuria, and no contraindications, a trial of these medications may be considered. If treatment is ineffective, the drugs should be gradually discontinued.
Avoidance of Factors That Worsen Renal Damage
Factors such as infections, excessive physical exertion, pregnancy, and nephrotoxic drugs (e.g., aminoglycoside antibiotics, and nonsteroidal antipyretic analgesics) can damage the kidneys and lead to worsening renal function. These should be avoided.
Prevention and Management of Cardiovascular and Cerebrovascular Complications
Modifiable risk factors for cardiovascular disease, such as smoking, obesity, hyperlipidemia, hyperglycemia, and lack of physical activity, require active intervention and treatment to reduce the risk of cardiovascular and cerebrovascular events.
Prognosis
Chronic glomerulonephritis is characterized by a prolonged course, with gradual progression of pathological changes ultimately leading to chronic renal failure. The rate of disease progression varies significantly between individuals and largely depends on the type and severity of renal pathology, the implementation of effective treatment measures, and the avoidance of various risk factors.