What Is Glomerular Disease?

Glomerular disease is a group of diseases that mainly affect the renal glomeruli, which have different etiology, pathogenesis, clinical manifestations, pathological changes, course and prognosis. Can be divided into primary, secondary and hereditary; primary glomerular disease is often unknown, secondary glomerular disease refers to the glomerular damage caused by systemic disease, hereditary glomerular disease is Caused by heredity. Primary glomerular disease, which accounts for the majority of glomerular diseases, is still the most important cause of chronic renal failure in China.

Basic Information

English name

Glomerular disease

Visiting department

Nephrology

Common causes

Secondary to systemic disease, inherited

Common symptoms

Proteinuria, hematuria, edema, hypertension, impaired kidney function

Glomerular disease classification

1. Clinical classification of primary glomerular disease

(1) Acute glomerulonephritis;

(2) Radical glomerulonephritis;

(3) chronic glomerulonephritis;

(4) Asymptomatic hematuria or (and) proteinuria (occult glomerulonephritis);

(5) Nephrotic syndrome.

2. Pathological classification of glomerular diseases (developed by the World Health Organization in 1995)

(1) Mild glomerulopathy includes micropathy nephropathy.

(2) Focal segmental lesions include focal segmental glomerulosclerosis.

(3) Diffuse glomerulonephritis membranous nephropathy. Proliferative nephritis: mesangial proliferative glomerulonephritis; intracapillary proliferative glomerulonephritis; mesangial capillary glomerulonephritis; crescentic and necrotic glomerulonephritis. sclerosing glomerulonephritis.

(4) There is a certain relationship between the clinical and pathological types of unclassified glomerulonephritis , but most of them cannot be one-to-one. They are both important components of disease diagnosis. In addition, in the pathological classification of the World Health Organization in 1995, it was not appropriate to classify IgA nephropathy as glomerulonephritis caused by systemic diseases. At present, most experts believe that it should be classified as primary glomerular disease. Pathological types are diverse.

Pathogenesis of glomerular disease

Most glomerulonephritis is an immune-mediated inflammatory disease. It is generally believed that the immune mechanism is the initiation mechanism of glomerulopathy. On the basis of this, the involvement of inflammatory mediators (such as complement, cytokines, reactive oxygen species, etc.) will lead to glomerular damage and clinical symptoms. There are also non-immune and non-inflammatory mechanisms involved in chronic progression.

The importance of genetic factors in the susceptibility of glomerulonephritis, the severity of the disease, and the response to treatment has received attention in recent years. In addition, the evidence that autoimmune causes or participates in various nephritis has also attracted widespread attention.

Clinical manifestations of glomerular disease

Proteinuria

Normal humans have low levels of urinary protein and qualitative negative urine routinely. When the urine protein of an adult exceeds 150 mg / day, the urine protein is qualitatively positive and is called proteinuria.

(1) According to different formation mechanisms, proteinuria can be divided into glomerular proteinuria due to abnormal glomerular filtration barrier proteinuria. It is found in many glomerular diseases, and is characterized by nephropathy-level proteinuria. The composition is mainly composed of medium and large molecules such as albumin. Renal tubular proteinuria Due to renal tubular lesions, the ability to reabsorb proteins is reduced, so that the small molecule protein filtered from the glomerulus cannot be effectively reabsorbed by the renal tubules in normal times. The resulting proteinuria is called renal tubules Sexual proteinuria, the general amount of protein <2g / day. Overflowing proteinuria There are a large number of small molecular proteins that can be freely filtered from the glomeruli in the blood circulation, which exceeds the reabsorption limit of the renal tubules, resulting in proteinuria. It is found in light chain urine in multiple myeloma, myoglobinuria in rhabdomyolysis, and hemoglobinuria in intravascular hemolysis. Tissue proteinuria Seen in pyelonephritis and urinary tract tumors, proteinuria is produced by secreting protein into the urine. Urine protein is generally <0.5g / day, and rarely> 1g / day.

(2) The glomerular filtration membrane is composed of glomerular capillary endothelial cells, basement membrane, and visceral epithelial cells. The filtration membrane barrier effects include molecular barriers. The glomerular filtration membrane allows only molecules of a certain size to pass through; Charge barrier The endothelial and epithelial cell membranes contain sialoproteins, while the basement membrane contains heparin sulfate, which together form the glomerular filtration membrane with negative charges. By the principle of repulsion of the same sex, the negatively charged plasma proteins (such as white Protein). Damage to any of these barriers can cause proteinuria, and glomerular proteinuria is often dominated by albumin. A large amount of proteinuria (mainly albumin) in MC-day patients with normal glomerular structure under light microscopy is mainly caused by damage to the charge barrier; when the molecular barrier is destroyed, larger molecules of plasma proteins other than albumin can appear in urine Such as immunoglobulin, C3, etc., suggest that the glomerular filtration membrane has more serious structural damage.

Hematuria

After centrifugation, the urine sediment microscopic examination of more than 3 red blood cells per high power field is hematuria, and 1L of urine contains 1 ml of blood to show gross hematuria. Glomerular hematuria is usually painless, full-length hematuria, which can be microscopic or gross hematuria, without coagulation, and can also be accompanied by proteinuria and cast urine. If accompanied by a large amount of proteinuria and / or cast urine (especially red blood cell cast), it is suggested that glomerular hematuria.

The following two tests can be used to help distinguish the source of hematuria:

(1) Phase contrast microscopy of fresh urine sediment Deformed red blood cell hematuria is of glomerular origin, and homogeneous normal red blood cell urine is of non-glomerular origin.

(2) Volume distribution curve of urinary red blood cells Glomerular hematuria is often asymmetrical, and its peak red blood cell volume is smaller than the peak venous red blood cell volume; Non-glomerular hematuria is often a symmetrical curve, and its peak red blood cell volume is greater than the venous peak Red blood cell volume.

The main cause of glomerular hematuria is the rupture of the glomerular basement membrane (GBM). The red blood cells are damaged when they are squeezed out by intravascular pressure when they pass through the crack. The damaged red blood cells then pass through different sections of the renal tubule. Osmotic pressure and pH effect, deformed red blood cell hematuria, red blood cell volume becomes smaller, or even rupture.

3. Edema

The basic pathophysiology of renal edema is water and sodium retention. Edema in glomerulopathy can be basically divided into two categories:

(1) Nephrotic edema is mainly caused by long-term, large amounts of proteinuria caused by low plasma protein, decreased plasma colloid osmotic pressure, and fluid infiltration into the interstitial space from the blood vessel, resulting in edema; in addition, some patients have reduced effective blood volume and stimulated renin- Increased angiotensin-aldosterone activity and increased secretion of antidiuretic hormones can further increase water retention and edema. Recent studies have suggested that certain sodium and water retention factors that are primary in the kidney play a role in nephrotic edema, and this effect has nothing to do with plasma renin-angiotensin-aldosterone levels.

(2) Nephritis edema is mainly due to the decrease in glomerular filtration rate, and the renal tubular reabsorption function is basically normal, resulting in "bulb-tubular imbalance" and glomerular filtration fraction (glomerular filtration rate / renal plasma flow) ) Drop, causing water and sodium retention. In nephritic edema, blood volume is often dilated, with renin-angiotensin-aldosterone activity inhibition, decreased antidiuretic hormone secretion, and sustained and exacerbated edema due to factors such as hypertension and increased capillary permeability. Nephrotic edema tissue contains low levels of interstitial protein, and edema usually starts from the lower extremities; while nephritis edema (such as acute glomerulonephritis) has high levels of interstitial protein, and most of the edema starts from the eyelids and face.

4. Hypertension

Glomerular disease is often associated with hypertension, and 90% of patients with chronic renal failure develop hypertension. Persistent hypertension can accelerate the deterioration of kidney function. The mechanism of glomerulopathy hypertension:

(1) Sodium and water retention Due to various factors, sodium and water retention increase blood volume and cause volume-dependent hypertension;

(2) Increased renin secretion NS renal parenchymal ischemia stimulates increased renin-angiotensin secretion, arteriolar contraction, increased peripheral resistance, and causes renin-dependent hypertension;

(3) Decreased secretion of antihypertensive substances in the kidney after renal parenchymal damage. Reduced kallikrein-kinin production and reduced prostaglandin production are also one of the causes of renal hypertension. Most of the hypertension caused by glomerulopathy are volume-dependent and a few are renin-dependent. But the two types of hypertension are often mixed and sometimes difficult to separate.

5. Impaired renal function

Acute glomerulonephritis often leads to acute renal failure. Some patients with acute glomerulonephritis may have transient renal impairment. Chronic glomerulonephritis and nephrotic syndrome patients with poorly controlled proteinuria progress to advanced stages with NS It often develops into chronic renal failure.

Glomerular disease treatment

1. Due to the unclear etiology of primary glomerular disease and mostly immune inflammatory diseases, the treatment principles are:

(1) The current treatment is still based on hormones or hormones plus cytotoxic drugs. In principle, side effects should be minimized while enhancing the efficacy. In the case of contraindications to hormones, the use of cytotoxic drugs alone can be considered when necessary. Patients should be treated individually according to the pathological type of glomerular disease, age, renal function, and whether there are relative contraindications.

(2) Formulation of treatment plans based on different pathological types and degree of pathology: The treatment response, progression of impaired renal function, and recurrence after remission are very different for different pathological types. Based on the different pathological types and the severity of the pathological changes, the treatment plan is developed, It is an important progress in the treatment of glomerular diseases in modern nephrology.

(3) The treatment should not only reduce and eliminate the clinical symptoms of patients, but also strive to prevent and reduce important complications such as infection, thromboembolism, protein and fat metabolism disorders, and adjust water, electrolyte and acid-base imbalances.

(4) Efforts to protect renal function, prevent or delay the deterioration of renal function are important goals of treatment.

(5) Patients with end-stage renal failure should receive blood purification (hemodialysis, peritoneal dialysis) or kidney transplantation.

2. The treatment principles of secondary glomerular disease are:

(1) Treatment of primary system diseases.

(2) Treatment for kidney damage caused by primary disease.

(3) Attention should be paid to kidney damage that may be caused during the treatment and examination of primary system diseases.