Increased glomerular volume
Introduction
Introduction An increase in glomerular volume refers to a physiologic and pathological characteristic morphological change in the glomerular volume of the glomerulus due to lipoprotein glomerulopathy. Lipoprotein glomerulopathy (lipoprotein glomerulopathy) is a kidney disease characterized by the presence of lipoprotein emboli in the glomerular capillaries and extrarenal lipoprotein embolism. Lipoprotein glomerulopathy is more common in men, with a male to female ratio of 15:8; the average age of onset is 32 years (4 to 49 years). Most cases are sporadic and a few are familial. Lipoprotein glomerulopathy (lipoprotein glomerulopathy) is a kidney disease characterized by the presence of lipoprotein emboli in the glomerular capillaries and extrarenal lipoprotein embolism. The clinical manifestations were similar to type III hyperlipidemia with elevated plasma apolipoprotein E (apoE). The disease was first reported by Saito T et al. at the 17th Annual Meeting of the Society of Nephrology in 1987. In 1989, Sakaguchi et al. proposed the disease as an independent glomerular disease based on the patient's clinical manifestations and pathological features. In the same year, the disease was named lipoprotein glomerulopathy. However, lipoprotein glomerulopathy does not improve glomerular lesions by lowering blood lipids. It is currently believed that this disease is a rare disease in which the glomerular type III is limited to the lipidation of the kidney.
Cause
Cause
The pathogenesis of lipoprotein glomerulopathy has not been fully elucidated, and most are thought to be associated with abnormal lipid metabolism. It is now known that abnormal lipid metabolism can cause glomerular damage; glomerular lesions also affect lipid metabolism. Many systemic diseases (including rare Fabry disease, NiemanPick, and Gaucher disease) increase intrarenal lipid deposition. It is quite common that intrarenal lipid deposition is secondary to nephrotic syndrome, and hyperlipidemia is characteristic. The performance of renal syndrome is normalized by effective treatment of nephrotic syndrome, in which case hyperlipidemia is a consequence of kidney disease.
Examine
an examination
Related inspection
Glomerular filtration fraction glomerular filtration fraction (GFF) urinary 2 microglobulin clearance glomerular function test renal angiography
Under normal circumstances, the kidneys may contain a small amount of lipids. When the kidneys have a large amount of unusual lipid deposits or involve specific structures, they can be considered as renal lipidosis. Clinically, it can be divided into two major categories, primary and secondary, and should be identified with lipoprotein glomerulopathy.
In summary, for pathologically characteristic morphological changes - increased glomerular volume, highly expanded capillary vasospasm, kidney disease patients with layered changes in the "embolic", should pay attention to the existence of Lipoprotein glomerulopathy, if histochemical staining for lipoprotein is negative, evidence of lipoprotein embolization and extrarenal lipoprotein embolism confirmed by electron microscopy, combined with experimental evidence of abnormal lipid metabolism, the diagnosis of lipoprotein glomerulopathy can be established .
Laboratory inspection:
1. Urine examination All patients have different degrees of proteinuria, 1g ~ 3g / 24h; there are microscopic hematuria.
2. Patients with blood tests have varying degrees of hyperlipidemia. Saito et al have compared hyperlipidemia in patients with lipoprotein glomerulopathy and primary nephrotic syndrome, and found that plasma triacylglycerol levels in patients with lipoprotein glomerular disease appear to be significantly higher than their total cholesterol levels. They further analyzed that their cholesterol was mainly dominated by the increase of very low density lipoprotein and medium density lipoprotein. This feature is very similar to familial type III hyperlipoproteinemia. The most characteristic of the laboratory tests was that all cases showed a significant increase in plasma apolipoprotein E levels (103 to 388 mg/L). The gene phenotype test of apoE found that the gene phenotype containing E2 predominates.
Other auxiliary inspections:
1. Light microscopy: The characteristic lesion under light microscope is the high expansion of the glomerular capillary lumen. The cavity is filled with a lot of light-stained, reticular materials, and the capillaries are balloon-like. Some people call it capillary angioplasty. Special staining of the material in the cavity, including PAS, PASM, MASSON staining, negative Sudan 3 and oil red 0 staining showed that there were a lot of positive lipid droplets in the expanded capillary lumen, and scattered small lipid droplets were also seen in the surrounding renal tubular cells. . Mesangial cells and matrix often show mild hyperplasia. Membrane dissolution, mesangial separation from the basement membrane, and mesangial insertion may also be present in a double track shape. The glomerular basement membrane generally has no abnormalities such as thickening and nail formation. There was no significant change in tubulointerstitial, and there were no signs of abnormal lipid deposition such as foam cells. No changes in abnormal blood proteinemia were observed in the renal blood vessels. Repeated renal biopsy found that with the prolongation of the disease course, the lipoprotein embolization-like substance in the capillary lumen gradually decreased, the mesangial cells and the matrix showed obvious hyperplasia, with segmental mesenteric insertion and sclerosis, and the lipoprotein thrombus-like substance gradually became hyperplasia. Replacement of the mesangium. Correlative tubule atrophy, interstitial lymphocyte and monocyte infiltration, and fibrous tissue hyperplasia often appear in the tubulointerstitial.
2. Electron microscopy: The capsule is obviously expanded. The cavity is filled with a large number of particles of different sizes and electron densities. These particles can be arranged in stripes, similar to the fingerprint structure. There are also cavities filled with cavities of varying sizes, often in clusters or layers. The intraluminal red blood cells and endothelial cells are squeezed between the lipoprotein thrombus-like substance and the capillary wall. Mesangial area only showed mild hyperplasia in the early stage. When the lesion progressed, the mesangial area was significantly widened, mesangial cells and mesangial matrix proliferated, and sometimes mesangial insertion and mesangial lysis were observed. No thickening or dense deposits were found in the glomerular basement membrane.
3. Immunofluorescence Conventional immunofluorescence staining such as IgG, IgA, IgM, C1q, Fg staining showed no characteristic changes. The deposition of -lipoprotein and apoE in the glomerular capillary lumen was observed by staining with monoclonal antibodies against lipoproteins and apolipoproteins. In addition, a small amount of scattered fine-grained apolipoprotein deposits were also observed in the mesangial area. Alpha lipoprotein staining was negative. The disease can also be combined with IgA nephropathy, lupus nephritis, membranous nephropathy, etc. At this time, immunofluorescence, light microscopy and electron microscopy each show its characteristic changes, which is of great value in diagnosis.
Diagnosis
Differential diagnosis
Primary lipid deposition disease
(1) Fabry disease: a congenital lysosomal storage disease caused by a deficiency of the innate lysosomal enzyme -galactosidase A, which occurs mostly in men. The disease can affect almost all tissues of the body. The main clinical manifestations are paresthesia, pain in the extremities, and vascular keratomatosis in the skin. It is more common in the middle of the trunk, often involving the scrotum, buttocks, thigh roots, umbilicus and oral mucosa. Red with purple, the pressure does not fade, especially in adolescent lesions. Cardiovascular and cerebrovascular diseases can be manifested as angina pectoris, myocardial infarction, ischemic stroke, and other lesions include corneal opacity or atrophy, retinal or conjugate membrane distortion, cataract and so on. Renal changes manifested as mild proteinuria, occasional hematuria, and rare nephrotic syndrome. Mild hypertension can be seen, and a small number of patients present with more severe tubular dysfunction, such as renal diabetes insipidus or distal renal tubular acidosis. Pathological examination showed that glomerular visceral epithelial cells were highly swollen and vacuolated as a typical change in this disease. Sometimes lesions can affect parietal epithelial cells, and in a few cases, similar vacuoles can be found in glomerular endothelial cells and mesangial cells. Ultrastructural observation by electron microscopy The vacuolated cells seen under light microscopy are called "inclusion bodies". Most of this special structure is in the lysosome, with a membranous structure, also known as zebra body, myelin-like changes. It can also be seen that the fusion of the foot processes, the "inclusion bodies" in the endothelial cells and mesangial cells are smaller and less, and if the amount of "inclusion bodies" is large, it can occupy the entire cavity.
(2) Niemann-Pick disease: due to the lack of sphingosine phosphatase in the body, the sphingomyelin can not be hydrolyzed and deposited in the reticuloendothelial system, hepatocytes, renal tubular epithelial cells, nerve cells and some other cells. Causes cell dysfunction. Since a large number of foam cells accumulate in the reticuloendothelial system including the bone marrow, liver, spleen, and superficial lymph nodes can be enlarged. The disease is a rare autosomal dominant hereditary disease. The main feature of renal involvement is the large number of foam cells in the epithelial cells of the renal tubules (especially the distal tubules and the medullary ridge), and sometimes the entire tubule is foamy. Under the electron microscope, the distal renal tubules and medullary epithelial cells are occupied by a large number of lipid inclusion bodies, which are inconsistent in size and shape, and can be zebra-like or concentric. Clinically, superficial lymphadenopathy with renal insufficiency and/or proteinuria should be considered to rule out the disease.
(3) Metachromatic white matter atrophy: The brain is the main affected organ of the disease. Renal lipid deposition occurs in the distal tubules, collecting ducts, and cells of the medullary canal, and occasionally in the lumen, and the glomeruli and proximal convoluted tubules are rarely involved. Renal function is often unaffected.
(4) Mucosal lipid disease: a congenital abnormal substance storage disease. This substance contains a combination of mucopolysaccharides and lipids. The disease mainly involves fibroblasts. The renal involvement mainly manifests as a balloon-like change in renal fibroblasts and glomerular podoid epithelial cells, which contains a large amount of clear vacuoles. Proximal tubules are rarely affected.
(5) Wolman's disease: an abnormal lipid deposition disease caused by a deficiency of congenital lysosomal acid esterase. The disease mainly affects newborns and children. Clinically characterized by vomiting, diarrhea, and abdominal distension. Pathologically, a large amount of esterified cholesterol and triacylglycerol often accumulate in the liver, spleen and adrenal gland. The kidney is not the main affected organ. When the kidney is involved, vacuolization cells are formed in the mesangial area and pericardium, and the renal tubules are basically normal.
(6) Batten's disease: a group of congenital diseases with blurred classification between lesions. Their common manifestations include mental disorders, various neurological symptoms, and accumulation of complex lipids with unknown components in neurons and glial cells. In the kidney, lipid storage occurs mostly in glomerular endothelial cells and distal convoluted tubule epithelial cells.
(7) familial lecithin cholesterol acyltransferase (LCAT) deficiency: the disease is mainly characterized by corneal opacity, anemia, arteriosclerosis and the like. Kidney damage is also one of its main manifestations. Patients may have proteinuria, microscopic hematuria, and advanced end-stage renal failure. The pathological manifestations are mainly the accumulation of foam cells (significantly altered endothelial cells) in the glomerulus and a large number of dense irregular-like particles (which may be abnormal lipid substances) in the mesangial area and under the endothelium. None of the above seven hereditary lipid metabolic diseases were filled with glomerular capillary lipoprotein thrombus-like substances, which was different from lipoprotein glomerulopathy.
(8) Familial hyperlipoproteinemia: This disease is the most common type of disease in abnormal lipid metabolism. According to the characteristics of lipoprotein electrophoresis, it can be divided into six types: I, IIa, IIb, III, IV and V. Occasionally, the disease may be accompanied by symptoms of kidney involvement and formation of lipid-thrombogenic substances in the glomerular capillaries. Patients may present with nephrotic syndrome, progressive proteinuria, and renal insufficiency in the advanced stage. Laboratory tests showed a significant increase in plasma total cholesterol, triglyceride, and pre-beta-lipoprotein. Immunofluorescence was used to examine thrombus-like substances as beta or pre-beta-lipoprotein. Lipoprotein glomerulopathy has many similarities with this disease, but lipoprotein glomerulopathy lacks corneal arch, xanthoma, atherosclerosis and intermittent claudication. Clinical manifestations and signs. Laboratory examination of lipoprotein glomerulopathy is characterized by elevated plasma apoE levels, and immunofluorescence shows that lipoprotein thrombus contains apoE components. In addition, the detection of gene phenotypes of apoE also found that it is quite different from familial hyperlipoproteinemia.
2. Secondary lipid deposition disease
(1) nephrotic syndrome: nephrotic syndrome caused by any cause, a large number of lipids have been filtered, reabsorbed, will lead to its renal deposition, which mainly involves the proximal tubules, showing a vacuolization. In addition, the tubular basement membrane may also be involved, causing thickening, tearing and vacuolarization of the basement membrane. Interstitial cells are involved to make it a foam cell. Occasionally, glomerular podocytes, mesangial cells, and endothelial cells can also be affected. Even form cholesterol granuloma in the stroma.
(2) Alport syndrome: There is no abnormal plasma lipid level in this disease, often accompanied by hearing loss and eye diseases. Renal lesions are mainly characterized by thickening, tearing and thinning of the basement membrane. In the late stage of the disease, a large number of foam cells were found in the renal interstitium under light microscopy, and obvious lipid droplets appeared in the renal tubules.
(3) Liver cirrhosis: The main manifestations of liver disease involving the kidney are the widening of the mesangial area, the proliferation of mesangial matrix, and the formation of dense irregular lipid particles in the mesangial area and under the endothelium.
(4) fatty liver in idiopathic pregnancy: this disease is relatively rare. The main lesions in the liver are characterized by the accumulation of large amounts of lipids. Lipid droplets can also occur in renal tubular cells.
(5) Other lipid deposition diseases: some poisons or drugs, ischemic injury and other causes can cause lipid accumulation in the kidney. In addition, some chronic infectious diseases, such as yellow granulomatous pyelonephritis, can also accumulate foam cells, all of which are different from lipoprotein glomerulopathy in glomerular lesions and laboratory tests. Under normal circumstances, the kidneys may contain a small amount of lipids. When the kidneys have a large amount of unusual lipid deposits or involve specific structures, they can be considered as renal lipidosis. Clinically, it can be divided into two major categories, primary and secondary, and should be identified with lipoprotein glomerulopathy. In summary, for pathologically characteristic morphological changes - increased glomerular volume, highly expanded capillary vasospasm, kidney disease patients with layered changes in the "embolic", should pay attention to the presence of lipids Protein glomerulopathy, if histochemical staining for lipoprotein is negative, evidence of lipoprotein embolization and extrarenal lipoprotein embolism confirmed by electron microscopy, combined with experimental evidence of abnormal lipid metabolism, the diagnosis of lipoprotein glomerulopathy can be established.
