intercapillary glomerulosclerosis

毛細血管間糸球体硬化症

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/06/30 20:44:30」(JST)

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Diabetic nephropathy
Classification and external resources
Photomicrography of nodular glomerulosclerosis in Kimmelstein-Wilson syndrome. Source: CDC
ICD-10	E10.2, E11.2, E12.2, E13.2, E14.2
ICD-9	250.4
MedlinePlus	000494
MeSH	D003928

Diabetic nephropathy (nephropatia diabetica), also known as Kimmelstiel-Wilson syndrome, or nodular diabetic glomerulosclerosis and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nephrotic syndrome and diffuse glomerulosclerosis. It is due to longstanding diabetes mellitus, and is a prime indication for dialysis in many Western countries.

History

The syndrome was discovered by British physician Clifford Wilson (1906–1997) and German-born American physician Paul Kimmelstiel (1900–1970) and was published for the first time in 1936.

Epidemiology

The syndrome can be seen in patients with diabetes (usually less than 15 years after onset) after about 5 years in type 1 diabetes. Clinical nephropathy secondary to glomerular disease usually manifests 15–25 years after diagnosis of diabetes and affects 25-35% of patients under the age of 30 years. It is the leading cause of premature death in young diabetic patients (between 50 and 70 years old). The disease is progressive and may cause death two or three years after the initial lesions, and is more frequent in men. Diabetic nephropathy is the most common cause of chronic kidney failure and end-stage kidney disease in the United States. People with both type 1 and type 2 diabetes are at risk. The risk is higher if blood-glucose levels are poorly controlled. Furthermore, once nephropathy develops, the greatest rate of progression is seen in patients with poor control of their blood pressure. Also people with high cholesterol level in their blood have much more risk than others.

Etiology

The word diabetes means "passing through", referring to the polyuria (abnormal increase of urine production), a symptom historically present on those affected by the disease. When the level of blood glucose rises beyond the kidney's capacity to reabsorb glucose from the renal ultrafiltrate, glucose remains diluted in the fluid, raising its osmotic pressure and causing more water to be carried out, thus, increasing the excreted urine volume. The increased volume dilutes the sodium chloride in the urine, signalling the macula densa to release more renin, causing vasoconstriction, a survival mechanism to retain water by passing less blood through the kidneys. Because the kidney is nurtured exclusively by the blood it filtrates, the vasoconstriction also reduces the nutrients supplied to it, causing infarct of its tissues and reduction of renal function.

Pathophysiology

The earliest detectable change in the course of diabetic nephropathy is a thickening in the glomerulus. At this stage, the kidney may leak more serum albumin (plasma protein) than normal in the urine (albuminuria), and this can be detected by sensitive medical tests for albumin. This stage is called "microalbuminuria". As diabetic nephropathy progresses, increasing numbers of glomeruli are destroyed by progressive nodular glomerulosclerosis. Consequently, urine albumin increases to the point that it may be detected by ordinary urinalysis techniques. At this stage, a kidney biopsy generally clearly shows diabetic nephropathy.

The Armanni-Ebstein change (or Armanni-Ebstein cells) consists of deposits of glycogen in the tubular epithelial cells (pars straight of proximal convoluted tubule and loop of Henle). Because most diabetics are treated before this stage, it is very rare to see it at the present time. It appears in decompensated diabetics with glycemia higher than 500 mg/dL and in the presence of severe glycosuria; it is a reversible alteration without functional manifestations. The interstitium shows nonspecific chronic changes.

Signs and symptoms

Kidney failure provoked by glomerulosclerosis leads to fluid filtration deficits and other disorders of kidney function. There is an increase in blood pressure (hypertension) and fluid retention in the body plus a reduced plasma oncotic pressure causes edema. Other complications may be arteriosclerosis of the renal artery and proteinuria.

Throughout its early course, diabetic nephropathy has no symptoms. They develop in late stages and may be a result of excretion of high amounts of protein in the urine or due to renal failure:

• edema: swelling, usually around the eyes in the mornings; later, general body swelling may result, such as swelling of the legs
• foamy appearance or excessive frothing of the urine (caused by the proteinuria)
• unintentional weight gain (from fluid accumulation)
• anorexia (poor appetite)
• nausea and vomiting
• malaise (general ill feeling)
• fatigue
• headache
• frequent hiccups

The first laboratory abnormality is a positive microalbuminuria test. Most often, the diagnosis is suspected when a routine urinalysis of a person with diabetes shows too much protein in the urine (proteinuria). The urinalysis may also show glucose in the urine, especially if blood glucose is poorly controlled. Serum creatinine and BUN may increase as kidney damage progresses.

A kidney biopsy confirms the diagnosis, although it is not always necessary if the case is straightforward, with a documented progression of proteinuria over time and presence of diabetic retinopathy on examination of the retina of the eyes.

Treatment

The goals of treatment are to slow the progression of kidney damage and control related complications. The main treatment, once proteinuria is established, is ACE inhibitor drugs, which usually reduces proteinuria levels and slows the progression of diabetic nephropathy. Several effects of the ACEIs that may contribute to renal protection have been related to the association of rise in Kinins which is also responsible for some of the side effects associated with ACEIs therapy such as dry cough. The renal protection effect is related to the antihypertensive effects in normal and hypertensive patients, renal vasodilatation resulting in increased renal blood flow and dilatation of the efferent arterioles. Many studies have shown that related drugs, angiotensin receptor blockers (ARBs), have a similar benefit. However, combination therapy, according to the ONTARGET study, is known to worsen major renal outcomes, such as increasing serum creatinine and causing a greater decline in estimated glomerular filtration rate (eGFR).

Blood-glucose levels should be closely monitored and controlled. This may slow the progression of the disorder, especially in the very early ("microalbuminuria") stages. Medications to manage diabetes include oral hypoglycemic agents and insulin injections. As kidney failure progresses, less insulin is excreted, so lesser doses may be needed to control glucose levels.

Diet may be modified to help control blood-sugar levels. Modification of protein intake can affect hemodynamic and nonhemodynamic injury.

High blood pressure should be aggressively treated with antihypertensive medications, in order to reduce the risks of kidney, eye, and blood vessel damage in the body. It is also very important to control lipid levels, maintain a healthy weight, and engage in regular physical activity.

Patients with diabetic nephropathy should avoid taking the following drugs:

• Contrast agents containing iodine

• Commonly used non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen, or COX-2 inhibitors like celecoxib, because they may injure the weakened kidney.

Urinary tract and other infections are common and can be treated with appropriate antibiotics.

Dialysis may be necessary once end-stage renal disease develops. At this stage, a kidney transplantation must be considered. Another option for type 1 diabetes patients is a combined kidney-pancreas transplant.

C-peptide, a by-product of insulin production, may provide new hope for patients suffering from diabetic nephropathy.

Several compounds are in development for diabetic kidney disease. These include, but are not limited to, bardoxolone methyl, olmesartan medoxomil, sulodexide, and avosentan.

Prognosis

Diabetic nephropathy continues to get gradually worse. Complications of chronic kidney failure are more likely to occur earlier, and progress more rapidly, when it is caused by diabetes than other causes. Even after initiation of dialysis or after transplantation, people with diabetes tend to do worse than those without diabetes.

Complications

Possible complications include:

• hypoglycemia (due to decreased renal clearance of insulin)
• rapidly progressing chronic kidney failure
• end-stage kidney disease
• hyperkalemia
• severe hypertension
• complications of hemodialysis
• complications of kidney transplant
• coexistence of other diabetes complications
• peritonitis (if peritoneal dialysis used)
• increased infections

See also

• Diabetic diet
• Hyperbaric medicine
• Nephrology

Additional images

• Histopathological image of diabetic glomerulosclerosis with nephrotic syndrome. H&E stain.

• Histopathological image of diabetic glomerulosclerosis with nephrotic syndrome. Another glomerulus. H&E stain.

• Histopathological image of diabetic glomerulosclerosis with nephrotic syndrome. Another glomerulus. H&E stain.

• Histopathological image of diabetic glomerulosclerosis with nephrotic syndrome. PAS stain.

• Histopathological image of diabetic glomerulosclerosis with nephrotic syndrome. PAS stain.

• Histopathological image of diabetic glomerulosclerosis with nephrotic syndrome. PAM stain.

• Histopathological image of diabetic glomerulosclerosis with nephrotic syndrome. PAM stain.

References

External links

• Diabetic nephropathy. HealthCentral.
• Diabetic nephropathy. MedlinePlus Medical Encyclopedia. Text from this public domain article was partially used here.
• Texas University Classification

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 糖尿病性腎症の概要 overview of diabetic nephropathy
• 2. 巣状分節性糸球体硬化症の疫学、分類、および病因 epidemiology classification and pathogenesis of focal segmental glomerulosclerosis
• 3. 原発性巣状分節性糸球体硬化症の治療 treatment of primary focal segmental glomerulosclerosis
• 4. 移植腎における巣状分節性糸球体硬化症 focal segmental glomerulosclerosis in the transplanted kidney
• 5. HIV感染に関連しない巣状分節性糸球体硬化症 collapsing focal segmental glomerulosclerosis not associated with hiv infection

English Journal

• Acute kidney injury in patients infected by H1N1: clinical histological correlation in a series of cases.

• Sevignani G, Soares MF, Marques GL, Freitas AK, Gentili A, Chula DC, Nascimento MM.
• Jornal brasileiro de nefrologia : ʹorgão oficial de Sociedades Brasileira e Latino-Americana de Nefrologia.J Bras Nefrol.2013 Jul-Sep;35(3):185-90. doi: 10.5935/0101-2800.20130030.
• INTRODUCTION: Influenza A (H1N1) virus was first reported on April 2009 and, since then, several studies have reported the characteristics concerning the clinical presentation and pulmonary involvement. However, accurate information about the acute kidney injury (AKI) and kidney histopathological fi
• PMID 24100737

• Renal morphologic lesions reminiscent of diabetic nephropathy.

• Raparia K1, Usman I, Kanwar YS.
• Archives of pathology & laboratory medicine.Arch Pathol Lab Med.2013 Mar;137(3):351-9. doi: 10.5858/arpa.2012-0243-RA.
• CONTEXT: Nodular, intercapillary glomerulosclerotic lesions resembling Kimmelstiel-Wilson nodules commonly observed in diabetic nephropathy can also be seen in patients without any clinical history or evidence of diabetes.OBJECTIVES: To discuss the pathobiology of lesions reminiscent of diabetes nep
• PMID 23451746

• Isolation and propagation of glomerular mesangial cells.

• Menè P1, Stoppacciaro A.
• Methods in molecular biology (Clifton, N.J.).Methods Mol Biol.2009;466:3-17. doi: 10.1007/978-1-59745-352-3_1.
• Cultures of glomerular mesangial cells (MC) of rodent or human origin have been extensively employed in renal research laboratories since the early 1980s. Cultured MC retain extensive analogies with the fairly undifferentiated in vivo phenotype of an intercapillary mesenchymal cell population, i.e.,
• PMID 19148614

Japanese Journal

• Carlbon Disulfide Poisoning in Korea with Social and Historical Background.

• Journal of Occupational Health 38(4), 155-161, 1996
• NAID 130003416421

• Adult polycystic kidney disease with diabetic intercapillary glomerulosclerosis

• J Diabet Complications 1, 32-33, 1987
• NAID 30027233850

• 高濃度造影剤注入後急性腎不全を呈し剖検により腎乳頭壊死のみられた糖尿病の1例

• 糖尿病 20(5), 660-666, 1977
• NAID 130004114729

Related Links

• Intercapillary Glomerulosclerosis - National Center for ...

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (906K), or click on a page image ... Intercapillary glomerulosclerosis. KIMMELSTIEL P, PORTER WB. N Engl ...

• intercapillary glomerulosclerosis - definition of intercapillary ...

glomerulosclerosis /glo·mer·u·lo·scle·ro·sis/ (glo-mer″u-lo-sklĕ-ro´sis) fibrosis and scarring resulting in senescence of the renal glomeruli. diabetic glomerulosclerosis intercapillary g. focal segmental glomerulosclerosis a syndrome of ...

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intercapillary glomerulosclerosis