Diabetic nephropathy pathophysiology: Difference between revisions

Jump to navigation Jump to search
No edit summary
No edit summary
Line 2: Line 2:
{|class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;
{|class="infobox" style="position: fixed; top: 65%; right: 10px; margin: 0 0 0 0; border: 0; float: right;
|-
|-
| {{#ev:youtube|https://https://www.youtube.com/watch?v=T_me5EF0ne4&t=8s |350}}
| {{#ev:youtube|https://https://www.youtube.com/watch?v=LtdWg4ygm_E&t=9s|350}}
|-
|-
|}
|}

Revision as of 16:08, 13 July 2017

https://https://www.youtube.com/watch?v=LtdWg4ygm_E&t=9s%7C350}}

Diabetic nephropathy Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Diabetic nephropathy from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Diabetic nephropathy pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Diabetic nephropathy pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Diabetic nephropathy pathophysiology

CDC on Diabetic nephropathy pathophysiology

Diabetic nephropathy pathophysiology in the news

Blogs on Diabetic nephropathy pathophysiology

Directions to Hospitals Treating Diabetic nephropathy

Risk calculators and risk factors for Diabetic nephropathy pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]

Overview

The hallmark of diabetic nephropathy is mesangial expansion. Nonetheless, diabetic nephropathy is characterized by the presence of abnormalities in the glomeruli, such as glomerular hypertrophy, in the tubules and interstitium, such as tubular atrophy and interstitial fibrosis, and in the blood vessels, such as arteriosclerosis in both the afferent and the efferent renal arteries. Findings on histopathological analysis may be evident very early in diabetes, but are often clinically present approximately 15 years after the onset of metabolic abnormalities. A 2010 classification has been proposed that correlated the histopathological findings with the severity of disease. Diabetic nephropathy (DN) is characterized by the presence of proteinuria or decreased renal function in patients with diabetes mellitus. Diabetic nephropathy may be early or overt. The hallmark of diabetic nephropathy is mesangial expansion. Nonetheless, diabetic nephropathy is characterized by the presence of abnormalities in the glomeruli, such as glomerular hypertrophy, in the tubules and interstitium, such as tubular atrophy and interstitial fibrosis, and in the blood vessels, such as arteriosclerosis in both the afferent and the efferent renal arteries. Findings on histopathological analysis may be evident very early in diabetes, but are often clinically present approximately 15 years after the onset of metabolic abnormalities.

Pathophysiology

The pathophysiology of diabetic nephropathy is related to chronic hyperglycemia. However, it is not completely understood. It is thought to be related to the effects of the following:[1][2]

The onset of diabetic nephropathy generally takes place at least 15 years after the onset of diabetes mellitus. The pathogenesis of diabetic nephropathy occurs in distinct stages. Early pathogenesis - which may start as early as 2 years after the onset of diabetes - may include no visible lesions with mild global and diffuse hypertrophy of the renal glomeruli only.[3] This process is called "GBM thickening", a linear process that is caused by the accumulation of extracellular matrix.[3][4] These changes may not be detectable by light microscopy and require electron microscopy to identify. When the accumulation of the extracellular matrix becomes significant, pathological changes on light microscopy will be evident, typically first seen 5 years after onset of type 1 diabetes and usually occurs at a faster frequency after 15 years of onset.[5][6][7] While an increase in cellularity is often observed early in the disease, mesangial expansion without hypercellularity is common as the disease further progresses.[8] Disorganized mesangial expansion - the hallmark of diabetic nephropathy - is not a linear process and is in fact the result of a vicious circle that is characterized by the presence of frequently mesangiolysis followed by the formation of micro-aneurysms and balloon formation of glomeruli, hyaline accumulation, and mesangial repair with concomitant thickening of the GBM lamina densa.[9]

Advanced diabetic nephropathy is typically seen approximately 15 years after the onset of diabetes type I.[10] It is characterized by the abundant sclerosis of the mesangium and mesangial expansion in an irregular nodular (round/oval) pattern, called Kimmelstiel-Wilson nodules.[8] These nodules are acellular or pauci-cellular nodules with a lamellated appearance that stain positively by silver methenamine stain.[8] They are a non-specific finding in diabetic nephropathy but are frequently found in glomerular tufts in up to 25% of patients with advanced diabetic nephropathy.[8] Kimmelsteil-Wilson nodules may also be found in other disease entities, such as multiple myeloma and other gammopathies, membranoproliferative glomerulopathies, post-infectious glomerulonephritis, amyloidosis, as well as idiopathic nodular glomerulosclerosis in patients with no renal disease.[11][12]

Hyalinosis, defined as the exudation of hyaline material (usually lipid particles) between the basement membrane of Bowman's capsule and the parietal epithelium.[8] Meanwhile, the irreversible loss of podocytes plays a crucial role in the disease pathogenesis and the clinical finding of proteinuria in patients with diabetic nephropathy.[13] Podocyte injury first starts with widening of the podocyte foot processes with consequent detachment from the GBM.[13]24) As podocytes are lost, glomerulotubular junctions are exposed to further injury and formation of atubular glomeruli.[14][15] Typically, patients with diabetic nephropathy do not demonstrate any specific findings on immunofluorescence, but IgG deposition is common in these patients. The presence of IgG is not believed to be a cause of the disease, but rather as a by-product due to the presence of an abnormal sticky GBM.[8]

Gross Pathology

In the early stages of diabetic nephropathy, there is renal hypertrophy, due to expansion of the glomeruli. The resultant increase in kidney size is due to enlargement of the mesangium, the glomerular basement membrane, as well as the afferent and efferent renal arterioles. However, in the later stages of diabetic nephropathy and ESRD, the kidneys become small and atrophic, with diffuse glomerulosclerosis.[16]

Microscopic Pathology

Glomerular Lesions[8]

Light Microscopy

Immunofluorescence

Electron Microscopy

Lesions of Tubules & Interstitium[8]

Light Microscopy

Immunofluorescence

Electron Microscopy

Blood Vessels[8]

Light Microscopy

Immunofluorescence

  • No specific changes

Electron Microscopy

  • Subendothelial and transmural hyaline arterial deposition in small arteries and arterioles

Associated Conditions

Genetics

References

  1. Lim A (2014). "Diabetic nephropathy - complications and treatment". Int J Nephrol Renovasc Dis. 7: 361–81. doi:10.2147/IJNRD.S40172. PMC 4206379. PMID 25342915. Vancouver style error: initials (help)
  2. Kasper, Dennis (2015). Harrison's Principles of Internal Medicine. New York, New York: McGraw-Hill. ISBN 0071802150.
  3. 3.0 3.1 Drummond K, Mauer M, International Diabetic Nephropathy Study Group (2002). "The early natural history of nephropathy in type 1 diabetes: II. Early renal structural changes in type 1 diabetes". Diabetes. 51 (5): 1580–7. PMID 11978659.
  4. Hørlyck A, Gundersen HJ, Osterby R (1986). "The cortical distribution pattern of diabetic glomerulopathy". Diabetologia. 29 (3): 146–50. PMID 3699305.
  5. østerby R (1974). "Early phases in the development of diabetic glomerulopathy". Acta Med Scand Suppl. 574: 3–82. PMID 4533587.
  6. Mauer SM, Sutherland DE, Steffes MW (1992). "Relationship of systemic blood pressure to nephropathology in insulin-dependent diabetes mellitus". Kidney Int. 41 (4): 736–40. PMID 1513095.
  7. Drummond KN, Kramer MS, Suissa S, Lévy-Marchal C, Dell'Aniello S, Sinaiko A; et al. (2003). "Effects of duration and age at onset of type 1 diabetes on preclinical manifestations of nephropathy". Diabetes. 52 (7): 1818–24. PMID 12829652.
  8. 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8 Najafian B, Alpers CE, Fogo AB (2011). "Pathology of human diabetic nephropathy". Contrib Nephrol. 170: 36–47. doi:10.1159/000324942. PMID 21659756.
  9. Alpers CE, Hudkins KL (2011). "Mouse models of diabetic nephropathy". Curr Opin Nephrol Hypertens. 20 (3): 278–84. doi:10.1097/MNH.0b013e3283451901. PMC 3658822. PMID 21422926.
  10. Tervaert TW, Mooyaart AL, Amann K, Cohen AH, Cook HT, Drachenberg CB; et al. (2010). "Pathologic classification of diabetic nephropathy". J Am Soc Nephrol. 21 (4): 556–63. doi:10.1681/ASN.2010010010. PMID 20167701.
  11. Kimmelstiel P, Wilson C (1936). "Intercapillary Lesions in the Glomeruli of the Kidney". Am J Pathol. 12 (1): 83–98.7. PMC 1911022. PMID 19970254.
  12. Alpers CE, Biava CG (1989). "Idiopathic lobular glomerulonephritis (nodular mesangial sclerosis): a distinct diagnostic entity". Clin Nephrol. 32 (2): 68–74. PMID 2766585.
  13. 13.0 13.1 Toyoda M, Najafian B, Kim Y, Caramori ML, Mauer M (2007). "Podocyte detachment and reduced glomerular capillary endothelial fenestration in human type 1 diabetic nephropathy". Diabetes. 56 (8): 2155–60. doi:10.2337/db07-0019. PMID 17536064.
  14. Najafian B, Crosson JT, Kim Y, Mauer M (2006). "Glomerulotubular junction abnormalities are associated with proteinuria in type 1 diabetes". J Am Soc Nephrol. 17 (4 Suppl 2): S53–60. doi:10.1681/ASN.2005121342. PMID 16565248.
  15. Najafian B, Kim Y, Crosson JT, Mauer M (2003). "Atubular glomeruli and glomerulotubular junction abnormalities in diabetic nephropathy". J Am Soc Nephrol. 14 (4): 908–17. PMID 12660325.
  16. Nathan DM (1993). "Long-term complications of diabetes mellitus". N. Engl. J. Med. 328 (23): 1676–85. doi:10.1056/NEJM199306103282306. PMID 8487827.