Diabetic nephropathy

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Diabetic nephropathy
Nodular glomerulosclerosis.jpeg
Two glomeruli in diabetic nephropathy: the acellular light purple areas within the capillary tufts are the destructive mesangial matrix deposits.
Classification and external resources
Specialty endocrinology
ICD-10 E10.2, E11.2, E12.2, E13.2, E14.2
ICD-9-CM 250.4
MedlinePlus 000494
MeSH D003928

Diabetic nephropathy (diabetic kidney disease) (DN)[1] is the chronic loss of kidney function occurring in those with diabetes mellitus. It is a serious complication, affecting around one-quarter of adult diabetics in the United States. It usually is slowly progressive over years. [2] Pathophysiologic abnormalities in DN begin with long-standing poorly controlled blood glucose levels. This is followed by multiple changes in the filtration units of the kidneys, the nephrons. (There are normally about 3/4-1 1/2 million nephrons in each adult kidney).[3] Initially, there is constriction of the efferent arterioles and dilation of afferent arterioles, with resulting glomerular capillary hypertension and hyperfiltration; this gradually changes to hypofiltration over time.[4] Concurrently, there are changes within the glomerulus itself: these include a thickening of the basement membrane, a widening of the slit membranes of the podocytes, an increase in the number of mesangial cells, and an increase in mesangial matrix. This matrix invades the glomerular capillaries and produces deposits called Kimmelstiel-Wilson nodules. The mesangial cells and matrix can progressively expand and consume the entire glomerulus, shutting off filtration.[5]

The status of DN may be monitored by measuring two values: the amount of protein in the urine - proteinuria; and a blood test called the serum creatinine. The amount of the proteinuria is a reflection of the degree of damage to any still-functioning glomeruli. The value of the serum creatinine can be used to calculate the estimated glomerular filtration rate (eGFR), which reflects the percentage of glomeruli which are no longer filtering the blood.[citation needed]

Treatment with an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), which dilates the arteriole exiting the glomerulus, thus reducing the blood pressure within the glomerular capillaries, may delay - but not stop - progression of the disease. Also, three classes of diabetes medications - GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors - may delay progression.[6]

The proteinuria may become massive, and cause a low serum albumin with resulting generalized body swelling (edema): the nephrotic syndrome. Likewise, the eGFR may progressively fall from a normal of over 90 ml/min/1.73m2 to less than 15, at which point the patient is said to have end-stage kidney disease (ESKD).[7] Diabetic nephropathy is the most common cause of ESKD,[8][9] which may require hemodialysis and eventually kidney transplantation to replace the failed kidney function.[10] Diabetic nephropathy is associated with an increased risk of death in general, particularly from cardiovascular disease.[8][11]

Video explanation

Signs and symptoms[edit]

The onset of symptoms is 5 to 10 years after the disease begins.[12] A usual first symptom is frequent urination at night: nocturia. Other symptoms include tiredness, headaches, a general feeling of illness, nausea, vomiting, frequent daytime urination, lack of appetite, itchy skin, and leg swelling.[12]

Risk factors[edit]

The incidence of diabetic nephropathy is higher in diabetics with one or more of the following conditions:[12]


Diagram showing the basic outline of nephron structure and function: diabetic nephropathy is associated with changes in the afferent and efferent arterioles, causing capillary hypertension; and damage to the glomerular capillaries of multiple causes, including mesangial matrix deposition

The pathophysiology of the glomerulus in DN can best be understood by considering the three involved cells as a unit: the endothelial cell, the podocyte, and the mesangial cell. These cells are in physical contact with one another at various locations within the glomerulus; they also communicate with one another chemically at a distance. All three cells are abnormal in DN. [13]

Diabetes causes a number of changes to the body's metabolism and blood circulation, which likely combine to produce excess reactive oxygen species (chemically reactive molecules containing oxygen). These changes damage the kidney's glomeruli (networks of tiny blood vessels), which leads to the hallmark feature of albumin in the urine (called albuminuria).[14] As diabetic nephropathy progresses, a structure in the glomeruli known as the glomerular filtration barrier (GFB) is increasingly damaged.[8] This barrier is composed of three layers including the fenestrated endothelium, the glomerular basement membrane, and the epithelial podocytes.[8] The GFB is responsible for the highly selective filtration of blood entering the kidney's glomeruli and normally only allows the passage of water, small molecules, and very small proteins (albumin does not pass through the intact GFB).[8] Damage to the glomerular basement membrane allows proteins in the blood to leak through, leading to proteinuria. Deposition of abnormally large amounts of mesangial matrix causes periodic-acid schiff positive nodules called Kimmelstiel–Wilson nodules.[citation needed]

High blood sugar, which leads to formation of advanced glycation end products; and cytokines have also been implicated as mechanisms for the development of diabetic nephropathy.[15]


Ultrasonography showing hyperechogenicity of the renal cortex, visualized in the image as brighter than the liver.

Diagnosis is based on the measurement of abnormal levels of urinary albumin in a diabetic[16]coupled with exclusion of other causes of albuminuria. Albumin measurements are defined as follows:[17]

It is recommended that diabetics have their albumin levels checked annually, beginning immediately after a diagnosis of type 2 diabetes and five years after a diagnosis of type 1 diabetes.[16][18]Medical imagingof the kidneys, generally by ultrasonography, is recommended as part of a differential diagnosisif there is suspicion of urinary tract obstruction, urinary tract infection, or kidney stonesor polycystic kidney disease.[19]


CKD Stage[20] eGFR level (mL/min/1.73 m2)
Stage 1 ≥ 90
Stage 2 60 – 89
Stage 3 30 – 59
Stage 4 15 – 29
Stage 5 < 15

To stage the degree of damage in this (and any) kidney disease, the serum creatinine is determined and used to calculate the estimated glomerular filtration rate (eGFR). Normal eGFR is equal to or greater than 90ml/min/1.73 m2.[21]


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 medications, which usually reduce proteinuria levels and slow the progression of diabetic nephropathy.[22] Other issues that are important in the management of this condition include control of high blood pressure and blood sugar levels (see diabetes management), as well as the reduction of dietary salt intake.[23]


Diabetic nephropathy in type 2 diabetes can be more difficult to predict because the onset of diabetes is not usually well established. Without intervention, 20-40 percent of patients with type 2 diabetes/microalbuminuria, will evolve to macroalbuminuria.[24]

Diabetic nephropathy is the most common cause of end-stage kidney disease,[8][9] which may require hemodialysis or even kidney transplantation.[25] It is associated with an increased risk of death in general, particularly from cardiovascular disease.[8][26]


In the U.S., diabetic nephropathy affected an estimated 6.9 million people during 2005–2008.[27] The number of people with diabetes and consequently diabetic nephropathy is expected to rise substantially by the year 2050.[28]

See also[edit]


  1. ^ Kittell F (2012). "Diabetes Management". In Thomas LK, Othersen JB. Nutrition Therapy for Chronic Kidney Disease. CRC Press. p. 198. 
  2. ^ Afkarian M, Zolnick LR, Hall YN, et al. Clinical manifestations of kidney disease among US adults with diabetes 1988-2014. JAMA 2016;316:602-1o
  3. ^ Guyton, Arthur C.; Hall, John E. (2006). Textbook of Medical Physiology. Philadelphia: Elsevier Saunders. p. 310. ISBN 0-7216-0240-1
  4. ^ "diabetic nephropathy". Retrieved 2015-06-27. 
  5. ^ The Mesangial Cell Revisited: No Cell Is an Island. doi: 10.1681/ASN.2008050549 JASN June 2009 vol. 20 no. 6 1179-1187
  6. ^ de Boer IH. A new chapter for diabetic kidney disease. N Engl J Med 2017;377:885-887
  7. ^ Longo et al., Harrison's Principles of Internal Medicine, 18th ed., p.2982
  8. ^ a b c d e f g Mora-Fernández C, Domínguez-Pimentel V, de Fuentes MM, et al. (2014). "Diabetic kidney disease: from physiology to therapeutics". J. Physiol. 592 (Pt 18): 3997–4012. doi:10.1113/jphysiol.2014.272328. PMC 4198010Freely accessible. PMID 24907306. 
  9. ^ a b Ding Y, Choi ME (January 2015). "Autophagy in diabetic nephropathy". J Endocrinol. 224 (1): R15–30. doi:10.1530/JOE-14-0437. PMC 4238413Freely accessible. PMID 25349246. 
  10. ^ Lizicarova D, Krahulec B, Hirnerova E, Gaspar L, Celecova Z (2014). "Risk factors in diabetic nephropathy progression at present". Bratisl Lek Listy. 115 (8): 517–21. doi:10.4149/BLL_2014_101. PMID 25246291. 
  11. ^ Pálsson R, Patel UD (2014). "Cardiovascular complications of diabetic kidney disease". Adv Chronic Kidney Dis. 21 (3): 273–80. doi:10.1053/j.ackd.2014.03.003. PMC 4045477Freely accessible. PMID 24780455. 
  12. ^ a b c "Diabetes and kidney disease: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-06-27. 
  13. ^ The Mesangial Cell Revisited: No Cell Is an Island. doi: 10.1681/ASN.2008050549 JASN June 2009 vol. 20 no. 6 1179-1187
  14. ^ Cao, Zemin; Cooper, Mark E (2011). "Pathogenesis of diabetic nephropathy". Journal of Diabetes Investigation. 2 (4): 243–247. doi:10.1111/j.2040-1124.2011.00131.x. ISSN 2040-1116. PMC 4014960Freely accessible. PMID 24843491. 
  15. ^ "Diabetic Nephropathy: Background, Pathophysiology, Etiology". 2015-06-20. 
  16. ^ a b Lewis G, Maxwell AP (2014). "Risk factor control is key in diabetic nephropathy". Practitioner. 258 (1768): 13–7, 2. PMID 24689163. 
  17. ^ "CDC - Chronic Kidney Disease - Glossary". Retrieved 2015-07-02. 
  18. ^ Koroshi, A (2007). "Microalbuminuria, is it so important?". Hippokratia. 11 (3): 105–107. ISSN 1108-4189. PMC 2658722Freely accessible. PMID 19582202. 
  19. ^ Gross, J. L.; de Azevedo, M. J.; Silveiro, S. P.; Canani, L. H.; Caramori, M. L.; Zelmanovitz, T. (2004). "Diabetic Nephropathy: Diagnosis, Prevention, and Treatment". Diabetes Care. 28 (1): 164–176. doi:10.2337/diacare.28.1.164. ISSN 0149-5992. 
  20. ^ Fink, Howard A.; Ishani, Areef; Taylor, Brent C.; Greer, Nancy L.; MacDonald, Roderick; Rossini, Dominic; Sadiq, Sameea; Lankireddy, Srilakshmi; Kane, Robert L. (2012). "Introduction". 
  21. ^ "Glomerular filtration rate: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-07-02. 
  22. ^ Lim, Andy KH (2014). "Diabetic nephropathy – complications and treatment". International Journal of Nephrology and Renovascular Disease. 7: 361–381. doi:10.2147/IJNRD.S40172. ISSN 1178-7058. PMC 4206379Freely accessible. PMID 25342915. 
  23. ^ "Diabetic Nephropathy Treatment & Management: Approach Considerations, Glycemic Control, Management of Hypertension". 2015-06-20. 
  24. ^ Shlipak, Michael. "Clinical Evidence Handbook: Diabetic Nephropathy: Preventing Progression - American Family Physician". www.aafp.org. Retrieved 2015-06-27. 
  25. ^ Lizicarova D, Krahulec B, Hirnerova E, Gaspar L, Celecova Z (2014). "Risk factors in diabetic nephropathy progression at present". Bratisl Lek Listy. 115 (8): 517–21. doi:10.4149/BLL_2014_101. PMID 25246291. 
  26. ^ Pálsson R, Patel UD (2014). "Cardiovascular complications of diabetic kidney disease". Adv Chronic Kidney Dis. 21 (3): 273–80. doi:10.1053/j.ackd.2014.03.003. PMC 4045477Freely accessible. PMID 24780455. 
  27. ^ Lerma, Edgar V. (2014-01-01). Diabetes and Kidney Disease. Springer. ISBN 9781493907939. 
  28. ^ Lai, K. N.; Tang, S. C. W. (2011-06-08). Diabetes and the Kidney. Karger Medical and Scientific Publishers. ISBN 9783805597432. 

Further reading[edit]