Diabetic nephropathy

from Wikipedia, the free encyclopedia
Classification according to ICD-10
N08.3 * Glomerular diseases in diabetes mellitus
ICD-10 online (WHO version 2019)
Nodular glomerulosclerosis

The diabetic nephropathy ( diabetic nephropathy ), also Kimmelstiel-Wilson syndrome (for type I diabetes) , intercapillary glomerulonephritis , nodular glomerulosclerosis or diabetic glomerulosclerosis , is a progressive kidney disease due to angiopathy of capillaries of the renal corpuscle . The characteristic histological feature is a nodular (Latin: nodular) increase in connective tissue (nodular sclerosis ). The cause of diabetic nephropathy is longstanding diabetes mellitus . In Germany, diabetic nephropathy is the most common cause of kidney failure requiring dialysis .

history

The syndrome was discovered by the British doctor Clifford Wilson (1906–1997) and the doctor Paul Kimmelstiel (1900–1970), who came from Germany and later lived in the USA , and was published for the first time in 1936.

Epidemiology

The syndrome can occur in patients with long-term poorly controlled diabetes mellitus (i.e. permanently high blood sugar levels), regardless of the cause of the diabetic metabolic disorder. The disease is progressive and, if left untreated, can lead to complete loss of kidney function within two to three years after the first changes appear . In Germany in 2005, diabetic nephropathy was the most common cause of new kidney failure requiring dialysis, with a share of 35% . In developing countries, a dramatic increase in type 2 diabetes mellitus and thus diabetic nephropathy has been observed in recent years, especially in the poorer classes who adopt a western lifestyle with cheap, high-energy food and a lack of exercise. Since dialysis treatment is not generally available in these countries, the diagnosis usually amounts to a death sentence. India and China are particularly hard hit.

The information on the frequency of glomerulosclerosis in diabetics varies widely. In autopsies reacting corresponding histological changes place the cases in 7.3 to 66 percent of biopsies in up to 93 percent of cases. Linear relationships ( proportionality ) between the severity of the fine tissue changes and the severity of renal insufficiency are not described. There is also no evidence of a proportionality between the average blood sugar level ( HbA1c ) and the stage of renal insufficiency. The prevalence of kidney failure in type 1 diabetes mellitus is 40% and in type 2 20–30%. So about 70 percent of all diabetics do not develop nephropathy.

pathology

Changes in the kidney corpuscles (glomerulum) occur in patients with longstanding diabetes before albumin is detected in the urine.

In 2010 a classification of diabetic nephropathy according to the severity of the histologically detectable tissue changes was published:

  • Class I: Thickening of the glomerular basement membrane (in women> 395  nm , in men> 430 nm).
  • Class IIa: Mild enlargement in more than 25% of the observed mesangium (connective tissue between the capillary loops of the kidney corpuscle): The mesangium is not wider than the lumen of the capillary loops.
  • Class IIb: Severe widening in more than 25% of the observed mesangium: the mesangium is wider than the lumen of the capillary loops.
  • Class III: Nodular sclerosis: At least one typical nodular scarring (sclerosis) of the capillary loops with the inclusion of structureless material (hyaline) (classic Kimmelstiel-Wilson lesion).
  • Class IV: Advanced diabetic glomerulosclerosis: More than 50% of the kidney corpuscles are completely scarred.

This classification (four classes) is independent of the stage classification of chronic kidney failure (five stages).

Pathogenesis

Several mechanisms that can lead to diabetic nephropathy are discussed:

Diabetic nephropathy is not a uniform disease with uniform histological findings. Ultimately, the pathogenesis of the diabetic secondary diseases and thus also the actual mechanism of the organic malfunctions in chronic hyperglycaemia are still unknown. However, it is undisputed that the reduction in renal perfusion and glomerular filtration is the direct consequence of a reduced cardiac output (CO). The extrarenal kidney syndrome in diabetes according to Wilhelm Nonnenbruch must therefore be considered; That is the renal insufficiency even without anatomically demonstrable kidney disease in diabetic patients . Each failure causes hemodynamically renal insufficiency. A significantly increased cardiovascular risk as a defining criterion for diabetic nephropathy leads to a reduction in CO and GFR.

Microalbuminuria

The earliest sign of diabetic nephropathy is evidence of increased excretion of albumin in the urine. Normally, the kidneys excrete 20 mg of albumin within 24 hours (normal albumin). The excretion of 30 to 300 mg albumin per day is called microalbuminuria , the excretion of over 300 mg albumin per day is called macroalbuminuria or proteinuria . Microalbuminuria cannot be detected with conventional urine test strips. The gold standard is the determination of albumin in urine, which was collected over 24 hours. With the simultaneous determination of albumin and creatinine in the urine and calculation of the albumin-creatinine quotient, the urine need not be collected: microalbuminuria is defined by an albumin / creatinine quotient of 30 to 300 mg / g, macroalbuminuria by an albumin / creatinine Quotients> 300 mg / g. For early detection, special test strips are used to detect low albumin concentrations in the urine (so-called micro test).

Early detection and diagnosis

In patients with diabetes mellitus (DM), chronic kidney disease can be caused by diabetic nephropathy, but also by other kidney diseases. Therefore, the cause of kidney involvement should be sought in patients with DM and kidney disease. Patients with DM should be examined annually for the presence of diabetic nephropathy, immediately after diagnosis of type 2 diabetes and from the 5th year after diagnosis of type 1 diabetes. As part of the early detection examination, the albumin / creatinine quotient in the urine and the creatinine in the serum are determined. The glomerular filtration rate (GFR) as a measure of kidney function is estimated from the serum creatinine with the help of an approximation formula . If micro- or macroalbuminuria is found in 2 out of 3 urine samples, chronic kidney damage is present. A diabetic nephropathy is most likely present in macroalbuminuria, in microalbuminuria after at least 10 years of type 1 diabetes, or in microalbuminuria and simultaneous diabetic retinal damage (diabetic retinopathy) . In the absence of diabetic retinopathy, another cause of the kidney damage should be considered. Another cause can also be considered in the case of poor or rapidly deteriorating kidney function, rapidly increasing protein excretion (proteinuria) or nephrotic syndrome , untreatable high blood pressure, red blood cells (erythrocytes) or erythrocyte cylinders in the urine, signs or symptoms of other systemic diseases or a decrease in the glomerular ones Filtration rate greater than 30% within 2 to 3 months of starting treatment with an ACE inhibitor or AT1 antagonist .

Risk factors

Not all diabetics develop diabetic nephropathy. Family examinations show a strong influence of the hereditary disposition (genetic predisposition). Men are at higher risk than women. The risk of illness increases with poor blood sugar control . If diabetic nephropathy has already occurred, the further course depends primarily on a consistent lowering of blood pressure ; an optimization of the metabolism should also be sought. The increase in protein excretion in the urine indicates the progression of the disease. A halving of protein excretion through drug therapy halves the risk of kidney failure. Other risk factors are increased blood lipid levels and nicotine abuse .

Course of the disease

Ten years after the onset of the disease, microalbuminuria can be detected in 25% of all diabetics , proteinuria in 5% , and impaired kidney function in 0.8%. If left untreated, the impairment of kidney function generally progresses rapidly. The final stage requiring dialysis is reached within 25 years on average.

Staging

Comparison of the staging according to Mogensen and KDOQI
stage Classification according to Mogensen Classification according to KDOQI (GFR ml / min / 1.73 m²)
1 Hyperfiltration ≥ 90
2 Normoalbuminuria 60-89
3 Microalbuminuria 30-59
4th Macroalbuminuria 15-29
5 Kidney failure <15

Diabetic nephropathy can be classified according to both the extent of protein excretion and the impairment of kidney function. In the Mogensen staging of 1983, hyperfiltration is the earliest stage. As the disease progresses, kidney function pseudo normalizes. At this stage, kidney function is normal, protein excretion is not detectable. However, a histological examination of a kidney sample reveals characteristic morphological changes. Stage 3 is characterized by the occurrence of microalbuminuria, stage 4 by proteinuria of> 0.5 g / d and stage 5 requires chronic dialysis treatment.

The staging of the KDOQI from 2002 divides chronic kidney disease into five stages according to the glomerular filtration rate.

Often the decline in kidney function is preceded by an increase in protein excretion, but in about a third of patients there is an increasing loss of kidney function without any increased protein excretion being detected beforehand.

A more recent staging of diabetic nephropathy classifies as follows:

  • Kidney damage with normal kidney function (creatinine clearance over 90 ml / min)
    • Microalbuminuria (albumin excretion 20–200 mg / l)
    • Macroalbuminuria (albumin excretion over 200 mg / l)
  • Kidney damage with renal insufficiency (creatinine clearance below 90 ml / min)
    • mild
    • moderate
    • highly
    • terminal (creatinine clearance below 15 ml / min)

Symptoms

  • In the stage of microalbuminuria and in the early stage of proteinuria there are no symptoms, but an increase in blood pressure can occur. At this stage the disease can only be recognized by determining microalbuminuria.
  • If the protein excretion (proteinuria) continues to increase in the course of the disease, a nephrotic syndrome can occur. The nephrotic syndrome is defined by a protein excretion of over 3.5 g per 24 hours, water retention in the tissues (edema) and increased blood lipids (hyperlipidemia) . As a visible consequence of the increased protein content for the patient, the urine foams. The water retention leads to swelling mainly in the legs and eyelids, the water retention leads to an increase in weight. Blood clots (vein thrombosis) and infections of the urinary tract can occur as complications .
  • Chronic kidney failure occurs as the disease progresses . Even in the microalbuminuria stage, the risk of life-threatening complications of the cardiovascular system is increased and increases dramatically with increasing renal impairment. Symptoms of chronic kidney failure do not appear until the end stage of uremia . The uremic syndrome manifests itself in decreased performance, general malaise, fatigue, itching, loss of appetite, nausea and vomiting.

Prevention and therapy

The following measures are recommended for the prevention (prevention) of diabetic nephropathy:

  • Strict adjustment of blood sugar, possibly adjustment to intensified insulin therapy . To monitor therapy, the HbA1c value is determined in the blood. This should be below 6.5–7.5%, depending on the age and comorbidities of the patient.
  • Medicinal lowering of blood pressure to values ​​below 130/80 mmHg. ACE inhibitors or AT1 antagonists , usually in combination with a diuretic, are recommended as the first choice . Even in patients with an initial blood pressure below 120/80 mmHg, lowering blood pressure further can further reduce the risk of diabetic nephropathy.
  • Preventing cardiovascular complications by lowering blood lipids, e.g. B. by giving a statin and taking low-dose acetylsalicylic acid (ASA).

The treatment (therapy) of diabetic nephropathy essentially pursues two goals:

  • Lowering the risk of cardiovascular complications such as heart attack or stroke ,
  • Inhibition of the progression ( progression ) of impaired kidney function.

The beneficial influence of ACE inhibitors and AT 1 antagonists is explained by the inhibition of hyperfiltration and scarring in the renal corpuscle. If the protein excretion is above 1 g / 24h, the blood pressure should even be reduced to values ​​below 125/75 mmHg. The aim of treatment is to reduce protein excretion to below 0.5–1 g / 24h, as higher protein excretion leads to a progressive deterioration in kidney function. If this therapeutic goal cannot be achieved with conventional measures, a combination of ACE inhibitors and AT1 antagonists or treatment in very high doses has recently been recommended. A combination treatment consisting of an AT1 antagonist and aliskiren may also have a beneficial effect. However, the combination treatment of aliskiren with AT1 antagonists or ACE inhibitors has been contraindicated since February 2012 based on the results of the ALTITUDE study. If macroalbuminuria is present, treatment with an ACE inhibitor or AT1 antagonist should be used even with normal blood pressure; in the case of microalbuminuria, this treatment should at least be considered. The aim of therapy in patients with diabetic nephropathy and normal blood pressure is to reduce the excretion of albumin in the urine.

In stage 1–4 of diabetic kidney disease, the LDL cholesterol should be reduced to values ​​below 100 mg / dl (optionally <70 mg / dl), the drug of choice is a statin . If, in patients with type 2 diabetes, therapy with a statin is only started in stage 5 of the kidney disease, which requires dialysis, the medicinal lowering of blood lipids is no longer useful.

Patients with diabetic kidney disease should moderate their daily protein intake; the recommended intake is 0.8 g protein per kg body weight. The body weight should be normalized, aiming for a body mass index between 18.5 and 24.9 kg / m².

Patients with diabetes and kidney involvement can actively contribute to the success of the treatment

  • regular blood sugar self-checks and, if necessary, adjustment of medication,
  • regular self-monitoring of blood pressure,
  • Compliance with dietary recommendations (low proportion of animal fats, reduced sodium),
  • Cessation of smoking,
  • regular physical activity,
  • regular medication use.

If the kidney function falls below 60% of the norm, disorders of the bone metabolism, blood formation, acid-base and electrolyte balance can occur. For the prevention and treatment of these secondary diseases, see Chronic kidney failure .

If the kidney function is less than 15% of the norm, a kidney replacement procedure is necessary.You can choose between blood washing (hemodialysis) , peritoneal dialysis or a transplant . For patients with type 2 diabetes mellitus, a kidney transplant is an option, for patients with type 1 diabetes mellitus, a combined transplantation of kidney and pancreas (pancreas) may also be possible.

If an extrarenal kidney syndrome is present , the underlying disease ( heart disease , liver disease , lung disease ) must first be treated in order to increase cardiac output and thus improve renal perfusion. Severe cardiorenal syndrome is treated with a heart transplant , and hepatorenal syndrome may be treated with a liver transplant ; in rare cases, a lung transplant should also be considered. A kidney transplant would mostly be contraindicated here .

Pregnancy and diabetic nephropathy

Pregnancies in patients with diabetic nephropathy are high-risk pregnancies and should be cared for on a multidisciplinary basis ( gynecologist , diabetologist , nephrologist ). ACE inhibitors and AT1 antagonists, taken before pregnancy, can reduce maternal and fetal risk. However, both substance classes must be discontinued immediately after the first failed menstrual period or after a positive pregnancy test, as they increase the risk of childhood malformations if taken during pregnancy. If a patient with diabetes and kidney disease requires drug therapy for diabetes during pregnancy, this must be done with insulin. Alpha-methyldopa is primarily used to control blood pressure , alternative substances are selective β-1 receptor blockers or dihydralazine .

literature

  • Christoph Hasslacher: Diabetic Nephropathy - Prevention and Therapy. 2nd Edition. Verlag Uni-Med, 2006, ISBN 3-89599-944-X .
  • Christoph Hasslacher: Diabetes and Kidney - Prevention, Detection, Treatment . Verlag Kirchheim, Mainz 2001, ISBN 3-87409-335-2 .

Web links

Individual evidence

  1. ^ Paul Kimmelstiel, Clifford Wilson: Benign and malignant hypertension and nephrosclerosis. A clinical and pathological study. In: American Journal of Pathology 12, 1936, pp. 45-48.
  2. ↑ U. Frei, Hans-Jürgen Schober-Halstenberg: Renal replacement therapy in Germany. QuaSi-Niere annual report 2005/2006, Berlin.
  3. ^ Parvez Hossain, so far Kawar, Meguid El Nahas: Obesity and Diabetes in the Developing World - A Growing Challenge . In: The New England Journal of Medicine . 2007, 356, pp. 213-215.
  4. ^ J. Richter: Insulin - Physiology and Pathophysiology, Consequences of Insulin Deficiency , Hoechst , Frankfurt am Main 1982, p. 67.
  5. ^ The Merck Manual , 20th Edition, Merck Sharp & Dohme , Kenilworth 2018, ISBN 978-0-911910-42-1 , p. 2117.
  6. ^ Willibald Pschyrembel: Clinical Dictionary , 267th edition, Verlag de Gruyter , Berlin, Boston 2017, ISBN 978-3-11-049497-6 , p. 1241.
  7. ↑ Thijs W. Cohen Tervaert et al: Pathologic classification of diabetic nephropathy . In: Journal of the American Society of Nephrology . tape 21 , no. 4 , April 2010, ISSN  1533-3450 , p. 556-563 , doi : 10.1681 / ASN.2010010010 , PMID 20167701 .
  8. ↑ The thickness of the healthy basement membrane is 50 nm and can increase to 170 to 500 nm in diabetic nephropathy. Source: J. Richter: Insulin - Physiologie und Pathophysiologie , Hoechst , Frankfurt am Main 1982, p. 67.
  9. ↑ The width of the gaps between the podocyte processes is 7.5 nm in healthy individuals; In the diabetic kidney, the basement membranes swell and thus enlarge these gaps. This leads to functional losses in the podocytes.
  10. ↑ S. Hakroush et al .: Effects of Increased Renal Tubular Vascular Endothelial Growth Factor (VEGF) on Fibrosis, Cyst Formation, and Glomerular Disease . In: The American Journal of Pathology . No. 175 (5) , 2009, pp. 1883-1895 .
  11. ↑ Juan F. Navarro-González, Carmen Mora-Fernández: The role of inflammatory cytokines in diabetic nephropathy . In: Journal of the American Society of Nephrology : JASN . tape 19 , no. 3 , March 2008, ISSN  1533-3450 , p. 433-442 , doi : 10.1681 / ASN.2007091048 , PMID 18256353 .
  12. ↑ Luigi Gnudi et al: Mechanical Forces in Diabetic Kidney Disease: A Trigger for Impaired Glucose Metabolism . In: Journal of the American Society of Nephrology . No. 18 , 2007, p. 2226-2232 ( abstract ).
  13. ↑ B. Isermann et al .: Activated protein C protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis . In: Nature Medicine . No. 13 (11) , 2007, pp. 1349-1358 , PMID 17982464 .
  14. ^ Rudolf Groß , Paul Schölmerich : 1000 memoranda of internal medicine , 2nd edition, FK Schattauer Verlag , Stuttgart, New York 1978, ISBN 3-7945-0511-5 , p. 157.
  15. ↑ Harrison's Internal Medicine , 18th edition, Volume 3, McGraw-Hill , Berlin 2012, ISBN 978-3-940615-20-6 , p. 3219.
  16. ^ Wilhelm Nonnenbruch : The double-sided kidney diseases , Ferdinand Enke Verlag , Stuttgart 1949, p. 189.
  17. ↑ Gerd Harald Herold : Internal Medicine 2019 , self-published , Cologne 2019, ISBN 978-3-9814660-8-9 , p. 725.
  18. ↑ Ralf Dikow, Eberhard Ritz: Microalbuminuria: early warning system for diabetics with kidney disease . In: Deutsches Ärzteblatt . 100, Issue 17, April 25, 2003, pp. A-1100 / B-926 / C-870
  19. ^ BI Freedman et al.: Genetic Factors in Diabetic Nephropathy . In: Clinical Journal of the American Society of Nephrology . No. 2 , 2007, p. 1306-1316 ( abstract ).
  20. ^ Adler et al .: Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64). In: Kidney International . 2003, 63, p. 225.
  21. ↑ George Jerums, Sianna Panagiotopoulos, Erosha Premaratne, Richard J. MacIsaac: Integrating albuminuria and GFR in the assessment of diabetic nephropathy . In: Nature Reviews Nephrology . tape 5 , no. July 7 , 2009, ISSN  1759-507X , p. 397-406 , doi : 10.1038 / nrneph.2009.91 , PMID 19556994 .
  22. ^ CE Mogensen, CK Christensen, E. Vittinghus: The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy . In: Diabetes . 32 Suppl 2, May 1983, ISSN  0012-1797 , p. 64-78 , PMID 6400670 .
  23. ↑ K / DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification . In: American Journal of Kidney Diseases . tape 39 , 2 Suppl 1, February 2002, ISSN  1523-6838 , p. S1-266 , PMID 11904577 . Full text ( Memento of the original from December 20, 2008 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.kidney.org
  24. ↑ Bruce A. Perkins et al .: In patients with type 1 diabetes and new-onset microalbuminuria the development of advanced chronic kidney disease may not require progression to proteinuria . In: Kidney International . tape 77 , no. 1 , January 2010, ISSN  1523-1755 , p. 57-64 , doi : 10.1038 / ki.2009.399 , PMID 19847154 .
  25. ^ Richard J. MacIsaac et al.: Nonalbuminuric renal insufficiency in type 2 diabetes . In: Diabetes Care . tape 27 , no. 1 , January 2004, ISSN  0149-5992 , p. 195-200 , PMID 14693989 .
  26. ↑ Richard Daikeler, idols Use, Sylke Waibel: diabetes. Evidence-based diagnosis and therapy. 10th edition. Kitteltaschenbuch, Sinsheim 2015, ISBN 978-3-00-050903-2 , p. 153 f.
  27. ↑ a b Werner Scherbaum, Eberhard Ritz: Prevention and therapy of diabetic nephropathy . (PDF) In: Deutsches Ärzteblatt . 102, Issue 3, January 21, 2005, pp. A-137 / B-113 / C-109
  28. ↑ KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease . In: American Journal of Kidney Disease Vol. 49, No. 2, Suppl. 2, February 2007 PDF - 4.5 MB ( Memento of the original from March 6, 2009 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.kidney.org
  29. ↑ Bastiaan E. de Galan, Vlado Perkovic, Toshiharu Ninomiya, Avinesh Pillai, Anushka Patel, Alan Cass, Bruce Neal, Neil Poulter, Stephen Harrap, Carl-Erik Mogensen, Mark Cooper, Michel Marre, Bryan Williams, Pavel Hamet, Giuseppe Mancia , Mark Woodward, Paul Glasziou, Diederick E. Grobbee, Stephen MacMahon, John Chalmers: Lowering blood pressure reduces renal events in type 2 diabetes . In: Journal of the American Society of Nephrology: JASN . tape 20 , no. 4 , April 2009, ISSN  1533-3450 , p. 883-892 , doi : 10.1681 / ASN.2008070667 , PMID 19225038 .
  30. ↑ Ellen Burgess, Norman Muirhead, Paul Rene de Cotret, Anthony Chiu, Vincent Pichette, Sheldon Tobe: Supramaximal dose of candesartan in proteinuric renal disease . In: Journal of the American Society of Nephrology: JASN . tape 20 , no. 4 , April 2009, ISSN  1533-3450 , p. 893-900 , doi : 10.1681 / ASN.2008040416 , PMID 19211712 .
  31. ↑ Hans-Henrik Parving, Frederik Persson, Julia B. Lewis, Edmund J. Lewis, Norman K. Hollenberg: Aliskiren combined with losartan in type 2 diabetes and nephropathy . In: The New England Journal of Medicine . tape 358 , no. 23 , June 5, 2008, ISSN  1533-4406 , p. 2433-2446 , doi : 10.1056 / NEJMoa0708379 , PMID 18525041 .
  32. ↑ Another view, albeit without justification: Götz Use: Diabetes Therapy Today , "Current Knowledge Hoechst", Hoechst , Frankfurt am Main without year, page 4.3.
  33. ↑ S1 guideline for the diagnosis and treatment of hypertensive pregnancy diseases ( AWMF guideline), accessed August 18, 2018.