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Diabetic Nephropathy
Diabetic Nephropathy
Adalah syndrome yang dikarakteristikan dengan ekresi urine albumin, diabetic glomerular lesion,
and loss of GFR in diabetics.
- Epid :
Diabetic nephropathy dapat terjadi pada pasien type 1 dan type 2 diabetes. Diabetic
nephropathy merupakan penyebab yang umum dari Chronic renal failure di united states.
Diabetic nephropathy menyebabkan end-stage renal disease di United States. Sekitar 30-40%
pasien diabetes terjadi nephropathy,dengan Type 2 DM (90%) type 1 (10%). Renal lesion banyak
terjadi pada Afirican-American, Native America, Polynesian, dan Maori population. 45% pasien
menerima renal replacement therapy dan telah menjadi permasalahan dunia.
- Risk factor :
Gene :
Genes involved in the genetic predisposition to diabetic nephropathy, are likely to be those
involved in reninangiotensin system, nitric oxide pathway, aldose reductase pathway, GLUT-1,
and lipoproteins metabolism.
Polymorphism in the 5′ end of aldose reductase gene and the development of diabetic
nephropathy in type 1 diabetes
Family history :
Familial predisposition to raised arterial pressure increases the susceptibility to renal disease in
patients with diabetes. Studies have demonstrated that mean blood pressure levels are
significantly higher in those who progress to microalbuminuria, than in those who do not,
indicating that hypertension is an important risk factor for diabetic nephropathy
Hyperglycemia :
mesangial cells cause hypertrophy, increase gene expression and protein secretions like
collagen, laminin and fibronectin
interaction of AGEs with its receptors in the kidney induces the synthesis and
release of many cytokines like TGF-b1, and IGF and results in enhanced
production of collagen, laminin and fibronectin
- Lesion :
1. Glomerular lesion
Yang terpenting dari lesi glomerular adalah adanya penebalan pada glomerular capillary
basement membrane (GBM) terjadi di hampir semua kasus diabetic nephropathy.
Penebalan terjadi dimulai pada sekitar 2 tahun setelah onset type 1 diabetes dan dalam 5
tahun terjadi kenaikan 30%. Penebalan terjadi secara progresif dan biasanya terdapat
pelebaran mesangial dan penebalan tubular basement membranes.
Pyelonephritis, inflamasi akut atau kronis pada ginjal biasanya dimulai di jaringan
interstitial dan menyebar ke afferent tubules.special pattern pada acute pyelonephritis yaitu
necrotizing papillitis (papillary necrosis), banyak terjadi di pasien diabetes dibanding yang
tidak DM.
- Natural history :
Bergantung kepada type DM, pada type 1 untreated DM, sekitar 80% pasien with
sustained microalbuminuria meningkatkan albumin ekresi 10-20% per tahun hingga
nephropathy berkembang. Dengan berkembangnya nephropathy, GFR menurun 2-
20ml/menit/tahun dan ESRD berkembang sekitar 50 % within 10 years dan sekitar 75%
within 20 years. Albuminuria dan penurunan GFR, dengan penebalan glomerular basement
membrane dan ekspansi mesangial dapat dideteksi as early as 2-8 years after onset DM.
In type 2 DM, kebanyakan diabetic nephropathy, pada saat di diagnosis DM type 2 dapat
tidak disadari dalam beberapa tahun. 20-40% type 2 DM dengan microalbuminuria terjadi
nephropathy dan sekitar 20% berkembang ESRD setelah perkembangan nephropathy.
1. Stage 1: Renal pathology develops at the onset of diabetes. The growth of the
kidney increases by several centimetres. By the time of diagnosis, the GFR and
urinary albumin excretion (UAE) have been increased. It can be controlled at
this level by onset of insulin
2. Stage 2: The second phase typically lasts for 5-15 years after diagnosis of
diabetes. The characteristics of the second phase include: 1. GFR remains
elevated due to hyperfiltration. 2. Kidneys remain hypertrophied and UAE rate
stays normal.
- Metabolic Abnormality
Dyslipidemia :
Most patients with DN have dyslipidaemia, characterised by low levels of HDL cholesterol, high
triglycerides (TG levels), and a shift from larger towards smaller LDL cholesterol. Dyslipidaemias
in diabetic patients may contribute to the development of glomerulosclerosis and progressive
renal disease.
- Pat-Pat
- Diagnosis
‘
- Classification
- Treatment :
In both types of diabetes, persistent proteinuria is a common finding. Long-term studies show that the
life expectancy of type 1 diabetic patients is approximately 10 years after the onset of proteinuria, with
two-thirds of deaths related to end stage renal failure (ESRF) and one third to cardiovascular disease.
In type 2 diabetes, due to the presence of comorbid conditions and cardiovascular disease in those with
overt nephropathy, the risk of mortality is so extraordinary that many die before they reach end-stage
renal failure (ESRF)
According to NICE guidelines, the following patients should be referred early to the specialist :
4) Hypertension that remains poorly controlled despite use of at least four antihypertensive drugs at
therapeutic doses
The mortality of DN patients is extremely high. For example, patients with type 1 diabetes have a
mortality 20 times greater than that of the general population, and this relative risk may be magnified by
a further 25 times for those with proteinuria (e.g. 2 years mortality for 30% of patients with ESRD). The
mortality of DN patients is largely the result of comorbid cardiovascular disease. Most patients with
stage 4 DN die before they reach ESRF.
Sumber :
Robbin, harrison
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206379/pdf/ijnrd-7-361.pdf
https://www.hindawi.com/journals/jdr/2015/697010/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4484995/
https://link.springer.com/article/10.1007/s13410-011-0055-x
http://www.aafp.org/afp/2012/0501/p883.html
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083882/pdf/WJD-1-48.pdf
http://www.jnephropharmacology.com/PDF/NPJ-3-15.pdf