What is diabetic nephropathy?
Diabetic nephropathy, also Kimmel stem-Wilson syndrome intercapillary glomerulonephritis, glomerulosclerosis nodular diabetic glomerulosclerosis or, is a progressive kidney disease due to angiopathy of capillaries of the renal corpuscle. The characteristic histologic feature is a nodular (lat. Nodular) connective tissue (nodular sclerosis). Cause of diabetic nephropathy is a long-standing diabetes mellitus. Diabetic nephropathy is the most common cause of Germany in dialysis-dependent renal failure.
Epidemiology
The syndrome may occur in patients with long-standing diabetes mellitus poorly controlled (ie permanently high blood sugar levels), regardless of the cause of diabetic metabolic disorder. The disease is progressive and, if left untreated, lead within two to three years after the occurrence of the first changes in the complete loss of kidney function. In Germany in 2005 was diabetic nephropathy with a share of 35% common cause of new onset renal insufficiency requiring dialysis. In developing countries, in recent years, especially in poorer on the acquisition of a Western lifestyle with cheap, energy-rich food and lack of exercise, a dramatic increase in diabetes mellitus type 2 Watch and thus of diabetic nephropathy. Since in these countries a dialysis treatment is not generally available, the diagnosis usually is tantamount to a death sentence. Particularly affected are India and China.
Diabetic nephropathy pathology
Changes in the renal (glomerular) occur in patients with longstanding diabetes on prior to the detection of albumin in the urine.
2010. Classification of diabetic nephropathy has been published on the severity of histological lesions:
Class I: thickening of the glomerular basement membrane (women> 395 nm, in men> 430 nm).
Class IIa: Mild broadening in more than 25% of the observed mesangium (connective tissue between the capillary loops of the renal corpuscle): The mesangium is no wider than the lumen of the capillary loops.
Class IIb: Heavy broadening 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 (nodular) scarring (sclerosis) of the capillary loops with storage of structureless material (hyaline) (Classical Kimmel stem-Wilson lesion).
Class IV: Advanced diabetic glomerulosclerosis: More than 50% of the glomeruli are completely healed.
Pathogenesis of diabetic nephropathy
We discuss several mechanisms that can lead to diabetic nephropathy:
-An extension of the renal vessels or pressure by hyaline deposits lead to an increase in pressure within the renal corpuscle, this leads to an increased filtration (hyperfiltration), this in turn leads to scarring of the renal corpuscle (nephrosclerosis).
-The increased blood sugar levels leading to increased deposition of intercellular substance (matrix) in the glomeruli, additional glucose binds to the matrix proteins.
-The increased blood sugar levels also leads to the binding of glucose to tissue proteins.
-A variety of growth and differentiation factors seem to be involved in the pathogenesis of diabetic nephropathy, are of particular importance TGF-β and VEGF (Vascular Endothelial Growth Factor). The second option is believed to play an essential role by increasing its systemic concentration. Also inflammatory cytokines, in particular interleukin-1, interleukin-6, interleukin-18 and TNF-α are involved in development and progression of diabetic nephropathy.
-The structural protein nephrin, which is the final, most selective filtration membrane of the three-layered blood-urine barrier is reduced in diabetic nephropathy.
-Elevated blood sugar and hyperfiltration bring about increased expression of the glucose transporter GLUT-1 in mesangial cells of the renal corpuscle. This leads to increased glucose uptake and activation of excessive glucose-dependent pathways. Result is ultimately an increased formation of TGF-β. The upregulation of TGF-β promotes excessive production of extracellular matrix. In addition, TGF-β promotes the expression of GLUT1 and so maintains the pathomechanism.
-Elevated blood sugar inhibits the expression of thrombomodulin in the endothelial cells of the renal corpuscles. Thrombomodulin activated protein C. Activated protein C prevents hyperglycemia-induced programmed cell death (apoptosis) of endothelial cells and podocytes of renal corpuscle. Decreases thrombomodulin expression, it comes to an increased destruction of renal corpuscles.
Microalbuminuria
The earliest signs of diabetic nephropathy is the detection of an increased excretion of albumin in the urine. Normally, the kidneys excrete 20 mg albumin within 24 hours (Normalbuminurie). Excretion of 30 to 300 mg of albumin per day is referred to as microalbuminuria, the excretion of more than 300 mg per day as albumin or macroalbuminuria proteinuria. Microalbuminuria is not detectable using conventional urine test strips. Gold standard is the determination of albumin in urine was collected over 24 hours. The simultaneous determination of albumin and creatinine in urine and calculation of the albumin-creatinine ratio can be dispensed with collecting the urine: Microalbuminuria is defined by an albumin / creatinine ratio of 30 to 300 mg / g, macroalbuminuria by an albumin / creatinine -Quotienten> 300 mg / g. For early detection, special test strips are used to detect low concentrations of albumin in the urine (so-called Mikraltest).
Diabetic nephropathy diagnosis
In patients with diabetes mellitus (DM) is a chronic kidney disease caused by diabetic nephropathy, but also by other renal diseases. It should therefore be sought in patients with DM and kidney disease for the cause of renal involvement. Patients with DM should be tested 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 screening examination of the albumin / creatinine ratio in urine and creatinine in the serum. From serum creatinine, glomerular filtration rate is estimated as a measure of renal function using an approximation formula. Appears in 2 of 3 urine samples micro- or macroalbuminuria a determined, there is a chronic renal injury. Diabetic nephropathy is almost certainly caused at macroalbuminuria in microalbuminuria after at least 10 years of duration of type 1 diabetes and microalbuminuria and co-existing diabetic retinal damage (diabetic retinopathy). In the absence of diabetic retinopathy, should be considered another cause of kidney damage. Another cause is contemplated in poor or rapidly deteriorating renal function rapidly increasing proteinuria (proteinuria) or nephrotic syndrome, untreatable high blood pressure, red blood cells (RBCs) or erythrocytes cylinders in the urine, signs or symptoms of other systemic diseases or a decrease in the glomerular filtration rate of more than 30% within 2 to 3 months after initiation of treatment with an ACE inhibitor or AT1 antagonists.
Risk factors of diabetic nephropathy
Not all diabetics develop diabetic nephropathy. Family studies show a strong influence of heredity (genetic predisposition). Men carry a higher risk than women. The risk of disease increases with poor glycemic control. Is diabetic nephropathy already occurred, the next steps depend primarily on a consistent lowering of blood pressure, metabolic optimization should also be sought. The increase in protein excretion in the urine indicates the progression of the disease. Halving the protein excretion by drug therapy halved the risk of renal failure. Other risk factors include elevated blood lipids, and cigarette smoking.
Diabetic nephropathy symptoms
-Exist at the stage of microalbuminuria and proteinuria in the early stages of any discomfort, however, can lead to an increase in blood pressure. At this stage, the disease can only be detected by determination of microalbuminuria.
-Increases the protein excretion (proteinuria) in the course of the disease continues to rise, it may come to Nephrotic syndrome. The nephrotic syndrome is defined by a proteinuria of more than 3.5 g per 24 hours, water retention in the tissues (edema) and high blood fats (hyperlipidemia). As a visible consequence of the increased protein content for the patient froths the urine. The water retention leading to swelling, mainly in the legs and eyelids, the water retention it comes to weight gain. As a complication of blood clots (venous thrombosis), and urinary tract infections can occur.
-In the further course of the disease leads to chronic renal failure. Already at the stage of microalbuminuria, the risk of life-threatening complications of the cardiovascular system is increased, and increases with increasing renal impairment dramatically. Symptoms of chronic renal failure occur only in end-stage uremia. The uremic syndrome manifests itself in decreasing performance, general malaise, fatigue, itching, loss of appetite, nausea and vomiting.
Diabetic neuropathy treatment
For prevention of diabetic nephropathy following measures are recommended:
-Strict glycemic control, possibly setting on intensified insulin therapy. For therapy monitoring of HbA1c is determined in the blood. This should be less than 6.5-7.5%, depending on age and comorbidities of the patient.
-Drug lowering blood pressure to below 130/80 mmHg. As a drug of first choice are ACE inhibitors or AT1 antagonists, usually recommended in combination with a diuretic. Even in patients with a baseline blood pressure below 120/80, a further reduction in blood pressure reduce the risk of diabetic nephropathy on.
-Prevention of cardiovascular complications by reducing blood fat, for, as by a statin and taking low-dose acetylsalicylic acid (ASA).
The treatment of diabetic nephropathy has two main objectives:
-Reduce the risk of cardiovascular complications such as heart attack or stroke
-Inhibiting the progression (progression) of renal impairment.
The beneficial effect of ACE inhibitors and AT1 antagonists is explained by an inhibition of hyperfiltration and renal scarring. If the protein excretion greater than 1 g / 24 h, blood pressure should be even lowered to values below 125/75 mmHg. Treatment goal is / reduce proteinuria under 0.5-1 g of 24 as a higher protein excretion leads to a progressive deterioration of renal function. Is this therapeutic goal can not be achieved with conventional measures, a combination of ACE inhibitors and AT1 antagonist or a treatment at very high dose is recommended recently. Perhaps a combination treatment consisting of AT1 antagonist and aliskiren has a beneficial effect. However, the combination of aliskiren treatment with AT1 antagonists or ACE inhibitors is contraindicated in February 2012 due to the results of the ALTITUDE study. If there is a macroalbuminuria should even be treated with normal blood pressure with an ACE inhibitor or AT1 antagonists in microalbuminuria this treatment should be taken at least. Goal of therapy in patients with diabetic nephropathy and normal blood pressure is to reduce the albumin excretion in the urine.
Patients with diabetes and renal involvement may actively contribute to the success of treatment
-Regular blood glucose self-checks and, if necessary, adjustment of medication,
-Regular blood pressure self-control,
-Compliance with dietary recommendations (low proportion of animal fats, sodium-reduced)
-Smoking cessation,
-Regular exercise,
-Regular medication.
Decreases the renal below 60% of normal, disorders of bone metabolism, blood formation, acid-base and electrolyte imbalance can occur. For the prevention and treatment of these sequelae see Chronic renal failure.
In renal below 15% of normal renal replacement therapy is necessary to choose between hemodialysis (HD), peritoneal dialysis (peritoneal dialysis) or transplantation. In patients with type 2 diabetes occurs in the transplantation of a kidney transplant only in question in patients with type 1 diabetes, the combined transplantation of kidney and pancreas (pancreatitis) may be possible.
Pregnancy and diabetic nephropathy
Pregnancies in patients with diabetic nephropathy are high-risk pregnancies and should multidisciplinary (gynecologist, diabetologist, nephrologist) are supported. ACE inhibitors and AT1 antagonists may, taken before pregnancy, reduce the maternal and fetal risk. But both agents should be discontinued immediately after the first failed menstrual period or after a positive pregnancy test because, taken during pregnancy increase the risk of childhood malformations. Is in a patient with diabetes and kidney disease drug therapy of diabetes during pregnancy required, this must be done with insulin. For blood pressure control is used primarily alpha-methyldopa, alternative substances are selective β 1 receptor blockers or hydralazine.