Oct 13, Diabetic nephropathy is a common kidney disease in people with diabetes. Learn how treating your diabetes may help prevent serious. Diabetic nephropathy (diabetic kidney disease) is kidney damage that results from having diabetes. Having high blood glucose levels due to diabetes can. May 3, Diabetic nephropathy is a clinical syndrome characterized by the following: Persistent albuminuria (> mg/d or > μg/min) that is.
PCK activation leads to increased vascular permeability, increased synthesis of extracellular matrix components, and increased production of reactive oxygen species ROS , which are important mediators of kidney injury [ 40 ]. The regulation of heparanase expression plays an important role in the pathogenesis of diabetic nephropathy.
The reduction in heparin sulfate on the surface of endothelial cell changes the negative charge of glycocalyx and consequently increases albumin permeability of the glomerular filtration membrane [ 41 ]. Increasing evidence shows the importance of reactive oxygen species ROS in the pathogenesis of diabetic nephropathy.
Although the ROS production may be influenced by numerous mechanisms, the most important role in their production is played by superoxide produced by glycolysis and oxidative phosphorylation in the mitochondria. ROS activate all important pathogenetic mechanisms, such as increased production of AGEs, increased glucose entry into the polyol pathway, and PKC activation [ 42 ].
In addition, ROS directly damage endothelial glycocalyx, which leads to albuminuria without the concurrent damage to the GBM itself. Increased serum prorenin plays a role in the development of diabetic nephropathy in children and adolescents [ 43 ]. Prorenin binds to a specific tissue receptor, leading to the activation of the signal pathway of mitogen-activating protein kinases MAPK , which potentiate the development of kidney damage [ 44 ]. Using an experimental model of diabetic nephropathy, Ichihara et al.
In their study, a prolonged prorenin receptor blockade cancelled the activation of MAPK, which prevented the development of diabetic nephropathy despite the increased activity of angiotensine II. Hyperglycemia stimulates increased expression of different growth factors and activation of cytokines, which overall contributes to further kidney damage [ 46 , 47 ].
In the kidney biopsy samples from patients with type 2 DM, a significant increase in platelet derived growth factor PDGF expression was found. Moreover, the site of expression of this factor is adjacent to the areas of interstitial fibrosis, which is important in the pathogenesis of fibrosis in kidney injury [ 48 ]. Hyperglycemia also increases the glomerular expression of TGF-beta; matrix proteins are specifically stimulated by this growth factor [ 49 ].
Furthermore, the expression of bone morphogenic protein 7 BMP-7 in DM is decreased, and the expression of profibrinogenic TGF-beta is increased [ 50 , 51 ]. Nephrine is a transmembrane protein, the main structural element in slit diaphragm and as such, it is important for the maintenance of filtration membrane integrity.
More recent studies have shown the association between the decreased expression of nephrine and albuminuria progression in the model of human diabetic nephropathy [ 52 , 53 ]. There are several risk factors for the development of diabetic nephropathy. They can be divided into those that cannot be altered genetic factors, age, and race and those that can and must be changed hyperglycemia, hypertension, dyslipidemia, and GFR [ 53 ].
Genetic predisposition substantially determines the occurrence and severity of diabetic nephropathy [ 18 , 40 ]. The likeliness of diabetic nephropathy is higher in siblings and children of parents with diabetic nephropathy, independently of the type of DM [ 54 ]. This increased risk cannot be explained by the duration of DM, increased blood pressure or gycemic regulation.
However, genetic predisposition for excessive salt intake and arterial hypertension could play a role. Although likeliness of chromosomes 3, 7, 18, and 20 to be associated with diabetic nephropathy is relatively high, we still cannot confirm the role of particular predisposing genetic determinants due to inconsistent results of the studies of genetic factors important in the development of this disease.
The incidence of diabetic nephropathy is increased in African American, Mexican American, and Asian Indian ethnic groups. Occurrence and severity of the disease are higher in Blacks 3- to 6-fold in comparison with Caucasians , American Mexicans, and especially in Pima Indians in the North West part of the United States [ 55 ].
This observation in genetically incongruent populations suggests that socioeconomic factors, such as nutrition and poor control of glycemia, blood pressure, and body weight, play the key role.
In patients with type 2 DM, age and duration of DM increase the risk for albuminuria [ 53 ]. In the population study of Pima Indians with type 2 DM, subjects diagnosed with DM before age 20 had a higher risk of developing terminal kidney failure 25 vs.
According to Svensson et al. Moreover, at least three factors have been shown to contribute to the development of increased arterial pressure in this metabolic disorder including hyperinsulinemia, excessive extracellular fluid volume, and increased arterial rigidity.
Hyperinsulinemia contributes to the development of increased arterial pressure via insulin resistance in type 2 DM or via administration of insulin per se. This hypertensive response, although not reported in all clinical studies, is most likely mediated by weight gain combined with pro-hypertensive effect of insulin. Hyperinsulinemia could be the link between overweight and increased blood pressure in patients with or without DM, since it increases sympathetic activity and retention of sodium in the kidneys.
Sodium and water retention are induced by insulin itself, while the increased filtration of glucose is induced by hyperglycemia.
The excess filtered glucose is reabsorbed as long as there is a moderate hyperglycemia in the proximal tubule via sodium-glucose co-transport, which concurrently leads to the increase in sodium reabsorption [ 59 ]. Sodium reabsorption increases blood pressure, which may be prevented and regulated by salt-free diet. Patients with DM have increased arterial stiffness, which develops due to the increased glycation of proteins and consequent development of arteriosclerosis. Decreased arterial elasticity in patients with glucose intolerance or DM contributes to the increased systolic pressure as an independent mortality risk factor [ 60 ].
Increased GFR at diagnosis is a risk factor for the development of diabetic nephropathy. These patients have a higher risk of developing diabetic nephropathy [ 61 ]. Dynamics of structural and hemodynamic changes is influenced by increased intraglomerular pressure, with the resulting glomerular hyperfiltration and hypertrophy and damage to the endothelial wall. Strict glycemic control, limited protein intake, and blood pressure control may slow down the progress of renal disease in type 1 DM [ 62 ].
The situation with type 2 DM is somewhat different. Patients with type 2 DM are older and, therefore, have greater likelihood of developing atherosclerotic vascular changes that influence GFR and glomerular size [ 64 ]. The role of intraglomerular hypertension in the pathogenesis of diabetic nephropathy explains why systemic hypertension is such an important risk factor for the development of this kidney disease [ 65 ]. Studies on animal models showed that DM is associated with damage of renal autoregulation.
As a result, increased blood pressure does not induce the expected vasoconstriction in the afferent arteriole, which would reduce the influence of systemic hypertension on intraglomerular pressure [ 66 ]. Diabetic nephropathy often develops in patients with poor glycemic control. The degree of glycemic control is an important predictor of terminal kidney failure [ 67 ].
It is generally accepted that the degree of glycemic control is a very important risk factor for the development diabetic nephropathy. High body mass index BMI increases the risk of development of chronic kidney disease in patients with DM [ 53 ]. Furthermore, adequate diet and reduction in body weight decrease proteinuria and improve kidney function in these patients [ 69 ]. The role of overweight as a risk factor for diabetic nephropathy independent of DM and glycemic control has not been clearly confirmed.
Although recent studies have shown the association between smoking and progression of diabetic nephropathy, a large prospective study by Hovind et al.
Each of the above-described factors increases the risk of diabetic nephropathy, but none is predictive enough for the development of diabetic nephropathy in an individual patient. Patients with type 1 DM and nephropathy almost always have other complications related to the underlying disease, such as retinopathy and neuropathy [ 9 ].
Retinopathy has easily recognizable clinical manifestations and always precedes the clinically manifest signs of nephropathy in the same patient. The vice versa is not the case. A small number of patients with advanced retinopathy have glomerular histological changes and microalbuminuria, but most have no biopsy evidence of kidney disease [ 72 ].
The association between diabetic nephropathy and retinopathy is weaker in patients with type 2 DM. In a study carried out by Parving et al. Diabetic retinopathy was present in 15 of these 27 patients and in none of the eight patients without diabetic nephropathy. Further analysis showed that approximately one-third of patients without retinopathy had no biopsy evidence of diabetic nephropathy [ 74 ]. Thus, patients with type 2 DM and significant proteinuria and retinopathy were most likely to develop diabetic nephropathy, whereas those with proteinuria but without retinopathy had a greater likelihood of having an underlying non-diabetic kidney disease [ 75 ].
In the study by Schwartz et al, biopsy was performed in 36 patients with type 2 DM and nephropathy. In 17 of them, biopsy showed visible glomerulosclerosis with Kimmelstiel-Wilson nodules, whereas in the remaining 15 patients, biopsy showed changes characteristic of diabetic nephropathy mesangial sclerosis , but with no classical nodules present.
There was no difference in the duration of disease and glycemic regulation between patients with and those without nodules. A strong association was found between severe retinopathy and presence of Kimmelstiel-Wilson nodules. The reason is still unknown [ 76 ]. In case that no retinopathy is present, non-diabetic causes of kidney disease should be investigated.
Albuminuria remains the only biomarker acceptable for diagnostic purposes, although some growth factors are expected to replace albuminuria in future. Proteinuria is sometimes present in DM because of the primary glomerular disease rather than diabetic nephropathy. The main clinical signs of primary glomerular disease are as follows:. Proteinuria, which started in the first five years after the diagnosis of type 1 DM.
Latent nephropathy, is present between 10 and 15 years after the onset of type 1 DM. This period is probably the same in type 2 DM, but the exact time of the onset of the disease is difficult to determine.
The presence of erythrocytes mostly acanthocytes and rouleaux formations in urine sediment. The absence of diabetic retinopathy or neuropathy in patients with type 1 DM. As opposed to that, the absence of retinopathy in patients with type 2 DM does not exclude the presence of diabetic retinopathy. Proteinuria and kidney failure in patients with DM may also be caused by other diseases apart from primary glomerular diseases.
The most frequent cause is atherosclerotic vascular disease nephrosclerosis in older patients with type 2 DM [ 82 ]. This disease cannot be clinically discerned from diabetic nephropathy without kidney biopsy. However, kidney biopsy is not necessary in most cases, because the correct diagnosis in this patient group is not clinically important. What speaks in favor of nephrosclerosis is the significant increase in serum creatinine after the introduction of ACEI or ARB for the treatment of hypertension or slowing down the progress of chronic kidney disease.
The same occurs when there is a bilateral renal artery stenosis. The effect of strict glycemic control depends on the DM stage in which it was started and consequent normalization of glucose metabolism. Intensified insulin therapy has the following effects on the kidney:. It partly decreases glomerular hypertrophy and hyperfiltration in fasting state and after protein-rich meal , both of which are important risk factors for permanent glomerular damage.
It postpones the development of albuminuria [ 83 ]. Intensified insulin therapy that keeps glucose values within normal ranges decreases the development or progress of diabetic nephropathy.
It stabilizes or decreases the elimination of proteins in patients with pronounced proteinuria. This effect is not apparent in patients who are not relatively normogycemic during two years. Renal tubular acidosis proximal distal Acute tubular necrosis Genetic Fanconi syndrome Bartter syndrome Gitelman syndrome Liddle's syndrome. Interstitial nephritis Pyelonephritis Balkan endemic nephropathy. Renal artery stenosis Renal ischemia Hypertensive nephropathy Renovascular hypertension Renal cortical necrosis.
Cystitis Interstitial cystitis Hunner's ulcer Trigonitis Hemorrhagic cystitis Neurogenic bladder dysfunction Bladder sphincter dyssynergia Vesicointestinal fistula Vesicoureteral reflux. Diseases of the endocrine system E00—E35 , — Hypoglycemia beta cell Hyperinsulinism G cell Zollinger—Ellison syndrome. Iodine deficiency Cretinism Congenital hypothyroidism Myxedema Myxedema coma Euthyroid sick syndrome. Hyperthyroxinemia Thyroid hormone resistance Familial dysalbuminemic hyperthyroxinemia Hashitoxicosis Thyrotoxicosis factitia Graves' disease Thyroid storm.
Endemic goitre Toxic nodular goitre Toxic multinodular goiter Thyroid nodule. Primary Secondary Tertiary Osteitis fibrosa cystica. Cushing's syndrome Pseudo-Cushing's syndrome sex hormones: Polycystic ovary syndrome Premature ovarian failure testicular: Hypogonadism Delayed puberty Hypergonadism Precocious puberty Hypoandrogenism Hypoestrogenism Hyperandrogenism Hyperestrogenism Postorgasmic illness syndrome. Diabetes E10—E14 , Blood sugar level Glycosylated hemoglobin Glucose tolerance test Postprandial glucose test Fructosamine Glucose test C-peptide Noninvasive glucose monitor Insulin tolerance test.
Diabetic diet Anti-diabetic drugs Insulin therapy intensive conventional pulsatile Cure Embryonic stem cells Artificial pancreas Other Gastric bypass surgery. Glossary of diabetes Notable people with type 1 diabetes. Retrieved from " https: Kidney diseases Vascular diseases Diabetes.
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Abnormal levels of urinary albumin . If you have diabetes , your blood glucose, or blood sugar , levels are too high. Over time, this can damage your kidneys.
Your kidneys clean your blood. If they are damaged, waste and fluids build up in your blood instead of leaving your body. Kidney damage from diabetes is called diabetic nephropathy.
It begins long before you have symptoms. People with diabetes should get regular screenings for kidney disease.
Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects ∼40% of type 1 and type 2 diabetic. Diabetic nephropathy (DN), also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Protein loss in. Oct 13, Diabetic nephropathy refers to kidney disease that occurs in people with diabetes . The kidneys help regulate the amount of fluids and salts in.