Kidney Disease (Nephropathy): American Diabetes Association®
Jul 28, Keywords: Type 2 diabetes, Diabetic kidney disease, Diabetes we detail the relationship between diabetes and kidney disease, addressing. May 30, Diabetes is the most common cause of kidney failure in the U.S. Kidney damage from Diabetes is called Diabetic Nephropathy. Your doctor; Juvenile Diabetes Research Foundation Australia Tel. 4 KIDNEY ( ), TTY Back to top . Hyperglycaemia means too much glucose is circulating in the blood. . Reiki, Relationship counselling, Relaxation therapy, Respite care, Rheumatology.
Insulin resistance IR is one of the pillars dictating the pathogenesis of DM2 and may differ according to body tissues. However, where does IR begin? Some authors argue it starts in the liver, others in the muscle, and others in the brain. What we know is that IR is present in various body tissues liver, peripheral muscle, central nervous system, adipocytes, etc.
Several studies show that insulin has an anorexigenic action in the central nervous system [ 3 — 5 ]. However, the caloric intake in obese individuals is enhanced even in the presence of hyperinsulinemia, suggesting a clinical picture of IR in the brain [ 2 ].
Regarding peripheral IR, it is well established that IR directly correlates with deposits of visceral [ 6 ] and intramyocellular within the myocyte fat [ 78 ]. In the muscle, when deposition of intramyocellular fat occurs, especially in the cytoplasm far from mitochondria, cytoplasmic diacylglycerol production increases, which leads to a decreased membrane expression of GLUT4, subsequent reduction of muscle glucose uptake, and hyperglycemia [ 7 ].
Diabetes mellitus and renal failure: Prevention and management
Hyperglycemia is not observed in a clinical picture of impaired glucose tolerance or pre-diabetes, since hyperinsulinemia can still compensate for IR and maintain normal levels of blood glucose. When hyperinsulinemia can no longer compensate for IR and insulin secretion begins to decline, the disruption of these variables results in hyperglycemia and a diagnosis of DM.
In the early stages of DM2, the clinical picture of hyperinsulinemia persists. However, reduced insulin secretion is mainly responsible for the clinical picture of hyperglycemia. In the later stages of the disease, IR persists.
However, the clinical picture, characterized by deficient insulin secretion, worsens, thus exacerbating the loss of glycemic control. The gold standard to evaluate insulin resistance is the euglycemic insulin clamp technique.
However, this technique is difficult to perform, expensive to apply, and is only used in clinical studies [ 9 ]. On the other hand, the Matsuda index can estimate hepatic and peripheral insulin sensitivity, using glycemia and insulinemia values obtained through an oral glucose tolerance test [ 11 ].
In addition to IR, insulin deficiency is essential to manifest hyperglycemia in DM2. There are several factors involved in the process of insulin secretion, and incretins are one of the most important. Incretins are hormones secreted by the gut that have different functions upon binding to their receptors, expressed in various organs and tissues. There are two main incretins: Both are involved in glucose homeostasis. When released into the circulation, GLP-1 binds to its receptor, which is expressed in different tissues, and promotes different actions.
The GLP-1 receptor is a G-protein-coupled receptor, and binding activates adenylyl cyclase, leading to a subsequent increase in cyclic adenosine monophosphate, which activates protein kinase A and increases the release of insulin [ 14 ].
It is worth noting that incretins stimulate glucose-dependent insulin secretion, i.
The GLP-1 receptor is expressed in multiple organs besides the pancreas, such as the intestine, kidneys, heart, and central nervous system. It exerts different functions in different tissues: A decreased effect of incretins affects not only the secretion of insulin, but also other beneficial effects promoted via the GLP-1 receptor. This supports several modern proposed DM2 pharmacological therapies aimed at improving the effects of incretins.
In addition to the pancreas, adipocytes, liver, and intestines, the kidneys also play important roles in glycemic control. Increase in the level of ROS, which induces oxidative stress, has been considered the major cause of renal failure.
Other than diabetes, renal failure itself also increases oxidative stress. The morphologic characteristics of diabetic nephropathy include tubular atrophy, glomerular hypertrophy, arteriolar thickening, basement membrane thickening, mesangial expansion, and interstitial fibrosis, which are among the microvascular complications of diabetes. Recent research studies have determined that both high glucose-induced changes in antioxidant function and high glucose-induced cellular ROS production contribute to the diabetes induction of renal failure.
Treatments that target one or more diabetes-induced alterations for the regulation of ROS might lead to effective protection against or treatment of diabetic kidney disease.
In this regard, the use of antioxidants seems to be effective in diabetes and protection against kidney disease. In this regard, it is better that we try using plants that have shown good results for controlling both DM and kidney disease. Control of hypertension with medications that modulate the renin-angiotensin system RAS has been shown to decrease the incidence as well as progression of diabetic kidney disease. Furthermore, several new approaches, including the consumption of antifibrotic agents, endothelin receptor antagonists, inhibitors of advanced glycation end-products AGEsreceptor antagonists of advanced glycation end-products; growth factors and protein kinase C; oxidase inhibitors; NADPH; and glycosaminoglycans has shown promising results in preventing the progression of diabetic nephropathy.
Moreover, tight control of blood glucose may increase the risk of hypoglycemic attacks. Tight glycemic control increases the risk of hypoglycemia in dialysis patients, especially patients with reduced appetite; Symptoms of hyperglycemia in dialysis patients are less than those in patients without kidney failure.
Despite these evidences, some researchers suggest that damage to organs such as the eyes and heart will increase if blood sugar levels do not stay within an acceptable range. Therefore, based on the recent scientific evidence, it is recommended that glycemic control be considered as the main therapeutic goal in the treatment of diabetic patients with ESRD, too.
Therefore, monitoring of blood glucose levels will help in early detection.
Kidney Disease (Nephropathy)
This should be even more serious for patients with peritoneal dialysis because of their exposure to high glucose concentrations during peritoneal dialysis. This study also showed an inverse relationship between 3-year survival of patients and poorly controlled blood sugar.
Thus, it is essential to know the metabolism of these drugs in ESRD patients, and they are briefly discussed below. Sulfonylureas Sulfonylureas, which are widely used to treat type 2 diabetes, stimulate insulin secretion from pancreatic beta cells.
These drugs inhibit the adenosine triphosphate ATP -dependent channels by binding to their receptors in pancreatic beta cells, leading to calcium influx and stimulation of insulin secretion. Thus, sulfonylureas are only effective in diabetic patients with some remaining beta cell function. These drugs have been reported to increase tissue sensitivity to insulin, but the clinical importance of this effect is negligible.
These drugs are usually used in patients whose weight is normal or slightly increased. These drugs should not be used in patients who are losing weight, or are ketotic despite adequate caloric intake. In these cases, insulin should be used. Chlorpropamide and tolbutamide are substantially excreted by the kidney in patients with normal renal function, but in patients with chronic kidney disease, the elevated serum levels caused by these drugs may cause severe hypoglycemia.
Active metabolites of glibenclamide are also excreted by the kidney and increased serum levels caused by them have been observed in patients with renal failure.
Glimepiride is similar to glibenclamide in this aspect. Therefore, glipizide is considered the oral hypoglycemic drug of choice from this group of drugs for patients with CRF. The recommended initial dose for patients with normal renal function is 2. The recommended dose for patients with renal failure is 2.
Biguanides reduce glucose production and release by the liver, increase insulin-stimulated glucose uptake by all peripheral tissues such as muscles, and decrease plasma levels of free fatty acids, and thus gluconeogenesis.
The most serious side effect of metformin is lactic acidosis, which happens rarely. This drug is usually excreted unchanged by the kidney, and its administration to patients with renal failure can cause drug retention and lactic acidosis. Both these drugs and their metabolites are not retained in kidney failure; however, they can cause heart failure in patients receiving insulin.
The administration of these drugs should be avoided in patients with ESRD, especially if they also have heart failure. The plasma levels of acarbose and its metabolites increase in patients with renal failure, but their relationship with an increased risk of hypoglycemia has not been established.
Miglitol is also significantly excreted by the kidneys and expected to increase in the serum of patients with renal failure, so their administration is not recommended in patients with renal insufficiency. They are short-acting blood glucose-lowering medicines. Although their structural features and receptors are different from sulfonylurea, they also increase insulin secretion from pancreatic beta cells through ATP-dependent potassium channels.
The suggested dose of nateglinide is mg before every meal. Although nateglinide is metabolized by the liver, its active metabolites are excreted by the kidney.
In renal failure, active metabolites accumulate and cause hypoglycemia, so this drug should be used carefully or not prescribed in patients with renal failure. Thus its use may be allowed in patients with ESRD. Therefore the recommended starting dose of this drug for patients with renal failure is 0. These adjustments are general, and insulin dosage adjustments should be based on regular blood glucose measurements.
It should be noted that correction of uremia with dialysis on the one hand reduces insulin resistance and on the other hand increases insulin degradation; the ultimate effect of these on glycemic control in patients is different and glycemic control should be based on the final effect. These facts are clinically important in the treatment of diabetes. Although insulin resistance increases the insulin requirement, decreased insulin degradation reduces the need for administration of insulin in diabetic patients with advanced CRF, which increases the risk of hypoglycemia.
Severe hyperglycemia in oliguric or anuric ESRD patients is not associated with features of osmotic diuresis, which is seen in patients without renal failure, but it can cause hyponatremia, hyperkalemia, and acute increase in the intravascular volume. In several large studies on ESRD patients, there was no correlation between increased survival and tight blood glucose control of patients.
It is suggested that the incidence of hypoglycemia was significantly higher in patients receiving strict glycemic control. It is recommended that blood sugar control be considered an important goal in the treatment of ESRD diabetic patients to prevent additional damage to other organs including the eyes, kidneys, and heart.
The factors determining perfect glycemic control are the following: Glipizide, an oral hypoglycemic agent, is administered at a daily dose of 2.
Although thiazolidines and their metabolites are not retained in kidney failure, they can lead to edema and cardiac failure, particularly in patients receiving insulin. Hence their use has been prohibited in patients with advanced renal failure, particularly if they also have heart failure.
Thus its use in ESRD patients may be allowed with meticulous care and with regard to the risk of hypoglycemia. Lactic acidosis is a rare but potentially fatal complication of metformin, so the administration of this drug should also be avoided in CRF patients.
Insulin can be administered subcutaneously or intraperitoneally in patients on peritoneal dialysis with safety and accurate monitoring. DM induces renal failure, which increases oxidative stress and oxidative aggravate them.
Therefore, the use of antioxidants, especially the ones which are effective in treating these two diseases,[,] should be beneficial. Financial support and sponsorship There was no funding for this manuscript. HN provided critical revisions of the manuscript. Acknowledgments There was no financial support for this manuscript.
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J Renal Inj Prev.
Diabetic Nephropathy | Diabetic Kidney Disease | MedlinePlus
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