Diabetic Nephropathy (Practical Diabetes)

A new class of anti-inflammatory drugs could offer a promising treatment for diabetic kidney disease (DKD) if the results of a Phase II trial are.
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Also noted is that microalbuminuria is not always predictive of diabetic nephropathy. Three major histologic changes occur in the glomeruli of persons with diabetic nephropathy. Second, thickening of the glomerular basement membrane GBM occurs. Third, glomerular sclerosis is caused by intraglomerular hypertension induced by dilatation of the afferent renal artery or from ischemic injury induced by hyaline narrowing of the vessels supplying the glomeruli.

These different histologic patterns appear to have similar prognostic significance. The key change in diabetic glomerulopathy is augmentation of extracellular matrix. The earliest morphologic abnormality in diabetic nephropathy is the thickening of the GBM and expansion of the mesangium due to accumulation of extracellular matrix. The image below is a simple schema for the pathogenesis of diabetic nephropathy.

Light microscopy findings show an increase in the solid spaces of the tuft, most frequently observed as coarse branching of solid positive periodic-acid Schiff reaction material diffuse diabetic glomerulopathy. Large acellular accumulations also may be observed within these areas. Immunofluorescence microscopy may reveal deposition of albumin, immunoglobulins, fibrin, and other plasma proteins along the GBM in a linear pattern, most likely as a result of exudation from the blood vessels, but this is not immunopathogenetic or diagnostic and does not imply an immunologic pathophysiology.

The renal vasculature typically displays evidence of atherosclerosis, usually due to concomitant hyperlipidemia and hypertensive arteriosclerosis. Electron microscopy provides a more detailed definition of the structures involved. In advanced disease, the mesangial regions occupy a large proportion of the tuft, with prominent matrix content. Further, the basement membrane in the capillary walls ie, the peripheral basement membrane is thicker than normal. The glomeruli and kidneys are typically normal or increased in size initially, thus distinguishing diabetic nephropathy from most other forms of chronic renal insufficiency, wherein renal size is reduced except renal amyloidosis and polycystic kidney disease.

In addition to the renal hemodynamic alterations, patients with overt diabetic nephropathy dipstick-positive proteinuria and decreasing glomerular filtration rate [GFR] generally develop systemic hypertension. Hypertension is an adverse factor in all progressive renal diseases and seems especially so in diabetic nephropathy.

The deleterious effects of hypertension are likely directed at the vasculature and microvasculature. Evidence suggests that hypertension associated with obesity, metabolic syndrome, and diabetes may play an important role in the pathogenesis of diabetic nephropathy. Central obesity, metabolic syndrome, and diabetes lead to increased blood pressure. Central obesity induces hypertension initially by increasing renal tubular reabsorption of sodium and causing a hypertensive shift of renal-pressure natriuresis through multiple mechanisms, including activation of the sympathetic nervous system and renin-angiotensin-aldosterone system, as well as physical compression of the kidneys.

Diabetic Nephropathy

Similar to obesity-associated glomerular hyperfiltration, renal vasodilation, increases in the glomerular filtration rate and intraglomerular capillary pressure, and increased blood pressure also are characteristics of diabetic nephropathy. The exact cause of diabetic nephropathy is unknown, but various postulated mechanisms are hyperglycemia causing hyperfiltration and renal injury , advanced glycation products, and activation of cytokines.

Many investigators now agree that diabetes is an autoimmune disorder, with overlapping pathophysiologies contributing to both type 1 and type 2 diabetes; and recent research highlights the pivotal role of innate immunity toll-like receptors and regulatory T-cells Treg.

Glycemic control reflects the balance between dietary intake and gluconeogenesis and tissue uptake or utilization through storage as glycogen or fat and oxidation. Insulin regulates serum glucose through its actions on liver, skeletal muscle, and fat tissue. When there is insulin resistance, insulin cannot suppress hepatic gluconeogenesis, which leads to hyperglycemia.

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Familial or perhaps even genetic factors also play a role. Certain ethnic groups, particularly African Americans, persons of Hispanic origin, and American Indians, may be particularly disposed to renal disease as a complication of diabetes. It has been argued that the genetic predisposition to diabetes that is so frequent in Western societies, and even more so in minorities, reflects the fact that in the past, insulin resistance conferred a survival advantage the so-called thrifty genotype hypothesis.


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Some evidence has accrued for a polymorphism in the gene for angiotensin-converting enzyme ACE in either predisposing to nephropathy or accelerating its course. However, definitive genetic markers have yet to be identified. More recently, the role of epigenetic modification in the pathogenesis of diabetic nephropathy has been highlighted.

What is diabetes mellitus?

A study by Bherwani et al suggested that an association exists between decreased serum folic acid levels and diabetic nephropathy. In the study, which involved patients with diabetes mellitus, including 50 with diabetic nephropathy and 50 without it, multivariate logistic regression analysis indicated that reduced folic acid levels increased the risk of diabetic nephropathy by In terms of diabetic kidney disease in the United States, the prevalence increased from in proportion to the prevalence of diabetes.


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Striking epidemiologic differences exist even among European countries. In some European countries, particularly Germany, the proportion of patients admitted for renal replacement therapy exceeds the figures reported from the United States. Exact incidence and prevalence from Asia are not readily available.

A study from the Netherlands suggested that diabetic nephropathy is underdiagnosed. Using renal tissue specimens from autopsies, Klessens et al found histopathologic changes associated with diabetic nephropathy in of patients with type 1 or type 2 diabetes. However, 20 of the patients did not during their lifetime present with the clinical manifestations of diabetic nephropathy.

A retrospective study from China, by Fan and Wang, indicated that in type 2 diabetes patients with renal injury, there is a high prevalence of nondiabetic renal disease NDRD. The investigators found that among 88 patients with type 2 diabetes who underwent renal biopsy, the incidence of NDRD was Membranous nephropathy, immunoglobulin A IgA nephropathy, and focal segmental glomerulosclerosis were the most common NDRDs identified.

The mean age of patients who reach end-stage kidney disease is about 60 years. Although in general, the incidence of diabetic kidney disease is higher among elderly persons who have had type 2 diabetes for a longer generation, the role of age in the development of diabetic kidney disease is unclear. In Pima Indians with type 2 diabetes, the onset of diabetes at a younger age was associated with a higher risk of progression to end-stage kidney disease.

The severity and incidence of diabetic nephropathy are especially great in blacks the frequency being 3- to 6-fold higher than it is in whites , Mexican Americans, and Pima Indians with type 2 DM. The relatively high frequency of the condition in these genetically disparate populations suggests that socioeconomic factors, such as diet, poor control of hyperglycemia, hypertension, and obesity, have a primary role in the development of diabetic nephropathy. Currently, the primary approach to slow nephropathy progression is to address the renin-angiotensinaldosterone system RAAS.

Guidelines have changed to include new findings about RAAS blockade. In the past, they've recommended RAAS blockade in all patients. A significant issue is the likelihood of chronic kidney disease CKD comorbid with diabetic neuropathy.


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Using RAAS blocking agents in certain patients can worsen renal outcomes. RAAS inhibition is no longer indicated for normotensive and normoalbuminuric individuals. In addition, studies have looked at diabetic patients with hypertension who were either normoalbuminuric or had high albuminuria. They found that regardless of whether a RAAS blocker or calcium channels blocker are employees, aggressive management of blood pressure slowed neuropathy. Most studies have failed to demonstrate any benefit from combining drugs that block RAAS. Acute kidney injury, hypotension and hyperkalemia are concerns.

One potential approach to using RAAS blockers in patients with advanced CKD might be addition of a drug that binds excess potassium in the colon.

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New potassium-binding agents may allow patients to continue full-dose RAAS inhibition. Patiromer, FDA-approved since October , is one such drug. If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click on download.

In common with all countries in the developed world, the United Kingdom is experiencing a dramatic increase in the incidence of diabetes and chronic kidney disease. The most common cause of renal impairment is diabetes. The evolution of diabetic nephropathy is usually predictable with evidence-based interventions available at each stage. This review examines this evidence and gives practical advice on the management of patients with diabetic nephropathy.

Br J Diabetes Vasc Dis , ; 8: Skip to main content. The problem of diabetic nephropathy and practical prevention of its progression. Vol 8, Issue 6, pp. Download Citation If you have the appropriate software installed, you can download article citation data to the citation manager of your choice.

Diabetic nephropathy - Clinical presentation & treatment (video) | Khan Academy

Via Email All fields are required. Send me a copy Cancel. Article first published online: November 1, ; Issue published: Keywords cardiovascular morbidity and mortality , diabetic nephropathy , renin—angiotensin system. Remember me Forgotten your password? Recommend to your library. Vol 8, Issue 6, Synthesis of substituted 2H-benzo[e]indazolecarboxylate as a potent antihyperglycemic agent that