The Diabetic Kidney Pathophysiological - Literature review Example

DIABETIC NEPHROPATHY PATHOPHYSIOLOGY Abstract Diabetic nephropathy is one of the major causes of cardiovascular mortality as well as the major cause of renal diseases. Measuring the content of albumin in the urine helps in the detection of diabetic nephropathy among the diabetic patients. Arterial hypertension and hyperglycaemia are considered to the two risk factors for diabetic nephropathy. Other risk factors include dyslipidemia, smoking, dietary factors, glomerular hyper filtration and proteinuria. The incident rates of diabetic nephropathy are higher in type 2 and type 1 diabetic patient. It is characterized by thickening of tubular and glomerular basal membranes as well as the expansion of the mesangial system. This lead to the reduction of the filtration surface of the glomerular. Patients suffering from type 2 diabetes experience more complex and heterogeneous renal lesions than patients suffering from type 1 diabetes. Diabetic nephropathy treatment is undertaken following multiple approaches. The goal of diabetic nephropathy treatment is to reduce or prevent the disease progression as well as reducing the risks of contracting heart related and cancerous diseases. In order to prevent microalbiminuria development and thus reduce the chances or renal leakage which causes diabetic nephropathy or damage of the kidney, treating of dyslipedemia and hypertension are considered the initial key steps of reducing further progression of diabetic nephropathy. Diabetic nephropathy pathophysiological mechanisms are not completely understood. However, some of the established pathophysiological mechanisms include hypertension and circulating glycosylation intrarenal proteins. Increased studies in this area have established that type 1 and type 2 diabetic patients have higher risks of developing diabetes nephropathy. However, due to the increased discovery of preventive measures targeting type 1 and type 2 diabetic patients, the incident rates of renal failure that cause kidney damage or diabetic nephropathy have also been on the decreasing trend. The purpose of this paper is to undertake a comprehensive review of diabetic nephropathy as one of the topics in diabetic kidney pathophysiology. Key words: Diabetic nephropathy, pathophysiology, renal failure, nephrons, ACE inhibitors, diabetes microvascualr complications. Introduction Diabetic nephropathy is one of the topics in diabetic kidney pathophysiology. According to the American Diabetes Association (2011) diabetic nephropathy can be defined as the damage or a kidney disease that occurs mainly in diabetic patients. Diabetic nephropathy results from the damage of the small units located in the kidney called nephrons. The function of nephrons is to remove waste from the body by filtering the blood. In diabetic patients, nephrons become scarred and thicken over time making it difficult for blood filtering and removal of waste (American Diabetes Association, 2011). This leads to the passage of protein in urine due to leakage that occurs in the kidney. It means therefore that diabetic nephropathy is the damage of the urinary system. The urinary system also called the excretory system comprises of the muscles, tubes, nerves and organs that work together to carry urine out of the body as a waste product. One of the key organs in the urinary system are the two kidneys. Hence, the leakage in the kidney results into passage of protein in the urine because the damaged kidneys are unable to filter and remove wastes from the body. This leads to diabetic nephropathy mainly in diabetic patients. Among the Data from the American Diabetes Association (2011) reveal that poor blood sugar control is thought to be the major cause of kidney damage in patients with diabetes that leads to the leakage of the kidneys. Other causes associated with diabetes nephropathy include high blood pressure and patients with type 1 diabetes with smoking habits (American Diabetes Association, 2011). Among the notable symptoms in patients with diabetes nephropathy include loss of appetite, tiredness, swelling of the feet, vomiting, headache and nausea (American Diabetes Association, 2011). Review According to American Diabetes Association (2011) diabetic nephropathy symptoms take more than 5 years to appear. Examination tests by the doctor particularly urine tests helps to diagnose the amount of protein in the urine. A high amount of protein in the urine is a sign of the extent of damage in the kidney. Other types of tests carried out to establish the presence of diabetic nephropathy include serum creatinine and BUN. Other tests that may be done in the lab to ascertain the presence of diabetes nephropathy include haemoglobin tests and hematocrit tests (American Diabetes Association, 2011). Inzucchi & Sherwin (2007) noted that the major goal of treating diabetic nephropathy is to ensure that the damage to the kidney does not get worse. As noted in the American Diabetes Association, high blood pressure is one of the key causes of diabetic nephropathy. Hence, Inzucchi & Sherwin (2007) observed that controlling the blood pressure is one of the key steps towards preventing further damage to the kidney in diabetic patients. Some of the medicines that can be use to control the blood pressure in diabetic patients include angiotensin receptor blockers (ARB) and ACE inhibitors. The authors held that controlling lipids, eating diets with low fat content and engaging in regular exercises are additional routines that can prevent further damage to the kidney in diabetic patients (Inzucchi & Sherwin, 2007). According to Parving, Mauer & Ritz (2007) persons with diabetic nephropathy experience three major changes. The first change is called mesangial expansion. This is condition brought about by direct hyperglycaemia inducement. This occurs through glycosylation and matrix production of matrix proteins (Parving, Mauer & Ritz, 2007). The second change experienced by diabetic nephropathy patients is glomerular basement membrane (GBM) thickening (Parving, Mauer & Ritz, 2007) and the third change is the occurrence of glomerular sclerosis in patients with diabetes nephropathy (Parving, Mauer & Ritz, 2007). Basing their studies on the three major changes experienced by patients with diabetic nephropathy, Perkins & Krolewski (2009) noted that hypertension and hyperglycaemia are the major risk factors for Diabetic nephropathy (Perkins & Krolewski, 2009, p.12). However, the authors noted that only 40% of patients develop diabetic nephropathy even when elevated blood pressure or hypertension and hyperglycaemia develop in patients with DN (Perkins & Krolewski, 2009, p.12). In this regard, it is evident that only a subset of diabetic patients develops the diabetic nephropathy condition which follows that not all diabetic patients are at risk of experiencing kidney damage. Introducing a new discovery in their study undertaken among the families with diabetic patients, the authors noted that diabetic nephropathy is genetically contributed. This is particularly the case among the patients with type 2 and type 1 diabetes. Bergman et al. (2007) noted that long-standing hyperglycaemia is one of the known risk factors that cause diabetic nephropathy (Bergman et al, 2007). The authors reiterated that hyperglycaemia condition results into mesangial injury and expansion through the increased concentration of mesangial glucose in the cells. The expansion of mesangial is fuelled by cell hypertrophy as well as cell proliferation (Bergman et al, 2007, p.1862). The other risk factor for diabetic nephropathy as established in the study undertaken by the authors is proteinuria. According to Bergman et al (2007, p.1864) proteinuria results into DN progression because it results into albumin leakage which induces the damage of the glomerular membrane (Bergman et al, 2007, p.1865). As a result, inflammatory cascades occur in the kidney resulting into further damage of the kidney among the diabetic patients. Reiterating the argument presented in American Diabetes Association (2011), Holman et al (2008) noted that thickening of glomerulus was the earliest change that could be detected among the patients with diabetic nephropathy. The authors agreed with previous studies above that glomerulus thickening results into the plasma protein leakage (albumin serum) leakage. Sensitive albumin medical tests are some of the best tests that can be used to detect any form of albumin leakage (Holman et al, 2008). However, the authors added that progressive glomerulosclerosis results into the destruction of glomerulus which increases the amount of albumin in the urine. At this stage, ordinary techniques for urinalysis can be used to detect albumin in the urine. Hence, a biopsy of the kidney at this stage shows the presence or severe kidney damage or diabetic nephropathy (Krolewski A, Fogarty D, Warram, 2008). The damage of the basement membrane is considered the central event in diabetic nephropathy pathophysiology (Kobrin, 2008). With the damage that occurs in the renal system, a pathologic change in vascular and mesangial cells occur as well as the thickening of the basement membrane (Kobrin, 2008, p214). Other problems that follow the damage of the renal system include SGEs formation, polyols accumulation via the reductase aldose pathway, kinase protein activation (Kobrin, 2008, p216). The author held that hypertension results into the progression of diabetic nephropathy and early intervention to prevent and treat hypotension is an important successful point of intervention towards prevention of diabetic nephropathy progression. As stated there above other risk factors that cause the progression of diabetic nephropathy include smoking. According to MacLeod & McLay (2008) smoking does not only result into diabetic nephropathy progression but it also results into higher chances of contracting cancer and cardiovascular diseases particularly among the patients with type 2 and type 1 diabetes. Hence, diabetic nephropathy patients must quit smoking in order to reduce the incident rate of suffering from heart related and cancerous disease (Krolewski, Fogarty &Warram, 2008). DeFronzo (2005) noted that the prevalence rate of hypertension is high in diabetic patients than in nondiabetic patients (DeFronzo, 2005, p.510). The author observed that hypertension results into diabetes microvascular complications. However, the control of hypertension reduced the amount of albumin, improves the health condition of type 2 and type 1 diabetic patient and delays the incident rates of diabetic nephropathic patients (DeFronzo, 2005, p.515). Hypertension control can be undertaken through the rennin-angiostensin mechanism which helps in the reduction of renal leakage. In order to effectively control hypertension among the diabetic nephropathic patients, the use of ACE inhibitors is advised as one way of decreasing microalbuminuria in order to prevent renal leakage, a factor, which causes progression of kidney damage (Krolewski, Fogarty & Warram, 2008). References American Diabetes Association. (2011). Standards of medical care in diabetes--2011. Diabetes Care. Jan; 34 Suppl 1:S11-61. Bergman, A et al. (2007). Effect of renal insufficiency on the pharmacokinetics of sitagliptin, a dipeptidyl peptidase-4 inhibitor. Diabetes Care 2007, 30:1862-1864. DeFronzo, R. (2005). Diabetic nephropathy: etiologic and therapeutic considerations. Diabetes Rev 3:510-64. Holman, R. et al. (2008). 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008, 359:1577-1589. Inzucchi, S., & Sherwin, R. (2007). Diabetes Mellitus. In: Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; chap 248. Kobrin, S. (2008). Diabetic nephropathy. Disease-A-Month 44:214-34. Krolewski A, Fogarty D, Warram J. (2008). Hypertension and nephropathy in diabetes mellitus: what is inherited and what is acquired? Diabetes Res Clin Pract 39 (Suppl):S1-14. MacLeod, M, McLay J. (2008). Drug treatment of hypertension complicating diabetes mellitus. Drugs 56:189-202. Parving H, Mauer M, Ritz E. (2007). Diabetic Nephropathy. In: Brenner BM. Brenner and Rector's The Kidney. 8th ed. Philadelphia, Pa: Saunders Elsevier; chap 36. Perkins, B., & Krolewski A. (2009). Early nephropathy in type 1 diabetes: the importance of early renal function decline. Curr Opin Nephrol Hypertens, 18:233-240 Read More