ogy: iol Cu ys r h re P n t & R y e s Anatomy & Physiology: Current m e o a t r a c n h Saxena, Anat Physiol 2015, 5:4 A Research ISSN: 2161-0940 DOI: 10.4172/2161-0940.1000181 Review Article Open Access Nutritional Approach to Diabetic Nephropathy Anita Saxena* Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India *Corresponding author: Anita Saxena, Department of Nephrology, Sanjay Gandhi Post Graduate Institute Of Medical Sciences, Raebarelly 226014, Lucknow, India, Tel: +05222668004; E-mail: [email protected] Rec date: Aug 13, 2015; Acc date: Sep 29, 2015; Pub date: Oct 5, 2015 Copyright: © 2015 Saxena A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Diabetes is an important cause of renal disease. Diabetic nephropathy (DN) is characterized by albuminuria, which is usually accompanied by hypertension, progressive rise in proteinuria (albuminuria >0.5 g/24 h), and decline in renal function. Long term complications of diabetes are macrovascular disease (coronary heart disease), cerebrovascular disease, peripheral arterial disease and microvascular disease retinopathy and nephropathy. DN carries a 20- to 40-fold increased risk for cardiovascular (CV) mortality. To delay progression of DN to ESRD following measures are recommended a) good control of blood glucose, b) low-protein diet, c) control of hypertension, d) restriction of dietary salt, phosphorus and potassium in advanced cases and e) control of hyperfiltration, usually through angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blocking (ARB) agents. ACE inhibitors reduce proteinuria and glomerulosclerosis. Mangement of proteinuria with diet has shown that antiproteinuric effect is strongly dependent on dietary sodium restriction. Keywords: Diabetic nephropathy; Diabetes; Renal function; Long term complications of diabetes are macrovascular disease Cardiovascular (coronary heart disease), cerebrovascular disease, peripheral arterial disease and microvascular disease retinopathy and nephropathy. DN Introduction carries a 20- to 40-fold increased risk for cardiovascular (CV) mortality. Figure 1 illustrates interaction between metabolic and India among all the SAARC countries has become the diabetes hemodynamic pathways in the pathophysiology of diabetic capital of the world. Twenty to forty percent of type 2 diabetes patients nephropathy. To delay progression of DN to ESRD following measures having microalbuminuria progress to overt nephropathy i.e., diabetic are recommended a) good control of blood glucose, b) low-protein nephropathy (DN), and ~20% progress to end stage renal disease diet, c) control of hypertension, d) restriction of dietary salt, (ESRD) making it the leading cause of ESRD in the past two decades. phosphorus and potassium in advanced cases and e) control of Diabetic nephropathy (DN) is characterized by albuminuria, which is hyperfiltration, usually through angiotensin-converting enzyme (ACE) usually accompanied by hypertension, progressive rise in proteinuria inhibitors or angiotensin-receptor blocking (ARB) agents. ACE (albuminuria >0.5 g/24 h), and decline in renal function. inhibitors reduce proteinuria and glomerulosclerosis. Mangement of proteinuria with diet has shown that antiproteinuric effect is strongly dependent on dietary sodium restriction. A low-sodium diet is known to enhance the renoprotective and cardioprotective effect of ACE inhibitors (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study ) and Irbesartan Type II Diabetic Nephropathy Trial (IDNT)) in DM patients with nephropathy. Compared to higher sodium intake groups, the patients in the low sodium group had better renal (by 43%) and cardiovascular (by 37%) outcomes. These studies support low dietary salt intake, particularly in patients with DM and nephropathy treated with angiotensin receptor blockers. Dietary sodium intake of less than 2.4 g/d (one teaspoon salt) is recommended in adults with CKD and hypertension. Studies have shown fall in blood pressure by 2-3 mmHG when sodium intake is lowered from 4.0 g to 2.0 g per day. This fall of Figure 1: Interaction between metabolic and hemodynamic blood pressure may lead to a cumulative decrease by 10 mmHg over pathways in the pathophysiology of diabetic nephropathy. SNS: several years and may eventually lower the risk of heart disease. Target Sympathetic Nervous System; RAAS: Renin Angiotensin blood pressure should be <130/80 mm Hg. LDL cholesterol should be Aldosterone System; PGc, intraglomerular capillary pressure <100 mg/dl and those with cardiovascular disease should maintain <70 (Adapted from Christine Maric and John E. Hall Obesity, metabolic mg/dl [1-8]. syndrome and diabetic nephropathy Contrib Nephrol. 2011; 170: 28–35). Anat Physiol Volume 5 • Issue 4 • 1000181 ISSN:2161-0940 APCR, an open access journal Citation: Saxena A (2015) Nutritional Approach to Diabetic Nephropathy . Anat Physiol 5: 181. doi:10.4172/2161-0940.1000181 Page 2 of 5 Pathophysiology of Diabetic Nephropathy glomerular sclerosis. Hyperglycemia, angiotensin II, TGF-β, and proteinuria play role in stimulating this fibrosis. There is an epithelial- The exact cause of diabetic nephropathy is unknown, however, it is mesenchymal transition that takes place in the tubules, with proximal postulated that tubular cell conversion to fibroblast-like cells. These cells then migrate i) hyperglycemia (which causes hyperfiltration and renal injury), ii) into the interstitium and produce collagen and fibronectin [9-12]. advanced glycosylation products (AGEs), and iii) activation of Hence, medical nutritional management is important for the cytokines play key role in causing renal injury. Hyperglycemia prevention of DN. The goals of medical nutritional therapy which will increases expression of transforming growth factor-beta (TGF-beta) in be dealt in this article are: the glomeruli and of matrix proteins specifically stimulated by this cytokine. TGF-beta and vascular endothelial growth factor (VEGF) 1. Maintenance of near normal blood glucose levels (glycemic may contribute to the cellular hypertrophy, enhanced collagen control) by controlling food intake and exercise synthesis, and vascular changes observed in persons with diabetic 2. Achieving optimal serum lipids and blood pressure to reduce the nephropathy. Hyperglycemia also may activate protein kinase C, which risk of cardiovascular disease (CVD) may contribute to renal disease and other vascular complications of diabetes. Familial or perhaps even genetic factors also play a role. 3. Management of body weight. Three major histologic changes occur in the glomeruli in diabetic 4. Maintaining biochemical parameters and fluid status nephropathy. 5. Prevention of long term complications The earliest morphologic abnormality in diabetic nephropathy is the thickening of the GBM and expansion of the mesangium due to 6. Prevention of malnutrition and strategies to control diabetic accumulation of extracellular matrix. gastroparesis. 1. Mesangial expansion induced by hyperglycemia via increased An important marker of good diabetes therapy is that blood glucose matrix production or glycosylation of matrix proteins. is maintained below the renal threshold (250 mg/dL), so that it is not passed into the urine. Insulin resistance and glucose intolerance are 2. Thickening of the glomerular basement membrane (GBM). characteristic features in patients with kidney disease. The Diabetes 3. Glomerular sclerosis caused by intraglomerular hypertension. Control and Complications Trial (DCCT 1993) and the United Kingdom Prospective Diabetes Study (UKPDS) have shown that Intraglomerular hypertension is induced by dilatation of the intensive insulin therapy can significantly reduce the risk of the afferent renal artery or from ischemic injury induced by hyaline development of microalbuminuria and overt nephropathy. According narrowing of the vessels supplying the glomeruli. The key change in to American Diabetes Association (ADA), after five years of diabetic glomerulopathy is augmentation of extracellular matrix. diagnosing DM, microalbuminuria must be tested annually as The severity of diabetic glomerulopathy is estimated by the microalbuminuria is also associated with elevated HbA1C levels thickness of the peripheral basement membrane and mesangium and (>8.1). Target HbA1C should be ≤ 7.0 % (Table 1). However, the values matrix expressed as a fraction of appropriate spaces (eg, volume may be falsely elevated or decreased in patients with chronic kidney fraction of mesangium/glomerulus, matrix/mesangium, or matrix/ disease (CKD) because of factors given in Table 2. glomerulus). The glomeruli and kidneys are typically normal or Glycemic target ADA* ACE** IDF*** increased in size initially, thus distinguishing diabetic nephropathy from most other forms of chronic renal insufficiency, wherein renal A1c% <7.0 ≤6.5 <6.5 size is reduced (except renal amyloidosis and polycystic kidney disease). Fasting Glucose mg/dl 90-130 <110 <100 Patients with overt diabetic nephropathy generally develop systemic Postprandial glucose mg/dl <180 <140 <145 hypertension. The deleterious effects of hypertension are seen in the vasculature and microvasculature. Proteinuria, a marker and potential Table 1: Target HbA1C for diabetics with kidney disease. contributor