Diabetic nephropathy overview

# Overview
Diabetic kidney disease (Diabetic Nephropathy) is the most common cause of chronic kidney disease and end stage renal disease (ESRD) in the United States  . Due to the ongoing world wide increase in the incidence of diabetes mellitus, Diabetic nephropathy (DN) is increasingly a major cause of ESRD disease worldwide .
Diabetic Nephropathy affects male and female patients equally. The incidence of DN in African-Americans, Native Americans and people of Mexican origins is greater than the incidence in white Americans . 
Currently, the main goal in the treatment of diabetic nephropathy is to slow the progression of chronic kidney disease. This is achieved by excellent control of hyperglycemia, dyslipidemia, and blood pressure.  Antiproteinuric therapy through renin-angiotensin-aldosterone system Inhibitors is considered to be a major pillar of the treatment . Renin-angiotensin-aldosterone system inhibition it thought to be beneficial in the early stages of diabetic nephropathy through decreasing proteinuria and progression . Therefore, early diagnosis and institution of prompt treatment is very important in the management of diabetes nephropathy. Also, the role of diabetes prevention becomes paramount patients at high risk (e.g. metabolic syndrome, impaired glucose tolerance).
Diabetic nephropathy (DN) is characterized by the presence of proteinuria or decreased renal function in patients with diabetes mellitus however, diabetic nephropathy can also present in form of non-proteinuric decline in GFR. Nonetheless, proteinuria remains the hallmark of diagnosis for diabetic nephropathy, despite emerging trends suggestive of non proteinuric diabetic nephropathy. 

## Early Diabetic Nephropathy
The range of proteinuria in early DN is shown below:
- Males: Microalbuminuria in the range of 30-300 mg/24 hrs or a spot urinary albumin/creatinine ratio of 30-300 mg/g
- Females: Microalbuminuria in the range of 30-300 mg/24 hrs or a spot urinary albumin/creatinine ratio of 20-200 mg/g

## Overt Diabetic Nephropathy
Overt DN is defined according to the presence of proteinuria or according to renal function. 
The following ranges in overt DN are shown below:
- Proteinuria > 500 mg/24 hrs or albuminuria > 300 mg/24 hrs.
- Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2

# Historical Perspective
Diabetic nephropathy was first described by Clifford Wilson and Paul Kimmelstiel in 1936.

# Classification
Diabetic nephropathy can be classified according to the type of underlying diabetes mellitus or the histopathological findings of the disease.

# Pathophysiology
Diabetic nephropathy is a serious complication in patients with long standing Type 1 or Type 2 Diabetes Mellitus. It usually occurs in about 10 to 15 years following the onset of diabetes mellitus. Poor glycemic control, dyslipidemia, smoking, and environmental and genetic factors play important roles in the development of diabetic nephropathy.

# Causes
The exact cause of diabetic nephropathy is unknown. However, it is thought that hyperfiltration through the renal glomeruli may be responsible for the manifestations of the disease.

# Differentiating Diabetic nephropathy from other Diseases
Diabetic nephropathy should be differentiate from other causes of glomerular disease such as nephritic syndrome, nephrotic syndrome, Fabry's disease, poststreptococcal glomerulonephritis, lupus nephritis, antiglomerular basement membrane disease (goodpasture's syndrome), Cryoglobulinemia, Henoch-Schonlein purpura, amyloidosis, pulmonary-renal syndromes (vasculitis), thin basement membrane disease, Alport's Syndrome, anti-GBM Disease, hypertensive nephrosclerosis, and subacute bacterial endocarditis. The various types of glomerular diseases may be differentiated from each other based on associations, presence of pitting edema, hemeturia, hypertension, hemoptysis, oliguria, peri-orbital edema, hyperlipidemia, type of antibodies, light and electron microscopic features.

# Epidemiology and Demographics
In the United States, prevalence of diabetic nephropathy (DN) has increased from 7.4% to 9.6% within a 20 years period (1988 to 2008), and this trend will likely continue due to the increasing incidence of diabetes in the American populace . Studies by de Boer et al showed that DN accounts for 44% of new ESRD cases with 6% attributed to type 1 DM, 38% attributed to type 2 DM, and a projected increase of 3 million cases over the course of 20 years. This increased incidence and prevalence of DN is notably greater among African Americans, Asians, and Native Americans than it is among Caucasians.

# Risk Factors
Risk factors of diabetic nephropathy can be modifiable such as hypertension, dyslipidemia, and smoking or non-modifiable such as advanced age and positive family history.

# Screening
Microalbuminuria is an excellent tool for the early detection of diabetic nephropathy.

# Natural History, Complications and Prognosis

# Diagnosis

## History and Symptoms
Patients with diabetic nephropathy can develop the manifestations of renal failure such as edema and unintentional weight gain late in the course of the disease.

## Physical Examination
The majority of patients with diabetic nephropathy are asymptomatic. However, patients may present with other signs of diabetes mellitus or chronic renal failure.

## Laboratory Findings
Microalbuminuria, as defined by an urinary albumin-to-creatinine ratio of >30mg/g is an early diagnostic clue to diabetic nephropathy. Some patients may go on to develop high-grade nephrotic range proteinuria, while others may develop diabetic nephropathy without any measurable albuminuria.

## Other Diagnostic Studies
The diagnosis of diabetic nephropathy is based on history, physical examination and laboratory investigations. Renal imaging, such as ultrasound, is often done to rule out other kidney and urinary tract pathologies. However, the ultrasound findings in diabetic nephropathy are highly non-specific and may be normal. Some of the findings in chronic kidney disease due to diabetic nephropathy or other causes include: reduced renal length, reduced renal cortical thickness, increased renal cortical echogenicity, poor visibility of the renal pyramids and the renal sinus, marginal irregularities, papillary calcifications.

# Treatment

## Medical Therapy
The goals of treatment are to slow the progression of kidney damage and control related complications. The main treatment, once proteinuria is established, is ACE inhibitor drugs, which usually reduce glomerular hypertension, proteinuria levels, systemic hypertension and slow the progression of diabetic nephropathy.

## Primary Prevention
Primary prevention of diabetic nephropathy is aimed at preventing diabetes in the first place.

## Secondary Prevention
Once diabetic nephropathy develops, secondary prevention to halt the progression of the disease is aimed at strict control of blood pressure, blood glucose levels, as well as lipids.