Is diabetic nephropathy a leading cause of kidney disease

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Posted by : Heenakhan on | Apr 23,2019

Introduction

Diabetic nephropathy is a condition characterized by increased excretion of urinary albumin, kidney lesions and decreased glomerular filtration rate (GFR) in diabetics. This disease is the leading cause of death among end-stage renal disease patients. Strict measures for control of glucose and blood pressure with inhibition of the angiotensin aldosterone system constitutes the effective management strategies for diabetic nephropathy.

Statistics

End-stage kidney disease due to diabetes has been estimated to affect around 30–47% of the population worldwide.

Pathogenesis

A sequence of different events leads to diabetic nephropathy. The characteristic feature is thickened basement membrane (kidneys) leading to pathologic changes in the vascular and mesangial cells.

Secondly observed renal abnormality is the glomerular hyper-filtration related to glomerular hypertension. This is accompanied by the onset of microalbuminuria, the first sign of diabetic nephropathy.

The exact pattern observed in the pathophysiology of diabetic nephropathy is:

  • Hyperglycaemia

  • Thickened glomerular basement membrane

  • Increased glomerular filtration

  • Altered endothelial integrity

  • Initiation of microalbuminuria

  • Impaired nitric oxide transport system

  • Failure of glomerular filtration capabilities

Etiology (Causative factors)

All individuals with diabetes do not progress to diabetic nephropathy and in individuals with diabetic nephropathy the progression varies. The risk factors which can be modified include

  • Hypertension

  • High blood sugar

  • Dyslipidemia

  • Smoking

The unmodifiable risks include age, gender, and genetics. Diabetic nephropathy is most common among males and individuals with a family history of diabetic nephropathy.

Genetic variation in the genes associated with diabetic nephropathy includes ALR2, ACE, APOE, APOC1, EPO, VEGF, FRMD3, eNOS, CARS, UNC13B, CPVL/CHN2, HSPG2, and GREM1.

Clinical features

The primary clinical manifestations of diabetic nephropathy are microalbuminuria, hematuria (less often), and, in many patients, progressive chronic kidney disease, which can be slowed with optimal therapy.

Microalbuminuria (30-300 mg/day albumin in the urine) is the first elicited sign of diabetic nephropathy, and is highly associated with other complications of diabetes like cardiovascular disease and retinopathy.

Overt proteinuria is excretion of more than 300 mg/day of albumin, and at this stage, total protein loss in the urine exceeds 1g/day. 5-7 years after the development of overt proteinuria the individuals usually develop end-stage renal disease.

Complications

This condition is a significant cause of chronic kidney disease leading to end-stage renal disease and premature death. It is often associated with other vascular complications like diabetic retinopathy.

Diagnosis

1. Natural history

Macroalbuminuria (≥300 mg urinary albumin) initiates after several years in type 1 diabetes however is present during the diagnosis of type 2 diabetes. This is because type 2 diabetes goes unrecognized for many years. Patients with macroalbuminuria are more probable to develop end-stage renal disease.

2. Clinical examination

Diabetic nephropathy characterized by microalbuminuria should be confirmed by repeating the urine sample after 3-6 months. This is because increased urinary albumin excretion can also occur due to hypertension, congestive heart failure, urinary tract infection and physical exertion.

The additional diagnostic criteria include a decreased glomerular filtration rate (GFR) and increased arterial blood pressure.

Microalbuminuria is the earliest clinically detectable sign of diabetic nephropathy

  • Normal: 300 mg

  • Microalbuminuria: 30-300 mg

  • Overt proteinuria: >300 mg

  • Nephrotic syndrome: >3000 mg

Albumin/creatinine ratio also helps diagnose microalbuminuria. This can be analyzed through urine samples. A ratio of 2.5 confirms microalbuminuria.

Treatment

Intensive treatment therapy to delay the progression of diabetic nephropathy includes

  • Reduced dietary fat intake

  • Exercise

  • Smoking cessation

  • Control of blood pressure

  • Anti-lipid medications (reduce cholesterol level)

  • Angiotensin-converting enzyme inhibitors

  • Good glycemic control (blood sugar)

Good glycemic control reduces the associated diabetic microvascular (blood vessel) complications. This therapy decreases the risk of end-stage renal disease by 65%

Treatment of high cholesterol levels is by lifestyle changes like dietary habits, exercise, weight reduction and statins (anti-lipid drugs)

Smoking cessation reduces the development of macroalbuminuria and improved renal prognosis.

Angiotensin enzyme inhibitors (captopril, lisinopril, enalapril, quinapril) are first-line agents that reduce both blood pressure and progression of proteinuria (urinary protein excretion)

Prevention

  • Control of blood glucose levels

  • Maintaining blood pressure levels at 120/70 mmHg

  • Avoid nephrotoxic drugs such as aminoglycosides, nonsteroidal anti-inflammatory drugs, etc.

Glycemic control

The diabetes association recommends lifestyle changes like diet and weight reduction and then proposes the use of insulin, sulfonylurea and thiazolidinedione if blood sugar is not controlled in the initial stages of diabetic nephropathy.

 

Blood pressure control

Control of blood pressure delays the end-stage renal disease. In type 1 diabetic patients with microalbuminuria, ACE inhibitors reduce the risk of progressive kidney disease.

There are many other drugs used as antihypertensive agents in diabetic nephropathy. This includes

  • Diuretics (Furosemide, Ethacrynic acid)

  • Calcium channel blockers (Amlodipine, diltiazem, nifedipine, verapamil)

  • Beta-blockers (Atenolol, propranolol, timolol)

  • Renin inhibitors (aliskiren)

References

1. Lim AK. Diabetic nephropathy–complications and treatment. International journal of nephrology and renovascular disease. 2014;7:361.

 

2. Nazar CM. Diabetic nephropathy; principles of diagnosis and treatment of diabetic kidney disease. Journal of nephropharmacology. 2014;3(1):15.

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