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Incidence:
The incidence of Diabetes Mellitus (DM) in the Western World has increased dramatically over the past two decades. The prevalence of DM in the US rose from 8.9% in 1976 to 12.3% in 1994. This rate of increase is greater for type II than type I diabetes mellitus. Diabetic nephropathy affects 25-45% of patients diagnosed with DM under age of 30 years. It also less commonly occurs in those diagnosed at an older age.
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Predisposing Factors:
1. Diabetes Mellitus - type I and type II 2. Uncontrolled diabetes - Increased rate of progression 3. Hypertension- Increased rate of progression 4. Smoking- Accelerates the deterioration in renal function
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Macroscopic Features:
No macroscopic morphological features are present in this disease, for it affects the renal vessels at a microscopic level. As patients with diabetes are more susceptible to urinary tract infection, the kidneys may demonstrate scars or features consistent with past or present pyelonephritis (kidney infection). As DM also affects larger vessels, renal infarction may result from severe hypertrophy and hyalinisation of afferent and efferent arterioles.
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Microscopic Features:
There are three microscopic features that may occur in diabetic nephropathy: 1. Capillary Basement Membrane Thickening - This occurs throughout the kidney in glomerular capillaries. Glomerular basement membrane (GBM) thickening can only be detected with electron microscopy. The prevalence of this change is 30% after only five years of diabetes mellitus. 2. Diffuse Glomerulosclerosis - Diffuse increase in mesangial matrix within the glomerulus and proliferation of the mesangial cells. This change lags behind GBM thickening but is usually present on light microscopy after 10-20 years. With progression, the mesangial matrix expands to obliterate the mesangial cells, resulting in the destruction of glomerular function (obliterative diabetic glomerulosclerosis.) 3. Nodular Glomerulosclerosis - This describes the appearance of round or ovoid lesions within the glomeruli of the outer cortex. These nodules have been shown to contain lipids and fibrin. With time, these lesions expand and engiulf the entire glomerulus resulting in its ultimate destruction. Many believe that nodular glomerulosclerosis and diffuse glomerulosclerosis are the same entity. The microscopic image below is indicative of the nodular lesions present in diabetic neuropathy. 
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Natural History:
Once diabetic nephropathy is established, it cannot be reversed and will eventually result in End Stage Renal Disease. A renal specialist should be sought at the earliest sign of diabetic nephropathy to maximise efforts in slowing the deterioration of renal function. When compared to non-diabetic individuals, the diabetic will more frequently encounter problems with dialysis such as hypotension, difficult vascular access and accelerated progression of diabetic retinopathy. The greater incidence of complications on dialysis significantly reduce the survival time of diabetic patients recieving dialysis support.
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Prognosis:
Once proteinuria is present, 50% of patients will enter End Stage Renal Disease (ESRD) in 7-10 years. However, this progression can be marked slowed with aggressive therapy with antihypertensives. Angiotensin-converting enzyme inhibitors are the drug of choice. Associated diabetic retinopathy tends to progress rapidly and therefore frequent ophthalmic supervision is necessary.
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Clinical History:
The development of diabetic nephropathy is asymptomatic in the majority of cases. This fact highlights the importance of regular assessment of diabetics for the development of microalbuminuria. With more overt proteinuria, patients may complain that their urine is becoming "frothy" or present with recurring urinary tract infections.
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Clinical Examination:
In the early stages of disease, physical examination will reveal no specific signs of diabetic nephropathy. A complete physical examination is appropriate to assess the presence and severity of diabetic complications. General - Check for hypertension and postural hypotension Cardiovascular - Check for beat to beat variation, signs of heart failure and presence of peripheral pulses in the lower limbs Neurological - Check for peripheral neuropathy and cranial nerve deficits Ophthalmoscopy - Check for presence of cataracts and diabetic retinopathy changes Dipstick Urinalysis - Check for proteinuria (nephropathy) and indicators of infection
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Specific Investigations:
- Urine should be checked for the presence of protein (microalbuminuria)
- 24hr urinary protein (or albumin-creatinine ratio) - Gold standard assessment for proteinuria
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Treatment Overview:
The ultimate treatment is prevention. The following measures should be undertaken in all patients with diabetes with or without diabetic nephropathy: - Stabilisation of blood glucose concentration
- Strict blood pressure control (preferably <130/85 in diabetics without proteinuria)
- Administration of ACE inhibitors
Once microalbuminuria is present, the above measures are still recommended but their impact on disease progression is somewhat reduced. The recommended target blood pressure in those with proven microalbuminuria is <120/80 to adequately slow the disease process. The dose of ACE inhibitors should be titrated against urinary protein such that proteinuria is eliminated or minimised without overt side-effects. If the side-effects of ACE inhibitors becomes intolerable, other agents such as angiotensin II receptor blockers or calcium channel blockers can be used.
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References:
- Braunwald, Fauci, Kasper, Hauser, Longo, Jameson. Harrison's Principles of Internal Medicine. 15th Edition. McGraw-Hill, 2001
- Cotran, Kumar, Collins 6th edition. Robbins Pathologic Basis of Disease. WB Saunders Company. 1999.
- Kumar P, Clark M. Clinical Medicine, 5th Ed, WB Saunders, 2002.
- Longmore M, Wilkinson I, Torok E. Oxford Handbook of Clinical Medicine, 6th Ed, Oxford University Press, 2004.
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