Diabetic nephropathy (DN)
Diabetes mellitus (DM), commonly referred to as diabetes, is a group of metabolic disorders in which there is high blood sugar levels over a prolonged period. Recent statistics from the World Health Organisation (WHO) project an increase in the prevalence of diabetes world-wide particularly in developing countries. Currently, India leads the world with the largest number of diabetic subjects and this is expected to further rise in the coming years.
Symptoms of high blood sugar include frequent urination, increased thirst, and increased hunger.If left untreated, diabetes can cause many complications. Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death.
Serious long-term complications include damage to the eyes, cardiovascular disease, stroke, foot ulcersand chronic kidney disease. These occur mainly due to damage in small blood vessels in these organs. Let us look at what could happen in the kidney.
Diabetic nephropathy (DN) (diabetic kidney disease – DKD) is the chronic loss of kidney function occurring in those with diabetes mellitus. It is a serious complication, affecting around 45% of adult diabetics. It usually progresses slowly over the years. Pathophysiologic abnormalities in DN begin with long-standing poorly controlled blood glucose levels. This is followed by multiple changes in the filtration units of the kidneys, the nephrons. (There are normally arounda million nephrons in each adult kidney). Basic function of nephron is to remove waste from blood.
Glomerulus and tubules are 2 main parts of kidney. In glomerulus fluid is filtered from blood. This filtered fluid is collected in Bowmans capsule. Tubule is a long narrow tube where the filtered fluid from Bowmans capsule is processed and converted into urine.
I Initially, there is constriction of the efferent arterioles (the exit pathway) and dilation of afferent arterioles,(entry way) with resulting glomerular capillary hypertension and hyperfiltration; this gradually changes to hypofiltration over time.
Concurrently, there are changes within the glomerulus itself: these include a thickening of the basement membrane, a widening of the slit membranes of the podocytes, an increase in the number of mesangial cells, and an increase in mesangial matrix. This matrix invades the glomerular capillaries and produces deposits called Kimmelstiel-Wilson nodules.
The mesangial cells and matrix can progressively expand and consume the entire glomerulus, shutting off filtration. As this process affects more and more glomeruli, filtration in both kidneys progressively declines: the pathological process called nephrosclerosis.
The status of DN may be monitored by measuring two values: the amount of protein in the urine – proteinuria or Albuminuria; and a blood test for serum creatinine. The amount of the proteinuria is a reflection of the degree of damage to glomeruli. The value of the serum creatinine can be used to calculate the estimated glomerular filtration rate (eGFR), which reflects the percentage of glomeruli which are no longer filtering the blood.
How does Diabetic Nephropathy progress?
Hyperglycemia is known to play a crucial part in the pathogenesis of Diabetic Nephropathy. High glucose levels induce metabolic abnormalities in several glucose metabolic pathways and induce mitochondrial dysfunction, with subsequent overproduction of Reactive Oxygen Species (ROS). These may in turn contribute to the development of the various microvascular pathologies observed in diabetes.
Uncontrolled production of Reactive Oxygen Species (ROS) and their associated damage products- such as lipid peroxides – have been shown to play a central role in both early glomerular and subsequent tubular changes in DN. Agents targeting renal oxidative stress- by blocking enzymatic production or bolstering antioxidant defenses- have demonstrated anti-inflammatory and anti-fibrotic effects,
It has been suggested that increased generation of ROS in diabetes mellitus, reduces vascular endothelial function.
DIAGNOSIS OF DIABETIC NEPHROPATHY
Diagnosis is usually based on clinical evidence, most important of which is the appearance and progression of proteinuria from micro-albuminuria (between 30 to 300 mg/gm) to macro-albuminuria (over 300 mg/gm per day) in a patient with diabetes mellitus. Proteinuria is often associated with hypertension and increasing serum creatinine (Cr).
