comorbidity Early identification of renal impairment due to chronic kidney disease associated with diabetes is key to timely intervention and management Denise Blanchfield
Type 2 and CKD – what’s going on? Approximately 13% of the adult population suffers from chronic kidney disease (CKD) with numbers expected to continue to climb.1 Diabetes is the leading cause of established renal failure in the western world.2 Failure to identify renal impairment of CKD associated with diabetes may lead to a delay in timely management of this problem. This has important healthcare management implications such as increased mortality and morbidity, cost and duration of hospitalisation.3 An effective disease management strategy requires consolidation of all aspects of the disease, such as assessment of renal function to ensure timely and appropriate interventions which can have a significant impact of slowing the progression of CKD together with effective hypertension, lipid, and glycaemic management. 4 Kidney structure The kidney is a complex organ involved in the excretion of the waste products of metabolism. Within the kidney, the nephron is the basic structural and functional unit which eliminates waste products, regulates water concentration, electrolyte and pH balance. Each nephron has three parts: the afferent arteriole which is a small blood vessel which brings unfiltered blood to the glomeruli, which is a capillary tuft which in turn filters the blood; and the efferent arteriole which returns filtered blood to the body (see Figure 1).5 Renal pathology Diabetic nephropathy is a chronic condition which develops over a period of years
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diabetes&cardiologyreview
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characterised by Figure 1: Excretion of waste products by nephron increasing urinary albumin excretion Afferent Efferent rate and blood arteriole arteriole pressure, which 1. Filtration results in declining 2. Reabsorption Glomerular glomular filtra3. Secretion capillaries tion rate (GFR). The 4. Excretion main pathology Bowman’s of nephropathy capsule occurs within the 1 glomeruli and the 2 nephron support Peritubular capillaries structure: tubular interstitium.6 3 What damages the kidney? 4 Renal vein Estimated glomerular filtration rate (eGFR) can Urinary excretion be interpreted as Excretion = filtration – reabsorption + secretion the percentage of normal kidney function such that an eGFR of 50ml/ filtering unit which separates the blood min/1.73m2 approximates 50% of normal from the urine. Within the capillaries of kidney clearance. Three distinct metabolic the renal glomeruli, plasma proteins bind pathways are attributed to the pathogento the glycated basement membrane esis of long-term diabetic complications resulting in the basement membrane such as nephropathy,6 the primacy of thickening. This thickening is the earliest these has yet to established; detectable change in renal glomeruli and Non-enzymatic glycosylation is the prois associated with diabetic glomerulopacess by which glucose chemically attaches thy as demonstrated by Figure 2.6 Damage to this membrane causes proteins to leak to free amino groups of proteins without from the blood into the urine. the aid of enzymes. This is glucose dependActivation of protein kinase C (PKC) ent, a higher blood glucose level results in Intracellular hyperglycaemia can stimuan increased proportion of non-enzymatic late the de novo synthesis of diacylglycerol glycosylation. (DAG), a messenger resulting in the The glomular capillary wall is the