University of Manchester
Diabetic Kidney disease: causes and consequences
Abbreviations: A2RBs: Angiotensin-II Receptor Blockers, ABP: Arterial Blood Pressure, ACE:
Angiotensin Converting Enzyme, ACR: Albumin: Creatinine Ratio, AER: Albumin Excretion Rate,
AGEs: Advanced Glycation End-products: CKD: Chronic Kidney Disease, DCCT: Diabetes Control and Complications trial, DCT: Distal Convoluted Tubule, DM: Diabetes Mellitus, DN: Diabetic
Nephropathy, ECM: Extracellular Matrix, ESRF: End-Stage Renal Failure, GBM: Glomerular
Basement Membrane, GFR: Glomerular Filtration Rate, HbA1c: Haemoglobin A1c, NADPH:
Nicotinamide Adenine Dinucleotide Phosphate, PCT: Proximal Convoluted Tubule, PKC: Protein
Kinase C, ROS: Reactive Oxygen Species, TGF-β1: Transforming growth factor-beta1, UAE: Urinary
Albumin Excretion, UTI: Urinary Tract Infection, UKPDS: United Kingdom Prospective Diabetes Study,
VEGF: Vascular Endothelial Growth Factor.
Diabetes is a condition in which the patient is unable to lower their blood glucose concentration leading to hyperglycaemia. The kidney is the major excretory organ in the body and also plays a role in the regulation of blood pressure.. Poor glycaemic control amid other factors results in structural changes that lead to a decline in renal function. This paper identifies the multiple aetiologies that lie behind the development of diabetic kidney disease and the consequences that will eventually follow.
Hyperglycaemia creates a glucotoxic environment that damages insulin-independent cells via increases in the polyol pathway flux, increased production of advanced glycation end-products and protein kinase C over activation. These changes combined cause histopathological changes in the glomerulus and an eventual decline in renal function is seen. Early detection of abnormal renal function is critical in attaining a positive prognosis. Currently, there is no efficient treatment for diabetic kidney disease and the search for an effective one remains ongoing.
Diabetes is a condition in which the patient is unable to lower their blood sugar level. Over a long period of time, diabetics may develop diabetic kidney disease; a serious long term complication of diabetes. The kidney is responsible for the excretion of waste products in the body. High blood sugar levels create a toxic environment that harms special structures in the kidney. This toxic environment is responsible for the changes in these specialized structures and lead to a fall in kidney function. This paper describes the causes that lead to diabetic kidney disease and the subsequent consequences.
Early detection of abnormal kidney function provides a patient with a much better outlook than if detected when the disease is in its later stages.
DM is a chronic disease common worldwide affecting 346 million people according to the World
Health Organisation (WHO) (World Health Organisation, 2013). The two most prevalent types of diabetes are Type 1 DM (T1DM) and Type 2 DM (T2DM). T1DM is characterized by the loss of insulin production from the pancreas as a result of autoimmune beta cell destruction. In contrast, T2DM arises when an individual does not produce enough insulin or when their cells no longer respond to insulin. This is commonly known as insulin resistance (Becker, 2004). Irrespective of the type of diabetes, patients with this disease have elevated blood glucose concentration (hyperglycaemia) as glucose is unable to enter the cells of the body. In T1DM, hyperglycaemia occurs because the absence of insulin halts glucose entry into cells whereas in T2DM it arises due to cells being unable to respond to insulin present in the body. This leads to a disruption in the homeostatic balance of glucose and in most incidences where the balance of a metabolite in the body is disturbed, the likelihood of