Diabetic nephropathy

Diabetes is a disease that prevents the body from using glucose (sugar) properly. If glucose stays in the blood instead of being used by the tissues (metabolized), it can cause toxicity. The damage that excess blood glucose causes to the nephrons It is called diabetic nephropathy. This pathology can be diagnosed thanks to microalbuminuria, which is the loss of small amounts of protein in the urine, specifically albumin. If blood glucose concentrations are maintained within their normal range (60 - 110 mg/dL) almost all forms of diabetic nephropathy can be delayed or prevented.

In addition, another definition could be that diabetic nephropathy is a disorder or pathology of the kidney, which includes inflammatory, degenerative and sclerotic processes related to persistent hyperglycemia associated with other factors (hypertension, dyslipidemia, genetic predisposition).

Diabetic nephropathy is one of the main causes of Chronic Kidney Failure.

Stages of Diabetic Nephropathy

Stage I.: Does not cause symptoms. There is glomerular hyperfiltration, and urinalysis and creatinine are normal. There are also no histological changes.

Stage II.: Appears approximately after five years of evolution. It is silent. He maintains normal renal function and there is no loss of albumin. Minimal changes in the glomerulus, such as the beginning of thickening of the basement membranes or a slight increase in the mesangial matrix.

Stage III: Presence of microalbuminuria (more than 30 mg of albumin in 24 hours or 20 mg/liter of urine). Blood creatinine is normal. Associated arterial hypertension can worsen renal damage. Mesangial and basement membrane expansion.

Stage IV: Persistent proteinuria, decreased renal function. Serum creatinine in high limits of normal or elevated (greater than or equal to 1.3 mg/dl in women or men weighing less than 65 kg or greater than or equal to 1.5 mg/dl in men). It can present as nephrotic syndrome. Histology: patchy glomerulosclerosis. Thickening of basement membranes. mesangial expansion. Onset 15 years after diagnosis. It is associated with retinopathy in more than 75%, coronary artery disease in more than 45%, and cerebrovascular disease in more than 25% of cases.

Stage V: Proteinuria. Creatinine greater than 200 µmol/liter or 2.2 mg/dl, arterial hypertension. Glomerulosclerosis, nodular lesions, interstitial fibrosis, tubular atrophy. Appearance in general after twenty years of evolution.

The presence of microalbuminuria is a sign of incipient nephropathy and is used as screening for early detection of renal involvement.

Symptoms of Diabetic Nephropathy

The main symptoms are the following:

• Edema de miembros inferior - Ascitis
• Loss of appetite
• Cansancio
• Fatigue
• Spray or excessive foam in the urine
• Frequent disease
• Sensation of general discomfort
• Generalized pruritus
• Headache
• Nausea and vomiting
• These symptoms are unspecific and depend on the degree of renal involvement (see before stages of nephropathy).

Pathogenesis

The pathogenesis of diabetic glomerulosclerosis is closely related to generalized diabetic microangiopathy. Its main aspects are the following:

• Evidence indicates that it is due to a metabolic effect, i.e. insulin deficiency, resulting hyperglycemia or some other aspects of glucose intolerance. These phenomena are responsible for the alterations of the glomerular basal membrane (MBG), including the increase of type IV collagen and fibronectin and the decline of proteoglucan heparan sulfate and the increase in the production of free radicals, which can aggravate the lesions to the glomerular filter.
• Non-enzymatic glucosylation of proteins, which results in the emergence of advanced glucosylation products, which could also contribute to glomerulopathy.
• Hemodynamic changes. Increased GF, glomerular capillary pressure, glomerular hypertrophy and increased filtration surface.

'How to prevent and treat diabetic nephropathy?'

In the UKPDS study, it was observed that the risk of microvascular complications (nephropathy, neuropathy and/or retinopathy) is reduced by 37% in 10 years for each drop in Glycosylated Hemoglobin (HbA1c) and likewise a 37% for every 10 mm Hg drop in systolic blood pressure. Therefore, the correct control of both factors is necessary for the prevention and slowing down of the evolution of microvascular complications.

Early diagnosis of nephropathy: it is recommended to perform an annual determination of microalbuminuria under 75 years of age. The screening will be carried out by determining the albumin/creatinine ratio in a morning urine sample. In the presence of microalbuminuria, even stricter control of the factors of progression is necessary: arterial hypertension, smoking, dyslipidemia, prohibition of nephrotoxic drugs and treatment of urinary tract infections.

Quantification of renal function: it is recommended to perform an annual determination to detect its deterioration early and later assess its evolution. For its calculation in diabetics, it is preferable to use the MDRD equation (www.kidney.org/professionals/kdoqi/gfr_calculator.cfm) although that of Cockcroft and Gault can also be used; both allow us to estimate its value based on sex, age (years), plasma creatinine (mg/dl) or weight (kg). The different degrees of renal failure are determined by the level of glomerular filtration.

HBP control: strict control reduces the risk of microalbuminuria progression by 29%. The treatment of choice for hypertension in diabetics with microalbuminuria or nephropathy is ACE inhibitors (enalapril) or ARA II (losartan).

Glycemic control: In patients with nephropathy, adequate glycemic control is recommended (HbA1c ≤7%). In case of severe renal insufficiency, insulin, glinides and pioglitazone can be used; The other antidiabetics cannot be used.

Microalbuminuria without HBP: It is advisable to use an ACEI or ARAII, which have been shown to reduce its amount.

In case of moderate or severe renal failure, protein restriction below 0.8 g/kg of weight/day is recommended (ADA, 2011).

When ACE inhibitors and/or ARA II are used in patients with nephropathy, it is necessary to monitor serum potassium levels due to the risk of hyperkalemia.