Definition

Chronic Kidney Disease (CKD) is the progressive loss of renal function over a period of months or years, and develops as a complication of systemic diseases or as a complication of many renal diseases.

Key Terms

• Glomerular Filtration Rate (GFR): The metric used to estimates how much blood passes through the glomeruli each minute. Glomeruli are the tiny filters in the kidneys that filter waste from the blood. GFR is measured via the levels of creatinine in urine.
  

Pathophysiology

Chronic Kidney Disease decreases the glomerular filtration rate and tubular functions with changes manifesting throughout all organ systems.

Kidneys are adaptable to loss of nephron mass and symptomatic changes as a result of increased creatinine, urea, potassium and alterations in sodium and water balance usually do not become apparent until renal function declines to less that 25% of normal functions, in which case renal compensation is depleted.

Uraemia is a syndrome of CKD and includes elevated blood urea and creatinine levels accompanied with fatigue, anorexia, nausea, vomiting, pruritis (itchy skin) and neurological changes. Uraemia represents consequences ralted to CKD including retention of toxic wastes, deficiency states and electrolyte disorders.

Risk Factors

1 in 3 Australian adults are at risk of developing Chronic Kidney Disease as result of lifestyle & biological factors such as smoking, obesity, diabetes, age > 50yrs or indigenous descent. The infographic below shows the most common risk factors.

Risk factors that are known specifically to contribute to Chronic Kidney Disease are explained below:

• Diabetes: Increased glucose damages nephron
• Hypertension: Prolonged, uncontrolled hypertension causes arterioles to harden, weaken or narrow leading to decreased blood flow to nephron = necrosis. Poor kidney function also leads to inability to control the renin-angiotensin-aldosterone system, further exacerbating hypertension.
• Poor cardiovascular health: Congestive Heart Failure impedes venous return and/or poor blood flow to kidneys
• Obesity/smoking: Increased risk of comorbidities such as hypertension and diabetes
• Aboriginal/Torres Straight Islanders are three times as likely as non-Indigenous people to have indicators of Stage 1 chronic kidney disease, and more than four times as likely to have indicators of Stages 4 and 5. The greater prevalence of chronic kidney disease in some Aboriginal and Torres Strait Islander communities is due to the high incidence of traditional risk factors, including diabetes, high blood pressure and smoking, in addition to higher levels of inadequate nutrition, alcohol abuse, streptococcal throat and skin infection, poor living conditions and low birth weight, which is linked to reduced nephron development.

Causes

There are 3 known contributing factors to Chronic Kidney Disease:

Increase glomerular pressure (GP)

As diabetes mellitus causes an increased blood pressure, the pressure coming through the afferent arteriole also increases.

Normally, the renin-angiotensin aldosterone system (RAAS) is triggered by hypotension, however an increase in glucose also triggers the RAAS which causes vasoconstriction in the efferent arteriole, thus adding to the increase in glomerular pressure. This increase in pressure in the glomerulus damages the glomeural basement membrane (GBM) and eventually allow molecules through the GBM which otherwise wouldn’t fit.

Barotrauma to mesangial cells

As mesangial cells undergo prolonged pressure, inflammation occurs which cause expansion of cells. Cell expansion damages podocytes which further stretches and damages the GBM resulting in an increased thickness to the GBM.

Nephron Ischemia

As the renin-angiotensin-aldosterone system causes vasoconstriction, the peritubular capillaries (blood vessels which wrap around the rest of the nephron) have decreased blood flow and thus decreased ability to reabsorb and secrete. This leads to loss of essential nutrients and the retention of toxins.

Initial clinical findings will include an increased glomerular filtration rate (during stage 1, however will drop as chronic kidney disease advances), increased proteinuria (especially albumin, due to mesangial expansion) and haematuria (due to nephron death).

Major causes in Australia:

Glomerulonephritis (25%)

There are a large group of diseases characterised by damage of the glomerulus. Most of the diseases are caused by inflammation in the glomeruli (increasing inflammation leads to decreasing GFR). Most commonly affected areas:

• Glomerular Basement Membrane (GBM)
• Mesangial cells
• Capillary endothelium
• Risk factors include: TB, HIV, hepatitis, cardiac defects, obesity and constant use of NSAIDs.

Hypertension (16%)

The glomerular blood pressure is approximately 60mmHg and this BP is controlled by smooth muscles (juxtaglomerular cells) surrounding the arterioles. If the systemic hypertension is uncontrolled, these juxtaglomerular cells become overworked. Eventually they weaken, harden and narrow and are unable to control BP within the glomerulus.

Hypertension within the glomerulus damages mesangial cells, podocytes and the glomerular basal membrane. Once damaged, these cells are unable to filter correctly and chronic renal failure begins.

Treatment

See Renal Dialysis