**2. Stages of chronic kidney disease**

The early stages of kidney dysfunction are often clinically silent, especially when the condition is only slowly progressive and symptoms are nonspecific. Stages 1 & 2 show decreased kidney function without signs or symptoms of disease although the estimated GFR is less than 120 ml/min per 1.73 m2 but greater than 60 ml/min per 1.73 m2. The rate of progression is influenced by a wide range of factors which may or may not have the potential of modification and varies among different individuals and with the underlying cause of nephropathy.When the patient enters Stage 3 he or she has lost approximately half their kidney function. It is less likely for the kidney disease to progress unless more than 50% of the nephron function is lost. For example, individuals with a solitary kidney after unilateral nephrectomy for living kidney donation usually do not progress to CKD.Increased risk of natural progression with less than 50% of nephron loss can occur in persons of African ancestry with hypertensive nephrosclerosis. In 2008, the U.K National Institute of Health and Clinical Excellence (NICE) sub divided the stage 3 into 3A and 3B with estimated GFRs of 45 to 59 ml/min per 1.73 m2 and 44 to 30 ml/min per 1.73 m2

Severity and Stages of Chronic Kidney Disease 15

factors which increase the risk for CKD are further classified into susceptibility and initiation factors; whereas factors which effect adverse outcomes are classified as progression factors and end stage factors. The association between variables and disease

A susceptibility factor is one that increases susceptibility to kidney damage following exposure to an initiation factor. An ideal study design to study these factors would be to identify a population of individuals who are free of kidney disease and are exposed to an

An initiation factor is one that directly initiates kidney damage in an individual who is susceptible to kidney damage. An ideal study design for identification of initiation factors is a prospective cohort study. This would involve identification and follow up of a group of individuals free of kidney disease at baseline, with known susceptibility factors and with or

Progression factors worsen the kidney damage caused by initiation factors and lead to further decline in kidney function. Indicators of progression may include progression of microalbuminuria to overt proteinuria or reduced GFR, rate of decrease of GFR, or

End –stage factors are those that exacerbate the morbidity and mortality associated with kidney failure. Examples of indicators of mobidity include hospitalizations, poor quality of

Proteinuria is associated with faster rates of CKD progression. It contributes to nephron loss; filtered proteins are reabsorbed by the proximal tubular cells. Tubular cell contents may leak into the interstitium. This can cause macrophage infiltration and inflammatory mediators produced by them. The MDRD study showed proteinuria to be the strongest predictor of kidney disease progression in non diabetic patients. The REIN study done in non diabetic patients with proteinuria, showed the protein excretion rate to be the best single predictor of GFR decline to ESRD. This finding was independent of

The US Collaborative Study in type 1 diabetic patients with >500mg proteinuria/day and serum creatinine values of 2.5mg% or less showed a 50% reduction in the risk of combined endpoints (death, dialysis, transplantation) in patients treated with an ACE

may be due to chance, a non-causal relation or may signify a true risk factor.

without exposure to initiation factors, for the development of kidney disease.

development of kidney failure necessitating dialysis or transplantation.

**3.1 Risk factors for development of CKD** 

initiation factor and follow them for a period of time.

**3.2 Risk factors effecting adverse outcome of CKD** 

life measures, and cardiovascular disease complications.

**3.3 Risk factors for progression of chronic kidney disease** 

**1. Susceptibility Factors** 

**2. Initiation Factor** 

**1. Progression Factors** 

**2. End-Stage Factors** 

1. Proteinuria

the initial insult.

inhibitor.

respectively. The NICE CKD guideline also suggested adding the suffix *p* to the stages in proteinuric patients.It has generally been assumed that the majority of patients with CKD stages 3B to 5 eventually progress to ESRD. A Canadian study showed the natural history of CKD stages 3 and 4 to be variable and reflecting the patient's risk factor profile.Stage 4 may present with hyperkalemia or problems with salt and water retention. The kidneys are no longer able to adjust to abrupt changes in sodium, potassium and fluid intake (or loss). Prior to initiation of renal replacement therapy, the patient's appetite may decrease, accompanied by weight loss and a decrease in the serum albumin. In CKD clinics, with patients seen at frequent intervals, the goal is to initiate dialysis before the patient becomes malnourished.


Table 1. Stages of CKD.

Two commonly used formulas to calculate creatinine clearance are the Cockcroft-Gault formula and MDRD formula.

**Cockcroft-Gault formula:** <sup>140</sup> 0.85 72 *Age Mass Kgs if female GFR Serum Cr* 

#### **Modification of diet in renal disease (MDRD) formula:**

1.154 0.203 *GFR SCr A* 186 . *ge i* 1.212 0.742 *f black if female*
