STAGING CHRONIC KIDNEY DISEASE
The increasing incidence of CKD was first recognized in the 1990s. The need to care for the patient with CKD was understood, but there was a dearth of standardized management practices. Research was hindered by the many names used to identify kidney disease in the literature: from mildly elevated serum creatinine to low clearance to renal insufficiency.7 To rectify this, the National Kidney Foundation (NKF) convened an expert panel to develop a standard language and units of measurement to define kidney disease. The panel was tasked with developing classifications and an evaluation system for renal disease; identifying ways to attain more timely referrals to nephrology; clarifying research objectives; and delineating how to improve medication dosing. Ultimately, the main objective was to improve management of the patient with CKD.
In 2002, the NKF’s Dialysis Outcomes Quality Initiative (K/DOQI) defined the stages of kidney disease based on assessment of GFR and other kidney disease markers.8 GFR is a mathematical calculation for determining kidney function that corrects for loss of kidney function and incorporates the patient’s gender, race, age, and body size—the nonmodifiable risk factors known in 2001. GFR is expressed in mL/min/1.73 m2. Classifying patients with CKD according to the stage of kidney disease by GFR provides a mechanism for studying the efficacy and adverse reactions of medications while correlating them to each stage. This is of particular importance when treating patients with diabetes and kidney disease, as it can help to avoid adverse effects associated with inappropriate renal dosing. Many medications are renally eliminated; as kidney function diminishes, the pharmacokinetics of drugs are altered, potentially causing toxicity and an increased risk for drug interactions. As the GFR falls, even drugs not eliminated by the kidney may have altered pharmacokinetics and pharmacodynamics that may cause renal or systemic toxicity.1
Determining the precise method for renally dosing medication has been one of the most vigorously debated topics in CKD. Many medications were prescribed using the patient’s serum creatinine (SCr) concentration, a marker but not an exact measure of kidney disease.8 The Cockcroft-Gault equation, which provides an estimate of creatinine clearance (eCrCl; an alternate GFR measurement), was primarily used to determine renal drug dosing. 9
In 1999, a multisite study group worked to develop an equation to measure loss of kidney function in the patient with CKD.10,11 The new formula, known as the MDRD (Modification of Diet in Renal Disease) equation, standardized the measurement of loss of kidney function and provided an estimated GFR (eGFR) that was more accurate then eCrCl. At that time, the National Kidney Disease Education Program (NKDEP) decided to use the MDRD equation to assess renal function and use the eCrCl for dosing medications. The latter was chosen because most drugs were analyzed using eCrCl.9 More recently, the NKDEP stated that either the eCrCl or the eGFR is acceptable for renal drug dosing. Hudson and Nyman9 advise that when discrepancies occur between eGFR and eCrCl, clinical judgment should be applied in the elderly and in those with extremes in body weight. In those cases, therapeutic outcomes and risk versus benefit need to be considered when determining renal dosing.
The publication of CKD stages by K/DOQI in 2002 sparked research that has uncovered additional criteria that might be useful in slowing the progression and improving the management of CKD. Thus, in 2013, new guidelines by KDIGO incorporating the latest international findings were published.1 KDIGO expands the definition of CKD to include albuminuria (ALB) as an added risk factor (see Figure) and has modified K/DOQI stages 3 and 5. ALB was included because it has predictive value for progression of CKD to kidney failure. In the new classification, there are three ranges defined for ALB measured in mg/g (see Table 1). The KDIGO guidelines, like K/DOQI, classify kidney disease using a 1-to-5 staging system; however, the stage numbers in the KDIGO classification are prefaced by a G (ie, G1, G2). Also, as mentioned above, stages G3 and G5 in the KDIGO classification have been further categorized.
CKD stage 3 was divided for practical reasons. It was found that the original CKD stage 3 was too large and diverse a classification to use for research studies, tracking of hospitalizations, and precise dosing of medications.12 K/DOQI stage 3 encompassed a GFR from 30 to 59 mL/min/1.73 m2. The KDIGO guideline divides K/DOQI stage 3 into G3a (GFR of 45 to 59 mL/min/1.73 m2) and G3b (GFR of 30 to 44 mL/min/1.73 m2). The staging is then further classified by the presence or absence of ALB. The patient with a GFR of 56 mL/min/1.73 m2 with ALB is in CKD stage 3aA3 (very high and nephrotic ALB) and has a greater risk for disease progression than the patient with a GFR of 56 mL/min/1.73 m2 without ALB. The latter patient is in CKD stage 3aA1(optimal and mildly high ALB). Finally, many medication dosages that were acceptable at a GFR of 56 mL/min/1.73 m2 had to be further adjusted for patients with a GFR of 30 mL/min/1.73 m2 to avoid toxicity. This further justified the KDIGO reclassification of stage 3.
Stage 5 from K/DOQI only reflected a GFR < 15 mL/min/1.73 m2. KDIGO utilizes the same GFR but splits the stage into patients not receiving dialysis and those receiving dialysis, G5 and G5D, respectively. The dosing and timing of medications due to drug dialyzability—including renal-specific medications—may be quite different for patients on dialysis as compared to those with a GFR < 15 mL/min/1.73 m2 not on dialysis, making the distinction beneficial.
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