Staging and Management of Chronic Kidney Disease

Course of Chronic Kidney Disease

Fig. 51.1 shows a conceptual model for CKD, and Table 51.1 outlines the outcomes. This model describes the natural history of CKD, beginning with antecedent conditions associated with increased risk for developing kidney disease, followed by the stages of CKD (kidney damage, decreased glomerular filtration rate [GFR], and kidney failure), and associated complications.

Risk factors for the development of CKD include exposure to factors that cause kidney disease, such as hypertension, diabetes, autoimmune diseases, and kidney stones, and characteristics that increase susceptibility to kidney disease, such as older age, minority racial and ethnic status, and reduced nephron mass. The mechanisms underlying increased susceptibility have not been completely described or proven. For example, minority race or ethnicity may imply an underlying genetic tendency or it may be a marker for lack of access to healthcare. Susceptibility factors may explain why a family history of kidney disease, regardless of the cause, places an individual at increased risk for development of kidney disease.

The horizontal arrows in Fig. 51.1 indicate transitions among kidney outcomes. The arrows pointing from left to right emphasize the progressive nature of CKD. However, the rate of progression is variable, and not all CKD progresses; thus, not all patients with CKD develop kidney failure. Early stages of kidney disease may be reversible with treatment, as shown as dashed arrowheads pointing from right to left, and even individuals with kidney failure can revert to earlier stages through kidney transplantation. Studies suggest that CKD is a risk factor for development of AKI and that episodes of AKI may increase the risk for progression of CKD. The earlier stages and the risk factors for progression to later stages can be identified, permitting improvements in outcome by prevention, earlier detection, and initiation of therapies that can slow progression and prevent the development of kidney failure.

The diagonal arrows emphasize complications of CKD other than kidney outcomes. It is well accepted that both decreased GFR and albuminuria are associated with an independent risk of CVD and all-cause mortality. Metabolic and endocrine complications of decreased GFR, including anemia, bone and mineral disorders, malnutrition, and neuropathy, collectively comprising the uremic syndrome, have long been recognized as consequences of kidney failure, but these abnormalities may appear with lesser reduction in GFR. Similarly, nephrotic syndrome occurs in patients with marked albuminuria, but hyperlipidemia and hypercoagulability may be observed with lesser increases in albuminuria. Other complications include threats to patient safety from systemic toxicity from drugs and procedures, as well as an increased risk of infections and impaired cognitive and physical function. Strategies for prevention, early detection, and treatment of CKD complications may prolong survival and improve quality of life, even if there is no effect on kidney disease progression.

Definition of Chronic Kidney Disease

The 2012 KDIGO guideline update defines CKD as abnormalities of kidney structure or function, present for longer than 3 months, with implications for health. Criteria for CKD include either kidney damage or GFR of less than 60 mL/min/1.73 m ² of body surface area lasting for longer than 3 months (90 days; Table 51.2 ). Of note, CKD can be diagnosed without knowledge of its cause.

Kidney damage can be within the parenchyma, large blood vessels, or collecting systems, and is usually inferred from markers rather than direct examination of kidney tissue. The markers of kidney damage often provide a clue to the likely site of damage within the kidney and, in association with other clinical findings, the cause of kidney disease. Because most kidney diseases in North America are caused by diabetes or hypertension, persistent albuminuria is the principal marker. Other markers of damage include abnormalities in urine sediment (e.g., blood cells, tubular cells, or casts), abnormal findings on imaging studies (e.g., hydronephrosis, asymmetry in kidney size, polycystic kidney disease, stones, small echogenic kidneys), and abnormalities in blood and urine chemistry measurements (related to altered tubular function, such as renal tubular acidosis). A history of kidney transplantation is also defined as a marker of kidney damage, and patients with a functioning transplant are considered to have CKD, irrespective of the presence of other markers of kidney damage or the level of GFR.

Decreased GFR for more than 3 months, specifically GFR less than 60 mL/min/1.73 m ² , represents CKD, irrespective of age. The level of GFR is usually accepted as the best overall index of kidney function in health and disease. GFR less than 60 mL/min/1.73 m ² represents the loss of half or more of the young adult level of normal kidney function, and it is associated with an increased prevalence of systemic complications. The normal level of GFR varies according to age, sex, and body size. Normal GFR is approximately 120 to 130 mL/min/1.73 m ² in a young adult and declines with age by approximately 1 mL/min/1.73 m ² per/yearafter the third decade. More than 25% of individuals aged 70 years and older have GFR of less than 60 mL/min/1.73 m ² ; whether this results from normal aging or the high prevalence of systemic vascular diseases that cause kidney disease remains controversial. Whatever its cause, GFR less than 60 mL/min/1.73 m ² in the elderly is an independent predictor of adverse outcomes such as death and CVD.

Kidney failure is defined either as a GFR less than 15 mL/min/1.73 m ² or initiation of kidney replacement therapy (dialysis or transplantation). A number of terms refer to a severe decrease in kidney function, which is not synonymous with kidney failure. Uremia is defined as severely elevated concentrations within the blood of urea, creatinine, and other nitrogenous end products of amino acid and protein metabolism that are normally excreted in the urine. The uremic syndrome, the terminal clinical manifestation of kidney failure, is the constellation of symptoms, physical signs, and abnormal findings on diagnostic studies that result from the failure of the kidneys to maintain adequate function. End-stage kidney disease (ESKD) generally refers to kidney failure treated by dialysis or transplantation, regardless of the level of kidney function, and is used administratively in the United States and elsewhere. The availability of dialysis and transplantation for the treatment of kidney failure varies around the world, and not all patients with kidney failure choose to receive kidney replacement therapy. Therefore, populations defined as having ESKD might not include patients with kidney failure who are not treated with dialysis or transplantation, and the term kidney failure with replacement therapy (KFRT) has been suggested as an alternative to ESKD.

Classification of Chronic Kidney Disease

The NKF-KDOQI classification system for stages of CKD was based on the severity of the disease defined only by the level of GFR. The KDIGO classification adds cause of the disease and level of albuminuria to the level of GFR (CGA classification). Because recent epidemiologic data demonstrate strong graded relationships of the level of albuminuria, as well as the level of GFR, with risks of kidney disease progression, CVD, and mortality, this more detailed classification relates more closely to prognosis (see Table 51.1 ). The cause of disease is generally classified according to the presence or absence of systemic diseases (secondary or primary) and the presumed location of the pathologic-anatomic lesions (glomerular, tubulointerstitial, vascular, cystic, or disease in the kidney transplant; Table 51.3 ). Categories for GFR and albuminuria levels are shown in Tables 51.4 and 51.5 . Fig. 51.2 shows the two-dimensional grid relating the risk of kidney outcomes and mortality to level of GFR and albuminuria. The green, yellow, orange, and red shaded categories represent patients at low, moderate, high, and very high risk of kidney outcomes and mortality, respectively.

Prevalence

Fig. 51.2 shows the prevalence estimates derived from measurements of serum creatinine to estimate GFR (eGFRcr) and albumin-to-creatinine ratio (ACR) during National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2006. The prevalence of ACR greater than 30 mg/g or estimated GFR less than 60 mL/min/1.73 m ² is approximately 11.5% of the US adult population. The proportion of participants with CKD in the groups at moderate, high, and very high risk is about 73%, 18%, and 9%, respectively, representing a prevalence in the general population of about 8.5%, 2%, and 1%, respectively. This prevalence is more than 50 times greater than the prevalence of treated ESKD of approximately 0.2% reported by the US Renal Data System during this interval. Because kidney disease usually begins late in life and progresses slowly, most people in the earlier stages of CKD die of other causes before reaching kidney failure. In these patients, the burden of CKD is reflected in the complications of earlier stages, including increased mortality and morbidity, reduced ­quality of life, and high cost.