Course of Chronic Kidney Disease

Fig. 52.1 shows a conceptual model for CKD, and Table 52.1 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.

Conceptual model for chronic kidney disease.

The continuum of development, progression, and complications of chronic kidney disease (CKD) and strategies to improve outcomes. Dark green circles, Stages of CKD; light green circles, potential antecedents of CKD; lavender circles, consequences of CKD; thick arrows between circles, development, progression, and remission of CKD. Complications refers to all complications of CKD, including decreased glomerular filtration rate (GFR) and cardiovascular disease. Complications may also arise from adverse effects of interventions to prevent or treat the disease. Horizontal arrows pointing from left to right emphasize the progressive nature of CKD. Dashed arrowheads pointing from right to left signify that remission is less frequent than progression.

(Reproduced with modifications from the National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1–S266; Levey AS, Stevens LA, Coresh J. Conceptual model of CKD: applications and implications, Am J Kidney Dis. 2009;53:S4–S16.)

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 health care. 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. 52.1 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, and individuals with kidney failure can revert to earlier stages through kidney transplantation, shown as dashed arrowheads pointing from right to left. 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, 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 per 1.73 m ² of body surface area lasting for longer than 3 months (90 days; Table 52.2 ). 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 it 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 per 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 per 1.73 m ² represents the loss of half or more of the 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, gender, and body size. Normal GFR is approximately 120 to 130 mL/min per 1.73 m ² in a young adult and declines with age by approximately 1 mL/min per 1.73 m ² per year after the third decade. More than 25% of individuals aged 70 years and older have GFR of less than 60 mL/min per 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 per 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 per 1.73 m ² or initiation of kidney replacement therapy (dialysis or transplantation). A number of terms refer to severe decrease in kidney function, which is not synonymous with kidney failure. Uremia is defined as 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.

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 a 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 52.1 ). 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 52.3 ). Categories for GFR and albuminuria levels are shown in Tables 52.4 and 52.5 . Fig. 52.2A 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.

Table 52.3

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