Recognizing the link between CKD and CVD in the primary care setting: accurate and early diagnosis for timely and appropriate intervention.Abstract: Chronic kidney disease Chronic kidney disease (CKD), also know as chronic renal disease, is a progressive loss of renal function over a period of months or years through five stages. Each stage is a progression through an abnormally low and progressively worse glomerular filtration rate, which is (CKD See count-key-data. ), which is becoming increasingly prevalent in the US and worldwide, eventually progresses to end-stage renal disease End-stage renal disease (ESRD)
Total kidney failure; chronic kidney failure is diagnosed as ESRD when kidney function falls to 5-10% of capacity.
Mentioned in: Chronic Kidney Failure
end-stage renal disease (ESRD ESRD end-stage renal disease.
End-stage renal disease; chronic or permanent kidney failure.
Mentioned in: Dialysis, Kidney
ESRD End-stage renal disease, see there ), requiring renal replacement therapy Renal replacement therapy is a term used to encompass life-supporting treatments for renal failure.
Disease that affects the heart and blood vessels.
Mentioned in: Lipoproteins Test
cardiovascular disease . Indeed, CKD patients are more likely to die of cardiovascular complications than progress to ESRD. However, data indicate that early recognition and management of CKD can have a significant positive impact on disease outcome. This creates an important interventional opportunity for the primary care physician. This report describes the major risk factors and comorbidities associated with the development and progression of CKD and offers suggestions for timely diagnosis and management of CKD in the primary care setting.
Key Words: chronic kidney disease, diabetes, hypertension, cardiovascular disease, proteinuria proteinuria /pro·tein·uria/ (-ur´e-ah) an excess of serum proteins in the urine, as in renal disease or after strenuous exercise.proteinu´ric
1. , anemia
Chronic kidney disease (CKD) is a significant problem in the United States (US), and its incidence is increasing at an alarming rate. Nearly 20 million Americans are affected by CKD, and some 20 million more are at risk of developing it. (1,2) CKD progresses through stages of severity until renal failure renal failure
Acute or chronic malfunction of the kidneys resulting from any of a number of causes, including infection, trauma, toxins, hemodynamic abnormalities, and autoimmune disease, and often resulting in systemic symptoms, especially edema, occurs, requiring renal replacement therapy (RRT RRT Rapid Response Team
RRT Registered Respiratory Therapist
RRT Renal Replacement Therapy
RRT Regional Response Team
RRT Right Side (philately)
RRT Relative Retention Time
RRT Round Robin Test
RRT Rating Region Table ) in the form of dialysis or transplantation. An increasing amount of literature suggests that timely diagnosis and treatment of CKD can delay disease progression and may decrease adverse cardiovascular outcomes. Nevertheless, data continue to report that CKD is not recognized in its early stages, and when it is diagnosed, care is often suboptimal Suboptimal
A solution is called suboptimal if a part of the solution has been optimized without regards to the overall objective. , such that many more CKD patients die than reach dialysis. (3)
CKD and its associated risk factors are likely to be encountered in a primary care setting. The fact that CKD remains under-diagnosed and under-treated means that opportunities for intervention are being lost. The need for increased awareness presents an important opportunity for the primary care physician to recognize the risk factors associated with CKD, screen high-risk patients, and start treatment early enough to positively impact disease progression. This paper will describe the risk factors for the development and progression of CKD with emphasis on cardiovascular disease (CVD CVD Cardiovascular disease, see there ) in CKD. The importance of early diagnosis and management, and suggestions for CKD diagnosis and management in the primary care setting will be discussed.
Definition of CKD
The National Kidney Foundation Not to be confused with American Kidney Fund.
The National Kidney Foundation, Inc. (NKF) is a major voluntary health organization in the United States. Its mission is to prevent kidney and urinary tract diseases, improve the health and well-being of individuals and (NKF NKF National Kidney Foundation
NKF Norges Kampsportforbund
NKF Norges Klatreforbund (Norway)
NKF Norges Kofferttenking Forbund ) Kidney Disease Kidney Disease Definition
Kidney disease is a general term for any damage that reduces the functioning of the kidney. Kidney disease is also called renal disease. Outcome Quality Initiative (KDOQI KDOQI Kidney Disease Outcomes Quality Initiative (National Kidney Foundation) ) describes the identification and classification of CKD, and the stratification of risk factors that increase the progression of CKD. (1) The established criteria for a diagnosis of CKD is 1) kidney damage kidney damage Kidney injury Nephrology A structural or functional compromise in renal function due to external–eg, athletic, occupational, or other trauma, resulting in bruising or hemorrhage, which can be profuse and life threatening Etiology Vascular for at least 3 months as defined by structural or functional abnormalities with or without decreased glomerular filtration rate glomerular filtration rate
n. Abbr. GFR
The volume of water filtered out of the plasma through glomerular capillary walls into Bowman's capsules per unit of time. (GFR GFR - Grim File Reaper ), or 2) a GFR <60 mL/min/1.73 [m.sup.2] with or without kidney damage. Functional and structural kidney damage can be detected by aberrations in blood or urine composition, and abnormalities found in imaging studies, respectively.
CKD is divided into 5 stages based on the criteria of GFR and/or kidney damage (Table 1). Stage 5 is defined as a GFR less than 15 mL/min/1.73 [m.sup.2], and constitutes renal failure requiring RRT, while stages 1 to 4 represent the CKD population with varying degrees of renal insufficiency renal insufficiency A defect in renal ability to 'clear' waste products, a sign of inadequate glomerular filtration . Stages 1 through 3 are the most prevalent, and it is in this population that recognition and treatment of CKD can have the greatest impact on disease outcome, although slowing the rate of progression is still possible in Stage 4. (4)
Timely diagnosis and treatment of chronic kidney disease can delay disease progression and may decrease adverse cardiovascular outcomes.
CKD Risk Factors
There are a variety of risk factors that contribute to the development and progression of CKD, but diabetes and hypertension are by far the most common (Table 2). (5)
Hypertension and CKD form a "vicious cycle" such that untreated hypertension can lead to CKD, and CKD to hypertension. (6) Thus, hypertension is both a risk factor for, and a serious comorbidity of, CKD. Hypertension is defined as a systolic blood pressure Systolic blood pressure
Blood pressure when the heart contracts (beats).
Mentioned in: Hypertension of 140 mm Hg or higher, or a diastolic blood pressure Diastolic blood pressure
Blood pressure when the heart is resting between beats.
Mentioned in: Hypertension of 90 mm Hg or higher. (7) Between 50% and 75% of patients with a GFR less than 60 mL/min/1.73 [m.sup.2] are hypertensive hypertensive /hy·per·ten·sive/ (-ten´siv)
1. characterized by increased tension or pressure.
2. an agent that causes hypertension.
3. a person with hypertension. . (1) The strong association between hypertension and the risk of developing CKD starts at blood pressure levels considered to be prehypertensive (130-139 mm Hg systolic Systolic
The phase of blood circulation in which the heart's pumping chambers (ventricles) are actively pumping blood. The ventricles are squeezing (contracting) forcefully, and the pressure against the walls of the arteries is at its highest. ; 85-89 mm Hg diastolic Diastolic
The phase of blood circulation in which the heart's pumping chambers (ventricles) are being filled with blood. During this phase, the ventricles are at their most relaxed, and the pressure against the walls of the arteries is at its lowest. ). (8) Recent data have demonstrated that even a modest increase in blood pressure in the absence of baseline renal disease Renal disease
Mentioned in: Glycogen Storage Diseases
hypertension High blood pressure Cardiovascular disease An abnormal ↑ systemic arterial pressure, corresponding to a systolic BP of > 160 mm Hg is an independent risk factor for the progression of CKD to ESRD. (9) These results suggest that high blood pressure is a strong predictor of, and may be an initiation factor initiation factor
n. Abbr. IF
Any of several soluble proteins involved in the initiation of protein synthesis and released from the ribosome as it progresses into chain elongation. for, the development of CKD.
Nephropathy nephropathy /ne·phrop·a·thy/ (ne-frop´ah-the) disease of the kidneys.nephropath´ic
analgesic nephropathy is characterized by the presence of protein (albumin) in the urine as a result of increased glomerular glomerular /glo·mer·u·lar/ (glo-mer´u-ler) pertaining to or of the nature of a glomerulus, especially a renal glomerulus.
adj. permeability secondary to glomerular damage. Normal urinary excretion of albumin is less than 30 mg/d (Table 3). Microalbuminuria refers to an albumin concentration between 30 and 300 mg/d, and is most accurately detected by determination of the albumin-to-creatinine ratio. Microalbuminuria is often the first sign of kidney disease, predicts progressive kidney damage, and increases the risk of the development of CVD. (10) Albuminuria albuminuria /al·bu·min·uria/ (al-bu?mi-nu´re-ah) presence in the urine of serum albumin, the most common kind of proteinuria.albuminu´ric
n. (macroalbuminuria) is defined as an albumin concentration of greater than 300 mg/d and denotes advanced kidney disease that is typically followed by a decline in the GFR.
The strong association between hypertension and the risk of developing chronic kidney disease starts at prehypertensive blood pressure levels.
CVD in CKD
CVD is extremely prevalent in CKD, more so than in the general population. Nearly half of all patients with CKD die of cardiovascular event, particularly heart failure (HF) and acute myocardial infarction acute myocardial infarction (·kyōōtˑ mī·ō·karˑ·dē· (MI). (11) The NKF task force on CVD in CKD suggested that CKD patients be considered the highest risk group for subsequent cardiovascular events. (12)
The strong predictive capacity of elevated serum creatinine or decreased GFR for CVD risk and mortality has been demonstrated in a variety of trials. Elevated serum creatinine/decreased GFR is as important a CV risk factor in predicting poor CV outcome as the more traditional risk factors of diabetes, hypertension, atherosclerosis, or previous MI. (13) CKD patients at high risk for CV events include those who have established CVD or those in whom a number of CV risk factors is present. However, patients with even mild renal insufficiency and few or no CV risk factors are also at higher risk for developing CVD. (14) A recent retrospective analysis of several large trials demonstrated that CKD was significantly associated with CVD and all-cause mortality in a relatively healthy community-based population, compared with subjects without CKD. This was true even though patients without CKD had some traditional CV risk factors, such as smoking and diabetes. (15)
While the burden of CVD morbidity and mortality Morbidity and Mortality can refer to:
Elevated serum creatinine/decreased glomerular filtration rate is as important in predicting poor cardiovascular outcome as the more traditional risk factors of diabetes, hypertension, atherosclerosis, or previous myocardial infarction myocardial infarction: see under infarction. .
CV Risk Factors in CKD: Appropriate Management Strategies
Traditional risk factors for the progression of CVD in CKD include diabetes, proteinuria/albuminuria, hypertension, and hyperlipidemia hyperlipidemia /hy·per·lip·id·emia/ (-lip?i-de´me-ah) elevated concentrations of any or all of the lipids in the plasma, including hypertriglyceridemia, hypercholesterolemia, etc. . A nontraditional factor that increases CV risk in CKD patients, perhaps by enhancing some of the traditional risk factors, is anemia. An understanding of the various interventional strategies available may influence the course of CKD. Many CV risk factors in patients with CKD are modifiable.
Hypertension is common in all stages of CKD, contributes to nephropathy, gets progressively worse in parallel with declining kidney function, and increases the risk of coronary heart disease coronary heart disease: see coronary artery disease.
coronary heart disease
or ischemic heart disease
Progressive reduction of blood supply to the heart muscle due to narrowing or blocking of a coronary artery (see atherosclerosis). and stroke. (11) Increased systemic blood pressure directly damages the small vessels of the kidney, thereby compromising glomerular filtration rate. Hypertension can also lead to left ventricular hypertrophy left ventricular hypertrophy Cardiology Enlargement of the left ventricle often linked to the prolonged hemodynamic stress of CHF, characterized by myocardial cell hypertrophy, ↑ left ventricular wall thickness, ↓ ventricular compliance, ↑ (LVH LVH
left ventricular hypertrophy
left ventricular hypertrophy.
LVH Left ventricular hypertrophy, see there ), and in patients with CKD, the prevalence of LVH is inversely proportional to the level of kidney function, and affects approximately 31 to 45% of patients with Stage 3 or 4 CKD. (16)
Proteinuria is a powerful risk multiplier in CKD, and accurately predicts the progression of renal damage. (17) It is generally accepted that proteinuria, as a consequence of renal damage, mediates tubular injury resulting in the progression of renal disease and end-organ failure. (11) However, evidence is accumulating which suggests that microalbuminuria is a reflection of general vascular endothelial dysfunction that is associated with a higher susceptibility to renal and CV events. (18) Proteinuria is also associated with clinical factors that directly or indirectly result in CVD, including hyperglycemia hyperglycemia: see diabetes. , hypertension, renal dysfunction, and dyslipidemia. The presence of small amounts of protein in the urine, even in the setting of normal GFR and blood pressure, remains a strong predictor for cardiovascular risk. (19) For this reason, the definition of proteinuria and microalbuminuria for hypertensive patients is more stringent than that for normotensive normotensive /nor·mo·ten·sive/ (-ten´siv)
1. characterized by normal tone, tension, or pressure, as by normal blood pressure.
2. a person with normal blood pressure. patients (Table 3). (7) Increased CV risk occurs with an elevation in the albumin/creatinine ratio, and starts well below the traditional cutoff for microalbuminuria. (10)
Hypertension Management/Proteinuria Reduction
Aggressive blood pressure control retards the progression of renal disease. (20) Maintenance of optimal blood pressure slows the reduction in GFR, reduces the degree of proteinuria, and reduces the risk of poor CV outcomes. (21,22) To underscore the importance of blood pressure control in reducing the rate of renal decline and the risk of CV events in patients with CKD, the recommended target blood pressure is less than 130/80 mm Hg. (7)
Microalbuminuria is a reflection of general vascular endothelial dysfunction that is associated with a higher susceptibility to renal and cardiovascular events.
Several lines of evidence have shown that antihypertensives that disrupt the renin-angiotensin system (RAS (1) See network access server.
(2) (Remote Access Service) A Windows NT/2000 Server feature that allows remote users access to the network from their Windows laptops or desktops via modem. See RRAS and network access server. ) can reduce proteinuria, preserve GFR and kidney function, and reduce CV morbidity and mortality. (20,23) The RAS-targeting angiotensin-converting enzyme inhibitors Angiotensin-Converting Enzyme Inhibitors Definition
Angiotensin-converting enzyme inhibitors (also called ACE inhibitors) are medicines that block the conversion of the chemical angiotensin I to a substance that increases salt and water retention in the (ACEIs) and angiotensin receptor blockers (ARBs) may have renoprotective effects independent of blood pressure control. Several lines of evidence suggest that the degree of proteinuria reduction with ACEIs and ARBs is correlated with the degree of cardioprotection, irrespective of the effects on other CV risk factors. (18) ACEIs have been shown to have positive effects, including reducing the amount of proteinuria, the decline of GFR, and the progression to ESRD beyond that attributed to blood pressure reduction. (24) On the other hand, some evidence suggests that the degree of renoprotection with antihypertensive antihypertensive /an·ti·hy·per·ten·sive/ (-ten´siv) counteracting high blood pressure, or an agent that does this.
Reducing high blood pressure.
n. therapy is directly proportional to the extent of blood pressure reduction. (25) Optimal blood pressure control is often achieved by a combination of medications and indeed, dual blockade of the RAS can achieve better blood pressure control as well as additional renal and cardiovascular protection in patients with nephropathy. (26) Additional randomized controlled trials examining the various combinations of antihypertensive medications and their effect on blood pressure control and proteinuria reduction are needed to better understand the contributions of these two parameters on the ability to provide cardio- and renoprotection.
Proteinuria is a powerful risk multiplier in chronic kidney disease, and accurately predicts the progression of renal damage.
Hyperlipidemia is a risk factor for CVD, and is relatively common in CKD, especially as renal decline progresses. (27) Lipid abnormalities in CKD patients include elevated triglycerides Triglycerides
Fatty compounds synthesized from carbohydrates during the process of digestion and stored in the body's adipose (fat) tissues. High levels of triglycerides in the blood are associated with insulin resistance. and an increased ratio of low-density lipoprotein low-density lipoprotein
n. Abbr. LDL
A lipoprotein that contains relatively high amounts of cholesterol and is associated with an increased risk of atherosclerosis and coronary artery disease. (LDL LDL - ["LDL: A Logic-Based Data-Language", S. Tsur et al, Proc VLDB 1986, Kyoto Japan, Aug 1986, pp.33-41]. ) cholesterol to high-density lipoprotein high-density lipoprotein
n. Abbr. HDL
A lipoprotein that contains relatively small amounts of cholesterol and triglycerides and is associated with a decreased risk of atherosclerosis and coronary artery disease. (HDL (Hardware Description Language) A language used to describe the functions of an electronic circuit for documentation, simulation or logic synthesis (or all three). Although many proprietary HDLs have been developed, Verilog and VHDL are the major standards. ) cholesterol. Micro- and macroalbuminuria are associated with elevated cholesterol, and the combination of microalbuminuria and early renal disease is associated with an increase in LDL cholesterol LDL cholesterol
See low-density lipoprotein.
Low-density lipoprotein cholesterol is the primary cholesterol molecule. High levels of LDL increase the risk of coronary heart disease. and a significant decrease in HDL cholesterol. (11) These conditions set the stage for the development of atherosclerosis and heart disease. (27)
In addition to dietary modifications, lipid-lowering statins Statins
A class of drugs commonly used to lower LDL cholesterol levels.
Mentioned in: C-Reactive Protein are effective in reducing cholesterol and albuminuria, and can be used safely in patients with mild renal insufficiency; but without clinical trial evidence, it remains unclear whether statin stat·in
Any of a class of drugs that inhibit a key enzyme involved in the synthesis of cholesterol and promote receptor binding of LDL cholesterol, resulting in decreased levels of serum cholesterol. therapy can decrease progression of renal decline in this population. (18,28) Nonetheless, the KDOQI guidelines recommend lipid lowering therapy in CKD patients, and suggest that LDL cholesterol levels be less than 100 mg/dL (ie, CKD as a cardiovascular equivalent) and triglyceride levels be under 200 mg/dL. (28)
Anemia is a common feature of CKD and worsens as kidney function declines. Anemia is an important CVD risk factor in those with CKD because of its association with LVH. (16,29) Indeed, anemia has been recognized as the "fifth CV risk factor," along with smoking, hypercholesterolemia Hypercholesterolemia Definition
Hypercholesterolemia refers to levels of cholesterol in the blood that are higher than normal.
Cholesterol circulates in the blood stream. It is an essential molecule for the human body. , diabetes, and hypertension in those with CKD. (30) In conjunction with CKD and HF, anemia becomes a risk multiplier, increasing the risk of mortality compared either to CKD and HF alone, or in combination. Anemia is a modifiable risk factor, and correction of anemia with recombinant human erythropoietin erythropoietin /eryth·ro·poi·e·tin/ (-poi´e-tin) a glycoprotein hormone secreted by the kidney in the adult and by the liver in the fetus, which acts on stem cells of the bone marrow to stimulate red blood cell production (rHuEPO) in patients not yet on dialysis may decrease the progression of CKD, delay renal failure, improve quality of life, and improve overall cardiac function. (31) Because of the large amount of information regarding the impact of anemia in CKD and CVD, the identification and management of anemia will be discussed in detail in the next paper of this series.
Anemia has been recognized as the "fifth CV risk factor," along with smoking, hypercholesterolemia, diabetes, and hypertension in patients with chronic kidney disease.
CKD and Comorbidity Identification and Management in the Primary Care Setting
CKD is highly under-recognized and under-treated, and although many patients are at risk for CKD, only a small number are being screened for it. (32) As a result, by the time many patients are referred to a nephrologist Nephrologist
A doctor who specializes in the diseases and disorders of the kidneys.
Mentioned in: Kidney Biopsy
nephrologist , substantial loss of renal function has already occurred. (33) In light of these recent findings, an enormous opportunity presents itself for primary care physicians to be aware of CKD risk factors in their patients, initiate testing for renal function in their high-risk patients, and deliver timely and appropriate treatment of comorbidities. The 2002 NKF KDOQI guidelines include practical clinical information for assessing and treating CKD (Table 1). (1) Assessments to identify high risk patients and diagnose CKD can be as simple as obtaining blood pressure measurements, a urinalysis, and blood work, and are easily performed in the office. Diagnostic codes corresponding to the different stages of CKD have been developed to better differentiate patients based on the severity of their disease (Table 1). (34) The following segments describe diagnostic and interventional strategies that can be easily performed in the primary care setting to identify and properly manage patients at risk for CKD.
Is the Patient at Risk?
Table 2 lists the risk factors that either directly cause, or are associated with, the development of CKD. All routine healthcare visits should include evaluations to determine whether an individual is at increased risk for developing CKD. (1) Simple office assessments and physical examination and history can be extremely helpful in deciding whether a patient is at risk for CKD. Blood pressure measurements are usually taken at each office visit, and lipid and glucose levels can be determined by a routine blood test. If a patient is deemed high risk, kidney damage should be evaluated by estimating the GFR and assessing the presence of proteinuria. If there is no evidence of renal damage, high risk patients should be counseled for appropriate risk reduction, and reevaluated periodically. (35)
Calculate the GFR
Although creatinine levels alone are relatively inaccurate in determining the presence of kidney disease, especially mild kidney disease, physicians can estimate GFR using standard equations such as the Cockroft-Gault or the MDRD MDRD Modification of Diet in Renal Disease
MDRD Mobilization, Deployment, Redeployment and Demobilization
MdRD Median Round Delay
MDRD Maximum Deflection Ratio Detector (modification of diet in renal disease) (Table 4) that are available on the NKF web site. (36-38) Many clinical labs are now routinely reporting the estimated GFR based on these calculations when reporting the serum creatinine. Normal GFR varies according to age, sex, and body size; in young adults, it is approximately 120 to 130 mL/min/1.73 [m.sup.2] and declines with age. (35) A persistent reduction in GFR is a specific indication of CKD. KDOQI guidelines advise that patients be referred to a nephrologist when the GFR declines to less than 30 mL/min/1.73 [m.sup.2], or when the physician is unable to develop an action plan. (1) Even before reaching CKD stages 4 or 5, the progression of renal decline can be attenuated Attenuated
Alive but weakened; an attenuated microorganism can no longer produce disease.
Mentioned in: Tuberculin Skin Test
having undergone a process of attenuation. , and the guidelines suggest action steps that can be taken at different stages of CKD to achieve this goal (Table 1). (1) Individuals with an estimated GFR of under 60 mL/min/1.73 m2, who often go unrecognized in daily clinical practice, should have their blood pressure reduced to the recommended goal of less than 130/80 mm Hg. (7)
Assessment of Proteinuria
A urine dipstick dipstick /dip·stick/ (dip´stik) a strip of cellulose chemically impregnated to render it sensitive to protein, glucose, or other substances in the urine. can usually detect proteinuria of 1+ or greater (between 300-500 mg/d), and should be performed on any patient with risk factors, regardless of GFR (Fig.). If the dipstick test is negative for protein, an albumin-to-creatinine ratio should be determined from a fresh (1st morning void) sample. In high risk patients, an albumin-to-creatinine ratio of greater than 300 mg/g (macroalbuminuria) warrants further diagnostic evaluation. A ratio of higher than 30 mg/g on successive measurements (microalbuminuria) suggests progressive kidney disease, and is a powerful predictor of cardiac disease as well as renal disease. (33,39) Patients with CKD should have urine protein levels measured quantitatively by an albumin-to-creatinine ratio. (1) While proteinuria remains a powerful risk factor in those with hypertension and diabetes, and reflects the degree of underlying CKD, no clinical trial evidence currently exists for reducing urinary protein to a specific level for outcome improvement.
Chronic kidney disease affects millions of people in the US and worldwide. The prevalence of CKD has been increasing, and this trend is likely to continue. Not surprisingly, many of the risk factors that contribute to the development of CKD also contribute to its progression. Fortunately, many risk factors that lead to the progression of CKD are modifiable, and primary care physicians should be aware that these conditions can be routinely detected and managed in the office setting. Physicians have an opportunity to potentially modify the course of a disease that affects millions of patients through integration of diagnostic and therapeutic guidelines. As discussed, this will translate into the early detection and appropriate treatment of CKD in the primary care setting.
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JFE Joint Force Employment
JFE joint fires element (US DoD)
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34. Centers for Medicare and Medicaid Services The Centers for Medicare and Medicaid Services (CMS), previously known as the Health Care Financing Administration (HCFA), is a federal agency within the United States Department of Health and Human Services (DHHS) that administers the Medicare program and . ICD-9 Coding Resources. www.cms.hhs.gov/medlearn/icd9code.asp. Accessed March 2, 2007.
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36. Cockroft DW, Gault n. 1. (Geol.) A series of beds of clay and marl in the South of England, between the upper and lower greensand of the Cretaceous period. MH. Prediction of creatinine clearance from serum creatinine. Nephron nephron: see urinary system.
Functional unit of the kidney that removes waste and excess substances from the blood to produce urine. Each of the million or so nephrons in each kidney is a tubule 1.2–2.2 in. (30–55 mm) long. 1976;16:31-41.
37. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation: Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461-470.
38. http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm. Accessed. March 2, 2007.
39. Bakris GL. Implications of albuminuria on kidney disease progression. J Clin Hypertens (Greenwich) 2004;6(suppl 3):18-22.
40. Basile J. Chronic kidney disease: it's time to recognize its presence in our patients with hypertension. J Clin Hypertens 2004;6:548-552.
A cynic is a man who, when he smells flowers, looks around for a coffin. --H.L. Mencken
Jan N. Basile, MD
From Ralph H. Johnson Ralph Henry Johnson (1949-1968) was a United States Marine who was posthumously awarded the Medal of Honor for heroism in March 1968 during the Vietnam War. He sacrificed his life to save the life of a fellow Marine. VA Medical Center, Charleston, Medical University of South Carolina “MUSC” redirects here. For Abel Santa María airport in Santa Clara, Cuba (ICAO code MUSC), see Abel Santa María Airport.
The Medical University of South Carolina , Charleston, South Carolina.
Reprint requests to Dr. Jan N. Basile, Ralph H. Johnson VA Medical Center, Medical University of South Carolina, 109 Bee Street, Charleston, SC 29401. E-mail: Jan.Basile@med.va.gov
Accepted July 28, 2006.
RELATED ARTICLE: Key Points
* Chronic kidney disease (CKD) is becoming increasingly prevalent, due in part to the increase in its two leading causes: diabetes and hypertension. CKD eventually progresses to end-stage renal disease (ESRD), a condition requiring renal replacement therapy such as dialysis or renal transplantation.
* CKD is a significant risk factor for cardiovascular disease (CVD).
* Treatable comorbidities such as proteinuria, hyperlipidemia, and anemia can exacerbate CVD in those with CKD and significantly hasten the progression of CKD to ESRD, increasing the risk of death.
* CKD in its early stages often goes unrecognized and is underdiagnosed, such that CKD patients are often referred to a specialist in the later stages of the disease.
* More patients with CKD die from cardiovascular complications than reach renal replacement therapy.
* Evidence shows that appropriate and timely management of traditional risk factors and comorbidities can result in increased quality of life and a decrease in the rate of progression to ESRD.
* Primary care physicians have an important opportunity, through the recognition of risk factors, for early screening and diagnosis of CKD. Appropriate treatment of associated comorbidities can delay CKD progression and improve disease outcome.
Table 1. Stages of CKD defined by GFR. ICD-9 diagnostic codes, and action steps CKD stage GFR* (mL/min/1.73 [m.sup.2]) Description 1 ([double dagger]) [greater than or equal to]90 Kidney damage and DM with normal or [up arrow] GFR 2 ([double dagger]) 60-89 Kidney damage with mild [down arrow] GFR 3 30-59 Moderate [down arrow] GFR 4 15-29 Severe [down arrow] GFR 5 [less than or equal to]15 Kidney Failure (or dialysis) ICD-9 Diagnostic CKD stage codes ([dagger]) Action 1 ([double dagger]) 585.1 Screening and CKD risk reduction 2 ([double dagger]) 585.2 Diagnosis and treatment, management of comorbidities, slow progression of CKD, and CVD risk reduction 3 585.3 Estimate CKD progression 4 585.4 Evaluate and treat complications 5 585.5 Prepare for RRT *GFR estimated from serum creatinine using Modification of Diet in Renal Disease (MDRD). Study equation based on age, gender, race and calibration for serum creatinine. ([dagger]) www.cms.hhs.gov/medlearn/icd9code.asp, accessed October 10, 2005. (34) ([double dagger]) Kidney damage estimated by spot albumin-to-creatinine ratio [greater than or equal to]17 mg/g in men or [greater than or equal to]25 mg/g in women in two measurements. CKD = chronic kidney disease; CVD = cardiovascular disease; GFR = glomerular filtration rate; RRT = renal replacement therapy. Adapted from NKF KDOQI Clinical Practice Guidelines for Chronic Kidney Disease. (1) Table 2. CKD risk factors Disease states that directly cause renal damage Autoimmune disease (lupus nephritis, Goodpasture syndrome) Antibody deposition disease and IgA nephropathy Focal segmented glomerular sclerosis Modifiable CKD associations or risk factors Diabetes mellitus Hypertension Obesity Smoking Hyperlipidemia Analgesic abuse Illicit drug use Nonmodifiable CKD associations or risk factors Advanced age (>60 years of age) Family history Non-Caucasian race Low socioeconomic status/low education level Summarized in McClellan. (5) Table 3. Normal and elevated urine levels of protein/albumin JNC Definition* NKF Definition ([dagger]) (mg/g) (mg/g) Description <20 <30 Normal urinary albumin excretion 20-200 30-300 Microalbuminuria >200 >300 Macroalbuminuria (clinical proteinuria) >3000 DM-related nephrotic syndrome Adapted from: *Chobanian (7), and ([dagger]) Grundy. (21) JNC -- Joint National Committee; NKF -- National Kidney Foundation; DM -- diabetes mellitus. Table 4. Equations to estimate GFR Abbreviated Modification of Diet in Renal Disease (MDRD) study Equation GFR (mL/min/1.73 [m.sup.2]) = 186 X (sCr)[.sup.-1.154] X (Age)[.sup.-0.203] X 0.742 if female X 1.210 if African American Cockroft-Gault equation Creatinine clearance (mL/min) = (140-Age) X Weight X 0.85 if Female 72 X sCr sCr = serum creatinine. From Cockroft and Levey. (36,37)