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It is usually not necessary to obtain a timed urine collection (overnight or 24-hour) for these evaluations in either children or adults.
First morning specimens are preferred, but random specimens are acceptable if first morning specimens are not available. Patients with a positive dipstick test (1+ or greater) should undergo confirmation of proteinuria by a quantitative measurement (protein-to-creatinine ratio or albumin-to-creatinine ratio) within 3 months. Patients with two or more positive quantitative tests temporally spaced by 1 to 2 weeks should be diagnosed as having persistent proteinuria and undergo further evaluation and management for chronic kidney disease as stated in Guideline 2. Monitoring proteinuria in patients with chronic kidney disease should be performed using quantitative measurements. Orthostatic proteinuria must be excluded by repeat measurement on a first morning specimen if the initial finding of proteinuria was obtained on a random specimen.
When monitoring proteinuria in children with chronic kidney disease, the total protein-to-creatinine ratio should be measured in spot urine specimens.
Screening and monitoring of post-pubertal children with diabetes of 5 or more years of duration should follow the guidelines for adults.
Screening and monitoring other children with diabetes should follow the guidelines for children without diabetes.
The measurement of urinary protein excretion provides a sensitive marker of many types of kidney disease from early to advanced stages. The American Diabetes Association8 and the NKF-PARADE6,7 have recommended assessment of proteinuria to detect chronic kidney disease. It is important to consider the timing of urine specimens and the methods for detection of urine proteins.
Concentration of protein in a spot urine sample provides a rough index of the protein excretion rate, but is also affected by hydration (R, C).
Urine protein-to-creatinine and albumin-to-creatinine ratios provide accurate estimates of the urinary protein and albumin excretion rate, and are not affected by hydration (R, C). Since urine proteins and creatinine are highly soluble in water, they will undergo similar, if not identical, dilution in urine. A first morning urine specimen is preferred, but random urine specimens are acceptable if first morning urine specimens are not available (R, O). Table 60 compares the advantages and disadvantages of the various modalities of collecting urine for evaluating kidney function. Consistent with recommendations by ADA and NKF-PARADE, the Work Group recommended screening using either standard or albumin-specific dipsticks, or protein-to-creatinine or albumin-to-creatinine ratio.
Special care should be taken to avoid false negative results which may delay implementation of treatment early in the course of kidney disease. Monitoring proteinuria in patients with chronic kidney disease should be performed using quantitative measurements (O). Albuminuria is a more sensitive marker than total protein for chronic kidney disease due to diabetes, hypertension, and glomerular diseases (R). In adults, the most common types of chronic kidney disease are due to diabetes, hypertension, and glomerular diseases.
The interpretation of albuminuria in kidney transplant recipients is more complicated than in other patients with chronic kidney disease. The cost or technical difficulty of measuring albumin may exceed that for measuring total protein.
Total protein detects albumin, which usually is present in large quantities in glomerular diseases of childhood (R).
Total protein detects low molecular weight proteins which are present in other types of chronic kidney disease (non-glomerular diseases) in childhood (R).
The prevalence of chronic kidney damage due to diabetes and hypertension is far lower in children than in adults. Albuminuria is a more sensitive marker than total protein for chronic kidney disease due to diabetes (R).
The risk of diabetic kidney disease in children is higher in post-pubertal children with duration of diabetes greater than 5 years than in other diabetic children.
The main limitations of assessment of proteinuria as a marker of chronic kidney disease is potential misclassification of individuals due variability of levels of total protein or albumin in an individual over time and the extent to which conditions at the time of testing may obscure the true level. A limitation of this guideline is the use of correlation coefficients, rather than more detailed assessments of precision and bias, to assess the accuracy of spot urine measurements of protein-to-creatinine ratios as a measure of protein excretion rates. The identification of persistent proteinuria or albuminuria in patients of all ages has importance when considering diagnosis, prognosis, and therapeutic options. Finally, the most important clinical application of defining patients with proteinuria is potentially beneficial therapy.
The optimal frequency and timing of urine screening for proteinuria in children have not been well established. The implementation of the guidelines in this section will encounter at least two potential obstacles.
The second potential problem involves the adoption of urine protein measurements factored by urine creatinine. A less obvious implementation issue relates to measuring albumin rather than total protein in the urine specimens. DISCLAIMER: All background wallpapers found here are believed to be in the "public domain".
Adverse outcomes of chronic kidney disease can often be prevented or delayed through early detection and treatment.
The presence of chronic kidney disease should be established, based on presence of kidney damage and level of kidney function (glomerular filtration rate [GFR]), irrespective of diagnosis. Among patients with chronic kidney disease, the stage of disease should be assigned based on the level of kidney function, irrespective of diagnosis, according to the KDOQI CKD classification Table 10. The USRDS provides reliable nationwide data regarding the incidence, prevalence, treatment patterns, outcomes, and cost of kidney failure treated by dialysis and transplantation, the most severe stage of chronic kidney disease.
Chronic kidney disease is defined according to the presence or absence of kidney damage and level of kidney function—irrespective of the type of kidney disease (diagnosis). Table 12 illustrates the classification of individuals based on the presence or absence of markers of kidney disease and level of GFR, according to definition and staging of chronic kidney disease proposed by this guideline.
All individuals with kidney damage are classified as having chronic kidney disease, irrespective of the level of GFR.
The methods to estimate GFR and assess markers of kidney damage are not completely sensitive or specific in detecting decreased GFR and kidney damage, respectively.
Other causes of chronically decreased GFR without kidney damage in adults include vegetarian diets, unilateral nephrectomy, extracellular fluid volume depletion, and systemic illnesses associated with reduced kidney perfusion, such as heart failure and cirrhosis.
High blood pressure in chronic kidney disease and in individuals with decreased GFR without kidney disease (R). Prevalence of chronic kidney disease and level of kidney function in the general population (S). Definition (O) Kidney damage is defined as structural or functional abnormalities of the kidney, initially without decreased GFR, which over time can lead to decreased GFR.
Albuminuria was persistent on repeat evaluation in only 61% of individuals; hence, these prevalence estimates based on a single spot urine are likely overestimates, especially for microalbuminuria. Among adults, the prevalence of albuminuria varies by age (Table 19) and presence (Table 20) or absence (Table 21) of diabetes.
Similarly, the prevalence of increased urine albumin excretion on initial screening varies from 1% to 10% (Table 23). Data from NHANES III are shown in Figs 9 and 10; these include men and women in the general population, including those with chronic kidney disease. In part, the inclusion of women and individuals with chronic kidney disease may account for the slightly lower mean values observed in the NHANES III compared to the data from normal men in Fig 9. As discussed earlier, individuals with decreased GFR should be evaluated for markers of kidney damage to determine whether they have chronic kidney disease and to determine the cause of reduced kidney function. The KDOQI definition of kidney failure differs in two important ways from the definition of ESRD. The Work Group anticipated that most kidney transplant recipients would be considered to have chronic kidney disease according to the proposed classification.
Nutritional indications for the initiation of renal replacement therapy are detailed in Guideline 27 of the KDOQI Clinical Practice Guidelines on Nutrition in Chronic Renal Failure, part of which is reproduced as Guideline 2 of the PD Adequacy Guideline.
The CKD Work Group searched for studies of measures of kidney function, dietary intake, and nutritional status at the onset of kidney replacement therapy.
These data show that estimated GFR provides only a rough approximation of other measures of kidney function.
Tables 30, 31, and 32 summarize other studies of the level of kidney function at initiation of dialysis.
Overall, the results of these studies are consistent with the data from the MDRD Study (Table 27) and the large study shown in Fig 11.
There are a number of limitations to the proposed definition and classification of chronic kidney disease. First, as described later in Guideline 6, the known markers of kidney damage are not sensitive, especially for tubulointersitial and vascular disease and for diseases in the kidney transplant. There are a large number of clinical applications of the proposed definition and stages of chronic kidney disease. Implementation of a new approach to the patient, classification of severity, and assessment of risk for chronic kidney disease will require appropriate professional, patient, and public education effort, as well as administrative and regulatory changes.
Components of the implementation plan, which determined the success of KDOQI, are under development and will be applied to these guidelines. The Workgroup acknowledges that the proposed definition and classification chronic kidney disease and stages is arbitrary and can be refined by further research. By clicking Submit, I agree to the MedicineNet's Terms & Conditions & Privacy Policy and understand that I may opt out of MedicineNet's subscriptions at any time.
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The most pertinent question with respect to screening for proteinuria is whether early detection of kidney disease associated with this abnormality will result in a more timely introduction of therapy that may slow the course of disease? Although the basic concepts of measuring and interpreting urinary protein excretion have changed little over several decades, clinicians must now decide whether simple qualitative or more cumbersome quantitative tests are necessary and whether albumin or total protein should be measured.
These ratios correct for variations in urinary concentration due to hydration and provide a more convenient method of assessing protein and albumin excretion than that involved with timed urine collections. The assessment of protein excretion in the urine can be accomplished by several different techniques.
Timed overnight collections or shorter timed daytime collections may reduce the inconvenience of a 24-hour collection, but are still associated with collection errors.
The concentration of protein in the urine is affected by urine volume as well as protein excretion rate. Several studies have addressed the relationships between total excretion of protein or albumin and the ratio of either to creatinine in patients of all ages (Tables 56, 57, 58, and 59). In principle, if the excretion of creatinine is relatively constant throughout the day, and similar among individuals, then the ratio of protein-to-creatinine in an untimed sample would reflect the excretion of protein. A first morning urine specimen is preferred because it correlates best with 24-hour protein excretion and is required for the diagnosis of orthostatic proteinuria. Screening with a dipstick for proteinuria or albuminuria is often a satisfactory first approach to evaluation of kidney disease; however, clinicians need to be cognizant of causes of false positive and more importantly false negative results (Table 61), and in both instances repeat analyses of urine with quantitative total protein or albumin and creatinine analyses are strongly advised when a result may be inconsistent with the clinical evaluation.
First, depending on the interval since transplantation, the patients’ native kidneys may still excrete small amounts of protein, which may be sufficient to cause a positive test for albumin. In contrast, the prevalence of kidney disease due to urinary tract abnormalities and congenital tubular disorders is far more common in children than in adults.219 These latter diseases may be characterized by low molecular weight proteinuria, which would be detected by tests for total urine protein, but not by tests for albumin. For these reasons, the American Diabetes Association recommends screening these children for chronic kidney disease, using the same algorithm as for adults. Excretion of total protein or albumin in the urine are highly variable in individuals with or without kidney disease. The relative ease with which proteinuria can be assessed and monitored allows clinicians to identify individuals with completely asymptomatic forms of progressive kidney disease during the early stages of their disease. The relationship between the level of proteinuria and the type (diagnosis) of chronic kidney disease is reviewed in Guideline 6 and in Part 9. The prognosis of patients with a variety of kidney disorders often correlates with their level of and persistence of proteinuria over time—even when other variables are controlled. Many lines of evidence now indicate that medications that reduce proteinuria may provide significant long term benefits for patients with chronic kidney disease.
At one end of the spectrum, the governments of some countries have mandated that such screening be done on all school children every year.

This approach has been developed to some extent for urine calcium-to-creatinine measurements, but many physicians are not aware of the accuracy and validity of protein-to-creatinine ratios.
Assays for albumin may not be as available as those for total protein in some smaller communities. Examples include elevated levels of ? 2-microglobulin and other tubular proteins in the urine of diabetic patients. Here is a number stimulating illustrations or photos approximately High Creatinine Levels Kidney Cares Community.
Earlier stages of chronic kidney disease can be detected through routine laboratory measurements. Adverse outcomes of chronic kidney disease can be prevented through early detection and treatment. This guideline provides a definition of chronic kidney disease as well as definitions and estimates of prevalence of earlier stages of kidney disease. Among individuals with chronic kidney disease, the stages are defined based on the level of kidney function.
Among individuals with chronic kidney disease, the stage is defined by the level of GFR, with higher stages representing lower GFR levels. In addition, it includes columns for the presence or absence of high blood pressure, because of the complex relationship of high blood pressure and chronic kidney disease.
The rationale for including these individuals is that reduction in kidney function to this level or lower represents loss of half or more of the adult level of normal kidney function, which may be associated with a number of complications (Part 6). Thus, misclassification is possible, and clinicians should carefully consider all aspects of the patient’s clinical presentation in interpreting test results and determining evaluation and management.
High blood pressure is not included in the definition of chronic kidney disease or its stages. The prevalence of chronic kidney disease, based on the definition above, was estimated using data from NHANES III and USRDS (Fig 7 and Tables 13 and 14). As described earlier, markers of kidney damage include abnormalities in the composition of the blood or urine or abnormalities in imaging tests. Proteinuria is an early and sensitive marker of kidney damage in many types of chronic kidney disease. Table 15 shows definitions for proteinuria and albuminuria, including gender specific cut-off values for microalbuminuria and albuminuria. Table 18 shows the prevalence of albuminuria estimated from the albumin-to-creatinine ratio in a single spot urine collection in 14,836 adults studied in NHANES III. On repeat examination, 73% of a subsample with albuminuria (n = 44) had a persistently positive test.
NHANES III did not ascertain other markers of kidney damage, such as abnormalities of the urine sediment and abnormal imaging tests; thus, any estimate based on NHANES III data is likely to underestimate the true prevalence of chronic kidney damage. The level of GFR is accepted as the best measure of overall kidney function in health and disease.
Even if there is no evidence of kidney damage, individuals with chronically decreased GFR may be at increased risk for adverse outcomes (for example, toxicity from drugs excreted by the kidney, and acute kidney failure in a wide variety of circumstances). Decreased GFR is associated with a wide range of complications in other organ systems, manifested by high blood pressure, laboratory abnormalities, and symptoms.
The Schwartz formula was used to estimate GFR in children aged 12 to 19 years in the NHANES III database. End-stage renal disease (ESRD) is an administrative term in the United States, based on the conditions for payment for health care by the Medicare ESRD Program, specifically the level of GFR and the occurrence of signs and symptoms of kidney failure necessitating initiation of treatment by replacement therapy.
First, GFR is lower in patients with a solitary kidney and is even lower in kidney transplant recipients because of toxicity from immunosuppressive agents used to prevent and treat rejection, such as cyclosporine and tacrolimus.
A number of measurements, including GFR, have been used to quantify the level of kidney function among patients with kidney failure.
Urea clearance should be normalized to total body water (V) and creatinine clearance should be expressed per 1.73 m2 of body surface area.
The largest and most comprehensive study is the one reported in abstract by the MDRD Study Group.76 This study included 88 patients who were referred to their physicians by the MDRD Study investigators for initiation of dialysis because of symptoms or findings of uremia prior to the end of the study. Clinicians initiate replacement therapy based on the level of kidney function, presence of signs and symptoms of uremia, the availability of therapy, and patient or surrogate preferences.
Timing of initiation of replacement therapy varies by modality, clinical characteristics, and sociodemographic characteristics. The incidence and the prevalence of reported ESRD have doubled in the past 10 years in the United States (Fig 2). On December 31, 1998, there were approximately 75,000 adults over 70 years of age (97 per million) with kidney failure treated by dialysis, compared to approximately 1,800 children (2.1 per million). The Work Group believes that these limitations should be identified, but does not think that they invalidate the proposal.
Thus, the prevalence of chronic kidney disease may be substantially higher than the Work Group has estimated, and recognition of patients with chronic kidney disease may be limited due to misclassification. An overall approach to evaluation and treatment of patients with chronic kidney disease is given in Guideline 2, and recommendations for individuals at increased risk of chronic kidney disease are given in Guideline 3.
For example, classification of kidney disease by the International Classification of Disease (9th Edition) (ICD-9) is based on duration (acute versus chronic), diagnosis, clinical presentation, markers of damage, and kidney function impairment. It would be useful to conduct a large cross-sectional study of GFR in general population, across the full range of age, gender, race, ethnicity, protein intake, with adjustment for other factors, including high blood pressure, diabetes, and other conditions that affect GFR. A cohort study of patients with chronic kidney disease would enable definition of the relationship between factors and outcomes of stages of chronic kidney disease. Charles "Pat" Davis, MD, PhD, is a board certified Emergency Medicine doctor who currently practices as a consultant and staff member for hospitals. The excretion of specific types of protein, such as albumin or low molecular weight globulins, depends on the type of kidney disease that is present. In clinical practice, most screening methods use a commercial dipstick, which measures total protein or albumin. However, in recent years some studies have advocated that the measurement of protein excretion should be done on an overnight specimen. The issue to be explored in this section is whether this increased level of convenience can be achieved without a reduced level of precision.
In addition to standard methods of measuring total protein, there are now multiple versions of immunoassays capable of detecting albumin levels at concentrations present in the majority of normal people. In addition, errors due to incomplete bladder emptying are relatively more important in shorter collection intervals.
Although creatinine excretion varies among individuals according to age, gender, race, and body size, the results from these studies in adults and children demonstrate a strong correlation between these measures. In children, orthostatic proteinuria must be excluded by a first morning urine protein measurement if the initial finding of proteinuria was obtained on a random specimen during the day. The differences among these protocols balance ease of collection of samples with the need to collect urine to reflect kidney function over the course of the day or overnight.
Second, the main causes of damage in kidney transplant, rejection or toxicity from immunosuppressive drugs, are not characterized by proteinuria. However, there is no reliable method to convert ratios of albumin-to-creatinine to total protein-to-creatinine or vice versa.
Therefore, the Work Group recommends that total urine protein should be measured to detect and monitor kidney damage in most children, one exception being children with diabetes mellitus. In addition, other than distinguishing normal from abnormal, the exact level of proteinuria is not usually required for clinical decision-making.
Such patients may benefit from subsequent changes in management that forestall or prevent additional kidney problems.
This is important because of the obvious therapeutic implications for patients who are in the high risk category that is characterized by persistent, heavy proteinuria. This even applies to some pediatricians who continue to request 24-hour urine studies in small children despite the high degree of difficulty involved. In such instances, the use of a spot urine and expression of the urine protein-to-creatinine ratio is still preferable to the 24-hour collection. Click image to get bigger picture, and if you find High Creatinine Levels Kidney Cares Community interesting, you might pin it to Pinterest. Identifying the presence and stage of chronic kidney disease in an individual is not a substitute for accurate assessment of the cause of kidney disease, extent of kidney damage, level of kidney function, comorbid conditions, complications of decreased kidney function, or risks for loss of kidney function or cardiovascular disease in that patient. For the definition of chronic kidney disease, the Work Group selected cut-off levels for GFR and markers of kidney damage that maximize specificity, acknowledging potential loss of sensitivity. However, high blood pressure is a common cause and consequence of chronic kidney disease, and as reviewed later, patients with chronic kidney disease and high blood pressure are at higher risk of loss of kidney function and development of cardiovascular disease. This section will emphasize proteinuria as a marker of kidney damage because it has been studied most thoroughly, including in NHANES III.
Albumin (molecular weight [MW] = 68,000 daltons) is the most abundant urine protein in most types of chronic kidney disease. Albumin excretion is increased by physiological variables, such as upright posture, exercise, pregnancy, and fever. Because protein excretion varies throughout the day, the normal ratio varies throughout the day.
Although increased urine albumin excretion reflects glomerular injury better than other urinary proteins in both adults and children, many pediatric nephrologists continue to monitor levels of total protein rather than albumin in patients with proteinuria. A compilation of studies shows that 1% to 10% of children may have proteinuria on initial screening using the urine dipstick, but that <1% have persistent proteinuria, as defined by positive results on repeated testing (Table 22).
In principle, the level of GFR is the product of the number of nephrons and the single nephron GFR. GFR estimated from serum creatinine using MDRD Study equation based on age, gender, and race (see Part 10, Appendix 3).
The interpretation of decreased GFR varies depending on age, duration, and the presence or absence of markers of kidney damage. For example, it is well known that a brief period of mildly decreased blood flow to the kidneys or transient partial obstruction of the urinary tract may cause decreased GFR without kidney damage. Severity of complications worsens as level of GFR declines (Part 6, Guidelines 7 through 12).
The prevalence of persistent albuminuria by GFR level and age group have not been determined, preventing an accurate estimate of the prevalence of chronic kidney disease among the elderly. ESRD includes patients treated by dialysis or transplantation, irrespective of the level of GFR.
Second, biopsy studies demonstrate pathologic damage due to acute and chronic rejection in virtually all transplant recipients, even if serum creatinine is normal. The KDOQI Nutrition in Chronic Renal Failure Guidelines75 and Peritoneal Dialysis Adequacy Guidelines Update 200016 recommend the decision to initiate dialysis in adults be based on a combination of measurements of kidney function, as well as nutritional status. There is variability among individuals in the relationship of level of kidney function to signs and symptoms of uremia. Patients who receive a pre-emptive transplant or who are started on peritoneal dialysis begin replacement therapy at higher mean levels of GFR than patients starting hemodialysis.
Data from the 2000 Annual Data Report of the USRDS documents the incidence of ESRD in 1998 of more than 85,000, or 308 per million individuals per year at risk. Instead, these limitations should serve to stimulate further research to refine the definition and classification.
The KDOQI classification proposes that both diagnosis and stage (severity) should be included in the classification of chronic kidney disease. This study would permit validation of prediction equations based on serum creatinine or other filtration markers within the normal range of GFR. This would be particularly useful in defining the relationships among stages of chronic kidney disease, progression of chronic kidney disease, initiation and progression of cardiovascular disease, health service utilization, and barriers to care. It would be useful to conduct cross-sectional and cohort studies of elderly individuals with normal and abnormal blood pressure and GFR to assess the effect of high blood pressure and decreased GFR in this population. There he was involved in research in radiation biology and received the Huisking Scholarship. Increased excretion of albumin is a sensitive marker for chronic kidney disease due to diabetes, glomerular disease, and hypertension. For example, in diabetic kidney disease, early detection of albuminuria appears to permit effective therapy early in the course of disease. Algorithms for screening and evaluation of proteinuria in asymptomatic, healthy individuals and in patients at increased risk for chronic kidney disease recommended by NKF-PARADE are given in Part 9. These dipsticks, which are of course simple to use, usually afford high specificity; ie, they have relatively few false positive results, thereby creating a practical advantage for the clinician.
The rationale for measuring proteinuria in timed overnight urine collections rather than 24-hour specimens relates to the lack of consistency when hourly protein excretion rates are examined in the same individual at different times during the day.

In general, the literature does not provide substantial information concerning the relative merits of measuring total protein versus albumin to detect and monitor kidney damage.
Otherwise, for ease and consistency of collection, a random urine specimen for protein or albumin to creatinine ratio is acceptable if a first-morning urine specimen is not available. The reagent pad contains a colorimetric pH indicator dye which changes color when bound by negatively charged serum proteins, including albumin and most globulins.
Decreasing proteinuria, either spontaneously or after treatment, is associated with a lower risk of loss of kidney function. Preliminary data suggest that elevated albumin excretion is also a marker of kidney damage in adults with hypertension. However, diabetic kidney disease is the underlying cause for a large fraction of kidney transplant patients, which may recur in the transplant.
Examples of conditions that affect protein excretion other than kidney disease include activity, urinary tract infection, diet, and menstruation. The relationship between the level of proteinuria and risk for loss of kidney function is considered further in Guideline 13. It is interesting to speculate whether the increasing incidence of end-stage renal disease in the elderly could be due, in part, to age-associated decline in GFR. In clinical practice, it may be difficult to determine whether individuals with decreased GFR have chronic kidney disease.
High blood pressure is also common in older individuals without chronic kidney disease and is associated with accelerated GFR decline with age and more marked pathological abnormalities in the kidneys. Elevated albumin-to-creatinine excretion was persistent in 61% of the subjects with albuminuria (n = 163). Low molecular weight (LMW) globulins are the most abundant urine proteins in some types of chronic kidney disease.
The ratio in a first morning specimen correlates most closely with overnight protein excretion rate, whereas the ratio in mid-morning specimens correlates most closely with 24-hour protein excretion rate. Hence, reports of normal albumin rates in children are relatively few in number, and most have been published in the past 15 years. Therefore, GFR can be affected by chronic kidney disease, which reduces the number of nephrons, or by hemodynamic factors that affect single nephron GFR. Pregnancy has a major effect on GFR, with GFR reaching values of 140% of normal during the end of the second trimester. However, a sustained decrease in blood flow or prolonged obstruction is often associated with kidney damage.
Reliable estimates of prevalence of categories of decreased GFR (mild, moderate, or severe) in children are not available from NHANES III.
The Work Group acknowledges that the level of GFR selected for this definition is arbitrary and may need to be modified based on advances in kidney replacement therapy.
The median interval from final GFR to initiation of dialysis in the study group was 89 days.
Notably, there is variability within and among health care systems in the availability of therapy.
Dialysis is initiated at higher mean levels of GFR among patients who are older, or who have diabetes, cardiovascular disease, and other comorbid conditions.
The point prevalence of ESRD on December 31, 1998 was more than 320,000, or 1,160 per million population, of whom 72% were treated by dialysis (230,000 patients, or 835 per million population) and 28% had functioning kidney transplants (90,000 patients, or 325 per 100,000). Third, as described earlier, the cause of age-related decline in GFR and high blood pressure is not known.
Finally, additional recommendations for evaluation, diagnosis, and treatment of chronic kidney disease are given in Part 9. This would facilitate using administrative databases for epidemiological and outcomes surveys.
Creatinine is produced from creatine, a molecule of major importance for energy production in muscles.
Increased excretion of low molecular weight globulins is a sensitive marker for some types of tubulointerstitial disease.
However, they afford low sensitivity; ie, they may fail to detect some forms of kidney disease during the early stages, when the level of proteinuria is below the sensitivity of the test strip used. This inconsistency results from varying levels of activity and possibly other factors that are not well documented. Different guidelines for children and adults reflect differences in the prevalence of specific types of chronic kidney disease.
Despite this, there is a rough correlation between protein concentration in a spot urine sample and protein excretion rate (Tables 53, 54, and 55). This recommendation is consistent with the recommendations by the American Diabetes Association8 and by the NKF PARADE,6,7 which recommend a first-morning sample, but accept a random sample if a first-morning specimen is not available. The standard urine dipstick is insensitive for low concentrations of albumin that may occur in patients with microalbuminuria.
Moreover, hypertension is very common after transplantation and is strongly associated with a more rapid loss of kidney function in transplant patients. Attempts to avoid these pitfalls include careful definition of events that should preclude the interpretation of abnormal results and consideration of repeat studies when abnormal results are obtained.
Thus, the Work Group concludes that the uniformly high correlation coefficients are sufficiently strong evidence to warrant the conclusions presented here. Nonetheless, staging of chronic kidney disease will facilitate application of clinical practice guidelines, clinical performance measures and quality improvement efforts to the evaluation, and management of chronic kidney disease. Recommendations for a clinical approach to elderly individuals with decreased GFR is given in Part 9. Individuals with high blood pressure should be carefully evaluated for the presence of chronic kidney disease, especially those with decreased GFR. Therefore, these estimates of prevalence should be considered as rough approximations of the true prevalence. In this and later guidelines, the term proteinuria includes albuminuria, increased urinary excretion of other specific proteins, and increased excretion of total urine protein. Major constituents of normal urine protein are albumin, LMW proteins filtered from the blood, and proteins derived from the urinary tract.
Creatinine excretion is higher in normal men than women; therefore, the values in the general population (Fig 8) and cut-off values for abnormalities in urine albumin-to-creatinine ratio are lower for men than women (Table 15). However, a literature search of articles describing albumin excretion in children revealed one study in 1970. On repeat examination, 54% (n = 102) of a subsample with albuminuria had a persistently positive result. In chronic kidney disease, as in normal individuals, GFR is modulated by hemodynamic factors. Although these definitions are arbitrary, evidence compiled in later guidelines supports these broad categories and cut-off levels.
Such patients would not be classified as having chronic kidney disease by the proposed classification. Because these patients were participating in a clinical trial, the mean level of kidney function and nutritional status may be higher than in patients beginning dialysis in the general population. He is a Clinical Professor (retired) in the Division of Emergency Medicine, UT Health Science Center at San Antonio, and has been the Chief of Emergency Medicine at UT Medical Branch and at UTHSCSA with over 250 publications. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. The high intra-individual variability that ensues makes serial comparisons in individual patients very difficult unless multiple measurements are taken. In addition, the standard dipstick is also insensitive to positively charged serum proteins, such as some immunoglobulin light chains.
Therefore, the Work Group concluded that albumin should be measured to detect and monitor kidney damage in adults. Finally, recurrent glomerular disease may occur after transplantation and is associated with a greater risk of graft loss.
Some authors have advocated that multiple (up to 5) specimens be obtained in order to obtain a reliable result.42 The Work Group does not believe that such an approach is feasible in most instances.
The rationales for these assumptions and cut-off levels are discussed in more detail below. On the other hand, the term albuminuria has been used only when referring to increased urinary albumin excretion. This original paper20 considered the best measurement of glomerular integrity to be albumin clearance factored by creatinine clearance. The Work Group arbitrarily chose a cut-off value of greater than 3 months for the definition of chronic kidney disease. Tables 27 and 28 show measures of kidney function and nutritional status in these patients with kidney failure just prior to initiation of dialysis.
This problem is particularly troublesome for individuals with orthostatic proteinuria—who may excrete more than 1 g of protein during waking hours, but less than 100 mg during sleep.
Albuminuria is a better marker than total urine protein of kidney damage due to diabetes, hypertension, and glomerular disease.
However, the Work Group acknowledges the need to repeat abnormal tests, especially low levels of total protein or albumin and the necessity to carefully consider the clinical setting in interpretation of urine protein measurements.
Older laboratory methods, such as the urine dipstick or acid precipitation, detect most urine proteins. It concluded that the ratio of the concentration of albumin to creatinine in spot urine samples is the most accurate method for estimating albumin clearance and provides a better marker of glomerular permeability to albumin than the 24-hour albumin excretion rate. Thus, all patients with a kidney transplant would be considered either to have chronic kidney disease or to be at increased risk of chronic kidney disease. The kidneys filter out most of the creatinine and dispose of it in the urine.Because the muscle mass in the body is relatively constant from day to day, the creatinine production normally remains essentially unchanged on a daily basis.Why is it important to check blood creatinine levels? Guidelines for detection and monitoring of proteinuria in adults and children differ because of differences in the prevalence and type of chronic kidney disease. For these reasons, the Work Group recommends testing and monitoring for albuminuria, rather than total protein, in kidney transplant recipients, as well as in patients with other causes of chronic kidney disease.
Microalbuminuria refers to excretion of small but abnormal amounts of albumin, which requires recently developed, more sensitive laboratory methods that are now widely available. The results were expressed as mg albumin per mg creatinine, but subsequent papers have used a variety of methods to express albumin excretion, making comparisons between studies very difficult. Fifth, the association of level of GFR with complications of chronic kidney disease does not prove a causal relationship between the two. Tables 16 and 17 give mean values and ranges for albumin excretion rate and albumin-to-creatinine ratio in children (neonates through age 20 years), and also emphasize some of the ways in which published reports have differed. Nonetheless, in many cases there is adequate evidence of a causal relationship, and even if there is not, the associations accurately describe the burden of illness associated with the severity of chronic kidney disease. Sixth, prevalence estimates for stages of chronic kidney disease and the associations of level of GFR with complications are based largely on an analysis of data from NHANES III that has not yet been peer-reviewed.
However, the Work Group believes that Appendix 2 provides sufficient detail to evaluate the methods. Elevated creatinine level signifies impaired kidney function or kidney disease.As the kidneys become impaired for any reason, the creatinine level in the blood will rise due to poor clearance of creatinine by the kidneys.
Abnormally high levels of creatinine thus warn of possible malfunction or failure of the kidneys.
It is for this reason that standard blood tests routinely check the amount of creatinine in the blood.A more precise measure of the kidney function can be estimated by calculating how much creatinine is cleared from the body by the kidneys. This is referred to as creatinine clearance and it estimates the rate of filtration by kidneys (glomerular filtration rate, or GFR). It can be calculated (estimated) by a formula using serum (blood) creatinine level, patient's weight, and age.
Creatinine clearance can also be more directly measured by collecting a 24-hour urine sample and then drawing a blood sample. The BUN-to-creatinine ratio generally provides more precise information about kidney function and its possible underlying cause compared with creatinine level alone. BUN also increases with dehydration.Recently, elevated creatinine levels in infants were associated with bacteremia while elevated levels in adult males have been linked to incresed risk of prostate cancer.

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