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We assessed the association between renal and cognitive function based . Demographic confounders included age, sex, ethnicity, and total Greene. T. Rogers. N. Roth. D. A more accurate method to estimate . Massy. ZA. Cognitive disorders and dementia in CKD: the neglected kidney–brain axis. Background-—Detection of preclinical cardiac dysfunction and prognosis of left within Æ years, and sex- and age-matched controls who did not BA, Kellmann M, Kolch W, Massy Z, Novak J, Rossing K, Schanstra JP, Schiffer Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D; for the Modification. Advances in pharmacotherapy for treating female sexual dysfunction. . Research on sexual dysfunction in females typically starts with age 18 years or over. Lenz, Destin U; Crutcher, Effie L; Greene, Elisa M Rogers, Rebecca G; Pauls, Rachel N; Thakar, Ranee; Morin, Melanie; Kuhn, Annette; Petri, Eckhard; Fatton.

The development of formulas estimating glomerular filtration rate eGFR from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease CKDwhich is based on eGFR values and albuminuria.

This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C.

The disagreements Roger massy greene wife sexual dysfunction limitations for all eGFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and, particularly, biomarkers of early renal tissue injury.

Detection of the presence and severity of chronic kidney disease CKD is currently based on estimates of glomerular filtration rate based on serum creatinine and cystatin C concentrations plus factors that affect the rate of production of these two biomarkers, and on albuminuria.

This scheme has improved detection of CKD and Roger massy greene wife sexual dysfunction its course and the effects of therapeutic interventions. Research in this field is directed towards finding better biomarkers of glomerular filtration rate and, particularly, biomarkers indicating early injury of the renal tissues.

Chronic kidney disease CKD has been recognized as a major health problem worldwide with rising incidence, pronounced morbidity and mortality, and rising costs[ 1 ]. Early diagnosis, prevention and management of CKD, including treatment of its underlying disease and prevention and treatment of medical conditions for which the presence of CKD is a risk factor, has acquired great importance for health providers[ 1 ].

The prevalence of CKD in the United States during the years was estimated to be equal to Reported prevalence of CKD in various regions of the world varies. For example, recent estimates using different approaches computed a CKD prevalence of The prevalence of CKD is high in populations with conditions predisposing to it.

For example, CKD was detected in The diagnosis of CKD is associated with important risks of Roger massy greene wife sexual dysfunction in other organs. For example, cardiovascular disease has been recognized as a major risk associated with CKD[ 47 ]. In a cross sectional study of a large number of subjects with low and middle income in 12 countries, the incidence of CKD was Adverse effects of CKD on cardiac function have been reported in patients with heart failure, but preserved ejection fraction[ 9 ], diabetics with a doubling of their serum creatinine levels[ 10 ], and even healthy kidney transplant donors[ 11 ].

In a study from Korea, CKD was associated primarily with increased mortality risks from cardiovascular disease, but also with risks for other morbid conditions including malignancies[ 12 ].

Despite the universal recognition of the importance of its early detection, CKD is diagnosed late in several parts of the world[ 13 ]. Primary care services have a major role in the diagnosis and management of CKD[ 6 ]. Guidelines for detection and management of CKD addressed to primary care medical practitioners have been published for adult[ 14 ] and pediatric patients[ 15 ]. Education of the public is an important step for early management of CKD.

Patients with CKD aware of its importance desire to be informed about its risks and management[ 16 ]. Information about CKD is provided to the public in the medical press[ 17 ]. Finally, methods for evaluation of the economic impact of CKD[ 18 ] and for technological developments addressing the detection and prevention of early stages of CKD[ 19 ] are studied.

In this report, we address the current methods for diagnosing CKD. The derivation, uses and limitations of these methods will be detailed. Finally, emerging methods for early diagnosis of CKD will be briefly presented. Establishing the presence and degree of renal dysfunction has been based on measuring glomerular filtration rate GFR. The rational for this is a rough correlation between GFR levels and clinical manifestations of renal failure.

Serum creatinine level was the traditional surrogate index of GFR. The first development leading to substitution of eGFR for serum creatinine was the computation of the Cockroft-Gault formula[ 20 ], which estimates creatinine clearance from serum creatinine, age, body weight and gender and was used extensively in the past for the diagnosis and management of CKD.

The differences between these two clearances will be addressed later in this report. The next important step in the diagnosis and staging of CKD was the development of carefully developed equations computing eGFR based on serum creatinine levels in large prospective studies in which GFR was measured by standard methods.

In addition to serum creatinine, the determinants of eGFR in the currently used 4-variable MDRD Roger massy greene wife sexual dysfunction include gender, age and race black or not black.

A second 6-variable MDRD formula, which utilizes serum urea nitrogen and albumin levels in addition to the four determinants of eGFR used in the first formula, has similar performance characteristics with the 4-variable formula[ 22 ]. However, the estimates of eGFR by the two formulas do not differ substantially for patients with moderate and advanced CKD, in general.

Modification of Diet in Renal Disease[ 22 ] and Chronic Kidney Disease Epidemiology Collaboration[ 23 ] formulae for estimating glomerular filtration rate fit to variations in serum creatinine X axis and age Y axis assuming males of Caucasian race. Estimating glomerular filtration rate. Modification of Diet in Renal Disease[ 22 ] and Chronic Kidney Disease Epidemiology Collaboration[ 23 ] formulas for estimating glomerular filtration rate fit to variations in serum creatinine X axis and age Y axis assuming females of Black race.

Scatterplot demonstrating close relationships between estimating glomerular filtration rate values calculated by the Chronic Kidney Disease Epidemiology Collaboration formula[ 23 ] Y axis and the Modification of Diet in Renal Disease formula[ 22 ] X axis. Different colors are used to indicate the races and genders depicted in this figure: A straight line to fit the data minimizes Roger massy greene wife sexual dysfunction least square error with an intercept of Chronic Kidney Disease Epidemiology Collaboration.

The next step in the development of eGFR formulas was the introduction of cystatin C, which is a small molecular weight Serum cystatin C levels were reported to be superior to serum creatinine levels as indices of GFR. Currently, several eGFR equations have been developed or are being developed[ 35 ].

Extensive sets of guidelines base the diagnosing and staging of CKD on combinations of eGFR cut-off values and albuminuria[ 36 - 39 ]. In the next section, we will discuss the applications of these guidelines. The limitations of this approach are of importance. In a population study mean measured GFR was higher in men than women but was not different between blacks and whites[ 40 ]. The authors of this study concluded that the different incidences of renal disease between blacks and whites were not due to the baseline renal function.

The differences between the various equations computing eGFR are also not due to the baseline renal factors, but are keys to understanding the limitations of these equations as will be examined later in this text.

A number of studies compared Roger massy greene wife sexual dysfunction accuracy of various eGFR formulas in various populations and clinical conditions[ 41 - 63 ]. The great majority of these studies concluded that formulas based on serum cystatin C alone or on combined cystatin-creatinine levels are superior to other formulas[ 41 - 47495052 - 5456 - 5860 - 63 ]. Another study found that in Roger massy greene wife sexual dysfunction Korean Roger massy greene wife sexual dysfunction an eGFR formula developed in a Japanese population was superior to other formulas[ 55 ].

Two studies found superiority of different eGFR formulas in different patient groups[ 4248 ]. Finally, one study[ 59 ] found that the CKD-EPI Roger massy greene wife sexual dysfunction 23 ] and a Japanese formula for eGFR based on serum creatinine[ 64 ] are superior to measured creatinine clearance in monitoring patients receiving cisplatin in high doses.

The older method for the diagnosis of CKD was to compare the serum level of creatinine of a subject to a normal range of creatinine concentrations.

The clear advantage of eGFR formulas over this older method is that the formulas allow earlier detection of CKD and more precise following of its course in the early stages of CKD, Roger massy greene wife sexual dysfunction large decreases in GFR lead to small rises in serum creatinine. Formulas computing eGFR have been applied in clinical studies for a variety of purposes[ 43454657586065 - 74 ]. Risk prediction in various patient groups with CKD[ 4345464857586067 - 6971 ], choice and outcome of surgical and medical interventions in patients with CKD[ 5672 - 74 ], and association of the CKD stage with specific clinical manifestations in various patient groups[ 6670 ] are conditions for which eGFR equations based on cystatin C or on cystatin-creatinine have been shown to provide accuracy.

In clinical studies targeting specific end-points of decline in renal function, use of eGFR instead of serum creatinine has the potential of reducing substantially both the required number of participants[ 75 ] and the targeted degree of Roger massy greene wife sexual dysfunction in renal function[ 76 ]. Nevertheless, this approach to CKD has significant limitations. Discrepancies between various formulas estimating eGFR and between these formulas and measurements of GFR by standard methods have been reported.

To illustrate the types of conditions in which eGFR formulas may be inaccurate, we will discuss a few examples of these discrepancies. Clinical conditions affecting the accuracy of estimating glomerular filtration rate formulas. The increasing incidence of diabetes mellitus in many parts of the world has been the major cause of the increasing incidence of CKD. CKD secondary to diabetic nephropathy, which particularly in its early stages may not be associated with albuminuria, especially in type 2 diabetics, has its Roger massy greene wife sexual dysfunction diagnostic difficulties[ 79 - 92 ].

Several studies concluded that some creatinine-based eGFR formulas are not as accurate in detecting early CKD as cystatin-based formulas[ 80 - 8486 - 8891 ].

In addition, cystatin-based eGFR formulas were the only ones found to be independent predictors of diabetic complications[ 8386 ] and creatinine-based eGFR formulas did not detect early declines in renal function[ 8990 ]. A study using inulin clearance to measure GFR concluded that cystatin-based and creatinine-based eGFR formulas have significant inaccuracies in the diagnosis and staging of diabetic CKD[ 92 ].

Based on the discrepancies of eGFR formulas, one report proposed the use of one of the standard techniques, iohexol clearance, for evaluation of renal function in type 1 diabetics[ 85 ]. Screening for CKD is of great importance for patients treated with nephrotoxic antiretroviral medications[ 95 ].

Extrarenal influences on cystatin C and creatinine metabolism may cause eGFR formula computations differing from the actual renal function[ 97 ]. Other studies in HIV-infected subjects found superiority of either cystatin-based eGFR formulas[ 98] or creatinine-based formulas[ 99 ] in detecting CKD and determining the risks associated with it. Chronic liver disease is associated with inaccuracy of the eGFR formulas[ - ]. Creatinine-based eGFR formulas systematically overestimate measured GFR in this patient group and the degree of overestimation increases with the severity of liver disease[ ].

Cystatin-based eGFR equations are more accurate in these patients[ ], but cystatin-based formulas derived in populations with liver disease may prove to have the greater usefulness[ ]. Limitations of various eGFR formulas have been reported in subjects with cardiovascular diseases[ - ]. One Roger massy greene wife sexual dysfunction calculated similar assessment of cardiovascular risks by the Cockroft-Gault formula and by serum cystatin C level[ ].

However, a larger study found substantial differences between eGFR values calculated by creatinine-based and cystatin-based formulas in patients with varying severity of cardiac disease, with creatinine-based eGFR values exceeding the cystatin-based values in most patient categories[ ]. Another study concluded that measured GFR, not eGFR formulas, should be used for evaluating the relationship between retinal vasculopathy and renal disease[ ].

Differences in the association of creatinine-based and cystatin-based eGFR formulas with non-traditional cardiovascular risk factors Roger massy greene wife sexual dysfunction and symmetric dimethylarginine blood levels, insulin resistance in subjects without diagnosed cardiovascular disease, diabetes or CKD was reported in another study[ ].

Finally, eGFR formulas were found to be inaccurate in heart transplant recipients[ ]. The authors of this last study proposed the use of measured GFR for assessing kidney function in this patient group.

Roger massy greene wife sexual dysfunction between eGFR formulas have been found in recipients and donors of kidney transplants. Of note is that the eGFR formulas used in this last study were derived in different Roger massy greene wife sexual dysfunction groups.

Various problems posed by creatinine-based and cystatin-based eGFR formulas in renal transplant recipients were reviewed by Santos and Martins[ ]. Prospective renal transplant donors illustrate the limitations of eGFR formulas in subjects in whom the need of accuracy in establishing absence of CKD is critical. Issues with the eGFR formulas were reported in patients with neurological diseases causing sarcopenia[], critically ill patients[ ], and patients with hereditary disease[ ].

Sarcopenia in subjects with neuromuscular disease is the source of systematic overestimation of GFR by creatinine-based eGFR formulas. Studies have found differences between various eGFR formulas in obese subjects[ - ]. One large study concluded Roger massy greene wife sexual dysfunction cystatin-based eGFR formulas are deficient in detecting CKD stage 3 or 4 in obese subjects[ ].

In contrast, two smaller studies concluded that creatinine-based equations produce higher eGFR values than cystatin-based formulas and may lead to underestimation of the presence and degree of CKD[].

The development of formulas estimating glomerular filtration rate eGFR from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease CKD , which is based on eGFR values and albuminuria.

This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course.

These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C.

The disagreements create limitations for all eGFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and, particularly, biomarkers of early renal tissue injury. Detection of the presence and severity of chronic kidney disease CKD is currently based on estimates of glomerular filtration rate based on serum creatinine and cystatin C concentrations plus factors that affect the rate of production of these two biomarkers, and on albuminuria.

This scheme has improved detection of CKD and monitoring its course and the effects of therapeutic interventions. Research in this field is directed towards finding better biomarkers of glomerular filtration rate and, particularly, biomarkers indicating early injury of the renal tissues. Chronic kidney disease CKD has been recognized as a major health problem worldwide with rising incidence, pronounced morbidity and mortality, and rising costs[ 1 ].

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