•Nandrolone treatment with or without training increased 8-OHdG as a DNA damage marker.•Nandrolone treatment with or without training increased nephrin and podocin gene expression.•Nandrolone ...treatment with or without training led to kidney function alteration.
Among the various adverse effects of nandrolone administration with or without strenuous exercise, kidney abnormalities, where there are associations between nandrolone decanoate consumption, have not been well defined yet. The aim of this study was to investigate the effect of nandrolone decanoate intake with or without strenuous exercise on nephrin and podocin gene expressions, cystatin C, oxidative DNA damage, and histological changes in the kidneys of rats. Thirty-two male wistar rats were assigned into four groups, namely control, nandrolone, nandrolone with strenuous exercise, and strenuous exercise groups. After six weeks of treatment, the results revealed a significant increase in the nephrin and podocin gene expression, plasma cystatin C, and the amount of 8-OHdG in the kidney tissue; as well as a decrease in creatinine clearance in nandrolone and nandrolone with strenuous exercise groups compared to the control group. Moreover, compared to the control group, the nandrolone and the nandrolone with strenuous exercise groups, showed histological changes such as fibrosis and kidney tissue cells proliferation. These findings indicate that nandrolone induces kidney abnormalities, which may in part be associated with overexpression of nephrin and podocin genes mediated by oxidative stress, which was manifested in increased 8-OHdG in kidney tissue.
Cathepsin S (CTSS) is a cysteine protease involved in atherogenesis. We compared the plasma CTSS as well as other biomarkers of atherosclerosis in patients with abdominal aortic aneurysms (AAA) and ...aortoiliac occlusive disease (AOD), aiming to identify the underlying pathogenic mechanisms of the disease development. Also, we hypothesised that the level of plasma CTSS simultaneously increases with a decrease of plasma high-density lipoprotein cholesterol (HDL-C) values.
33 patients with AAA and 34 patients with AOD were included in this study.
There was no difference in the level of plasma CTSS between the two analysed groups (p=0.833). In the patients with AAA, the plasma CTSS was correlated with HDL-C (r = -0.377, p = 0.034) and total bilirubin (r =0.500, p = 0.003) while, unexpectedly, it was not correlated with cystatin C (Cys C) (r =0.083, p = 0.652). In the patients with AOD, the plasma CTSS correlated with triglycerides (r = 0.597, p< 0.001), only. When the patients were divided according to HDL-C (with HDL-C ≤0.90 and HDL-C >0.90 mmol/L), the plasma CTSS values differed among these groups (31.27
.25.61 μg/L, respectively, p<0.001).
These results provide the first evidence that CTSS negatively correlated with HDL-C and bilirubin in patients with AAA. It is possible that differences in the association of the CTSS and other markers of atherosclerosis can determine whether atherosclerotic aorta will develop dilatation or stenosis.
Given that thyroid function influences serum cystatin C and creatinine levels, the question arises as to whether it is possible to accurately estimate glomerular filtration rate (GFR) in patients ...with thyroid dysfunction. The objective of the study was to determine serum cystatin C and creatinine levels and estimate GFR in patients with thyroid dysfunction. The study included 32 cases with newly diagnosed hyperthyroidism and 27 cases with newly diagnosed hypothyroidism, as well as 20 healthy controls matched for sex and age with the cases. Serum concentrations of thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4), creatinine and cystatin C were measured in all study subjects. GFR was estimated using the Modification of Diet in Renal Disease (MDRD), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and cystatin C-based equations. Serum cystatin C levels were significantly higher in hyperthyroid subjects compared to controls (1.32±0.31 vs. 0.89±0.15; p<0.01). Serum creatinine levels were significantly lower in hyperthyroid subjects compared to controls (60.6±10.2 vs. 76.4±8.6; p<0.01), and significantly higher in hypothyroid subjects compared to controls (94.5±13.2 vs. 76.4±8.6; p<0.01). GFR estimated with the MDRD equations was significantly higher in hyperthyroid subjects compared to hypothyroid subjects (101.6±20.7 vs. 64.1±11.6 mL/min/1.73m2; p<0.01). GFR estimated with the equation based on serum cystatin C was significantly lower in hyperthyroid subjects compared to hypothyroid subjects (59.2±22.1 vs. 92.1±16.0 mL/min/1.73m2; p<0.01). Although serum cystatin C is regarded a reliable marker of GFR and more sensitive than serum creatinine, it has limitations in patients with thyroid dysfunction, due to significant changes in its serum concentrations regardless of renal function. In patients with thyroid dysfunction GFR should therefore be estimated using the equations based on serum creatinine.
S obzirom na uticaj tireoidne funkcije na nivo cistatina C i kreatinina, postavlja se pitanje mogućnosti pravilne procene (GFR) brzine glomerularne filtracije kod bolesnika sa tireoidnom disfunkcijom. Cilj ove studije je evaluacija vrednosti cistatina C i kreatinina uz procenu (GFR) kod bolesnika sa poremećajem funkcije štitaste žlezde. U ispitivanje je uključeno 32 bolesnika sa novodijagnostikovanom hipertireozom i 27 bolesnika sa novodijagnostikovanom hipotireozom. Kontrolnu grupu sačinjava 20 zdravih ispitanika koji odgovaraju ispitivanoj grupi prema starosti i polu. Svim ispitanicima je određena koncentracija fT3, fT4, TSH, kreatinina i cistatina C. Procenjena je vrednost GFR jednačinama na osnovu serumske koncentracije kreatinina, kao i jednačinom baziranom na vrednosti cistatina C. Značajno su više vrednosti cistatina C u grupi hipertireoidnih bolesnika u odnosu na kontrolnu grupu (1,32±0,31 vs. 0,89±0,15; p<0,01). Vrednosti kreatinina statistički su značajno niže u grupi hipertireoidnih bolesnika u odnosu na kontrolnu grupu (60,6± 10,2 vs. 76,4±8,6; p<0,01), za razliku od značajno viših vrednosti kreatinina u grupi hipotireoidnih bolesnika u odnosu na kontrolnu grupu (94,5± 13,2 vs. 76,4±8,6; p<0,01). GFR procenjena MDRD i CKD-EPI jednačinama u grupi hipertireoidnih bolesnika značajno je viša u odnosu na GFR u grupi hipotireoidnih bolesnika (101,6±20,7 vs. 64,1±11,6 mL/min/1,73m2; p<0,01). GFR procenjena jednačinom baziranom na serumskoj koncentraciji cistatina C u grupi hipertireoidnih ispitanika statistički je značajno niža u odnosu na iste vrednosti u grupi hipotireoidnih subjekata (59,2± 22,1 vs. 92,1±16,0 mL/min/1,73m2; p<0,01). Iako se smatra da je cistatin C pouzdan parametar u proceni GFR, senzitivniji od serumske koncentracije kreatinina, njegova upotreba je ograničena kod bolesnika sa tireoidnom disfunkcijom usled značajnih promena njegove serumske koncentracije nezavisno od bubrežne funkcije, odnosno, kod bolesnika sa tireoidnom disfunkcijom za procenu GFR treba koristiti jednačinu baziranu na serumskoj koncentraciji kreatinina.
Beta-trace protein (BTP), also known as prostaglandin D synthase, is a low-molecular-mass protein which belongs to the lipocalin protein family. It was found to be increased in the serum of patients ...with renal diseases. The aim of this study was to compare the clinical usefulness of serum levels of beta-trace protein for the detection of renal dysfunction in patients with chronic kidney disease (CKD) with levels of other renal markers: creatinine, cystatin C and β2-microglobulin (B2M). The study included 134 patients with a wide range of renal dysfunction that encompassed all five CKD stages. Obtained data showed that beta-trace protein highly correlated (Spearman test) with creatinine (r = 0.890), cystatin C (r = 0.904) and B2M (r = 0.933) and its levels in serum significantly increased from CKD stage 1 to 5. Furthermore, the values of glomerular filtration rate (GFR) estimated from a BTP-based formula significantly correlated with GFR calculated from creatinine-based and cystatin C-based formulas. ROC analyses showed that BTP had similar diagnostic accuracy for detection of reduced renal function in CKD stages as other renal markers, for estimated GFRs of < 30, < 60 and < 90 mL/min/1.73 m2. The areas under the ROC curves (AUC) for BTP, for these GFR limits, were from 0.983 to 0.917 and they were not significantly different from AUCs for other renal markers. The results of this study showed that BTP may be a useful and reliable serum marker for identifying the magnitude of renal dysfunction in patients with CKD and may have its place beside serum cystatin C and creatinine as an alternative endogenous GFR marker.
Beta-trace protein (BTP), takođe poznat kao prostaglandin D sintaza, je protein male molekulske mase koji pripada familiji lipokalinskih proteina. Pronađeno je da je povećan u serumu pacijenata sa renalnim bolestima. Cilj ovog rada je bio da se uporedi klinička korisnost serumskih nivoa beta-trace proteina u detekciji renalne disfunkcije kod pacijenata sa hroničnom bolešću bubrega (CKD) sa nivoima drugih renalnih markera: kreatinina, cistatina C i β2-mikroglobulina (B2M). Studija je uključila 134 pacijenta sa širokim opsegom renalne disfunkcije koji obuhvata svih 5 CKD stadijuma. Dobijeni podaci su pokazali da beta-trace protein veoma dobro koreliše (Spearmanov test) sa kreatininom (r = 0,890), cistatinom C (r = 0,904) i B2M (r = 0,933) i da se njegovi nivoi u serumu značajno povećavaju od (1. do 5.) CKD stadijuma. Osim toga, vrednosti jačine glomerulske filtracije (GFR) procenjene iz formule bazirane na BTP značajno korelišu sa GFR izračunatom iz formula baziranih na kreatininu i cistatinu C. ROC analiza je pokazala da BTP ima sličnu dijagnostičku tačnost za detekciju redukovane renalne funkcije u CKD stadijumima kao drugi renalni markeri, pri procenjenim GFR od < 30, < 60 i < 90 mL/min/1,73 m2. Površine ispod ROC krivih (AUC) za BTP, za ove nivoe GFR, bile su od 0,983 do 0,917 i one se nisu značajno razlikovale od AUC za druge renalne markere. Rezultati ove studije su pokazali da BTP može biti koristan i pouzdan serumski marker za identifikaciju obima renalne disfunkcije kod pacijenata sa CKD i može se koristiti uz serumski cistatin C i kreatinin kao alternativni endogeni GFR marker.
The aim of the present study is to describe the influence of glucocorticoid immunosuppression on serum cystatin C concentration in renal transplant patients. To evaluate the influence of ...immunosuppressive regimens, especially glucocorticoids, on serum cystatin C level, 38 clinically stable patients on immunosuppression therapy with low-dose glucocorticoids were compared to 30 clinically stable patients receiving cyclosporin A alone, and 18 clinically stable patients receiving cyclosporin A together with azathioprine. Clinical stability was defined as the absence of acute rejection, febrile infection, and cyclosporin A toxicity, as well as stability of creatinine clearance as estimated by the formula of Cockroft and Gault. All groups were compared for estimated creatinine clearance (CrCl) values and had comparable gender, age and time since transplantation. The group receiving short-course, high-dose methylprednisolone was analyzed at four time points: a) before methylprednisolone commencement (median, 15 days); b) the day methylprednisolone was introduced (before medication); c) after 3 days of methylprednisolone therapy; and d) on a follow-up 9-10 days after the last dose. Intravenous administration of high-dose methylprednisolone led to significant differences in cystatin C levels at different time points (before administration, after three doses, and 8 days after discontinuation). Glucocorticoid medication in adult renal transplant patients is associated in a dose-de pendent manner with increased cystatin C, leading to systematic under estimation of GFR. Moreover, our data illustrate the need for specific reference intervals in patients on glucocorticoid therapy. In clinical routine settings, as well as in future clinical studies, it is important to take glucocorticoid medication into account when interpreting serum cystatin C concentrations in renal transplant patients presumably, as well as in other patient groups.
U radu je opisan uticaj glukokortikoidne imunosupresije na koncentraciju cistatina C u serumu pacijenata posle transplantacije bubrega. Kako bi se odredio uticaj imunosupresivne terapije, naročito glukokortikoida, na nivo cistatina C u serumu, upoređeno je 38 klinički stabilnih pacijenata koji su primali niske doze glukokortikoida sa 30 klinički stabilnih pacijenata koji su primali samo ciklosporin A, i 18 klinički stabilnih pacijenata koji su primali ciklosporin A zajedno sa azatioprinom. Klinička stabilnost je definisana kao odsustvo akutne reakcije, febrilne infekcije i ciklosporinske nefrotoksičnosti uz stabilan klirens kreatinina utvrđen pomoću formule Kokrofta i Golta. Grupa pacijenata koji su primali u kratkom periodu visoke doze metilprednizolona analizirana je 15 dana ranije, na dan aplikacije, trećeg i 9-10 dana po završetku terapije. Rezultati su potvrdili da u prva tri dana od primene (500 mg/dan) postoji značajno povećanje koncentracije cistatina C, koja se normalizovala po završetku terapije. Rezultati dobijeni primenom niskih doza glukokortikosteroidne terapije pokazuju značajno povećanje koncentracije cistatina C u odnosu na kontrolnu grupu. Ova preliminarna ispitivanja ukazuju na potrebu uvođenja specifičnog referentnog intervala za pacijente na glukokortikoidnoj terapiji.
Cystatin C (CysC) is a nonglycosylated 13 KD protein that belongs to the type II cystatin gene family. It is a strong inhibitor of cysteine proteinases, freely filtered by the kidney glomerulus and ...reabsorbed by the tubulus, where it is almost totally catabolized. Remainder of the nonmetabolized CysC is eliminated in urine and may represent a useful marker of tubular dysfunction. The aim of the study was to confirm the clinical importance of the quantitative determination of CysC by an automated immunonephelometric method (DADE Behring). Two groups of patients were examined: one with glomerular (GD, n=36) and one with tubular dysfunction (TD, n=31), and compared with the control group (CG, n=31) of healthy males and females from laboratory personnel (n=11) and patients on routine systematic examination (n=20), from 25 to 58 years old. The patient groups were categorised according to the urine analysis of total proteins, creatinine and adequate proteins electrophoretic panel. CysC concentration in CG was in the range of 0.02-0.15 mg/L; 0.01-0.48 mg/L and 0.25-18 mg/L in GD and TD groups respectively. Values of means ± SD for patient groups (GD=0.11 ± 0.14; TD=3.92 ± 3.75 mg/L) showed statistical significance (p<0.001) in the TD group in relation to GD and CG groups. It confirms that quantitative determination of CysC in one urine portion, with a fast laboratory method, might be a useful marker of tubular dysfunction, especially in emergency situations, taking into account that there is no interference of circadian variation on its concentration.
Cistatin C (CysC) je neglikozirajući protein molekulske mase od 13 KD koji pripada tipu II genske familije cistatina. Ima funkciju inhibitora cistein proteinaze koji se potpuno filtrira u glomerulima a zatim reapsorbuje i kataboliše u proksimalnim tubulima. Preostali i nerazgrađen CysC biva eliminisan urinom pa zato može da bude koristan marker tubulskih oštećenja. Cilj ispitivanja bio je da se utvrdi klinički značaj kvantitativnog određivanja CysC automatizovanom imunonefelometrijskom metodom (DADE Behring). Ispitane su dve grupe bolesnika: sa tubulskom (TI) i glomerulskom (GI) insuficijencijom, i upoređene sa kontrolnom grupom (KG) koju su činile zdrave osobe oba pola (n=31), laboratorijski personal (n=11) i pacijenti na sistematskom pregledu (n = 20), starosne dobi od 25 do 58 godina. Kategorizacija grupa sa GI (n=36) i TI (n=31) ustanovljena je na osnovu koncentracije ukupnih proteina, kreatinina i adekvatnih elektroforetskih denzitometrijskih varijanti karakterističnih za obe grupe. Koncentracija CysC u KG bila je u opsegu 0,02-0,15 mg/L, u grupi sa GI 0,01-0,48 mg/L, a u grupi sa TI 0,25-18 mg/L. Rezultati vrednosti (medijana±SD) za grupu sa GI (0,11 ± 0,14 mg/L) i grupu sa TI (3,92 ± 3,75 mg/L) pokazali su statistički značajnu razliku (p< 0,0001) između grupe sa TI i grupa sa GI i KG. Pokazano je da određivanje CysC u jednom uzorku urina brzim laboratorijskim postupkom može biti koristan test za diferencijalnu dijagnostiku tubulskih u odnosu na glomerulska oštećenja, posebno u urgentnim stanjima, s obzirom na činjenicu da na njegovu koncentraciju nema uticaja cirkadijalnih ritmova.
Proteins in clinical practice are analyzed as important parameters in the determination and treatment of different diseases. The scopes of the analyses are mainly concentrated in two levels - ...analyses of the complete protein profile, or determination of an isolated protein. In this work, despite of the use of conventional methods, mainly electrophoresis, new techniques have been implemented in protein analyses. Lab-on-a-chip is an electrophoretic technique that, when optimized, provides analyses of the total protein profile. When normal samples are compared to samples obtained from patients with different neurological diseases, characteristic patterns can be noted. Also, correlation and comparison can be made between the newly developed microchip electrophoresis method and the results obtained using the conventional techniques. When an analysis of a specific protein is necessary, mass spectrometry has proven to give best results, in both the se lectivity and specificity of analyses. It is believed that cystatin C is a potential biomarker in neurological diseases; therefore, the mass spectrometry method has been developed in order to obtain qualitative and quantitative analyses of biological fluids. Using the developed method of mass spectrometry immunoassay (MSIA), cystatin C was easily isolated and analyzed, obtaining complete analysis within minutes. The resulting mass spectra revealed various levels of cystatin C isoforms in serum and CSF samples.
U kliničkoj praksi, proteini se analiziraju kao parametri važni za određivanje i lečenje različitih bolesti. Postoje dva opsega analiza: analize kompletnog proteinskog profila ili određivanje izolovanog proteina. U ovom radu, pored korišćenja uobičajenih metoda, pre svega elektroforeze, u analizu proteina uključene su nove tehnike. Laboratorija na čipu je elektroforetska tehnika koja, optimizovana, omogućava analize ukupnog proteinskog profila. Kada se normalni uzorci uporede sa uzorcima dobijenim od pacijenata s različitim neurološkim oboljenjima, postaju uočljivi karakteristični obrasci. Takođe, moguće je uspostaviti korelaciju i poređenje između nedavno razvijenih metoda »mikročip« elektroforeze i rezultata dobijenih korišćenjem uobičajenih tehnika. Kada je neophodna analiza specifičnog proteina, masena spektrometrija je dala najbolje rezultate, što se tiče selektivnosti kao i specifičnosti analiza. Postoji uverenje da je cistatin C potencijalni biomarker za neurološka oboljenja, stoga je razvijen metod masene spektrometrije kako bi se postigle kvalitativne i kvantitativne analize bioloških tečnosti. Pomoću metode imunoeseja masenom spektrometrijom (MSIA), cistatin C je lako izolovan i analiziran a kompletna analiza trajala je nekoliko minuta. Maseni spektri koji su nastali kao rezultat otkrili su različite nivoe izoformi cistatina C u serumu i uzorcima cerebrospinalne tečnosti.
Using serum cystatin C in estimating glomerular filtration rate (GFR) has in recent times been recommended. A number of simple formulas for calculating GFR have been derived specifically from serum ...cystatin C concentrations. The purpose of this study was to assess the significance of cystatin C and of the two most frequently applied of these formulas in estimating glomerular filtration rate compared to serum creatinine and its derived formulas for estimating glomerular filtration rate from creatinine concentrations. The study included 74 patients: 59 were in various stages of chronic renal insufficiency (divided into two subgroups: I with GFR ≥ 60 mL/min/1.73m2 and II with GFR<60 mL/min/1.73m2) and 15 on hemodialysis. A control group of 30 healthy participants was also included in the study. Serum values of cystatin C ranged from: 0.86 ± 0.16 mg/L in subgroup I, and 1.77 ± 0.79 mg/L in subgroup II, to 6.9 ± 1.83 mg/L in patients on hemodialysis. The correlation between the two formulas derived from cystatin C and the clearance of creatinine, as well as the Cockcroft and Gault's formula, was significant, while one of the formulas derived from cystatin C did not show a significant correlation with MDRD. It was concluded that serum cystatin C is a significant marker in estimating glomerular filtration rate, especially in the advanced stages of chronic renal insufficiency.
U novije vreme preporučena je upotreba serumskog cistatina C u proceni jačine glomerulske filtracije (GFR). Upravo iz serumske koncentracije cistatina C je izvedeno nekoliko jednostavnih formula za izračunavanje GFR. Cilj ove studije je bio da proceni značaj cistatina C i dve najčešće primenjivane od tih formula u proceni jačine glomerulske filtracije u poređenju sa serumskim kreatininom i izvedenim formulama za procenu jačine glomerulske filtracije iz koncentracija kreatinina. U studiju je uključeno 74 ispitanika: 59 u različitim stadijumima hronične bubrežne insuficijencije (podeljenih u dve podgrupe: I sa GFR ≥ 60 mL/min/1,73m2 i II sa GFR< 60 mL/min/1,73m2) i 15 na hemodijalizi. U studiju je bila uključena i kontrolna grupa od 30 zdravih ispitanika. Serumske vrednosti cistatina C su se kretale: u podgrupi I 0,86 ± 0,16 mg/L, u podgrupi II 1,77 ± 0,79 mg/L i kod ispitanika na hemodijalizi 6,9 ± 1,83 mg/L. Korelacija između obe formule izvedene iz cistatina C i klirensa kreatinina kao i Kokroft-Gaultove formule bila je značajna, dok jedna od ovih formuli izvedenih iz cistatina C nije pokazala značajnu korelaciju sa MDRD. Može se zaključiti da je serumski cistatin C značajan parametar u proceni jačine glomerulske filtracije, naročito u odmaklim stadijumima hronične bubrežne insuficijencije.
Brzina glomerularne filtracije (GFR) je široko prihvaćena kao najbolja opšta mera funkcije bubrega. Vodiči američke Nacionalne fondacije za bubreg definišu hroničnu bubrežnu bolest (HBB) bilo sa ...vrednošću GFR koja je manja od 60 mL/min/1,73 m2 ili sa prisustvom oštećenja bubrega, bez obzira na uzrok, u toku 3 ili više meseci i klasifikuju stadijume težine HBB prema GFR. GFR se može meriti kao urinarni ili plazma klirens egzogenih filtracionih markera kao što je inulin. Međutim, zbog teškoća u primeni, troškova i radijacionog izlaganja, ove metode imaju ograničenu upotrebu u rutinskim laboratorijama. Klirens kreatinina može biti korisna alternativa kada egzogeni markeri nisu dostupni, ali sakupljanje urina u vremenskim intervalima nije pogodno za pacijente i osetljivo je na grešku pri sakupljanju. GFR se često procenjuje klinički iz serumskih koncentracija egzogenog kreatinina ili cistatina C. Cistatin C u serumu još uvek nije adekvatno procenjen kao indeks GFR, a na kreatinin u serumu utiču GFR i faktori nezavisni od GFR, uključujući godine, pol, rasu, telesnu veličinu, ishranu, izvesne lekove i laboratorijske analitičke metode. Prema kliničkim vodičima Nacionalne fondacije za bubreg, kliničke laboratorije bi trebalo da izdaju >>procenjenu<< GFR (estimated GFR), izračunatu iz prediktivnih jednačina, kao dodatak izveštavanja vrednosti markera u serumu. Trenutno preporučena jednačina za procenu je razvijena iz MDRD (Modification of Diet in Renal Disease) studije. Ova jednačina koristi godine, pol, rasu (afro-američka prema ne-afro-američkoj) i koncentraciju kreatinina u serumu, a ne zahteva varijablu za telesnu težinu zato što normalizuje GFR za standardnu telesnu površinu od 1,73 m2. Da bi se postigla poboljšana tačnost preračunate GFR sa ovom jednačinom, preporučuje se da komercijalne metode za kreatinin budu kalibrisane prema sertifikovanim referentnim materijalima i sledljive sa IDMS (isotope dilution mass spectrometry) metodologijom. Za MDRD jednačinu je pokazano da je korisna za pacijente sa HBB, ali njena upotreba je još uvek nejasna za ljude sa niskim vrednostima kreatinina u serumu i visokim vrednostima za GFR, uključujući zdrave pojedince, decu i trudnice. Validacione studije su u razvoju kako bi se procenila MDRD jednačina za druge etničke grupe i različita bolesna stanja.
The glomerular filtration rate (GFR) is widely accepted as the best overall measure of kidney function. American National Kidney Foundation guidelines define chronic kidney disease (CKD) by either a GFR of less than 60 mL/min/1.73 m2 or the presence of kidney damage, regardless of the cause, for 3 or more months, and classify stages of CKD severity according to GFR. GFR can be measured as the urinary or plasma clearance of exogenous filtration markers such as inulin. However, because of difficulty in use, expenses and radiation exposure, these methods have limited use in the routine laboratories. Creatinine clearance may be a useful alternative when exogenous markers are not available, but timed urinary collection is not convenient for patients and is susceptible to error during collection. GFR is often estimated clinically from serum concentrations of endogenous creatinine or cystatin C. Serum cystatin C has not yet been adequately evaluated as an index of GFR, and serum creatinine is affected by the GFR and by factors independent of GFR, including age, sex, race, body size, diet, certain drugs and laboratory analytical methods. According to National Kidney Foundation clinical guidelines, clinical laboratories should report an estimated GFR, calculated from prediction equations, in addition to reporting the serum marker value. The currently recommended estimating equation was developed from the Modification of Diet in Renal Disease (MDRD) study. This equation uses age, sex, race (African-American vs. non-African-American), and serum creatinine concentration, and does not require a body weight variable because it normalizes GFR for a standard body surface area of 1.73 m2. To achieve improved accuracy of calculated GFR with this equation, it is recommended that commercial creatinine methods should be calibrated against certified reference material and should be traceable to IDMS (isotope dilution mass spectrometry) methodology. MDRD equation has been shown to be useful for CKD patients, but its use is still unclear for people with low values for serum creatinine and high values for GFR, including healthy individuals, children and pregnant women. Validation studies are in progress to evaluate the MDRD equation for other ethnic groups and various disease conditions.
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