Glomerular Filtration Rate Biomarkers Research Articles

Assessing GFR With Proenkephalin

In clinical practice, kidney (dys)function is monitored through creatinine-based estimations of glomerular filtration rate (eGFR: Modification of Diet in Renal Disease [MDRD], Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). Creatinine is recognized as a late and insensitive biomarker of glomerular filtration rate (GFR). The novel biomarker proenkephalin (PENK) may overcome these limitations, but no PENK-based equation for eGFR is currently available. Therefore, we developed and validated a PENK-based equation to assess GFR. In this international multicenter study in 1354 stable and critically ill patients, GFR was measured (mGFR) through iohexol or iothalamate clearance. A generalized linear model with sigmoidal nonlinear transfer function was used for equation development in the block-randomized development set. Covariates were selected in a data-driven fashion. The novel equation was assessed for bias, precision (mean ± SD), and accuracy (eGFR percentage within ±30% of mGFR, P30) in the validation set and compared with MDRD and CKD-EPI. Median mGFR was 61 [44-81] ml/min per 1.73 m2. In order of importance, PENK, creatinine, and age were included, and sex or race did not improve performance. The PENK-based equation mean ± SD bias of the mGFR was 0.5 ± 15 ml/min per 1.73 m2, significantly less compared with MDRD (8 ± 17, P< 0.001) and 2009 CKD-EPI (5 ± 17, P< 0.001), not reaching statistical significance compared with 2021 CKD-EPI (1.3 ± 16, P= 0.06). The P30 accuracy of the PENK-based equation was 83%, significantly higher compared with MDRD (68%, P< 0.001) and 2009 CKD-EPI (76%, P< 0.001), similar to 2021 CKD-EPI (80%, P= 0.13). Overall, the PENK-based equation to assess eGFR performed better than most creatinine-based equations without using sex or race.

Investigation of N,N,N-Trimethyl-L-alanyl-L-proline Betaine (TMAP) as a Biomarker of Kidney Function.

Glomerular filtration rate (GFR) is the most widely used tool for the measurement of kidney function, but endogenous biomarkers such as cystatin C and creatinine have limitations. A previous metabolomic study revealed N,N,N-trimethyl-L-alanyl-L-proline betaine (TMAP) to be reflective of kidney function. In this study, we developed a quantitative LCMS assay for the measurement of TMAP and evaluated TMAP as a biomarker of GFR. An assay to measure TMAP was developed using liquid chromatography-mass spectrometry. After validation of the method, we applied it to plasma samples from three distinct kidney disease patient cohorts: nondialysis chronic kidney disease (CKD) patients, patients receiving peritoneal and hemodialysis, and living kidney donors. We investigated whether TMAP was conserved in other mammalian and nonmammalian species, by analyzing plasma samples from Wistar rats with diet-induced CKD and searching for putative matches to the m/z for TMAP and its known fragments in the raw sample data repository "Metabolomics Workbench". The assay can measure plasma TMAP at a lower limit of quantitation (100 ng/mL) with an interday precision and accuracy of 12.8 and 12.1%, respectively. In all three patient cohorts, TMAP concentrations are significantly higher in patients with CKD than in controls with a normal GFR. Further, TMAP concentrations are also elevated in rats with CKD and TMAP is present in the sap produced from Acer saccharum trees. TMAP concentration is inversely related to GFR suggesting that it is a marker of kidney function. TMAP is present in nonmammalian species suggesting that it is part of a biologically conserved process.

An Endorsement of the Removal of Race From GFR Estimation Equations: A Position Statement From the National Kidney Foundation Kidney Disease Outcomes Quality Initiative

An Endorsement of the Removal of Race From GFR Estimation Equations: A Position Statement From the National Kidney Foundation Kidney Disease Outcomes Quality Initiative

Relationship between FGF 23, SDMA, Urea, Creatinine and Phosphate in Relation to Feline Chronic Kidney Disease.

Simple SummaryChronic kidney disease (CKD) is the most frequent metabolic disorder affecting geriatric cats, and is a major cause of mortality among this species. Due to its progressive nature and non-specific clinical signs, an effort is being made to discover new, more efficient biomarkers of glomerular filtration for the timely diagnosis of renal insufficiency. Symmetric dimethylarginine (SDMA) and fibroblast growth factor 23 (FGF 23) are promising new markers currently of interest in veterinary medicine. This study discusses the relationship between SDMA, FGF 23 and previously used indicators of kidney function, mainly creatinine, urea and phosphate, to establish their efficacy in a clinical setting. An increase in FGF 23 in CKD patients compared to healthy cats has been recognized, despite the lack of an evident correlation of FGF 23 with other analyzed markers.Chronic kidney disease (CKD) is a common diagnosis in older cats, and its prevalence increases with age. Conventional indirect biomarkers of glomerular filtration rate (GFR) have their limitations, and are not efficient in detecting early decreases in glomerular filtration rate. Recently, symmetric dimethylarginine (SDMA) concentrations have been proposed as a novel biomarker of GFR for the early detection of CKD. This study discusses the relationship between SDMA, FGF 23 and previously used indicators of kidney function, mainly creatinine, urea and phosphate. Ninety-nine cats were included in this study. Based on their SDMA values, 48 cats had CKD and the remaining 51 cats were used as a healthy control group. Serum of these cats was assayed for creatinine, urea and phosphate concentrations as well as FGF 23 values, and correlations between them were evaluated. Cats with CKD had higher FGF 23 concentrations than healthy cats, and no correlation was found between FGF 23 and SDMA, nor between FGF 23 and phosphate. On the other hand, phosphate strongly correlated with SDMA, urea and creatinine, making it a possible independent factor of CKD progression.

Association of Serum Beta-Trace Protein Levels in Patients with Chronic Kidney Disease: A Case-control Study

Introduction: Chronic Kidney Disease (CKD) is common disorder showing decreased Glomerular Filtration Rate (GFR) value (&lt;60 mL/min/1.73 m2 ). Because of limitations of creatinine as a biomarker of GFR, new alternative biomarkers are being investigated, such as Beta-Trace Protein (BTP) is low molecular weight proteins that are filtered by the glomeruli. Serum BTP have been shown to be more helpful for estimating GFR. Aim: To assess the role of Beta-Trace Protein (BTP) as a potential biomarker of Chronic Kidney Disease (CKD) in comparison to serum urea, serum creatinine, fasting blood sugar and Creatinine Clearance Rate (CCR). Materials and Methods: This case-control study was conducted at Government Medical College, Rajouri, Jammu and Kashmir, India, from February 2021 to December 2021. Total 50 known patients of kidney diseases and 50 healthy individuals above the age of 18 years were enrolled in the study. Blood samples were collected from all individuals and serum BTP, serum urea level, serum creatinine level, fasting blood sugar were measured. Correlation of BTP with serum urea level, serum creatinine level, Fasting Blood Glucose (FBG) level, and CCR was calculated by Pearson Correlation test. Results: In present study, 50 patients in case groups (33 male and 17 females) and 50 healthy controls (25 males and 25 females) were included. Among controls, the mean age of patients was 52.12±5.66 years and among cases 55.94±10.51 years. BTP level was increased two times (from 32.06±11.25 µg/ml to 66.36±27.80 µg/ml) in CKD patients than controls individuals. BTP level was positively correlated with serum urea level, serum creatinine level, and FBG level while negatively correlated with CCR. Conclusion: 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 creatinine as an alternative endogenous GFR marker.

The furosemide stress test and computational modeling identify renal damage sites associated with predisposition to acute kidney injury in rats

Acute kidney injury (AKI) diagnosis relies on plasma creatinine concentration (Crpl), a relatively insensitive, surrogate biomarker of glomerular filtration rate that increases only after significant damage befalls. However, damage in different renal structures may occur without increments in Crpl, a condition known as subclinical AKI. Thus, detection of alterations in other aspects of renal function different from glomerular filtration rate must be included in an integral diagnosis of AKI. With this aim, we adapted to and validated in rats (for preclinical research) the furosemide stress test (FST), a tubular function test hitherto performed only in humans. We also tested its sensitivity in detecting subclinical tubular alterations. In particular, we predisposed rats to AKI with 3 mg/kg cisplatin and subsequently subjected them to a triggering insult (ie, 50 mg/kg/d gentamicin for 6 days) that had no effect on nonpredisposed animals but caused an overt AKI in predisposed rats. The FST was performed immediately before adding the triggering insult. Predisposed animals showed a reduced response to the FST (namely, reduced furosemide-induced diuresis and K+ excretion), whereas nonpredisposed animals showed no alteration, compared to the controls. Computational modeling of epithelial transport of solutes and water along the nephrons applied to experimental data suggested that proximal tubule transport was only minimally reduced, the sodium-chloride symporter was upregulated by 50%, and the renal outer medullary potassium channel was downregulated by 85% in predisposed animals. In conclusion, serial coupling of the FST and computational modeling may be used to detect and localize subclinical tubular alterations.

Abstract 3015: Tucatinib inhibits creatinine and metformin renal tubule secretion but has no effect on renal function (GFR)

Abstract Background: Tucatinib (TUC) is a potent, highly selective investigational HER2 tyrosine kinase inhibitor in development for treatment of patients with HER2+ metastatic breast cancer (MBC). In HER2CLIMB (H2C), a pivotal study of patients with HER2+ MBC, a modest transient, reversible increase in serum creatinine (SCr) levels was observed in patients who received TUC. Similarly, in a study with healthy volunteers, SCr increased after 300 mg BID TUC and returned to baseline levels after TUC discontinuation. Clinically, SCr is used as a biomarker for glomerular filtration rate (GFR) and is routinely measured to monitor for potential renal injury. However, SCr renal elimination also depends on the kidney transporters OCT2 (uptake), MATE1 (efflux) and MATE2-K (efflux). Inhibition of OCT2 and MATE1/2-K has been associated with SCr increases in the absence of kidney damage (e.g., abemaciclib). In vitro assessments and a clinical study were performed to assess the impact of TUC on OCT2 and MATE1/2-K-mediated transport. Methods: Inhibition of OCT2, MATE1, and MATE2-K-mediated transport by TUC was estimated in transfected MDCK-II cells using creatinine and metformin (MF), a sensitive OCT2 and MATE1/2-K substrate used to quantify transport inhibition in vivo, as probe substrates. Subsequently, a single-arm drug-drug interaction study was performed in 17 healthy volunteers to evaluate the effects of TUC on MF PK. MF (850 mg, PO) was administered in the absence and presence of TUC (300 mg BID, PO). Iohexol was administered to calculate actual GFR (aGFR) in the absence and presence of TUC. Plasma (iohexol, MF and TUC) and urine (MF) samples were collected for PK analysis; drug concentrations were measured using validated LC-MS/MS methods. Serum and urine creatinine levels were also measured. Results: In MDCK II cells, TUC inhibited creatinine transport by OCT2 (IC50 = 0.107 µM) and MATE1 (IC50 = 0.086 µM) and MF transport by MATE1 (IC50 = 0.340 µM) and MATE2-K (IC50 = 0.135 µM), but not by OCT2 (IC50 = 14.7 µM). Using these IC50 values, physiologically-based pharmacokinetic (PBPK) model simulations predicted a 1.16 to 1.35-fold increase of MF exposure in the presence of TUC. Consistent with the PBPK prediction, in healthy volunteers MF exposure (AUCinf) increased ~1.4-fold and renal clearance decreased from 29.99 L/h to 17.64 L/h in the presence of TUC with no effect on MF Cmax. Iohexol clearance was unaffected in the presence of TUC indicating no change in aGFR. SCr increased in the presence of TUC and returned to baseline 8 days after TUC discontinuation. Conclusions: Together, these data demonstrate that the observed SCr increase in clinical studies with TUC is due to inhibition of tubular secretion of creatinine via OCT2 and MATE1 and not due to an effect on kidney function. An alternative, non-creatinine-based measure of renal function should be considered for tucatinib. Citation Format: Ariel R. Topletz-Erickson, Anthony Lee, JoAl Mayor, Evelyn Rustia, Layth Abdulrasool, Luke Walker, Christopher J. Endres. Tucatinib inhibits creatinine and metformin renal tubule secretion but has no effect on renal function (GFR) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3015.

Dissecting the Genetic Architecture of Cystatin C in Diversity Outbred Mice.

Plasma concentration of Cystatin C (CysC) level is a biomarker of glomerular filtration rate in the kidney. We use a Systems Genetics approach to investigate the genetic determinants of plasma CysC concentration. To do so we perform Quantitative Trait Loci (QTL) and expression QTL (eQTL) analysis of 120 Diversity Outbred (DO) female mice, 56 weeks of age. We performed network analysis of kidney gene expression to determine if the gene modules with common functions are associated with kidney biomarkers of chronic kidney diseases. Our data demonstrates that plasma concentrations and kidney mRNA levels of CysC are associated with genetic variation and are transcriptionally coregulated by immune genes. Specifically, Type-I interferon signaling genes are coexpressed with Cst3 mRNA levels and associated with CysC concentrations in plasma. Our findings demonstrate the complex control of CysC by genetic polymorphisms and inflammatory pathways.

Association between breed and renal biomarkers of glomerular filtration rate in dogs

BackgroundKidney disease, especially chronic kidney disease (CKD), is common in older dogs. The biomarkers symmetric dimethylarginine (SDMA) and creatinine (Cr) are indicators of glomerular filtration rate (GFR). This retrospective study...

Fibroblast growth factor 23 and symmetric dimethylarginine concentrations in geriatric cats.

BackgroundFibroblast growth factor 23 (FGF23) is a phosphaturic hormone that is increased in azotemic cats with chronic kidney disease (CKD) and predictive of the onset of azotemia in older cats. The introduction of symmetric dimethylarginine (SDMA) as a biomarker of glomerular filtration rate has led to the identification of cats in which SDMA is increased, but plasma creatinine concentrations remains within reference range. There is currently little understanding of the metabolic changes present in such cats.ObjectivesTo examine the relationship between plasma FGF23 and SDMA concentrations in non‐azotemic geriatric cats.AnimalsRecords of a cross section of client‐owned cats (n = 143) without azotemic CKD.MethodsClinicopathological information was obtained from cats (≥ 9 years) from records of 2 first opinion practices. The relationship between plasma SDMA and FGF23 concentrations was examined using Spearman's correlation and variables compared using the Mann‐Whitney U test.ResultsCats with increased SDMA concentrations had significantly higher plasma FGF23 (P < .001) and creatinine (P < .001) concentrations compared to cats with SDMA concentrations within reference range. A weak positive relationship was demonstrated between plasma FGF23 and SDMA concentrations (r = .35, P < .001) and between plasma FGF23 and creatinine (r = .23, P = .005) concentrations.Conclusions and Clinical ImportanceMore cats with increased SDMA concentrations had higher FGF23 concentrations than those with SDMA concentrations within the reference range, suggesting the presence of an alteration in phosphate homeostasis. Further studies are warranted to identify influencing factors and to explore the utility of FGF23 concentration to inform management of cats with early stage CKD.

Determination of glomerular filtration rate using cystatin C in healthy Nigerian newborns

ABSTRACTBackground: The value of Cystatin C as a biomarker of Glomerular filtration rate (GFR) among African newborns is unknown, due to paucity of studies, restricting the measurement of GFR in this population of newborns to creatinine clearance despite its limitations. This study was therefore conducted to estimate GFR from serum Cystatin C in a population of Nigerian newborns and explored the relationship with anthropometrics.Methods: This was a cross-sectional, analytical study. A total of 60 healthy preterm and 30 healthy term babies were recruited at a tertiary hospital in North-central, Nigeria. Serum Cystatin C was determined using ELISA according to standard methods. Anthropometric measurements were done with standard methods. The GFR was estimated using Zappitelli’s equation. Data were analyzed using SPSS Version 20, and p-value < 0.05 was considered significant.Results: Mean serum Cystatin C was 1.20 ± 0.33 (range 0.80–2.20) mg/L with comparable values in males and females (1.19 ± 0.35 vs 1.15 ± 0.31 mg/L, p = 0.481)). Mean serum Cystatin C among preterm babies were higher than term babies (1.31 ± 0.36 vs 1.01 ± 0.11 mg/L, p = < 0.001). Mean estimated GFR was 65.36 ± 16.9 ml/min/1.732 and was comparable in males and females (64.39 ± 17.95 vs 66.52 ± 15.76 ml/min/1.73 m2,p = 0.555). Estimated GFR was lower among preterm than term babies (60.10 ± 17.53 vs 75.89 ± 9.1 ml/min/1.73 m2, p = < 0.001). Serum cystatin C and estimated GFR moderately correlated with gestational age and anthropometrics (length, occipitofrontal circumference and weight).Conclusions: Serum cystatin C as a biomarker GFR among newborns is low compared with most studies done out of Africa. The serum cystatin C and estimated GFR correlated with the gestational age and anthropometric parameters. The findings relationship between the serum Cystatin C, estimated GFR and anthropometrics among the newborns suggested a need for more studies.

Indirect markers of glomerular filtration rate in dogs and cats: a review

Early diagnosis of kidney disease continues to be a subject of intense interest. Direct measurement of glomerular filtration rate is too complicated for first-line practices; thus, indirect markers of renal function have also been evaluated. Creatinine, traditionally measured as a readout of renal function, has limitations in its sensitivity. In dogs and cats, cystatin C became popular approximately 15 years ago, but recent reports question its usefulness, especially in cats. Symmetric dimethylarginine seems to be very promising as a marker of glomerular filtration rate with the ability to detect renal impairment earlier than creatinine. This article presents current knowledge of qualities, limitations, advantages and availability of novel and traditionally used biomarkers of glomerular filtration rate in dogs and cats.

Serum creatinine: advantages and pitfalls

Serum creatinine (sCr) is today the most commonly used marker to estimate glomerular filtration rate (GFR). However, measuring and interpreting creatinine is not so simple. Some physiological reasons, particularly its dependence on muscle mass makes sCr an imperfect biomarker of GFR. However, there are also analytical reasons that could be further improved. The implementation of ID-MS traceable creatinine assays (enzymatic and compensated Jaffe) improved estimation of GFR by reducing bias. Enzymatic methods which are more precise and less susceptible to interfere with non-creatinine chromogens than compensated Jaffe methods, provide more reliable estimations of GFR.

Cystatin C Is a More Reliable Biomarker for Determining eGFR to Support Drug Development Studies.

Glomerular filtration rate (GFR) is routinely used as a surrogate endpoint for the development of investigational drugs in clinical trials. GFR and staging of chronic kidney disease are typically assessed by measuring the concentration of endogenous serum biomarkers such as albumin and creatinine. However, creatinine is subject to high biological variability, and levels of creatinine do not rise until nearly 50% of kidney function is damaged, leading to inaccurate chronic kidney disease staging and false negatives. A newer biomarker for GFR, cystatin C, has been shown to be subject to less biological interference and more sensitive to early declines in kidney function. Cystatin C has also been shown to outperform creatinine as an indicator of true GFR and to add information about the occurrence of acute kidney injury. Comparison studies of cystatin C and creatinine continue to demonstrate its increased accuracy and sensitivity for changes in true GFR. While challenges remain for use of cystatin C, international agencies and working groups continue to validate cystatin C as a biomarker and accompanying GFR estimating equations for diagnostic and drug development use. In this review, we summarize these comparison studies, regulatory and industry guidelines, and clinical trial case studies for use of cystatin C in drug development.

Cystatin C Is a Gender-Neutral Glomerular Filtration Rate Biomarker in Patients with Cirrhosis.

Lower serum Cr levels in women as compared to men result in underestimation of renal dysfunction and lower model for end-stage liver disease-sodium scores leading to reduced access to liver transplantation in women compared to men with comparable hepatic dysfunction. The aim of this study was to determine the gender differences in serum Cr, cystatin C, and other endogenous glomerular filtration rate (GFR) biomarkers, measured and estimated GFR, Cr clearance, and Cr production rates. We measured GFR by iothalamate plasma clearance in 103 patients with cirrhosis and assessed gender differences in GFR, Cr clearance and production rate, serum Cr, cystatin C and other endogenous GFR biomarkers including beta-trace protein, beta-2 microglobulin, and dimethylarginines. Comparison of men and women showed significantly lower values for mean serum Cr (0.97 vs. 0.82mg/dl, P=0.023), and Cr production rate (13.37 vs. 11.02mg/kg/day, P=0.022). In contrast to the serum Cr and Cr production rate, men and women exhibited no significant differences in the means of serum cystatin C and other GFR biomarkers, measured GFR, GFR estimated using Cr-cystatin C GFR equation for cirrhosis, measured and estimated Cr clearances. After controlling for age, race, weight, height, and GFR, female gender remained associated with lower serum Cr levels (P=0.003). Serum cystatin C levels were not associated with gender, age, race, weight, height, C-reactive protein, and history of hypothyroidism. Our results suggest that cystatin C and endogenous GFR biomarkers other than Cr, measured GFR, GFR estimated by Cr-cystatin C GFR equation for cirrhosis, measured and estimated Cr clearance minimized between-gender biases in accounting for renal function in patients with cirrhosis. Therefore, serum cystatin C should be measured as a complementary test to serum Cr when renal function is assessed in patients with cirrhosis, particularly in women and those with sarcopenia.

Redefining acute kidney injury

Specific criteria using easily available biomarkers such as serum creatinine and urine output have been developed to define and stage acute kidney injury(AKI) at the bedside. The RIFLE criteria and the AKIN criteria are used for adults, the pRIFLE criteria for children and the KDIGO classification for both adults and children. The chief limitation in all the current criteria lies with the physiological limitations of using an insensitive functional marker such as serum creatinine as a surrogate marker for glomerular filtration rate (GFR). Varying methodologies for measuring serum creatinine and the lack of validation using isotope dilution mass spectrometry(IDMS), are additional technological limitations that challenge uniformity in India. Calculation of eGFR by the Schwartz formula is compromised by these technological limitations as well as by the lack of a validated k value for Indian children. Serum Cystatin C is superior to creatinine as a biomarker for GFR and appears at least 24 hours earlier than serum creatinine in the presence of AKI. However, expense and non- availability in clinical laboratories precludes its use. Urinary biomarkers appear very sensitive and reflect different stages of cell injury. Neutrophil Gelatinase associated Lipocalin (NGAL) has been shown to appear in the urine as early as 2 hours after renal injury. However, it is not specific for AKI alone and may also be increased in many inflammatory states and co-morbid conditions. The redefined criteria for AKI are invaluable in the critical care setup but need further refinement.

Assessment of Kidney Function in Patients With Cancer.

Cancer patients are living longer. The sequelae of cancer treatment and the role of comorbid conditions present before the diagnosis, such as CKD, have been increasingly recognized. The interface between CKD and cancer is multifaceted. CKD is frequently observed in patients with cancer, and cancer treatment contributes to CKD development and progression. In addition, CKD has been recognized as an important risk factor for cancer development and reduced specific cancer survival. In this context, an accurate evaluation of the glomerular filtration rate (GFR) during oncologic treatment is pivotal and is used to define surgery strategies, program prophylactic management of contrasted examinations, make decisions on cisplatin eligibility, and adjust drug prescriptions, particularly chemotherapy agents. Although the most commonly used equations to estimate GFR based on serum creatinine levels in clinical practice (Cockcroft-Gault, Modification of Diet in Renal Disease Study, and CKD Epidemiology Collaboration equations) have not been validated in patients with cancer in large prospective studies, there is increasingly evidence supporting the use of CKD Epidemiology Collaboration equation to assess the GFR in patients with cancer, including for the use of chemotherapy prescriptions. Many patients with cancer may have changes in nutrition status and clearance measurements such as exogenous filtration markers might be extremely useful when clinical decisions differ depending on the GFR level. Future perspectives include the advent of new serum GFR biomarkers such as cystatin C, beta-trace protein, and beta-2 microglobulin as well as the GFR assessment by measuring total kidney parenchymal volume through image examinations.

Beta Trace Protein does not outperform Creatinine and Cystatin C in estimating Glomerular Filtration Rate in Older Adults

Despite intense research the optimal endogenous biomarker for glomerular filtration rate (GFR) estimation has not been identified yet. We analyzed if ß-trace protein (BTP) improved GFR estimation in elderly. 566 participants aged 70+ from the population-based Berlin Initiative Study were included in a cross-sectional validation study. BTP, standardized creatinine and cystatin C were measured in participants with iohexol clearance measurement as gold standard method for measured GFR (mGFR). In a double logarithmic linear model prediction of mGFR by BTP was assessed. Analyses with BTP only and combined with creatinine and cystatin C were performed. Additionally, performance of GFR estimating equations was compared to mGFR. We found that the combination of all three biomarkers showed the best prediction of mGFR (r2 = 0.83), whereat the combination of creatinine and cystatin C provided only minimally diverging results (r2 = 0.82). Single usage of BTP showed worst prediction (r2 = 0.67) within models with only one biomarker. Subgroup analyses (arterial hypertension, diabetes, body mass index ≤23 and >30) demonstrated a slight additional benefit of including BTP into the prediction model for diabetic, hypertensive and lean patients. Among BTP-containing GFR equations the Inker BTP-based equation showed superior performance. Especially the use of cystatin C renders the addition of BTP unnecessary.

Long-term follow-up of renal function assessing serum cystatin C in dogs with diabetes mellitus or hyperadrenocorticism.

Serum cystatin C (sCysC) is used as biomarker for glomerular filtration rate (GFR). The effects of diabetes mellitus (DM) on renal function in dogs are unclear. Some renal variables have been evaluated in dogs with hyperadrenocorticism (HAC), but not sCysC. The purpose of this study was the validation of a particle-enhanced nephelometric immunoassay (PENIA) for measuring canine sCysC, and to assess renal function in dogs with DM or HAC. A PENIA was analytically validated for canine sCysC by determining imprecision and linearity. In a longitudinal 6-month study, renal function of 14 DM dogs was assessed, using serum creatinine, GFR, urinary protein-to-creatinine (UPC) ratio, urinary markers, systolic blood pressure (SBP), and sCysC, and compared to 17 healthy dogs at baseline. Furthermore, sCysC was measured at initial presentation and during a 12-month follow-up in 22 HAC dogs. The sCysC intra- and inter-assay variation coefficients were < 8% and highly linear (r = .997). About 33% and 67% of DM dogs had persistent proteinuria and systemic hypertension, respectively, but there were no significant differences in GFR, UPC, and urinary markers over time, and compared with healthy dogs at initial presentation. Serum CysC decreased significantly (P < .05) over time within the DM group. It did not change significantly over time within the HAC group. A PENIA measured sCysC linearly and precisely. There were no clinically relevant renal alterations over time in dogs with DM, although persistent proteinuria was observed. In dogs with HAC, sCysC measurement was not useful, although significant GFR changes occurred over time.

Assessment of glomerular filtration rate in the neonate: is creatinine the best tool?

This article answers the question of whether creatinine is the best biomarker for monitoring neonatal glomerular filtration rate (GFR) in view of recent advances in measuring neonatal renal function. We rely largely on serum creatinine for the estimation of GFR in the newborn, even though creatinine is freely exchanged through the placenta. During the first few days of life, the serum creatinine reflects maternal renal function or the maternal creatinine. Back filtration of creatinine in preterm newborns is also a serious limitation. This review summarizes current knowledge on the prenatal and postnatal handling of creatinine as well as that of other, more novel biomarkers of GFR, such as cystatin C (CysC) and β-trace protein (BTP). Only small amounts of CysC cross the placenta, whereas BTP does not cross the placenta at all. However, BTP measurements are not widely available. Recent studies on renal volumetry are also discussed. Currently, CysC may be the most suitable marker of neonatal renal function, but its availability is still limited, it is more costly, and the best method of reporting acute kidney injury and neonatal estimated GFR remains to be established.