Filtration Markers Research Articles

Metabolite profiling of CKD progression in the chronic renal insufficiency cohort study.

BACKGROUNDMetabolomic profiling in individuals with chronic kidney disease (CKD) has the potential to identify novel biomarkers and provide insight into disease pathogenesis.METHODSWe examined the association between blood metabolites and CKD progression, defined as the subsequent development of end-stage renal disease (ESRD) or estimated glomerular filtrate rate (eGFR) halving, in 1,773 participants of the Chronic Renal Insufficiency Cohort (CRIC) study, 962 participants of the African-American Study of Kidney Disease and Hypertension (AASK), and 5,305 participants of the Atherosclerosis Risk in Communities (ARIC) study.RESULTSIn CRIC, more than half of the measured metabolites were associated with CKD progression in minimally adjusted Cox proportional hazards models, but the number and strength of associations were markedly attenuated by serial adjustment for covariates, particularly eGFR. Ten metabolites were significantly associated with CKD progression in fully adjusted models in CRIC; 3 of these metabolites were also significant in fully adjusted models in AASK and ARIC, highlighting potential markers of glomerular filtration (pseudouridine), histamine metabolism (methylimidazoleacetate), and azotemia (homocitrulline). Our findings also highlight N-acetylserine as a potential marker of kidney tubular function, with significant associations with CKD progression observed in CRIC and ARIC.CONCLUSIONOur findings demonstrate the application of metabolomics to identify potential biomarkers and causal pathways in CKD progression.FUNDINGThis study was supported by the NIH (U01 DK106981, U01 DK106982, U01 DK085689, R01 DK108803, and R01 DK124399).

Acute Changes in Serum Creatinine and Kinetic Glomerular Filtration Rate Estimation in Early Phase of Acute Pancreatitis.

In patients with acutely changing kidney function, equations used to estimate glomerular filtration rate (eGFR) must be adjusted for dynamic changes in the concentrations of filtration markers (kinetic eGFR, KeGFR). The aim of our study was to evaluate serum creatinine-based KeGFR in patients in the early phase of acute pancreatitis (AP) as a marker of changing renal function and as a predictor of AP severity. We retrospectively calculated KeGFR on day 2 and 3 of the hospital stay in a group of 147 adult patients admitted within 24 h from the onset of AP symptoms and treated in two secondary-care hospitals. In 34 (23%) patients, changes in serum creatinine during days 1–3 of the hospital stay exceeded 26.5 µmol/L; KeGFR values almost completely differentiated those with increasing and decreasing serum creatinine (area under receiver operating characteristic curve, AUROC: 0.990 on day 3). In twelve (8%) patients, renal failure was diagnosed during the first three days of the hospital stay according to the modified Marshall scoring system, which was associated with significantly lower KeGFR values. KeGFR offered good diagnostic accuracy for renal failure (area under receiver operating characteristic—AUROC: 0.942 and 0.950 on days 2 and 3). Fourteen (10%) patients developed severe AP. KeGFR enabled prediction of severe AP with moderate diagnostic accuracy (AUROC: 0.788 and 0.769 on days 2 and 3), independently of age, sex, comorbidities and study center. Lower KeGFR values were significantly associated with mortality. Significant dynamic changes in renal function are common in the early phase of AP. KeGFR may be useful in the assessment of kidney function in AP and the prediction of AP severity.

Characterising acute kidney injury: The complementary roles of biomarkers of renal stress and renal function.

Although epidemiological studies have enhanced our understanding of acute kidney injury, defining the biologic processes corresponding to the clinical phenotype remains challenging. We have examined biomarkers associated with renal stress plus markers of glomerular function to assess whether this approach may aid prediction of AKI or other relevant endpoints. Urinary [TIMP-2]·[IGFBP7], serum creatinine, plasma cystatin C and plasma proenkephalin 119-159 2 were analyzed in patients enrolled in the prospective, international, Sapphire study. Heterogenous critically ill patients (n = 723) were examined with a primary endpoint of development of KDIGO stage 2-3 within 12 h and a secondary endpoint of major adverse kidney events at 30 days (MAKE30). 100 patients (14%) reached the primary endpoint. Markers of renal stress outperformed those associated with glomerular function. Combining [TIMP-2]•[IGFBP7] with serum creatinine, but not the other functional markers, significantly (p = 0.02) increased the area under the ROC curve (AUC) from 0.80 (0.76-0.84) to 0.85 (0.81-0.89). In patients who did not develop AKI, all markers of glomerular filtration, but not [TIMP-2]·[IGFBP7], were significantly elevated in patients with a history of CKD (p < 0.05). The combination of cell-cycle arrest biomarkers, TIMP-2 and IGFBP7, with serum creatinine but not cystatin C or PENK improved risk stratification for the development of stage 2 or 3 AKI over [TIMP-2]·[IGFBP7] alone.

Association of Kidney Function Measures With Signs of Neurodegeneration and Small Vessel Disease on Brain Magnetic Resonance Imaging: The Atherosclerosis Risk in Communities (ARIC) Study

Chronic kidney disease (CKD) is a risk factor for cognitive decline, but evidence is limited on its etiology and morphological manifestation in the brain. We evaluated the association of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) with structural brain abnormalities visible on magnetic resonance imaging (MRI). We also assessed whether this association was altered when different filtration markers were used to estimate GFR. Cross-sectional study nested in a cohort study. 1,527 participants in the Atherosclerosis Risk in Communities (ARIC) Study. Log(UACR) and eGFR based on cystatin C, creatinine, cystatin C and creatinine in combination, or β2-microglobulin (B2M). Brain volume reduction, infarcts, microhemorrhages, white matter lesions. Multivariable linear and logistic regression models fit separately for each predictor based on a 1-IQR difference in the predictor value. Each 1-IQR lower eGFR was associated with reduced cortex volume (regression coefficient:-0.07 [95% CI,-0.12 to-0.02]), greater white matter hyperintensity volume (logarithmically transformed; regression coefficient: 0.07 [95% CI, 0.01-0.15]), and lower white matter fractional anisotropy (regression coefficient:-0.08 [95% CI,-0.17 to-0.01]). The results were similar when eGFR was estimated with different equations based on cystatin C, creatinine, a combination of cystatin C and creatinine, or B2M. Higher log(UACR) was similarly associated with these outcomes as well as brain infarcts and microhemorrhages (odds ratios per 1-IQR-fold greater UACR of 1.31 [95% CI, 1.13-1.52] and 1.30 [95% CI, 1.12-1.51], respectively). The degree to which brain volume was lower in regions usually susceptible to Alzheimer disease and LATE (limbic-predominant age-related TDP-43 [Tar DNA binding protein 43] encephalopathy) was similar to that seen in the rest of the cortex. No inference about longitudinal effects due to cross-sectional design. We found eGFR and UACR are associated with structural brain damage across different domains of etiology, and eGFR- and UACR-related brain atrophy is not selective for regions typically affected by Alzheimer disease and LATE. Hence, Alzheimer disease or LATE may not be leading contributors to neurodegeneration associated with CKD.

Comparison of 24‐hour urinary creatinine clearance and estimated glomerular filtration rate based on a panel of filtration markers in patients with chronic kidney disease

Diagnosis and management of chronic kidney disease (CKD) requires accurate assessment of glomerular filtration rate (GFR). In practice, GFR is typically estimated by equations based on creatinine concentration in blood, but creatinine is affected by non‐GFR factors such as age and sex. Alternative filtration markers such as cystatin C, beta‐trace protein (BTP), and beta‐2 microglobulin (B2M) may be less dependent on age and sex, but equations combining these markers have not been investigated in patients with chronic kidney disease (CKD). In this cross‐sectional study of 50 patients with CKD stage 3–4, we compared kidney function estimates based on creatinine, cystatin C, BTP, B2M, or a combination of markers. Compared to the creatinine/cystatin C combination equation, the panel equation yielded a mean difference of only 2.8 ml/min/1.73 m2, indicating that switching to the panel equation would be unlikely to affect management.

P8.030: Post-kidney Transplant Prospective Comparison of Measured Urinary Creatinine Clearance With Estimated -eGFR Based on Serum Creatinine or Kinetic- KeGFR for Rapid Changes in Serum Creatinine

Introduction: Post kidney transplant (KTx) with functioning renal allograft, serum creatinine continues to decrease at a variable rate until it stabilizes. Currently, the Cockcroft- Gault (C-G) and Modification of Diet in Renal Disease MDRD-4 formulae, and are based on a single serum creatinine value to estimate GFR for chronic kidney disease. For rapid changes in serum creatinine, the kinetic estimated GFR (KeGFR)1 formula was developed for recovering acute kidney injury. However, post-KTx with functioning allograft eGFR and KeGFR formulae/calculators’ values are not compared with measured urinary creatinine clearance by any glomerular isotope excretion methods. Hence, the medications requiring dose adjustment based on renal function might not be adjusted appropriately. The aim of the present study is to compare actual urinary creatinine clearance every 12 hours with C-G, MDRD-4, and (KeGFR) after functional KTx. Patient and method: 34 consenting subjects (mean age 55.2 +/- 13.8 years; 14 male) were enrolled of which 24 had immediate primary allograft function. These were prospectively studied under IRB-approved protocol. Urine was collected every 12 hours through a Foley catheter post-KTx until serum creatinine was stabilized. Creatinine clearance was calculated {U (urinary creatinine) x V (urinary volume)/ S (serum creatinine); (UV/S)}. Over 200 creatinine clearance values were compared with C-G, MDRD-4, and Chen’s KeGFR calculator at 12, 24- and 48-hours intervals. Results: At each time point, the measured urinary creatinine clearance was consistently higher compared with eGFR by C-G, MDRD-4 formula, and KeGFR by Chen calculator1 until serum creatinine was stabilized around 2mg/dL (Figure-1). The mean creatinine clearance was 68.1 ± 22.1 mL/min. Twenty-two (91%) subjects had a >50% decrease in serum creatinine at the time of discharge. Of these 22 subjects, 20 (90%) had a urinary creatinine clearance >50 mL/min and 18 (81%) had a creatinine clearance of >60 mL/min. Conclusion: Our prospective observations suggest that eGFR by C-G, MDRD-4, and KeGFR at 12, 24, and 48 hours, underestimates the GFR compared to urinary creatinine clearance for post-KTx functioning allograft recipients. We suggest adjusting post-KTx medications based on a 50% decrease in pre-transplant serum creatinine, where measured urinary creatine clearance is >50 mL/min in 92% of cases and >60 mL/min in 81% of cases. Renally dosed medication could be adjusted with a 50% decrease in serum creatinine in post-KTx. Future studies are required with exogenous glomerular filtration markers for more accurate formulae with functioning allografts in the immediate post-KTx period.Reference: 1.https://www.mdcalc.com/kinetic-estimated-glomerular-filtration-rate-kegfr

Urinary single-cell sequencing captures kidney injury and repair processes in human acute kidney injury

Acute kidney injury (AKI) is a major health issue, the outcome of which depends primarily on damage and reparative processes of tubular epithelial cells. Mechanisms underlying AKI remain incompletely understood, specific therapies are lacking and monitoring the course of AKI in clinical routine is confined to measuring urine output and plasma levels of filtration markers. Here we demonstrate feasibility and potential of a novel approach to assess the cellular and molecular dynamics of AKI by establishing a robust urine-to-single cell RNA sequencing (scRNAseq) pipeline for excreted kidney cells via flow cytometry sorting. We analyzed 42,608 single cell transcriptomes of 40 urine samples from 32 patients with AKI and compared our data with reference material from human AKI post-mortem biopsies and published mouse data. We demonstrate that tubular epithelial cells transcriptomes mirror kidney pathology and reflect distinct injury and repair processes, including oxidative stress, inflammation, and tissue rearrangement. We also describe an AKI-specific abundant urinary excretion of adaptive progenitor-like cells. Thus, single cell transcriptomics of kidney cells excreted in urine provides noninvasive, unprecedented insight into cellular processes underlying AKI, thereby opening novel opportunities for target identification, AKI sub-categorization, and monitoring of natural disease course and interventions.

The race coefficient in glomerular filtration rate-estimating equations and its removal.

To review new publications about the use of the race coefficient in glomerular filtration rate (GFR)-estimating equations since this topic was last reviewed a year ago in Current Opinion in Nephrology and Hypertension . Accounting for race (or genetic ancestry) does improve the performance of GFR-estimating equations when serum creatinine (SCr) is used as the filtration marker but not when cystatin C is used. The National Kidney Foundation (NKF)-American Society of Nephrology (ASN) Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease recommended immediate adoption of a new refitted SCr-based equation without race and increased use of cystatin C. This report has created consensus but the endorsed new SCr equation without race underestimates GFR in Black Americans and overestimates GFR in non-Black Americans, which may result in diminished ability to detect racial disparities. The approach recommended by the NKF-ASN Task Force represents a compromise attempting to balance a number of competing values, including racial justice, benefit of classifying more Black Americans as having (more severe) chronic kidney disease, accuracy compared with measured GFR, and financial cost. The full implications of adopting the race-free refitted CKD-EPI SCr equation are yet to be known.

Analysis of Apoptotic, Clinical, and Laboratory Parameters in Type 1 Diabetes and Early Diabetic Nephropathy: Clustering and Potential Groups Evaluation for Additional Therapeutic Interventions

Objective:Type 1 diabetes (T1D) is one of the most prevalent chronic illnesses diagnosed in childhood. Diabetic nephropathy (DN) is one of the commonest complication of T1D. Therefore the development of specific treatment that arrests progression of DN based on an individual approach would be beneficial. Analysis of criteria of apoptosis, and clinical, and laboratory characteristics in T1D and early DN in the framework of clustering may be helpful in the identification of potential groups for additional therapeutic interventions.Methods:A survey of 104 children (62 males, 42 females) with T1D and DN aged 2 to 17 years in the Endocrinology unit of Clinical Pediatric Hospital No 6 (Kyiv, Ukraine) was performed. Clinical data (age, gender, disease duration, blood pressure), conventional laboratory markers including complete blood count, serum cholesterol, hemoglobin A1c (Hb1Ac), glomerular filtration rate (GFR), and microalbuminurea (MAU), and markers of apoptosis (BcL-xL, caspase-3) and transcriptional factor HIF-1alfa were analyzed.Results:A cluster group in T1D children was characterized by somewhat higher number of platelets (PLT) - 344.9±7.88·109/L, increased GFR up to hyperfiltration level 124.5±8.86 mL/min/1.73 m2 and decreased anti-apoptotic defense - BcL-xL 144.9±2.35 a.u. was identified. Children with DN may be divided into three groups based on age, body mass index, systolic blood pressure, PLT count, erthyrocyte sedimentation rate, albumin/globulin ratio, serum cholesterol, Hb1Ac, number of diabetic ketoacidosis (DKA) episodes, GFR, MAU, HIF-1alfa, Bcl-xL, caspase-3 levels. Among children with early DN a cluster characterized by the following parameters was found: PLT count - 311.±12.05·109/L, frequency of DKA episodes - 4.82±0.26 episodes/year, MAU - 112.0±10.12 mm/24 h, HIF - 200.5±3.49 a.u., BcL-xL - 128.8±3.1 a.u., and caspase-3 - 159.6±5.5 a.u.Conclusion:Thus, we hypothesize that T1D pediatric patients with increased PLT count, hyperfiltration and reduced anti-apoptotic defense may represent a group for additional therapeutic interventions, such as antioxidants along with stndard therapies to achieve optimal glycemic control. Within the DN group there was a sub-group with somewhat increased PLT count, high frequency of DKA episodes/year, high MAU, prominent increase in HIF level, prominent disturbances in apoptosis controlling factors BcL-xL and caspase-3 tht may require additional therapeutic interventions, again including antioxidants, but may additionally benefit from anti-apoptotic effectors along with optimal glycemic control, and management of hypertension and albuminuria.

Serum Uromodulin and All-Cause Mortality in Peritoneal Dialysis Patients: A Chinese Cohort Study

Serum Uromodulin and All-Cause Mortality in Peritoneal Dialysis Patients: A Chinese Cohort Study

Cystatin C and lipocalin — endogenous markers of glomerular filtration in children born prematurely

The need to search for new markers of the functional state of the kidneys is increasing due to the gain in the number of extremely premature infants. The review analyzes publications on the possibilities of assessing kidney function using cystatin C and lipocalin in children born prematurely. The constant rate of cystatin C production in all tissues, its elimination through the renal glomerular filter, the absence of secretion in the proximal tubules, as well as independence from many factors, including gender, age, diet, inflammation are ideal conditions for its use as an endogenous biochemical marker of glomerular filtration. Due to biochemical features, the analysis of serum levels of cystatin C was established to be a promising method in the diagnosis of acute renal injury (AKI) in premature infants. For a comprehensive assessment of kidney function in premature infants, simultaneous determination of lipocalin and cystatin C levels in the blood may be important. At the same time, the evaluation of these indicators may have diagnostic significance in predicting the development of chronic kidney disease in children who underwent AKI in infancy. The absence of reference values of lipocalin and cystatin C in premature infants was concluded to hinder the clinical use of their quantitative analysis for a comprehensive assessment of the functional state of the kidneys.

Estimating Analytical Errors of Glomerular Filtration Rate Measurement.

Few studies are available on how to optimize time points for sampling and how to estimate effects of analytical uncertainty when glomerular filtration rate (GFR) is calculated. We explored the underlying regression mathematics of how analytical variation of a kidney filtration marker affects 1-compartment, slope-and-intercept GFR calculations, using 2 or 3 time points following a bolus injection, and used this to examine the results from 731 routine 3-point iohexol plasma clearance measurements. GFR calculations inflated analytical uncertainty if the time points were taken too late after the bolus injection and too close after each other. The uncertainty in GFR calculation was, however, the same as the analytical uncertainty if optimal time points were used. The middle of the 3 samples was of little value. The first sample should be taken as early as possible after the distribution phase. Sampling before the patient specific half-life of the kidney filtration marker resulted in an exponential error inflation whereas no error inflation was seen when sampling occurred later than 2 half-lives. Theoretical GFR uncertainty could be lowered 2.6-fold if individually optimized time points for sampling had been used in our 731 clearance measurements. Using Taylor expansions to approximate the moments of transformed random variables, the uncertainty of an individual GFR measurement could be calculated in a simple enough way to be applicable by laboratory software. We provide a theoretical foundation to select patient-optimal time points that may both limit errors and allow calculation of GFR uncertainty.

Novel Biomarkers of Kidney Disease in Advanced Heart Failure: Beyond GFR and Proteinuria.

Kidney disease is a common finding in patients with heart failure and can significantly impact treatment decisions and outcomes. Abnormal kidney function is currently determined in clinical practice using filtration markers in the blood to estimate glomerular filtration rate, but the manifestations of kidney disease in the setting of heart failure are much more complex than this. In this manuscript, we review novel biomarkers that may provide a more well-rounded assessment of kidney disease in patients with heart failure. Galectin-3, ST2, FGF-23, suPAR, miRNA, GDF-15, and NAG may be prognostic of kidney disease progression. L-FABP and suPAR may help predict acute kidney injury (AKI). ST2 and NAG may be helpful in diuretic resistance. Several biomarkers may be useful in determining prognosis of long-term kidney disease progression, prediction of AKI, and development of diuretic resistance. Further research into the mechanisms of kidney disease in heart failure utilizing many of these biomarkers may lead to the identification of therapeutic targets.

Continuous Infusion of Iohexol to Monitor Perioperative Glomerular Filtration Rate.

Continuous monitoring of the glomerular filtration rate (GFR) in the perioperative setting could provide valuable information about acute kidney injury risk for both clinical and research purposes. This pilot study aimed to demonstrate that GFR measurement by a continuous 72 hrs iohexol infusion in patients undergoing colorectal cancer surgery is feasible. Four patients undergoing robot-assisted colorectal cancer surgery were recruited from elective surgery listings. GFR was determined preoperatively by the single-sample iohexol clearance method, and postoperatively at timed intervals by a continuous iohexol infusion for 72 hrs. Plasma concentrations of creatinine and cystatin C were measured concurrently. GFR was calculated as (iohexol infusion rate (mg/min))/(plasma iohexol concentration (mg/mL)). The association of the three different filtration markers and GFR with time were analysed in generalized additive mixed models. The continuous infusion of iohexol was established in all four patients and maintained throughout the study period without interfering with ordinary postoperative care. Postoperative GFR at 2 hours were elevated compared to the preoperative measurements for patients 1, 2, and 3, but not for patient 4. Whereas patients 1, 2, and 3 had u-shaped postoperative mGFR curves, patient 4 demonstrated a linear increase in mGFR with time. We conclude that obtaining continuous measurements of GFR in the postoperative setting is feasible and can detect variations in GFR. The method can be used as a tool to track perioperative changes in renal function.

Urinary KIM-1 Correlates with the Subclinical Sequelae of Tubular Damage Persisting after the Apparent Functional Recovery from Intrinsic Acute Kidney Injury.

Acute kidney injury (AKI) poses an increased risk factor for new AKI episodes, progression to chronic kidney disease, and death. A worsened evolution has been linked to an incomplete renal repair beyond the apparent functional recovery based on plasma creatinine (pCr) normalization. However, structural sequelae pass largely unnoticed due to the absence of specific diagnostic tools. The urinary kidney injury molecule 1 (KIM-1) participates in renal tissue damage and repair and is proposed as a biomarker of early and subclinical AKI. Thus, we study in this paper the evolution of KIM-1 urinary excretion alongside renal tissue sequelae after an intrinsic AKI episode induced by cisplatin in Wistar rats. Creatinine clearance, pCr, proteinuria and the fractional excretion of Na+ and glucose were used to monitor renal function. Renal tissue damage was blindly scored in kidney specimens stained with hematoxylin–eosin and periodic acid–Schiff. KIM-1 urinary excretion and renal mRNA expression were also assessed. Finally, we analyzed urinary KIM-1 in patients apparently recovered from AKI. Our results show that, after the normalization of the standard markers of glomerular filtration and tubular function, the extent of persistent histological findings of tissue repair correlates with the renal expression and urinary level of KIM-1 in rats. In addition, KIM-1 is also elevated in the urine of a significant fraction of patients apparently recovered from an AKI. Besides its potential utility in the early and subclinical diagnosis of renal damage, this study suggests a new application of urinary KIM-1 in the non-invasive follow-up of renal repair after AKI.

Creatinine: An Inaccurate Measure of Renal Function in Men with Testosterone-Induced Muscle Hypertrophy

ABSTRACT Introduction Renal function is often estimated using validated study equations and serum creatinine (Cr) as a filtration marker. Contemporary studies suggest that cystatin C may be used as a more accurate alternative to Cr, as it avoids limitations related to diet and muscle mass that affect Cr and predispose to an overdiagnosis of chronic kidney disease. Elite athletes are often noted to have an elevated body mass index (BMI) despite maintaining an overall favorable level of percent body fat (PBF) and fitness. This is due to an increase level of body muscle. Objective This study evaluates the relationship between Cr, cystatin C, BMI, and PBF in fitness and elite athlete populations. Methods Elite athletes presenting to a men's health tertiary referral center with muscle-induced hypertrophy were evaluated for renal function through serum levels of Cr and cystatin C. BMI and PBF were obtained through bioimpedance testing at the time of serum level determinations. Elite athletes were those identified as pursuing competition in professional or amateur sporting events. Cr and cystatin c were plotted for correlation in best fit models for percentage increments of BMI (“normal”, “overweight”, and “obese”) and PBF. Results A total of 228 elite athletes were identified and stratified by BMI and PBF (Figures 1,2). The majority of athletes were classified as “overweight” (n = 88) or “obese” (n = 129) per BMI. None of the BMI groups demonstrated a significant correlation between Cr and cystatin C levels (Figure 1). The obese cohort demonstrated increased levels of cystatin C (mean = 1.00337, P&amp;lt;0.0001) compared with the overweight cohort (mean = 1.474462, p P&amp;lt;0.0001). The majority of athletes maintained a PBF of 10-20% (n = 87). PBF did not demonstrate a significant correlation between Cr and cystatin C levels, with the PBF 20-30% cohort approaching moderate correlation (R2 = 0.49, p =&amp;lt;0.0001). Conclusions Our study affirms that elite athletes maintain an increased BMI and low PBF. Hence, cystatin C may demonstrate a more accurate reflection of renal function in these patients, as Cr may be inaccurately elevated. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Abbie, American Medical Systems, Augmenta LLC, Clarus Therapeutics, Endo Pharmaceuticals, Lipocine, Vault Health

Performance of Serum β2-Microglobulin– and β-Trace Protein–Based Panel Markers and 2021 Creatinine- and Cystatin-Based GFR Estimating Equations in Pakistan

Performance of Serum β2-Microglobulin– and β-Trace Protein–Based Panel Markers and 2021 Creatinine- and Cystatin-Based GFR Estimating Equations in Pakistan

Measurement of glomerular filtration rate and its current status in African countries GFR measurement and its status in Africa

Glomerular filtration rate (GFR) is usually estimated rather than measured as this only requires measurement of an endogenous filtration marker. In certain clinical settings a more accurate measure of GFR is essential. The most commonly used endogenous filtration marker is creatinine. Exogenous filtration markers include nonradiopharmaceuticals such as inulin, iohexol and unlabelled iothalamate, or radiopharmaceuticals such as 51Crethylenediaminetetraacetic acid (51Cr-EDTA) and 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). Inulin is considered an ideal filtration marker but the clearance of iothalamate, 99mTc-DTPA, 51Cr-EDTA and iohexol have all been shown to have sufficient accuracy for measuring GFR. For radiopharmaceuticals, a well counter is required to measure the amount of activity in patient samples. Iohexol or unlabelled iothalamate require samples to be measured using high performance liquid chromatography with ultraviolet detection (HPLC-UV), liquid chromatography-tandem mass spectrometry (LC-MS/MS) or x-ray fluorescence (XRF). Due to the practical challenges of measuring urinary clearance, measurement of GFR in clinical settings is almost exclusively based on plasma clearance of a filtration marker. This can follow a long-established approach based on the ratio of the tracer administered to the area under the plasma concentration curve. Alternatively, a single plasma sample giving an apparent volume of distribution at a given time point can be used to accurately measure GFR. While techniques exist for the measurement of GFR in a number of African countries, preliminary evidence suggests that facilities are very limited. There is a need for support for both equipment and training to establish GFR measurement facilities in several centres on the continent. Keywords: measured glomerular filtration rate;, mGFR;, Africa

Management of Psychiatric Disorders in Patients with Chronic Kidney Diseases.

Management of Psychiatric Disorders in Patients with Chronic Kidney Diseases.

Resolving the Debate: The Future of Using Race in Estimating Kidney Function.

Racial and social unrest witnessed during 2020 ignited a national conversation about the appropriateness of the use of race in health care algorithms and in the estimation of kidney function in particular. The growing concerns over the use of race in kidney function-estimating equations prompted the National Kidney Foundation (NKF) and American Society of Nephrology to launch an effort for change by establishing a task force on reassessing the use of race in diagnosing kidney disease. After nearly a year examining the evidence and obtaining testimony from experts and stakeholders, the task force recommended the immediate implementation of the 2020 Chronic Kidney Disease-Epidemiology creatinine equation refit without race in all US laboratories; increased routine use of cystatin C for confirmation of estimated glomerular filtration rate in clinical decision-making and a call for research on glomerular filtration rate estimation with new endogenous filtration markers and on addressing disparities in health and health care. The NKF and American Society of Nephrology strongly encouraged rapid adoption of these new recommendations. Leadership efforts of the NKF have begun to lay the foundation for national implementation through laboratory engagement, clinician awareness, and patient education.