A nuclear magnetic resonance-based method for accurate assessment of glomerular filtration rate (GFR)
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An oral presentation held by numares at the ASN KidneyWeek 2018 about a new method of GFR testing to assess kidney function using metabolic constellations and NMR diagnostics.
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INTRODUCTION GFR is best index of kidney function in health and disease and accurate values are needed for optimal decision making in clinical settings. Estimated GFR eGFR based on serum creatinine is first line test of kidney function. CG formula is creatinine based equation and widely applied. Tc99m DTPA Diethylene Triamine Penta Acetic acid is the most commonly used radiopharmaceutical for GFR studies. The Gate method has been most common in the routine setting. AIM AND OBJECTIVES To study correlation of serum creatinine based calculation of GFR with measured ratio isotope GFR in healthy individuals and CKD patients. To assess the accuracy of GFR as calculated by CG GFR formulae using serum creatinine against measured RI GFR Tc 99m DTPA . METHODS This study observational study, which is done in department of medicine and department of nuclear medicine at Army Hospital RandR, Delhi Cantt in CKD and healthy individuals. Our study includes a total of 100 subjects with varying renal functions which includes 50 healthy individual and 50 CKD patients. RESULTS In this study it has been observed that in healthy group CG GFR has weak correlation with DTPA GFR r = 0.104 with p 0.471 . Lt Col (Dr.) Rahul Soni | Dr. Jayita Debnath "Correlation of Serum Creatinine Based Calculation of Glomerular Filtration Rate with Measured Radio Isotope Glomerular Filtration Rate in Healthy Individuals and Chronic Kidney Disease Patients" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-2 , February 2021, URL: https://www.ijtsrd.com/papers/ijtsrd38443.pdf Paper Url: https://www.ijtsrd.com/medicine/other/38443/correlation-of-serum-creatinine-based-calculation-of-glomerular-filtration-rate-with-measured-radio-isotope-glomerular-filtration-rate-in-healthy-individuals-and-chronic-kidney-disease-patients/lt-col-dr-rahul-soni
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3. Steps for resuscitating patients in septic shock are outlined, including fluid administration, vasopressor use, transfusions based on ScvO2 goals, and steroid and drotrecogin
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This document provides an overview of acute renal failure (ARF):
1) ARF remains a major therapeutic challenge and is defined as a rapid decrease in kidney function manifested by a buildup of waste products like urea and creatinine.
2) Prerenal ARF, the most common type, occurs when external factors like low blood pressure decrease blood flow to the kidneys. Parenchymal ARF results from direct kidney damage.
3) Urea, creatinine, and urine output are used to diagnose ARF despite limitations. New biomarkers show promise but require more research. Classification of ARF types is challenging without agreed standards.
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- The nephron is the functional unit of the kidney, which filters blood to form urine and regulates electrolytes and acid-base balance.
- Glomerular filtration rate (GFR) and creatinine clearance are tests used to assess kidney filtration function. Creatinine clearance is estimated based on creatinine levels in serum and urine.
- Tubular function tests include urine concentration and acidification to evaluate the kidney's reabsorption and regulatory roles. Assessing these functions provides insight into renal disorders.
Biochemical kidney function tests with their clinical applications
1. Biochemical kidney function tests are used to measure glomerular function and tubular function in the kidneys. This includes clearance tests, urine analysis, and blood tests to detect substances like creatinine, urea, electrolytes, and beta-2-microglobulin.
2. Common clearance tests measure the excretion of creatinine and inulin, which are freely filtered by the glomerulus and not reabsorbed. Creatinine clearance is widely used to estimate glomerular filtration rate.
3. Interpreting the results of kidney function tests can provide information about the presence, nature, and severity of renal disease or dysfunction and help monitor treatment effectiveness. Elevated cre
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2. Two main methods exist: plasma clearance methods involving blood or urine sampling, and dynamic imaging methods using curve fitting or compartment models.
3. Accuracy of MRI GFR measurement depends on factors like temporal resolution, contrast dose, motion correction, renal segmentation, and choice of kinetic model. Studies show reasonable correlation with nuclear medicine tests but heterogeneity in protocols.
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This document discusses glomerular filtration rate (GFR) and factors that influence it. It provides details on:
- How GFR is determined by glomerular capillary hydrostatic and oncotic pressures.
- Average GFR in humans is 125 mL/min but can be influenced by transglomerular pressure, renal plasma flow, glomerular permeability, and oncotic pressure.
- GFR is maintained relatively constant through autoregulation and tubuloglomerular feedback mechanisms.
- Clinical assessment of GFR can be done by measuring clearance of substances like inulin, radiolabeled compounds, or creatinine. Estimated GFR formulas like Cockcroft-
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The document discusses cystatin C as a marker for renal function and compares it to creatinine. It notes that cystatin C is superior to creatinine for estimating glomerular filtration rate (GFR) and detecting early stages of chronic kidney disease. Unlike creatinine, cystatin C levels are unaffected by factors like age, muscle mass, and gender. Multiple studies cited found cystatin C to be more accurate than creatinine-based estimates for detecting early renal impairment in diabetes patients and predicting cardiovascular outcomes. The document concludes cystatin C is a more sensitive GFR marker that can improve detection of kidney disease.
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1) CRRT is a form of renal replacement therapy used for patients with hemodynamic instability from acute kidney injury who cannot tolerate intermittent hemodialysis. It provides slower solute and fluid removal through a venovenous circuit.
2) Optimal timing for initiating RRT in AKI is unclear as there are no definitive biomarkers. It is usually started preemptively based on clinical assessment before complications develop.
3) Complications of CRRT include those from vascular access like infection, bleeding from anticoagulation, and fluid and electrolyte imbalances during therapy.
limitation and scope.pptx
The document discusses the assessment of renal function through various tests and methods. It describes:
1. Tests to measure glomerular filtration rate (GFR) including inulin clearance, creatinine clearance, iohexol clearance, and cystatin C.
2. Other renal function tests including urine analysis, blood tests of blood urea nitrogen and creatinine, and combined analyses like fractional excretion of sodium.
3. Methods for evaluating GFR including predicting GFR from creatinine levels using the Schwartz formula and nuclear medicine techniques using radioactive tracers.
Approach to Chronic Kidney Diseases
1) The document discusses the approach to chronic kidney disease (CKD). It defines CKD and outlines its stages based on glomerular filtration rate and albuminuria levels.
2) Risk factors for CKD mentioned include diabetes, hypertension, family history of kidney disease, use of certain medications, and prior acute kidney injury. The pathogenesis of CKD involves initial injury followed by adaptive hyperfiltration and long-term damage to remaining nephrons.
3) Evaluation of patients with suspected CKD involves obtaining a history, physical exam, lab tests including serum creatinine and urine analysis, and imaging like renal ultrasound. A kidney biopsy may be done if disease-specific therapy is still possible.
Kidney Donor evaluation
This document summarizes guidelines for evaluating kidney function in potential living donors. It recommends estimating glomerular filtration rate (GFR) using serum creatinine and/or cystatin C to assess kidney function. An initial GFR of 90 mL/min/1.73m2 or greater is acceptable for donation, while GFR between 60-89 mL/min/1.73m2 requires individual assessment. Donors with less than 60 mL/min/1.73m2 are not eligible. The guidelines provide criteria for measurement and interpretation of GFR to safely evaluate and select living kidney donors.
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The document provides guidance from NICE on testing and managing chronic kidney disease (CKD) and diabetic kidney disease. It recommends testing people with diabetes, hypertension, cardiovascular disease or a family history of CKD to check for renal disease. It advises measuring estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) annually. Abnormal results should be confirmed with a repeat test. The guidance outlines treatment targets for blood pressure and referral criteria for nephrology assessment. It discusses the rationale for the guidelines, including evidence that angiotensin-converting enzyme inhibitors (ACEi) can slow CKD progression independently of blood pressure lowering.
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The document discusses renal function tests and their interpretation. It provides information on various tests used to evaluate kidney function, including blood urea nitrogen, serum creatinine, and creatinine clearance. It defines different types of azotemia and outlines stages of chronic kidney disease based on estimated glomerular filtration rate and albumin-creatinine ratio. The document also discusses equations used to estimate glomerular filtration rate, including MDRD4, CKD-EPI, Cockcroft-Gault, and Jelliffe, noting their uses and limitations.
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1. A study of over 13,000 AF patients found higher baseline BNP levels were associated with increased risk of AF progression and major adverse cardiovascular events.
2. A direct comparison of dabigatran, rivaroxaban, and apixaban found apixaban and rivaroxaban had comparable safety and effectiveness to dabigatran in real-world practice, though major bleeding occurred more frequently with apixaban and rivaroxaban.
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This document discusses various potential therapies for acute heart failure. It begins by reviewing the historical focus on diuresis, vasodilators, and inotropes from 1970-2010. Currently, over 90% of patients receive intravenous diuretics as the primary treatment. The document then evaluates several promising new treatment approaches that are being studied, including natriuretic peptides, levosimendan, relaxin, soluble guanylate cyclase activators, rolofylline, cardiac myosin activators, and SERCA2a activators. It provides details on clinical trials and mechanisms of action for these novel therapies. Throughout, the document provides a critical look at challenges and limitations for further developing these new
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The document discusses the interpretation of kidney function through laboratory tests. It describes the physiologic role and functional units of the kidney. Key points include:
- The nephron is the functional unit of the kidney, which filters blood to form urine and regulates electrolytes and acid-base balance.
- Glomerular filtration rate (GFR) and creatinine clearance are tests used to assess kidney filtration function. Creatinine clearance is estimated based on creatinine levels in serum and urine.
- Tubular function tests include urine concentration and acidification to evaluate the kidney's reabsorption and regulatory roles. Assessing these functions provides insight into renal disorders.
Biochemical kidney function tests with their clinical applications
1. Biochemical kidney function tests are used to measure glomerular function and tubular function in the kidneys. This includes clearance tests, urine analysis, and blood tests to detect substances like creatinine, urea, electrolytes, and beta-2-microglobulin.
2. Common clearance tests measure the excretion of creatinine and inulin, which are freely filtered by the glomerulus and not reabsorbed. Creatinine clearance is widely used to estimate glomerular filtration rate.
3. Interpreting the results of kidney function tests can provide information about the presence, nature, and severity of renal disease or dysfunction and help monitor treatment effectiveness. Elevated cre
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Renal_function_and_GFR_with_MR_imaging.pdf
1. MRI can measure differential renal function and glomerular filtration rate (GFR) through dynamic contrast-enhanced imaging after injection of a gadolinium-based contrast agent.
2. Two main methods exist: plasma clearance methods involving blood or urine sampling, and dynamic imaging methods using curve fitting or compartment models.
3. Accuracy of MRI GFR measurement depends on factors like temporal resolution, contrast dose, motion correction, renal segmentation, and choice of kinetic model. Studies show reasonable correlation with nuclear medicine tests but heterogeneity in protocols.
E Gfr 2008
The document discusses estimated glomerular filtration rate (eGFR) and its clinical applications and limitations. It provides background on assessing kidney function, defining chronic kidney disease (CKD) stages, and estimating GFR. It also addresses limitations of eGFR including assumptions of steady state, creatinine standardization issues, and inaccuracy at higher GFR levels or with rapid changes in kidney function. The document emphasizes using eGFR in conjunction with other clinical factors for CKD evaluation and management.
Acute kidney injury
This document provides an overview of acute kidney injury (AKI), including its definition, prevalence, diagnosis, pathophysiology, biomarkers, and staging criteria according to RIFLE, AKIN, and KDIGO. It discusses the need for biomarkers to detect AKI early before increases in serum creatinine. Commonly used biomarkers mentioned include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), interleukin-18 (IL-18), and cystatin C. The pathophysiology of AKI involves alterations in renal perfusion, tubular dysfunction and cell death, intrat
Determinant of Glomerular Filtration
This document discusses glomerular filtration rate (GFR) and factors that influence it. It provides details on:
- How GFR is determined by glomerular capillary hydrostatic and oncotic pressures.
- Average GFR in humans is 125 mL/min but can be influenced by transglomerular pressure, renal plasma flow, glomerular permeability, and oncotic pressure.
- GFR is maintained relatively constant through autoregulation and tubuloglomerular feedback mechanisms.
- Clinical assessment of GFR can be done by measuring clearance of substances like inulin, radiolabeled compounds, or creatinine. Estimated GFR formulas like Cockcroft-
Cystatin-C-as-a-Marker-of-Renal-Function.pptx
The document discusses cystatin C as a marker for renal function and compares it to creatinine. It notes that cystatin C is superior to creatinine for estimating glomerular filtration rate (GFR) and detecting early stages of chronic kidney disease. Unlike creatinine, cystatin C levels are unaffected by factors like age, muscle mass, and gender. Multiple studies cited found cystatin C to be more accurate than creatinine-based estimates for detecting early renal impairment in diabetes patients and predicting cardiovascular outcomes. The document concludes cystatin C is a more sensitive GFR marker that can improve detection of kidney disease.
CRRT-f
1) CRRT is a form of renal replacement therapy used for patients with hemodynamic instability from acute kidney injury who cannot tolerate intermittent hemodialysis. It provides slower solute and fluid removal through a venovenous circuit.
2) Optimal timing for initiating RRT in AKI is unclear as there are no definitive biomarkers. It is usually started preemptively based on clinical assessment before complications develop.
3) Complications of CRRT include those from vascular access like infection, bleeding from anticoagulation, and fluid and electrolyte imbalances during therapy.
limitation and scope.pptx
The document discusses the assessment of renal function through various tests and methods. It describes:
1. Tests to measure glomerular filtration rate (GFR) including inulin clearance, creatinine clearance, iohexol clearance, and cystatin C.
2. Other renal function tests including urine analysis, blood tests of blood urea nitrogen and creatinine, and combined analyses like fractional excretion of sodium.
3. Methods for evaluating GFR including predicting GFR from creatinine levels using the Schwartz formula and nuclear medicine techniques using radioactive tracers.
Approach to Chronic Kidney Diseases
1) The document discusses the approach to chronic kidney disease (CKD). It defines CKD and outlines its stages based on glomerular filtration rate and albuminuria levels.
2) Risk factors for CKD mentioned include diabetes, hypertension, family history of kidney disease, use of certain medications, and prior acute kidney injury. The pathogenesis of CKD involves initial injury followed by adaptive hyperfiltration and long-term damage to remaining nephrons.
3) Evaluation of patients with suspected CKD involves obtaining a history, physical exam, lab tests including serum creatinine and urine analysis, and imaging like renal ultrasound. A kidney biopsy may be done if disease-specific therapy is still possible.
Kidney Donor evaluation
This document summarizes guidelines for evaluating kidney function in potential living donors. It recommends estimating glomerular filtration rate (GFR) using serum creatinine and/or cystatin C to assess kidney function. An initial GFR of 90 mL/min/1.73m2 or greater is acceptable for donation, while GFR between 60-89 mL/min/1.73m2 requires individual assessment. Donors with less than 60 mL/min/1.73m2 are not eligible. The guidelines provide criteria for measurement and interpretation of GFR to safely evaluate and select living kidney donors.
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Liquid biopsy: Overcome Challenges of Circulating DNA with Automated and Stan...
Circulating cell-free DNA (ccfDNA) originating from malignant tumors, a developing fetus and also from inflammatory tissues, is present in the cell-free nucleic acids in plasma, serum and other body fluids and is considered a “liquid biopsy”. Access to ccfDNA for analysis allows for specific detection of certain disease states based on a simple blood sample. Circulating cell-free DNA shows distinctive properties – it is present mostly as shorter fragments of less than 500 bp and the concentration of ccfDNA in a plasma or serum sample is low (approximately 1–100 ng/ml) compared to cellular materials and varies considerably between different individuals.
Because of their fragmented nature and low concentration, ccfDNA presents a particular challenge for efficient extraction / purification and quantification, such as by qPCR. We present data on solutions for the following critical problems concerning the purification of ccfDNA for research and molecular diagnostic applications:
• Pre-analytical workflow (blood processing) for analyzing ccfDNA
• Optimization of ccfDNA extraction from plasma samples: low target concentrations require efficient ccfDNA enrichment from larger sample volumes
• Novel automated extraction of ccfDNA using the QIAsymphony SP instrument for liquid biopsy diagnostic applications.
Creatinine and Creatinine Clearance
This document discusses creatinine and creatinine clearance as measures of kidney function. It describes how creatinine is produced in the body and excreted by the kidneys, and how measuring levels of creatinine in the blood and urine can provide information about glomerular filtration rate and kidney health. Specifically, creatinine clearance can be used as an indicator of glomerular filtration rate, since creatinine is produced at a constant rate and freely filtered by the kidneys. Both high and low levels of blood creatinine can indicate kidney abnormalities. The document also outlines the procedure for determining creatinine levels in samples.
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A nuclear magnetic resonance-based method for accurate assessment of glomerular filtration rate (GFR)
- 1. -CONFIDENTIAL- 1 A NUCLEAR Real-time Precision Medicine. Mastering Metabolomic Networks. San Diego | ASN Kidney Week | October 2018 MAGNETIC RESONANCE-BASED OF GLOMERULAR FILTRATION RATE (GFR) METHOD FOR ACCURATE ASSESSMENT
- 2. -CONFIDENTIAL- 2 Gold standard • Measured GFR (mGFR), e.g. renal clearance of inulin or 125I-iothalamte • Very elaborate, expensive and/or associated with radiation • Rarely used in clinical routine Current routine: • GFR estimated based on serum creatinine (eGFR) • Creatinine depends on muscle mass, activity, age (biological variability) • Creatinine blind range of GFR 60-90 mL/min/1.73m² MacGregor NDT 2007 GFR: Current clinical practice eGFR (mL/min/1.73 m²) 125I-iothalamtemGFR(mL/min/1.73m²) Aim: New test for simple but precise estimation of GFR
- 3. -CONFIDENTIAL- 3 Retrospective samples from two European centers Hopital Edouard Herriot, Lyon • 139 samples • Adults and children University of Gothenburg • 77 samples • Exclusively children 216 samples 183 NMR spectra 33 had insufficient volume for preparation Discovery cohort (96) • Biomarker discovery • Modelling Test cohort (87) • Performance testing Study cohorts Data analysis
- 4. -CONFIDENTIAL- 4 Biomarker discovery in training cohort (n=96) Correlation of NMR signals with measured GFR 29 17 13 NMR signals found to be significantly correlated with mGFR Substances successfully verified (+ 7 unknown substances) Substances of physiological relevance remained for biostatistical modeling
- 5. -CONFIDENTIAL- 5 mGFR Hypofiltration Constellation �y𝐴𝐴 Hyperfiltration Constellation �y𝐵𝐵 Crea Val Myo Crea DMS Contribution Substance Pool Modelling Constellations Selection Selected constellations … Biomarker modelling and constellation selection +
- 6. -CONFIDENTIAL- 6 Filtration marker ROS Altered filtration, reabsorption, secretion Metabolic acidosis Oxidative stress Renalco-morbidityRenalfailure Biomarkers and their pathophysiology Creatinine Myo-Inositol Dimethyl sulfone Valine Accumulation of uremic toxins pH ↓ Uremia marker Oxidative stress marker Metabolic acidosis marker Clinicalmanifestation Increase when GFR declines to 50-60% Late marker Serum levels in renal impairment Impaired degradation in diseased kidneys Oxidative stress may increase serum levels Metabolic acidosis induces degradation Pathophysiological link
- 7. -CONFIDENTIAL- 7 CKD-EPI Creatinine eGFR(NMR) r = 0.848 RMSE =28.00 r = 0.880 RMSE =19.24 CKD-EPI Cystatin C r = 0.636 RMSE =32.81 eGFR(NMR) Test performance in independent cohort (n=87) In the “creatinine blind spot” eGFR(NMR) reduces variation from 24.5 to 11.0 compared to CKD-EPI Creatinine.
- 8. -CONFIDENTIAL- 8 Clinical need • Serum creatinine systematically overestimates renal organ reserve Utility Precise GFR estimation for detecting patients with renal involvement. Clinical need • Serum creatinine overestimates GFR • significantly decreased GFR is associated with AKI during or immediately after surgery. Utility Precise GFR estimation for selecting patients most likely benefitting from transplantation. Congestive heart failure Liver failure N=11 RMSE =15.64 N=11 RMSE =7.95 N=13 RMSE =26.41 N=13 RMSE =21.32 Pilot data for clinical utility: Subgroup analysis eGFR(NMR)eGFR(NMR)
- 9. -CONFIDENTIAL- 9 71% 95%82% 86% eGFR Blood sample Plasma clearance Tracer injection Blood samples Renal clearance Tracer injection Urine volume Urine sample Blood samples eGFR(NMR) Blood sample P30-Value Test performance continuum Am J Kidney Dis. 2014; 64(3): 411-424
- 10. -CONFIDENTIAL- 10 • As simple as serum creatinine testing • Outperforms creatinine and cystatin C-based estimations • With P30 > 80% almost as accurate as plasma clearance • Reduces variance in the creatinine blind spot between 60-90 ml/min/1.73 m² • Applicable to adults and children • Additional pathophysiological insights eGFR(NMR): Serum test for precise estimation of GFR Thank you for your attention! Interested? Email me at maulik.shah@numares.com