Currently, there is no dedicated equation to estimate glomerular filtration rate (GFR) for transplanted kidneys. This study aimed to compare the performance of serum creatinine (Scr)- and cystatin C (CysC)-based equations in Chinese renal transplant recipients.

A total of 252 stable renal transplant recipients were enrolled in this study. The plasma clearance of ^99mTc-DTPA (rGFR) was used as a reference standard. The Scr, CysC, and rGFR of the patients were measured on the same day. The bias, precision, accuracy (percentage of estimates within 10%, 30%, and 50% of rGFR), and agreements of 8 Scr and 5 CysC eGFR equations were assessed. The factors affecting the accuracy were also evaluated.

Among the Scr-based equations, the Japanese Society of Nephrology-Chronic Kidney Disease Initiatives (JSN-CKDI) equation had the best overall performance with a bias of -6.2 mL/min/1.73 m², and 96.1% of its estimates were within 30% of the rGFR. For the CysC-based equations, the Filler equation had the best performance with a bias of -3.9 mL/min/1.73 m², and 93.7% of its estimates were within 30% of the rGFR. Overall, the CysC-based equations showed better performance than the Scr-based equations. In addition, significant differences were observed between bias and gender and between bias and rGFR value in some equations, whereas transplantation time and immunosuppressive regimens were not correlated with the bias.

The JSN-CKDI equation provides the best estimation of the GFR equations, and the CysC-based equations performed better than the Scr-based equations in this population.

A prototype medical device for monitoring kidney function by transdermal measurement of the clearance rate of the exogenous fluorescent tracer agent MB-102 (administered intravenously) was developed. Verification of the device with an in vitro protocol is described. The expected renal clearance of the agent was mimicked by preparing a dilution series of MB-102 in the presence of a scattering agent. The slope of a linear fit to the logarithm of fluorescence intensity as a function of dilution step agreed with predictions within 5%, a level of accuracy that would be adequate in assessment of GFR to prevent misdiagnosis of kidney disease. Transdermal measurement was validated using a rat model. A two-compartment pharmacokinetic dependence was observed, with equilibration of the fluorescent agent between the vascular space into which it was injected and the extracellular space into which it subsequently diffused. The best observed signal-to-noise ratios were about 150, allowing determination of the renal clearance time with 5% precision using a 10-min fitting window. Based on the verification and validation methods for transdermal fluorescence detection described herein, the instrument has been approved by the FDA for a first-in-human clinical study, and a first transdermal clearance curve in a human is presented herein.

Accurate determination of glomerular filtration rate (GFR) is crucial for the diagnosis of kidney disease. Estimated GFR (eGFR) calculated by serum creatinine and/or cystatin C is a mainstay in clinical practice and epidemiologic research but lacks precision and accuracy until GFR <60 mL/min/1.73 m². Furthermore, eGFR may not precisely and accurately represent changes in GFR longitudinally. The lack of precision and accuracy is of concern in populations at high risk for kidney disease, as the dissociation between changes in eGFR and GFR may lead to missed diagnoses of early kidney disease. Therefore, improved methods to quantify GFR are needed. Whereas direct measures of GFR have been too cumbersome for screening and ambulatory care, a practical method of measuring GFR by iohexol clearance using dried capillary blood spots exists. In this review, we examine the current literature and data addressing GFR measurements by dried capillary blood spots and its potential application in high-risk groups.

Kinetic glomerular filtration rate estimation may have more power and versatility than the Modification of Diet in Renal Disease or Cockcroft-Gault formula for evaluating kidney function when plasma creatinine fluctuates rapidly. After kidney donation, glomerular filtration rate rapidly fluctuates in otherwise healthy patients. We compared 3 formulas for estimating glomerular filtration rate: kinetic, Modification of Diet in Renal Disease, and Cockcroft-Gault, for determining stages of acute kidney injury early after kidney donation.

In 42 living kidney donors, we measured serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin, and glomerular filtration rates before uninephrectomy and 3 days afterward. To estimate glomerular filtration rate, we used Cockcroft-Gault, Modification of Diet in Renal Disease, and kinetic equations. We sought the most accurate formula for staging acute kidney injury according to the risk, injury, failure, loss, and end-stage criteria.

The kinetic glomerular filtration rate model found more cases of stage 3 acute kidney injury than did the Modification of Diet in Renal Disease or Cockcroft-Gault formula. Receiver operating characteristic curves showed that the kinetic glomerular filtration rate model had more sensitivity and specificity than the Cockroft-Gault formula for discriminating among risk, injury, failure, loss, and end-stage criteria stages of acute kidney injury, based on serum creatinine changes. On day 2 after donation, a more sensitive marker with a shorter half-life (serum neutrophil gelatinase-associated lipocalin) was more significantly correlated with kinetic glomerular filtration rate estimation.

The kinetic glomerular filtration rate model was able to discriminate stages of acute kidney injury early after kidney donation according to risk, injury, failure, loss, and end-stage criteria better than the Modification of Diet in Renal Disease or Cockcroft-Gault formulas. The kinetic model detected failure-stage acute kidney injury ≥ 1 to 2 days earlier than the MDRD formula, CG formula detected no failure.

Chronic kidney disease (CKD) is an increasing clinical problem. Although clinical risk factors and biomarkers for the development and progression of CKD have been identified, there is no commercial surveillance technology to definitively diagnose and quantify the severity and progressive loss of glomerular filtration rate (GFR) in CKD. This has limited the study of potential therapies to late stages of CKD when FDA-registerable events are more likely. Because patient outcomes, including the rate of CKD progression, correlate with disease severity and effective therapy may require early intervention, being able to diagnose and stratify patients by their level of decreased kidney function early on is key for translational progress. In addition, renal reserve, defined as the increase in GFR following stimulation, may improve the quantification of GFR based solely on basal levels. Various groups are developing and characterizing optical measurement techniques using new minimally invasive or noninvasive approaches for quantifying basal and stimulated kidney function. This development has the potential to allow widespread individualization of therapy at an earlier disease stage. Therefore, the purposes of this review are to suggest why quantifying stimulated GFR, by activating renal reserve, may be advantageous in patients and to review fluorescent technologies to deliver patient-specific GFR.

Acute kidney injury (AKI) remains a vexing clinical problem that results in unacceptably high patient mortality, development of chronic kidney disease, and accelerated progression to end-stage kidney disease. Although clinical risks factors for developing AKI have been identified, there is no reasonable surveillance technique to definitively and rapidly diagnose and determine the extent of severity of AKI in any patient. Because patient outcomes correlate with the extent of injury, and effective therapy likely requires early intervention, the ability to rapidly diagnose and stratify patients by their level of kidney injury is paramount for translational progress. Many groups are developing and characterizing optical measurement techniques using novel minimally invasive or noninvasive techniques that can quantify kidney function independent of serum or urinary measurements. The use of both one- and two-compartment models, as well as continuous monitoring, are being developed. This review documents the need for glomerular filtration rate measurement in AKI patients and discusses the approaches being taken to deliver this overdue technique that is necessary to help propel nephrology to individualization of care and therapeutic success.

Acute kidney injury (AKI) is common. Clear criteria and accurate diagnostic tools are essential to diagnose AKI early and correctly. The aims of this review are to outline some of the pitfalls of the Kidney Disease Improving Global Outcomes (KDIGO) classification and to describe other traditional and novel tools to diagnose AKI.

The KDIGO classification of AKI is based on changes in serum creatinine and urine output. Misdiagnosis of AKI can occur when using only the KDIGO criteria. Potential pitfalls are related to the fact that neither creatinine nor urine output are renal-specific. Other traditional tools to diagnose AKI are blood urea nitrogen, urine chemistry, urine microscopy and renal biopsy. New diagnostic tools, including novel AKI biomarkers and techniques to measure glomerular filtration rate in real time, are being developed and validated.

Knowledge about the strengths and weaknesses of traditional diagnostic tests is essential to make the correct diagnosis of AKI. New tests and technical innovations offer the prospect of diagnosing AKI earlier and more accurately.

Alterations in kidney function are common in critically ill patients and are generally assessed by changes in serum creatinine (sCr) or urine output, which are considered surrogates for glomerular filtration rate (GFR) but do not reflect the overall kidney function. There is a great need for more reliable measurements of glomerular filtration in order to guide diagnosis and therapy for acute kidney injury. In this review, we will focus on recent advances to measure GFR that could help to better evaluate kidney function and improve patient care.

Standardized assays for sCr measurements, the use of a more precise scale with more frequent measurements, and the interpretation of the results based on patient's characteristics can increase the clinical value of sCr. New endogenous and exogenous markers will provide a more precise estimation. Imaging techniques are being developed and will probably be available in the near future. New gold standards for glomerular filtration will help in the development and improvement in the use of new biomarkers of kidney injury.

The first consensus definition of Acute Kidney Injury (AKI) was published a decade ago. In this mini narrative review we look at the history of the changes in the definition of AKI and consider how it may change again in the near future. The epidemiology of small changes in creatinine and the difficulties with determining baseline creatinine have driven the changes. Recent evidence on urinary output and the application of structural injury biomarkers are likely to change the definition once more.

Acute kidney injury (AKI) is a common and frequently fatal illness in critically ill patients. The reliance on daily measurements of serum creatinine as a surrogate of glomerular filtration rate (GFR) not only delays diagnosis and development of successful therapies but also hinders insight into the pathophysiology of human AKI. Measurement of GFR under non-steady-state conditions remains an elusive gold standard against which biomarkers of renal injury need to be judged. Approaches to the rapid (near real-time) measurement of GFR are explored. Even if real-time GFR was available, absent baseline information will always limit diagnosis of AKI based on GFR or serum creatinine to a detection of change. Biomarkers of renal cellular injury have provided new strategies to facilitate detection and early intervention in AKI. However, the diagnostic and predictive performance of urinary biomarkers of injury vary, depending on both the time after renal injury and on the preinjury GFR. Progress in understanding the role of each novel biomarker in the causal pathways of AKI promises to enhance their diagnostic potential. We predict that combining rapid measures of GFR with biomarkers of renal injury will yield substantive progress in the treatment of AKI.