Estimation Of Kidney Function Research Articles

Advances in management of hepatorenal syndrome.

Hepatorenal syndrome (HRS) is encountered frequently in patients with end-stage liver disease and remains an important cause of morbidity and mortality in this patient population. This review will focus and provide updates on pathophysiology, assessment of kidney function, new definitions, and treatment and prevention of HRS. Pathophysiology of HRS has been elucidated more recently and in addition to hemodynamic changes, the role of systemic inflammatory response contributes significantly to this process. Assessment of kidney function in patients with liver cirrhosis remains challenging. Novel glomerular filtration rate equations have been developed in patients with liver disease to better estimate kidney function and changes made in the definition of acute kidney injury (AKI), which are more aligned with KDIGO criteria for AKI. Vasoconstrictors, especially terlipressin, along with albumin remain the mainstay of pharmacological treatment of HRS-AKI. Biomarkers have been useful in differentiating ATN from HRS at an early stage. HRS remains a significant cause of morbidity and mortality for patients with end-stage liver disease. Newer understanding of mechanisms in development and pathophysiology of HRS have helped with elucidation of the disease process.

Discordance Between Using Estimated and Measured Glomerular Filtration Rate for Drug Dosing in Kidney Transplant Recipients.

Introduction. Estimating glomerular filtration rate (eGFR) using different formulas is common clinical practice for evaluating kidney function and drug dosing. But, the performance of available eGFR equations is questionable during early days after kidney transplantation. Methods. This study compared the performance of three common eGFR equations (Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) in relation with measured GFR (mGFR) using clearance of Tc-99m-diethylenetriaminepentaacetic acid, 7 to 10 days post kidney transplantation. Agreement of mGFR and different eGFR equations in the staging of kidney function and dosing of 8 common antimicrobials were assessed. Result. Thirty kidney and 5 simultaneous pancreas-kidney transplant recipients were included. CG applying total body weight (CGTBW) had the lowest bias (-12 mL/min/ 1.73 m2) and the highest percentage of estimation within 30% of mGFR (71.4%). MDRD showed the best precision (13.14 mL/min/ 1.73m2) and linear correlation with mGFR. CKD-EPI and MDRD acted better than CG for staging the level of kidney function. CGTBW had the lowest discordance rate with mGFR for antimicrobials dosing (33.6%). Discordance rates of drug dosing between mGFR and eGFR formulas were greater for drugs that have higher dosing levels such as (val)-ganciclovir (≥ 54.3%). Conclusion. Until developing more accurate methods for estimating kidney function during first 1 to 2 weeks after kidney transplantation, CGTBW method is suggested for drug dose adjustment and MDRD or CKD-EPI equation for the staging of kidney function in these patients, keeping in mind that these formulas underestimate the level of kidney function in new transplant recipients.

Clinical Presentations and Usefulness of 99mTechnetium-Ethylene-Dicysteine (99mTc-EC) Renal Scintigraphy in Estimation of Thoracic Kidney Function in Children

: Thoracic kidney is a rare congenital abnormality with the lowest frequency of all renal ectopias. Most cases are discovered incidentally via routine imaging and have a benign clinical course. Here, we report three pediatric cases of thoracic kidney among 156 children with renal ectopy (1.9%). Thoracic kidney was asymptomatic in two children; in one child, it was associated with a recurrent diaphragmatic hernia. All diagnoses were made by chest ultrasonography (USG) and/or radiography in children and confirmed by computed tomography (CT) scan. Moreover, 99mtechnetium-ethylene-dicysteine (99mTc-EC) renal scintigraphy was carried out to visualize and assess the function of ectopic kidneys. All thoracic kidneys were left-sided, and their functions were comparable to their normally located counterparts. During an observation period of 5 - 10 years, two children with thoracic kidneys presented with unstable proteinuria/microalbuminuria and hypertension, respectively. The 99mTc-EC renal scintigraphy is an uncomplicated and safe method for imaging the thoracic kidneys and can be used for detecting the thoracic kidney function in children. Thoracic ectopic kidneys are associated with complications, such as hypertension and proteinuria. Children with thoracic kidneys need long-term follow-ups.

More than Creatinine but Less than Perfect: Challenges of Estimated Kidney Function in HCT Patients

More than Creatinine but Less than Perfect: Challenges of Estimated Kidney Function in HCT Patients

Noninvasive assessment of radiation-induced renal injury in mice

Purpose The kidney is a radiosensitive late-responding normal tissue. Injury is characterized by radiation nephropathy and decline of glomerular filtration rate (GFR). The current study aimed to compare two rapid and cost-effective methodologies of assessing GFR against more conventional biomarker measurements. Methods C57BL/6 mice were treated with bilateral focal X-irradiation (1x14Gy or 5x6Gy). Functional measurements of kidney injury were assessed 20 weeks post-treatment. GFR was estimated using a transcutaneous measurement of fluorescein-isothiocyanate conjugated (FITC)-sinistrin renal excretion and also dynamic contrast-enhanced CT imaging with a contrast agent (ISOVUE-300 Iopamidol). Results Hematoxylin and eosin (H&E) and Periodic acid-Schiff staining identified comparable radiation-induced glomerular atrophy and mesangial matrix accumulation after both radiation schedules, respectively, although the fractionated regimen resulted in less diffuse tubulointerstitial fibrosis. Albumin-to-creatinine ratios (ACR) increased after irradiation (1x14Gy: 100.4 ± 12.2 µg/mg; 6x5Gy: 80.4 ± 3.02 µg/mg) and were double that of nontreated controls (44.9 ± 3.64 µg/mg). GFR defined by both techniques was negatively correlated with BUN, mesangial expansion score, and serum creatinine. The FITC-sinistrin transcutaneous method was more rapid and can be used to assess GFR in conscious animals, dynamic contrast-enhanced CT imaging technique was equally safe and effective. Conclusion This study demonstrated that GFR measured by dynamic contrast-enhanced CT imaging is safe and effective compared to transcutaneous methodology to estimate kidney function.

Elderly Patients in a Large Nephrology Unit: Who Are Our Old, Old-Old and Oldest-Old Patients?

The world population is aging, and the prevalence of chronic kidney disease (CKD) is increasing. Whether this increase is also due to the methods currently being used to assess kidney function in the elderly is still a matter of discussion. We aimed to describe the actual referral pattern of CKD patients in a large nephrology unit and test whether the use of different formulae to estimate kidney function could affect the staging and the need for specialist care in the older subset of our population. In 2019, 1992 patients were referred to our center. Almost 28% of the patients were aged ≥80 and about 6% were ≥90 years old. Among the causes of kidney disease, glomerulonephritis displayed a higher prevalence in younger patients whereas hypertensive or diabetic kidney disease were more prevalent in older patients. The prevalence of referred patients in advanced CKD stages increased with age; estimated glomerular filtration rate (eGFR) decreased with age regardless of which equation was used (chronic kidney disease epidemiology collaboration (CKD-EPI), Lund–Malmö Revised (LMR), modification of diet in renal disease (MDRD), Full Age Spectrum (FAS), or Berlin Initiative Study 1 (BIS)). With CKD-EPI as a reference, MDRD and FAS underestimated the CKD stage while LMR overestimated it. The BIS showed the highest heterogeneity. Considering an eGFR threshold limit of 45 mL/min for defining “significant” CKD in patients over 65 years of age, the variability in CKD staging was 10% no matter which equation was used. Our study quantified the weight of “old” and “old-old” patients on follow-up in a large nephrology outpatient unit and suggested that with the current referral pattern, the type of formula used does not affect the need for CKD care within the context of a relatively late referral, particularly in elderly patients.

Creatinine Assessment in Non-Steady-State Conditions: A Critical Review.

To discuss methods for the assessment of creatinine clearance (Clcr) when serum creatinine (SCr) is not at steady state in order to estimate kidney function and apply the estimate to kidney function staging for clinical assessment or drug dosing. A PubMed search was conducted from 1976 to mid-January 2021 with other articles identified through review of bibliographies of retrieved articles and citations in Scopus. Articles assessing Clcr under non-steady-state conditions and studies evaluating predictive equations were selected. When SCr is systematically changing (ie, trending up or down), kinetic methods to estimate Clcr are appropriate. Estimates from kinetic methods should be individual based and not indexed to body surface area, and careful monitoring is required to confirm predictions as the situation evolves. Standard methods intended for steady-state conditions should not be used to estimate Clcr in patients with unstable SCr. Creatinine continues to be a monitoring parameter of choice and is an important variable in all the commonly used equations for estimating Clcr and most important for estimating glomerular filtration rate. However, standard methods of estimating Clcr for medication dosing are not accurate under non-steady-state conditions. The methods for kinetic clearance estimation and standards methods for clearance estimation, such as the Cockcroft-Gault equation, are mutually exclusive. There are no benefits of using the kinetic method in patients with stable SCr concentrations, and standard equations are not appropriate with unstable SCr concentrations.

Antimicrobial Dosing in Specific Populations and Novel Clinical Methodologies: Kidney Function.

Kidney function is a common parameter used to define antimicrobial drug dosage and frequency of administration. Several methods exist to measure kidney function but for pragmatic reasons rely on estimated kidney function equations based on the endogenous biomarker serum creatinine and common clinical variables. Current regulatory guidance on the design of studies in patients with abnormal kidney function in the United States also recommend consideration of estimated kidney function for this reason. Over the past few decades, alternate endogenous biomarkers, administration of exogenous biomarkers for noninvasive measurement, use of probe substrates to characterize individual kidney drug clearance pathways, modifications to conventional equations to account for time-varying clearance, and improved clinical trial modeling and simulation to factor in these uncertainties have occurred. Furthermore, major changes to kidney replacement therapy delivery in the outpatient, inpatient, and at-home setting are occurring. Antimicrobial drug dose adjustment in this diverse population is complex and in a state of flux due to technical innovations. Over-reliance on kidney function estimates to guide drug dosing in patients with infectious diseases can bias underdosing especially among the acutely ill. A holistic approach to drug dose adjustment in patients with abnormal kidney function is necessary to optimize clinical outcomes.

Racial Disparities in Eligibility for Preemptive Waitlisting for Kidney Transplantation and Modification of eGFR Thresholds to Equalize Waitlist Time.

Patients may accrue wait time for kidney transplantation when their eGFR is ≤20 ml/min. However, Black patients have faster progression of their kidney disease compared with White patients, which may lead to disparities in accruable time on the kidney transplant waitlist before dialysis initiation. We compared differences in accruable wait time and transplant preparation by CKD-EPI estimating equations in Chronic Renal Insufficiency Cohort participants, on the basis of estimates of kidney function by creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys). We used Weibull accelerated failure time models to determine the association between race (non-Hispanic Black or non-Hispanic White) and time to ESKD from an eGFR of ≤20 ml/min per 1.73 m2. We then estimated how much higher the eGFR threshold for waitlisting would be required to achieve equity in accruable preemptive wait time for the two groups. By eGFRcr, 444 CRIC participants were eligible for waitlist registration, but the potential time between eGFR ≤20 ml/min per 1.73 m2 and ESKD was 32% shorter for Blacks versus Whites. By eGFRcys, 435 participants were eligible, and Blacks had 35% shorter potential wait time compared with Whites. By the eGFRcr-cys equation, 461 participants were eligible, and Blacks had a 31% shorter potential wait time than Whites. We estimated that registering Blacks on the waitlist as early as an eGFR of 24-25 ml/min per 1.73 m2 might improve racial equity in accruable wait time before ESKD onset. Policies allowing for waitlist registration at higher GFR levels for Black patients compared with White patients could theoretically attenuate disparities in accruable wait time and improve racial equity in transplant access.

Metformin doses to ensure efficacy and safety in patients with reduced kidney function.

We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regression analysis. The maintenance dose range was predicted at different bands of kidney function to achieve an efficacy target of 1 mg/L for steady-state plasma concentrations. The dosing strategy was evaluated using simulations from a published metformin pharmacokinetic model to determine the probability of concentrations exceeding those associated with lactic acidosis risk, i.e. a steady-state average concentration of 3 mg/L and a maximum (peak) concentration of 5 mg/L. A strong relationship between metformin clearance and estimated kidney function using the Cockcroft and Gault (r2 = 0.699), MDRD (r2 = 0.717) and CKD-Epi (r2 = 0.735) equations was found. The probability of exceeding the safety targets for plasma metformin concentration was <5% for most doses and kidney function levels. The lower dose of 500 mg daily was required to maintain concentrations below the safety limits for patients with an eGFR of 15–29 mL/min. Our analysis suggests that a maximum daily dose of 2250, 1700, 1250, 1000, and 500 in patients with normal kidney function, CKD stage 2, 3a, 3b and 4, respectively, will provide a reasonable probability of achieving efficacy and safety. Our results support the cautious of use metformin at appropriate doses in patients with impaired kidney function.

Comparison of Equations To Estimate Glomerular Filtration Rate and Their Impact on Frequency of Cisplatin-associated Acute Kidney Injury.

Accurate estimation of kidney function is essential for patient selection and drug dosing in patients with cancer. eGFR equations are necessary for decision making and monitoring. Our aim was to identify which of these equations-estimated creatinine clearance (eCrCl) by Cockcroft-Gault (CG), eGFR by Modification of Diet in Renal Disease (eGFRMDRD), CKD Epidemiology Collaboration (eGFRCKD-EPI) or the recently proposed Janowitz-Williams equation (eGFRJ-W)-would be most suitable for GFR estimation among patients with cancer receiving cisplatin. We assembled a cohort of 5274 patients with cancer treated with cisplatin-based chemotherapy at two large cancer centers. We ascertained the frequency of cisplatin-associated AKI (C-AKI) defined as a ≥0.3 mg/dl rise in serum creatinine over baseline. We compared baseline eGFR and eCrCl using Bland-Altman (B-A) plots, coefficients of variation (CV), and concordance correlation coefficients. We calculated the positive predictive value (PPV), negative predictive value (PPV), accuracy, and area under the curve (AUC). Patients were predominantly middle aged (median 58 years, IQR 49-66 years), overweight (median BMI 26.2, IQR 23.1-29.8 kg/m2), and White (88%), with a median baseline creatinine of 0.8 mg/dl and median cisplatin dose of 99 mg. C-AKI developed in 12% of the cohort. eGFRCKD-EPI had the highest PPV and AUC. eGFRCKD-EPI and eGFRMDRD, along with their BSA-modified counterparts, had the closest agreement with the lowest CV (7.2, 95% CI, 7.0 to 7.3) and the highest concordance. C-AKI was lowest when using eGFRCKD-EPI to define eGFR ≥60 ml/min per 1.73 m2. On the basis of its superior diagnostic performance, eGFRCKD-EPI should be used to estimate GFR in patients being considered for cisplatin-based chemotherapy.

Berlin Initiative Study 1 equation and HUGE formula for more accurate estimation of kidney function in elderly

Berlin Initiative Study 1 equation and HUGE formula for more accurate estimation of kidney function in elderly

Assessment of calculated glomerular filtration rate using percutaneous nephrostomy creatinine clearance

Background: Radionuclide scintigraphy is considered the most widely used method for estimation of glomerular filtration rate (GFR) in clinical use. The present study was conducted to assess calculated glomerular filtration rate (cGFR) using percutaneous nephrostomy creatinine clearance and comparing it with measured glomerular filtration rate (mGFR) calculated by radionuclide scintigraphy. Materials & Methods: 40 cases of kidney disease of both genders were included. The mGFR and cGFR estimation was done after complete stabilization of the patient and resolution of the indication for which PCN was inserted and after stabilization of PCN output. The DTPA/EC scan was performed by Gates method. Results: Out of 40 patients, males were 22 and females were 18. mGFR (mean) was 11.4 ml/min, cGFR (mean) was 7.42 ml/min, highest calculated GFR was 8.74 ml/min, mGFR 30 was seen in 5 and mGFR could not calculated in 1 patient. A strong overall correlation was found between the two methods of GFR estimation. Conclusion: GFR calculated by PCN creatinine clearance can be used to estimate kidney function when radionuclide scan is not available. However, further studies are required due to small sample size of our study.

Clinical Implications of Removing Race From Estimates of Kidney Function

This study uses NHANES data to compare estimated glomerular filtration rate from serum creatinine (eGFRcr) values calculated with vs without race as a variable, and to estimate the number of patients for whom nephrologist referrals and drug and renal replacement recommendations would change as a result according to KDIGO guidelines and Medicare benefit policies.

Removal of Race From Estimates of Kidney Function

Removal of Race From Estimates of Kidney Function

Effect of Cystatin C on Vancomycin Clearance Estimation in Critically Ill Children Using a Population Pharmacokinetic Modeling Approach.

Vancomycin is eliminated by glomerular filtration, but current approaches to estimate kidney function in children are unreliable. The authors sought to compare the suitability of cystatin C (CysC)-based glomerular filtration rate equations with the most commonly used creatinine-based equation, bedside Schwartz, to estimate vancomycin clearance (CL). This prospective observational study enrolled critically ill patients (2-18 years) receiving intravenous vancomycin at the Children's Hospital of Philadelphia during December 2015-November 2017. Vancomycin levels were collected during clinical care and at 3 times during a single dosing interval. Plasma CysC was measured within 24 hours before intravenous vancomycin (baseline) initiation or immediately after enrollment and along with the third pharmacokinetic sample. Nonlinear mixed effects modeling was performed using NONMEM software. Covariate selection was used to test model fit with inclusion of the estimated glomerular filtration rate (eGFR) on CL using bedside Schwartz versus various published CysC-based equations. In total, 83 vancomycin levels were obtained from 20 children. The median age was 12.7 years; 6 patients were women. A 1-compartment model best described the data; CL was allometrically scaled to 0.75. During covariate selection, inclusion of the eGFR calculated using a CysC-based equation significantly improved model fit [reduction in objective function value (OFV) range: -17.191 to -18.704] than bedside Schwartz ([INCREMENT]OFV -12.820). Including the full age spectrum equation, an eGFR equation based on both creatinine and CysC, led to the largest OFV reduction (-22.913); female sex was also a significant covariate of CL in the model. Final model pharmacokinetic indices were CL = 0.29 L/h/kg and volume of distribution = 0.48 L/kg. CysC-based equations help better estimate vancomycin CL than bedside Schwartz in critically ill children.

Variability in Kidney Function Estimates in Emerging Adults With Spina Bifida: Implications for Transitioning From Pediatric to Adult Care

ObjectiveTo examine the variability of estimated glomerular filtration rate (eGFR) in emerging adults with spina bifida (SB) by comparing multiple equations across the transitional age period, hypothesizing that creatinine (Cr)-based equations show greater variability than cystatin-C (CysC)- or combination-based equations. MethodsA retrospective cohort study was performed from 2012 to 2017 at a multidisciplinary SB clinic. Emerging adults were defined as patients ages 18-28 years old. Four pediatric, 3 adult, and 3 averaged eGFR equations were considered. Cross-sectional variability in eGFR data was assessed using coefficients of variation, chronic kidney disease (CKD) stage classification, and pairwise percent relative difference in eGFR between analogous pediatric and adult equations based on included lab values. Longitudinal changes in eGFR over time were compared across equations using a covariance pattern model accounting for repeated measures. ResultsSeventy-five emerging adults with SB (median age 21.8 years; 55% female; 83% with myelomeningocele) were included in cross-sectional analyses. Adult equations gave higher median eGFRs by 22%-27% and generally milder CKD stage classification than analogous pediatric equations. In longitudinal analyses (median follow-up of 22 months), all equations conferred negative eGFR changes over time (range −1.9 to −4.3 mL/min/1.73m2 per year) that were not significantly different. ConclusionIn emerging adults with SB, adult equations demonstrated higher median eGFRs by 22%-27% compared to analogous pediatric equations, even with Cystatin-C, and generally downstaged CKD stage classification. The same eGFR equation should be used for serial kidney function monitoring in emerging adults with SB who transition care from pediatric to adult services.

Cystatin C-Based Renal Function in Predicting the Long-Term Outcomes of Chronic Total Occlusion After Percutaneous Coronary Intervention.

Renal function estimated by various biomarkers predicting for adverse cardiovascular events has not been well-identified in received percutaneous coronary intervention (PCI) for chronic total occlusion (CTO), the advanced stages of atherosclerosis. We aim to determine whether the serum cystatin C-based-estimated glomerular filtration rate (eGFR) can have an improved predictive value in patients with CTO lesions undergoing PCI as compared with multiple creatinine-based estimates of kidney function. Six hundred and seventy-one patients received CTO PCI were retrospectively included in the study. The eGFR was calculated by modification of diet in renal disease equation for Chinese (cMDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations at baseline, respectively. Then, the cohort was categorized into three groups according to standard KDIGO kidney stages based on eGFR. The primary endpoint was all-cause mortality, and the secondary endpoint was cardiac death. Strikingly, cystatin C-based eGFR showed a better performance with the greater area being under the receiver operating characteristic (ROC) curve (0.73 for all-cause mortality and 0.73 for cardiac death, separately) and a better assessment for survival free from adverse event across renal levels among four eGFR equations. Compared with eGFR calculated by other formulas, serum cystatin C-based eGFR showed the highest prognostic value for both all-cause mortality (adjusted HR 3.6, 95% CI 1.6–8.1, P = 0.002) and cardiac death (adjusted HR 2.9, 95% CI 1.0–8.1, P = 0.028). Moreover, cystatin C-based eGFR significantly improved the risk reclassification of event with a high value of net reclassification improvement and integrated discrimination improvement. This study may prove that cystatin C-based eGFR is a better predictor of both all-cause mortality and cardiac death than other equations in populations with CTO undergoing PCI.

Quality improvement at scale: evaluation of the drivers and barriers to adoption and sustainability of an intervention to reduce late referral in chronic kidney disease

This quality improvement project aimed to drive large scale and sustained change to reduce the burden of chronic kidney disease in the UK. The intervention is a software program that...

Umbelliferone attenuates gentamicin-induced renal toxicity by suppression of TLR-4/NF-κB-p65/NLRP-3 and JAK1/STAT-3 signaling pathways

Nephrotoxicity is the most common adverse effect of gentamicin (GNT). This study aimed to investigate the possible nephroprotective effect of umbelliferone (UMB), against GNT-induced nephrotoxicity. Rats were allocated into the control group; UMB group (50 mg/kg/day, P.O. for 15 days); GNT group (100 mg/kg/day, i.p., for 8 days); and GNT + UMB group. By the end of the experimental period, serum creatinine, urea, and uric acid as well as urine KIM-1 and urine albumin/creatinine ratio were evaluated to estimate kidney function. Moreover, tissue samples were collected for assessment of ERK1/2, p-ERK1/2, TLR-4, p38 MAPK, NF-κB-p65, NLRP-3, IkBα, TNF-α, IL-1β, JAK1, STAT-3, p-STAT, and cleaved caspase-3. In support, the histopathological examination of renal tissues was performed. UMB improves kidney function through regulation of renal serum biomarkers, with alleviations of histological abrasions induced by GNT. Besides, UMB downregulates renal protein expressions of ERK1/ERK2, TLR-4, and p38MAPK, with subsequent suppression of NF-κB-p65/NLRP-3 inflammasome and JAK1/STAT-3 pathways as well as cleaved caspase-3. In parallel, UMB induced IkBα upregulation. Collectively, UMB markedly amended all GNT-induced renal changes. These nephroprotective outcomes could be attributed to its ability to impede TLR-4/NF-κB-p65/NLRP-3 inflammasome and JAK1/STAT-3 pathways activation, as well as to its anti-inflammatory property.