Plasma Disappearance Research Articles

Intraoperative simulation of remnant liver function during anatomic liver resection with indocyanine green clearance (LiMON) measurements

ObjectivePost-hepatectomy liver failure (PHLF) is the major cause of death following liver resection. The aim of this study was to evaluate the feasibility of an intraoperative simulation of post-resection liver function. MethodsIntraoperative liver function was measured by indocyanine green (ICG) clearance using the LiMON™ technology. In 20 patients undergoing anatomic liver resection, ICG plasma disappearance rate (PDR (%/min) and ICG retention at 15 min (R15) (%) were measured immediately after the induction of anaesthesia (t0), after selective arterial and portovenous inflow trial clamping (TC) of the resected liver segments (t1), after the completion of resection (t2) and before the closure of the abdominal cavity (t3). ResultsThe median baseline (t0) PDR was 16.5%/min. Trial clamping of the inflow (t1) resulted in a significant reduction in PDR to 10.5%/min. Results under TC were similar to those obtained after resection (t2) (median PDR: 10.5%/min). Linear regression modelling showed that post-resection liver volume could be accurately predicted by TC of liver inflow (P < 0.0001), but not by determining the resected liver volume. Simulated post-resection liver function under TC correlated well with PHLF and length of hospital stay. ConclusionsIntraoperative ICG clearance measurements allow real-time monitoring of intraoperative liver function during surgery. Trial clamping of arterial and portovenous inflow accurately predicts immediate post-resection liver function. The intraoperative measurement of liver function and simulation of post-resection liver function may help to avoid PHLF.

Characterization of early disease status in treatment-naive male paediatric patients with Fabry disease enrolled in a randomized clinical trial.

Trial DesignThis analysis characterizes the degree of early organ involvement in a cohort of oligo-symptomatic untreated young patients with Fabry disease enrolled in an ongoing randomized, open-label, parallel-group, phase 3B clinical trial.MethodsMales aged 5–18 years with complete α-galactosidase A deficiency, without symptoms of major organ damage, were enrolled in a phase 3B trial evaluating two doses of agalsidase beta. Baseline disease characteristics of 31 eligible patients (median age 12 years) were studied, including cellular globotriaosylceramide (GL-3) accumulation in skin (n = 31) and kidney biopsy (n = 6; median age 15 years; range 13–17 years), renal function, and glycolipid levels (plasma, urine).ResultsPlasma and urinary GL-3 levels were abnormal in 25 of 30 and 31 of 31 patients, respectively. Plasma lyso-GL-3 was elevated in all patients. GL-3 accumulation was documented in superficial skin capillary endothelial cells (23/31 patients) and deep vessel endothelial cells (23/29 patients). The mean glomerular filtration rate (GFR), measured by plasma disappearance of iohexol, was 118.1 mL/min/1.73 m2 (range 90.4–161.0 mL/min/1.73 m2) and the median urinary albumin/creatinine ratio was 10 mg/g (range 4.0–27.0 mg/g). On electron microscopy, renal biopsy revealed GL-3 accumulation in all glomerular cell types (podocytes and parietal, endothelial, and mesangial cells), as well as in peritubular capillary and non-capillary endothelial, interstitial, vascular smooth muscle, and distal tubules/collecting duct cells. Lesions indicative of early Fabry arteriopathy and segmental effacement of podocyte foot processes were found in all 6 patients.ConclusionsThese data reveal that in this small cohort of children with Fabry disease, histological evidence of GL-3 accumulation, and cellular and vascular injury are present in renal tissues at very early stages of the disease, and are noted before onset of microalbuminuria and development of clinically significant renal events (e.g. reduced GFR). These data give additional support to the consideration of early initiation of enzyme replacement therapy, potentially improving long-term outcome.Trial RegistrationClinicalTrials.gov NCT00701415

Effects of Different Positive End-Expiratory Pressure Values on Liver Function and Indocyanine Green Clearance Test in Liver Transplantation Donors: A Prospective, Randomized, Double-Blind Study

IntroductionThe aim of this study was demonstrate the influence of different positive end-expiratory pressure (PEEP) values on blood flow of the liver by indocyanine green (ICG) clearance test in donor patients. MethodsICG clearance tests were conducted concurrently using a noninvasive monitor that tracks the plasma disappearance rate of ICG (PDR-ICG%/min) and 15-minute retention rate after administration of ICG (ICG-R15%). This study was performed in 40 patients who underwent right hepatectomy. ResultsThe positive end-expiratory pressure (PEEP) was 0 cm H20 in the first (control) group (group K) and 10 mm Hg in the second study group (group P). ICG clearance test values before general anesthesia (T0), after induction of general anesthesia (T1), after transection (T2), 24 hours postoperative (T3), and 72 hours postoperative (T4) were recorded. Simultaneously, hemoglobin (Hgb), hematocrit (Hct), platelet count, plasma levels of prothrombin (PT), International Normalized Ratio (INR), total bilirubin, direct bilirubin, albumin, aspartate aminotransferase, and alanine aminotransferase values were analyzed. In terms of the plasma disappearance rate and retention rate of ICG 15 minutes after administration, significant difference was not observed between groups. PT and INR values were different within comparisons groups (P < .05). There were significant differences in Hgb and Hct values compared with the baseline values (T0) within group (T1, T2, T3, T4) measurements and between group comparisons at T0 and T4 (P < .05). Systemic arterial pressure, mean arterial pressure, and central venous pressure were significantly different between the groups (P < .05). ConclusionsGiven the small magnitude and limited clinical significance of these changes, we conclude that PEEP values between 0 and 10 cm H2O have no effect on global liver function and liver-related liabilities tests in patients undergoing elective liver donor surgery.

Alterations in hepatic lobar function in regenerating rat liver

BackgroundLigation of a branch of the portal vein redirects portal blood to nonligated lobes resulting in lobar hypertrophy. Although the effect of portal vein ligation on liver volume is well documented, the parallel alterations in liver function are still the subject of controversy. Our aim was to assess the time-dependent reactions of regional hepatic function to portal vein ligation by selective biliary drainage. MethodsMale Wistar rats (n = 44) underwent 80% portal vein ligation. Before the operation as well as 1, 2, 3, 5, and 7 d after circulation, morphology and function (laboratory blood test; hepatic bile flow; plasma disappearance rate of indocyanine green; and biliary indocyanine green excretion) of the liver were examined. ResultsAlthough portal vein ligation affected liver circulation and morphology to a great extent, serum albumin levels, bilirubin levels, and total hepatic bile flow did not change significantly after the operation. Nevertheless, plasma disappearance rate and biliary indocyanine green excretion indicated a temporary impairment of total liver function with the lowest value on the second day and normalization by the fifth day. Bile production and biliary indocyanine green excretion of ligated lobes decreased rapidly after the operation and remained persistently suppressed, whereas the secretory function of nonligated lobes—after a temporary decline—showed a greater increase than the weight of the lobes. ConclusionsPortal vein ligation induced temporary impairment of total liver function, followed by rapid recovery mainly by reason of increase in the function of nonligated lobes. Functional increase in nonligated lobes was more pronounced than suggested by the degree of volume gain.

A rapid, reproducible, noninvasive predictor of liver graft survival

BackgroundClinical and laboratory criteria are not reliable predictors of deceased donor liver graft quality. Intraoperative assessment of experienced surgeons is the gold standard. Standardizing and quantifying this assessment is especially needed now that regional sharing is the rule. We prospectively evaluated a novel, simple, rapid, noninvasive, quantitative measure of liver function performed before graft procurement. Materials and methodsUsing a portable, finger-probe–based device, indocyanine green plasma disappearance rates (ICG-PDR) were measured in adult brain-dead donors in the local donor service area before organ procurement. Results were compared with graft function and outcomes. Both donor and recipient teams were blinded to ICG-PDR measurements. ResultsMeasurements were performed on 53 consecutive donors. Eleven liver grafts were declined by all centers because of quality; the other 42 grafts were transplanted. Logistic regression analysis showed ICG-PDR to be the only donor variable to be significantly associated with 7-d graft survival. Donor risk index, donor age, and transaminase levels at peak or procurement were not significantly associated with 7-d graft survival. ConclusionsWe report the successful use of a portable quantitative means of measuring liver function and its association with graft survival. These data warrant further exploration in a variety of settings to evaluate acceptable values for donated liver grafts.

Impact of morbid obesity on the kidney function of patients with type 2 diabetes

AimsType 2 diabetes and obesity impair kidney function. We examined their respective contributions to urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in patients with type 2 diabetes and morbid obesity. MethodsCross-sectional, monocentric study of kidney function in patients with type 2 diabetes classified into four body mass index (BMI) stages: non-obese (<25kg/m2, n=157); overweight (25 to <30, n=311); obesity (30 to <40, n=310); and morbid obesity (≥40, n=77), with 84 similarly staged controls without diabetes. UAE classes were defined as normal (<30μg/mg creatinine), microalbuminuria (30–299), or macroalbuminuria (≥300) from 3 consecutive urine samples. GFR was measured by 51Cr EDTA plasma disappearance (adjusted and unadjusted to 1.73m2 body surface area, as obesity increases body surface). ResultsParticipants with type 2 diabetes had same age, diabetes duration, and HbA1c across BMI stages. UAE was higher in participants with type 2 diabetes (p<0.0001), and increased with obesity stages (p<0.0001). After adjustment for age, sex, systolic blood pressure and type 2 diabetes status, morbid obesity was associated with a risk of microalbuminuria (OR 1.99, 95%CI 1.35–2.98, p=0.0007) and macroalbuminuria (OR 2.33, 95%CI 1.25–4.22, p=0.006). The body surface adjusted GFR was lower in patients with type 2 diabetes than in controls (p<0.0001), and declined with obesity stages, contrary to controls. An interaction of diabetes and obesity was seen with unadjusted GFR values (p=0.002). ConclusionsMorbid obesity interacts with type 2 diabetes to aggravate UAE and GFR. Treatment strategies should focus on both conditions to protect kidney function in these patients.

Central Venous-Arterial pCO2 Difference Identifies Microcirculatory Hypoperfusion in Cardiac Surgical Patients With Normal Central Venous Oxygen Saturation: A Retrospective Analysis.

Parameters such as central venous oxygen saturation (ScvO2) are used increasingly to monitor adequate hemodynamic treatment. However, it still remains challenging to identify patients with assumed adequate circulatory status quantified by ScvO2 who suffer from macro- and microcirculatory hypoperfusion. The authors hypothesized that central venous-arterial pCO2 difference (dCO2) could serve as an additional parameter to evaluate the adequacy of perfusion in cardiac surgery patients. Retrospective data analysis of a prospective interventional study. University medical center. Patients undergoing surgery with cardiopulmonary bypass. The dCO2 was measured postoperatively. The patients with an ScvO2≥70% were divided into 2 groups, the high-dCO2 group (≥8 mmHg) and the low-dCO2 group (<8 mmHg). Sixty patients were included in this analysis. Twenty-five patients had ScvO2≥70%, 4 patients were assigned to the high-dCO2 group. Patients of the high-dCO2 group had significantly longer intensive care unit (ICU) stays (4 d; 1-29 v 1 d; 1-1; p = 0.02), significantly prolonged need for mechanical ventilation (41.5 h; 11-263.5; v 10 h; 7-11; p = 0.03), and higher cardiovascular complication rates in the ICU on postoperative days 3, 4, and 5 (p = 0.02). The mixed venous saturation (SvO2) after 1 hour in the ICU was significantly lower, lactate levels were significantly higher, and the plasma disappearance rate of indocyanine green was significantly lower after 1 hour in the ICU (14.6%/min; 11.6-19.8%/min v 23.6%/min; 22.5-27.3%/min; p = 0.02) in the high-dCO2 group. Cytokines increased significantly postoperatively in the high-dCO2 group. The authors described dCO2 as a routinely available tool to detect global and microcirculatory hypoperfusion in postoperative cardiac surgical patients. The authors showed that in patients with an ScvO2≥70%, a high dCO2 (≥8 mmHg) was associated with increased postoperative lactate levels and decreased splanchnic function. These findings were associated with a longer need for mechanical ventilation and longer ICU stay.

PROGNOSTIC IMPACT OF ICG-PDR IN PATIENTS WITH HYPOXIC HEPATITIS AT THE INTENSIVE CARE UNIT

Hypoxic hepatitis (HH) is a frequent cause of acute hepatocellular damage in critically ill patients associated with high mortality. Indocyanine green, a medical dye, is removed solely by the liver without entering enterohepatic circulation. Therefore its plasma disappearance rate (ICG-PDR) is an effective clinical tool for assessment of liver function in acute and chronic hepatic disease.

The 99mTc-DTPA Urinary Clearance Method May Be Preferable to the Plasma Disappearance Method for Assessing Glomerular Filtration Rate in Diabetic Nephropathy

Background: Isotopic glomerular filtration rate (iGFR) measurement is comparable to the inulin method. In this study, we compared urinary and plasma iGFR methodologies in patients with diabetic nephropathy. Methods: A total of 147 patients from 3 sites in the Diabetic Intervention with Vitamins to Improve Nephropathy (DIVINe) trial provided 213 sets of urine and blood collections, at baseline, 18 and 36 months. Results: The mean (with standard deviation) plasma iGFR of 60.7 (24.9) ml/min/1.73 m² compared to urinary iGFR of 52.0 (28.0) ml/min/1.73 m² was statistically significant (p value <0.001). Although plasma and urinary iGFRs were highly related (R² = 0.86), plasma iGFR increasingly overestimated urinary iGFRs at lower GFRs. In contrast to the cross-sectional analyses, the two measures of iGFR were weakly related (R² = 0.32) in regard to patients' change over 18 months of follow-up. Conclusion: Plasma iGFR may not be a suitable method for accurately measuring GFR in patients with advancing degrees of chronic kidney disease from diabetic nephropathy.

Measures of GFR in Health and Disease

Glomerular filtration rate (GFR) is the most important measure of kidney function used for chronic kidney disease screening, dosing medications, and following kidney disease progression. Gold standard GFR measurement is inulin clearance; however, GFR is most commonly measured by plasma disappearance of exogenously administered substances. Recent improvements in GFR measurement have been made, and understanding the limitations of different methods is important. In clinical practice, GFR is typically estimated using equations. Most equations are based on serum creatinine, but other markers, in particular Cystatin C have been investigated as well. In the last 10 years, several GFR estimation equations have been published, each associated with strengths and limitations. Understanding how these equations were derived and considering individual patient characteristics is helpful to determine what equations are most likely to estimate GFR most accurately. This review will address each of these issues, highlighting recent literature and focusing on clinical application.

The combination of MELD score and ICG liver testing predicts length of stay in the ICU and hospital mortality in liver transplant recipients.

BackgroundEarly prediction of outcome would be useful for an optimal intensive care management of liver transplant recipients. Indocyanine green clearance can be measured non-invasively by pulse spectrophometry and is closely related to liver function.MethodsThis study was undertaken to assess the predictive value of a combination of the model of end stage liver disease (MELD) score and early indocyanine plasma disappearance rates (ICG-PDR) for length of stay in the intensive care unit (ICU), length of stay in the hospital and hospital mortality in liver transplant recipients.ResultsFifty consecutive liver transplant recipients were included in this post Hoc single-center study. ICG-PDR was determined within 6 hours after ICU admission. Endpoints were length of stay in the ICU, length of hospital stay and hospital mortality. The combination of a high MELD score (MELD >25) and a low ICG-PDR clearance (ICG-PDR < 20%/minute) predicts a significant longer stay in the ICU (p = 0.004), a significant longer stay in the hospital (p < 0.001) and a hospital mortality of 40% vs. 0% (p = 0.003).ConclusionThe combination of MELD scores and a singular ICG-PDR measurement in the early postoperative phase is an accurate predictor for outcome in liver transplant recipients. This easy-to-assess tool might be valuable for an optimal intensive care management of those patients.

Indocyanine green plasma disappearance rate as dynamic liver function test in critically ill patients.

Indocyanine green (ICG) is a water-soluble fluorescent dye that is bound to plasma protein when administered intravenously. Removal of ICG from the blood depends on hepatic blood flow, function of the parenchymal cells and biliary excretion. ICG elimination is described as a useful dynamic liver function test. In this review, we looked at the most recent literature to clarify why ICG is useful in critically ill patients, the validity of the ICG plasma disappearance rate (ICG-PDR) measured transcutaneously and whether ICG-PDR has any prognostic value. In conclusion, measuring ICG-PDR is a valuable method for dynamic assessment of liver function, and is found to be a valuable prognostic tool in predicting survival for septic patients, patients presenting with acute liver failure and critically ill patients.

Prognostic value of enzymatic liver function for the estimation of short-term survival of liver transplant candidates: a prospective study with the LiMAx test

LiMAx has been recently proposed as a new quantitative liver function test. Thus, we aimed to evaluate the diagnostic ability of LiMAx to assess short-term survival in liver transplant candidates and compare its performance to the model for end-stage liver disease (MELD) and indocyanine green plasma disappearance rate (ICG-PDR). Liver function of 167 chronic liver failure patients without hepatocellular carcinoma was prospectively investigated when they were evaluated for liver transplantation. Primary study endpoints were liver-related death within 6months of follow-up. Within 6months of follow-up, 18 patients died and 36 underwent liver transplantation. Median LiMAx results on evaluation day were significantly lower in patients who died (99μg/kg/h vs. 55μg/kg/h; P=0.024), while median ICG-PDR results did not differ within both groups (4.4%/min vs. 3.5%/min; P=0.159). LiMAx showed a higher negative predictive value (NPV: 0.93) as compared with ICG-PDR (NPV: 0.90) and the MELD (NPV: 0.91) in predicting risk of death within 6months. In conclusion, LiMAx provides good prognostic information of liver transplant candidates. In particular, patients who are not at risk of death can be identified reliably by measuring actual enzymatic liver function capacity.

ICG-liver test versus new biomarkers as prognostic markers for prolonged length of stay in critically ill patients - a prospective study of accuracy for prediction of length of stay in the ICU.

BackgroundPrognostic abilities of medical parameters, which are scoring systems, measurements and biomarkers, are important for stratifying critically ill patients. Indocyanine green plasma disappearance (ICG-PDR) is an established clinical tool for the assessment of liver perfusion and function. Copeptin, MR-proANP and pro-ADM are biomarkers whose prognostic value is still unclear. The goal of this prospective study was to evaluate ICG-PDR, copeptin, MR-proANP and pro-ADM to predict prolonged length of stay (pLOS) in the ICU.MethodsThis study was conducted as a prospective single center study including 110 consecutively admitted ICU patients. Primary endpoint was prolonged length of stay (pLOS) in the ICU, defined as more than three days of stay there.ResultsROC analysis showed an AUC of 0.73 for ICG-PDR, 0.70 for SAPS II, 0.65 for MR-proANP, 0.64 for pro-ADM and 0.54 for copeptin for pLOS in the ICU.ConclusionsThe prediction of pLOS in the ICU might be better by means of ICG-PDR than with the new biomarkers copeptin, MR-proANP or pro-ADM. Nevertheless, there is more need for research to evaluate whether ICG-PDR is an overall prognostic marker for pLOS.Trial registration(ClinicalTrials.gov number, NCT01126554).

Hepatoprotective effect by pretreatment with olprinone in a swine partial hepatectomy model

Excessive portal flow to a small remnant liver or small-for-size graft is a primary factor of small-for-size syndrome. We demonstrated that olprinone (OLP), a phosphodiesterase III inhibitor, had a hepatoprotective effect in a rat extended hepatectomy model and a small-for-size liver transplantation model through a modification of the portal venous pressure (PVP). To identify the appropriate dose and duration of treatment for clinical applications, we conducted experiments with a swine partial hepatectomy model. Twenty microminipigs were divided into 4 groups that received the following treatments: (A) saline (control group), (B) OLP at 0.3 μg/kg/minute (preoperative and postoperative administration), (C) OLP at 0.1 μg/kg/minute (preoperative administration), and (D) OLP at 0.3 μg/kg/minute (preoperative administration). The pigs underwent 70% partial hepatectomy. Hemodynamic changes, including changes in PVP, were examined. Liver biopsy was performed 1 and 3 hours after hepatectomy. Blood samples were collected until postoperative day 7 (POD7). In comparison with group A, PVP elevations, periportal edema, and sinusoidal hemorrhaging were attenuated after left Glisson's ligation in groups C and D. Pretreatment with OLP in groups C and D preserved the microstructure of sinusoids and improved the prothrombin activity 1 and 3 hours after hepatectomy. These animals showed better recovery of the remnant liver volume and the plasma disappearance rate of indocyanine green on POD7. In contrast, group B showed exacerbation of liver damage. Measurements of the serum OLP concentration showed that 10 ng/mL OLP was appropriate for a hepatoprotective effect. In conclusion, pretreatment with OLP shows hepatoprotective effects in a swine partial hepatectomy model. OLP may have the potential to ameliorate patients' outcomes after hepatectomy or liver transplantation.

Performance of formulas for estimating glomerular filtration rate in Indigenous Australians with and without Type 2 diabetes: the eGFR Study

It has been proposed that the Chronic Kidney Disease Epidemiology Collaboration formula estimates glomerular filtration rate more accurately than the Modification of Diet in Renal Disease formula. With the very high incidence of diabetes and end-stage kidney disease in Indigenous Australians, accurate estimation of glomerular filtration rate is vital in early detection of kidney disease. We aimed to assess the performance of the Chronic Kidney Disease Epidemiology Collaboration, Modification of Diet in Renal Disease and Cockcroft-Gault formulas in Indigenous Australians with and without diabetes. Indigenous Australians with (n=224) or without (n=340) Type2 diabetes had a reference glomerular filtration rate measure using plasma disappearance of iohexol (measured glomerular filtration rate) over 4h. Serum creatinine was measured by an enzymatic method. Performance was assessed by bias (measured glomerular filtration rate-estimated glomerular filtration rate) and accuracy (percentage of estimated glomerular filtration rate within 30% of measured glomerular filtration rate). The median measured glomerular filtration rate (interquartile range) in participants with or without diabetes was 97 (68-119) and 108 (90-122) mlmin(-1) 1.73m(-2) , respectively. The Chronic Kidney Disease Epidemiology Collaboration formula had smaller bias and greater accuracy than the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall, for participants both with and without diabetes. However, for estimated glomerular filtration rate >90mlmin(-1) 1.73m(-2) , the Chronic Kidney Disease Epidemiology Collaboration formula had greater bias in participants with diabetes, underestimating measured glomerular filtration rate by 7.4 vs. 1.0mlmin(-1) 1.73m(-2) in those without diabetes. The Chronic Kidney Disease Epidemiology Collaboration formula was less accurate across the whole range of estimated glomerular filtration rates in participants with vs. those without diabetes (87.1% vs. 93.3%). The Chronic Kidney Disease Epidemiology Collaboration formula outperforms the Modification of Diet in Renal Disease and Cockcroft-Gault formulas overall in Indigenous Australians with and without diabetes. However, the Chronic Kidney Disease Epidemiology Collaboration formula has greater bias in people with diabetes compared with those without diabetes, especially in those with normal renal function.

Inhibition of glycogen synthase kinase (GSK)-3-β improves liver microcirculation and hepatocellular function after hemorrhagic shock

Ischemia and reperfusion may cause liver injury and are characterized by hepatic microperfusion failure and a decreased hepatocellular function. Inhibition of glycogen synthase kinase (GSK)-3β, a serine-threonine kinase that has recently emerged as a key regulator in the modulation of the inflammatory response after stress events, may be protective in conditions like sepsis, inflammation and shock. Therefore, aim of the study was to assess the role of GSK-3β in liver microcirculation and hepatocellular function after hemorrhagic shock and resuscitation (H/R). Anesthetized male Sprague-Dawley rats underwent pretreatment with Ringer´s solution, vehicle (DMSO) or TDZD-8 (1mg/kg), a selective GSK-3β inhibitor, 30min before induction of hemorrhagic shock (mean arterial pressure 35±5mmHg for 90min) and were resuscitated with shed blood and Ringer´s solution (2h). 5h after resuscitation hepatic microcirculation was assessed by intravital microscopy. Propidium iodide (PI) positive cells, liver enzymes and alpha-GST were measured as indicators of hepatic injury. Liver function was estimated by assessment of indocyanine green plasma disappearance rate. H/R led to a significant decrease in sinusoidal diameters and impairment of liver function compared to sham operation. Furthermore, the number of PI positive cells in the liver as well as serum activities of liver enzymes and alpha-GST increased significantly after H/R. Pretreatment with TDZD-8 prevented the changes in liver microcirculation, hepatocellular injury and liver function after H/R. A significant rise in the plasma level of IL-10 was observed. Thus, inhibition of GSK-3β before hemorrhagic shock modulates the inflammatory response and improves hepatic microcirculation and hepatocellular function.

Time-to-Peak Values Can Estimate Hepatic Functional Reserve in Patients Undergoing Surgical Resection

To evaluate the potential usefulness of perfusion computed tomography (CT) for the estimation of hepatic functional reserve in patients scheduled for surgical resection and to compare the results with those of the indocyanine green retention test results. Thirty-one patients with hepatobiliary malignancies were included. Perfusion CT and indocyanine green retention test were performed on the same day, and their results were compared using Pearson correlation test. A strong correlation was found between perfusion CT time-to-peak values and indocyanine green retention rate at 15 minutes and indocyanine green plasma disappearance rate values (R, 0.789 and -0.790; R, 0.832 and -0.823, respectively; P < 0.0001). Perfusion CT may be useful for the preoperative noninvasive estimation of hepatic functional reserve for patients undergoing liver resection.

Disordered FGF23 and Mineral Metabolism in Children with CKD

In children with CKD, information is limited regarding the prevalence and determinants of fibroblast growth factor 23 excess and 1,25-dihyroxyvitamin D deficiency across the spectrum of predialysis CKD. This study characterized circulating concentrations of fibroblast growth factor 23 and 1,25-dihyroxyvitamin D, and investigated their interrelationships and associations with GFR and secondary hyperparathyroidism in children with CKD who were enrolled in the Chronic Kidney Disease in Children observational cohort study. Plasma fibroblast growth factor 23 concentrations and determinants of mineral metabolism were measured in 464 children ages 1-16 years with predialysis CKD. GFR was measured by plasma disappearance of iohexol in 70% of participants and estimated by the Chronic Kidney Disease in Children estimating equation using serum creatinine and cystatin C concentrations in the remainder of the participants. Participants were grouped according to CKD stage and by 10-ml/min categories of GFR. Median GFR for the cohort was 45 ml/min per 1.73 m(2) (interquartile range=33-57; range=15-109). Plasma fibroblast growth factor 23 concentration was above the normal range in 67% of participants (with higher levels observed among participants with lower GFR) before higher levels of serum parathyroid hormone and phosphorus were observed. Plasma fibroblast growth factor 23 levels were 34% higher in participants with glomerular disease than in participants with nonglomerular disease, despite similar GFR. Serum phosphorus levels, adjusted for age, were significantly lower at GFR of 60-69 ml/min per 1.73 m(2) than higher GFR, but thereafter they became higher in parallel with fibroblast growth factor 23 as GFR declined. Serum 1,25-dihyroxyvitamin D concentrations were lower in those participants with low GFR values, high fibroblast growth factor 23 levels, 25-hydroxyvitamin D deficiency, and proteinuria. Secondary hyperparathyroidism was present in 55% of participants with GFR<50 ml/min per 1.73 m(2). In children with predialysis CKD, high plasma fibroblast growth factor 23 is the earliest detectable abnormality in mineral metabolism, and levels are highest in glomerular diseases.

Validation of the CKiD formulae to estimate GFR in children post renal transplant

The Chronic Kidney Disease in Children (CKiD) study reported new formulae to estimate glomerular filtration rate (eGFR). The study reported here aimed to assess the accuracy of these formulae in estimating levels and changes in GFR in pediatric renal transplant recipients and generate a new formula in our cohort. Two hundred and fifty-two studies of plasma disappearance of (125)I-iothalamate (CIO) were used to measure GFR in 155 renal transplant recipients. The CKiD bedside formula (CKiD-BS) was compared with CIO. A mixed logistic regression model was fit to evaluate the performance of estimating change in posttransplant CIO using CKiD-BS. We used mixed-effects linear regression to fit a multiplicative model of CIO. The CKiD cystatin-C-based formula (CKiD-Cys) was also used for comparison in 32 additional transplant recipients. Comparisons were made using Bland-Altman plots. CKiD-BS underestimates CIO by 20 % for GFR >25 ml/min per 1.73 m(2). Percentage change in CKiD-BS performed reasonably well in estimating 15 % change of CIO beginning 6 months posttransplant [area under the curve (AUC) = 0.791)] The multiplicative constant in the CKiD-BS was recalibrated [R-Bedside = 0.461 × ht(cm)/SCr).]A GFR model [GFR-M) = 10.73 × [(ht(cm)]0.51/(SCr)0.90 × (BUN)0.23] has higher specificity but similar sensitivity for CIO compared with R-Bedside. CKiD-Cys overestimates CIO by 10 ml/min per 1.73 m(2) across a broad range of GFR. In our cohort, the CKiD-BS underestimates CIO; however, changes in CKiD-BS can be used to estimate changes in CIO. CKiD-Cys overestimates CIO and is not accurate in estimating CIO.