• Analgesic pharmacokinetics
• Cirrhosis
• Nonopioid analgesics
• Opioid analgesics
• Pain management

• Humans
• Liver Cirrhosis/complications
• Analgesics/pharmacokinetics
• Analgesics/administration & dosage
• Pain/drug therapy
• Pain/etiology
• Pain Management/methods
• Caregivers

• Liver transplantation
• chronic kidney disease
• estimated glomerular filtration rate
• hepatobiliary disease
• kidney failure
• simultaneous liver-kidney transplantation

• Humans
• Liver Transplantation/adverse effects
• Kidney
• Renal Insufficiency/etiology
• Kidney Transplantation/adverse effects
• Glomerular Filtration Rate
• Risk Factors
• Retrospective Studies

• Creatinine
• Cystatin C
• Glomerular filtration
• eGFR

• Humans
• Glomerular Filtration Rate
• Creatinine
• Critical Illness
• Biomarkers
• Renal Insufficiency, Chronic

• Chronic liver disease
• Creatinine
• Cystatin C
• GFRNMR
• eGFR

• Humans
• Retrospective Studies
• Glomerular Filtration Rate/physiology
• Liver Diseases/diagnosis
• Liver Diseases/pathology
• Renal Insufficiency, Chronic/complications
• Kidney/pathology
• Cystatin C
• Creatinine
• Male
• Female
• Adolescent
• Adult
• Middle Aged
• Aged
• Aged, 80 and over

• creatinine
• cystatin C
• glomerular filtration rate
• liver cirrhosis
• liver transplantation
• simultaneous liver-kidney transplantation

• End-stage kidney disease
• Liver transplantation
• Liver–kidney transplantation
• end-stage liver disease

• Creatinine
• Fibrosis
• Glomerular Filtration Rate
• Hospitals
• Humans
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Renal Insufficiency, Chronic/diagnosis
• Renal Insufficiency, Chronic/epidemiology
• Retrospective Studies

• endothelin-1
• heart failure
• heart transplantation
• inflammation
• interleukin-6

• Albumin to creatinine ratio
• Chronic kidney disease
• Estimated glomerular filtration rate
• Kidney function markers
• Non alcoholic fatty liver disease

• Albuminuria/urine
• Cardiometabolic Risk Factors
• Creatinine/metabolism
• Diabetes Mellitus, Type 2/epidemiology
• Diabetes Mellitus, Type 2/metabolism
• Dyslipidemias/epidemiology
• Dyslipidemias/metabolism
• Glomerular Filtration Rate
• Glucose Intolerance/epidemiology
• Glucose Intolerance/metabolism
• Humans
• Hypertension/epidemiology
• Hypertension/metabolism
• Inflammation/metabolism
• Insulin Resistance
• Kidney Function Tests
• Non-alcoholic Fatty Liver Disease/epidemiology
• Non-alcoholic Fatty Liver Disease/metabolism
• Obesity/epidemiology
• Oxidative Stress
• Renal Insufficiency, Chronic/epidemiology
• Renal Insufficiency, Chronic/metabolism
• Renin-Angiotensin System
• Risk Factors
• Severity of Illness Index

Cystatin C (Cys‐C) is a marker of renal function that has shown prognostic value for cardiovascular risk stratification across different patient populations. The incremental value of Cys‐C beyond established cardiac and renal biomarkers remains incompletely explored.

SOLID‐TIMI 52 (Stabilization of Plaques Using Darapladib‐Thrombolysis in Myocardial Infarction 52; http://www.clinicaltrials.gov, NCT01000727) randomized patients ≤30 days post–acute coronary syndrome were treated with darapladib or placebo. The association between Cys‐C and long‐term risk (median follow‐up 2.5 years) was assessed in 4965 individuals with adjustments made for clinical variables and other risk markers (eg, estimated glomerular filtration rate, high‐sensitivity troponin I, brain‐type natriuretic peptide, and fibroblast growth factor‐23). The prespecified outcome of interest was cardiovascular death (CVD) or heart failure hospitalization. Cys‐C was strongly correlated with creatinine (r=0.60) and estimated glomerular filtration rate (r=−0.68), moderately correlated with fibroblast growth factor‐23 (r=0.39), and weakly correlated with brain‐type natriuretic peptide (r=0.28) and high‐sensitivity troponin I (r=0.06) (all P<0.0001). After multivariate adjustment, increasing concentration of Cys‐C (per SD of log‐transformed Cys‐C) was significantly associated with a 28% higher hazard of CVD or heart failure hospitalization (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.12‐1.46, P<0.001), including CVD (HR 1.24, 95% CI 1.04‐1.47, P=0.01) and heart failure hospitalization (HR 1.42, 95% CI 1.19‐1.69, P<0.001). Cys‐C was also associated with a higher hazard of CVD, myocardial infarction, or stroke (HR 1.15, 95% CI 1.04‐1.28, P<0.01), including myocardial infarction (HR 1.17, 95% CI 1.02‐1.33, P=0.02). The addition of Cys‐C to a fully adjusted model without estimated glomerular filtration rate improved the C‐statistic from 0.80 to 0.81 (P=0.03) for CVD or heart failure hospitalization. In contrast, the addition of estimated glomerular filtration rate to a fully adjusted model without Cys‐C failed to improve model discrimination (P=0.17).

Cys‐C is associated with the risk of adverse outcomes in patients after acute coronary syndrome. This relationship is independent of established and novel biomarkers of the cardiorenal axis.

• acute coronary syndrome
• biomarker
• cystatin C
• prognosis

• Acute Kidney Injury/diagnosis
• Adult
• Area Under Curve
• Cohort Studies
• Female
• Hepatorenal Syndrome/diagnosis
• Hepatorenal Syndrome/epidemiology
• Hospitalization/statistics & numerical data
• Humans
• Intensive Care Units
• Liver Cirrhosis/diagnosis
• Logistic Models
• Male
• Middle Aged
• Patient Admission/statistics & numerical data
• Retrospective Studies
• Severity of Illness Index

• UL1 TR000445 NCATS NIH HHS
• I01 HX001280 HSRD VA
• 1U2COD023196 NIH HHS
• I01 HX001284 HSRD VA

Chronic kidney disease of uncertain aetiology (CKDu) is one of the major health concerns among agricultural communities in Sri Lanka. Individuals involved in severe agricultural works for their livelihood are highly vulnerable for this disease and patients have been detected with persisting proteinuria at community-level screening. The current study was designed to evaluate the diagnosis of two functional markers of kidney damage using individuals with persisting proteinuria as the baseline.

One hundred and fifty hard-working agricultural farmers from high-prevalence area for CKDu (Madawachchiya) were screened three times for proteinuria; 66 proteinuric and 21 non-proteinuric were identified as the baseline classification. Selected individuals were analysed further for creatinine, protein and cystatin C in urine and creatinine, cystatin C in serum. Urine protein-to-creatinine ratio (UP/UC) was calculated.

Based on creatinine and cystatin C cut-off levels in serum, individuals were classified as high or normal. Diagnosis of two functional markers (creatinine and cystatin C) were evaluated using receiver operating characteristic (ROC) curve and in terms of sensitivity and specificity using UP/UC as the baseline. Creatinine and cystatin C-based eGFR (estimated Glomerular filtration rate) levels were calculated, and Pearson’s correlation coefficient was determined between different eGFR measurements using UP/UC. Mean (SD) UP/UC ratio, serum creatinine, and serum cystatin C levels of the proteinuric subjects were 129.0 (18.4) mg/mmol, 1.35 (0.39) mg/dL, 1.69 (0.58) mg/L. For non-proteniuric individuals, the results were found to be 14.4 (2.28), 1.22 (0.40) mg/dL, 0.82 (0.25) mg/L. The ROC analysis showed excellent accuracy in using cystatin C for identifying proteinuric patients than creatinine area under the curve (AUC): 0.9675, P < 0.001). Cut-off points were identified as 1.015 mg/dL for serum creatinine and 0.930mg/L for cystatin C. Furthermore, cystatin C based Hoek formula showed the better correlation (0.635, P < 0.001) with UP/UC compared with creatinine based modification of diet in renal disease (MDRD) formula.

The study showed elevated serum cystatin C in patients with persisting proteinuria compared with non-responding serum creatinine. Moreover, cystatin C-based eGFR equations were more accurate to determine the kidney function than serum creatinine in proteinuric patients who are vulnerable for CKDu in high-prevalence areas.

• Sri Lanka
• chronic kidney disease of uncertain aetiology
• cystatin C
• persistent proteinuria

• Children
• Creatinine
• Cystatin C
• Height-independent
• eGFR

• Adolescent
• Adult
• Age Factors
• Biomarkers/blood
• Biomarkers/urine
• Body Height
• Child
• Child, Preschool
• Creatinine/blood
• Creatinine/metabolism
• Creatinine/urine
• Cystatin C/blood
• Cystatin C/metabolism
• Cystatin C/urine
• Female
• Glomerular Filtration Rate
• Humans
• Inulin/administration & dosage
• Inulin/blood
• Inulin/metabolism
• Inulin/urine
• Kidney/physiopathology
• Kidney Diseases/blood
• Kidney Diseases/diagnosis
• Kidney Diseases/physiopathology
• Kidney Diseases/urine
• Kidney Function Tests/methods
• Male
• Renal Elimination
• Retrospective Studies
• Sex Factors
• Young Adult

• anti-infectives
• infectious diseases
• monitoring drug therapy

As end-stage liver disease progresses, renal blood flow linearly correlates with mean arterial blood pressure (MBP) due to impaired autoregulation. We investigated whether the lower degree of postoperative MBP would predict the occurrence of postoperative acute kidney injury (AKI) after liver transplantation.

This retrospective study enrolled 1,136 recipients with normal preoperative kidney function. Patients were categorized into two groups according to the averaged postoperative MBP: <90 mmHg (MBP_below90) and ≥90 mmHg (MBP_over90). The primary endpoint was occurrence of postoperative AKI, defined by the creatinine criteria of the Kidney Disease Improving Global Outcomes. The logistic regression model with inverse probability treatment weighting (IPTW) of propensity score was used to compare the risk of postoperative AKI between two groups.

MBP_below90 group (83.0±5.1 mmHg) showed higher prevalence and risk of postoperative AKI (74.2% versus 62.6%, p<0.001; IPTW-OR 1.34 [1.12–1.61], p=0.001) compared with MBP_over90 group (97.3±5.2 mmHg). When stratified by quartiles of baseline cystatin C glomerular filtration ratio (GFR), the association between MBP_below90 and postoperative AKI remained significant only with the lowest quartile (cystatin C GFR ≤85 mL/min/1.73 m²; IPTW-OR 2.24 [1.53–3.28], p<0.001), but not with 2^nd–4^th quartiles.

Our results suggest that maintaining supranormal MBP over 90 mmHg may be beneficial to reduce the risk of post-LT AKI, especially for liver transplant recipients with cystatin C GFR ≤85 mL/min/1.73 m².

The Cockcroft-Gault (CG) equation has become perhaps the most popular practical approach for estimating renal function among health care professionals. Despite its widespread use, clinicians often overlook not only the limitations of the original serum creatinine (SCr) based equation, but also may not appreciate the validity of the many variations used to compensate for these limitations. For cirrhotic patients in particular, the underlying pathophysiology of the disease contributes to a falsely low SCr, thereby overestimating renal function with use of the CG equation in this population. We reviewed the original CG trial from 1976 along with data surrounding clinician specific alterations to the CG equation that followed through time. These alterations included different formulas for body weight in obese patients and the “rounding up” approach in patients with low SCr. Additionally, we described the pathophysiology and hemodynamic changes that occur in cirrhosis; and reviewed several studies that attempted to estimate renal function in this population. The evidence we reviewed regarding the most accurate manipulation of the original CG equation to estimate creatinine clearance (CrCl) was inconclusive. Unfortunately, the homogeneity of the patient population in the original CG trial limited its external validity. Elimination of body weight in the CG equation actually produced the estimate closest to the measure CrCl. Furthermore, “rounding up” of SCr values often underestimated CrCl. This approach could lead to suboptimal dosing of drug therapies in patients with low SCr. In cirrhotic patients, utilization of SCr based methods overestimated true renal function by about 50% in the literature we reviewed.

• Cockcroft-Gault
• Cirrhosis
• Renal function
• Pharmacokinetics
• Creatinine clearance

In the past decades liver transplantation (LT) has become the treatment of choice for patients with end stage liver disease (ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of a greater number of marginal donors such as older donors or donors after circulatory death (DCD). The improved survival of transplanted patients has increased the frequency of long-term complications, in particular chronic kidney disease (CKD). Acute kidney injury (AKI) post-LT has been recently recognized as an important risk factor for the occurrence of de novo CKD in the long-term outcome. The onset of AKI post-LT is multifactorial, with pre-LT risk factors involved, including higher Model for End-stage Liver Disease score, more sever ESLD and pre-existing renal dysfunction, either with intra-operative conditions, in particular ischaemia reperfusion injury responsible for post-reperfusion syndrome (PRS) that can influence recipient’s morbidity and mortality. Post-reperfusion syndrome-induced AKI is an important complication post-LT that characterizes kidney involvement caused by PRS with mechanisms not clearly understood and implication on graft and patient survival. Since pre-LT risk factors may influence intra-operative events responsible for PRS-induced AKI, we aim to consider all the relevant aspects involved in PRS-induced AKI in the setting of LT and to identify all studies that better clarified the specific mechanisms linking PRS and AKI. A PubMed search was conducted using the terms liver transplantation AND acute kidney injury; liver transplantation AND post-reperfusion syndrome; acute kidney injury AND post-reperfusion syndrome; acute kidney injury AND DCD AND liver transplantation. Five hundred seventy four articles were retrieved on PubMed search. Results were limited to title/abstract of English-language articles published between 2000 and 2015. Twenty-three studies were identified that specifically evaluated incidence, risk factors and outcome for patients developing PRS-induced AKI in liver transplantation. In order to identify intra-operative risk factors/mechanisms specifically involved in PRS-induced AKI, avoiding confounding factors, we have limited our study to “acute kidney injury AND DCD AND liver transplantation”. Accordingly, three out of five studies were selected for our purpose.

• Liver transplantation
• Acute kidney injury
• Post-reperfusion syndrome
• Donation after circulatory death
• Chronic kidney disease

• Acute Kidney Injury/diagnosis
• Acute Kidney Injury/etiology
• Acute Kidney Injury/mortality
• Animals
• Donor Selection
• End Stage Liver Disease/diagnosis
• End Stage Liver Disease/mortality
• End Stage Liver Disease/surgery
• Graft Survival
• Humans
• Liver Transplantation/adverse effects
• Liver Transplantation/mortality
• Reperfusion Injury/diagnosis
• Reperfusion Injury/etiology
• Reperfusion Injury/mortality
• Risk Factors
• Syndrome
• Tissue Donors/supply & distribution
• Treatment Outcome

• Child
• Creatinine
• Cystatin C
• Glomerular filtration rate
• Kidney disease

• acute kidney injury
• animal models
• cirrhosis
• experimental models
• hepatorenal syndrome
• portal hypertension
• splanchnic vasodilation
• vasodilation and renal vasoconstriction

• Cirrhosis
• Estimated GFR

• APACHE II
• Creatinine
• Cystatin C
• GFR
• Intensive care unit
• Urea

• creatinine
• cystatin C
• glomerular filtration rate
• liver transplantation

• Cirrhosis
• Estimated GFR

• Kidney transplantation
• Liver transplantation
• Organ allocation
• Organ utilization
• Survival outcomes

• Acute kidney injury
• Biomarkers
• Creatinine
• Liver transplant
• Model for end-stage liver disease

• acute kidney injury
• cystatin C
• hemorrhagic shock
• trauma

Chronic kidney disease (CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate (GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine (SCr) and cystatin C (CysC). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associations with disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 mL/min per 1.73 m². Equations combining CysC and SCr perform better than the equations using either CysC or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, CysC and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD.

• Chronic kidney disease
• Estimated glomerular filtration rate
• Kidney damage
• New biomarkers
• MicroRNA

Renal function in patients with advanced cirrhosis is an important prognostic factor for survival both prior to and following liver transplantation. The importance of renal function is reflected by the introduction of the model for end stage liver disease (MELD) score, which includes serum creatinine. The MELD score has been shown to predict the short term risk of death for transplant wait listed patients and is currently used by many countries to allocate liver transplants on the basis of severity of underlying illness. Changes in serum creatinine are also used to stage acute kidney injury. However prior to liver transplantation the serum creatinine typically over estimates underlying renal function, particularly when a colorimetric Jaffe based assay is used, and paradoxically then under estimates renal function post liver transplantation, particularly when immunophyllins are started early as part of transplant immunosuppression. As acute kidney injury is defined by changes in serum creatinine, this potentially leads to over estimation of the incidence and severity of acute kidney injury in the immediate post-operative period.

• Serum creatinine
• Acute kidney injury
• Liver transplantation

• Acute Kidney Injury/physiopathology
• Acute Kidney Injury/therapy
• Aged
• Creatinine/urine
• Female
• Glomerular Filtration Rate/physiology
• Humans
• Intensive Care Units
• Kidney Function Tests/methods
• Length of Stay/statistics & numerical data
• Male
• Middle Aged
• Outcome Assessment, Health Care
• Sensitivity and Specificity
• Treatment Outcome

• acute tubular necrosis
• biomarker
• dialysis
• hepatorenal syndrome
• renal failure

• end-stage liver disease
• liver transplantation
• cystatin c
• glomerular filtration rate
• gender disparity

• Adult
• Aged
• Biomarkers/blood
• Comorbidity
• Creatinine/blood
• Cystatin C/blood
• Female
• Glomerular Filtration Rate/physiology
• Humans
• Iothalamic Acid/metabolism
• Kidney/physiopathology
• Liver Cirrhosis/blood
• Liver Cirrhosis/epidemiology
• Male
• Middle Aged
• Models, Biological
• Renal Insufficiency, Chronic/blood
• Renal Insufficiency, Chronic/diagnosis
• Renal Insufficiency, Chronic/epidemiology
• Retrospective Studies

• K23 DK089008 NIDDK NIH HHS
• 5 K23 DK089008-03 NIDDK NIH HHS

The ratio of the steady-state 24-hour area under the concentration-time curve (ssAUC₂₄) to the MIC (AUC₂₄/MIC) for vancomycin has been recommended as the preferred pharmacodynamic index. The aim of this study was to assess whether the calculated AUC₂₄ (cAUC₂₄) using the creatinine clearance (CLcr) differs from the ssAUC₂₄ based on the individual pharmacokinetic data estimated by a commercial software.

The cAUC₂₄ was compared with the ssAUC₂₄ with respect to age, body mass index, and trough concentration of vancomycin and the results were expressed as median and interquartile ranges. A correlation between the cAUC₂₄ and ssAUC₂₄ and the trough concentration of vancomycin was evaluated. The probability of reaching an AUC₂₄/MIC of 400 or higher was compared between the cAUC₂₄ and ssAUC₂₄ for different MICs of vancomycin and different daily doses by simulation in a subgroup with a trough concentration of 10 mg/L and higher.

The cAUC₂₄ was significantly lower than the ssAUC₂₄ (392.38 vs. 418.32 mg·hr/L, P < 0.0001) and correlated weakly with the trough concentration (r = 0.649 vs. r = 0.964). Assuming a MIC of 1.0 mg/L, the probability of reaching the value of 400 or higher was 77.5% for the cAUC₂₄/MIC and 100% for the ssAUC₂₄/MIC in patients with a trough concentration of 10 mg/L and higher. If the MIC increased to 2.0 mg/L, the probability was 57.7% for the cAUC₂₄/MIC and 71.8% for the ssAUC₂₄/MIC at a daily vancomycin dose of 4,000 mg.

The cAUC₂₄ using the calculated CLcr is usually underestimated compared with the ssAUC₂₄ based on individual pharmacokinetic data. Therefore, to obtain a more accurate AUC₂₄, therapeutic monitoring of vancomycin rather than a simple calculation based on the CLcr should be performed, and a more accurate biomarker for renal function is needed.

• Area under curve
• Drug monitoring, Therapeutic
• Pharmacodynamics
• Vancomycin

Background. Acute kidney injury (AKI) is a common and severe complication in patients with cirrhosis. Progression of AKI to a higher stage associates with increased mortality. Intervening early in AKI when renal dysfunction is worsening may improve outcomes. However, serum creatinine correlates poorly with glomerular filtration in patients with cirrhosis and fluctuations may mask progression early in the course of AKI. Cystatin C, a low-molecular-weight cysteine proteinase inhibitor, is a potentially more accurate marker of glomerular filtration. Methods. We conducted a prospective multicenter study in patients with cirrhosis comparing changes in cystatin and creatinine immediately following onset of AKI as predictors of a composite endpoint of dialysis or mortality. Results. Of 106 patients, 37 (35%) met the endpoint. Cystatin demonstrated less variability between samples than creatinine. Patients were stratified into four groups reflecting changes in creatinine and cystatin: both unchanged or decreased 38 (36%) (Scr−/CysC−); only cystatin increased 25 (24%) (Scr−/CysC+); only creatinine increased 15 (14%) (Scr+/CysC−); and both increased 28 (26%) (Scr+/CysC+). With Scr−/CysC− as the reference, in both instances where cystatin rose, Scr−/CysC+ and Scr+/CysC+, the primary outcome was significantly more frequent in multivariate analysis, P = 0.02 and 0.03, respectively. However, when only creatinine rose, outcomes were similar to the reference group. Conclusions. Changes in cystatin levels early in AKI are more closely associated with eventual dialysis or mortality than creatinine and may allow more rapid identification of patients at risk for adverse outcomes.

In the clinical context of the patients with liver cirrhosis, accurate evaluation of the renal function is potentially crucial. Indeed, it can lead to early diagnosis of both acute kidney injury and chronic kidney disease and to reliable characterization of the renal status of the patient before performing a liver transplantation. Despite some limitations, the assay of serum creatinine (SCr) is universally used to estimate glomerular filtration rate (GFR) because of its wide availability, its simplicity and because it is inexpensive. Nevertheless, several reports show that the value of this assay to estimate GFR is strongly challenged in cirrhotic patients, especially in patients with liver failure and/or severely impaired renal function. This has led to seek new alternatives to estimate more reliably the GFR in these patients. Although the reference methods, based on the utilization of exogenous markers, allow measuring GFR and thereby constitute the “gold standard” to evaluate renal function, they are not feasible in routine clinical practice. Several studies have shown that a cystatin C (CysC) based formula perform better than the SCr-based estimates in cirrhotic patients and the estimation of GFR by these formulas could therefore lead to optimize the management of the patients. A new estimate based on CysC has been recently developed using a large number of patients and the first results regarding the evaluation of its performance are promising, making this new formula the best candidate for a reference estimate of the renal function in cirrhotic patients.

• Cirrhosis
• Glomerular filtration rate
• Formula
• Estimation
• Agreement
• Plasma creatinine
• Cystatin C

• Acute Kidney Injury/blood
• Acute Kidney Injury/complications
• Acute Kidney Injury/diagnosis
• Acute Kidney Injury/physiopathology
• Acute Kidney Injury/therapy
• Biomarkers/blood
• Creatinine/blood
• Cystatin C/blood
• Early Diagnosis
• Glomerular Filtration Rate
• Humans
• Kidney/physiopathology
• Kidney Function Tests
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Liver Cirrhosis/therapy
• Models, Biological
• Predictive Value of Tests
• Prognosis
• Renal Insufficiency, Chronic/blood
• Renal Insufficiency, Chronic/complications
• Renal Insufficiency, Chronic/diagnosis
• Renal Insufficiency, Chronic/physiopathology
• Renal Insufficiency, Chronic/therapy
• Reproducibility of Results

• AKI
• AKIN
• ATN
• Acute Kidney Injury Network
• Acute Tubular Necrosis
• Ascites
• CKD
• Cirrhosis
• FENa
• GFR
• HRS
• Hepatorenal
• IAC
• ICU
• International Ascites Club
• KIM-1
• Kidney Injury
• MDRD
• Modification of Diet in Renal Disease
• NGAL
• OR
• PRA
• RAAS
• Urinary Biomarkers
• acute kidney injury
• acute tubular necrosis
• chronic kidney disease
• fractional excretion of sodium
• glomerular filtration rate
• hepatorenal syndrome
• intensive care unit
• kidney injury molecule-1
• neutrophil gelatinase–associated lipocalin
• odds ratio
• prerenal azotemia
• renin-angiotensin-aldosterone system

• Biomarkers/metabolism
• Comorbidity
• Creatinine/blood
• Disease Progression
• Glomerular Filtration Rate
• Hemodynamics
• Humans
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Prognosis
• Renal Insufficiency/classification
• Renal Insufficiency/complications
• Renal Insufficiency/diagnosis
• Severity of Illness Index

• K23 DK089008 NIDDK NIH HHS
• 5 K23 DK089008-04 NIDDK NIH HHS

Various estimating equations have been developed to estimate glomerular filtration rate (GFR) for use in clinical practice. However, the unique renal physiological and pathological processes that occur in sickle cell disease (SCD) may invalidate these estimates in this patient population. This study aims to compare GFR estimated using common existing GFR predictive equations to actual measured GFR in persons with homozygous SCD. If the existing equations perform poorly, we propose to develop a new estimating equation for use in persons with SCD.

98 patients with the homozygous SS disease (55 females: 43 males; mean age 34±2.3 years) had serum measurements of creatinine, as well as had GFR measured using ^99mTc-DTPA nuclear renal scan. GFR was estimated using the Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault (CG), and the serum creatinine based CKD-EPI equations. The Bland-Altman limit of agreement method was used to determine agreement between measured and estimated GFR values. A SCD-specific estimating equation for GFR (JSCCS-GFR equation) was generated by means of multiple regression via backward elimination.

The mean measured GFR±SD was 94.9±27.4 mls/min/1.73 m² BSA, with a range of 6.4–159.0 mls/min/1.73 m². The MDRD and CG equations both overestimated GFR, with the agreement worsening with higher GFR values. The serum creatinine based CKD-EPI equation performed relatively well, but with a systematic bias of about 45 mls/min. The new equation developed resulted in a better fit to our sickle cell disease data than the MDRD equation.

Current estimating equations, other than the CKD-EPI equation, do not perform very accurately in persons with homozygous SS disease. A fairly accurate estimating equation, suitable for persons with GFR >60 mls/min/1.73 m² has been developed from our dataset and validated within a simulated dataset.

• Adult
• Anemia, Sickle Cell/blood
• Anemia, Sickle Cell/genetics
• Creatinine/blood
• Female
• Glomerular Filtration Rate
• Homozygote
• Humans
• Kidney Function Tests/methods
• Male
• Risk Factors

• Acute Kidney Injury/diagnosis
• Acute Kidney Injury/etiology
• Acute Kidney Injury/metabolism
• Acute-Phase Proteins/analysis
• Biomarkers/analysis
• Cystatin C/analysis
• Humans
• Lipocalin-2
• Lipocalins/analysis
• Liver Cirrhosis/complications
• Liver Cirrhosis/metabolism
• Proto-Oncogene Proteins/analysis

• Cystatin C
• chronic kidney disease
• glomerular filtration rate (GFR) estimation