- Email: [email protected]
Creatinine Versus Cystatin C for Estimating GFR in Patients With Liver Cirrhosis
Correspondence 3. Cruikshank DP, Pitkin RM, Reynolds WA, Williams GA, Hargis GK. Effects of magnesium sulfate treatment on perinatal calcium metabolism. I. Maternal and fetal responses. Am J Obstet Gynecol. 1979;134(3):243-249. 4. Gough IR, Balderson GA, Lloyd HM, Galligan J, Willgoss D, Fryar BG. The effect of intravenous magnesium sulphate on parathyroid function in primary hyperparathyroidism. World J Surg. 1988;12(4):463-469. 5. Suzuki K, Nonaka K, Kono N, et al. Effects of the intravenous administration of magnesium sulfate on corrected serum calcium level and nephrogenous cyclic AMP excretion in normal human subjects. Calcif Tissue Int. 1986;39(5):304-309. 6. Gonella M, Buzzigoli G, Bencivelli W, Bartolini V, Betti G. The determination of whole blood magnesium concentration in uremics on chronic dialysis. Nephron. 1981;28(2):88-89. 7. Nilsson P, Johansson SG, Danielson BG. Magnesium studies in hemodialysis patients before and after treatment with low dialysate magnesium. Nephron. 1984;37(1):25-29. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. http://dx.doi.org/10.1053/j.ajkd.2015.10.026
Serum Fractalkines and Cardiovascular Outcomes in the CRIC Study Cohort To the Editor: In a recently published article in AJKD based on findings from the CRIC (Chronic Renal Insufficiency Cohort), Shah et al1 conclude that serum CX3CL1 (fractalkine) level may contribute to both atherosclerosis and diabetes. However, the authors did not take into consideration the use of statins in CRIC participants, which is relevant because this treatment may potentially decrease serum CX3CL1 levels. CX3CL1 is expressed in certain cell types, such as macrophages and endothelial cells, and may contribute to atherogenesis by affecting cell migration, adhesion, and proliferation.2 Upregulation of CX3CL1 and its receptor, CX3CR1, is associated with plaque rupture in patients with unstable angina pectoris.3 Cimato and Palka4 observed that statins can reduce levels of circulating CX3CL1 and other inflammatory cytokines that regulate CX3CL1, and further experiments demonstrated that atorvastatin downregulates the expression of CX3CL1 and CX3CR1, which are primarily responsible for monocyte recruitment.5 Interestingly, statin therapy, an important therapeutic advance in cardiovascular and metabolic diseases, recently has been associated with newonset diabetes mellitus. 6 Therefore, any analysis of cardiovascular outcomes related to serum fractalkines should adjust for statin use in research participants. Unfortunately, the present article reporting on serum fractalkines and cardiovascular outcomes did not address or account for statin use in its analysis. Pingping Yang, MD, Gaosi Xu, MD, PhD Second Affiliated Hospital of Nanchang University, Nanchang, China Corresponding author: [email protected]
Acknowledgements Financial Disclosure: The authors declare that they have no relevant financial interests.
References 1. Shah R, Matthews GJ, Shah RY, et al. Serum fractalkine (CX3CL1) and cardiovascular outcomes and diabetes: findings from 342
the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2015;66(2):266-273. 2. Cefalu WT. Fractalkine: a cellular link between adipose tissue inflammation and vascular pathologies. Diabetes. 2010;60(5): 1380-1382. 3. Ikejima H, Imanishi T, Tsujioka H, et al. Upregulation of fractalkine and its receptor, CX3CR1, is associated with coronary plaque rupture in patients with unstable angina pectoris. Circ J. 2010;74(2):337-345. 4. Cimato TR, Palka BA. Fractalkine (CX3CL1), GM-CSF and VEGF-a levels are reduced by statins in adult patients. Clin Transl Med. 2014;3:14. 5. Nie P, Li D, Hu L, et al. Atorvastatin improves plaque stability in ApoE-knockout mice by regulating chemokines and chemokine receptors. PLoS One. 2014;9(5):e97009. 6. Fitchett DH, Hegele RA, Verma S. Statin intolerance. Circulation. 2015;131(13):e389-e391. Ó 2016 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2015.05.027
In Reply to ‘Serum Fractalkines and Cardiovascular Outcomes in the CRIC Study Cohort’ We thank Drs Yang and Xu for their commentary1 on our article.2 We agree that recent literature supports modulation of the fractalkine system by statins. As expected, a large number of patients from the CRIC Study reported statin use, though statin use did not differ among serum fractalkine quartiles in our preliminary analysis. Further analysis of how statin use modulated the effect of serum fractalkine on diabetes or cardiovascular outcomes in the CRIC cohort will be valuable. Rachana Shah, MD Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
References 1. Yang P, Xu G. Serum fractalkines and cardiovascular outcomes in the CRIC Study cohort. Am J Kidney Dis. 2016;67(2): 342. 2. Shah R, Matthews GJ, Shah RY, et al. Serum fractalkine (CX3CL1) and cardiovascular outcomes and diabetes: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2015;66(2):266-273. Ó 2016 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2015.10.028
RESEARCH LETTERS Creatinine Versus Cystatin C for Estimating GFR in Patients With Liver Cirrhosis To the Editor: Kidney function abnormalities worsen the prognosis of patients with liver cirrhosis1; a systematic review of patients with liver cirrhosis revealed a 7-fold increase in mortality (OR, 7.6) in those also having reduced kidney function.2 Therefore, kidney function is routinely evaluated in patients with liver cirrhosis; ideally this should be by highly accurate GFR measurement (by inulin, iothalamate, or 99Tc-DTPA clearance). This is often unavailable or difficult to perform due to cost and technical Am J Kidney Dis. 2016;67(2):341-347
Correspondence Table 1. Baseline Demographics Variable
All Groups (N 5 91)
MELD # 10 (n 5 34)
MELD .10-15 (n 5 31)
MELD . 15 (n 5 26)
Men:women Age, y Liver cirrhosis cause Hepatitis C virus Autoimmune hepatitis Cryptogenic Alcohol Primary biliary cirrhosis Nonalcoholic steatohepatitis Hepatitis C virus Others
43:48 50.7 6 11.8
19:15 50.6 6 11.1
17:14 52.3 6 10.9
12:14 49.1 6 13.9
29 (32) 14 (15) 12 (13) 10 (11) 9 (10) 7 (8) 2 (2) 8 (9)
7 (21) 5 (15) 6 (18) 3 (9) 6 (21) 3 (9) 2 (6) 2 (6)
15 (49) 6 (19) 2 (6) 2 (6) 1 (3) 3 (10) 0 (0) 2 (6)
7 (27) 3 (12) 4 (15) 5 (19) 2 (8) 1 (4) 0 (0) 4 (15)
Total bilirubin, mg/dL Albumin, g/dL Creatinine, mg/dL Serum urea nitrogen, mg/dL Cystatin C, mg/L Body mass index, kg/m2 mGFR, mL/min/1.73 m2 eGFRcr, mL/min/1.73 m2 eGFRcys, mL/min/1.73 m2 eGFRcr-cys, mL/min/1.73 m2
2.6 6 1.1 3.4 6 0.6 0.7 6 0.2 16.5 6 6.1 1.2 6 0.3 25.8 6 3.7 71.7 6 28.1 101.4 6 22.8 70.3 6 25.4 83.5 6 22.7
1.1 6 0.4 3.9 6 0.6 0.7 6 0.2 15.7 6 5.1 1.0 6 0.2 25.6 6 3.5 80.2 6 24.4 102.9 6 20.7 80.8 6 24.6 90.9 6 21.6
2.5 6 1.5 3.1 6 0.6 0.7 6 0.2 16.2 6 6.6 1.2 6 0.3 25.5 6 3.8 69.7 6 27.8 101.8 6 23.6 68.4 6 23.2 83.1 6 22.9
4.1 6 1.8 2.9 6 0.5 0.8 6 0.2 17.0 6 6.6 1.4 6 0.4 26.5 6 4.0 62.8 6 30.5 98.9 6 25.4 58.8 6 24.1 74.3 6 21.2
Note: Values for continuous variables are given as mean 6 standard deviation; for categorical variables, as number (percentage). Abbreviations: eGFR, estimated glomerular filtration rate; MELD, Model for End-Stage Liver Disease [score]; mGFR, measured glomerular filtration rate.
complexity. Serum creatinine (cr) is the most commonly used marker for estimating kidney function, including in individuals with liver cirrhosis. Nevertheless, it is unreliable in these patients because cr production is decreased (due to decreased hepatic synthesis of creatine, decreased muscle mass, restricted dietary protein intake, and a coexisting dilutional effect), particularly in advanced stages of liver cirrhosis.3,4 Cystatin C (cys) may be a better marker in patients with liver cirrhosis because it is produced by all nucleated cells and its serum levels are not significantly affected by race, age, muscle mass, or liver function.5 We designed an open cross-sectional observational study to compare the performance in patients with liver cirrhosis of 3 CKD Epidemiology Collaboration eGFR equations based on standardized cr and/or cys: CKD-EPIcr, CKD-EPIcys, and CKD-EPIcr-cys. The reference standard was mGFR based on urinary clearance of
mGFR – eGFR mL/min/1.73 m2
80
CKD-EPI creaƟnine equaƟon
= MELD ≤10 80
99
Tc-DTPA, as recommended in the KDOQI and KDIGO guidelines.6,7 Between January 2013 and July 2014, we included 95 patients older than 18 years who had a diagnosis of liver cirrhosis established after examination by a hepatologist and according to results of biochemical, histologic, endoscopic, and imaging studies. In addition, serum cr had to have remained stable for 3 months (variation # 0.3 mg/dL). Exclusion criteria were pregnancy; hyperthyroidism; active hepatocellular carcinoma; dialysisdependent CKD; inability to obtain mGFR due to technical, medical, or laboratory difficulties (in particular due to low urine volumes); or lack of written consent. In accordance with KDOQI guideline recommendations for validating eGFR equations,7 we defined bias as mGFR minus eGFR; percentage bias as bias divided by mGFR; accuracy as the percentage of eGFRs varying ,30% from mGFR (P30); and precision as the
= MELD >10 - < 15 CKD-EPI cystaƟn C equaƟon
= MELD ≥ 15 80 CKD-EPI creaƟnine-cystaƟn C equaƟon
60
60
60
40
40
40
20
20
20
0
0
0
-20
-20
-20
-40
-40
-60
r2
-80 -100
-60
= 0.57 Bias = -29.6 (-34.6 to -24.6) %Bias = -59.9 (-73.2 to -46.6) P30 = 40.6 (30.4 to 51.4) Precision = 31.0 (26.1 to 35.9)
0
25
50
75
100
-80 125
-100 0
-40 r2
= 0.59 Bias = 1.4 (-3.5 to 6.4) %Bias = -6.6 (-15.0 to 1.6) P30 = 62.6 (51.8 to 72.5) Precision = 25.9 (20.8 to 30.9)
25 50 75 100 125 EsƟmated GFR mL/min/1.73 m2
-60 r2 = 0.67 Bias = -11.7 (-16.1 to -7.4)
-80 %Bias = -28.6 (-38.1 to -19.1 ) -100 0
P30 = 60.4 (49.6 to 70.5) Precision = 23.1 (18.7 to 27.4)
25
50
75
100
125
Figure 1. Performance of eGFRcr, eGFRcys, and eGFRcr-cys in patients with liver cirrhosis. For detailed methods, see Item S1; r 5 Pearson correlation. Am J Kidney Dis. 2016;67(2):341-347
343
Correspondence interquartile range of the difference between mGFR and eGFR. A negative bias means mGFR overestimation, whereas a positive value reflects mGFR underestimation. Four patients were excluded due to difficulties measuring GFR; baseline demographics for the remaining 91 patients are in Table 1. As shown in Fig 1, eGFRcys performs better than eGFRcr, demonstrating less bias and better accuracy (P30 5 62.6%). However, bias of eGFRcr and eGFRcys vary according to eGFR. In contrast, bias of eGFRcr-cys is intermediate and appears to vary less by eGFR, while accuracy is similar to eGFRcys (60.4%). These results agree with others recently reported in different ethnic groups.8,9 Estimating kidney function is highly relevant in patients with liver cirrhosis, including in some cases the need to decide candidacy for liver or combined liver and kidney transplantation.10 The accuracies of eGFRcys and eGFRcr-cys are higher than eGFRcr, but are limited at low eGFRs. Therefore, we suggest measuring GFR (by inulin or 99Tc-DTPA clearance) if possible to make important decisions. Finally, due to difficulties involved in obtaining mGFR, there is an urgent need for an eGFR equation with superior performance to be developed, designed, and validated in liver cirrhosis populations. Aldo Torre, MSc, Jonathan Manuel Aguirre-Valadez, MD José Manuel Arreola-Guerra, MD Octavio René García-Flores, MD Ignacio García-Juárez, MD, Cristino Cruz-Rivera, BSc Ricardo Correa-Rotter, MD, José Antonio Niño-Cruz, MD Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México Corresponding author (JA Niño-Cruz): [email protected]
Acknowledgements The authors thank Drs Haydee Verduzco-Aguirre and Ariadna Karen Flores-Balbuena for assistance in sample collection. Support: None. Financial Disclosure: The authors declare that they have no relevant financial interests. Contributions: Research idea and study design: AT, JMA-V, JAN-C; data acquisition: ORG-F, CC-R; data analysis/interpretation: JAN-C, AT, JMA-G, JMA-V, IG-J, RC-R; statistical analysis: JMA-G; supervision or mentorship: AT, JAN-C. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. JAN-C takes responsibility that this study has been reported honestly, accurately, and transparently; that no important aspects of the study have been omitted, and that any discrepancies from the study as planned (and registered) have been explained.
Supplementary Material Item S1: Detailed methods. Note: The supplementary material accompanying this article (http://dx.doi.org/10.1053/j.ajkd.2015.09.022) is available at www.ajkd.org
References 1. Gines P, Schrier RW. Renal failure in cirrhosis. N Engl J Med. 2009;361(13):1279-1290. 2. Fede G, D’Amico G, Arvaniti V, et al. Renal failure and cirrhosis: a systematic review of mortality and prognosis. J Hepatol. 2012;56(4):810-818. 3. Orlando R, Floreani M, Padrini R, Palatini P. Evaluation of measured and calculated creatinine clearances as glomerular 344
filtration markers in different stages of liver cirrhosis. Clin Nephrol. 1999;51(6):341-347. 4. Cocchetto DM, Tschanz C, Bjornsson TD. Decreased rate of creatinine production in patients with hepatic disease: implications for estimation of creatinine clearance. Ther Drug Monit. 1983;5(2): 161-168. 5. White CA, Akbari A, Doucette S, et al. Effect of clinical variables and immunosuppression on serum cystatin C and betatrace protein in kidney transplant recipients. Am J Kidney Dis. 2009;54(5):922-930. 6. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Inter. 2013;3(suppl 1):1-150. 7. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(2)(suppl 1):S1S266. 8. De Souza V, Hadj-Aissa A, Dolomanova O, et al. Creatinineversus cystatine C-based equations in assessing the renal function of candidates for liver transplantation with cirrhosis. Hepatology. 2014;59(4):1522-1531. 9. Mindikoglu AL, Dowling TC, Weir MR, Seliger SL, Christenson RH, Magder LS. Performance of chronic kidney disease epidemiology collaboration creatinine-cystatin C equation for estimating kidney function in cirrhosis. Hepatology. 2014;59(4): 1532-1542. 10. Nadim MK, Sung RS, Davis CL, et al. Simultaneous liverkidney transplantation summit: current state and future directions. Am J Transplant. 2012;12(11):2901-2908. Received May 12, 2015. Accepted in revised form September 15, 2015. Originally published online October 31, 2015. Ó 2016 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2015.09.022
Latinos With Chronic Kidney Failure Treated by Dialysis: Understanding Their Palliative Care Perspectives To the Editor: Latinos are the fastest growing minority in the United States and have a nearly 2-fold faster progression from earlier stages of CKD to ESRD compared with non-Latino whites.1(pp96,101) Dialysis patients experience debilitating symptom burdens and high mortality; however, the literature suggests that despite growing awareness of the need for palliative care, symptoms are often untreated and care at the end of life (EOL) is aggressive and may not align with patient goals and values.2-5 Latinos bear a disproportionate burden of ESRD and are under-represented in existing ESRD palliative care research. Studies that highlight Latino EOL care and preferences have predominantly shown that Latinos are less likely to have advance directives, more likely to die in a hospital, and when faced with EOL decisions, prefer a familycentered decision-making model.6 As efforts are made to improve palliative care for all dialysis patients regardless of their ethnicity, it is important to recognize that cultural values profoundly affect care preferences. In this study, we describe the palliative care preferences and needs of adult Latino patients with chronic kidney failure treated by dialysis. This observational descriptive survey was approved by the Colorado Multi-Institutional Review Board (COMIRB no. 140938). Patients were consented and then surveyed one on one by Am J Kidney Dis. 2016;67(2):341-347
Serum Fractalkines and Cardiovascular Outcomes in the CRIC Study Cohort To the Editor: In a recently published article in AJKD based on findings from the CRIC (Chronic Renal Insufficiency Cohort), Shah et al1 conclude that serum CX3CL1 (fractalkine) level may contribute to both atherosclerosis and diabetes. However, the authors did not take into consideration the use of statins in CRIC participants, which is relevant because this treatment may potentially decrease serum CX3CL1 levels. CX3CL1 is expressed in certain cell types, such as macrophages and endothelial cells, and may contribute to atherogenesis by affecting cell migration, adhesion, and proliferation.2 Upregulation of CX3CL1 and its receptor, CX3CR1, is associated with plaque rupture in patients with unstable angina pectoris.3 Cimato and Palka4 observed that statins can reduce levels of circulating CX3CL1 and other inflammatory cytokines that regulate CX3CL1, and further experiments demonstrated that atorvastatin downregulates the expression of CX3CL1 and CX3CR1, which are primarily responsible for monocyte recruitment.5 Interestingly, statin therapy, an important therapeutic advance in cardiovascular and metabolic diseases, recently has been associated with newonset diabetes mellitus. 6 Therefore, any analysis of cardiovascular outcomes related to serum fractalkines should adjust for statin use in research participants. Unfortunately, the present article reporting on serum fractalkines and cardiovascular outcomes did not address or account for statin use in its analysis. Pingping Yang, MD, Gaosi Xu, MD, PhD Second Affiliated Hospital of Nanchang University, Nanchang, China Corresponding author: [email protected]
Acknowledgements Financial Disclosure: The authors declare that they have no relevant financial interests.
References 1. Shah R, Matthews GJ, Shah RY, et al. Serum fractalkine (CX3CL1) and cardiovascular outcomes and diabetes: findings from 342
the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2015;66(2):266-273. 2. Cefalu WT. Fractalkine: a cellular link between adipose tissue inflammation and vascular pathologies. Diabetes. 2010;60(5): 1380-1382. 3. Ikejima H, Imanishi T, Tsujioka H, et al. Upregulation of fractalkine and its receptor, CX3CR1, is associated with coronary plaque rupture in patients with unstable angina pectoris. Circ J. 2010;74(2):337-345. 4. Cimato TR, Palka BA. Fractalkine (CX3CL1), GM-CSF and VEGF-a levels are reduced by statins in adult patients. Clin Transl Med. 2014;3:14. 5. Nie P, Li D, Hu L, et al. Atorvastatin improves plaque stability in ApoE-knockout mice by regulating chemokines and chemokine receptors. PLoS One. 2014;9(5):e97009. 6. Fitchett DH, Hegele RA, Verma S. Statin intolerance. Circulation. 2015;131(13):e389-e391. Ó 2016 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2015.05.027
In Reply to ‘Serum Fractalkines and Cardiovascular Outcomes in the CRIC Study Cohort’ We thank Drs Yang and Xu for their commentary1 on our article.2 We agree that recent literature supports modulation of the fractalkine system by statins. As expected, a large number of patients from the CRIC Study reported statin use, though statin use did not differ among serum fractalkine quartiles in our preliminary analysis. Further analysis of how statin use modulated the effect of serum fractalkine on diabetes or cardiovascular outcomes in the CRIC cohort will be valuable. Rachana Shah, MD Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
References 1. Yang P, Xu G. Serum fractalkines and cardiovascular outcomes in the CRIC Study cohort. Am J Kidney Dis. 2016;67(2): 342. 2. Shah R, Matthews GJ, Shah RY, et al. Serum fractalkine (CX3CL1) and cardiovascular outcomes and diabetes: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study. Am J Kidney Dis. 2015;66(2):266-273. Ó 2016 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2015.10.028
RESEARCH LETTERS Creatinine Versus Cystatin C for Estimating GFR in Patients With Liver Cirrhosis To the Editor: Kidney function abnormalities worsen the prognosis of patients with liver cirrhosis1; a systematic review of patients with liver cirrhosis revealed a 7-fold increase in mortality (OR, 7.6) in those also having reduced kidney function.2 Therefore, kidney function is routinely evaluated in patients with liver cirrhosis; ideally this should be by highly accurate GFR measurement (by inulin, iothalamate, or 99Tc-DTPA clearance). This is often unavailable or difficult to perform due to cost and technical Am J Kidney Dis. 2016;67(2):341-347
Correspondence Table 1. Baseline Demographics Variable
All Groups (N 5 91)
MELD # 10 (n 5 34)
MELD .10-15 (n 5 31)
MELD . 15 (n 5 26)
Men:women Age, y Liver cirrhosis cause Hepatitis C virus Autoimmune hepatitis Cryptogenic Alcohol Primary biliary cirrhosis Nonalcoholic steatohepatitis Hepatitis C virus Others
43:48 50.7 6 11.8
19:15 50.6 6 11.1
17:14 52.3 6 10.9
12:14 49.1 6 13.9
29 (32) 14 (15) 12 (13) 10 (11) 9 (10) 7 (8) 2 (2) 8 (9)
7 (21) 5 (15) 6 (18) 3 (9) 6 (21) 3 (9) 2 (6) 2 (6)
15 (49) 6 (19) 2 (6) 2 (6) 1 (3) 3 (10) 0 (0) 2 (6)
7 (27) 3 (12) 4 (15) 5 (19) 2 (8) 1 (4) 0 (0) 4 (15)
Total bilirubin, mg/dL Albumin, g/dL Creatinine, mg/dL Serum urea nitrogen, mg/dL Cystatin C, mg/L Body mass index, kg/m2 mGFR, mL/min/1.73 m2 eGFRcr, mL/min/1.73 m2 eGFRcys, mL/min/1.73 m2 eGFRcr-cys, mL/min/1.73 m2
2.6 6 1.1 3.4 6 0.6 0.7 6 0.2 16.5 6 6.1 1.2 6 0.3 25.8 6 3.7 71.7 6 28.1 101.4 6 22.8 70.3 6 25.4 83.5 6 22.7
1.1 6 0.4 3.9 6 0.6 0.7 6 0.2 15.7 6 5.1 1.0 6 0.2 25.6 6 3.5 80.2 6 24.4 102.9 6 20.7 80.8 6 24.6 90.9 6 21.6
2.5 6 1.5 3.1 6 0.6 0.7 6 0.2 16.2 6 6.6 1.2 6 0.3 25.5 6 3.8 69.7 6 27.8 101.8 6 23.6 68.4 6 23.2 83.1 6 22.9
4.1 6 1.8 2.9 6 0.5 0.8 6 0.2 17.0 6 6.6 1.4 6 0.4 26.5 6 4.0 62.8 6 30.5 98.9 6 25.4 58.8 6 24.1 74.3 6 21.2
Note: Values for continuous variables are given as mean 6 standard deviation; for categorical variables, as number (percentage). Abbreviations: eGFR, estimated glomerular filtration rate; MELD, Model for End-Stage Liver Disease [score]; mGFR, measured glomerular filtration rate.
complexity. Serum creatinine (cr) is the most commonly used marker for estimating kidney function, including in individuals with liver cirrhosis. Nevertheless, it is unreliable in these patients because cr production is decreased (due to decreased hepatic synthesis of creatine, decreased muscle mass, restricted dietary protein intake, and a coexisting dilutional effect), particularly in advanced stages of liver cirrhosis.3,4 Cystatin C (cys) may be a better marker in patients with liver cirrhosis because it is produced by all nucleated cells and its serum levels are not significantly affected by race, age, muscle mass, or liver function.5 We designed an open cross-sectional observational study to compare the performance in patients with liver cirrhosis of 3 CKD Epidemiology Collaboration eGFR equations based on standardized cr and/or cys: CKD-EPIcr, CKD-EPIcys, and CKD-EPIcr-cys. The reference standard was mGFR based on urinary clearance of
mGFR – eGFR mL/min/1.73 m2
80
CKD-EPI creaƟnine equaƟon
= MELD ≤10 80
99
Tc-DTPA, as recommended in the KDOQI and KDIGO guidelines.6,7 Between January 2013 and July 2014, we included 95 patients older than 18 years who had a diagnosis of liver cirrhosis established after examination by a hepatologist and according to results of biochemical, histologic, endoscopic, and imaging studies. In addition, serum cr had to have remained stable for 3 months (variation # 0.3 mg/dL). Exclusion criteria were pregnancy; hyperthyroidism; active hepatocellular carcinoma; dialysisdependent CKD; inability to obtain mGFR due to technical, medical, or laboratory difficulties (in particular due to low urine volumes); or lack of written consent. In accordance with KDOQI guideline recommendations for validating eGFR equations,7 we defined bias as mGFR minus eGFR; percentage bias as bias divided by mGFR; accuracy as the percentage of eGFRs varying ,30% from mGFR (P30); and precision as the
= MELD >10 - < 15 CKD-EPI cystaƟn C equaƟon
= MELD ≥ 15 80 CKD-EPI creaƟnine-cystaƟn C equaƟon
60
60
60
40
40
40
20
20
20
0
0
0
-20
-20
-20
-40
-40
-60
r2
-80 -100
-60
= 0.57 Bias = -29.6 (-34.6 to -24.6) %Bias = -59.9 (-73.2 to -46.6) P30 = 40.6 (30.4 to 51.4) Precision = 31.0 (26.1 to 35.9)
0
25
50
75
100
-80 125
-100 0
-40 r2
= 0.59 Bias = 1.4 (-3.5 to 6.4) %Bias = -6.6 (-15.0 to 1.6) P30 = 62.6 (51.8 to 72.5) Precision = 25.9 (20.8 to 30.9)
25 50 75 100 125 EsƟmated GFR mL/min/1.73 m2
-60 r2 = 0.67 Bias = -11.7 (-16.1 to -7.4)
-80 %Bias = -28.6 (-38.1 to -19.1 ) -100 0
P30 = 60.4 (49.6 to 70.5) Precision = 23.1 (18.7 to 27.4)
25
50
75
100
125
Figure 1. Performance of eGFRcr, eGFRcys, and eGFRcr-cys in patients with liver cirrhosis. For detailed methods, see Item S1; r 5 Pearson correlation. Am J Kidney Dis. 2016;67(2):341-347
343
Correspondence interquartile range of the difference between mGFR and eGFR. A negative bias means mGFR overestimation, whereas a positive value reflects mGFR underestimation. Four patients were excluded due to difficulties measuring GFR; baseline demographics for the remaining 91 patients are in Table 1. As shown in Fig 1, eGFRcys performs better than eGFRcr, demonstrating less bias and better accuracy (P30 5 62.6%). However, bias of eGFRcr and eGFRcys vary according to eGFR. In contrast, bias of eGFRcr-cys is intermediate and appears to vary less by eGFR, while accuracy is similar to eGFRcys (60.4%). These results agree with others recently reported in different ethnic groups.8,9 Estimating kidney function is highly relevant in patients with liver cirrhosis, including in some cases the need to decide candidacy for liver or combined liver and kidney transplantation.10 The accuracies of eGFRcys and eGFRcr-cys are higher than eGFRcr, but are limited at low eGFRs. Therefore, we suggest measuring GFR (by inulin or 99Tc-DTPA clearance) if possible to make important decisions. Finally, due to difficulties involved in obtaining mGFR, there is an urgent need for an eGFR equation with superior performance to be developed, designed, and validated in liver cirrhosis populations. Aldo Torre, MSc, Jonathan Manuel Aguirre-Valadez, MD José Manuel Arreola-Guerra, MD Octavio René García-Flores, MD Ignacio García-Juárez, MD, Cristino Cruz-Rivera, BSc Ricardo Correa-Rotter, MD, José Antonio Niño-Cruz, MD Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, México Corresponding author (JA Niño-Cruz): [email protected]
Acknowledgements The authors thank Drs Haydee Verduzco-Aguirre and Ariadna Karen Flores-Balbuena for assistance in sample collection. Support: None. Financial Disclosure: The authors declare that they have no relevant financial interests. Contributions: Research idea and study design: AT, JMA-V, JAN-C; data acquisition: ORG-F, CC-R; data analysis/interpretation: JAN-C, AT, JMA-G, JMA-V, IG-J, RC-R; statistical analysis: JMA-G; supervision or mentorship: AT, JAN-C. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. JAN-C takes responsibility that this study has been reported honestly, accurately, and transparently; that no important aspects of the study have been omitted, and that any discrepancies from the study as planned (and registered) have been explained.
Supplementary Material Item S1: Detailed methods. Note: The supplementary material accompanying this article (http://dx.doi.org/10.1053/j.ajkd.2015.09.022) is available at www.ajkd.org
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Latinos With Chronic Kidney Failure Treated by Dialysis: Understanding Their Palliative Care Perspectives To the Editor: Latinos are the fastest growing minority in the United States and have a nearly 2-fold faster progression from earlier stages of CKD to ESRD compared with non-Latino whites.1(pp96,101) Dialysis patients experience debilitating symptom burdens and high mortality; however, the literature suggests that despite growing awareness of the need for palliative care, symptoms are often untreated and care at the end of life (EOL) is aggressive and may not align with patient goals and values.2-5 Latinos bear a disproportionate burden of ESRD and are under-represented in existing ESRD palliative care research. Studies that highlight Latino EOL care and preferences have predominantly shown that Latinos are less likely to have advance directives, more likely to die in a hospital, and when faced with EOL decisions, prefer a familycentered decision-making model.6 As efforts are made to improve palliative care for all dialysis patients regardless of their ethnicity, it is important to recognize that cultural values profoundly affect care preferences. In this study, we describe the palliative care preferences and needs of adult Latino patients with chronic kidney failure treated by dialysis. This observational descriptive survey was approved by the Colorado Multi-Institutional Review Board (COMIRB no. 140938). Patients were consented and then surveyed one on one by Am J Kidney Dis. 2016;67(2):341-347