Deceased-Donor Kidneys: Is Past Performance an Indicator of Future Transplant Success?
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See Clinical Research on Page 2075 There continues to be a disparity between the number of kidneys available for transplantation and the number of patients with end-stage kidney disease. Although kidney transplantation remains the best treatment option for most patients with end-stage kidney disease, the current demand still outpaces organ supply. Because of the mortality associated with remaining on the waitlist, higher-risk kidneys, such as those from donors with acute kidney injury, are increasingly being considered for transplantation. Such kidneys are usually used in recipients with shorter post-transplant life expectancies. Historically, kidney allocation systems have attempted to optimize organ use by incorporating donor factors in prediction models and risk scores. This has helped health care professionals better stratify deceased-donor organs for allocation, while also facilitating clinical decision making and helping guide counseling of recipient candidates. As such, it is important to understand how donor kidney characteristics relate to recipient outcomes. Donor serum creatinine, in particular, continues to be the primary marker for determining donor kidney function and predicting recipient graft function, but which time point to use for the donor serum creatinine value remains an open question. Prior to 2014, deceased-donor kidneys in the United States were classified as either “standard criteria” or “expanded criteria” donor kidneys based on 4 factors—age, “terminal” serum creatinine, history of hypertension, and cause of death.1Organ Procurement and Transplantation Network Policy 8: Allocation of Kidneys.https://optn.transplant.hrsa.gov/governance/policies/Google Scholar Kayler et al.2Kayler L.K. Garzon P. Magliocca J. et al.Outcomes and utilization of kidneys from deceased donors with acute kidney injury.Am J Transplant. 2009; 9: 367-373Crossref PubMed Scopus (91) Google Scholar evaluated recipient outcomes of kidneys from adult donors using US transplant registry data from 1995 to 2007. They found that standard criteria donor kidneys with elevated terminal serum creatinine values were more likely to be discarded. However, when such organs were transplanted, the elevated terminal creatinine was not a significant risk factor for graft loss. On the other hand, in recipients of expanded criteria donor kidneys, higher terminal creatinine was associated with an increased risk of graft loss. As a part of the ongoing quest to better predict the future performance of deceased-donor kidneys, the new kidney allocation system in 2014 replaced the standard or expanded criteria donor classification with the kidney donor profile index (KDPI), which provides an estimate of the risk of post-transplant graft loss compared with deceased-donor kidneys from the previous year. As a continuous marker, the KDPI was thought to be a better indicator than the binary standard or expanded criteria donor classification.1Organ Procurement and Transplantation Network Policy 8: Allocation of Kidneys.https://optn.transplant.hrsa.gov/governance/policies/Google Scholar The KDPI is derived from the kidney donor risk index, which incorporates 10 donor factors, some of which were also used in the previous standard or expanded criteria donor classification. Interestingly, though the KDPI and kidney donor risk index scores are US-centric, they may have utility in other countries as well.3Dahmen M. Becker F. Pavenstadt H. Suwelack B. Schutte-Nutgen K. Reuter S. Validation of the Kidney Donor Profile Index (KDPI) to assess a deceased donor's kidneys' outcome in a European cohort.Sci Rep. 2019; 9: 11234Crossref PubMed Scopus (28) Google Scholar,4Clayton P.A. Dansie K. Sypek M.P. et al.External validation of the US and UK kidney donor risk indices for deceased donor kidney transplant survival in the Australian and New Zealand population.Nephrol Dial Transplant. 2019; 34: 2127-2131Crossref PubMed Scopus (17) Google Scholar Clayton et al.4Clayton P.A. Dansie K. Sypek M.P. et al.External validation of the US and UK kidney donor risk indices for deceased donor kidney transplant survival in the Australian and New Zealand population.Nephrol Dial Transplant. 2019; 34: 2127-2131Crossref PubMed Scopus (17) Google Scholar found that the US kidney donor risk index score was a moderately good predictor of death-censored and overall graft survival in the Australian and New Zealand populations. Although the kidney donor risk index is not used for allocation in Australia, it is reported to clinicians and has implications for decisions about organ acceptance. Subsequent research has focused on further improving the predictive power of the KDPI score by more carefully examining the role of the individual factors that comprise the score. Chiles et al.5Chiles M.C. Husain S.A. Skillen W. et al.Predictive value of using initial versus terminal deceased donor creatinine to calculate the kidney donor risk index.Am J Kidney Dis. 2017; 70: 153-154Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar explored the relationship between initial versus terminal donor creatinine and its impact on KDPI for predicting graft outcomes in the United States. They used data from the Organ Procurement and Transplantation Network to perform a retrospective cohort study of 104,510 kidney transplants (20% of which came from donors with acute kidney injury), and found that 55% of the kidneys changed KDPI categories when the initial serum creatinine was used instead of the terminal serum creatinine (35% changed to a worse KDPI category). They found no consequential differences in graft loss or death-censored graft failure at 1 and 3 years after transplant. Their results were similar when the analysis was limited to kidneys from donors with acute kidney injury. Although this was ultimately a negative study, a more nuanced understanding of the individual KDPI factors could lead to better predictions of post-transplant outcomes. In this edition of KI Reports, Irish et al.6Irish G.L. Coates P.T. Clayton P.A. Association of admission, nadir, and terminal donor creatinine with kidney transplantation outcomes.Kidney Int Rep. 2021; 6: 2075-2083Abstract Full Text Full Text PDF Scopus (2) Google Scholar investigate whether donor admission, terminal, or highest estimated glomerular filtration rate (eGFR) best predicted post-transplant outcomes. It is important to note that only admission and last recorded serum creatinine are collected in the registry, and “highest” eGFR is simply the higher of the 2 values. Data were obtained from the Australian and New Zealand organ donation dialysis and transplant registries (ANZDATA) between 2003 and 2019. The authors first focus on delayed graft function. An important finding was that higher terminal eGFR for both male and female donors was associated with lower risk of delayed graft function. For male donors, every 10–ml/min per 1.73 m2 increase in terminal eGFR corresponded to a 10% decrease in the likelihood of delayed graft function; for female donors, the same increase in terminal eGFR was associated with a 15% decrease in the likelihood of delayed graft function. Similar associations were observed using highest eGFR. Notably, admission eGFR did not appear to have as strong an association (4% for male donors and 10% for female donors). Next, the authors studied the impact of donor eGFR on 6-month and 12-month recipient eGFR. The same 10–ml/min per 1.73 m2 increase in terminal eGFR was associated with only a 0.69–ml/min per 1.73 m2 increase in 6-month recipient eGFR and a 0.62–ml/min per 1.73 m2 increase in 12-month recipient eGFR. The corresponding increases in recipient eGFR based on the highest donor eGFR were 0.8 ml/min per 1.73 m2 for 6-month and 0.83 ml/min per 1.73 m2 for 12-month recipient eGFR. In contrast, for the donor admission eGFR, these increases were 0.58 and 0.63 ml/min per 1.73 m2 for the 6-month and 12-month values, respectively. It is important to note that though the correlations are strong, the effect sizes for the 6-month and 12-month eGFRs are small in comparison to the effect sizes observed for delayed graft function. Similar small effect sizes were observed for graft loss and death-censored graft failure. Donor eGFR was a predictor for graft survival across all models, and the association was strongest for terminal eGFR. Overall, Irish et al. have produced a comprehensive study of donor kidney function at different time points showing strong evidence of association with clinically relevant outcomes; however, the strengths of association were more pronounced for the earlier post-transplant outcome (i.e., delayed graft function) rather than longer-term outcomes. Donor eGFR based on serum creatinine showed no evidence of association with patient survival, which is consistent with the idea that recipient factors are more likely to be influential at later time points. When analyzing the cumulative hazard for death-censored graft failure, donor terminal eGFR performed better than highest or admission eGFR. The authors acknowledge the small effect sizes across the board and recognize the marginal benefit of using terminal eGFR over admission and highest eGFR. They also note that calculating eGFR during the donor’s hospitalization limits its accuracy as the serum creatinine values may not be at a steady state during critical illness. Despite the aforementioned limitations, these findings appear to lend support to the current practice of using terminal eGFR/serum creatinine to predict early transplant outcomes. Moving forward, as we enter the era of precision medicine (Figure 1), investigators will likely further explore the relationship between other donor kidney variables, such as biomarkers or predisposing genetic variations, for their utility in risk prediction and organ allocation. For instance, Julian et al.7Julian B.A. Gaston R.S. Brown W.M. et al.Effect of replacing race with apolipoprotein L1 genotype in calculation of kidney donor risk index.Am J Transplant. 2017; 17: 1540-1548Crossref PubMed Scopus (44) Google Scholar showed that using APOL1 genotypes instead of race in donors of recent African ancestry as part of a refined kidney donor risk index could improve allocation by providing these good-quality kidneys to recipients with longer estimated post-transplant survival. Comparing donor and recipient HLA epitopes, which are antigenically important subunits critical for antibody binding, may also make certain antigen mismatches acceptable and provide additional information for decision making around kidney allocation and induction immunosuppression to improve transplant outcomes. However, these advances may pose challenges to health care professionals and policy makers seeking to balance utility and equity.8Caulfield T. Murdoch B. Sapir-Pichhadze R. Keown P. Policy challenges for organ allocation in an era of "precision medicine.".Can J Kidney Health Dis. 2020; 7 (2054358120912655)Crossref PubMed Scopus (3) Google Scholar The findings in this article constitute a small but important step in the endeavor to better understand the predictive power of deceased-donor score-based systems for recipient outcomes. Such score-based systems will likely help make better decisions in terms of organ discard and facilitate improved matching of donor kidneys with appropriate recipient profiles. This work not only has implications for patients from Australia and New Zealand but could help refine the interpretation of KDPI scores for patients in other countries as well. More evidence quantifying these effect sizes is needed, however, before large-scale re-evaluations of existing scoring systems are undertaken. All the authors declared no competing interests. Association of Admission, Nadir, and Terminal Donor Creatinine With Kidney Transplantation OutcomesKidney International ReportsVol. 6Issue 8PreviewWhen assessing deceased kidney donors, a key factor in organ acceptance and allocation is donor kidney function. It is unclear whether terminal, admission, or the highest of terminal and admission donor estimated glomerular filtration rate (eGFR) most predicts recipient outcomes. 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To compare the conventional creatinine clearance measured on 24-h urine collection with the estimated Glomerular Filtration Rate by Cockcroft & Gault (CG) and Modification of Diet in Renal Disease (MDRD) prediction equations in adults aged 20 years and above in Pakistani population.All the patients, including inpatient admitted in hospital and outpatients, more than 20 years of age, reporting for the test of creatinine clearance in clinical chemistry department of Dr. Ziauddin Hospital clinical laboratory from 1st January to 31st December 2006 were studied.Comparison was made between conventional creatinine clearance and Cockcroft & Gault (CG) and Modification of Diet in Renal Disease (MDRD) prediction equations on 369 cases which revealed strong correlation with conventional creatinine clearance, MDRD equation has better correlation as compared with Cockcroft- Gault creatinine clearance. Statistical correlation was better in cases where serum creatinine was more than 1.50 mg/dl (r = 0.625 for Cockcroft- Gault creatinine clearance and r = 0.724 for MDRD equation) as compared when serum creatinine levels were less than 1.50 mg/dl (r = 0.608 for Cockcroft- Gault creatinine clearance and r = 0.596 for MDRD equation). There was positive bias in both calculated GFRs from conventional creatinine clearance in healthy as well as diseased population.The creatinine based formulas with their inherent property of convenience and cost effectiveness can be a useful tool for monitoring the progression of disease. They can be applied in clinical practice on our population but they should be interpreted with caution as they over estimate the GFR.
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Background: Chronic kidney disease is a life threatening disease, which is a common cause of mortality and morbidity. The chronic kidney disease patients are at high risk of developing end stage renal disease, cardiovascular complications and stroke. Therefore, we carried out this study to know the functional status of kidneys in chronic kidney disease cases and to classify the chronic kidney disease into different stages by calculating estimated glomerular filtration rate. Material and Methods: Twenty five cases of chronic kidney disease, between 25-70 years of age of either sex, admitted at R.L.Jalappa Hospital and Research Centre, Kolar, India and twenty five healthy age and gender matched controls were enrolled into the study. For calculating estimated glomerular filtration rate serum creatinine values, age, sex, race, and weight of the patients are considered. Results: The mean estimated glomerular filtration rate in cases was 22.096 and in control group 118.28(p<0.001) as per Cockcroft Gault Equation and as per Modification of Diet in Renal Disease equation in cases it was 18.176 and in controls 113.796(p<0.001). The estimated glomerular filtration rate was significantly low in cases when compared with healthy subjects. Conclusion: Estimated glomerular filtration rate better predicts the functional status of kidneys and is more accurate than serum creatinine and can be used to classify chronic kidney disease. Key words: Chronic kidney disease (CKD), Cockcroft Gault Equation (CCG), Estimated Glomerular Filtration Rate (eGFR), End Stage Renal Disease (ESRD), glomerular filtration rate (GFR), Modification of Diet in Renal Disease(MDRD), Serum creatinine.
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We evaluated cystatin C concentration as a marker of glomerular filtration rate in renal transplant recipients, and its correlation with creatinine-based glomerular filtration rate by urinary creatinine clearance, and the Cockroft-Gault and Modification of Diet in Renal Disease formulas.In this cross-sectional study, we measured serum cystatin C levels and its correlation with serum creatinine, creatinine clearance, and glomerular filtration rate using the Cockroft-Gault formula and Modification of Diet in Renal Disease formulas.One hundred two recipients between June and December 2012, were examined. The mean subject age was 31.87 ± 8.37 years; the male:female ratio was 4.3:1. Mean serum creatinine concentration was 141.44 ± 43.31 mol/L (1.60 ± 0.49 mg/dL) and serum cystatin C 122.09 ± 38.95 nmol/L (1.63 ± 0.52 mg/L). Serum cystatin C was significantly correlated with serum creatinine (r=0.90; P<.001), creatinine clearance (r=0.77; P<.001), and the Cockroft-Gault (r=0.73; P<.001) and the Modification of Diet in Renal Disease formulas (r=0.82; P<.001). We assessed the correlation among serum cystatin C with serum creatinine, creatinine clearance, the Cockroft-Gault and Modification of Diet in Renal Disease at 1, 2-3, 4-5, and more than 5 years after transplant. The correlation between serum cystatin C and serum creatinine ranged from 0.8 to 1.0; cystatin C and creatinine clearance ranged from 0.8 to 0.85; serum cystatin C and the Cockroft-Gault Formula ranged from 0.7 to 0.8; and serum cystatin C and the Modification of Diet in Renal Disease formulas ranged from 0.8 to 0.84.Our results show that serum cystatin C is a reliable marker for estimating glomerular filtration rate among renal transplant recipients. This test can determine the glomerular filtration rate of renal transplant recipients on follow-up. Further studies are required to establish serum cystatin C as a standard test for monitoring glomerular filtration rate in transplanted patients.
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Creatinine-based equations are used as standard ways to estimate glomerular filtration rate and kidney function. Unfortunately, serum creatinine varies based on factors such as age, gender, and muscle mass. Overestimation of renal function by creatinine-based equations can be dangerous for renally dosed medications, such as enoxaparin. We present a patient who developed spontaneous bleeding on enoxaparin where kidney function was significantly overestimated by creatinine-based equations. The use of cystatin C levels, which are creatinine independent, can provide a better prediction of renal function.
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We compared creatinine concentrations in serum and urine and creatinine clearances determined by two Jaffé (Beckman's "Astra," Boehringer Mannheim Diagnostics) and two enzymatic (Kodak, Boehringer Mannheim Diagnostics) methods. Serum creatinine and creatinine clearances determined by each method were also compared with the glomerular filtration rate as measured with use of sodium [125I]iothalamate in patients with a wide range of renal function. Results between methods correlated excellently, but we saw clear method-dependent biases of up to 2.9 mg/L for serum. The highest serum creatinine values and the lowest creatinine clearances were obtained with Boehringer Mannheim Diagnostics' Jaffé method. The reciprocal of the serum creatinine and the creatinine clearance also correlated well with the glomerular filtration rate, but all methods over-estimated the glomerular filtration rates to varying degrees. Appropriate standardization of methods appears to be as important as method principle for establishing an accurate relationship between creatinine determinations and glomerular filtration rate.
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Serum creatinine remains the most widely used measure of renal function in clinical practice and in clinical trials. However, the serum concentration reflects not only renal excretion, which is composed of filtration and tubular secretion, but also the generation, intake, and metabolism of creatinine. Thus, serum creatinine does not provide an adequate estimate of glomerular filtration rate (GFR). Creatinine clearance is also an inaccurate and imprecise measure of GFR in clinical practice. The questions concerning the abnormality or the change of glomerular function can be answered with greater accuracy and precision by serum creatinine if the factors affecting its concentration are taken into account. The slope of the decline in reciprocal serum creatinine versus time does not accurately reflect changes in creatinine clearance and does not allow an accurate assessment of the rate of progression of renal disease. It can even be hazardous to use such value to observe the efficacy of treatments for progressive renal diseases.
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Objective To evaluation of endogenous clearance marker glomerular filtration rate(GFR) in patients with various types of renal diseases.Methods We determined the serum cystatin C,urea,creatinine,and creatinine clearance levels in 57 patients with renal diseases,and 39 healthy controls,and compared the concentrations of patients with of healthy controls.Results The concentratons of serum urea,creatinine,and creatinine clearance was found to be significantly higher in the patients with renal diseases in comparison to the healthy controls(P0.01).Correlation was observed between cystatin C and creatinine clearance levels(P0.05),and between cystatin C and creatinine levels(P0.01).However,there were not correlation between creatinine and urea concentrations(P0.05),and between creatinine and creatinine clearance lenels(P0.05).Conclusion Serum cystatin C is probably more attractive for estimation of renal function than urea,creatinine,and creatinine clearance for detection of GFR in patients with early kidney diseases.
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Creatinine is a metabolite excreted mainly by glomerular filtration, which makes it an important endogenous indicator of kidney function. Creatinine clearance is defined as the ratio of the concentration of creatinine in serum and urine. It assesses glomerular filtration. Creatinine and creatinine clearance have the leading role in the early diagnosis, monitoring and classification of chronic kidney disease. The routine method for determining the concentration of creatinine is the Jaffé photometric method. A newer version is the compensated method. Furthermore, the recommended equation for the estimation of glomerular filtration rate (GFR) is the one based on the MDRD study (eGFR) intended for people over 18 years. The aim of the study was to evaluate how the introduction of the compensated method would affect the clinical use and influence the assessment of GFR in the interpretation of findings and treatment monitoring for people over 20 years. The study group included 130 men and 142 women whose requested laboratory test was creatinine clearance. Data were collected over 20 days at Sestre milosrdnice University Hospital. Serum creatinine concentration and eGFR were determined by the compensated and uncompensated Jaffé method. In conclusion, the compensated creatinine method is not statistically comparable with the uncompensated method, but is clinically fully applicable to the general population above the age of 20, given that the reference intervals are changed. Comparison of eGFR as estimated by the compensated and uncompensated methods to determine creatinine concentration showed the same results as the comparison of clearance. Using the compensated method yielded statistically incomparable results in GFR estimation. However, in clinical practice, patient classification according to stages of chronic kidney disease (CKD) was comparable in the male group according to clearance and eGFR (pi=0.922 and pi=0.230, respectively), while the female group was classified significantly different according to clearance and eGFR (pi<0.016 and pi<0.001, respectively). Switching to the compensated creatinine method while simultaneously applying the eGFR formula was shown to be valid, as patient classification according to CKD stages was comparable (pi=0.921); thus, the methods are reliable for use instead of creatinine clearance in the general population with various diagnoses, which can be noted in all laboratories and which is, although inhomogeneous, routinely used to measure daily creatinine clearance.
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