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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2020  |  Volume : 31  |  Issue : 5  |  Page : 998-1005
Impact of One-Year Serum Creatinine on Long-term Renal Graft Survival in a Living-Related Renal Transplant Program


1 Department of Chemical Pathology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
2 Department of Urology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
3 Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan

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Date of Web Publication21-Nov-2020
 

   Abstract 


This study was carried out to determine the impact of one-year posttransplant serum creatinine (SCr) levels on the long-term outcomes of living-related donor kidney transplants. A retrospective cohort study included 773 adult living-related renal transplant recipients from 2010 to 2012, with a minimum follow-up period of five years. Demographics and posttransplantation follow-up data including immunosuppression regimens, rejection episodes, and survival rates were evaluated. Patients were divided into four cohorts (G1, G2, G3, and G4 based on SCr at the end of the 1st year: G1, SCr <88.4 μ mol/L; G2, 88.5≤ SCr ≤ 132.6 μmol/L; G3, 132.7≤ SCr ≤176.8 mol/L; and G4, SCr ≥176.9 μ mol/L). Comparisons between the groups used the Chi-square test for qualitative parameters and analysis of variance for continuous variables. Five-year graft survival for G1 was 98% as compared to 76% in G4 (P <0.001). Recipients of G4 encountered more acute rejection episodes in 21% of the cases as compared to 7.3% in G1 (P = 0.001). Donors were older in G4 (42.07 ± 10.4 years) as compared to G1 (30.1 ± 8.5 years) (P = 0.001). A third of the donors in G1 were HLA identical as compared to 7% in G4. Prediction of long-term graft survival is possible by the SCr level at one year post transplant. This can be of great importance, especially to identify those patients who require close monitoring in follow-up. Donor age, HLA, and acute rejection impact SCr at one year and hence graft outcome.

How to cite this article:
Nawaz SH, Zafar MN, Afzal M, Anwar Naqvi SA, Mubarak M, Hasan Rizvi S A. Impact of One-Year Serum Creatinine on Long-term Renal Graft Survival in a Living-Related Renal Transplant Program. Saudi J Kidney Dis Transpl 2020;31:998-1005

How to cite this URL:
Nawaz SH, Zafar MN, Afzal M, Anwar Naqvi SA, Mubarak M, Hasan Rizvi S A. Impact of One-Year Serum Creatinine on Long-term Renal Graft Survival in a Living-Related Renal Transplant Program. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2020 Dec 2];31:998-1005. Available from: https://www.sjkdt.org/text.asp?2020/31/5/998/301204



   Introduction Top


Kidney transplantation is the therapy of choice for patients with end-stage renal disease (ESRD).[1] Advancement in immunosuppression and surgical techniques has improved short-term graft survival; however, good long-term outcomes remain a challenge. A number of factors including recipient age and gender, donor age and gender, donor renal function, and acute rejection have been shown to influence graft outcomes.[3],[4],[5],[6] In recent years, serum creatinine (SCr) levels in the early transplant period have been identified as a surrogate marker to predict long-term outcomes in kidney transplantation.[5],[7],[8],[9] Prediction of outcome in recipients, who have reached one year post transplantation, is particularly important since graft survival beyond this period has largely been resistant to the therapeutic advances.[10] In this study, we have examined the impact of posttransplant SCr level at one year on long-term graft survival in a living-related donor kidney transplantation program in an emerging economy.


   Patients and Methods Top


This retrospective study was performed at the Sindh Institute of Urology and Transplantation, Karachi. We included 773 first living donor renal transplant recipients from January 2010 to December 2012, with a minimum follow-up period of five years. Exclusion criteria were children <18 years of age.

Recipient, donor demographics and clinical characteristics were obtained from our electronic database, which holds longitudinal information of all renal transplants performed at our center. Renal function in the 1st year was expressed as SCr obtained from the medical records. The study was approved by our institutional review board. Data were deidentified by removing patients’ names and hospital numbers. Patients were divided into four cohorts (G1, G2, G3, and G4 based on level of SCr at the end of the 1st year: Group G1, SCr <88.4 μmol/L; Group G2, 88.5≤ SCr ≤132.6 μmol/L; Group G3, 132.7≤ SCr ≤176.8 μmol/L; and Group G4, SCr ≥176.9 μmol/L).


   Statistical Analysis Top


The baseline characteristics of the recipients and donors were assessed by descriptive statistics. Categorical variables were summarized as frequencies and percentages. Continuous variables were assessed and presented means (standard deviation). For death censored graft survival analyses, the follow-up period was defined from the time of transplantation to the time of graft failure. Those who did not experience graft failure were censored at the time of death or at the end of the follow-up period. The proportions free from graft failure were calculated using the Kaplan–Meier method. Graft survival rates were determined using an actuarial method and compared with the log-rank test. The analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 10.0 (SPSS Inc., Chicago IL, USA), with P <0.05 considered to be statistically significant.


   Results Top


The demographic, clinical, and laboratory characteristics of the 773 renal transplant recipients are given in [Table 1]. The mean age was 32.5 ± 9.2 years, where 632 (82%) were male. The mean SCr at the end of the 1st year was 166.68 ± 30.05 μmol/L. Etiology of ESRD was unknown in 64.6% of the recipients as they presented late with small shrunken kidneys. In majority of the recipients, maintenance immunosuppression was by cyclosporine A (CyA), azathioprine, and steroids. In the follow-up period after the 1st year of transplant, 80 (10.3%) encountered acute rejection episodes. Majority (69.6%) developed hypertension, and 156 (22.5%) had recurrent urinary tract infections.
Table 1: Characteristics of renal transplant recipients (n = 773).

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The demographic, clinical, and laboratory characteristics of the 773 living-related kidney donors are given in [Table 2]. The mean age of the donors was 34.4 ± 9.8 years. Majority of the donors were male 440 (56.9%). The mean HLA match was 3.8 ± 1.6 where 179 (23.2%) were HLA identical. Majority of the donors were siblings 457 (59.1%).
Table 2: Characteristics of living-related kidney donors (n=773).

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The characteristics of recipients in different groups according to SCr at one-year post transplant are given in [Table 3]. Recipients of G1 encountered acute rejection episodes in 7.3% of the cases as compared to 21% in G4 (P = 0.001). Maintenance immunosuppression at the last follow-up in G1 was mainly CyA (87%) as compared to G4 where mTOR inhibitors were used in 37% of the recipients. There were no differences in comorbidities or chronic infections in the different groups. The characteristics of donors in different creatinine groups are given in [Table 4]. Donors were older in G4 as compared to G1 (P = 0.001).
Table 3: Characteristics of renal transplant recipients in different creatinine groups (n=773).

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Table 4: Characteristics of living-related kidney donors in different creatinine groups (n = 773).

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Donors in G1 had better HLA match as compared to other groups. A third of the donors in G1 were HLA identical as compared to 7% in Group 4. Donors in Group 4 were mostly parents and spouses. The impact of SCr at the 1st year after transplant on graft survival is given in [Figure 1]. Five-year graft survival for G1 was 98% as compared to 76% in G4 (P <0.001). The main causes of graft loss are given in [Figure 2]. Majority of the grafts were lost due to interstitial fibrosis tubular atrophy (IFTA). In the follow-up period, 21 (2.72%) recipients died. In these, 13 (61.9%) died due to sepsis, seven (33.33%) due to cardiovascular events, and one (4.76%) due to accident.
Figure 1: Impact of 1-year serum creatinine on graft survival.

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Figure 2: Causes of graft loss.
UTI: Urinary tract infection, IFTA: Interstitial fibrosis tubular atrophy.


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   Discussion Top


Our study on a large cohort of living-related donor kidney transplant has shown that SCr at one year is a good predictor of long-term outcomes. Five-year graft survival of patients with creatinine ≤88.44 mol/L was 98% and for those with SCr ≥ =176.94 mol/L 76%.

Several studies have shown SCr as a predictor of long-term outcomes.[3],[4],[7],[11],[12],[13],[14],[15] The level of SCr at discharge from hospital has been shown to be a predictor of long-term renal graft outcome.[3] SCr at 90 days after transplant is a predication factor of late graft dysfunction.[4] Donor age has been shown to be a predictor of long-term outcome.[16],[17],[18] Interesting observation in our study was the fact that the mean donor age in Group G4 (SCr ≥176.9 μmol/L) was 42.07 ± 10.49 as compared to G1 (SCr ≤88.4 μmol/L) of 30.10 ± 8.54 years (P <0.001). Donor age may well be a factor for better prevention of renal function at one year. Another finding was a better HLA match in patients of G1 as compared to G4. Donors in Group G4 were mostly parents and spouses who were older in age. Older donors, poorer HLA match, and a higher number of rejection episodes appear to be the major contribution of higher Cr at one year. Similar findings have been reported by others.[16]

SCr at one year appears to be an ideal time point as the graft has passed through the events of drug toxicity, rejections, and infections and thereafter stabilized. Our study on living donors has identified SCr at one year as a cost-effective biomarker to predict the long-term outcome of renal allografts. In conclusion, SCr at one year is an independent predictor of long-term graft survival in a living-related donor kidney transplantation. It is, therefore, a good marker for close monitoring of patients where Cr levels go beyond ≥88.4 μmol/L.

Conflict of interest: None declared.



 
   References Top

1.
Nemati E, Einollahi B, Lesan Pezeshki M, Porfarziani V, Fattahi MR. Does kidney transplantation with deceased or living donor affect graft survival? Nephrourol Mon 2014;6: e12182.  Back to cited text no. 1
    
2.
Pascual M, Theruvath T, Kawai T, Tolkoff-Rubin N, Cosimi AB. Strategies to improve long-term outcomes after renal transplantation. N Engl J Med 2002;346:580-90.  Back to cited text no. 2
    
3.
Hassanzadeh J, Hashiani AA, Rajaeefard A, et al. Long-term survival of living donor renal transplants: A single center study. Indian J Nephrol 2010;20:179-84.  Back to cited text no. 3
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4.
Zukowski M, Kotfis K, Kaczmarczyk M, et al. Influence of selected factors on long-term kidney graft survival – A multivariable analysis. Transplant Proc 2014;46:2696-8.  Back to cited text no. 4
    
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Lasserre J, Arnold S, Vingron M, Reinke P, Hinrichs C. Predicting the outcome of renal transplantation. J Am Med Inform Assoc 2012;19:255-62.  Back to cited text no. 5
    
6.
Lee SH, Oh CK, Shin GT, Kim H, Kim SJ, Kim SI. Age matching improves graft survival after living donor kidney transplantation. Transplant Proc 2014;46:449-53.  Back to cited text no. 6
    
7.
Helal I, Abderrahim E, Ben Hamida F, et al. The first year renal function as a predictor of long-term graft survival after kidney transplantation. Transplant Proc 2009;41:648-50.  Back to cited text no. 7
    
8.
Hariharan S, McBride MA, Cherikh WS, Tolleris CB, Bresnahan BA, Johnson CP. Post-transplant renal function in the first year predicts long-term kidney transplant survival. Kidney Int 2002;62:311-8.  Back to cited text no. 8
    
9.
Pascual J, Marcén R, Zamora J, et al. Very early serum creatinine as a surrogate marker for graft survival beyond 10 years. J Nephrol 2009;22:90-8.  Back to cited text no. 9
    
10.
Shabir S, Halimi JM, Cherukuri A, et al. Predicting 5-year risk of kidney transplant failure: A prediction instrument using data available at 1 year posttransplantation. Am J Kidney Dis 2014;63:643-51.  Back to cited text no. 10
    
11.
Koo DD, Welsh KI, McLaren AJ, Roake JA, Morris PJ, Fuggle SV. Cadaver versus living donor kidneys: Impact of donor factors on antigen induction before transplantation. Kidney Int 1999;56:1551-9.  Back to cited text no. 11
    
12.
Fonseca I, Almeida M, Martins LS, et al. First-year renal function predicts long-term renal allograft loss. Transplant Proc 2011;43:106-12.  Back to cited text no. 12
    
13.
Guedes AM, Malheiro J, Fonseca I, et al. Over ten-year kidney graft survival determinants. Int J Nephrol 2012;2012:302974.  Back to cited text no. 13
    
14.
Kwon OJ, Kwak JY. The impact of sex and age matching for long-term graft survival in living donor renal transplantation. Transplant Proc 2004;36:2040-2.  Back to cited text no. 14
    
15.
First MR. Renal function as a predictor of long-term graft survival in renal transplant patients. Nephrol Dial Transplant 2003;18 Suppl 1:i3-6.  Back to cited text no. 15
    
16.
Park YH, Min SK, Lee JN, et al. Risk factors on graft survival of living donor kidney transplantation. Transplant Proc 2004;36:2023- 5.  Back to cited text no. 16
    
17.
Feduska NJ Jr., Cecka JM. Donor factors. Clin Transpl 1994;381-94.  Back to cited text no. 17
    
18.
Zafar MN, Wong G, Aziz T, Abbas K, Adibul Hasan Rizvi S. Living donor risk model for predicting kidney allograft and patient survival in an emerging economy. Nephrology (Carlton) 2018;23:279-86.  Back to cited text no. 18
    

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Correspondence Address:
Syed Haider Nawaz
Department of Chemical Pathology, Sindh Institute of Urology and Transplantation, Karachi 74200
Pakistan
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DOI: 10.4103/1319-2442.301204

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