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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 19  |  Issue : 1  |  Page : 54-58
Pre-transplant Calcium-Phosphate-Parathormone Homeostasis as a Risk Factor for Early Graft Dysfunction


Tehran University of Medical Sciences, Tehran, Iran

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   Abstract 

While good organ quality and ideal transplant conditions eliminate many of the know factors that compromise initial graft function (IGF), poor early graft function (EGF) still occurs after living donor kidney transplantation (LDKT). Uncontrolled pre-transplant hypercalcemia and hyperparathyroidism are associated with impaired allograft function. Between April 2004 and January 2006, data were collected on 354 LDKT recipients including 252 males and 102 females, to determine risk factors for poor EGF, defined as either delayed or slow graft function (DGF or SGF). Of the 354 recipients, 318 (89%) had IGF, 22 (6.2%) had SGF and 14 (4%) had DGF. Donor female gender (P = 0.04) and duration on dialysis (P = 0.02) were associated with poor EGF. Recipients with DGF had higher serum phosphate (P = 0.07) and calcium x phosphate product ( P = 0.01) than recipients with IGF and SGF. The serum parathormone (PTH) levels were higher in recipients with SGF and DGF although the difference was not statistically significant (P = 0.1). Serum calcium levels did not correlate with the occurrence of poor EGF (P = 0.9). Our study suggests that serum phosphate and calcium x phosphate product serve as risk factors for DGF while serum PTH level may play a role as a risk factor for SGF and DGF.

How to cite this article:
Ahmadi F, Ali-Madadi A, Lessan-Pezeshki M, Khatami M, Mahdavi-Mazdeh M, Razeghi E, Maziar S, Seifi S, Abbasi M. Pre-transplant Calcium-Phosphate-Parathormone Homeostasis as a Risk Factor for Early Graft Dysfunction. Saudi J Kidney Dis Transpl 2008;19:54-8

How to cite this URL:
Ahmadi F, Ali-Madadi A, Lessan-Pezeshki M, Khatami M, Mahdavi-Mazdeh M, Razeghi E, Maziar S, Seifi S, Abbasi M. Pre-transplant Calcium-Phosphate-Parathormone Homeostasis as a Risk Factor for Early Graft Dysfunction. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2019 Nov 14];19:54-8. Available from: http://www.sjkdt.org/text.asp?2008/19/1/54/37433

   Introduction Top


One of the most common problems encountered in the first weeks after renal transplantation is delayed graft function (DGF), which occurs in 10 to 50% of deceased donor kidney transplantations (DDKT) in different cohorts. Yet, some recipients with DGF do not require dialysis. These recipients do not by definition have DGF. We categorized such recipients as having intermediate or slow graft function (SGF). Both DGF and SGF strongly pre­dispose to acute rejection. Living donor kidney transplantations (LDKT) have increased substantially during the past decade. It is well know that LDKTs enjoy superior outcome compared with DDKTs. [1] While excellent organ quality and ideal transplant conditions eliminate many of the know factors that compromise initial graft function (IGF), poor early graft function (EGF) still occurs after LDKT.

Although several studies have defined risk factors for DGF or SGF after DDKT, much less has been written in the setting of LDKT. Hypercalcemia and hyperparathyroi­dism are known to be associated with impaired renal function. The mechanisms by which hypercalcemia causes acute renal failure remain largely hypothetical. It is thought to be a result of tubular obstruction and tubular back-leak. Chemical nephro­calcinosis, assumed to be present even when macroscopic and microscopic nephro­calcinosis are excluded, affects glomerular filtration rate by causing vasoconstriction and natriuresis-induced volume contraction. [2] Calcium is a co-factor in the activation of proteolytic enzymes that are linked with maintaining tubular integrity. [3] High cytosolic concentration of free calcium has been shown to activate calcium-dependent enzymes such as phospholipase, nucleases and cysteine proteases. [4]

The widespread use of vitamin D analogues and calcium supplements in dialysis patients prompted us to investigate the role of serum calcium, phosphate and parathormone (PTH) on the occurrence of DGF or SGF.


   Patients and Methods Top


Patients who underwent LDKT between April 2004 and January 2006 were included in this study. Data were collected on 354 recipients (252 males, 102 females) to deter­mine risk factors for poor EGF defined as either delayed or slow graft function (DGF or SGF). According to graft function in the immediate post-operative period, recipients were divided into three groups as follows:

a). IGF: Immediate graft function; serum creatinine < 3 mg/dl by the fifth post-operative day

b). SGF: Slow graft function; serum creatinine >3 mg/dl on the fifth post-operative day but without requiring dialysis post-transplant.

c). DGF: Delayed graft function; dialysis needed in the first week post-transplant.

The standard immunosuppressive regimen consisted of prednisone, cyclosporine A (6-7 mg/kg/day) and mycophenolate mofetil (1.5­2 gm/day). Nearly all recipients also received calcium channel blocker (diltiazem) from the first day after transplant. The levels of calcium, phosphate and PTH were determined on serum samples obtained at admission for transplant. The serum calcium levels were not corrected for protein binding in the present analysis.

Comparison of continuous variables bet­ween groups was performed using Student's t-test or Pearson's test and non-parametric Mann Whitney test, where appropriate. Multivariate binary logistic regression was used to adjust for confounding variables. P < 0.05 was considered as statistically signi­ficant. Statiscal analysis was performed with SPSS software version 12.


   Results Top


Of the 354 recipients, 318 (89.9%) had IGF, 22 (6.2%) and 14 (4%) had SGF and DGF respectively. Duration on dialysis (P = 0.02) and donor female gender (P = 0.04) was associated with poor EGF. The three groups were not different in dialysis status, donor age and prevalence of diabetic etio­logy. A multivariate regression model was then constructed including recipient age, recipient BMI and donor BMI. The reci­pient BMI and donor BMI was lower in patients with IGF than those with SGF (OR: 1.24 CI (1.09-1.40) P < 0.001 and OR: 1.11 CI (0.99-1.25) P = 0.06 respectively). In patients with SGF, the recipient age was higher than in those with IGF (OR: 0.97 CI (0.88-.83) P = 0.06) [Table - 1]. Recipients with DGF had higher serum phosphate (P = 0.07) and calcium x phosphate product (P = 0.01) than recipients with IGF and SGF. Serum calcium level (P = 0.9) did not correlate with occurrence of poor EGF. The PTH level in recipients with SGF and DGF were higher but was not statistically significant (P = 0.1) [Table - 2].


   Discussion Top


While much is known regarding the inci­dence and impact of poor EGF in the setting of DDKT, little has been written on these issues in the setting of LDKT. The living donor graft provides a unique opportunity to investigate why poor EGF may develop is spite of optimized donor and transplant cha­racteristics and its impact on important post­transplant outcomes.

In our prospective study, the prevalence of DGF and SGF were 4% and 6.2% respec­tively. As expected, these prevalence rates are substantially lower than the reported rates of 20-29% for DGF and 27-31% for SGF after DDKT. [5],[6] In retrospective study of Brennan on LKDT, the incidence of DGF and SGF were 4.7% and 10.7% respect­tively. [7] Recognized risk factors for DGF included prolonged preservation, increased donor age and higher panel reactive anti­bodies (PRA). [8] In the absence of risk factors which dominate the DDKT setting, such as donor medical morbidities, brain-death com­promised renal function and prolonged cold ischemia time; only two factors emerged as independently and significantly associated with poor DGF in the LDKT setting; diabetic etiology of renal disease and prolonged warm ischemia time. Increased donor age, widely considered to be the most potent risk factor for DGF and SGF in DDKT did not achieve significance in our cohort of medically healthy live donors. [6]

In our study, donor age and diabetic etio­logy were not associated with increased DGF. The most likely explanation for this is that the donors and recipients in this study were relatively younger. Duration on dialysis and donor gender are independent risk factors for poor EGF.

Little is known about the effect of hyper­calcemia on the initial graft function. Torregosa et al, reported a significant effect of elevated PTH levels on the incidence of DGF, while serum vitamin D and calcium levels did not have a major impact. [9] Boom et al analyzed the pre-transplant PTH levels as a routine, and found no significant differences between the groups with primary function and those with DGF; however, pre­transplant serum calcium level was inde­pendently associated with DGF. [10] Another recent study reported a significant effect of serum calcium level at the time of kidney biopsy on renal calcification and on impair­ment of graft function. [11]

In a study by Kruger, the pretransplant calcium level had no effect on DGF, the occurrence of cardiovascular events, or survival. [12] In our population, the pretrans­plant serum calcium levels were not elevated; also, no difference was found in the calcium levels between the patients with poor EGF and IGF.

In conclusion, our study indicates that the serum phosphate and calcium x phosphate product serve as risk factors for DGF. We also noticed slightly higher levels of PTH in the patients with SGF and DGF although the difference was not statistically significant. Further studies on larger cohorts of patients are required to validate this observation.

Additionally, efforts to improve calcium, phosphate and PTH homeostasis in patients on the waiting list for renal transplantation should be encouraged.

 
   References Top

1.Hariharan S, Johnson CP, Breshnahan BA, Taranto SE, Melntosh MJ, Stablein D. Improved graft survival after renal transplantation in United States. N Engl J Med 2000;342(9):605-12.  Back to cited text no. 1    
2.Levi M, Ellis MA, Berl T. Control of renal hemodynamics and glomerular filtration rate in chronic Hypercalcemia, role of prostaglandins, rennin-angiotensin system, and calcium. J Clin Invest 1983;71(6): 1624-32.  Back to cited text no. 2    
3.Cheung JY, Bonventre JV, Mails CD, Leaf A. Calcium and ischemic injury. N Engl J Med 1986;314(26):1670-6.  Back to cited text no. 3    
4.Eldelstein CL, Shi Y, Schrier RW. Role of caspases in hypoxia-induced necrosis of rat renal proximal tubule. J Am Soc Nephrol 1999;10(9):1940-9.  Back to cited text no. 4    
5.Hallovan PF, Hunsicker LG. Delayed graft function: State of the art, November 10-11, 2000. Summit meeting, Scottsdale, Arizona, USA. Am J transplant 2001;1(2): 15-20.  Back to cited text no. 5    
6.Humar A, Ramcharan T, Kandaswamy R, Gillingham K, Payne WD, Matas AJ. Risk factors for slow graft function after kidney transplant: A multivariate analysis. Clin Transplant 2002;16(6):425-9.  Back to cited text no. 6    
7.Brennan TV, Freise CE, Fuller TF, Bostrom A, Tomlanovich SJ, Feng S. Early graft function after living donor kidney transplantation predicts rejection but not outcomes. Am J Transplant 2004;4(6):971-9.  Back to cited text no. 7    
8.Ojo AO, Wolfe RA, Held PJ, Port FK. Schmouder RL. Delayed graft function: risk factors and implications for renal allograft survival. Transplantation 1997;63 (7):968-74.  Back to cited text no. 8    
9.Torregrosa JV, Campistol JM, Fenollosa B, et al. Secondary hyperparathyroidism and posttransplant acute tubular necrosis. Nephron 1996;73(1):67-72.  Back to cited text no. 9    
10.Boom H, Mallat MJ, deFijter JW, Paul LC, Bruijn JA, van Es LA. Calcium levels as a risk factor for delayed graft function. Transplantation 2004;77(6):868-73.  Back to cited text no. 10    
11.Gwinner W, Suppa S, Mengel M, et al. Early calcification of renal allografts detected by protocol biopsies causes and clinical implication. Am J Transplant 2005;5(8):1934-41.  Back to cited text no. 11    
12.Kruger B, Schnitzbauer AA, Boger CA, et al. Pretransplant calcium levels have no predictive value for DGF, long-term function cardiovascular events or graft and patient survival in renal transplantation. Transplant Proc 2006;38(3):697-700.  Back to cited text no. 12    

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Correspondence Address:
M Abbasi
Nephrology Department, Imam Khomeini Medical Center, Keshavarz Blvd, Tehran
Iran
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PMID: 18087123

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    Tables

  [Table - 1], [Table - 2]

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    Abstract
    Introduction
    Patients and Methods
    Results
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    References
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