Influence of genetic polymorphisms in GSTM1, GSTM3, GSTT1 and GSTP1 on allograft outcome in renal transplant recipients

Abstract: Introduction: Glutathione S‐transferases (GSTs) are important in protection against xenobiotic compounds and toxicity caused by immunosuppressants in renal transplant recipients. In the present study we hypothesize that genetic variability in GSTM1, GSTM3, GSTP1 and GSTT1 genes may be associated with allograft outcome. Methods: The study included 223 controls and 273 transplant recipients categorized into 184 stable graft function (SGF), 57 rejection episodes (RE) and 32 delayed graft function (DGF). The polymorphism was studied using multiplex PCR and PCR‐RFLP. Results: GSTM1 null genotype showed a 3.35‐fold higher risk for rejection in SGF vs. RE category [95% confidence interval (CI) 1.27–8.84, p = 0.014]. Mutant (G) allele of GSTP1 was associated with a 5.52‐fold risk for DGF (95% CI 1.37–22.17, p = 0.016). Kaplan–Meier analysis revealed significantly lower mean time to first RE in null genotype as compared with GSTM1 present patients (Log p = 0.002). The dose adjusted C₂ levels in null genotype was higher as compared with GSTM1 present patients at one (p = 0.007) and three months (p = 0.027) post transplantation. Conclusion: Patients with variant genotype of GSTM1 and GSTP1 were at higher risk for rejection and delayed functioning of the allograft, respectively, supporting the hypothesis for involvement of GST isoform variants in allograft outcome in renal transplant recipients.     

Genetic association of interleukin-4, interleukin-10, and transforming growth factor-beta gene polymorphism with allograft function in renal transplant patients

Despite advances in immunosuppressive therapy in the past decade, allograft rejection remains the primary cause for kidney graft failure. Cytokines are known to be important mediators in renal allograft outcome. The aim of the present study was to ascertain whether interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-beta cytokine gene polymorphisms contributed to kidney graft outcome. We evaluated single nucleotide polymorphism in IL-4 (-1098G/T, -590C/T, -33C/T), IL-10 (-1082A/G, -819C/T, -592A/C), and TGF-beta (codon 10 and 25) in 100 renal transplant recipients and 139 normal healthy control using polymerase chain reactions based on sequence-specific primers. Recipients were clinically characterized as rejection episode (RE) versus stable graft function (SGF). The results showed the frequencies of IL-4 -33 T allele in the RE, SGF, and control group to be 7%, 73%, and 28%, respectively. IL-10 -592 A allele frequency was 39% in RE, 26% in SGF, and 28% in the control group. TGF-beta codon 10 T allele was 39% in RE, 35% in SGF, and 53% in control group. In conclusion, this study suggested that some cytokine gene alleles reflected SGF among kidney transplant recipients.     

Early Graft Function After Living Donor Kidney Transplantation Predicts Rejection But Not Outcomes

Poor early graft function (EGF) after deceased donor kidney transplantation (DDKT) has been intensely studied. Much less is known about poor EGF after living donor kidney transplantation (LDKT). Data were collected on 469 LDKTs performed between 1/1/97 and 12/31/01 to determine risk factors for and outcomes associated with poor EGF, defined as either delayed or slow graft function (DGF or SGF). The incidence of DGF and SGF were 4.7% and 10.7%, respectively. Diabetic etiology (OR 2.22; p = 0.021) and warm ischemia time (WIT) (OR 1.05 per min increment; p = 0.0025) emerged as independently associated with poor EGF. Neither functional graft survival nor 1-year graft function differed among the EGF groups. However, DGF and SGF strongly predisposed to acute rejection (AR), which compromised functional graft survival (p = 0.0007) and 1-year graft function. Therefore, we conclude that diabetic etiology of renal disease and WIT are the dominant risk factors for poor EGF after LDKT. Poor EGF did not directly compromise functional graft survival but strongly predisposed to AR. We suggest that immunosuppression should be intensified in the poor EGF setting to maximize LDKT longevity, as AR does impair functional graft survival.     

Cytokine gene polymorphism in kidney transplantation--impact of TGF-beta 1, TNF-alpha and IL-6 on graft outcome

Chronic allograft nephropathy (CAN) is one of the main causes of graft loss in renal transplantation. Polymorphisms with functional significance in the promoter and coding regions of cytokine genes have been suggested as a possible factor for graft rejection. The aim of this study was to investigate the impact of cytokine gene polymorphism of pro and anti-inflammatory cytokines on development of CAN in a group of renal transplant patients and donors. Eight single nucleotide polymorphisms (SNPs) including TNFA (-308), TGFB1 (cdns10, 25), IL-10 (-1082, -819, -592), IL-6 (-174) and IFNG (+874) were analyzed in 56 patients with stable graft function (SGF), 10 with CAN and 28 kidney donors by PCR-SSP method. CAN was significantly associated with the recipient TGFB1 cod10 T/T and combination of cods10, 25 T/T G/G genotypes (high producer), (p<0.05). Influence of patient's TNFA genotype correlated with high level of gene expression on the development of CAN was further demonstrated when the patients were stratified according to the HLA mismatches (HLA-DRB MMs). Additionally donor TNFA-308 G/A (high) and IL-6-174 CC (low) genotypes were increased in cases with CAN. No statistically significant differences in distribution of IL-10, IL-6 and IFNG genotypes between recipients with SGF and CAN were found. In conclusion our data suggest that the high producer genotype of profibrogenetic TGF-beta1, pro-inflammatory TNF-alpha and genetically determined low production of immunoregulatory IL-6 cytokine might be risk factors for CAN development.     

Risk factors for slow graft function after kidney transplants: a multivariate analysis

BACKGROUND: We previously defined an intermediate group of cadaver kidney transplant recipients who do not have immediate graft function (IGF), but do not have sufficient graft dysfunction to be classified as having delayed graft function (DGF). We showed that this group with slow graft function (SGF) had an increased risk of rejection and inferior long-term results vs. recipients with IGF. The aim of our current study was to determine risk factors for SGF, which have not been well defined (in contrast to risk factors for DGF). METHODS: Between January 1, 1984 and September 30, 1999, we performed 896 adult cadaver kidney transplants at the University of Minnesota. Recipients were analysed in three groups based on initial graft function: IGF [creatinine (Cr) < 3 mg/dL by post-operative day (POD) no. 5], SGF (Cr > 3 mg/dL on POD no. 5, but no need for dialysis), and DGF (need for dialysis in the first week post-transplant). A multivariate analysis looked specifically at risk factors for SGF, as compared with risk factors for DGF. Outcomes with regard to graft survival and acute rejection (AR) rates were determined for the three groups. RESULTS: Of the 896 recipients, 425 had IGF, 238 had SGF, and 233 had DGF. A multivariate analysis of risk factors for SGF showed donor age >50 yr (RR=3.3, p=0.0001) and kidney preservation time >24 h (RR=1.6, p=0.01) to be the most significant risk factors. A multivariate analysis of risk factors for DGF showed similar findings, although high panel-reactive antibodies (PRA) and donor Cr >1.7 mg/dL were also significant risk factors for DGF. Initial function of the graft significantly influenced the subsequent risk of AR: at 12 months post-transplant, the incidence of AR was 28% for those with IGF, 38% for those with SGF, and 44% for those with DGF (p=0.04 for SGF vs. DGF). Initial graft function also significantly influenced graft survival: the 5-yr death-censored graft survival rate was 89% for recipients with IGF, 72% for those with SGF, and 67% for those with DGF (p=0.01 for IGF vs. SGF; p=0.03 for SGF vs. DGF). CONCLUSIONS: SGF represents part of the spectrum of graft injury and post-transplant graft dysfunction. Risk factors for SGF are similar to those seen for DGF. Even mild to moderate graft dysfunction post-transplant can have a negative impact on long-term graft survival.     

Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients

Sadeghi M, Daniel V, Naujokat C, Schmidt J, Mehrabi A, Zeier M, Opelz G. Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients
Clin Transplant 2010: 24: 415–423. © 2009 John Wiley & Sons A/S. Abstract: Delayed graft function (DGF) increases the risk of acute allograft rejection and may affect long‐term graft survival. We compared pre‐transplant, early post‐transplant, and late post‐transplant serum creatinine (Cr) and plasma levels of neopterin, cytokines, and cytokine receptors/antagonists in patients with DGF (n = 39), slow graft function (SGF) (n = 43), or immediate graft function (IGF) (n = 30). Three and eight days post‐transplant, plasma neopterin (p < 0.001; p < 0.001), Soluble Interleukin‐6 (IL‐6) receptor (R) (p = 0.002; p = 0.001), and IL‐10 (p = 0.003; p = 0.001) were higher in DGF than IGF patients. One month post‐transplant, plasma neopterin (p < 0.001) and IL‐10 (p < 0.001) were higher in DGF than IGF patients. Three days post‐transplant, the results indicated reduced sIL‐1 receptor antognist (RA) production in DGF patients (p = 0.001). Simultaneously, plasma sIL‐6R and IL‐10 increased in DGF (p < 0.001; p = 0.003) and SGF (p = 0.007; p = 0.030) patients, indicating increased production of sIL‐6R and IL‐10. Lower sIL‐1 production in DGF than IGF patients early post‐transplant might promote the increased production of monocyte‐derived neopterin, sIL‐6R, and IL‐10. This monocyte/macrophage activation might induce inflammation in the graft and subsequently cause an impairment of graft function. Blocking of monocyte activity after renal transplantation may be considered a potential approach for improving graft outcome.     

Reduced graft function (with or without dialysis) vs immediate graft function--a comparison of long-term renal allograft survival.

BACKGROUND: Delayed graft function (DGF) is a common complication in cadaveric kidney transplants affecting graft outcome. However, the incidence of DGF differs widely between centres as its definition is very variable. The purpose of this study was to define a parameter for DGF and immediate graft function (IGF) and to compare the graft outcome between these groups at our centre. METHODS: The renal allograft function of 972 first cadaveric transplants performed between 1990 and 2001 in the Republic of Ireland was examined. The DGF and IGF were defined by a creatinine reduction ratio (CRR) between time 0 of transplantation and day 7 post-transplantation of <70 and >70%, respectively. Recipients with reduced graft function (DGF) not requiring dialysis were defined as slow graft function (SGF) patients. The serum creatinine at 3 months, 6 months, 1, 2 and 5 years after transplantation was compared between these groups of recipients. The graft survival rates at 1, 3 and 5 years and the graft half-life for DGF, SGF and IGF recipients were also assessed. RESULTS: Of the 972 renal transplant recipients, DGF was seen in 102 (10.5%) patients, SGF in 202 (20.8%) recipients and IGF in 668 (68.7%) patients. Serum creatinine levels were significantly different between the three groups at 3 and 6 months, 1, 2 and 5 years. Graft survival at 5 years for the DGF patients was 48.5%, 60.5% for SGF recipients and 75% for IGF patients with graft half-life of 4.9, 8.7 and 10.5 years, respectively. CONCLUSION: This study has shown that the CRR at day 7 correlates with renal function up to 5 years post-transplantation and with long-term graft survival. We have also demonstrated that amongst patients with reduced graft function after transplantation, two groups with significantly different outcomes exist.     

Immunosuppression for delayed or slow graft function in primary cadaveric renal transplantation: use of low dose tacrolimus therapy with post-operative administration of anti-CD25 monoclonal antibody

BACKGROUND: Patients who develop delayed graft function (DGF) following cadaveric renal transplantation have inferior survival to those who do not. Calcineurin inhibitors (CNI) may prolong recovery from DGF. Patients with DGF are therefore routinely treated with either polyclonal antilymphocyte preparations or monoclonal anti-CD3 monoclonal antibodies and delayed introduction of CNI. The purpose of this study was to evaluate the efficacy of the anti-CD25 monoclonal antibody basiliximab (BSLIX) started post-operatively in patients at high risk for DGF combined with low dose tacrolimus (TAC). METHODS: Patients who received a primary cadaveric renal transplant only after August 1998 were included in this retrospective study (n = 143). All patients received TAC and mycophenolate Mofetil (MMF) pre-operatively. At 6 h post-operatively, graft function was assessed clinically by urine output and serum creatinine. Those patients who had a urine output < 300 cc/6 h or a rising serum creatinine were presumed to be at risk for DGF (n = 46). These patients were treated with 20 mg BSLIX and had TAC dose reduced to maintain a trough blood level of < 5 ng/mL. Basiliximab was repeated at day 5. Patients not felt to be at risk for DGF were treated with standard TAC dose with trough level target of 9-12 ng/mL. Patients at risk were classified as DGF if they needed dialysis or as slow graft function (SGF) if they did not. The combined group (SGF/DGF) were analysed together. Patients with SGF/DGF had their TAC dose increased to achieve trough levels of 9-12 ng/mL when renal function improved. Patient groups were compared for demographics, need for dialysis, serum creatinine, glomerular filtration rate (GFR), TAC trough levels, MMF dosage, complications and 1- and 2-yr actuarial graft survival. RESULTS: Patients with SGF/DGF had a longer length of stay (8 vs. 5.7 d), were more likely to be black (41.3 vs. 25.7%), and required more post-operative haemodialysis (HD) (52.2 vs. 4.1%). SGF/DGF and non-SGF/DGF patients had similar rates of rejection (28.2 vs. 19.6%, p = 0.28) and steroid resistant rejection (SRR) (6.5 vs. 2.1%, p = 0.32). There were no differences in the rate of cytomegalovirus (CMV) infection (4.3 vs. 6.1%). Serum creatinine was higher and GFR lower at all time points in the SGF/DGF patients. The 1 and 2 yr actuarial survival in the non-SGF/DGF patients was 97.6 and 97.6% compared with 1 and 2 yrs actuarial survival of 94.1% and 80.0% in the SGF/DGF patients, p = 0.04. There were no differences in patient survival. There were no differences in actuarial survival for the SGF/DGF patients who received dialysis compared with those who did not receive dialysis. Comparison of patients who received HD (n = 28) to those who did not (n = 115), regardless of group demonstrated no difference in 1 and 2 yrs actuarial survival, 100 and 94.1% in HD patients vs. 98.2 and 92.5% in non-HD patients. CONCLUSIONS: The clinical diagnosis of SGF/DGF can be made 6 h post-operatively based on urine output and serum creatinine. Basiliximab can be started post-operatively in these patients and decreased levels of TAC can be used to achieve acceptably low rates of rejection in these patients. However, SGF/DGF patients, regardless of their need for dialysis, have worse function at 1 yr and lower 2-yr actuarial graft survival compared with non-SGF/DGF patients. Most of the poor survival can be attributed to the SGF group. Further strategies to either prevent SGF/DGF or to optimize treatment in these patients are needed.     

Similar impact of slow and delayed graft function on renal allograft outcome and function

Kidney transplant patients can be divided into three groups, according to the initial graft function. First-week dialyzed patients form the delayed graft function (DGF) group. Nondialyzed patients are divided into slow graft function (SGF) or immediate graft function (IGF) according to whether the day 5 serum creatinine was higher versus lower than 3 mg/dL, respectively. SGF patients showed worse graft survival, above higher incidence of acute rejection and lower renal function than IGF patients, although few reports have analyzed outcomes in these groups. We analyzed the impact of SGF on graft survival, first-year renal function, and incidence of acute rejection in 291 renal transplant patients. Creatinine was significantly worse at 12 months for SGF and DGF than for IGF patients (1.9 +/- 0.8 mg/dL, 1.8 +/- 0.7 mg/dL, 1.5 +/- 0.5 mg/dL, respectively; P < .05). There was no difference in first-year renal function between SGF and DGF. The acute rejection rate was higher among the SGF than the IGF group (45% vs 21%, P < .05), but not different from DGF patients (42%, P < .05). Graft survival was better among IGF than SGF or DGF patients, with no significant difference between the last two groups (3-year graft survival, 82%, 71%, 70%, respectively; log-rank test, P < .05). Kidney transplant recipients who develop SGF have a worse outcome than patients with IGF, similar to DGF patients. SGF patients show worse graft survival, worse renal function, and higher acute rejection rates than IGF patients, despite not needing dialysis.     

Comparisons of clinicopathological correlations between immediate and slow graft function in renal transplant recipients

Abstract: The functional recovery state of renal transplants can be divided into three types: immediate graft function (IGF), slow graft function (SGF) and delayed graft function (DGF). In contrast to the well-known clinical outcomes for IGF and DGF, the pathological findings and clinical outcomes of SGF are undetermined. This study evaluated possible clinicopathological correlations in 237 patients with SGF compared with patients with IGF. IGF and SGF were defined by serum creatinine levels (IGF < 1.2 mg/day l; SGF: ≥1.2 mg/dL) at day 14 after renal transplantation. Graft biopsy was performed on this day, and pathological classification was performed using the Banff schema. The SGF group of patients ( n  = 121) showed higher rates of cadaver donors and male recipients than the IGF group ( n  = 116), but there were no significant differences in recipient or donor age, numbers of HLA mismatches, types of immunosuppressant or follow-up periods between two groups. The SGF group showed higher serum creatinine levels at discharge, and a higher incidence of acute rejection than the IGF group (24.8% vs. 8.6%, P  < 0.05) and lower graft survival rates (1 year, 93.3% vs. 100%; 5 years, 85.4% vs. 98.6%, respectively; P  < 0.05). The presence of acute rejection in the SGF patients indicated a significantly decreased 5-year survival rate compared with the IGF group. The SGF group of patients with borderline pathology had a higher incidence of acute rejection than the IGF group, and significant increases in the expression of mRNA for pro-apoptotic genes (Fas-ligand, granzyme B and perforin) compared with the IGF group. In conclusion, SGF represents the activated immune state and is associated with poor graft outcome. Anti-rejection treatment or modified immunosuppressive regimen may thus be indicated for patients with SGF.     

Clinical Implications of Initial Renal Function After Deceased Donor Transplant

The aim of this study was to investigate whether slow graft function (SGF) after transplantation of deceased-donor kidneys affected the prevalence of anemia or the glomerular filtration rate (GFR). We retrospectively evaluated the records of 534 kidney transplant patients who were classified based on their initial renal function, namely, immediate graft function (IGF), slow graft function (SGF), or delayed graft function (DGF). Among the 534 kidney transplant patients studied, the occurrences of each condition were IGF 104, SGF 133, and DGF 297. Six months after transplantation, a greater percentage of DGF patients were anemic compared with the others (P = .028). However, at 12 months after transplantation, SGF patients showed more anemia than the IGF group. DGF and SGF patients displayed similar GFR values at 18 and 24 months after transplantation. However, IGF patients displayed higher GFRs, even when subjects who experienced acute rejection episodes were censored (P = .004). The incidence of acute rejection episodes was similar among SGF and DGF patients. Patients displaying SGF after deceased-donor transplantation showed a greater tendency to be anemic than those displaying IGF. This study also suggested that SGF patients were at risk for acute rejection episodes and/or significantly reduced kidney function as measured by GFR.     

Similar Outcomes with Different Rates of Delayed Graft Function May Reflect Center Practice, Not Center Performance

To better understand the implications for considering delayed graft function (DGF) as a performance measure, we compared outcomes associated with a 2- to 3-fold difference in the incidence of DGF at two transplant centers. We analyzed 5072 kidney transplantations between 1984 and 2006 at the University of Minnesota Medical Center (UMMC) and Hennepin County Medical Center (HCMC). In logistic regression the adjusted odds ratio for DGF at HCMC versus UMMC was 3.11 (95% Confidence Interval [CI]= 2.49–3.89) for deceased donors and 2.24 (CI = 1.45–3.47) for living donors. In Cox analysis of 4957 transplantations, slow graft function (SGF; creatinine ≥3.0 mg/dL [230 μmol/L] on day 5 without dialysis) was associated with graft failure at UMMC (Relative Risk [RR]= 1.43, CI = 1.25–1.64), but not HCMC (RR = 0.99, CI = 0.77–1.28). RR's of DGF were similar at both centers. Thus, the lower incidence of DGF at UMMC likely resulted in a higher incidence and higher risk of SGF compared to HCMC. Indeed, graft survival for recipients with DGF at HCMC was similar (p = 0.3741) to that of recipients with SGF at UMMC. We conclude that dialysis per se is likely not a cause of worse graft outcomes. A better definition is needed to measure early graft dysfunction and its effects across transplant programs.     

Delayed Graft Function Has an Equally Bad Impact on Deceased Donor Renal Graft Survival in Both Standard Criteria Donors and Expanded Criteria Donors

Introduction

The use of expanded criteria donors (ECDs) is still limited because of inferior graft survival compared to standard criteria donors (SCDs). We assessed the impact of immediate graft function (IGF) on renal graft survival among recipients of SCD and ECD grafts to determine whether these kidneys performed equally well under “ideal” conditions favoring IGF.

Methods

We included all cadaveric renal transplants performed from 1990 to 2002 (n = 335). Delayed graft function (DGF) was defined as the need for dialysis in the first 7 days posttransplant. Slow graft function (SGF) and IGF were defined as a serum creatinine fall by <20% versus >20% in the first 24 hours posttransplant, respectively. Non-death censored actual graft survivals are reported herein.

Results

Seventy-two of the 335 subjects (21.5%) received organs from ECDs and displayed IGF in 54.7%, SGF 16.2%, and DGF 29.1%. Among SCDs, the SGF and DGF rates were 15.3% and 23.4%, respectively. In ECD, the SGF and DGF rates were 19.4% and 50% (P < .02). Actual graft survivals at 1 and 5 years was 86.3% and 70.4%, respectively. Patients with IGF had higher actual graft survival at 5 years compared to SGF and DGF (83.5% vs 74.1% vs 45.4%). DGF had an equally bad impact on actual 5-year graft survival in SCDs and ECDs (42.6% vs 50%).

Conclusion

DGF has a strong detrimental impact on 5-year graft survival. There is a higher rate of DGF in ECD versus SCD kidneys. The detrimental impact on 5-year actual graft survival is equal in SCD and ECD kidneys. Minimizing DGF should be our goal.     

The Detrimental Effect of Poor Early Graft Function After Laparoscopic Live Donor Nephrectomy on Graft Outcomes

We undertook this study to assess the rate of poor early graft function (EGF) after laparoscopic live donor nephrectomy (lapNx) and to determine whether poor EGF is associated with diminished long-term graft survival. The study population consisted of 946 consecutive lapNx donors/recipient pairs at our center. Poor EGF was defined as receiving hemodialysis on postoperative day (POD) 1 through POD 7 (delayed graft function [DGF]) or serum creatinine ≥ 3.0 mg/dL at POD 5 without need for hemodialysis (slow graft function [SGF]). The incidence of poor EGF was 16.3% (DGF 5.8%, SGF 10.5%), and it was stable in chronologic tertiles. Poor EGF was independently associated with worse death-censored graft survival (adjusted hazard ratio (HR) 2.15, 95% confidence interval (CI) 1.34–3.47, p = 0.001), worse overall graft survival (HR 1.62, 95% CI 1.10–2.37, p = 0.014), worse acute rejection-free survival (HR 2.75, 95% CI 1.92–3.94, p < 0.001) and worse 1-year renal function (p = 0.002). Even SGF independently predicted worse renal allograft survival (HR 2.54, 95% CI 1.44–4.44, p = 0.001). Risk factors for poor DGF included advanced donor age, high recipient BMI, sirolimus use and prolonged warm ischemia time. In conclusion, poor EGF following lapNx has a deleterious effect on long-term graft function and survival.     

Interleukin-1β gene and receptor antagonist gene polymorphisms in patients with calcium oxalate stones

Interleukin-1 (IL-1) might play a role in the process of bone loss and hypercalciuria and is therefore considered to be involved in the formation of urinary stones. The aim of this study is to test whether the IL-1beta promoter region, exon 5 region and IL-1 receptor antagonist gene intron 2 polymorphisms could be genetic markers for the susceptibility to the formation of urinary stones. A control group of 152 healthy people and a group of 105 patients with recurrent calcium oxalate stone were examined in this study. Polymerase chain reaction (PCR) analyzed the variable number tandem repeats at intron 2 of the IL-1Ra gene for the polymorphisms. PCR-based restriction analysis was done for the IL-1beta gene polymorphisms of the promoter region and exon 5 by the endonucleases Ava I and Taq I, respectively. The polymorphisms studied in the IL-1beta genes did not reveal a strong association with calcium oxalate stone disease when compared with the control group (promoter region by chi-square test, P=0.627: exon 5 region by Fisher's exact test, P = 0.403). Only two frequent alleles of the IL-1Ra gene corresponding to one and two copies of an 86-bp sequence repeat were identified by PCR. The result revealed significant differences between control individuals and stone patients (P < 0.01. Fisher's exact test). In addition, the frequency of the type I allele in the stone group (99.0%) was higher than in the control group (94.0%). The odds ratio for the type I allele of the IL-1Ra gene in calcium oxalate stone disease is 6.041 (95% CI: 1.683 approximately 21.687). There is an association between urolithiasis and polymorphism in the IL-1Ra gene. No significant difference was found when dividing the stone patients into groups with normocalciuria and hypercalciuria in relation to these genetic polymorphisms. Further studies of the type I allele of the IL-IRa gene are worthwhile because of its correlation with stone disease. In our study, neither the IL-1beta promoter region nor the exon 5 polymorphisms were significantly different when comparing control subjects and calcium oxalate stone patients.     

应用血肌酐下降率预测肾移植患者术后早期肾功能恢复情况

目的 探讨肾移植术后患者SCr下降率(CRRz)与早期移植肾功能恢复情况的相关性,建立早期预测移植.肾功能恢复的标准. 方法同种异体肾移植术后患者80例.分3组:①移植肾功能立即恢复(IGF)组53例,术后5 d SCr＜265.2 gmol/L;②移植肾功能缓慢恢复(SGF)组14例,术后5 d SCr＞265.2gmol/L,但1周内不需要透析治疗;③移植肾功能延迟恢复(DGF)组13例,术后1周内需要透析治疗.比较分析3组患者CRR:值和CRRz的99%可信区间(99%CI).结果 IGF组、SGF组和DGF组患者CRR2值分别为(46.8±14.6)%、(25.6±13.5)%和(0.7±17.7)%,99%C1分别为41%～52%、15%～36%和-14%～16%.3组间CRR2值两两比较,差异有统计学意义(P≤0.01).由3组CRR2的99%CI设定IGF、SGF、DGF的早期预测标准分别为CRR2≥40%、15%＜CRR2＜40%和CRR2≤15%.结论 CRR2与术后早期移植肾功能恢复情况有较好的相关性,可用于早期预测移植术后患者发生明功能延迟恢复的风险.     

Fate of the Mate: The Influence of Delayed Graft Function in Renal Transplantation on the Mate Recipient

Delayed graft function (DGF) in a deceased-donor renal recipient is associated with allograft dysfunction 1-year posttransplant. There is limited research about the influence to allograft function on the mate of a DGF recipient over time . Using a retrospective cohort design, we studied 55 recipients from a single center. The primary outcome was the change in glomerular filtration rate (GFR) 1-year posttransplant. The secondary outcome was the GFR at baseline. We found that mates to DGF recipients had a mean change in GFR 1-year posttransplant of −11.2 mL/min, while the control group had a mean change of −0.4 mL/min. The difference in the primary outcome was significant (p = 0.025) in a multivariate analysis, adjusting for cold ischemic time, panel reactive antibody level, allograft loss, human leukocyte antibody (HLA)-B mismatches and HLA-DR mismatches. No significant difference between groups was found in baseline GFR. In conclusion, mates to DGF recipients had a significantly larger decline in allograft function 1-year posttransplant compared to controls with similar renal function at baseline. We believe strategies that may preserve allograft function in these ' at-risk ' recipients should be developed and tested.     

Impact of Slow and Delayed Graft Function on Kidney Graft Survival Between Various Subgroups Among Renal Transplant Patients

Objective

Renal allografts with excellent graft function show good long-term outcomes, while grafts with delayed function have been associated with poor long-term survivals, although few reports have analyzed outcomes among these groups. We compared first-week postoperative graft function among renal transplant patients to analyze the impact of slow graft function (SGF) and delayed graft function (DGF) on graft survival.

Materials and Methods

Renal transplantations were performed from 362 unrelated, 46 related, and 163 deceased donors. Kidney transplant patients were divided into 3 groups according to their initial graft function. First-week dialyzed patients formed the DGF group. Nondialyzed patients were divided into a SGF or an excellent graft function (EGF) cohort according to whether the serum creatinine at day 7 was higher vs lower than 2.5 mg/dL, respectively.

Results

Of the 570 renal transplant recipients, DGF was observed in 39 patients (6.8%), SGF in 64 (11.2%), and EGF in 467 (81.8%). There was no significant difference in SGF vs DGF between patients who received kidneys from unrelated vs related living or deceased donors. Graft survival was worse among the DGF than the SGF or EGF patients, with no significant difference between the last 2 groups. The 6-month graft survivals were 74%, 93%, and 96%; the 3-year graft survivals were 70%, 88%, and 90%, respectively (P < .001).

Conclusions

We observed a similar impact of EGF and SGF on kidney graft survival. Kidney transplant recipients who developed DGF showed worse graft survival than those with EGF or SGF.