Cytokine gene polymorphisms in kidney transplantation.

BACKGROUND: Acute and chronic rejections remain an important cause of graft loss after renal transplantation. It has been suggested that cytokine genotyping may have a predictive role to identify patients at greater risk of rejection regardless of human leukocyte antigen (HLA) compatibility and/or the presence of anti-HLA antibodies before the renal allograft. OBJECTIVES: We sought to investigate polymorphisms of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß1, interleukin (IL)-10, IL-6, and interferon (IFN)-γ as indices of differential cytokine production in kidney transplantation and to examine their predictive roles for acute or chronic rejection. PATIENTS AND METHODS: TNF-α (G/A -308), TGF -ß1 (haplotype codon 10/codon 25), IL-10 (haplotype-1082, -819, -592), IL-6 (C/G -174), and IFN-γ (T/A +874) single nucleotide polymorphisms (SNPs) were detected using polymerase chain reaction (PCR)-specific sequence primers (SSP) in 231 kidney transplant recipients (KTR) including 106 treated with mycophenolate mofetil (MMF+). RESULTS: We observed no significant associations of any of investigated polymorphism taken alone with acute rejection episodes (ARE) or chronic allograft dysfunction (CAD). Nevertheless, TGF-ß1 Low (L) production was correlated with greater graft survival at 20 years (81.8%) compared with intermediate (L) or high (H) levels (56.1%), affect that the difference was not significant (P = .2). Cytokine haplotype analysis in KTR (MMF-) without HLA-mismatches or presynthesized anti-HLA antibodies (n = 32) showed ARE to be significantly more prevalent among the TNF-α*H/TGF- ß1*H/IL-10*H production haplotype (75%) compared with the other haplotypes (16%; P = .03). CONCLUSION: The presence of TGF-ß1-H secretion profile may protect the kidney graft. TNF-α*H/TGF-ß1*H/IL-10*H haplotype was associated with a higher risk of ARE and with poorer graft survival.

Malformative uropathies and kidney transplantation.

INTRODUCTION: Malformative uropathies are a frequent cause of end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). Medical management of urinary tract infections and advances in surgical reconstruction procedures resulted in good outcomes of kidney transplantation among these patients. The aim of this article was to describe the epidemiological profiles and outcomes of patients who underwent transplantation for ESRD related to malformative uropathies. PATIENTS AND METHODS: Among 493 kidney recipients at our center from 1986 to 2009, 47 had malformative uropathies as the cause of ESRD. We retrospectively studied the incidence of acute rejection episodes, acute tubular necrosis, as well as patient and graft survivals, comparing these results to those observed in patients without malformative uropathies using chi-square tests for qualitative parameters and nonpaired Student t tests for continuous variables. Log-rank tests were used for comparisons of survival curves. RESULTS: The 47 patients, representing 9.53% of our kidney transplant recipients, included 27 men and 20 women (sex ratio=1.35) with an overall mean age of 27.6±9.1 years (range, 10-49). The common etiology was vesico-ureteral reflux (78.7%). Hemodialysis was the main RRT modality (68%) with a median duration of 41 months. Also, 82.9% of patients received transplants from living donors. Acute tubular necrosis occurred in 4 of these (8.5%) versus 22.06% of the other patients (P=.03). Acute rejection episodes were observed in 13 of these patients (27.6%) versus 23.1% of the other patients (P=not significant [NS]). After a cumulative follow-up period of 3744 months (median, 41.8 months), 5 patients had died (1.6 death/y/100 patients) and 5 had lost their allografts and returned to dialysis (1.6 case/y/100 patients). Graft survival rates at 1, 5, and 10 years were 97.8%, 93.2%, and 79.9%, which were comparable with 95.9%, 87.6%, and 78.9% among the other patients, respectively (P=NS). Patient survival rates at 1, 5, and 10 years were 100%, 88.5%, and 82.6% versus 96%, 87.6%, and 79.6%, respectively (P=NS). CONCLUSION: Kidney transplantation in patients with malformative uropathies is increasingly frequent. The incidence of acute rejection episodes as well as patient and graft survivals were comparable with those of subjects without malformative uropathies.

Plasma levels of soluble CD30 in kidney graft recipients as predictors of acute allograft rejection.

In renal transplant recipients elevated soluble serum CD30 levels are associated with increased rejection and graft loss. We sought to determine the sCD30 plasma levels before and after kidney transplantation and to assess whether sCD30 was a predictive factor of immunological risk. sCD30 plasma levels were determined by an enzyme-linked immunosorbent assay assay in 52 kidney graft recipients before as well as 7, 15, and 21 days after transplantation. Eighteen patients developed acute allograft rejection (group I) and 34 patients showed uneventful courses (group II). Before transplantation sCD30 plasma levels were elevated in both groups (mean: 162.6 +/- 89.5 U/mL). After transplantation, group I recipients with acute rejection showed higher relative levels of plasma sCD30 on days 7 and 15 (120.8 +/- 74.6 U/mL and 210.6 +/- 108.7 U/mL respectively) compared with group II patients without rejection (95 +/- 45 U/mL and 59.4 +/- 31.6 U/mL), a difference that was significant for group I (P = .0003) and not significant for group II (P = .09). On day 21, sCD30 decreased in the two groups but remained higher among group I patients (120.6 +/- 92.7 U/mL). HLA antibodies were positive in 18 patients (34.6%) with 9 (50%) experiencing at last one episode of acute rejection. Among 34 patients negative for anti-HLA antibodies, nine displayed acute rejection only (26.4%), a difference that was not significant (P > .05). If we consider 100 U/mL as the minimum predictive level for allograft rejection, our results suggested that levels of sCD30 should be taken into consideration with the presence of HLA-antibodies detectable before and after transplantation, especially in patients with more than three HLA mismatches [RR = 3.20 (0.94 < RR < 10.91)]. These data suggested that measurement of plasma sCD30 is a useful procedure for the recognition of rejection in its earliest stages.

Hepatitis C virus antibodies in dialysis patients in Tunisia: a single center study.

Fifty-eight patients on maintenance hemodialysis in a dialysis unit at Tunis, Tunisia were tested for anti-hepatitis C virus (anti-HCV) antibodies by second generation ELISA test, and for HCV-RNA by nested reverse transcriptase polymerase chain reaction (RT-PCR) of 5' non-coding region. Specificity of the antibodies was confirmed by immunoblot test. HCV genotype was defined using INNO-LIPA test. Twenty-seven out of 58 patients (46.5%) were reactive by ELISA. Transaminase levels were assessed over a six-month period and showed normal average values. Fourteen of the 27 anti-HCV positive patients (51%) were positive by RT-PCR. Type 1b HCV genotype was the most prevalent, seen in all the dialysis patients and one patient in addition, was co-infected with genotype 4. There was a significant correlation between the duration on dialysis (over five years) and the prevalence of anti-HCV-positive patients (P< 0.005) while no correlation existed between the number of blood transfusions and the presence of anti-HCV antibodies. The present study illustrates the high prevalence of HCV infection among Tunisian dialysis patients (51%) and indicates that the spread may be nosocomial rather than transfusion-related.