Association between gene polymorphisms of the components of the renin-angiotensin-aldosteron system, graft function, and the prevalence of hypertension, anemia, and erythrocytosis after kidney transplantation.

INTRODUCTION: Genetic predisposition, including polymorphisms of the renin-angiotensin system (RAS) genes, are among the potential factors that may affect the occurrence of hypertension, anemia, or erythrocytosis as well as transplanted kidney function. However, the association of the RAS genes polymorphism and the kidney transplant outcomes is controversial. The aim of this study was to analyze the association between polymorphic variants of the angiotensin-converting enzyme (insertion/deletion [I/D]), angiotensinogen (M235T), and angiotensin II receptor type 1 (A1166C) genes, and the early and long-term kidney graft outcomes, as well as the prevalence of hypertension, anemia and erythrocytosis after kidney transplantation. PATIENTS AND METHODS: We included 331 consecutive kidney transplant patients performed between 1998 and 2003. Of the total, 87.9% of patients completed a 5-year follow-up. Subjects were genotyped for the I/D, M235T, and A1166C polymorphisms. RESULTS: None of the examined polymorphism affected early or long-term graft function or was associated with hypertension before or after kidney transplantation. There was no significant difference in genotype distribution between patients with and without posttransplant erythrocytosis. However, posttransplant anemia (PTA) seemed to be significantly more common among kidney recipients with TT and MT than MM angiotensinogen genotypes (35.7% vs 20.7%; P=.03). The T allele was associated with the risk of development of PTA (odds ratio, 2.12; 95% confidence interval, 1.12-3.99; P=.02). CONCLUSION: Our results do not support the hypothesis that polymorphism of the genes coding RAS components may by an independent risk factor for the development of interstitial fibrosis/tubular atrophy, posttransplant hypertension, or PTE. Further studies are necessary to investigate the association between angiotensinogen M235T genotypes and PTA.

-174G/C interleukin-6 gene polymorphism and the risk of transplanted kidney failure or graft loss during a 5-year follow-up period.

The influence of cytokine gene polymorphisms on transplanted kidney outcome is not well understood. The aim of this one-centre study was to analyse the association between tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10, interferon-γ (IFN-γ) and transforming growth factor-ß1 (TGF-ß1) genotypes and the incidence of delayed graft function (DGF), acute rejection (AR) and 5-year kidney graft loss. Genotyping was performed in 199 subsequent kidney graft recipients from deceased donors without induction therapy based on polymerase chain reaction method using sequence-specific primers for TNF-α (-308A/G), IL-10 (-1082A/G, -819T/C and -592A/C), IL-6 (-174G/C), IFN-γ (+874T/A) and TGF-ß1 (in codons 10T/C and 25G/C). Genotypes were grouped according to the strength of cytokine expression. During a 5-year follow-up period, 14 patients died with functioning graft and 33 developed graft failure. The analysed polymorphisms were not associated with the incidence of DGF. The frequency of early episodes of AR was significantly associated only with TGF-ß1 genotype. There was an association between -174G/C IL-6 gene polymorphism and the death-censored kidney graft survival. The risk of graft loss during 5-year follow-up period was greater by 57% for GG or GC (higher IL-6 production) than for CC carriers. None of the other analysed polymorphisms significantly influenced both patients and kidney graft survival, also in the analysis of the subgroup with human leucocyte antigen-DR mismatch. -174G/C IL-6 genotype of the kidney graft recipient could modulate the rate of graft excretory function deterioration and the risk of graft loss by influencing their constitutional expression.

Anemia and erythrocytosis after kidney transplantation: a 5-year graft function and survival analysis.

INTRODUCTION: Both anemia and erythrocytosis frequently occur after kidney transplantation. The aim of this study was to analyze the influence of both anemia and erythrocytosis on kidney graft function and long-term patient outcomes following kidney transplantation. PATIENTS AND METHODS: Three hundred eight-five consecutive patients with at least 12 months of follow-up after successful kidney transplantation were enrolled into this study. Of the total, 88.3% of patients completed a 5-year follow-up. Anemia occurred in 30.4% of patients (with 17.7% showing a hemoglobin concentration (Hb) <11.0 g/dL), whereas erythrocytosis was observed in 19.0% of patients, including 9.6% with hematocrit (HTC) >55%. We also analyzed graft function every 6 months after transplantation for the impact of anemia or erythrocytosis on the 5-year risk of patient death or graft loss. RESULTS: In 57.3% of anemia patients the Hb did not reach the normal range during the observation time. The mean eGFR-Modification of Diet in Renal Disease (MDRD) at 12 months after transplantation was significantly lower among patients with anemia: 43.9 mL/min/1.73 m(2) (39.5-48.4) vs 55.3 mL/min/1.73 m(2) (53.0-57.6; P < .001). Better 12-month graft function was observed among patients with erythrocytosis, namely, 57.7 mL/min/1.73 m(2) (53.5-62.0). Anemia but not erythrocytosis was associated with an increased risk of graft loss (hazard ratio [HR] = 4.11 [95% confidence interval (CI) 2.02-8.37]; P < .001). CONCLUSION: Anemia after transplantation was associated with worse kidney graft function and was a strong predictor of graft loss. Erythrocytosis occurs among patients with excellent allograft function; when properly treated it did not increase the risk of graft loss or death.