Association between Kidney Donor Risk Index, kidney graft function and histological changes in early post-transplant graft biopsy.

Background: Proper assessment of donor organ quality is crucial for optimal kidney allocation and best long-term outcomes. The aim of this study was to analyze the association between the Kidney Donor Risk Index (KDRI) and histological parameters in early post-transplant graft biopsy in a Polish cohort of kidney transplant recipients. Methods: In 418 consecutive kidney transplant recipients, a histological evaluation of very early [at median 11 (9-13) post-transplant day] protocol core needle biopsy was performed and analyzed according to the Banff classification. Subjects were divided into quartiles of the KDRI value. Kidney graft function, patient and graft survival were also analyzed over a median follow-up period of 44 (26-56) months. Results: There was a significant trend toward greater intensity of chronic histology changes along the KDRI quartiles (χ2 = 20.8; P < .001), including interstitial fibrosis, tubular atrophy, mesangial matrix increase and arteriolar hyalinosis. Stepwise multivariate regression analysis revealed that only higher KDRI value independently increased the severity of chronic graft injury (rpartial = 0.340, P < .001). KDRI values were valuable in the determination of both early and long-term graft function. Conclusion: The KDRI values correlate with chronic histological changes found in early post-implantation kidney biopsies and can also be helpful in the prediction of graft outcome.

Beneficial Effect of Successful Simultaneous Pancreas-Kidney Transplantation on Plasma Profile of Metalloproteinases in Type 1 Diabetes Mellitus Patients.

It is not fully elucidated whether the restoring of normal glucose metabolism after successful simultaneous pancreas-kidney transplantation (SPK) improves vascular wall morphology and function in type 1 diabetic (T1D) patients. Therefore, we compared arterial stiffness, assessed by pulse wave velocity (PWV), carotid intima-media thickness (IMT), and biomarkers of arterial wall calcification in T1D patients after SPK or kidney transplantation alone (KTA). In 39 SPK and 39 KTA adult patients of similar age, PWV, IMT, circulating matrix metalloproteinases (MMPs) and calcification biomarkers were assessed at median 83 months post transplantation. Additionally, carotid plaques were visualized and semi-qualitatively classified. Although PWV and IMT values were similar, the occurrence of atherosclerotic plaques (51.3 vs. 70.3%, p < 0.01) and calcified lesions (35.9 vs. 64.9%, p < 0.05) was lower in SPK patients. There were significantly lower concentrations of MMP-1, MMP-2, MMP-3, and osteocalcin in SPK subjects. Among the analyzed biomarkers, only logMMP-1, logMMP-2, and logMMP-3 concentrations were associated with log HbA1c. Multivariate stepwise backward regression analysis revealed that MMP-1 and MMP-3 variability were explained only by log HbA1c. Normal glucose metabolism achieved by SPK is followed by the favorable profile of circulating matrix metalloproteinases, which may reflect the vasoprotective effect of pancreas transplantation.

The Effects of Short-Term Changes in Sodium Intake on Plasma Marinobufagenin Levels in Patients with Primary Salt-Sensitive and Salt-Insensitive Hypertension.

Increased marinobufagenin (MBG) synthesis has been suggested in response to high dietary salt intake. The aim of this study was to determine the effects of short-term changes in sodium intake on plasma MBG levels in patients with primary salt-sensitive and salt-insensitive hypertension. In total, 51 patients with primary hypertension were evaluated during acute sodium restriction and sodium loading. Plasma or serum concentrations of MBG, natriuretic pro-peptides, aldosterone, sodium, potassium, as well as hematocrit (Hct) value, plasma renin activity (PRA) and urinary sodium and potassium excretion were measured. Ambulatory blood pressure monitoring (ABPM) and echocardiography were performed at baseline. In salt-sensitive patients with primary hypertension plasma MBG correlated positively with diastolic blood pressure (ABPM) and serum NT-proANP concentration at baseline and with serum NT-proANP concentration after dietary sodium restriction. In this subgroup plasma MBG concentration decreased during sodium restriction, and a parallel increase of PRA was observed. Acute salt loading further decreased plasma MBG concentration in salt-sensitive subjects in contrast to salt insensitive patients. No correlation was found between plasma MBG concentration and left ventricular mass index. In conclusion, in salt-sensitive hypertensive patients plasma MBG concentration correlates with 24-h diastolic blood pressure and dietary sodium restriction reduces plasma MBG levels. Decreased MBG secretion in response to acute salt loading may play an important role in the pathogenesis of salt sensitivity.

Changes in Office Blood Pressure Control, Augmentation Index, and Liver Steatosis in Kidney Transplant Patients after Successful Hepatitis C Infection Treatment with Direct Antiviral Agents.

Hepatitis C virus (HCV) infection in kidney transplant recipients (KTRs) can be successfully treated with direct antiviral agents (DAA). The aim of our study was to analyze different measures of vascular function during and after the DAA treatment. As we have observed the improvement of blood pressure (BP) control in some individuals, we have conducted an analysis of potential explanatory mechanisms behind this finding. Twenty-eight adult KTRs were prospectively evaluated before and 15 months after start of DAA therapy. Attended office BP (OBP), augmentation index (AIx), pulse wave velocity (PWV), flow-mediated dilation (FMD), liver stiffness measurement (LSM), and liver steatosis assessment (controlled attenuation parameter (CAP)) were measured. In half of the patients, improvement of OBP control (decline of systolic BP by at least 20 mmHg or reduction of the number of antihypertensive drugs used) and parallel central aortic pressure parameters, including AIx, was observed. There was a significant decrease in CAP mean values (241 ± 54 vs. 209 ± 30 dB/m, p < 0.05) only in patients with OBP control improvement. Half of our KTRs cohort after successful HCV eradication noted clinically important improvement of both OBP control and central aortic pressure parameters, including AIx. The concomitant decrease of liver steatosis was observed only in the subgroup of patients with improvement of blood pressure control.

A Rare Mutation in The APOB Gene Associated with Neurological Manifestations in Familial Hypobetalipoproteinemia.

Clinical phenotypes of familial hypobetalipoproteinemia (FHBL) are related to a number of defective apolipoprotein B (APOB) alleles. Fatty liver disease is a typical manifestation, but serious neurological symptoms can appear. In this study, genetic analysis of the APOB gene and ophthalmological diagnostics were performed for family members with FHBL. Five relatives with FHBL, including a proband who developed neurological disorders, were examined. A sequencing analysis of the whole coding region of the APOB gene, including flanking intronic regions, was performed using the next-generation sequencing (NGS) method. Electrophysiological ophthalmological examinations were also done. In the proband and his affected relatives, NGS identified the presence of the pathogenic, rare heterozygous splicing variant c.3696+1G>T. Two known heterozygous missense variants-c.2188G>A, p.(Val730Ile) and c.8353A>C, p.(Asn2785His)-in the APOB gene were also detected. In all patients, many ophthalmologic abnormalities in electrophysiological tests were also found. The identified splicing variant c.3696+1G>T can be associated with observed autosomal, dominant FHBL with coexisting neurological symptoms, and both identified missense variants could be excluded as the main cause of observed clinical signs, according to mutation databases and the literature. Electroretinography examination is a sensitive method for the detection of early neuropathy and should therefore be recommended for the care of patients with FHBL.

Lactobacillus plantarum 299v Reduces the Incidence of Clostridium difficile Infection in Nephrology and Transplantation Ward-Results of One Year Extended Study.

Background: Lactobacillus plantarum 299v (LP299v) is a probiotic strain which influences on the intestinal bacterial flora. This is why, it has been introduced into clinical practice for the prevention and treatment of diarrheal disorders and alleviation of their symptoms in patients during antibiotic therapy. However, the use of probiotics in the prophylaxis of Clostridium difficile infections (CDI) in these patients is problematic. The aim of this clinical, retrospective, single-centre study was to analyse the incidence of CDI among patients hospitalized in the nephrology and transplantation ward in the period before, during and after stopping of LP299v prophylaxis. Methods: Among 5341 patients hospitalized in the nephrology and transplantation ward over a three year period, 34 patients with CDI were diagnosed and included in this analysis. From December 2013 to December 2014 all patients under antibiotic and immunosuppressive therapies received LP299v as a prophylaxis of CDI. The observation period consisted of three twelve-months periods: before, during LP299v use and after stopping of such method of CDI prevention. Results: A significant (p = 0.0003) reduction of CDI incidence during LP299v use (0.11%) was observed compared to two other periods, that is, before and after LP299v use (1.03% and 0.77%, respectively). Conclusions: Routine use of LP299v as a CDI prophylaxis may prevent CDI during antibiotics therapy in patients treated with immunosuppressive agents in nephrology and transplantation ward.

Arterial stiffness but not endothelial dysfunction is associated with multidrug antihypertensive therapy and nondipper blood pressure pattern in kidney transplant recipients.

Vascular injury related to chronic kidney disease results in increased arterial stiffness and endothelial dysfunction which may affect arterial blood pressure (BP) and influence patient and graft survival in kidney transplant recipients (KTRs).This cross-sectional study aims to elucidate the relationship between the above-mentioned measures of vascular damage and effectiveness of antihypertensive treatment in KTR.One hundred forty-five KTRs 7.6 ±â€Š2.7 years after transplantation were enrolled in our study. Pulse wave velocity (PWV), flow-mediated dilation (FMD), and nitroglycerin-mediated dilation (NMD) were measured, and 24-hour ambulatory BP monitoring was performed.Overall, there were 62 patients with well-controlled or borderline BP and 83 subjects who did not achieve target BP despite antihypertensive treatment. Patients with suboptimal BP control were characterized by greater PWV (median 9.6/interquartile range: 3.9 vs 8.0/3.3 m/s, P = .002), but borderline lower FMD (8.4% ±â€Š5.0% vs 9.9% ±â€Š5.7%; P = .09) as compared with the group with better BP control. When patients were allocated to subgroups based on the number of current antihypertensive medications, no differences in FMD and NMD were found. However, a significant trend was observed for higher PWV values and decreased proportion of dippers along with the increasing number of drugs. PWV, diabetes, and total cholesterol level, but not FMD or NMD, were explanatory variables for systolic BP in multivariate analysis.Arterial stiffness but not endothelial dysfunction is associated with suboptimal BP control in stable KTRs. Less efficient antihypertensive treatment appears to be caused by inadequate control of nocturnal BP.

Plasma marinobufagenin immunoreactivity in patients with chronic kidney disease: a case control study.

Experimental data have shown increased plasma levels of marinobufagenin in kidney failure. In this case-controlled retrospective analysis, we evaluated plasma marinobufagenin immunoreactivity in hemodialysis patients compared with subjects with normal kidney function. Sixty-eight adult hemodialysis patients with chronic kidney disease (34 females and 34 males) as well as 68 age-, gender-, and blood pressure-matched subjects without chronic kidney disease were enrolled. Patients on stable hemodialysis regimen for at least 3 mo before the study were included. Exclusion criteria were: age <18 yr, severe liver or heart insufficiency, and overhydration. Subjects without chronic kidney disease must have had an estimated glomerular filtration rate ≥60 ml·min-1·1.72 m-2 according to the Modification of Diet in Renal Disease formula. Plasma marinobufagenin immunoreactivity was significantly ( P < 0.001) higher in hemodialysis patients (1.66 ± 1.13 nmol/l) compared with subjects with normal kidney function (0.46 ± 0.23). In hemodialysis patients, plasma marinobufagenin immunoreactivity was higher in men compared with women. A significant positive correlation has been found between plasma marinobufagenin immunoreactivity and serum NT-proBNP, NT-proANP, or aldosterone concentrations in all analyzed subjects. In hemodialyzed patients with plasma marinobufagenin immunoreactivity above median value 5-yr, all-cause mortality was higher compared with those with plasma marinobufagenin concentration below median. We have shown that plasma marinobufagenin immunoreactivity is increased in patients with end-stage kidney failure treated with hemodialysis parallel to the increase in serum NT-proBNP, NT-proANP, and aldosterone concentrations. Higher marinobufagenin immunoreactivity has been associated with worse survival in hemodialyzed patients.

Type 1 diabetic patients have better endothelial function after simultaneous pancreas-kidney transplantation than after kidney transplantation with continued insulin therapy.

The purpose of this study was to analyse the influence of simultaneous pancreas-kidney or kidney transplantation on endothelial function and systemic inflammation in type 1 diabetic patients with end-stage renal disease. In 39 simultaneous pancreas-kidney, 39 type 1 diabetic kidney and 52 non-diabetic kidney recipients, flow-mediated dilatation was measured. Additionally, blood glycated haemoglobin, serum creatinine and lipids, plasma nitrites [Formula: see text] and nitrates, asymmetric dimethylarginine, soluble vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin, high-sensitivity C-reactive protein, tumour necrosis factor-α, interleukin 1ß and interleukin 6 concentrations were assessed. During 58 ± 31 months follow-up period, flow-mediated dilatation and [Formula: see text] were greater in simultaneous pancreas-kidney than in type 1 diabetic kidney recipients [10.4% ± 4.7% vs 7.7% ± 4.2%, p < 0.05 and 0.94 (0.74-1.34) vs 0.24 (0.20-0.43) µmol/L, p < 0.01, respectively]. In type 1 diabetic patients after simultaneous pancreas-kidney or kidney transplantation, [Formula: see text] correlated with flow-mediated dilatation (r = 0.306, p < 0.05) and with blood glycated haemoglobin (r = -0.570, p < 0.001). The difference in [Formula: see text] was linked to blood glycated haemoglobin and estimated glomerular filtration rate, whereas the difference in flow-mediated dilatation was linked to [Formula: see text]. The levels of inflammatory markers (except soluble vascular cell adhesion molecule-1) were similar in simultaneous pancreas-kidney and type 1 diabetic kidney recipients. Improved endothelial function in type 1 diabetic patients with end-stage renal disease after simultaneous pancreas-kidney compared to kidney transplantation is associated with normalisation of glucose metabolism but not with improvement in plasma pro-inflammatory cytokines.

Analysis of Clostridium difficile infections in patients hospitalized at the nephrological ward in Poland.

BACKGROUND: Few studies have evaluated the incidence and risk factors of Clostridium difficile infection (CDI) in the adult Polish population, in particular in solid organ recipients hospitalized at the nephrological ward. AIM: The aim of this study was to analyze Clostridium difficile infections (CDI) among patients hospitalized in the Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia in Katowice. MATERIAL/METHODS: Thirty-seven patients with Clostridium difficile infection diagnosed between October 2011 and November 2013 (26 months), identified among a total of 3728 patients hospitalized in this department during this period, were included in this retrospective, single-center study. The CDI definition was based on the current recommendations of the European Society of Clinical Microbiology and Infectious Diseases. RESULTS: The observation period was divided into two 13-month intervals. Increased incidence (of borderline significance) of CDI in the second period compared to the first period was observed (1.33% vs 0.65% respectively; p=0.057). Patients after kidney (n=11), kidney and pancreas (n=2) and liver (n=5) transplantation represented 48% of the analyzed CDI patients, and in half of these patients (50%) CDI symptoms occurred within the first 3 months after transplantation. Clostridium difficile infection leads to irreversible deterioration of graft function in 38% of kidney recipients. Most incidents of CDI (70%) were identified as nosocomial infection. CONCLUSIONS: 1. Clostridium difficile infection is particularly common among patients in the early period after solid organ transplantation. 2. Clostridium difficile infection may lead to irreversible deterioration of transplanted kidney function.

The Effect of Lactobacillus plantarum 299v on the Incidence of Clostridium difficile Infection in High Risk Patients Treated with Antibiotics.

BACKGROUND: Lactobacillus plantarum 299v (LP299v) has been used in order to reduce gastrointestinal symptoms during antibiotic exposure. However, it remains controversial whether or not probiotics are effective in the prevention of Clostridium difficile infections (CDI) among patients receiving antibiotics. The aim of this study was to analyze the CDI among patients receiving antibiotics and hospitalized in the period before and after starting routine use of LP299v as a prevention of this infection. METHODS: Among 3533 patients hospitalized in the nephrology and transplantation ward during a two-year period, 23 patients with CDI were diagnosed and enrolled in this retrospective study. Since November 2013, prevention of CDI with oral use of LP299v was performed in all patients treated with antibiotics and who were at a high risk of developing CDI. The observation period was divided into two twelve-month intervals before and after initiation of the use of LP299v as a prophylactic against CDI. RESULTS: A significant (p = 0.0001) reduction of the number of cases of CDI was found after routinely using LP299v (n = 2; 0.11% of all hospitalized patients) compared with the previous twelve-month period of observation (n = 21; 1.21% of all hospitalized patients). CONCLUSIONS: Routine use of LP299v during treatment with antibiotics may prevent C. difficile infection in the nephrology and transplantation ward.

Serum copeptin level predicts a rapid decrease of overhydration after kidney transplantation.

BACKGROUND: The assessment of proper hydration status in hemodialysis patients is difficult. None of currently available markers or measures is clinically relevant. Recently, human pre-pro-vasopressin (1-164) split product [copeptin (CPP)] - a new surrogate marker of hydration status - was introduced. The aim of the study was to analyze body weight changes in the early post-transplant period in relation to serum CPP levels before kidney transplantation. METHODS: Serum CPP and NT-proBNP concentrations and osmolality were measured in 130 kidney recipients directly prior to transplantation and, additionally, in 78 of them at 14th day post-transplant. Hydration status at transplantation was calculated from the difference in the patient's body weight before transplantation and at the discharge. RESULTS: During the post-transplant hospitalization, the average weight change was -1.6 kg, varying from 10.5 kg loss to weight gain of 5 kg. The overall weight loss was significantly related to pretransplant serum concentration of CPP (r=0.238), but not of NT-proBNP or osmolality. Patients with the lowest initial CPP level (first tertile) had smaller post-transplant weight loss. The early kidney graft function was unrelated to pretransplant CPP. Multivariate regression model revealed that variability of post-transplant weight loss is explained by the number of antihypertensive drugs used prior to transplantation [ß=0.213 (0.049-0.377)] and pretransplant CPP values [ß=0.233 (0.069-0.397)]. CONCLUSIONS: Elevated serum CPP level predicts a rapid weight loss after kidney transplantation and seems to characterize the subgroup of patients with the greatest overhydration. These results suggest the dysregulation of physiological mechanisms of CPP secretion in hemodialysis patients.

The association of long-functioning hemodialysis vascular access with prevalence of left ventricular hypertrophy in kidney transplant recipients.

Left ventricular hypertrophy (LVH) is frequently observed in chronic dialysis patients and is also highly prevalent in kidney transplant recipients. This study evaluates the impact of long-functioning hemodialysis vascular access on LVH in single center cohort of kidney transplant recipients. 162 patients at 8.7 ± 1.8 years after kidney transplantation were enrolled. Echocardiography, carotid ultrasound, and assessment of pulse wave velocity were performed. LVH was defined based on left ventricular mass (LVM) indexed for body surface area (BSA) and height(2.7). There were 67 patients with and 95 without patent vascular access. Both study groups were comparable with respect to gender, age, duration of dialysis therapy, and time after transplantation, kidney graft function, and cardiovascular comorbidities. Patients with patent vascular access were characterized by significantly elevated LVM and significantly greater percentage of LVH, based on LVMI/BSA (66.7 versus 48.4%, P = 0.02). OR for LVH in patients with patent vascular access was 2.39 (1.19-4.76), P = 0.01. Regression analyses confirmed an independent contribution of patent vascular access to higher LVM and increased prevalence of LVH. We concluded that long-lasting patent hemodialysis vascular access after kidney transplantation is associated with the increased prevalence of LVH in kidney transplant recipients.

Calcification of coronary arteries and abdominal aorta in relation to traditional and novel risk factors of atherosclerosis in hemodialysis patients.

BACKGROUND: Process of accelerated atherosclerosis specific for uremia increases cardiovascular risk in patients with chronic kidney disease (CKD) and may be influenced by the different structure of arteries. The study assesses the influence of traditional and novel risk factors on calcification of coronary arteries (CAC) and abdominal aorta (AAC) in hemodialysis patients (HD). METHODS: CAC and AAC were assessed by CT in 104 prevalent adult HD and 14 apparently healthy subjects with normal kidney function (control group). Mineral metabolism parameters, plasma levels of FGF-23, MGP, osteoprotegerin, osteopontin, fetuin-A, CRP, IL-6 and TNF-α were measured. RESULTS: CAC and AAC (calcification score ≥ 1) were found in 76 (73.1%) and 83 (79.8%) HD respectively, more frequent than in the control group. In 7 HD with AAC no CAC were detected. The frequency and severity of calcifications increased with age. Both CAC and AAC were more frequently detected in diabetics (OR = 17.37 and 13.00, respectively). CAC score was significantly greater in males. CAC and AAC scores were correlated significantly with pack-years of smoking and plasma osteoprotegrin levels. However the independent contribution of plasma osteoprotegerin levels was not confirmed in multiple regression analysis. Age (OR = 1.13) and hemodialysis vintage (OR = 1.14) were the independent risk factor favoring the occurrence of CAC; while age (OR = 1.20) was the only predictor of AAC occurrence in HD. CONCLUSIONS: 1. AAC precedes the occurrence of CAC in HD patients. 2. The exposition to uremic milieu and systemic chronic microinflammation has more deteriorative effect on the CAC than the AAC.

The lipid story in chronic kidney disease: a long story with a happy end?

Cardiovascular (CV) morbidity and mortality increase with the severity of kidney disease, reaching 30 times higher mortality rates in dialysis patients compared with the general population. Although dyslipidemia is a well-established CV risk factor in the general population, the relationship between lipid disorders and CV risk in patients with chronic kidney disease (CKD) is less clear. Despite the clear evidence that statins reduce the risk of atherosclerotic events and death from cardiac causes in individuals without CKD, the use of statins in patients with kidney disease is significantly less frequent. For a long time, one of the explanations was the lack of a prospective, randomized, controlled study designed specifically to CKD patients. After recent publication of the data from Study of Heart and Renal Protection trial, given the safety and potential efficacy of statins, this lipid-lowering treatment should be administered more frequently to individuals with CKD stage 1-4, as well as those undergoing dialysis.

[Gene polymorphisms of renin-angiotensin-aldosterone system components and the progression of chronic kidney diseases]. / Polimorfizm genów poszczególnych skladowych ukladu renina-angiotensyna-aldosteron a progresja przewleklej choroby nerek.

UNLABELLED: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of hypertension as well as cardiovascular diseases and chronic kidney diseases. Among the most frequently studied RAAS gene polymorphisms are the angiotensin-converting enzyme insertion/deletion (I/D), angiotensinogen M235T and angiotensin II receptor type 1 A1166C polymorphisms. A significant correlation was found between the I/D polymorphism and cardiovascular morbidity and mortality rates. However, there was no significant correlation between I/D, M235T, A1166C polymorphism and arterial hypertension. The role of I/D polymorphism in the development and progression of chronic kidney disease is also non-conclusive. However, DD genotype has been identified as relevant for loss of renal function both in patients with IgA nephropathy and in patients of Asian origin with diabetic nephropathy. The relationship between RAAS gene polymorphism and transplanted kidney function has not been confirmed in large prospective and retrospective studies. CONCLUSION: there is no clear opinion concerning the influence of RAAS genotypes on the prevalence of post-transplant hypertension or erythrocytosis. Although a role of RAAS gene polymorphism in kidney function deterioration could not be ruled out, it is more likely that a variety of genetic and environmental factors influence the progression of chronic kidney diseases.

[The influence of selected cytokine gene polymorphisms on the occurrence of acute and chronic rejection and on kidney graft survival]. / Wplyw polimorfizmów wybranych genów cytokin na wystepowanie ostrego i przewleklego odrzucania oraz na przezycie przeszczepionej nerki.

Genetically determined interindividual differences in the production of mediators of immune response may influence the outcomes of kidney transplantation. Of the cytokine gene polymorphisms that determine the level of gene expression, TNF-a -08G/A, IFN-g +874T/A and microsatellite (CA)n, TGF-b1 +869T/C and +915G/C, IL-6 -174G/C, and IL-10 -592C/A, -819C/T, and -1082G/A seem to have the strongest impact on graft survival. Increased risk of acute rejection (AR) was demonstrated for high-producing genotypes of pro-inflammatory cytokines such as TNF-a and IFN-g, while the association with polymorphisms of TGF-b1 and IL-10 remains unclear. A high production of profibrotic TGF-b1 is associated with interstitial fibrosis and tubular atrophy (IF/TA). In contrast, high genetically determined IL-6 gene expression played a protective role in the development of chronic rejection (CR). The risk of graft loss was greater among high TNF-a and low TGF-b1 or IL-6 producers. The results of kidney transplantation are also influenced by the donor's cytokine expression profile. Low IL-6 production donor genotype was associated with a higher prevalence of AR, CR, and IF/TA. Low donor transcriptional TGF-b1 gene activity predisposed the recipient to AR episodes and high IFN-g expression to IF/TA development. To date, study results are highly inconsistent, so the applicability of cytokine polymorphism genotyping remains questionable. In summary, it is difficult to conclude whether or not cytokine polymorphism genotyping is useful in the risk assessment of rejection and kidney graft survival and in applying optimal immunosuppressive medication.