Aureliusz Kolonko

Impact of early kidney resistance index on kidney graft and patient survival during a 5-year follow-up

BACKGROUND Resistance index (RI) measured by Doppler sonography during the early post-transplant period reflects interstitial oedema within the transplanted kidney. We have prospectively analysed the relationship between RI measured shortly after kidney transplantation (KTx), patient and graft survival, as well as kidney graft function during a 5-year follow-up. METHODS RI was measured at the second to fourth day after KTx in 364 consecutive patients, who were divided into tertiles, according to baseline RI value (Group 1: RI < 0.73, Group 2: RI between 0.73 and 0.85 and Group 3: RI > 0.85). The kidney graft function [estimated glomerular filtration rate (eGFR)] during the follow-up period was calculated according to the Modification of Diet in Renal Disease formula. RESULTS During the 5-year follow-up period, 23 patients died (2.6 versus 6.5 versus 9.6% in RI tertiles, respectively) and 59 lost their kidney graft (12.1 versus 17.7 versus 18.4%, respectively). Survival analyses showed that the effect of RI was significant for a combined outcome [graft loss or death; hazard ratio (HR) = 10.88] and in relation to death, it was of borderline significance (HR = 45.3, P = 0.09). The effect of delayed graft function (DGF) was only significant on graft loss (HR = 1.73). eGFR in the highest tertile was lower than in the lowest tertile during the entire follow-up period. CONCLUSIONS High RI values measured in segmental arteries in the very early post-transplant period predict worse kidney graft function and increased risk of all-cause graft loss, including patient death in the 5-year follow-up period. (ii) The predictive value of RI is not completely independent from the adverse influence of DGF on the premature graft loss.

‐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-β1 (TGF-β1) 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-β1 (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-β1 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.

Improved Kidney Graft Function After Conversion From Twice Daily Tacrolimus to a Once Daily Prolonged-Release Formulation

BACKGROUND Tacrolimus once daily (Tac-QD) formulation has been recently introduced to improve patient adherence to immunosuppressive medications. To evaluate long-term effects of conversion from tacrolimus twice daily (Tac-BID) to Tac-QD on kidney graft excretory function, we retrospectively analyzed kidney graft function after the conversion from Tac-BID to Tac-QD over 24 months. METHODS We enrolled 72 kidney transplant recipients, including 19 simultaneous pancreas-kidney cases, who were at least 9 months posttransplantation and showed stable graft function for 6 months. We analyzed kidney graft function (glomerular filtration rate [eGFR] by the Modification of Diet in Renal of Disease equation), tacrolimus daily dose and tacrolimus blood trough level changes over 24 months after conversion. RESULTS All patients completed the 12 months and 56 patients, 24 months observation. At 3 months, the eGFR increased significantly after conversion from 57.1 to 60.0 mL/min/1.73 m2 (P=.004) and at 24 months to 66.0 mL/min/1.73 m2 (P<.001). Tacrolimus daily dose diminished over time by almost 10%, a difference that reached statistical significance at 18 months. Tacrolimus blood trough levels did not change significantly until 24 months. There was no correlation between eGFR changes during the first 12 months after conversion and changes in tacrolimus blood trough levels (r=-0.118; P=.33). CONCLUSION Conversion from Tac-BID to Tac-QD formulation was followed by a clinically significant improvement in kidney graft function upon long-term observation. The improvement seemed to not be related to changes in tacrolimus blood trough levels.

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.

Extrarenal factors influencing resistance index in stable kidney transplant recipients.

Background Increased intrarenal resistance index (RI) has been associated with decreased long-term allograft and patient survival in kidney transplant recipients. Taking into account the potential role of endothelial dysfunction, systemic inflammation, arteriosclerotic lesions, and left ventricle remodeling, we performed a cross-sectional study that aimed to evaluate extrarenal factors that may have influence on kidney graft RI in a large cohort of stable kidney transplant recipients. Methods One hundred seventy-four kidney transplant recipients were enrolled into the study. Mean time after transplantation was 8.4±1.8 years. Echocardiography, carotid ultrasound (intima-media thickness), pulse wave velocity, and Doppler examination of kidney graft were performed. The inflammatory markers, adhesion molecules, and plasma N-terminal prohormone of brain natriuretic peptide concentrations were also measured. Patients were divided into quartile subgroups based on RI value (Q1: RI⩽0.68, Q2: RI=0.69–0.72, Q3: RI=0.73–0.76, and Q4: RI≥0.77). Results The analyzed subgroups were comparable with respect to demographics (except age) and anthropometric parameters as well as comorbidities. The values of age, serum phosphate, pulse wave velocity, left ventricular mass (LVM), and LVM index (LVMI) increased in subsequent RI quartile subgroups. The strongest correlation was found between RI and age, LVM, LVMI, and plasma parathormone concentration and was negative with estimated glomerular filtration rate. In backward stepwise multivariate regression analysis, the RI variability was explained by age, LVMI, and serum phosphate concentration. Conclusion Arterial stiffness and left ventricular hypertrophy may significantly influence the intrarenal vascular resistance measured using Doppler sonography in stable kidney transplant recipients.

Prediction of the severity and outcome of acute tubular necrosis based on continuity of Doppler spectrum in the early period after kidney transplantation

BACKGROUND Doppler flow spectrum, quantified in the segmental arteries of the graft early after kidney transplantation (KTx), reflects the exacerbation of interstitial oedema. In some patients, the spectrum is characterized by the absence of blood flow during part or during the whole diastole of the cardiac cycle. We have previously observed that such discontinuous flow is associated with a more severe clinical course of acute tubular necrosis (ATN). In order to further verify this hypothesis, we have quantified prospectively the timing of blood flow in Doppler spectrum within the cardiac cycle. METHODS Doppler sonography was performed in 173 recipients between 2 and 4 days after KTx. A total of 18 patients with a diagnosed episode of acute rejection or primary graft non-function were excluded from the analysis. Fifty-three out of 155 patients (34%) developed ATN, defined as a requirement for more than one haemodialysis session after KTx. In patients with a discontinuous spectrum of flow, we have quantified the ratio of time during the whole cardiac cycle in which the flow is present [flow time index (FTI) expressed as %]. RESULTS The discontinuous spectrum of flow was present in 35 out of 53 (66.0%) patients with ATN but only in 6 out of 102 (5.9%) patients with immediate or slow graft function. The relative risk of ATN occurrence for patients with discontinuous spectrum of flow was 5.98 (3.83-9.34) and the duration of ATN in these patients was twice as long-12 (10-14) versus 6 (5-8) days. In patients with ATN a significant correlation was found between FTI and duration of ATN (r = -0.357, P = 0.035). CONCLUSION The discontinuous spectrum of flow in the segmental arteries of the kidney graft in the early period after KTx is typical for ATN and predicts its duration.

Nephron Underdosing as a Risk Factor for Impaired Early Kidney Graft Function and Increased Graft Loss During the Long-Term Follow-up Period

BACKGROUND It is generally accepted that kidneys procured from female donors may not perform optimally in male recipients, mostly due to their smaller size and nephron underdosing. Nowadays, conflicting results have been published regarding the detrimental effect of H-Y incompatibility on the long-term prognosis of male kidneys transplanted into female recipient. The aim of this study was an analysis of the impact of donor-recipient gender matching on early function and survival of grafts among a relatively homogenous cohort of kidney recipients. METHODS We analyzed 477 consecutive first kidney transplants from deceased donors with longer than 3-month survival. Highly sensitized recipients and those with graft losses attributed to noncompliance were excluded from the study. Early kidney graft function was defined based on serum creatinine (Scr) concentrations at postoperative day 3 and the need for dialysis: immediate graft factors (IGF; Scr < 3mg/dL), slow graft function (Scr > 3mg/dL and no dialysis) or delayed graft function (DGF; dialysis in the first posttransplant week). RESULTS The lowest 10.7% incidence of IGF was observed among male recipients of female kidneys (F-M). For female donor, the relative risk for IGF in female recipient was 3.13 (1.35-7.26) than in male recipient. The frequencies of DGF were similar. During the 5-year follow-up, 54 grafts were lost. The risk for loss was significantly higher in the F-M group: 19.6% vs 8.8% in the three other combined groups (odds ratio = 2.54; 95 confidence interval (1.41-4.59); P = .002). CONCLUSIONS Transplantation of the female kidney to a male recipient impairs early kidney graft function increasing the risk of graft loss over a 5-year follow-up. This phenomenon seems to be related to nephron underdosing.

Plasma adiponectin concentration and left ventricular hypertrophy in kidney transplant patients

Adamczak M, Błach A, Kolonko A, Szotowska M, Chudek J, Franek E, Więcek A. Plasma adiponectin concentration and left ventricular hypertrophy in kidney transplant patients.
Clin Transplant 2011: 25: 561–568.

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 height2.7. 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.

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.