Preoperative Computed Tomography Parameters and Deterioration of Remaining Kidney Function in Living Donors.

INTRODUCTION: After living kidney donation, a decrease of kidney function (described as estimated glomerular filtration rate [eGFR]) is observed in majority of donors. However, the loss is more significant in some patients without an explicable reason. The aim of this study was to identify quantitative parameters in computed tomography (CT) of the abdomen that would predict greater eGFR reduction after kidney removal. MATERIAL AND METHODS: One hundred and ten preoperative multiphase CT examinations of the abdomen of kidney donors were analyzed for the following renal parameters: cortex, parenchyma and pyramids volume, scarring thickness (low grade: <1 cm, high grade: >1 cm), cortical gaps, vascularisation, and cortex-to-aorta enhancement index (CAEI). The radiologic and biometric (eg, donor weight) parameters were correlated with eGFR (CKD-EPI formula) change between baseline and at discharge. RESULTS: Donor weight was correlated with a loss of eGFR (P < .001). Kidney volumetric parameters including renal cortex and parenchyma volume, as well as renal artery cross-section area were associated with donor weight (r = 0.50 P < .001 and r = 0.39 P < .001). CAEI was correlated with a loss of eGFR (P = .003) and was related to the donor's sex in favor of men. Forty-one (37%) donors had an additional renal artery, which did not influence kidney function. No influence of cortical gaps or scarring on eGFR was observed. CONCLUSIONS: CAEI may be a helpful tool in predicting greater short-term kidney function decrease after living kidney donation. Male sex is the strongest risk factor of greater eGFR loss after kidney donation.

Pretransplant Immune Interplay Between Donor and Recipient Influences Posttransplant Kidney Allograft Function.

BACKGROUND: Renal transplant candidates present immune dysregulation caused by chronic uremia, and deceased kidney donors present immune activation induced by brain death. Pretransplant donor and recipient immune-related gene expression were examined in the search for novel predictive biomarkers crosslinking recipient and donor pretransplant immune status with transplant outcome. MATERIALS AND METHODS: This study included 33 low-risk consecutive renal transplant recipients and matched deceased donors. The expression of 29 genes linked to tissue injury, T-cell activation, cell migration, and apoptosis were assessed in postreperfusion kidney biopsies, as well as 14 genes in pretransplant peripheral blood of the kidney recipients. Gene expression was analyzed with real-time polymerase chain reaction on custom-designed low-density arrays. RESULTS: Donor MMP9 expression was related to delayed graft function occurrence (P = .036) and short term kidney allograft function (14th day rs = -0.44, P = .012; 1st month rs = -0.46, P = .013). Donor TGFB1 expression was associated with short- and long-term graft function (14th day rs = -0.47, P = .007; 3rd month rs = -0.63, P = .001; 6th month rs = -0.52, P = .010; 12th month rs = -0.45, P = .028; 24th month rs = -0.64, P = .003). Donor TGFB1 expression was not related to donor age (rs = 0.32, P = .081), which was also an independent factor influencing the outcome. Recipient gene expression was not related to graft function but determined the acute rejection risk. Recipient IFNG and, to a lesser extent, IL18 expression were protective against acute rejection (area under the curve [AUC] 0.84, P < .001, and AUC 0.79, P < .001, respectively). CONCLUSION: Kidney transplant outcome depends on the interplay between donor-related immune factors, which mostly affect allograft function and recipient immune milieu, influencing an alloreactive response.

Functional Activity of the Complement System in Deceased Donors in Relation to Kidney Allograft Outcome.

Complement activation is considered one of the mediators of renal ischemia-reperfusion injury. Elevated levels of C5b-9, C3a, and C5a are detected in sera of deceased kidney donors. The goal of the study was to characterize the functional activity of complement pathways in donor sera and to assess their influence on transplant outcome. MATERIALS AND METHODS: Sixty-four deceased kidney donors (age 45 ± 16 years; 28 female, 36 male) and 27 healthy controls (age 42 ± 12 years; 14 female, 13 male) were enrolled in the study. The results of transplantation for the respective 122 kidney recipients were included in the analysis. The functional activities of classical (CP), lectin (LP), and alternative (AP) pathways were measured using Wielisa-kit (reference normal level = 100%). In most cases, decreased functional activity reflects the activation status of the pathway. RESULTS: The median (interquartile range) functional activities of the pathways in donor sera were CP 118 (89-150)%, LP 80 (20-127)%, and AP 74 (50-89)%, and did not differ from the control values CP 110 (102-115)%, LP 81 (26-106)%, AP 76 (61-88)%. The frequency of pathway activation observed in controls was CP 0%, LP 11%, and AP 0%. Deceased donors did not differ in activation of classical (11%) and lectin (13%) pathways, but presented a higher rate of alternative pathway activation (19%, P = .03). No significant influence of any pathway functional activity or its activation was proved to influence the transplant outcome. CONCLUSION: Complement activation via alternative pathway was observed in diseased donor sera. No predictive potential of donor complement functional activity on the transplant outcome could be proved.

Kidney Transplantation From Old Deceased Donors: Impact of Uric Acid Level-A Quarter-Century of Experience in One Transplant Center.

BACKGROUND: The long-term burden of higher donor age on graft function and survival after kidney transplantation remains uncertain. Because both recipient and donor characteristics have evolved and the general population age is on the increase, we looked at the causes of kidney graft outcome. AIM: The aim of this study was to evaluate the impact of different clinical parameters on long-term outcome of older-donor kidney transplantation. This retrospective study included 345 adult patients (58 patients received kidney from donors at least 55 years old) transplanted between January 1993 and December 2005 and were followed in one center throughout the post-transplant course (median, 9.4 years). Data included recipient and donor age, cold ischemia time, delayed graft function, panel reactive antibodies, HLA mismatch, time on dialysis, graft function at different time points, uric acid level, proteinuria, immunosuppression, and biopsy-proven rejection. RESULTS: Improvement of estimated glomerular filtration rate at 36 months after transplantation was a good prognostic factor for long-term kidney function. Higher donor age decreased the chance for improvement of kidney function by 2.8% per year of life (P = .0244). Hyperuricemia was found in 46% of the study population; estimated glomerular filtration rate less than 50 mL/min/1.72 m2 was associated with hyperuricaemia. A higher uric acid level was associated with inferior kidney function in recipient of older kidneys. Graft failure occurred late (median, 6.3 years post-transplantation) in 26 (44.8%) of older-donor recipients and in 87 (30.3%) of the remaining patients. CONCLUSIONS: Our results suggest an important association between older donor age and decreased allograft function in kidney recipients with elevated uric acid level. Recipients of older kidneys with normal uric acid level presented satisfactory outcomes.

Expression of PBMC TLR4 in Renal Graft Recipients Who Experienced Delayed Graft Function Reflects Dynamic Balance Between Blood and Tissue Compartments and Helps Select a Problematic Patient.

Both Toll-like receptor 4 (TLR4) and monocytes focus stimuli, causing them to contribute differently to chronic injury of a transplanted kidney. AIM: The aim of our study was to determine if TLR4 monocyte is a diagnostic tool and possibly a target for therapeutic intervention. MATERIALS: We studied 143 kidney transplant (KT) patients (88 male, 55 female; 50.3 ± 12.8 years); median was 10.4 post KT, follow-up was 11.4 months, and 46 patients had delayed graft function (DGF+) history. Control group (38 healthy volunteers) had monocyte mRNA-TLR4 expression (TLR4ex). DGF+ were divided by median of TLR4ex (-0.1034) into 2 groups: low-TLR4 expression (L-TLR4ex) and high-TLR4 expression (H-TLR4ex). RESULTS: We showed that in comparison with DGF-, the DGF+ had much lower TLR4ex, and worse KT function both currently (TLR-day) (serum creatinine [sCr] P = .002; estimated glomerular filtration rate [eGFR] P = .001) and post follow-up (sCr P = .006; eGFR P = .005). The DGF+ with L/H-TLR4ex comparison showed no differences in TLR-day KT function but did show differences in post follow-up (sCr P = .01; eGFR P = .02; ΔeGFR% P = .001). Regression analysis showed an association between recipient age, tacrolimus concentration, and uremic milieu (ie, TLR-day sCr and GFR with TLR4ex). Reverse regression analysis indicated an association of TLR4ex (especially L/H-TLR4ex) with post follow-up parameters of KT function and numeric/qualitative measures of change. CONCLUSION: DGF affects the fate of a graft. Within a several months after transplantation, TLR4ex of peripheral blood mononuclear cells declines in DGF patients. Low LR4ex in patients with DGF+ is associated with poor prognosis for the efficiency of the KT. In patients with DGF+, the proper selection of immunosuppression (tacrolimus dosing) is very important. Higher concentrations of tacrolimus may improve prognosis. The analysis of TLR4ex change may be a useful parameter for the real assessment of immunosuppression efficacy. It is important for transplanted organ function that peripheral blood mononuclear cells effectively leave circulation and remain in the graft.

Pretransplantation Oral Glucose Tolerance Test Can Prevent Posttransplant Diabetes Mellitus After Renal Transplantation: Preliminary Study.

Posttransplant diabetes mellitus (PTDM) adversely affects renal graft and patient survival. Fasting plasma glucose (FPG) alone underestimates diagnosis of glucose metabolism disorders (GMD) detected using the oral glucose tolerance test (OGTT-75). Prediabetes including impaired fasting glucose (IFG): 100 to 125 mg/dL (5.6-6.9 mmol/L) and impaired glucose tolerance (IGT): 140 to 199 mg/dL (7.8-11 mmol/L) 2 hours post 75-g OGTT in the pretransplant period can have a connection with the occurrence of PTDM after renal transplantation (RTx). The aim of our study was to assess the benefit of performing OGTT-75 in dialyzed chronic kidney disease (stage 5) patients on the waiting list for kidney transplantation as a useful tool to prevent PTDM. MATERIALS AND METHODS: Pretransplant glucose testing using OGTT-75 was performed in nondiabetic dialyzed chronic kidney disease patients on the waiting list for renal transplantation in the southwest region of Poland. GMD were diagnosed according to current criteria. Patients with recognized prediabetic stage were recommended a low carbohydrate diet, lifestyle modification, and increased physical activity. In the 12-month posttransplant period we estimated the prevalence of PTDM in the study group based on FPG >126 mg/dL (7 mmol/L) in 2 measurements or random blood glucose >200 mg/dL (11.1 mmol/L). RESULTS: A total of 80 nondiabetic dialysis patients (65 hemodialysis/15 peritoneal dialysis; 47 male/33 female) met initial entry criteria. In pretransplant glucose testing prediabetes was found in 31 out of 80 patients (39%). Among them, 5 patients (6.25%) had combined IGT/IFG, 18 patients (22.5%) had IGT, and 8 patients (10%) had IFG. One year after RTx we recognized PTDM in 14% of all analyzed patients (11/80) and noticed a significant frequency of glucose disorders status change after RTx (P  = .002). CONCLUSION: Our findings suggest early detection of prediabetes using the OGTT-75 test in nondiabetic dialysis patients waiting for RTx to prevent occurrence of PTDM.

Endothelin A Receptors Expressed in Renal Blood Vessels of Renal Transplant Patients Are Connected With Acute Tubular Necrosis or Antibody-Mediated Rejection.

BACKGROUND: The role of non-HLA antibodies named antiendothelin A receptor antibodies is potentially significant but not established. The significance of the endothelin A receptor (ETAR) and its expression in renal biopsy has not been defined. We decided to evaluate the presence and relevance of ETARs in renal transplant biopsy for cause. The aim of our study was to evaluate the immunoreactivity of the ETAR and its significance in patients who had a renal transplant biopsy due to deterioration of transplant function (biopsy for cause) with detailed characterization of staining in small and intermediate arteries of renal transplant biopsies. METHODS: Immunohistochemical expression of ETARs was analyzed in 162 renal transplant biopsies. Microscopic evaluation of ETAR expression (polyclonal antibody) was performed on paraffin sections. ETAR expression was analyzed in renal blood vessels (small and intermediate arteries) based on three-step scale. RESULTS: We analyzed 154 patients who had renal allograft biopsy between 6 days and 24 years (median 597 days) after transplantation. Positive staining of ETAR in small and intermediate arteries was noticed in 9 patients. Among these patients, 4 had early biopsies (<3 months after transplantation), all developed acute tubular necrosis, and 1 developed additionally acute humoral rejection. Further, 4 patients had late biopsy (1-8 years after transplantation) and all developed characteristics of antibody mediated rejection. Lastly, 1 patient had no characteristic changes in the biopsy 4 months after transplantation. Graft loss 1 year after biopsy was higher in patients who were ETAR-positive but statistical significance was not achieved. CONCLUSIONS: The expression of endothelin receptors in renal blood vessels (small and intermediate arteries) seems to be important in diagnosis of damage during acute tubular necrosis and antibody-mediated rejection.

Serum 25-Hydroxyvitamin D Level Is Not Related to Regulatory T Cells or Kidney Function in Renal Transplant Recipients.

BACKGROUND: Vitamin D and regulatory T cells (Tregs) are both involved in promoting peripheral tolerance and limiting chronic inflammatory diseases. Renal transplant recipients (RTRs) are likely to have low vitamin D levels, which may influence their immune status. AIM: The aim of our study was to assess the usefulness of serum 25-hydroxyvitamin D (25(OH)D) and Tregs in estimation of the protolerogenic milieu in RTRs within 1 year after kidney transplantation. METHODS: 26 RTRs (15M/11F, aged 49.1 ± 15.4 years) 3 to 13 months after kidney transplantation and 24 healthy volunteers were enrolled for the study. The serum level of 25(OH)D was measured with ELISA and peripheral blood immune cell populations (T lymphocytes, helper T lymphocytes, and Tregs) were assessed by flow cytometry. RESULTS: Severe 25(OH)D deficiency (<10 ng/mL) was found in one RTR (3%) and moderate deficiency (<20 ng/mL) in 12 (46%), while vitamin D sufficiency was found in 6 patients (23%). The RTRs did not differ from the control group in observed 25(OH)D levels. None of the cell populations were related to the level of 25(OH)D in the control group. In RTRs, there was a negative association between 25(OH)D and total T lymphocyte count (rs = -0.45, P = .023), but 25(OH)D was not related to any other cell population or kidney function. CONCLUSION: The results of our study suggest that serum 25(OH)D is not sufficiently reflective of vitamin D status to apply this measure in assessment of protolerogenic milieu in RTRs.

Histopathological Relevance of Angiotensin II Type 1 Receptor in Renal Transplant Biopsy.

The occurrence of anti-angiotensin II type 1 receptor (AT1R) antibodies is thought to be a risk factor for transplant injury, but the relationship of AT1R to graft loss in renal transplantation has not been assessed. The aim of our study was to evaluate the expression of AT1R and its relationship with graft loss in patients who had a renal transplant biopsy for cause. METHODS: AT1R immunoreactivity was analyzed in 170 renal transplant biopsies. Immunohistochemical evaluation of AT1R expression was performed on 4 µm-thick paraffin sections mounted on silanized slides. AT1R expression was analyzed in 5 compartments: 1. glomeruli, 2. renal blood vessels (small and intermediate arteries), 3. peritubular capillaries, 4. tubular epithelium, and 5. interstitium based on a 3-step scale. RESULTS: Initially we checked 170 consecutive samples of biopsies for the immunoreactivity of the AT1R. The study finally included 118 renal transplant patients in 1-year observation after the biopsy. The renal allograft biopsy was performed between 6 days and 24 years after transplantation and the diagnosis was based on Banff criteria. We observed positive immunostaining of AT1R in tubular epithelium in 26.3% (42/118) of patients. A total of 7 patients had staining assessed as 2 and 35 as 1. One year post-biopsy graft loss in the AT1R (+) patients was 35.7 % (15/42) compared to 14.5% (11/76) in the AT1R (-) group (P = .008). CONCLUSIONS: The expression of AT1R in tubular epithelium of the biopsy for cause was associated with significantly higher graft loss. The relevance of AT1R should be considered for better transplant immunological risk assessment.

The Impact of Functioning Arteriovenous Fistula on Blood Pressure Control and Renal Allograft Function.

INTRODUCTION: The prevalence of hypertension in renal graft recipients is high. It was postulated that central arteriovenous anastomosis may significantly reduce blood pressure. This preliminary study evaluates the impact of functioning arteriovenous fistula (AVF) on blood pressure control and renal allograft function. MATERIALS AND METHODS: One hundred sixty-two previously hemodialyzed kidney transplant recipients (108 males, 54 females, aged 52.7 ± 13.2 years, mean 6.9 ± 5.1 years after transplantation), who had scheduled visits in the first two weeks of March 2015, were included in the study. The recipients were divided into two groups depending on AVF function (65 AVF+ and 97 AVF-). RESULTS: Functioning AVF was more prevalent in males than females (47.2 % vs 25.9 %, P = .009). Both groups presented similar allograft function despite the fact that interval from transplantation to examination day in the AVF+ group was significantly shorter than in the AVF- group (5.2 ± 5.3 vs 8.1± 4.5 years; P < .001). The mean systolic blood pressure (135.0 ± 17.0 vs 138.7 ± 14.1 mm Hg, P = .13) was similar in both study groups, but diastolic blood pressure in the AVF+ group was lower than in the AVF- group (80.0 ± 7.0 vs and 83.7 ± 9.2 mm Hg, P = .006). The proportion of patients with diastolic blood pressure >80 mm Hg was significantly higher in patients without functioning AVF (35 % in the AVF- group vs 20 % in the AVF+ group, P= .038). In multivariate analysis, AVF presence was the only factor significantly influencing a diastolic blood pressure with odds ratio 0.43 (95% CI 0.19-0.99, P = .048), which supports AVF as a potentially positive influence on blood pressure control. CONCLUSIONS: The presence of AVF in renal transplant recipients was associated with a slight decrease in diastolic blood pressure without clear effect on renal function.

Acute Brain Damage in a 56-Year-Old Woman With a 20-Year-Old Transplanted Kidney as a Complicated Differential Diagnostic Process: A Case Report.

INTRODUCTION: Acute central nervous system (CNS) damage in a patient who has received organ transplant is an extremely difficult and complex clinical issue that spans a wide spectrum of differential diagnoses with ischemia, post-transplant lymphoproliferative disorders (PTLDs), infections, lymphomas, and progressive multifocal leukoencephalopathy (PML). PTLDs are a clinically and histopathologically heterogeneous group of diseases that most often occur in heavily immunocompromised populations after solid organ transplantation (SOT), probably related to the infection or reactivation of Epstein-Barr virus (EBV) infection, whereas PML is an infectious disease caused by the John Cunningham virus (JCV). CASE DESCRIPTION: A 56-year-old female, 20 years after renal transplantation from a deceased donor, was admitted to the hospital as an emergency due to sensory aphasia and memory disorders. Computed tomography (CT) examination revealed a diffuse expansive process in the temporo-parieto-occipital and left frontal area. Magnetic resonance imaging (MRI) results suggested changes associated with PML; however, JCV was not found in the cerebrospinal fluid. The disorders progressed quickly, both clinically and radiologically-the patient developed central facial palsy, paresis of limbs, and positive Babinski sign on the left. A second radiological examination (CT) also suggested PML. Due to the rapid deterioration of the patient's general condition, further diagnostic examinations (magnetic resonance with contrast and brain stereotactic biopsy) could not be performed. After almost 2 months of the commencement of the diagnostic process, the patient died. Autopsy revealed that the cause of death was acute CNS damage in the course of monomorphic PTLD (CNS-PTLD). CONCLUSION: Rapid deterioration of mental status can be the first symptom of CNS-PTLD, a dangerous and life-threatening condition in immunocompromised patients after solid organ transplantation.

Issues of Immunological and Hemodynamic Monitoring Before and During Kidney Transplantation in Sensitized Heart Transplant Recipient.

Previously transplanted highly sensitized patients experience problems with subsequent transplantation. It is also difficult to provide optimal hemodynamic conditions during successive kidney transplantation in heart transplant recipients. PATIENT AND METHODS: We present a case of a 56-year old patient with end-stage renal failure after heart transplantation performed 21 years ago and hemodialyzed using arteriovenous fistula. The patient had 69% panel-reactive antibodies, had been on the active waiting list since 2013, and presented 335 positive crossmatches with deceased donors. He also positively crossmatched with a potential living donor. Detailed examination of anti-HLA antibodies revealed the absence of IgG donor-specific antibodies and negative crossmatch with dithiothreitol-treated serum. The transplantation from his wife was performed with positive crossmatch after 4 plasma exchanges and thymoglobulin induction. Because sympathetic and parasympathetic denervation of the transplanted heart and the presence of arteriovenous fistula induced volume overload of the right heart, we used central venous pressure (CVP) and the PiCCO2 for postsurgical assessment of cardiac output. RESULTS: Monitoring, like CVP and other static exponents of preload obtained by PICCO (extravascular lung water, global end-diastolic volume index) as well as the dynamic parameters obtained by PiCCO2 (pulse pressure variation, stroke volume variation), was not sensitive enough to describe recipient volume status. The immediate graft function was observed, and after 11 months satisfactory estimated glomerular filtration rate is noted with the absence of donor-specific antibodies. CONCLUSION: The history of heart transplantation with existing arteriovenous fistula makes clinical tools such as continuous cardiac output monitoring and CVP parameter inadequate for describing the hemodynamic situation. The high level of panel-reactive antibodies and positive crossmatch possibly caused by IgM antibodies do not have to withdraw the recipient from kidney transplantation.

Lowering of Messenger Ribonucleic Acid Toll-Like Receptors 2-4,9 in Peripheral Blood Mononuclear Cells in Kidney Allograft Recipients, Relationships With Immunosuppressive Treatment, and Delayed Graft Function Occurrence.

BACKGROUND: Both tacrolimus (Tac) and cyclosporine (CsA) inhibit control peripheral blood mononuclear cells (PBMC) after stimulation of various Toll-like receptors (TLR) at supra-pharmacological concentrations. Earlier studies demonstrated that 24 hours after kidney transplantation (KT), the expression of the TLR4 messenger RNA (mRNA) in PBMC from patients with subsequent delayed graft function (DGF+) was lower than in patients without DGF (DGF-). An assessment was made of the interaction of immunosuppression with TLR mRNA in PBMC and to verify whether the reduced expression of TLR-2,3,4,9 mRNA in PBMC is permanent in DGF+. METHODS: We investigated mRNA expression of TLR in non-stimulated PBMC. All patients were transplanted more than 1 month before PBMC acquisition. Patients were divided into groups with respect to positive or negative history of delayed graft function (DGF+/-). RESULTS: The expression of TLR2, TLR3, and TLR9 in patients was lower than that in the control group. We found an association of Tac C0 with expression of TLR4 only and CsA dose per 1 kg body weight with TLR2 or up to 6 months after KT with TLR9. Mofetil mycophenolate (MMF)contributed to the change of TLR4 expression in the CsA group but not in the Tac group. TLR3 and TLR9 were nearly equally sensitive to both Tac and CsA, with a decrease of expression with respect to control. DGF+ was associated with variable degree of reduction of TLR2, TLR3, TLR4, and TLR 9 expression. CONCLUSIONS: We showed the importance of immunosuppression and delayed graft function as factors that modify the overall expression of mRNA-TLR PBMC for a period of time after KT. Patients with a history of DGF have chronically decreased expression of mRNA TLR2, TLR3, TLR4, and TLR9. This fact is associated with poorer graft function. Measuring the expression of the TLR in the upper range of therapeutic doses of calcineurin inhibitors and MMF gives the opportunity to assess the strength, effectiveness, and toxicity of immunosuppression.

Prevalence of Left Ventricular Hypertrophy and Left Ventricular Dysfunction in Older Renal Transplant Recipients.

OBJECTIVE: Left ventricular hypertrophy (LVH) is a risk factor for premature cardiovascular morbidity and mortality in chronic kidney disease. The aim of the study was to determine echocardiographic evaluation morphology and function of the left ventricle in older renal transplantation patients. MATERIAL AND METHODS: We retrospectively analyzed clinical data of renal transplant recipients who underwent routine echocardiography. We compared the data from 38 patients who were older than 65 years with 49 patients who were a mean age of 47.8 ± 12 years (control group). RESULTS: At the time of cardiac evaluation, most patients were in stage 3 chronic kidney disease. In the older group of patients, the incidence of obesity and diabetes were significantly higher than in the control group. Also in the older patients, the serum level of albumin was lower (P < .001), and brain natriuretic peptide was higher (P = .046). The incidence of coronary heart disease, chronic heart failure, and atrial fibrillation were higher in the older patients (P = .011). LVH was common in older as well as younger patients (97.4% vs. 88.8%, P = .17). Left ventricle mass index ranged from 90.4 g/m(2) to 235.5 g/m(2) among examined kidney transplantation patients. In older patients, left ventricular mass index was 160.7 ± 34.5 g/m(2) compared to 141.8 ± 29.8 g/m(2) in younger patients (P = .008). Reduced ejection fraction was found only in 2 of 38 (5.3%) older patients. Diastolic dysfunction of left ventricle was present in 34 of 38 (89.5%) patients >65 years old and in 24 of 49 (49.9%) younger patients (P < .001). CONCLUSIONS: LVH and left ventricular dysfunction are more pronounced among older patients. Impaired renal function, proteinuria, diabetes, and severity of hypertension are the most important factors predisposing to LVH.

Progressive outer retinal necrosis in immunocompromised kidney allograft recipient.

Ocular complications in patients who underwent renal transplantation are attributed to side effects of the immunosuppressive regimen. Progressive outer retinal necrosis (PORN) syndrome is a clinical variant of necrotizing herpetic retinopathy and it occurs almost exclusively in patients with acquired immunodeficiency syndrome. We present a case of a human immunodeficiency virus-negative patient who underwent renal transplant and, after a few years, developed bilateral PORN associated with viral infections. Varicella zoster virus (VZV) and BK virus were identified by polymerase chain reaction from the vitreous fluid. It is unclear which of the viruses identified had the dominant role in the pathogenesis of PORN and other organ damage, or whether their actions were synergistic. Adequate antiviral immune surveillance, as well as pre-transplant vaccination against VZV, may reduce the incidence of VZV infection and its complications.

A significant role for anti-human leukocyte antigen antibodies and antibody-mediated rejection in the biopsy-for-cause population.

The role of anti-human leukocyte antigen (HLA) antibodies and antibody-mediated rejection is well known, but our comprehension and the preventive measures we take seem to be insufficient. One of the major causes of premature renal transplant loss is recepients' immunologic hyperactivity to donors' antigens. Monitoring of humoral alloreactivity gives hope for early diagnosis and adequate therapy. The goal of our analysis was the assessment of the influence of anti-HLA antibodies on the function and survival of transplants. In our study we included 60 consecutive renal transplant recipients who had a renal transplant biopsy-for-cause performed due to insufficiency. Transplant biopsies were performed between the 7th day and 12th year (median, 2 years) after transplantation. Anti-HLA antibodies were present in 20 patients (33%). The patients were divided into 2 groups according the presence of anti-HLA antibodies. In a 12-month observation, 10/20 (50%) patients in the anti-HLA(+) group returned to dialysis in contrast with 7/40 (17.5%; P = .014) in the anti-HLA(-) group. Also, 8/10 (80%) of the anti-HLA(+) patients who lost the transplant had anti-HLA Abs class II and only 2/10 (20%) had anti-HLA Abs class I. Anti-HLA antibodies were specific to a donor (donor-specific antibodies [DSA]) in 8/10 (80%) of the patients who lost the transplant. Anti-HLA antibodies appeared de novo in 50% of patients who lost the transplant. Nonadherence was suspected in 50% of patients. Acute humoral rejection occurred in 1 patient. Also, 8/10 (90%) developed chronic active humoral rejection. Our study revealed that graft loss in the renal transplant biopsy-for-cause population with the presence of anti-HLA Abs during a 12-month observation reached 50%. Nonadherence in these patients was very high and amounted to 50%. Monitoring of renal transplant recipients and individualization of therapy considering humoral activity should prolong renal graft survival.

Non-HLA antibodies: angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) are associated with renal allograft injury and graft loss.

INTRODUCTION: Non-HLA antibodies specific for angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) of vascular cells activate signaling pathways leading to cell proliferation and vascular injury. The aim of this study was to evaluate the impact of non-HLA antibodies on kidney allograft morphology and function in patients who underwent a kidney biopsy due to renal function impairment. PATIENTS AND METHODS: The study included 65 consecutive renal transplant patients who were evaluated for the presence of non-HLA and anti-HLA antibodies at the time of transplant biopsy. Results of pre-transplant CDC cross-match were negative. A kidney allograft biopsy was performed between 6 days and 13 years (42 ± 49 months) after transplantation, and the diagnosis was made on the basis of the Banff criteria. The level >9 U/L of anti-AT1R and anti-ETAR antibodies was considered high. RESULTS: A high level of non-HLA antibodies (anti-AT1R and/or anti-ETAR) was found in 7 (10.7%) of 65 patients at the time of biopsy. Graft loss in the non-HLA-positive patients was significantly higher (71% in non-HLA-positive cases after 7.8 ± 2.6 months vs 11% after 6 months in non-HLA-negative cases [P = .00099]). In these non-HLA-positive patients, the mean anti-AT1R level was 15.3 ± 9.4 U/L and the mean anti-ETAR level was 13.8 ± 8.6 U/L. In only 2 of these patients were anti-HLA antibodies additionally detected: anti-class I in 1 and anti-class II in both patients. The mean serum creatinine level was 2.34 ± 0.6 mg/dL at the time of biopsy. Results of an early biopsy revealed acute vascular rejection (Banff grade IIB). Chronic allograft injury was found (grading cg1-3, cv1-2, ci1-2, ct1-2) in the remaining 6 patients. C4d was present in 3 of 7 patients. CONCLUSIONS: High levels of anti-AT1R and/or anti-ETAR antibodies were associated with morphological and functional allograft injury and graft loss in these study patients. Non-HLA antibodies can be helpful in assessing the risk of graft failure.

Increased plasma matrix metalloproteinase-2 (MMP-2), tissue inhibitor of proteinase-1 (TIMP-1), TIMP-2, and urine MMP-2 concentrations correlate with proteinuria in renal transplant recipients.

BACKGROUND: The most frequent cause of kidney allograft loss is chronic allograft injury, often with proteinuria as the clinical feature. Occurrence of proteinuria late after kidney transplantation is associated with worse graft function and patient survival. AIM: The aim of the study was to assess plasma and urine matrix metalloproteinases (MMP-2 and MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in proteinuric renal transplant recipients (RTRs). The factors were determined by enzyme-linked immunosorbent assay in 150 RTRs (51 women and 99 men), aged 49.2 ± 11.5 years, at mean 73.4 ± 41.2 months after kidney transplantation (range: 12 to 240 months). RESULTS: Proteinuric RTRs compared with non-proteinuric RTRs had higher median plasma MMP-2 (P = .012), TIMP-1 (P = .0003), and TIMP-2 (P = .0021) concentrations, as well as higher urine MMP-2 (P < .0001) excretion. The presence of proteinuria had no impact on plasma MMP-9 and urine MMP-9, TIMP-1, and TIMP-2. Proteinuria and estimated daily proteinuria (uPr:uCr) correlated positively with plasma MMP-2 (rs = 0.226, P = .0054 and rs = 0.241, P = .003), TIMP-1 (rs = 0.305, P = .00015 and rs = 0.323, P = .000055), TIMP-2 (rs = 0.273, P = .0007 and rs = 0.269, P = .001) and urine MMP-2 (rs = 0.464, P < .0001 and rs = 0.487, P < .0001), respectively. Proteinuric RTRs had impaired graft function with higher median serum creatinine concentrations (1.91 [1.60-2.43] mg/dL versus 1.41 [1.20-1.65] mg/dL, P < .00001) and lower estimated glomerular filtration rate (36 [28-45] mL/min/1.73 m(2) versus 53 [43-61] mL/min/1.73 m(2), P < .00001) than RTRs without proteinuria. CONCLUSIONS: Our research revealed that in RTRs, proteinuria was significantly associated with increased concentrations of enzymes involved in extracellular matrix (ECM) degradation: plasma MMP-2, TIMP-1, TIMP-2, and urine MMP-2. Findings strongly emphasize increased plasma TIMPs in proteinuric RTRs that inhibit degradation of ECM by MMPs and favor excessive deposition of ECM proteins.

Advanced age of renal transplant recipients correlates with increased plasma concentrations of interleukin-6, chemokine ligand 2 (CCL2), and matrix metalloproteinase 2, and urine concentrations of CCL2 and tissue inhibitor of metalloproteinase 1.

BACKGROUND: Advanced age of renal transplant recipients (RTRs) has a negative impact on kidney allograft survival through impaired extracellular matrix degradation by the matrix metalloproteinases/tissue inhibitors of metalloproteinases (MMPs/TIMPs) system. Moreover, older RTRs are at risk of smoldering inflammation, known as inflammaging. AIM: The aim of the study was to assess the impact of a RTR's age on plasma and urine concentrations of interleukin 6 (IL-6), chemokine ligand 2 (CCL2), and the MMPs/TIMPs system. MATERIAL AND METHODS: One hundred fifty adult RTRs (8.7% ≥ 65 years) and 37 adult healthy volunteers (10.8% ≥ 65 years) were enrolled in the study. The studied factors (IL-6, CCL2, MMP-2, MMP-9, TIMP-1 and TIMP-2) were quantified in plasma and urine with enzyme-linked immunosorbent assay. The Mann-Whitney U test and Spearman's (rs) rank correlation were applied, and differences with a P < .05 were considered statistically significant. RESULTS: There was a weak but significant positive correlation between increasing RTR's age and plasma IL-6 (rs = 0.18, P = .028), CCL2 (rs = 0.27, P = .001), and MMP-2 (rs = 0.20, P = .017), as well as urine CCL2 (rs = 0.16, P = 0.050) and TIMP-1 (rs = 0.20, P = .014) concentrations. CONCLUSIONS: Advancing age of RTRs correlates with increasing plasma IL-6 and CCL2 concentrations, reflecting smoldering inflammation (known as inflammaging) and alterations in MMPs/TIMPs profiles, especially with increased plasma MMP-2 and urine TIMP-1 concentrations.

The impact of de novo donor-specific anti-human leukocyte antigen antibodies on 5-year renal transplant outcome.

Numerous studies have shown that circulating donor-specific antibodies targeting human leukocyte antigen (HLA) are associated with accelerated renal transplant failure, but many patients with these antibodies have good graft function. The aim of our study was to investigate the long-term graft function and survival in patients with de novo post-transplant donor-specific anti-HLA antibodies (DSA). Our prospective study included 78 consecutive recipients with a negative crossmatch before transplantation. Recipient serum samples were assayed for DSA in week 2 and 1, 3, 6, 9, 12 months after transplantation using a complement-dependent lymphocytotoxic technique with donor lymphocytes. Additionally, patients with DSA and stable renal function in the first year were tested with a more sensitive flow-panel-reactive antibody. DSA were present in 34 (44%) of our patients during the first 12 months after transplantation. Biopsy-proved acute rejection occurred in 11 DSA-positive and 10 DSA-negative patients. Seven DSA-positive patients had antibody-mediated rejection and no DSA-negative ones developed humoral rejection. The serum creatinine level in DSA-positive patients was significantly higher (2.48 vs 1.43 mg/dL) in year 5. The 13 (38%) DSA-positive patients with good graft function in month 12 were stable during a 5-year follow-up: their serum creatinine was 1.46 ± 0.4 in year 1 and 1.56 ± 0.4 mg/dL in year 5 and nobody lost their allograft. One- and 5- year graft survivals were appropriately 85% and 59% in DSA-positive patients compared to 93% and 93% in DSA-negative patients. To sum up, post-transplant DSA had a significant influence on kidney function and graft survival but in 38% of patients the presence of DSA did not decrease a 5-year renal function. A good renal allograft function in the presence of DSA in the first year after transplantation and cessation of their production in the subsequent years may be a good prognostic marker for a long-term allograft function and survival.