Assessment of the Relationship Between Inflammation and Glomerular Filtration Rate.

Background: Chronic kidney disease (CKD) is a global health problem. As it progresses to end stages, renal replacement therapy is required but ultimately, the best treatment is transplantation. Decreased renal function has been associated with an inflammatory state associated to primary CKD and in kidney transplant recipients (KTRs). Objective: To establish how the serum concentrations of some cytokines, such as interleukin (IL)-2, IL-8, IL-22, IL-17α, interferon-gamma, IL-4, and transforming growth factor-ß, correlate with various CKD stages. Methods: One hundred and forty-one KTRs between the ages of 18 and 75 years were included in the study. We also included 112 live kidney donors, 37 CKD PGCKD+3, and 76 GPhealthy. Participants were grouped according to their glomerular filtration rate (GFR) and their circulating cytokine levels, previously quantified by ELISA. Results: By linear regression analysis, we established the relation of each cytokine with the GFR. Transforming growth factor-ß correlated positively with the GFR in the study population, except in healthy individuals. A negative correlation of IL-8 and IL-17α and GFR was found in all cases. Conclusions: Whether these cytokines (IL-8 and IL-17α) could be used as inflammatory biomarkers indicating CKD progression, regardless of the type of population, remains to be prospectively determined.

Contexte: L'insuffisance rénale chronique (IRC) est un problème de santé mondial. Une thérapie de remplacement rénal est nécessaire au fur et à mesure que la maladie évolue vers les stades terminaux. Mais, en définitive, le meilleur traitement reste la transplantation. La réduction de la fonction rénale a été associée à un état inflammatoire associé à l'IRC primaire; une association observée aussi chez les receveurs d'une greffe de rein. Objectif: Déterminer la façon dont les concentrations sériques de certaines cytokines, notamment IL-2, IL-8, IL-22, IL-17a, IFN-γ, IL-4 et TGF-ß, corrèlent avec divers stades de l'IRC. Méthodologie: Ont été inclus dans l'étude 141 receveurs d'une greffe rénale âgés de 18 à 75 ans, 112 donneurs vivants de rein, 37 personnes atteintes d'IRC (PGIRC+3) et 76 personnes en bonne santé (PGen santé). Les sujets ont été regroupés en fonction de leur débit de filtration glomérulaire (DFGe) et de leur taux de cytokines en circulation, quantifiés préalablement par ELISA. Résultats: Une analyse de régression linéaire a servi à établir la relation entre chaque cytokine et le DFGe. Dans la population étudiée, une corrélation positive a été observée entre TGF-ß et le DFGe, sauf chez les individus sains. Dans tous les cas, la corrélation s'est avérée négative entre le DFGe et les taux d'IL-8 et d'IL-17a. Conclusion: Il reste à déterminer prospectivement si ces cytokines (IL-8 et IL-17a) pourraient être utilisées comme biomarqueurs inflammatoires pour indiquer la progression de l'IRC, quelle que soit la population.

Angiotensin II receptor agonist antibodies are associated with microvascular damage in lupus nephritis.

Angiotensin II type 1 receptor agonist antibodies (AT1R-AAs) have been associated with hypertension, atherosclerosis and vascular inflammation in human diseases. The aim of the study was to evaluate the prevalence of AT1R-AAs in active lupus nephritis (LN) patients and their association with vascular damage. One hundred and seven active LN patients underwent a complete clinical examination, measurement of AT1R-AAs, ambulatory blood pressure monitoring, carotid intima-media thickness measurement and morphometric analysis of subintimal fibrosis and medial hyperplasia of the vessels in the kidney tissue. Plasma AT1R-AAs were positive in 58 (54.2%) patients. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, complement C3 and C4 levels and titers of anti-dsDNA antibodies were higher in the group with positive AT1R-AAs compared with those with negative AT1R-AAs. The AT1R-AA titers correlated with anti-dsDNA antibody titers and with complement C3 and C4 serum levels. In the kidney biopsy, the percentage of subintimal fibrosis and the area of medial hyperplasia were greater in the AT1R-AA-positive patients. No differences in arterial pressure, carotid intima-media thickness and response to therapy were detected. In conclusion, AT1R-AAs are prevalent in active LN patients and are associated with histologic features of microvascular damage.

Long-term survival of kidney grafts in lupus nephritis: a Mexican cohort.

Kidney transplant for patients with lupus nephritis (LN) has satisfactory outcomes in studies with short-term or mid-term follow up. Nevertheless, information about long-term outcomes is scarce. We performed a retrospective matched-pair cohort study in 74 LN recipients compared with 148 non-LN controls matched by age, sex, immunosuppressive treatment, human leukocyte antigen (HLA) matches, and transplant period in order to evaluate long-term outcomes of kidney transplant in LN recipients. Matched pairs were predominantly females (83%), median age at transplant surgery of 32 years (interquartile range 23-38 years), and 66% received a graft from a living related donor. Among LN recipients, 5-, 10-, 15-, and 20-year graft survival was 81%, 79%, 57% and 51%, respectively, and it was similar to that observed in controls (89%, 78%, 64%, and 56%, respectively). Graft loss (27% vs. 21%, p = 0.24) and overall survival ( p = 0.15) were not different between LN recipients and controls. Also, there was no difference in episodes of immunological rejection, thrombosis, or infection. Only six LN recipients had biopsy-proven lupus recurrence and three of them had graft loss. In a cohort with a long follow up of kidney transplant recipients, LN recipients had similar long-term graft survival and overall outcomes compared with non-lupus recipients when predictors are matched between groups.

Prognostic significance of renal vascular pathology in lupus nephritis.

We performed a retrospective cohort analysis to define the prognostic significance of vascular lesions documented in renal biopsies of lupus nephritis patients. A total of 429 patients were segregated into five groups: (1) no vascular lesions (NVL), (2) arterial sclerosis (AS), (3) non-inflammatory necrotizing vasculitis (NNV), (4) thrombotic microangiopathy (TMA), and (5) true renal vasculitis (TRV). Renal outcomes were analyzed by Cox regression models, and correlations between vascular lesions and activity/chronicity scores were determined by Spearman's coefficients. A total of 200 (46.6%) had NVL, 189 (44.0%) AS, six NNV (1.4%), 23 (5.4%) TMA, and 11 (2.6%) TRV. Patients with NVL were younger, with higher renal function; patients with TMA and TRV had lower renal function and higher arterial pressure at baseline. Antiphospholipid syndrome and positive lupus anticoagulant were more frequently observed in the TMA group. Five-year renal survival was 83% for NVL, 63% for AS, 67% for NNV, 31% for TMA, and 33% for TRV. NNV and TRV were significantly correlated with activity scores, while AS and chronic TMA were correlated with chronicity scores. Renal vascular lesions are associated with renal outcomes but do not behave as independent factors. The addition of vascular lesions to currently used scores should be further explored.

Serum antibodies to human leucocyte antigen (HLA)-E, HLA-F and HLA-G in patients with systemic lupus erythematosus (SLE) during disease flares: Clinical relevance of HLA-F autoantibodies.

T lymphocyte hyperactivity and progressive inflammation in systemic lupus erythematosus (SLE) patients results in over-expression of human leucocyte antigen (HLA)-Ib on the surface of lymphocytes. These are shed into the circulation upon inflammation, and may augment production of antibodies promoting pathogenicity of the disease. The objective was to evaluate the association of HLA-Ib (HLA-E, HLA-F and HLA-G) antibodies to the disease activity of SLE. The immunoglobulin (Ig)G/IgM reactivity to HLA-Ib and ß2m in the sera of 69 German, 29 Mexican female SLE patients and 17 German female controls was measured by multiplex Luminex(®)-based flow cytometry. The values were expressed as mean flourescence intensity (MFI). Only the German SLE cohort was analysed in relation to the clinical disease activity. In the controls, anti-HLA-G IgG predominated over other HLA-Ib antibodies, whereas SLE patients had a preponderance of anti-HLA-F IgG over the other HLA-Ib antibodies. The disease activity index, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000, was reflected only in the levels of anti-HLA-F IgG. Anti-HLA-F IgG with MFI level of 500-1999 was associated with active SLE, whereas inactive SLE revealed higher MFI (>2000). When anti-HLA-F IgG were cross-reactive with other HLA-Ib alleles, their reactivity was reflected in the levels of anti-HLA-E and -G IgG. The prevalence of HLA-F-monospecific antibodies in SLE patients was also associated with the clinical disease activity. Anti-HLA-F IgG is possibly involved in the clearance of HLA-F shed from lymphocytes and inflamed tissues to lessen the disease's severity, and thus emerges as a beneficial immune biomarker. Therefore, anti-HLA-Ib IgG should be considered as a biomarker in standard SLE diagnostics.

Renal flare prediction and prognosis in lupus nephritis Hispanic patients.

We performed a retrospective cohort analysis focusing on lupus nephritis renal flare incidence and outcome predictors. One hundred and eighteen patients with biopsy-proven lupus nephritis were segregated by induction/maintenance regimes. The primary outcome was the proportion of patients experiencing renal flare. Secondary assessment included doubling of serum creatinine and development of end-stage renal disease. After a median follow-up of 31 months (interquartile range 21-46) from the date of response to induction therapy, 47 patients (39.8%) developed a renal flare. Azathioprine-maintained patients had a higher risk of renal flare compared with mycophenolate mofetil-maintained patients (hazard ratio 2.53, 95% confidence interval 1.39-4.59, p < 0.01). Age (hazard ratio 0.96, 0.92-0.99, p = 0.03), serum creatinine at presentation (hazard ratio 1.76, 1.13-2.76, p = 0.01), complete remission after induction therapy (hazard ratio 0.28, 0.14-0.56, p < 0.001) and azathioprine maintenance therapy (hazard ratio 4.78, 2.16-10.6, p < 0.001) were associated with renal flare on multivariate analysis. Ten patients progressed to end-stage renal disease (8.5%) by a median 32.5 months. Age (hazard ratio 0.88, 0.77-0.99, p = 0.05), complete remission after induction therapy (hazard ratio 0.08, 0.01-0.94, p = 0.04) and severe nephritic flare (hazard ratio 13.6, 1.72-107.7, p = 0.01) were associated with end-stage renal disease development. Azathioprine maintenance therapy is associated with a higher incidence of relapse in the Mexican-mestizo population. Younger age and nephritic flares predict development of end-stage renal disease.

Minor H antigen matches and mismatches are equally distributed among recipients with or without complications after HLA identical sibling renal transplantation.

Studies of the effect of minor H antigen mismatching on the outcome of renal transplantation are scarce and concern mainly single center studies. The International Histocompatibility and Immunogenetics Workshops (IHIW) provide a collaborative platform to execute crucial large studies. In collaboration with 16 laboratories of the IHIW, the role of 15 autosomal, 10 Y-chromosome encoded minor H antigens and 3 CD31 polymorphisms, was investigated in relation to the incidence of renal graft rejection and graft loss in 444 human leukocyte antigens (HLA)-identical sibling renal transplantations. Recipient and donor DNA samples were genotyped for the minor H antigens HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, SP110, PANE1, UGT2B17, C19Orf48, LB-ECGF-1, CTSH, LRH-1, LB-ADIR and HY. The correlation between minor H antigen mismatch and the primary outcome graft rejection or graft loss was statistically analyzed. The incidence of rejection was very low and no correlation was observed between one or more minor H antigen mismatch(es) and a rejection episode (n = 36), of which only eight resulted in graft loss. In summary, in our study cohort of 444 renal transplants, mismatching for neither autosomal nor HY minor H antigens correlate with rejection episodes or with graft loss.

Seroprevalence of Trypanosoma cruzi in kidney transplant donors and recipients in Mexico City.

Infectious diseases are common causes of morbidity and mortality among kidney transplant recipients. Chagas disease (CD) has been recognized as an emerging infectious complication of transplantation caused by the parasite Trypanosoma cruzi. CD is prevalent in Mexico, particularly in the southern coastal region. The impact on Mexican kidney transplant programs has not been previously studied prospectively. From 2009 through 2010, serum samples from 59 kidney transplant donors and 405 renal transplant recipients were screened for antibodies against T. cruzi. Serum was initially screened using a locally developed ELISA test; positive results were confirmed by an indirect immunofluorescense test, in accordance with Panamerican Health Organization/World Health Organization guidelines. None of the donors were seropositive for T. cruzi, while 8 (1.97%) kidney transplant recipients were confirmed to be seropositive for T. cruzi. None of them have developed clinical manifestations of CD, although specific screening of recipients was not performed. A prospective study is planned to define the epidemiology and outcome of CD among kidney transplant donors and recipients in Mexico more thoroughly.

Probability of deceased donor kidney transplantation based on % PRA.

UNLABELLED: Sensitization to HLA antigens creates an obstacle for the accessibility and success of kidney transplantation (KT). Highly sensitized patients have longer waiting times and some may never receive a KT. AIM: To determine the probability of patients on the deceased donor (DD) waiting list to receive a KT based on the panel reactive antibody percentage (% PRA) in our center. METHODS: The DD waiting list from our institution was analyzed from 01/05 to 08/12 documenting the clinical variables from donor and potential recipients (ABO blood group), lymphocyte cross-match [CxM (CDC-AHG)] results, highest % PRA determination, and time on the waiting list. The patients were classified into 4 groups based on the % PRA: 0%, 1-19%, 20-79% and 80-100%. The data was analyzed using odds ratio and logistic regression (significant p<0.05). RESULTS: 58 DD (F:M 34:24, ABO group O=35, A=13, B=10) and 179 potential recipients were analyzed (F:M 98:81, ABO group O=127, A=33, B=19, participating 4.2 ± 3.8 times with different donors to receive KT). The mean PRA for the whole group was 22 ± 32%, median [md] 0 (0-98). A total of 100 patients received KT (mean waiting time 2.2 ± 1.7 years, 12 days-7 years) and their mean % PRA was 11.6 ± 24, md 0 (0-94) vs. 31.4 ± 37 md 8.5 (0-98) in those who have not received a KT. An association between the % PRA group and KT (p<0.003) was observed. The probability of receiving KT with a 0% PRA vs. >0% was higher (OR 2.12, 1.17-3.84). There was no difference between the 0% vs. 1-19% group (OR 1); differences were observed between 0% vs. 20-79% (OR 2.5, 1.18-5.3) and 0% vs. 80-100% (OR 5, 1.67-14.9). For every percent increase in the PRA above 20%, the risk of not receiving a KT increased by 5% (1-9, p<0.01). CONCLUSIONS: The probability of receiving a DD kidney transplant is inversely related to the % PRA although a higher risk for not receiving a KT becomes evident with a PRA >20%.

Fever, haematuria, and acute graft dysfunction in renal transplant recipients secondary to adenovirus infection: two case reports.

We report two cases of adenoviral infection in kidney transplant recipients that presented with different clinical characteristics under similar demographic and posttransplant conditions. The first case presented with fever, gross haematuria, and acute graft dysfunction 15 days following renal transplantation. A graft biopsy, analyzed with immunohistochemistry, yielded negative results. However, the diagnosis was confirmed with blood and urine real-time PCR for adenovirus 3 days after the initial clinical manifestations. The immunosuppression dose was reduced, and ribavirin treatment was started, for which the patient quickly developed toxicity. Antiviral treatment allowed for transient response; however, a relapse occurred. The viral real-time PCR became negative upon immunosuppression reduction and administration of IVIG; graft function normalized. In the second case, the patient presented with fever and dysuria 1 month after transplantation. The initial imaging studies revealed graft enlargement and areas of hypoperfusion. In this case, the diagnosis was also confirmed with blood and urine real-time PCR for adenovirus 3 days after the initial clinical manifestations. Adenoviral nephritis was confirmed through a graft biopsy analyzed with light microscopy, immunohistochemistry, and PCR in frozen tissue. The immunosuppression dose was reduced, and IVIG was administered obtaining excellent clinical results along with a negative real-time PCR.

Infiltrating cellular pattern in kidney graft biopsies translates into forkhead box protein 3 up-regulation and p16INK4α senescence protein down-regulation in patients treated with belatacept compared to cyclosporin A.

Renal allograft survival is related directly to cell senescence. In the transplantation scenario many cellular events - participating as immunological and non-immunological factors - could contribute to accelerate this biological process, responsible for the ultimate fate of the graft. Mechanisms concerned in tolerance versus rejection are paramount in this outcome. For this reason, immunosuppressive treatment constitutes an extremely important decision to prevent organ dysfunction and, finally, graft loss. This study was conducted to document the proportion of CD4(+) /interleukin (IL)-17A(+) -, CD16(+) /indoleamine 2, 3-dioxygenase (IDO(+) )-, forkhead box protein P3 (FoxP3(+))-expressing cells, senescent cells (p16(INK) (4α)) and the percentage of interstitial fibrosis (IF) in graft biopsies of kidney transplant recipients participating in the BENEFIT (Bristol-Myers Squibb IM103008) study. CD4(+) /IL-17A(+) , CD16(+) /IDO(+), FoxP3(+) and p16(INK) (4α+) cells were evaluated by immunohistochemistry, and the percentage of IF by morphometry on graft biopsies obtained at time 0 (pre-implantation) and at 12 months post-transplant. Senescent cells and CD4(+) /IL-17A(+) cells were increased among graft biopsies in subjects receiving cyclosporin A (CsA) compared to those under belatacept treatment. Meanwhile, CD16(+) /IDO(+) and FoxP3(+) -expressing cells were lower in biopsies from CsA treatment compared to patients treated with Belatacept. Histological morphometric analyses disclosed more IF in 12-month CsA-treated patients in comparison to pre-implantation biopsy findings. Summing up, renal biopsies from patients receiving belatacept showed greater amounts of FoxP3(+) cells and lower amounts of CD4(+) /IL-17A(+) and senescent cells compared to patients under CsA treatment. Along with these findings, an increase in IF in annual CsA-treated-patients biopsies compared to pre-implantation and belatacept-treated patients were observed.

Immune response after rabies vaccine in a kidney transplant recipient.

A 48-year-old male kidney-transplant recipient was bitten by a rabid dog. His immunosuppressive treatment consisted of cyclosporine 60 mg b.i.d., mycophenolate mofetil (MMF) 250 mg t.i.d., and prednisone 5 mg. After wound care, he received 5 doses of purified vero cell rabies vaccine on days 0, 3, 7, 14, and 28, and human rabies immunoglobulin, according to international guidelines. Adequate levels of rabies virus neutralizing antibodies were observed after the administration of the third vaccine dose. However, a decrease of antibody titer was detected by day 28. Immunosuppressive medication was minimized, withdrawing MMF and reducing the dose of cyclosporine. Booster doses of the same vaccine were administered on days 38, 41, 45, 52, and 66. Adequate neutralizing antibody response was recovered during the ensuing 12 months, under reduced immunosuppression. Nineteen months after the incident, the patient remains with good graft function and is asymptomatic for rabies. It remains to be determined whether the attained immune response was either the result of the booster vaccinations or the reduction of immunosuppression alone. Nevertheless, such an outcome would have been possible only with the combined management strategy implemented.

Association of the metabolic syndrome and long-term renal function in kidney donors.

BACKGROUND: Metabolic syndrome (MetS) may represent risk factor for long-term renal function of kidneys from living donors. The aim of this study was to evaluate the impact of MetS on renal function in donors. METHODS: Data regarding the presence or absence of MetS and renal function, as assessed by estimated glomerular filtration rate (eGFR) were obtained from 140 kidney donors before nephrectomy (BN) and at follow-up (AF). Donors were divided into those with (group 1; n =28) versus without MetS (group 2; n = 112). RESULTS: Comparing the groups, we observed a significantly greater reduction in eGFR among the group with MetS BN versus AF 27.5% (19.3-33.0) versus 21.4% (9.6-34.1 P = .02) respectively using a Cox regression model, including age, gender, serum uric acid, body mass index (BMI), and basal eGFR, MetS BN (hazard ratio = 2.2; 95% confidence interval [CI], 1.21-4.01; p = .01) was an independent factor associated with a greater risk of a-eGFR <70 mL/min/1.73 m(2) at follow-up (P < .001). Additionally, age (hazard ratio = 1.03%; 95% CI, 1.01-1.06; P < .001), and female gender (hazard ratio = 1.86; 95% CI, 1.03-3.36; P = .03) were associated with a greater decrease in eGFR. Individuals with MetS BN showed a GFR <70 mL/min/1.73 m(2) at significantly shorter follow-up time (5.6 ± 0.8 years) versus persons without MetS (12.8 ± 1.0 years; P = .001) CONCLUSION: Kidney donors with MetS BN experiment a significantly greater decrease in eGFR at follow-up.

High levels of IDO-expressing CD16+ peripheral cells, and Tregs in graft biopsies from kidney transplant recipients under belatacept treatment.

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme that suppresses T-lymphocyte activity. Costimulation blockade through CTLA4lg increases IDO in antigen-presenting cells. The suppressive effect of IDO is thought to be mediated by Foxp3+CD4+CD25+ regulatory T-cells (Tregs). OBJECTIVE: In this descriptive study, we evaluated the percentage of IDO-expressing peripheral cell subpopulations as well as Tregs in 27 stable kidney transplant recipients receiving either belatacept (LEA29Y), a daughter compound of abatacept (CTLA4lg; n = 19) or cyclosporine (n = 8). METHODS: Blood samples were obtained at 24 ± 2 months (belatacept) and 23 ± 6 months (cyclosporine) of treatment. Intracellular IDO was analyzed by flow cytometry in CD14+, CD11c+, CD16+, CD56+, and CD8+ cell subpopulations. Tregs were assessed by intracellular Foxp3 detection in CD4+CD25+ cells. CD3+, CD4+, CD8+, CD20+, CD68+, IDO+, and Foxp3+ cells were evaluated by immunohistochemistry on graft biopsies obtained preimplantation, at 12 months posttransplant, and in subjects with dysfunction during the first 12 months. RESULTS: Only percentages of CD16+/IDO+-expressing peripheral monocytes were significantly increased among the group receiving belatacept. No differences were observed in peripheral Tregs between the groups. In contrast, higher percentages of Tregs, CD4+, CD8+, and CD68+ cells were noted in dysfunction and at 12 months vs baseline among graft biopsies in subjects receiving belatacept, and also among dysfunction cohorts of belatacept vs Cyclosporine treatment. CONCLUSION: Patients receiving belatacept showed greater amounts of peripheral blood CD16+/IDO+ cells and Tregs on graft biopsies than those under cyclosporine treatment.

Time of occurrence of kidney acute antibody-mediated allograft rejection/acute cellular rejection and cell senescence: implications for function outcome.

BACKGROUND: Late versus early acute antibody-mediated rejection (AAMR) or acute cellular rejection (ACR) episodes are associated with poorer kidney function and graft survival. We explored whether cell senescence upon detection of AAMR ± ACR contributes to these results. METHODS: We reviewed the renal transplant database of 2 Institutions. Biopsies performed for acute graft dysfunction from January 2000 to March 2007 were analyzed for morphological criteria of AAMR with or without ACR (n = 17 from 17 patients). Immunoperoxidase staining for p16(INK4B) was performed on the remaining paraffin-embedded tissue in 9 of 17 cases. The average number of positive cells/high power field (HPF) was calculated in every case. Cases with rejection were grouped according to the time of presentation: early (<3 months n = 8) versus late (>3 months; n = 9). Graft function was obtained using the Modification of Diet in Renal Disease (mDRD) glomerular filtration rate estimate (eGFR) before, during rejection, and at the last visit, to calculate ΔeGFR. RESULTS: Nuclear expression of p16(INK4B) was 12.2 ± 11.3 cells/HPF in 4 of 8 biopsies performed at a median of 23 (range = 4-80) days (early AAMR ± ACR), and 59.8 ± 51.3 cells/HPF in 5 of 9 biopsies performed at a median of 1171 (range = 279-3210) days (late AAMR ± ACR). eGFR before rejection was 48.5 ± 7.6 mL/min, and 43.7 ± 4.3 mL/min for early and late rejection episodes, respectively (P = not significant [NS]). ΔeGFR of 12.5 ± 25.9 mL/min (early rejection), and -13.7 ± -12.3 mL/min (late rejection), versus last follow-up visit (P = .02) occurred at a median of 143.9 ± 94.1 and 69.6 ± 35.1 weeks after the rejection episodes, respectively. CONCLUSIONS: Even though the number of biopsies analyzed for p16(INK4a) was small, it was evident that the number of cells expressing this marker of senescence was higher among biopsy specimens obtained with late rejection episodes. This finding suggests the presence of injuries prior to the rejection episode. The significantly lower eGFR at last follow-up in the late rejection group may translate to a reduced capacity of the repair process to sustain nephron function.

Risk factors for Banff borderline acute rejection in protocol biopsies and effect on renal graft function.

INTRODUCTION: The interpretation and handling of Banff borderline acute rejection observed in protocol biopsies from patients with stable renal function continues to be controversial. Our objective was to identify the risk factors for borderline acute rejection on 1-year protocol biopsies and to evaluate their effect on renal graft function after 2 years' follow-up. METHODS: We included 82 kidney transplant recipients (KTR), who underwent 1-year protocol biopsies with normal or stable graft function. All KTR had follow-up of at least 2 years posttransplantation. We formed three groups: (1) KTR with a normal biopsy, (2) KTR with borderline changes, and (3) KTR with interstitial fibrosis/tubular atrophy (IF/TA). We searched for risk factors related to borderline injury. The main outcome to evaluate was renal function at 1 month, at protocol biopsy, and 2 years posttransplant. RESULTS: The 82 patients included in this study showed no differences in immunosuppression, gender, etiology of renal failure, or percentage of panel-reactive antibodies. The risk factors associated with borderline lesions were: at least one biopsy due to allograft dysfunction and acute rejection events during the first year posttransplant (P = .011 and P = .021, respectively). Increased serum creatinine and estimated glomerular filtration rate decline were greater among the borderline lesion than the normal group, but similar to patients with IF/TA. CONCLUSION: Renal function decline was greater among borderline and IF/TA groups. However, the sum of insults, and not only the borderline injury itself, produces greater declines in renal function with greater risk for graft loss.

Parameters of Doppler ultrasound at five days posttransplantation as predictors of histology and renal function at one year.

INTRODUCTION: In our center, a Doppler ultrasound (DU) is performed at 5 days after transplantation. The normal upper limit of flow velocity (FV) in the renal artery is 200-250 cm/s. The resistance index (RI) is considered elevated when >0.8. Elevation of the RI can be shown in all the forms of graft dysfunction. OBJECTIVE: The objective of this study was to evaluate the capacity of the DU to predict the prognosis of graft function and histological damage at 1 year. METHODS: We examined a retrospective cohort of patients undergoing renal transplantation between January 2004 and May 2007. The renal function was evaluated with serum creatinine measurements and glomerular filtration rate (GFR) estimates by the quadratic Modification of Diet in Renal Disease study equation. The biopsy specimen was evaluated according to the Banff 1997 classification. RESULTS: The overall average age was 35 years, and 58% of the subjects were men. Eight cases (25.8%) showed abnormal DU. The Delta among those with normal DU was -0.94 versus 0.27 +/- 0.39 with abnormal DU (P < .005). There was no significance as far as the biopsy at 1 year. CONCLUSIONS: Renal DU allows physicians to suspect complications at the first posttransplantation year. It shows a tendency to elevated blood pressure, as well as increased deterioration of renal function over the first year.

Risk factors for urinary tract infections during the first year after kidney transplantation.

INTRODUCTION: Urinary tract infections (UTI) have been reported to occur with frequencies ranging from 30% to 60% in kidney transplant recipients during the first year posttransplantation. UTI is the main cause of infectious complications in this period. The objective of this study was to evaluate the incidence of UTI, during the first year posttransplantation and to identify the risk factors associated with its development, as well as its impact on graft function. PATIENTS AND METHODS: This retrospective cohort study had as a primary outcome the development of UTI, defined as the presence of more than 100,000 colony-forming units (CFU) of a pathogenic organism by mL of urine. The univariate analysis was performed with chi-square test for categorical variables and Student t test for continuous ones metrics. We performed multivariate analysis with logistic regression. P < .05 was considered statistically significant. RESULTS: We studied 176 kidney transplant recipients, including 54.5% of male gender and with an overall average age of 37 +/- 12 years. The UTI incidence was of 35.8% (n = 63). The bacterium most frequently found in urine cultures was Escherichia coli (n = 46). In this study, the risk factors that were independently associated with UTI development were age, female gender, days of bladder catheterization, genitourinary anatomic alterations, and UTI during 1 month prior to kidney transplantation. CONCLUSION: This type of study makes it possible to identify risk factors and to formulate strategies focused on particular risk factors.

Prevalence of HLA antibodies and its impact on graft function in a group of kidney transplant recipients: a cross-sectional study.

UNLABELLED: HLA alloantibodies (Abs) are associated with chronic rejection and poorer graft survival. The current study was designed to document the prevalence of HLA Abs in a group of kidney transplant recipients (KTR) and its impact on graft function. PATIENTS AND METHODS: 283 KTR transplanted between January 1990 and December 2003 who had a functional graft were invited to participate. 198 KTR were enrolled. HLA class I and II Abs were measured by Luminex-One Lambda. Graft function was assessed by DeltaCr and GFR calculated by the Levey formula. RESULTS: Median post-kidney transplant (post-KT) follow-up was 51.4 (4.3 to 176.3) months. Forty-four (22.2%) KTR were found to have class I and/or class II Abs. Eleven had both class I and II Abs, ten were positive only for class I, and 23 for class II. Overall, no significant difference was seen in renal function. The DeltaCr for Ab positive and Ab negative were -0.24+/-0.84 and -0.17+/-0.60 mg/dL (P=0.54), respectively. The GFR for Ab positive and Ab negative were 64.4+/-26 and 60.2+/-20 mL/min (P=0.25), respectively. No statistically significant difference was found between HLA Abs and number of HLA mismatches, gender, blood transfusions, pre-KT pregnancies, DGF, history of acute rejection, and chronic allograft nephropathy. Adjusting analysis by transplant year showed no significant difference. CONCLUSION: The prevalence of HLA antibodies was similar to previous reports. In this cross-sectional study, the presence of HLA antibodies was not related to a negative impact on renal function.