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BACKGROUND: We report large biofilm structures that covered almost the entirety of the lumen and surface of double-J stents in two postrenal transplant patients, with no development of urinary tract infection. Biofilm bacteria of one patient were integrated by coccus in a net structure, whereas overlapping cells of bacilli were present in the other patient. To the best of our knowledge, this is the first time that high-quality images of the architecture of noncrystalline biofilms have been found inside double-J stents from long-term stenting in renal transplant recipients. CASE PRESENTATION: Two renal transplant recipients, a 34-year-old male and a 39-year-old female of Mexican-Mestizo origin, who underwent a first renal transplant and lost it due to allograft failure, had a second transplant. Two months after the surgical procedure, double-J stents were removed and analyzed using scanning electron microscopy (SEM). None of the patients had an antecedent of UTI, and none developed UTI after urinary device removal. There were no reports of injuries, encrustation, or discomfort caused by these devices. CONCLUSION: The bacterial biofilm inside the J stent from long-term stenting in renal transplant recipients was mainly concentrated on unique bacteria. Biofilm structures from the outside and inside of stents do not have crystalline phases. Internal biofilms may represent a high number of bacteria in the double-J stent, in the absence of crystals.
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Ureter , Infecções Urinárias , Masculino , Feminino , Humanos , Adulto , Ureter/diagnóstico por imagem , Ureter/cirurgia , Biofilmes , Stents/efeitos adversos , Infecções Urinárias/microbiologia , BactériasRESUMO
Abstract Background: The state of Aguascalientes, Mexico, has been recognized as a chronic kidney disease hotspot. Screening studies have revealed a high prevalence of persistent albuminuria (pA), histologically characterized by glomerulomegaly, and incomplete podocyte fusion, probably associated with oligonephrony. To date, urinary biomarkers have not been explored in this population. Objective: The aim of the study was to identify the presence of potential biomarkers of early renal injury in patients with pA (pACR) and that correspond with the characteristic nephropathy profile that prevails in this entity. Methods: This is a cross-sectional, analytical, and comparative study. Four groups were recruited: adolescents aged 10-17 years with pACR, isolated albuminuria (iACR), no albuminuria (negative control), and adults with biopsy-confirmed glomerulopathy (positive control). Urinary excretion of SerpinA3, heat-shock protein-72 (HSP-72), podocalyxin (PCX), and nephrin was evaluated in urine samples. SerpinA3 and HSP-72 were analyzed by Western blot, and PCX and nephrin were quantified by enzyme-linked immunosorbent assay. Results: The mean GFR in the pACR group was 113.4 mL/min/1.73m2 and differed significantly only from that of the positive control group (65.1 mL/min/1.73m2). The mean albuminuria value in the pACR group was 48.9 mg/g. SerpinA3 concentration differed between groups (0.08 vs. 0.25 ng/mL, p < 0.001): it was significantly higher in the pACR group compared to the negative controls (p = 0.037). Conclusion: SerpinA3 was significantly associated with pA and could become a biomarker of early kidney injury. Further investigations are required to determine whether SerpinA3 precedes the development of albuminuria and its pathogenic role.
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Background: The state of Aguascalientes, Mexico, has been recognized as a chronic kidney disease hotspot. Screening studies have revealed a high prevalence of persistent albuminuria (pA), histologically characterized by glomerulomegaly, and incomplete podocyte fusion, probably associated with oligonephrony. To date, urinary biomarkers have not been explored in this population. Objective: The aim of the study was to identify the presence of potential biomarkers of early renal injury in patients with pA (pACR) and that correspond with the characteristic nephropathy profile that prevails in this entity. Methods: This is a cross-sectional, analytical, and comparative study. Four groups were recruited: adolescents aged 10-17 years with pACR, isolated albuminuria (iACR), no albuminuria (negative control), and adults with biopsy-confirmed glomerulopathy (positive control). Urinary excretion of SerpinA3, heat-shock protein-72 (HSP-72), podocalyxin (PCX), and nephrin was evaluated in urine samples. SerpinA3 and HSP-72 were analyzed by Western blot, and PCX and nephrin were quantified by enzyme-linked immunosorbent assay. Results: The mean GFR in the pACR group was 113.4 mL/min/1.73m2 and differed significantly only from that of the positive control group (65.1 mL/min/1.73m2). The mean albuminuria value in the pACR group was 48.9 mg/g. SerpinA3 concentration differed between groups (0.08 vs. 0.25 ng/mL, p < 0.001): it was significantly higher in the pACR group compared to the negative controls (p = 0.037). Conclusion: SerpinA3 was significantly associated with pA and could become a biomarker of early kidney injury. Further investigations are required to determine whether SerpinA3 precedes the development of albuminuria and its pathogenic role.
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Insuficiência Renal Crônica , Serpinas , Adulto , Humanos , Adolescente , alfa 1-Antiquimotripsina , Prevalência , Estudos Transversais , Albuminúria/epidemiologia , Albuminúria/etiologia , Insuficiência Renal Crônica/epidemiologia , Biomarcadores , Taxa de Filtração GlomerularRESUMO
Fosfomycin (Fos) has emerged as a potential treatment against multidrug-resistant organisms, however, there has been little work done on its influence on calcineurin inhibitor nephrotoxicity (CIN). This study was designed to evaluate the effect of Fos in combination with cyclosporine (CsA) on CIN. Two sets of experiments were undertaken. In the first, Wistar rats received different doses of Fos: 0, 62.5, 125, 250, and 500 mg/kg. In the second, rats were divided into four groups: control, CsA 15 mg/kg s.c., CsA + fosfomycin 62.5 mg/kg (CsA + LF), and CsA + Fos 500 mg/kg (CsA + HF). CsA was administrated daily for 14 days, whereas Fos administration started on the ninth day followed by two more doses, delivered 48 h apart. The administration of different Fos doses did not alter renal function. In contrast, CsA induced arteriolopathy, hypoperfusion, a reduction in the glomerular filtration rate, and downregulation of eNOS, angiotensinogen, and AT1R mRNA levels. Lower doses of Fos did not modify CIN. Instead, the CsA + HF group exhibited greater hypoperfusion, arteriolopathy, and oxidative stress, and increased mRNA levels of pro-inflammatory cytokines. This study shows that Fos administered by itself at different doses did not cause renal injury, but when it was given repeatedly at high dosages (500 mg/kg) in combination with CsA, it increased CIN through the promotion of greater oxidative stress and renal inflammation.
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The association between anti-AT1Rabs and microvascular injury observed in antibody-mediated rejection has been described in kidney graft Biopsies (KGBx). METHODS: We herein describe the histopathologic findings of KGBx performed during the first year of transplantation (Tx) in 134 patients tested for pre-Tx anti-AT1Rabs in cryopreserved sera (04/2009 to 09/2013). Protocol KGBx before implantation (time-zero), 1â¯year after Tx and for cause KGBx were included. 21/134 Tx patients were anti-AT1Rab positive (≥17â¯U/mL); 7/21 experienced acute rejection. For comparison a control group with anti-AT1Rabs <17â¯U/mL, with (nâ¯=â¯16) and without (nâ¯=â¯31) acute rejection was included. RESULTS: Preimplantation KGBx showed no differences in inflammatory and chronic findings, nor in subintimal fibrosis (25 vs 12.8%, pâ¯=â¯.42) between patients with anti-AT1Rabs ≥17â¯U/mL and those with <17â¯U/mL. Follow-up KGBx revealed a significantly greater proportion of arterial sub-intimal fibrosis (52.3 vs. 27.6%, pâ¯=â¯.049) and extension (15.7 vs. 5.3, pâ¯=â¯.015) in anti-AT1Rabs ≥17â¯U/mL compared to anti-AT1Rabs <17â¯U/mL KGBx. No differences were observed in microcirculation inflammation, nor in interstitial fibrosis or tubular atrophy between groups. Also, anti-AT1Rabs ≥17â¯U/mL (ß 10.1, 2.3 to 17.8, pâ¯=â¯.012) and more importantly anti-AT1Rabsâ¯≥â¯30â¯U/mL (ß12.1, 3.1 to 20.9, pâ¯<â¯.01), were independent risk factors associated with vascular occlusion resulting from sub-intimal fibrosis. CONCLUSION: Our study findings have shown that anti-AT1Rab values ≥17â¯U/mL are significantly associated to sub-intimal fibrosis and a greater percentage of vessel occlusion in kidney graft biopsies obtained during the first year posttransplant, particularly in coexistence with inflammation and de novo DSA.
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Aloenxertos/patologia , Oclusão de Enxerto Vascular/epidemiologia , Rejeição de Enxerto/imunologia , Transplante de Rim , Rim/patologia , Receptor Tipo 1 de Angiotensina/imunologia , Túnica Íntima/patologia , Adolescente , Adulto , Aloenxertos/irrigação sanguínea , Anticorpos/sangue , Feminino , Fibrose , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/epidemiologia , Humanos , Rim/irrigação sanguínea , Doadores Vivos , Masculino , México/epidemiologia , Transplantados , Adulto JovemRESUMO
The complement-binding capacity of anti-HLA antibodies (HLAabs) is recognized as a key pathogenic factor. The aim of this study is to describe the patient characteristics associated to the presence of C1q+ as well as those of the Abs per se when associated to C1q binding. METHODOLOGY: This is a cross-sectional, observational, descriptive study of patients with previous sensitizing factors and awaiting a kidney transplant (KT). We determined anti-HLA antibodies and their C1q binding capacity with the C1q assay. RESULTS: Among the 55 included patients, 26 (47.2%) had at least one C1q+ anti-HLAab. A previous transplant history, a greater number of HLAabs, a greater % of class I or class II PRA, the average MFI of all HLAabs, the MFI of the dominant HLAab and the HLAab antigenic specificities against HLA-B, -C and -DQ, all proved to be risk factors associated to the presence of C1q binding HLAabs (C1q+). In the total population, were detected 1268 HLAabs, 230 (18.1%) of which were C1q+. On multivariate analysis, both HLAabs against the HLA-DQ antigenic specificity (OR 9.82 95% CI 5.4-17.6, p<0.001) and the MFI documented by LABScreen®SAB (OR 1.2% CI 1.22-1.3, p<0.001), proved to be risk factors. CONCLUSION: Anti-HLA-DQ antibodies and the MFI (LABScreen®SAB) are highly and independently related to the C1q-binding capacity of HLA antibodies.
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Complemento C1q/imunologia , Antígenos HLA-DQ/imunologia , Isoanticorpos/imunologia , Transplante de Rim , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The aim of the present study was to describe the association of positive flow cross match (FXM) and C1q-SAB. Methods. In this observational, cross-sectional, and comparative study, patients included had negative AHG-CDC-XM and donor specific antibodies (DSA) and were tested with FXM. All pretransplant sera were tested with C1q-SAB assay. Results. A total of 50 donor/recipient evaluations were conducted; half of them had at least one C1q+ Ab (n = 26, 52%). Ten patients (20.0%) had DSA C1q+ Ab. Twenty-five (50%) FXMs were positive. Factors associated with a positive FXM were the presence of C1q+ Ab (DSA C1q+ Ab: OR 27, 2.80-259.56, P = 0.004, and no DSA C1q+ Ab: OR 5, 1.27-19.68, P = 0.021) and the DSA LABScreen-SAB MFI (OR 1.26, 95% CI 1.06-1.49, P = 0.007). The cutoff point of immunodominant LABScreen SAB DSA-MFI with the greatest sensitivity and specificity to predict FXM was 2,300 (sensitivity: 72% and specificity: 75%). For FXM prediction, DSA C1q+ Ab was the most specific (95.8%, 85-100) and the combination of DSA-MFI > 2,300 and C1q+ Ab was the most sensitive (92.0%, 79.3-100). Conclusions. C1q+ Ab and LABScreen SAB DSA-MFI were significantly associated with FXM. DSA C1q+ Ab was highly specific but with low sensitivity.
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BACKGROUND Due to the shortage of organs for transplantation, there has been increased interest in developing living-donor kidney transplantation (LDKT) programs. MATERIAL AND METHODS A total of 668 potential living kidney donors (PLKD) for 496 intended recipients were evaluated in a LDKT program between 2010 and 2014. Causes for PLKD exclusion were recorded, as well as patient survival. RESULTS After evaluation, 250 (37.4%) PLKD were considered suitable for kidney donation, 331 (49.6%) were excluded for medical reasons, and 87 (13.0%) withdrew their consent. The main cause of exclusion was metabolic syndrome and its components: 131 (39.6%) obesity, 37 (11.2%) new diagnosis of diabetes mellitus, and 25 (7.6%) new diagnosis of hypertension. Sixty-three (19.0%) were excluded for previously undetected renal diseases. Forty-six (13.9%) PLKD were excluded for immunological incompatibility. A total of 158 patients (31.9%) were transplanted from living donors and 31 (6.3%) from deceased donors (after the donor was considered non-suitable). Three-year patient survival was 99.4% for transplanted patients and 41.4% for patients who remained on dialysis. CONCLUSIONS Metabolic diseases constitute the main cause of donor exclusion in some LDKT programs. The high mortality rate of patients whose donor is excluded renews the debate over expanding donor criteria against the long-term risks they may pose to the living kidney donor.
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Seleção do Doador , Transplante de Rim , Doadores Vivos , Síndrome Metabólica/epidemiologia , Adolescente , Adulto , Idoso , Seleção do Doador/estatística & dados numéricos , Epidemias , Feminino , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/mortalidade , Falência Renal Crônica/cirurgia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Obtenção de Tecidos e Órgãos , Adulto JovemRESUMO
BACKGROUND: Renal thrombotic microangiopathy (TMA) may be associated with lupus nephritis. Its relationship to other disease factors and its specific effect on prognosis are not precisely known. Evidence regarding these aspects is controversial, and information focusing on kidney-limited TMA in systemic lupus erythematosus (SLE) patients is scarce. OBJECTIVES: The aims of this study were to identify risk factors for renal TMA in patients with lupus nephritis and to determine its impact on clinical outcomes. METHODS: A case-control study was performed. We studied 245 renal biopsies from SLE patients. We included patients with renal TMA, as well as control subjects adjusted for glomerulonephritis class, estimated glomerular filtration rate, activity and chronicity indices, and follow-up time. Serological and clinical features were measured at the time of the biopsy and during follow-up. RESULTS: Twenty-three patients with renal TMA and 21 control subjects were included. There were no differences in Systemic Lupus Erythematosus Disease Activity Index score, end-stage renal disease, or mortality between groups during follow-up. After multivariate analysis, lymphopenia (odds ratio, 10.69; 95% CI, 1.35-84.74) and anti-Ro antibody positivity (odds ratio, 8.96; 95% CI, 1.49-53.57) remained significantly associated with renal TMA. CONCLUSIONS: Lymphopenia and anti-Ro positivity are independent risk factors for renal TMA in SLE patients. This increased risk could be a consequence of the potential role of these factors in endothelial dysfunction and damage. Outcomes were similar for patients with the same estimated glomerular filtration rate and biopsy characteristics, regardless of the presence of TMA.