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1.
Biomedicines ; 9(10)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34680435

RESUMO

Caveolin-1 overexpression has previously been reported as a marker of endothelial injury in kidney chronic antibody-mediated rejection (c-ABMR), but conclusive evidence supporting its use for daily diagnostic practice is missing. This study aims to evaluate if Caveolin-1 can be considered an immunohistochemical surrogate marker of c-ABMR. Caveolin-1 expression was analyzed in a selected series of 22 c-ABMR samples and 11 controls. Caveolin-1 immunohistochemistry proved positive in peritubular and glomerular capillaries of c-ABMR specimens, irrespective of C4d status whereas all controls were negative. Multiplex gene expression profiling in c-ABMR cases confirmed Caveolin-1 overexpression and identified additional genes (n = 220) and pathways, including MHC Class II antigen presentation and Type II interferon signaling. No differences in terms of gene expression (including Caveolin-1 gene) were observed according to C4d status. Conversely, immune cell signatures showed a NK-cell prevalence in C4d-negative samples compared with a B-cell predominance in C4d-positive cases, a finding confirmed by immunohistochemical assessment. Finally, differentially expressed genes were observed between c-ABMR and controls in pathways associated with Caveolin-1 functions (angiogenesis, cell metabolism and cell-ECM interaction). Based on our findings, Caveolin-1 resulted as a key player in c-ABMR, supporting its role as a marker of this condition irrespective of C4d status.

2.
Am J Gastroenterol ; 116(9): 1924-1928, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465694

RESUMO

INTRODUCTION: We evaluated 8, 12, or 24 weeks of ledipasvir/sofosbuvir in patients with hepatitis C virus and end-stage renal disease undergoing dialysis. METHODS: Primary efficacy end point was sustained virologic response 12 weeks after treatment. Primary safety end point was treatment discontinuation because of adverse events (AEs). RESULTS: Ninety-four percent (89/95) achieved sustained virologic response 12 weeks after treatment. Six patients died during treatment (n = 4) or before study completion (n = 2); no deaths were related to treatment. No patients discontinued treatment because of AEs. Thirteen percent had serious AEs; none were related to treatment. DISCUSSION: Treatment with ledipasvir/sofosbuvir was safe and effective in patients with end-stage renal disease undergoing dialysis.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepatite C/tratamento farmacológico , Falência Renal Crônica/terapia , Sofosbuvir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Esquema de Medicação , Feminino , Fluorenos/administração & dosagem , Hepatite C/complicações , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Sofosbuvir/administração & dosagem , Resposta Viral Sustentada , Resultado do Tratamento
3.
Am J Transplant ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34464503

RESUMO

This study assessed the impact of cancer on the risk of death with a functioning graft of kidney transplant (KT) recipients, as compared to corresponding recipients without cancer. A matched cohort study was conducted using data from a cohort of 13 245 individuals who had undergone KT in 17 Italian centers (1997-2017). Cases were defined as subjects diagnosed with any cancer after KT. For each case, two controls matched by gender, age, and year at KT were randomly selected from cohort members who were cancer-free at the time of diagnosis of the index case. Overall, 292 (20.5%) deaths with a functioning graft were recorded among 1425 cases and 238 (8.4%) among 2850 controls. KT recipients with cancer had a greater risk of death with a functioning graft (hazard ratio, HR = 3.31) than their respective controls. This pattern was consistent over a broad range of cancer types, including non-Hodgkin lymphoma (HR = 33.09), lung (HR = 20.51), breast (HR = 8.80), colon-rectum (HR = 3.51), and kidney (HR = 2.38). The survival gap was observed throughout the entire follow-up period, though the effect was more marked within 1 year from cancer diagnosis. These results call for close posttransplant surveillance to detect cancers at earlier stages when treatments are more effective in improving survival.

4.
PLoS One ; 16(8): e0256306, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34428239

RESUMO

Amyloidosis comprises a spectrum of disorders characterized by the extracellular deposition of amorphous material, originating from an abnormal serum protein. The typing of amyloid into its many variants represents a pivotal step for a correct patient management. Several methods are currently used, including mass spectrometry, immunofluorescence, immunohistochemistry, and immunogold labeling. The aim of the present study was to investigate the accuracy and reliability of immunohistochemistry by means of a recently developed amyloid antibody panel applicable on fixed paraffin-embedded tissues in an automated platform. Patients with clinically and pathologically proven amyloidosis were divided into two cohorts: a pilot one, which included selected amyloidosis cases from 2009 to 2018, and a retrospective one (comprising all consecutive amyloidosis cases analyzed between November 2018 and May 2020). The above-referred panel of antibodies for amyloid classification was tested in all cases using an automated immunohistochemistry platform. When fresh-frozen material was available, immunofluorescence was also performed. Among 130 patients, a total of 143 samples from different organs was investigated. They corresponded to 51 patients from the pilot cohort and 79 ones from the retrospective cohort. In 82 cases (63%), fresh-frozen tissue was tested by immunofluorescence, serving to define amyloid subtype only in 30 of them (36.6%). On the contrary, the automated immunohistochemistry procedure using the above-referred new antibodies allowed to establish the amyloid type in all 130 cases (100%). These included: ALλ (n = 60, 46.2%), ATTR (n = 29, 22.3%), AA (n = 19, 14.6%), ALκ (n = 18, 13.8%), ALys (n = 2, 1.5%), and Aß2M amyloidosis (n = 2, 1.5%). The present immunohistochemistry antibody panel represents a sensitive, reliable, fast, and low-cost method for amyloid typing. Since immunohistochemistry is available in most pathology laboratories, it may become the new gold standard for amyloidosis classification, either used alone or combined with mass spectrometry in selected cases.

5.
Dig Liver Dis ; 53 Suppl 2: S49-S86, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34074490

RESUMO

Liver and kidney are strictly connected in a reciprocal manner, in both the physiological and pathological condition. The Italian Association for the Study of Liver, in collaboration with the Italian Society of Nephrology, with this position paper aims to provide an up-to-date overview on the principal relationships between these two important organs. A panel of well-recognized international expert hepatologists and nephrologists identified five relevant topics: 1) The diagnosis of kidney damage in patients with chronic liver disease; 2) Acute kidney injury in liver cirrhosis; 3) Association between chronic liver disease and chronic kidney disease; 4) Kidney damage according to different etiology of liver disease; 5) Polycystic kidney and liver disease. The discussion process started with a review of the literature relating to each of the five major topics and clinical questions and related statements were subsequently formulated. The quality of evidence and strength of recommendations were graded according to the GRADE system. The statements presented here highlight the importance of strong collaboration between hepatologists and nephrologists for the management of critically ill patients, such as those with combined liver and kidney impairment.

7.
PLoS One ; 16(4): e0249552, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33819285

RESUMO

BACKGROUND: Pre-existing chronic hypotension affects a percentage of kidney transplanted patients (KTs). Although a relationship with delayed graft function (DGF) has been hypothesized, available data are still scarce and inconclusive. METHODS: A monocentric retrospective observational study was performed on 1127 consecutive KTs from brain death donors over 11 years (2003-2013), classified according to their pre-transplant Mean Blood Pressure (MBP) as hypotensive (MBP < 80 mmHg) or normal-hypertensive (MBP ≥ 80 mmHg, with or without effective antihypertensive therapy). RESULTS: Univariate analysis showed that a pre-existing hypotension is associated to DGF occurrence (p<0.01; OR for KTs with MBP < 80 mmHg, 4.5; 95% confidence interval [CI], 2.7 to 7.5). Chronic hypotension remained a major predictive factor for DGF development in the logistic regression model adjusted for all DGF determinants. Adjunctive evaluations on paired grafts performed in two different recipients (one hypotensive and the other one normal-hypertensive) confirmed this assumption. Although graft survival was only associated with DGF but not with chronic hypotension in the overall population, stratification according to donor age revealed that death-censored graft survival was significantly lower in hypotensive patients who received a KT from >50 years old donor. CONCLUSIONS: Our findings suggest that pre-existing recipient hypotension, and the subsequent hypotension-related DGF, could be considered a significant detrimental factor, especially when elderly donors are involved in the transplant procedure.


Assuntos
Função Retardada do Enxerto/patologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Hipotensão/fisiopatologia , Transplante de Rim/efeitos adversos , Doadores de Tecidos/provisão & distribuição , Transplantados/estatística & dados numéricos , Idoso , Função Retardada do Enxerto/etiologia , Rejeição de Enxerto/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Obtenção de Tecidos e Órgãos
8.
Minerva Urol Nephrol ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33781021

RESUMO

BACKGROUND: Non-adherence (NA) to immunosuppressive drugs is to date considered a crucial issue in kidney transplanted patients (KTRs), leading to de novo donor-specific anti-HLA antibodies (dnDSA) development, acute and chronic rejection, and at least graft loss. However, NA assessment is challenging, often leading to underestimation in real-life settings. METHODS: NA evaluation in all KTRs referred to our post-transplantation clinic in the period between 01/01-15/07/2018 with self-report questionnaire combined to intra-patient variability (IPV) of the pivotal immunosuppressive drug (based on trough levels of tacrolimus/mTOR inhibitor). RESULTS: Based on both questionnaire and IPV, 86 out of the 504 tested KTRs (17%) were classified as NA. Male gender (OR, 2.0; 95% confidence interval [CI], 1.2 to 3.4), high educational level (OR for KTRs with a degree, 1.8 [95% CI, 1.0 to 3.1]), employment (OR, 2.0 [95% CI, 1.2 to 3.3]), young age at transplantation (p=0.017), longer time on the waiting list and after transplantation (p= 0.027 and 0.049 respectively) were all associated with NA. High IPV was mostly documented in KTRs treated with the twice-daily formulation of the immunosuppressive drug (OR, 1.5 [95% CI, 1.0 to 2.1]) and better associated with dnDSA appearance (OR, 2.1 [95% CI, 1.1 to 3.9]). CONCLUSIONS: NA is a significant problem, difficult to assess, and can lead to dnDSA development also in our population. Identifying risk factors for NA might be an underestimated tool to improve graft and patient outcome in KTRs.

9.
Clin Kidney J ; 14(1): 317-324, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33564434

RESUMO

Background: Management of patients with oncohaematological disorders such as monoclonal gammopathy of undetermined significance (MGUS) is a frequent problem in pre-transplant work-up. Insights on disease progression and long-term functional outcomes are still lacking in this setting. Methods: This was a retrospective analysis on all patients with MGUS who underwent kidney transplant (KT) at our centre between 1 January 2000 and 31 December 2017 (cases, n = 65). Patients were matched with a control group (KTs with similar characteristics but without history of haematological disease, controls, n = 1079). Primary endpoints were graft and patient survival; secondary endpoints were causes of graft failure, patient death, occurrence of allograft rejection, post-transplant neoplasia (not correlated to previous disorder) and/or infectious episodes. Results: The MGUS and control groups had a similar mean age [60 (29-79) versus 55.2 (19.3-79.5) years, respectively] and percentage of males (69.2% versus 64.6%, respectively). Median follow-up time since KT was 3.5 years (0-14) in cases and 8.3 years (0-14.9) in controls. All MGUS patients underwent KT following extensive multidiscliplinary investigations. No differences were found between cases and controls regarding patient and graft survival or post-transplant complications except for lower incidence of infections (58.7% versus 69.8%, P = 0.019) and increased use of mTOR inhbitors (30.3% versus 14.7%, P = 0.001) in MGUS. MGUS isotype did not influence graft and patient survival. The absence of difference in patients and graft survival was also confirmed in an adjunctive analysis where MGUS were compared with controls (ratio 1:2) matched for recipient age, gender, number of transplantations and transplant period. Conclusion: Patients with MGUS may undergo KT without significantly increased risks of complications, provided that appropriate diagnostic procedures are carefully followed. Multidiscipline-based studies are crucial for establishing well designed pre- and post-transplant protocols for the best management of patients with coexisting MGUS and end-stage renal disease.

10.
J Vasc Access ; 22(1): 129-134, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32524867

RESUMO

BACKGROUND: Kidney allograft resistive index (RI) is prognostic for graft and recipient survivals. Recipient hemodynamics could influence RI. In particular, dialysis arteriovenous fistula (AVF) has been involved in heart function changes, reversible after AVF ligation. Knowledge about AVF and RI is lacking. In this study, we prospectively evaluated RI changes after AVF ligation in kidney transplanted patients. METHODS: We enrolled 22 stable transplanted patients. Mean RI was measured before AVF ligation (T0), 18 to 24 h (T1) and 6 months (T6) after surgery; mean blood pressure (mBP), heart rate (HR), serum creatinine (sCr), estimated glomerular filtration rate (eGFR), 24 h proteinuria (24 h-P), immunosuppressive drug blood levels (IS) and antihypertensive drugs were also recorded. RESULTS: AVF ligation was performed 3.1 years (IQR: 2.1-3.8) after transplantation. Median AVF flow (Qa) was 1868 mL/min (IQR: 1538-2712) and 8 AVF were classified as high flow (Qa ≥ 2 L/min). At baseline, median sCr was 1.32 mg/dL (IQR: 1.04-1.76) and median eGFR was 57.1 mL/min. Median RI was 0.71 at T0, 0.69 at T1, 0.66 at T6. RI reduction at T1 and T6 was statistically significant (p < 0.05 and p < 0.001 respectively); in particular, 90.4% of patients had persistently improved values at T6. Furthermore, mBP increased while HR decreased. These changes were independent from sCr, 24 h-P, IS, antihypertensive drugs number, Qa and AVF type. CONCLUSIONS: AVF ligation improves kidney allograft RI; it may reflect better kidney perfusion.


Assuntos
Derivação Arteriovenosa Cirúrgica , Sobrevivência de Enxerto , Hemodinâmica , Transplante de Rim , Circulação Renal , Diálise Renal , Adulto , Idoso , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Derivação Arteriovenosa Cirúrgica/mortalidade , Velocidade do Fluxo Sanguíneo , Feminino , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Ligadura , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fluxo Sanguíneo Regional , Fatores de Tempo , Resultado do Tratamento , Resistência Vascular
12.
J Nephrol ; 34(4): 1127-1135, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33373028

RESUMO

Metformin is currently considered a first-line therapy in type 2 diabetic patients. After issuing warnings for decades about the risks of lactic acidosis in patients with chronic nephropathy, metformin is now being re-evaluated. The most recent evidence from the literature has demonstrated both a low, acceptable risk of lactic acidosis and a series of favorable effects, which go beyond its hypoglycemic activity. Patients treated with metformin show a significant mortality reduction and lower progression towards end-stage renal disease in comparison with those treated with other hypoglycemic drugs. Concerning lactic acidosis, in the last few years it has been shown how lactic acidosis almost always developed when patients kept taking the drug in the face of a concomitant disease or situation such as sepsis, fever, diarrhea, vomiting, which reduced metformin renal clearance. Actually, clearance of metformin is mainly renal, both by glomerular filtration and tubular secretion (apparent clearance 933-1317 ml/min, half-life < 3 h). As regards treatment, in cases of lactic acidosis complicated by acute kidney injury, continuous renal replacement therapy (CRRT) plays a crucial role. Besides the elimination of metformin, CRRT  improves survival by correcting acidosis, electrolyte alterations, and maintaining fluid balance. Lactic acidosis almost always develops because of preventable drug accumulation. Therefore, prevention is a key factor. Patients should be aware that discontinuation for a limited time does not affect their health, even when it may be inappropriate, but it may avoid a serious, potentially fatal adverse event.


Assuntos
Acidose Láctica , Diabetes Mellitus Tipo 2 , Falência Renal Crônica , Metformina , Acidose Láctica/induzido quimicamente , Acidose Láctica/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Nefrologistas
13.
Clin Med Insights Case Rep ; 13: 1179547620974672, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33281463

RESUMO

With the widespreading use of biologic drugs, reports of renal injury are increasing, most of which belong to the spectrum of secondary autoimmune syndromes. We present the case of a young man affected by Ankylosing Spondylitis, treated with tumor necrosis factor alpha inhibitors (Anti-TNF) that develop a peculiar renal damage: a coexistence of 2 glomerulonephritis due to different noxae, an IgA nephropaty with a Membranous nephropathy. The first one probably related to the rheumatologic disease, the second one related to Anti-TNF. Despite the underlying mechanisms, the renal involvement both related to Ankylosing Spondylitis and secondary to biologic treatment are currently rare and not predictable. Regular control of renal function and urinalysis during treatment with anti-TNF is mandatory. A concomitant treatment with Disease Modifying Anti Rheumatic Drugs or eventually a low dose of steroids may prevent the formation of anti-drug antibodies and could limit the renal damage related to this phenomenon.

14.
Sci Rep ; 10(1): 22000, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33319849

RESUMO

Despite type 2 diabetes mellitus (T2D) is commonly considered a detrimental factor in dialysis, its clear effect on morbidity and mortality on waitlisted patients for kidney transplant (KT) has never been completely elucidated. We performed a retrospective analysis on 714 patients admitted to wait-list (WL) for their first kidney transplant from 2005 to 2010. Clinical characteristics at registration in WL (age, body mass index -BMI-, duration and modality of dialysis, underlying nephropathy, coronary artery -CAD- and/or peripheral vascular disease), mortality rates, and effective time on WL were investigated and compared according to T2D status (presence/absence). Data about therapy and management of T2D were also considered. At the time of WL registration T2D patients (n = 86) were older than non-T2D (n = 628) (58.7 ± 8.6 years vs 51.3 ± 12.9) with higher BMI (26.2 ± 3.8 kg/m2 vs 23.8 ± 3.6), more frequent history of CAD (33.3% vs 9.8%) and peripheral vascular disease (25.3% vs 5.8%) (p < 0.001 for all analyses). Considering overall population, T2D patients had reduced survival vs non-T2D (p < 0.001). Transplanted patients showed better survival in both T2D and non-T2D groups despite transplant rate are lower in T2D (75.6% vs 85.8%, p < 0.001). T2D was also associated to similar waiting time but longer periods between dialysis start and registration in WL (1.6 years vs 1.2, p = 0.008), comorbidity-related suspension from WL (571 days vs 257, p = 0.002), and increased mortality rate (33.7% vs 13.9% in the overall population, p < 0.001). In T2D patients admitted to WL, an history of vascular disease was significantly associated to low patient survival (p = 0.019). In conclusion, T2D significantly affects survival also on waitlisted patients. Allocation policies in T2D patients may be adjusted according to increased risk of mortality and WL suspension due to comorbidities.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Transplante de Rim , Listas de Espera , Causas de Morte , Europa (Continente) , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento
16.
J Nephrol ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226606

RESUMO

BACKGROUND: A considerable minority of patients on waiting lists for kidney transplantation either have no diagnosis (and fall into the subset of undiagnosed cases) because kidney biopsy was not performed or histological findings were non-specific, or do not fall into any well-defined clinical category. Some of these patients might be affected by a previously unrecognised monogenic disease. METHODS: Through a multidisciplinary cooperative effort, we built an analytical pipeline to identify patients with chronic kidney disease (CKD) with a clinical suspicion of a monogenic condition or without a well-defined diagnosis. Following the stringent phenotypical and clinical characterization required by the flowchart, candidates meeting these criteria were further investigated by clinical exome sequencing followed by in silico analysis of 225 kidney-disease-related genes. RESULTS: By using an ad hoc web-based platform, we enrolled 160 patients from 13 different Nephrology and Genetics Units located across the Piedmont region over 15 months. A preliminary "remote" evaluation based on well-defined inclusion criteria allowed us to define eligibility for NGS analysis. Among the 138 recruited patients, 52 (37.7%) were children and 86 (62.3%) were adults. Up to 48% of them had a positive family history for kidney disease. Overall, applying this workflow led to the identification of genetic variants potentially explaining the phenotype in 78 (56.5%) cases. CONCLUSIONS: These results underline the importance of clinical exome sequencing as a versatile and highly useful, non-invasive tool for genetic diagnosis of kidney diseases. Identifying patients who can benefit from targeted therapies, and improving the management of organ transplantation are further expected applications.

17.
J Vasc Access ; : 1129729820971533, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33183181

RESUMO

INTRODUCTION: the external support device VasQ is intended to promote arteriovenous fistula (AVF) maturation by maintaining the optimal anastomotic angle in order to minimize blood flow disturbances around the anastomotic area. The aim of the study is to assess efficacy and safety of the VasQ device both in brachiocephalic and radiocephalic fistulae. METHODS: a single institution prospective study was conducted with implantation of the VasQ device during AVF creation. Clinical and Doppler ultrasounds evaluations were performed at day-1, 1, 6, and 12 months for assessment of device-related adverse events, AVF maturation and patency. Moreover, volume flow rate and diameter of outflow vein were measured. A total of 16 patients were enrolled. Ten brachiocephalic and 6 radiocephalic AVFs were created with VasQ. Preoperatively cephalic vein diameter was 3.6 ± 0.9 mm. RESULTS: our population included 13 male and 3 females patients, 9 end stage kidney disease in conservative therapy, 4 dialysis treated patients, and 3 transplanted patients; mean age was 74.0 ± 8.1 years; no severe device-related adverse events were observed. Primary patency at 1, 6, and 12 months was 100%, 87.5%, and 67.7%, respectively, while secondary patency was 100%, 100%, and 78.3%, respectively. Comparing brachiocephalic to radiocephalic AVFs no significant differences in patency rates were seen. Overall maturation rate was 94% (15/16). Mean vein diameter measured with Doppler ultrasound at postoperative day-1 and at 1, 6, and 12 months was 5.0 ± 1.0, 5.9 ± 0.9, 7.2 ± 1.6, and 7.9 ± 1.4 mm, respectively, with a mean flow rate at the brachial artery of 841 ± 176, 1052 ± 224, 1261 ± 490, and 1348 ± 477 ml/min, respectively. CONCLUSIONS: in our limited experience VasQ was safe, with high maturation and patency rates. Positive results suggest a potential benefit for VasQ in AVF.

18.
Sci Rep ; 10(1): 16362, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004982

RESUMO

Idiopathic membranous nephropathy (iMN) is considered an immune-mediated disease where circulating autoantibodies against podocyte targets (mainly the PLA2R) cause the deposition of in-situ subepithelial immune-complexes. The consequent podocyte damage may cause cell detachment in urine (Podocyturia-PdoU). PdoU has been assessed in different kidney diseases, but limited data are available in iMN. In this study all patients with a diagnosis of iMN between 15/12/1999-16/07/2014 were tested for PLA2R antibodies (Ab anti-PLA2R, ELISA kit) and PdoU by flow cytometry with anti-podocalyxin antibody. A semi-quantitative PdoU score was defined according to the percentage of podocalyxin positive cells normalized to the total volume of sample and set relative to the urine creatinine measured in the supernatant. PdoU was positive in 17/27 patients (63%; 1+ score in 6/27-22.2%, 2+ in 4/27-14.8%, 3+ in 2/27-7.4%, 4+ in 5/27-18.5%). Only 2/7 patients with complete remission showed a positive PdoU (1+) while all six patients without remission have significant PdoU. PdoU+ was statistically correlated with the absence of remission and Ab anti-PLA2R + (p < 0.05) but PdoU, analysed as a continuous variable, showed a non-linear correlation with proteinuria or PLA2R antibody levels also in the cohort of patients with two available PdoU tests. In conclusion, PdoU could be detected in iMN and seems to be associated with commonly considered markers of disease activity (proteinuria and Ab anti-PLA2R) with a non-linear correlation. Despite data should be confirmed in large and prospective cohorts, according to the podocyte depletion hypothesis PdoU may represent an early marker of immunological activation with potential prognostic utility.


Assuntos
Citometria de Fluxo , Glomerulonefrite Membranosa/diagnóstico , Podócitos/metabolismo , Receptores da Fosfolipase A2/imunologia , Adulto , Idoso , Autoanticorpos/imunologia , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/urina , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
19.
PLoS One ; 15(10): e0240335, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33057374

RESUMO

BACKGROUND: Increased acute rejection risk in rescue protocols with Belatacept may limit its use particularly in medically complex patients where preexisting increased risk of rejection couples with CNI toxicity. METHODS: Retrospective analysis was performed in 19 KTs shifted to a Belatacept-based immunosuppression with low-dose Tacrolimus (2-3 ng/mL) after evidence of allograft disfunction, including patients with primary non-function (PNF), chronic-active antibody-mediated rejection (cAMR), history of previous KTs and/or other concomitant transplants (liver, pancreas). Evaluation of CD28+ CD4+ effector memory T cell (TEM) before conversion was performed in 10/19. RESULTS: Kidney function significantly improved (median eGFR 16.5 ml/min/1.73m2 before vs 25 ml/min after; p = 0.001) at a median time after conversion of 12.5 months (9.1-17.8). Overall graft and patient survival were 89.5% and 100% respectively. Definitive weaning from dialysis in 5/5 KTs with PNF was observed, whereas 7/8 patients lost their graft within first year in a control group. eGFR significantly ameliorated in re-trasplants (p = 0.001) and stabilized in KTs with other organ transplants or cAMR. No acute rejection episodes occurred, despite the significant risk suggested by high frequency of CD28+ CD4+ TEM in most patients. Opportunistic infections were limited and most common in early vs late-converted. CONCLUSIONS: Rescue association of Belatacept with low-dose Tacrolimus in medically complex KTs is a feasible option that allows prevention of acute rejection and amelioration of graft function.


Assuntos
Abatacepte/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Tacrolimo/uso terapêutico , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Transplante Homólogo
20.
Viruses ; 12(9)2020 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-32962215

RESUMO

BACKGROUND: In kidney transplant patients, polyomavirus-associated nephropathy (PVAN) represents a serious complication; the key factor for the development of PVAN is immunosuppression level and modulation of anti-rejection treatment represents the first line of intervention. Allograft biopsy and histology remain the criterion standard for diagnosing PVAN. METHODS: All consecutive renal biopsies with the diagnosis of PVAN carried out at the University Hospital City of Health and Science of Turin over a five-years period were studied. Renal allograft biopsy was performed due to renal function alterations associated to medium-high polyomavirus BK (BKV)-DNA levels on plasma specimen. RESULTS: A total of 21 patients underwent a first biopsy to diagnose a possible BKV nephropathy, in 18, a second biopsy was made, in eight, a third biopsy, and finally, three underwent the fourth renal biopsy; following the results of each biopsies, immunosuppressant agents dosages were modified in order to reduce the effect of PVAN. CONCLUSIONS: In this study, the clinical and histological features of 21 kidney transplant recipients with BKV reactivation and development of PVAN are described. To date, the only treatment for PVAN consists in the reduction of immunosuppressive agents, constantly monitoring viral load.


Assuntos
Nefropatias/complicações , Transplante de Rim , Infecções por Polyomavirus/complicações , Polyomavirus , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Vírus BK , Biópsia , Feminino , Humanos , Imunossupressão , Imunossupressores/uso terapêutico , Rim/patologia , Rim/virologia , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Nefropatias/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/tratamento farmacológico , Infecções por Polyomavirus/patologia , Infecções por Polyomavirus/virologia , Fatores de Risco , Transplante Homólogo , Infecções Tumorais por Vírus/complicações , Carga Viral , Adulto Jovem
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