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1.
Am J Transplant ; 24(10): 1896-1900, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39029875

RESUMEN

The recurrence of primary focal segmental glomerulosclerosis (FSGS) after kidney transplantation is associated with a high graft loss rate with standard treatments based on plasmapheresis with/without rituximab. We present 2 consecutive cases of nongenetic early severe recurrent FSGS refractory to rituximab and anti-interleukin 1 treatment and with a partial response to plasmapheresis. Case 1 was a 22-year-old man who was rescue-treated for recurrence 36 weeks after transplantation with obinutuzumab (1000 mg/1.73 m2, 1 dose) and daratumumab (18 mg/kg each dose, 8 doses), resulting in plasmapheresis discontinuation and a drop of proteinuria from 29 to 2.3 g/d. Proteinuria increased with circulating CD38+ plasma cells and responded to an additional daratumumab dose. Currently, the proteinuria is 1.8 g/d, 14.5 months after discontinuing plasmapheresis and starting obinutuzumab and daratumumab therapy. Case 2 was a 15-year-old girl who was plasmapheresis dependent with 2 g/d proteinuria 82 weeks after transplantation, with a Tesio catheter in the right jugular vein as the only possible vascular access. After treatment with obinutuzumab and daratumumab (1 dose each), she achieved stable complete remission (0.3 g/d proteinuria) with persistent plasmapheresis discontinuation. These cases suggest the potential of combining obinutuzumab with daratumumab for the treatment of recurrent FSGS.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Anticuerpos Monoclonales , Glomeruloesclerosis Focal y Segmentaria , Trasplante de Riñón , Recurrencia , Humanos , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/etiología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Adulto Joven , Femenino , Adolescente , Trasplante de Riñón/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Células Plasmáticas/patología , Linfocitos B/efectos de los fármacos , Plasmaféresis , Pronóstico , Supervivencia de Injerto/efectos de los fármacos , Tasa de Filtración Glomerular , Complicaciones Posoperatorias/tratamiento farmacológico , Rechazo de Injerto/etiología , Rechazo de Injerto/tratamiento farmacológico , Adulto
2.
Clin Transplant ; 38(7): e15394, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39001595

RESUMEN

INTRODUCTION: Broad national or international programs contribute to mitigating the expected longer waiting list (WL) time for sensitized patients but with minor benefits for highly sensitized subjects. Therefore, strategies to prevent high sensitization are urgently required. In this study, we investigated the risk of developing highly sensitized patients with different immunosuppressive (IS) handling after kidney allograft failure (KAF). METHODS: Data from 185 patients with KAF, retransplanted/relisted from 2010 to 2020 in two regions of Italy that share the same regional WL, were analyzed. Patients were categorized according to IS management at 12 months after KAF as follows: patients maintaining IS with calcineurin inhibitors (CNI) (late withdrawal group [LWG], n = 58) and those who withdrew all IS therapy or were on steroids only (early withdrawal group [EWG], n = 127). RESULTS: Patients in the LWG showed lower panel reactive antibodies (PRA) at 12 (29.0% vs. 85.5%, p < 0.001) and 24 months (61.0% vs. 91.0%, p = 0.001), reduced risk of high sensitization (PRA ≥90%) at 12 (9.4% vs. 40.7%, p < 0.001, OR = 0.15) and 24 months (25.6% vs. 57.3%, p = 0.001, OR = 0.26) and almost no very high sensitization (PRA ≥ 98%) at 12 months (1.9% vs. 18.6%, p = 0.003, OR = 0.08) after KAF. In the LWG subgroup analysis, patients who maintained IS for up to 24 months after KAF did not show very high sensitization. The LWG showed shorter active WL times (406 vs. 813 days, p = 0.001) without an increased risk of complications. CONCLUSIONS: CNI maintenance for at least 12 months after KAF could be a useful approach to prevent high sensitization and reduce WL times in patients who are offered retransplantation, without a higher burden of complications.


Asunto(s)
Inhibidores de la Calcineurina , Rechazo de Injerto , Supervivencia de Injerto , Inmunosupresores , Trasplante de Riñón , Humanos , Masculino , Femenino , Trasplante de Riñón/efectos adversos , Inhibidores de la Calcineurina/uso terapéutico , Persona de Mediana Edad , Estudios de Seguimiento , Rechazo de Injerto/prevención & control , Rechazo de Injerto/etiología , Rechazo de Injerto/inmunología , Supervivencia de Injerto/efectos de los fármacos , Supervivencia de Injerto/inmunología , Factores de Riesgo , Inmunosupresores/uso terapéutico , Pronóstico , Fallo Renal Crónico/cirugía , Adulto , Tasa de Filtración Glomerular , Estudios Retrospectivos , Complicaciones Posoperatorias/prevención & control , Pruebas de Función Renal , Terapia de Inmunosupresión/métodos
3.
Blood Purif ; 52(5): 446-454, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36882012

RESUMEN

INTRODUCTION: In polytrauma patients with AKI continuous venovenous hemodialysis (CVVHD) with medium cutoff membrane filters is commonly adopted to increase the removal of both myoglobin and inflammatory mediators, but its impact on increasing molecular weight markers of inflammation and cardiac damage is debated. METHODS: Twelve critically ill patients with rhabdomyolysis (4 burns and 8 polytrauma patients) and early AKI requiring CVVHD with EMIc2 filter were tested for 72 h on serum and effluent levels for NT-proBNP, procalcitonin (PCT), myoglobin, C-reactive protein (CRP), alpha1-glycoprotein, albumin, and total protein. RESULTS: The sieving coefficients (SCs) for proBNP and myoglobin were as higher as 0.5 at the start, decreased to 0.3 at the 2nd h, and then slowly declined to the final value of 0.25 and 0.20 at the 72nd h, respectively. PCT showed a negligible SC at the 1st h, a peak of 0.4 at the 12th h, and a final value of 0.3. SCs for albumin, alpha1-glycoprotein, and total protein were negligible. A similar trend was observed for the clearances (17-25 mL/min for proBNP and myoglobin; 12 mL/for PCT; <2 mL/min for albumin, alpha1-glycoprotein, and total protein). No correlation was found between systemic determinations and filter clearances of proBNP, PCT, and myoglobin. Net fluid loss/hour during CVVHD positively correlated with systemic myoglobin for all patients and NT-proBNP in the burn patients. CONCLUSION: CVVHD with EMiC2 filter showed low clearances for NT-proBNP and procalcitonin. CVVHD did not significantly affect the serum levels of these biomarkers, which could be adopted in the clinical management of early CVVHD patients.


Asunto(s)
Lesión Renal Aguda , Terapia de Reemplazo Renal Continuo , Traumatismo Múltiple , Rabdomiólisis , Humanos , Polipéptido alfa Relacionado con Calcitonina , Mioglobina , Rabdomiólisis/complicaciones , Rabdomiólisis/terapia , Biomarcadores , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Albúminas , Glicoproteínas
4.
BMC Nephrol ; 22(1): 386, 2021 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-34789191

RESUMEN

BACKGROUND: Rare diseases (RDs) encompass many difficult-to-treat conditions with different characteristics often associated with end-stage renal disease (ESRD). However, data about transplant outcomes in adult patients are still lacking and limited to case reports/case series without differentiation between immunological/non-immunological RDs. METHODS: Retrospective analysis among all adult kidney transplanted patients (KTs) with RDs (RDsKT group) performed in our high-volume transplantation center between 2005 and 2016. RDs were classified according to the Orphanet code system differentiating between immunological and non-immunological diseases, also comparing clinical outcomes and temporal trends to a control population without RDs (nRDsKT). RESULTS: Among 1381 KTs, 350 patients (25.3%) were affected by RDs (RDsKTs). During a f/up > 5 years [median 7.9 years (4.8-11.1)], kidney function and graft/patient survival did not differ from nRDsKTs. Considering all post-transplant complications, RDsKTs (including, by definition, patients with primary glomerulopathy except on IgA nephropathy) have more recurrent and de-novo glomerulonephritis (14.6% vs. 9.6% in nRDsKTs; p = 0.05), similar rates of de-novo cancers, post-transplant diabetes, dysmetabolism, hematologic disorders, urologic/vascular problems, and lower infectious episodes than nRDsKTs (63.7% vs 72.7%; p = 0.013). Additional stratification for immunological and non-immunological RDsKTs or transplantation periods (before/after 2010) showed no differences or temporal trends between groups. CONCLUSIONS: Kidney transplant centers are deeply involved in RDs management. Despite their high-complex profile, both immunological and non-immunological RDsKTs experienced favorable patients' and graft survival.


Asunto(s)
Enfermedades del Sistema Inmune/epidemiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Enfermedades Raras/epidemiología , Adulto , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Enfermedades del Sistema Inmune/etiología , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Italia/epidemiología , Estimación de Kaplan-Meier , Fallo Renal Crónico/complicaciones , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Prevalencia , Enfermedades Raras/etiología , Estudios Retrospectivos , Factores de Riesgo
5.
Clin Transplant ; 34(8): e13908, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32415711

RESUMEN

INTRODUCTION: Chronic active antibody-mediated rejection (cAMR) is a major determinant of late allograft failure. Rituximab/immunoglobulins (IVIg) + plasma exchange (PLEX) showed controversial results in cAMR treatment. Tocilizumab (TCZ), a humanized anti-interleukin 6 receptor antibody, has been recently used as rescue therapy in patients non-responsive to rituximab/IVIg/PLEX with favorable outcomes. Whether TCZ acts "per se" or requires a priming effect from previous treatments is currently unknown. METHODS: Fifteen patients with cAMR were treated with TCZ as a first-line therapy and followed for a median time of 20.7 months. RESULTS: Despite the majority of patients experiencing advanced transplant glomerulopathy (TG) at diagnosis (60% with cg3), glomerular filtration rate and proteinuria stabilized during the follow-up, with a significant reduction in donor-specific antibodies. Protocol biopsies after 6 months demonstrated significant amelioration of microvascular inflammation and no TG, C4d deposition, or IF/TA progression. Gene-expression and immunofluorescence analysis showed upregulation of three genes (TJP-1, AKR1C3, and CASK) involved in podocyte, mesangial, and tubular restoration. CONCLUSION: Tocilizumab adopted as a first-line approach in cAMR was associated with early serological and histological improvements and functional stabilization even in advanced TG, suggesting a role for the use of TCZ alone with the avoidance of unnecessary previous immunosuppressants.


Asunto(s)
Trasplante de Riñón , Anticuerpos Monoclonales Humanizados/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/etiología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Rituximab/uso terapéutico
6.
Transpl Infect Dis ; 22(6): e13348, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32500936

RESUMEN

Few reports described the outcome of kidney transplanted patients (KTs) affected by COVID-19 treated with interleukin-6 receptor inhibitor tocilizumab (TCZ). We report our case series of 6 KTs with COVID-19 pneumonia who received TCZ: All were of male gender, with a mean age of 55.5 ± 8.4 years, a median time from transplantation of 3611 days (1465-5757); 5/6 had cardiovascular comorbidities, 1/6 had diabetes, and 3/6 have one or more previous KTs. Four out of six patients died, at an average time of 9.75 ± 2.4 days after tocilizumab administration, 3/6 due to a coexistent septic shock. Two patients improved after TCZ and were discharged at 20 and 21 days, respectively; in both patient, a significant increase of total lymphocyte count was observed. In conclusion, KTs, where the role of peculiar factors such as chronic immunosuppression is still undetermined, represent a high-risk group with significant COVID-19-associated mortality. The evaluation of the TCZ effect in COVID-19 pneumonia requires controlled studies (ideally RCTs) in this specific population.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Rechazo de Injerto/prevención & control , Huésped Inmunocomprometido/inmunología , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Lesión Renal Aguda/terapia , Adulto , Anciano , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Proteína C-Reactiva/inmunología , COVID-19/inmunología , COVID-19/mortalidad , Terapia de Reemplazo Renal Continuo , Inhibidores Enzimáticos/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Recuento de Leucocitos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Resultado del Tratamiento
7.
Clin Transplant ; 32(11): e13407, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30218593

RESUMEN

BACKGROUND: Transplant glomerulopathy (TG) is an important cause of late graft loss. The role of angiotensin type 1-receptor antibodies (AT1 R-Ab) in TG is not known. METHODS: All the TG cases (N = 137) between January 2007 and December 2014 (N = 1410) were analyzed. Donor-specific anti-HLA antibodies (DSA) at the time of biopsy and AT1 R-Ab IgG (positive, >17 UI/mL; "at risk," 10-17 UI/mL; negative, <10 UI/mL) in pre-transplant sera (PT-Ab) and at biopsy time (BT-Ab) were studied. RESULTS: AT1 R-PT-Ab+ and AT1 R-BT-Ab+ patients were 16.5% (51.5% "at risk") and 11.5% (27.4% "at risk"), respectively. Clinical correlations were found between AT1 R-Ab and HCV infection, number of transplants, and age. Considering Banff scores, ptc was higher in DSA+ patients vs AT1 R-PT-Ab+ (P = 0.002) or AT1 R-BT-Ab+ (P = 0.001) without differences in g and chronicity score (ci + ct); cg showed lower scores in DSA+ patients vs AT1 R-BT-Ab+ (P = 0.001). Graft survival was not influenced by the presence of AT1 R-Ab, AT1-R-Ab titer or MFI, but we observed a longer graft survival in patients with both AT1 R-BT-Ab+ or "at risk" and DSA+ vs patients positive only for DSA (P = 0.02), for AT1 R-BT-Ab (P = 0.019) or AT1 R-BT-Ab "at risk" (P = 0.039). CONCLUSION: AT1 R-Ab showed no independent prognostic role in TG in this pilot analysis.


Asunto(s)
Autoanticuerpos/sangre , Glomerulonefritis Membranosa/diagnóstico , Rechazo de Injerto/diagnóstico , Antígenos HLA/sangre , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Receptor de Angiotensina Tipo 1/sangre , Adolescente , Adulto , Anciano , Autoanticuerpos/inmunología , Femenino , Estudios de Seguimiento , Glomerulonefritis Membranosa/sangre , Glomerulonefritis Membranosa/etiología , Rechazo de Injerto/sangre , Rechazo de Injerto/etiología , Supervivencia de Injerto , Antígenos HLA/inmunología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Receptor de Angiotensina Tipo 1/inmunología , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
8.
Antibiotics (Basel) ; 13(9)2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39335037

RESUMEN

Bacterial infections frequently occur in patients in the ICU undergoing renal dialysis using extracorporeal procedures (KRT) that can be applied for different time periods, such as Prolonged Intermittent Renal Replacement Therapy (PIRRT) or Continuous Kidney Replacement Therapy (CKRT) [...].

9.
J Nephrol ; 37(6): 1449-1461, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38446386

RESUMEN

Based on the current projection of the general population and the combined increase in end-stage kidney disease with age, the number of elderly donors and recipients is increasing, raising crucial questions about how to minimize the discard rate of organs from elderly donors and improve graft and patient outcomes. In 2002, extended criteria donors were the focus of a meeting in Crystal City (VA, USA), with a goal of maximizing the use of organs from deceased donors. Since then, extended criteria donors have progressively contributed to a large number of transplanted grafts worldwide, posing specific issues for allocation systems, recipient management, and therapeutic approaches. This review analyzes what we have learned in the last 20 years about extended criteria donor utilization, the promising innovations in immunosuppressive management, and the molecular pathways involved in the aging process, which constitute potential targets for novel therapies.


Asunto(s)
Trasplante de Riñón , Donantes de Tejidos , Humanos , Donantes de Tejidos/provisión & distribución , Anciano , Factores de Edad , Selección de Donante , Envejecimiento/fisiología , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/cirugía , Supervivencia de Injerto
10.
Burns ; 50(5): 1213-1222, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38494395

RESUMEN

BACKGROUND: In burn patients, septic shock and acute kidney injury (AKI) with use of continuous renal replacement therapy (CRRT) severely increase morbidity and mortality. Sorbent therapies could be an adjunctive therapy to address the underlying metabolic changes in inflammatory and anti-inflammatory cytokines dysregulated production. METHODS: A retrospectively observational study of 35 severe burn patients admitted to the Burn Center (Turin, Italy, from January 2017 to December 2022), who underwent CRRT for AKI-associated septic shock. Out of 35 patients, 11 were treated with CytoSorb® as adjunctive therapy to CRRT (Sorbent group) and 24 patients only with CRRT (Control group). RESULTS: The application of CytoSorb® took place in a very dispersed way. Out of 11 patients, 7 started the CRRT together with the sorbent application. The patients of the sorbent group exhibited a significant reduction in norepinephrine use compared to that of the control group. A clinical improvement over the first 4 days of Cytosorb® was observed in both survivors and no survivors of the sorbent group, with significant norepinephrine decreased use on day 4 compared to day 1. In-hospital mortality was 45.4% and 70.8% in the sorbent and control group, respectively, and significantly better at Kaplan-Meier survival analysis at 270 days (p = 0.0445). In both groups, all survivor patients recovered renal function at discharge, whereas no survivors did not. CONCLUSIONS: Adjunctive treatment with CytoSorb® for burn patients with AKI-CRRT and septic shock poorly responsive to standard therapy led to a significant clinical improvement, and was associated with a lower mortality rate compared to CRRT alone.


Asunto(s)
Lesión Renal Aguda , Quemaduras , Terapia de Reemplazo Renal Continuo , Choque Séptico , Humanos , Choque Séptico/terapia , Choque Séptico/mortalidad , Choque Séptico/complicaciones , Lesión Renal Aguda/terapia , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/etiología , Quemaduras/complicaciones , Quemaduras/terapia , Quemaduras/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Terapia de Reemplazo Renal Continuo/métodos , Anciano , Adulto , Mortalidad Hospitalaria , Resultado del Tratamiento , Norepinefrina/uso terapéutico , Terapia de Reemplazo Renal/métodos
11.
Transplant Direct ; 10(6): e1638, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38769985

RESUMEN

Background: Transplant glomerulopathy (TG) is the hallmark of chronic antibody-mediated rejection but often occurs without anti-HLA donor-specific antibodies (DSAs) in the assumption that other DSAs may be the effectors of the tissue injury. Recently, we reported a positive effect of interleukin-6 (IL-6) receptor blocker tocilizumab (TCZ) in TG/DSA+. In the present study, we investigate the effect of TCZ in a cohort of TG cases without detectable anti-HLA DSAs. Methods: Single-center retrospective analysis of TG cases without anti-HLA DSAs (TG/DSA) treated with TCZ for chronic antibody-mediated rejection as first-line therapy evaluated through clinical, protocol biopsies, and gene expression analyses was included. Results: Differently from TG/DSA+, TG/DSA- showed a progressive reduction in the estimated glomerular filtration rate at 12 mo and after that with no significant modification in microvascular inflammation or C4d+. No upregulation in tight junction protein-1, aldo-keto reductase family 1 member C3, and calcium/calmodulin-dependent serine protein kinase, documented in TG/DSA+, was noted in post-TCZ biopsies. The reduction of microvascular inflammation was associated with natural killer-cell reduction in TG/DSA+, whereas TG/DSA- tends to maintain or increase periglomerular/interstitial infiltration. Conclusions: In the absence of anti-HLA DSAs, TG behavior seems not to be modified by IL-6 receptor blockade. These results are at variance with observational studies and previous trials with IL-6 inhibitors in TG associated with anti-HLA DSAs. These data may fuel the hypothesis of different mechanisms underlying TGs (including the potentially different roles of natural killer cells) and suggest carefully selecting patients with TG for clinical trials or off-label treatment based on their antidonor serologic status.

12.
Front Med (Lausanne) ; 11: 1342992, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38808134

RESUMEN

Background: Acute graft pyelonephritis (AGPN) is a relatively common complication in kidney transplants (KTs); however, the effects on allograft function, diagnostic criteria, and risk factors are not well established. Methods: Retrospective analysis of all consecutive adult KTs was performed between 01 January 2011 and 31 December 2018 (follow-up ended on 31 December 2019) to examine the association between the diagnosis of AGPN (confirmed with magnetic resonance imaging [MRI]) during the first post-transplantation year and graft outcomes. Results: Among the 939 consecutive KTs (≈50% with donors ≥60 years), we identified 130 MRI-confirmed AGPN episodes, with a documented association with recurrent and multidrug-resistant bacterial urinary tract infections (UTIs) (p < 0.005). Ureteral stenosis was the only risk factor associated with AGPN (OR 2.9 [95% CI, 1.6 to 5.2]). KTs with AGPN had a decreased allograft function at the first year (ΔeGFR 6 mL/min/1.73 m2 [-2-15] in non-AGPN vs. -0.2 [-6.5-8.5] in AGPN, p < 0.001), with similar and negative profiles in KTs from standard or elderly donors. However, only KTs with AGPN and a donor <60 years showed reduced death-censored graft survival (p = 0.015); most of this subgroup received anti-thymocyte globulin (ATG) induction (40.4% vs. 17.7%), and their MRI presented either a multifocal AGPN pattern (73.9% vs. 56.7%) or abscedation (28.3% vs. 11.7%). No difference was noted in death-censored graft survival between early (<3 months post-KT) or late (3-12 months) AGPN, solitary/recurrent forms, or types of multidrug-resistant pathogens. Linear regression confirmed the independent role of multifocal pattern, abscedation, ATG induction, and donor age on the eGFR at the first year. Conclusion: AGPN, influenced by multifocal presentation, ATG induction, donor age, and abscedation, affects kidney function and significantly impacts allograft survival in KTs with donors <60 years.

13.
Biomedicines ; 11(9)2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37761011

RESUMEN

For severe polytrauma patients with an early AKI requiring renal replacement therapy, anticoagulation remains a great challenge. Due to a high bleeding risk, hemodynamic instability, and increased lactate levels, continuous modality (CKRT) and citrate anticoagulation seem to be the most appropriate. However, their safety with regard to the potential risk of impaired citrate metabolism is not documented. A retrospective study of 60 severe polytrauma patients admitted to the emergency department between January 2000 and December 2021 was conducted; the patients requiring CKRT during the first 72 h were treated with citrate (n. 46, group Citrate) or with heparin (n. 14, group Heparin). Out of 60 patients, 31 survived (51.7%). According to logistic regression analysis, age and SOFA score were significant predictors of mortality. The incidence of rhabdomyolysis was more common in the survivors (77.4 vs. 51.7%), and Kaplan-Meyer analysis showed a better trend towards survival at 90 days for the group Citrate than the group Heparin (p 0.0956). In the group Citrate, hemorrhagic episodes were significantly less common (0.045 vs. 0.273 episodes/day, p < 0.001); the effective duration (h/day) of CKRT was longer; and the effective net ultrafiltration rate (mL/kg/h) and blood flow rate were lower. For severe polytrauma patients, early, soft CKRT with citrate anticoagulation at a low blood flow rate and circuit citratemia showed a better safety and hemodynamic stability, suggesting that citrate should be the first choice anticoagulant in this subset of patients.

14.
Minerva Urol Nephrol ; 75(1): 92-98, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33781021

RESUMEN

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.


Asunto(s)
Trasplante de Riñón , Humanos , Masculino , Trasplante de Riñón/efectos adversos , Autoinforme , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Factores de Riesgo
15.
Microorganisms ; 11(2)2023 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-36838423

RESUMEN

OBJECTIVES: To explore the Cytomegalovirus (CMV) burden on the long-term post-transplant course in different donor ages, we evaluated the incidence and risk factors for CMV in our kidney-transplanted patients (KTs) with extensive adoption of expanded-criteria donors (ECDs). METHODS: Retrospective evaluation of 929 consecutive first KTs (49.5% receiving an organ from a donor ≥ 60 years) performed between 01-2003 and 12-2013. Overall survival was estimated using Kaplan-Meier curves; cumulative incidence function was additionally analyzed to consider the potential role of death with a functioning graft as a competitive event with graft dysfunction and to avoid overestimation. Apart from regular DNAemia monitoring in all patients, prophylaxis was adopted in high-risk groups (D+/R- or recipients of anti-thymocyte globulin induction), with pre-emptive therapy in the remaining groups. RESULTS: CMV incidence was 19.5% (4-34.9% according to serostatus combination: D-/R-, D-/R+, D+/R+, D+/R-). Donor and recipient age, recipient pre-transplant hypertension, DR antigen compatibility, cold ischemia time, and post-transplant early complications, including rejection, urologic and renal artery stenosis, and lower renal function and proteinuria ≥ 0.5 g/day at one year after KT were associated with CMV. CMV determined lower death-censored graft survival (DCGS) (p < 0.01), with a prominent effect in R+ (p < 0.01) and without impact in R- (p = 0.32 in D-/R- and p = 0.006 in D+/R-). Interestingly, CMV occurrence influenced DCGS only in KTs who received grafts from donors < 50 or 50-69 years old (p < 0.01), while it was not significant with older donors (p = 0.07). The analysis of the cumulative incidence of graft loss accounting for death as a competing risk confirmed all these findings. In multivariate analysis, CMV replication/disease in the first year was an independent predictor for DCGS (HR 1.73 [1.3-2.3]). CONCLUSIONS: In a large population with extensive ECD adoption, CMV viremia in the first year demonstrates its harmful effect with an independent role for graft loss and significant impact among R+ recipients and KTs with donors < 70 years.

16.
Minerva Urol Nephrol ; 75(3): 388-397, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35274902

RESUMEN

BACKGROUND: Few reports have addressed the change in renal replacement therapy (RRT) management in the Intensive care Units (ICUs) over the years in western countries. This study aims to assess the trend of dialytic practice in a 4.5-million population-based study of the northwest of Italy. METHODS: A nine-year survey covering all the RRT provided in the ICUs. Consultant nephrologists of the 26 Nephrology and Dialysis centers reported their activities in the years 2007, 2009, 2012, and 2015. RESULTS: From 2007 to 2015 the patients treated increased from 1042 to 1139, and the incidence of RRT from 254 to 263 cases/10^6 inhabitants. The workload for dialysis center was higher in the larger hub hospitals. RRT for acute kidney injury (AKI), continuation of treatment in chronically dialyzed patients, or extrarenal indications accounted for about the stable rate of 70, 25 and 5% of all RRT sessions, respectively. Continuous modality days increased from 2731 days (39.5%) in 2007 to 5076 (70.6%) in 2015, when the continuous+prolonged treatment days were 6880/7196 (95.6% of total days). As to RRT timing, in 2015 only the classical clinical criteria, and no K-DIGO stage were adopted by most Centers. As to RRT interruption, in 2015 urine volume was the first criterion. Implementation of citrate anticoagulation (RCA) for RRT patients significantly increased from 2.8% in 2007 to 30.9% in 2015, when it was applied in all 26 Centers. CONCLUSIONS: From 2007 to 2015, current practice has changed towards shared protocols, with increasing continuous modality and RCA implementation.


Asunto(s)
Ácido Cítrico , Diálisis Renal , Humanos , Terapia de Reemplazo Renal/métodos , Unidades de Cuidados Intensivos , Italia , Citratos , Anticoagulantes
17.
Biomedicines ; 10(3)2022 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-35327510

RESUMEN

Kidney transplanted patients are a unique population with intrinsic susceptibility to viral and bacterial infections, mainly (but not exclusively) due to continuous immunosuppression. In this setting, infectious episodes remain among the most important causes of death, with different risks according to the degree of immunosuppression, time after transplantation, type of infection, and patient conditions. Prevention, early diagnosis, and appropriate therapy are the goals of infective management, taking into account that some specific characteristics of transplanted patients may cause a delay (the absence of fever or inflammatory symptoms, the negativity of serological tests commonly adopted for the general population, or the atypical anatomical presentation depending on the surgical site and graft implantation). This review considers the recent available findings of the most common viral and bacterial infection in kidney transplanted patients and explores risk factors and outcomes in septic evolution.

18.
Crit Rev Oncol Hematol ; 168: 103533, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34801702

RESUMEN

Over the past decade, the prognosis of advanced thyroid cancer (TC) patients has dramatically improved thanks to the introduction of tyrosine kinase inhibitors (TKIs). Despite their effectiveness, these drugs are burdened with several side effects that can negatively affect quality of life and compromise therapy continuation. Among renal adverse events (RAEs), proteinuria is the most frequently reported in clinical trials and real-life experiences, especially during treatment with lenvatinib or cabozantinib. This peculiar toxicity is commonly associated with targeted therapies with anti-angiogenic activity, even if the mechanisms underlying its onset and progression are not entirely clear. RAEs should be early recognized and properly managed to avoid renal function worsening and life-threatening consequences. Aiming at providing a comprehensive summary that can help clinicians to identify and manage TKIs-related RAEs in TC patients, we reviewed the current evidence about this topic, from pathogenesis and potential risk factors to diagnosis and treatment.


Asunto(s)
Antineoplásicos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neoplasias de la Tiroides , Antineoplásicos/efectos adversos , Humanos , Inhibidores de Proteínas Quinasas/efectos adversos , Calidad de Vida , Neoplasias de la Tiroides/tratamiento farmacológico
19.
Clin Kidney J ; 14(1): 317-324, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33564434

RESUMEN

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.

20.
PLoS One ; 16(4): e0249552, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33819285

RESUMEN

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.


Asunto(s)
Funcionamiento Retardado del Injerto/patología , Rechazo de Injerto/patología , Supervivencia de Injerto , Hipotensión/fisiopatología , Trasplante de Riñón/efectos adversos , Donantes de Tejidos/provisión & distribución , Receptores de Trasplantes/estadística & datos numéricos , Anciano , Funcionamiento Retardado del Injerto/etiología , Rechazo de Injerto/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Obtención de Tejidos y Órganos
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