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1.
Transplant Proc ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32143866

RESUMO

CONTEXT: Studies on the surgical outcome in living kidney donors mainly report perioperative complications with short follow-up. OBJECTIVE: The objectives of this study are to evaluate the long-term surgical outcome in living kidney donors and to identify donors with an increased risk for a complicated postoperative course. BASIC PROCEDURES: A prospectively collected database of 496 living kidney donors at the Department of General, Visceral, and Transplantation Surgery of the Ruprecht Karls University Heidelberg was retrospectively analyzed in a retrospective, observational single-center study. RESULTS: The median follow-up time was 37 months. The perioperative severe complication (Clavien-Dindo IIIb) rate was 2.8%, the early postoperative (PO) severe complication rate (1-3 months post operation) was 0.7%, and the late PO severe complication rate (> 3 months post operation) was 8.4%. In multivariate analyses, male sex was associated with higher overall perioperative complication rate (odds ratio [OR], 1.930; P = .005) as well as higher rate of late PO complications (OR, 2.243; P = .014). An increased body mass index was associated with a higher late and severe (Clavien-Dindo ≥ IIIb) PO complication rate (OR, 1.107; P = .009 and OR, 1.105; P = .008, respectively). CONCLUSIONS AND RELEVANCE: Long-term surgery-associated severe complications occur in 8.4% of kidney donors. Older age is associated with an increased operative time, greater intraoperative blood loss, and longer PO hospital stay. Male donors and donors with an increased body mass index have a higher risk for a complicated PO course after kidney donation. Within a shared decision-making process before living kidney donation, special awareness should be brought to these facts.

2.
Medicine (Baltimore) ; 99(10): e19335, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150070

RESUMO

BACKGROUND: Pancreas graft quality directly affects morbidity and mortality rates after pancreas transplantation (PTx). The criteria for pancreas graft allocation are restricted, which has decreased the number of available organs. Suitable pancreatic allografts are selected based on donor demographics, medical history, and the transplant surgeon's assessment of organ quality during procurement. Quality is assessed based on macroscopic appearance, which is biased by individual experience and personal skills. Therefore, we aim to assess the histopathological quality of unallocated pancreas organs to determine how many unallocated organs are potentially of suitable quality for PTx. METHODS AND ANALYSIS: This is a multicenter cross-sectional explorative study. The demographic data and medical history of donor and cause of rejection of the allocation of graft will be recorded. Organs of included donors will be explanted and macroscopic features such as weight, color, size, and stiffness will be recorded by 2 independent transplant surgeons. A tissue sample of the organ will be fixed for further microscopic assessments. Histopathologic assessments will be performed as soon as a biopsy can be obtained. We will evaluate up to 100 pancreata in this study. RESULT: This study will evaluate the histopathological quality of unallocated pancreas organs from brain-dead donors to determine how many of these unallocated organs were potentially suitable for transplantation based on a histopathologic evaluation of organ quality. CONCLUSION: The comprehensive findings of this study could help to increase the pancreas graft pool, overcome organ shortage, reduce the waiting time, and also increase the number of PTx in the future. Registration number: ClinicalTrials.gov: NCT04127266.


Assuntos
Morte Encefálica/patologia , Pâncreas/patologia , Doadores de Tecidos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/métodos , Distribuição de Qui-Quadrado , Protocolos Clínicos , Estudos Transversais , Alemanha , Sobrevivência de Enxerto , Humanos , Transplante de Pâncreas/métodos , Doadores de Tecidos/provisão & distribução , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/tendências
3.
J Virol ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32102884

RESUMO

The Epstein-Barr virus (EBV) causes human cancers and epidemiological studies have shown that lytic replication is a risk factor for some of these tumors. This fits with the observation that EBV M81 that was isolated in a Chinese patient with nasopharyngeal carcinoma induces potent virus production and increases the risk of genetic instability in infected B cells. To find out whether this property extends to viruses found in other parts of the world, we investigated 22 viruses isolated from Western patients. While one third of the viruses hardly replicated, the remaining ones showed variable levels of replication with three isolates replicating at levels close to M81 in B-cells. We cloned one strongly replicating virus into a bacterial artificial chromosome; the resulting recombinant virus (MSHJ) retained the properties of its non-recombinant counterpart and showed similarities with M81, undergoing lytic replication in vitro and in vivo after three weeks of latency. In contrast, B-cells infected with the non-replicating western B95-8 virus showed an early but abortive replication accompanied by cytoplasmic BZLF1 expression. Sequencing confirmed that rMSHJ is a western virus, being genetically much closer to B95-8 than to M81. Spontaneous replication in rM81- and rMSHJ-infected B-cells was dependent on phosphorylated Btk and was inhibited by exposure to ibrutinib, opening the way to clinical intervention in patients with abnormal EBV replication. As rMSHJ contains the complete EBV genome and induces lytic replication in infected B-cells, it is ideal to perform genetic analyses of all viral functions in western strains and their associated diseases.ImportanceThe Epstein-Barr virus (EBV) infects the majority of the world population but causes different diseases in different countries. Evidence that lytic replication, the process that leads to new virus progeny, is linked to cancer development is accumulating. Indeed, viruses such as M81 that were isolated from Far East nasopharyngeal carcinomas replicate strongly in B-cells. We now show that some viruses isolated from western patients, including the MSHJ strain share this property. Moreover, replication of both M81 and of MSHJ was sensitive to ibrutinib, a commonly used drug, thereby opening an opportunity for therapeutic intervention. Sequencing of MSHJ showed that this virus is quite distant from M81 and much closer to non-replicating western viruses. We conclude that western EBV strains are heterogeneous, some viruses being able to replicate stronger and therefore being potentially more pathogenic than others, and that the virus sequence information alone cannot predict this property.

4.
J Clin Invest ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31990685

RESUMO

BACKGROUND: Preclinical experiments have shown that donor blood cells, modified in vitro by an alkylating agent (MIC, modified immune cells), induced long-term specific immunosuppression against the allogeneic donor. METHODS: In this phase-I trial, patients received either 1.5x106 MIC per kg b.w. on day -2 (N=3, group A), or 1.5x108 MIC per kg b.w. on day -2 (N=3, group B) or day -7 (N=4, group C) before living donor kidney transplantation in addition to post-transplant immunosuppression. Primary outcome measure was the frequency of adverse events (AE) until day 30 (study phase) with follow-up to day 360. RESULTS: MIC infusions were extremely well tolerated. During the study phase, a total of 69 AE occurred in 10 treated patients which were unlikely/not related to MIC infusion. No donor-specific human leukocyte antigen antibodies or rejection episodes were noted even though the patients received up to 1.3x1010 of donor mononuclear cells prior to transplantation. Group C patients with low immunosuppression during follow-up showed no in vitro reactivity against stimulatory donor blood cells on day 360 while reactivity against third party cells was preserved. Frequencies of CD19+CD24highCD38high transitional B lymphocytes (Breg) increased from a median of 6% before MIC infusion to 20% on day 180, which was 19- and 68-fold higher, respectively, than in two independent cohorts of transplanted controls. The majority of Breg produced immunosuppressive cytokine IL-10. MIC-treated patients showed the Immune Tolerance Network operational tolerance signature. CONCLUSION: MIC administration was safe and could be a future tool for the targeted induction of tolerogenic Breg.

5.
J Clin Periodontol ; 47(1): 19-29, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31603565

RESUMO

AIM: To assess the prevalence and severity of periodontitis in patients with moderate chronic kidney disease (CKD) and comparing the results with the self-reported periodontitis awareness of the study subjects. MATERIAL AND METHODS: The periodontal status of 270 patients with moderate CKD randomly selected from a cohort of 5,217 subjects participating in the prospective observational German Chronic Kidney Disease (GCKD) project was analysed by recording bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment level (CAL). Furthermore, the awareness of the study subjects of their periodontal conditions was evaluated by a self-reported questionnaire. RESULTS: 24.4% of the CKD study patients showed no or only mild signs of periodontal disease, 47.6% displayed moderate and 27% severe periodontitis. Questionnaire data revealed that 62.3% of the study subjects with severe periodontitis were not aware of the presence of the disease, 44.4% denied having received any systematic periodontal therapy so far, although 50% of them indicated to visit their dentist regularly for professional tooth cleanings. CONCLUSION: While the clinical study data confirm an increased prevalence of periodontitis in CKD patients, their self-reported awareness of periodontitis was low.

6.
J Biomed Mater Res B Appl Biomater ; 108(1): 67-72, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30897297

RESUMO

Incidence of wound complications after kidney transplantation (KTx) is still considerable. Here, we report the impact of prophylactic absorbable polyglactin (Vicryl®) mesh reinforcement on the incidence of short-term post-KTx wound complications. Sixty-nine patients were analyzed; 23 with and 46 without preventive onlay mesh reinforcement. Surgical site infections (SSI) were seen in six (26%) patients in the mesh group and in 17 (37%) patients in no-mesh group. A lower, but not statistically significant, rate of early postoperative wound complications occurred in the mesh group. Wound complications were observed in seven (30%) patients in the mesh group and in 23 (50%) patients in the no-mesh group. There was no association between mesh placement and SSI incidence (odds ratios [OR] 0.60, 95% confidence interval [CI] 0.20-1.82, p = 0.369) and wound complications (OR 0.44, 95% CI 0.15-1.26, p = 0.126). Therefore, we conclude that mesh reinforcement does not increase the risk of SSI and overall wound complications. Long-term outcomes have to be evaluated in a randomized trial setting. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:67-72, 2020.

8.
9.
PLoS One ; 14(9): e0222847, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31568538

RESUMO

The Epstein-Barr virus (EBV) induces B-cell proliferation with high efficiency through expression of latent proteins and microRNAs. This process takes place in vivo soon after infection, presumably to expand the virus reservoir, but can also induce pathologies, e.g. an infectious mononucleosis (IM) syndrome after primary infection or a B-cell lymphoproliferation in immunosuppressed individuals. In this paper, we investigated the growth characteristics of EBV-infected B-cells isolated from transplant recipients or patients with IM. We found that these cells grew and withstood apoptosis at highly variable rates, suggesting that the expansion rate of the infected B-cells widely varies between individuals, thereby influencing the size of the B-cell reservoir and the ability to form tumors in infected individuals. All viruses investigated were type 1 and genetically close to western strains. EBV-infected B-cells expressed the transforming EBV latent genes and microRNAs (miRNAs) at variable levels. We found that the B-cell growth rates positively correlated with the BHRF1 miRNA levels. Comparative studies showed that infected B-cells derived from transplant recipients with iEBVL on average expressed higher levels of EBV miR-BHRF1 miRNAs and grew more rapidly than B-cells from IM patients, suggesting infection by more transforming viruses. Altogether, these findings suggest that EBV infection has a highly variable impact on the B-cell compartment that probably reflects the genetic diversity of both the virus and the host. It also demonstrates the unexpected finding that B-cells from different individuals can grow at different speed under the influence of the same virus infection.

10.
Crit Care Med ; 47(12): e999-e1007, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31584458

RESUMO

OBJECTIVES: Sepsis-induced acute kidney injury is the dominant acute kidney injury etiology in critically ill patients and is often associated with a need for renal replacement therapy. The indication and timing of renal replacement therapy are controversially discussed. We hypothesized that the product of the G1-cell cycle arrest biomarkers tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]), and the soluble urokinase-type plasminogen activator receptor are of diagnostic value for the prediction of septic acute kidney injury courses requiring renal replacement therapy. DESIGN: In this prospective study, critically ill patients were enrolled immediately after the fulfillment of Sepsis-3 criteria. Urinary [TIMP-2] × [IGFBP7] levels over time and serum soluble urokinase-type plasminogen activator receptor levels once at inclusion were measured. The primary endpoint was the development of septic acute kidney injury with the need for renal replacement therapy. Area under the receiver operating characteristic curves, de Long's tests, and logistic regression models were calculated. SETTING: Two ICUs at Heidelberg University Hospital between May 2017 and July 2018. PATIENTS: One-hundred critically ill patients with positive Sepsis-3 criteria. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Nineteen patients required renal replacement therapy. Diagnostic performance of urinary [TIMP-2] × [IGFBP7] improved over time with the highest area under the receiver operating characteristic curve of 0.89 (95% CI, 0.80-0.98) 24 hours after study inclusion. Soluble urokinase-type plasminogen activator receptor levels at inclusion showed an area under the receiver operating characteristic curve of 0.83 (0.75-0.92). The best discrimination ability for the primary outcome measure was achieved for [TIMP-2] × [IGFBP7] at 24 hours after inclusion by applying a cutoff value of greater than or equal to 0.6 (ng/mL)/1,000 (sensitivity 90.9, specificity 67.1). Soluble urokinase-type plasminogen activator receptor performed best by using a cutoff value of greater than or equal to 8.53 ng/mL (sensitivity 84.2, specificity 82.7). A combination of newly tested biomarkers with cystatin C resulted in a significantly improved diagnostic accuracy. Cystatin C in combination with [TIMP-2] × [IGFBP7] 24 hours outperformed all standard renal parameters (area under the receiver operating characteristic curve 0.93 [0.86-1.00]). CONCLUSIONS: [TIMP-2] × [IGFBP7] and soluble urokinase-type plasminogen activator receptor are promising biomarker candidates for the risk stratification of septic acute kidney injury patients with the need for renal replacement therapy.

11.
Medicine (Baltimore) ; 98(37): e17006, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517819

RESUMO

CD200 is an immunoglobulin superfamily membrane protein that binds to a myeloid cell-specific receptor and induces inhibitory signaling. The aim of this study was to investigate the role of CD200 and its receptor (CD200R1) on kidney transplant (KTx) outcome. In a collective of 125 kidney recipients (University hospital, Heidelberg, Germany), CD200 and CD200R1 concentrations were evaluated immediately before transplantation. Recipient baseline and clinical characteristics and KTx outcome, including acute rejection (AR), acute tubular necrosis, delayed graft function, cytomegalovirus (CMV) and human polyomaviridae (BK) virus infections, and graft loss were evaluated during the first post-transplant year. The association of CD200 and CD200R1 concentrations and CD200R1/CD200 ratios with the outcome of KTx was investigated for the first time in a clinical setting in a prospective cohort. There was a positive association between pre-transplant CD200R1 concentrations and CMV (re)activation (P = .041). Also, increased CD200R1 concentration was associated with a longer duration of CMV infection (P = .049). Both the frequency of AR and levels of creatinine (3 and 6 months after KTx) were significantly higher in patients with an increased CD200R1/CD200 ratio (median: 126 vs 78, P = .008). Increased pre-transplant CD200R1/CD200 ratios predict immunocompetence and risk of AR, whereas high CD200R1 concentrations predict immunosuppression and high risk of severe CMV (re)activation after KTx.


Assuntos
Antígenos CD/sangue , Antígenos de Superfície/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/cirurgia , Transplante de Rim , Complicações Pós-Operatórias/diagnóstico , Receptores de Superfície Celular/sangue , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Prognóstico , Estudos Prospectivos , Adulto Jovem
12.
HLA ; 94 Suppl 2: 11-15, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31403240

RESUMO

Monitoring of donor-specific HLA antibodies (DSA) has become part of the clinical routine in kidney transplantation. This paper gives a brief overview on data from the Collaborative Transplant Study (CTS) and the Heidelberg Transplant Center on the clinical relevance of post-transplant DSA monitoring in patients undergoing renal transplantation. The obtained findings underline the importance of DSA monitoring in the post-operative course in immunologically high-risk patients and patients with deterioration of graft function. Especially in patients with a pre-activated immune system, a gap in the immunosuppressive therapy appear to lead to persistence, reappearance or de novo occurrence of strong, complement-activating DSA, resulting in severe antibody-mediated rejection (AMR) and, without timely intervention, in AMR-related graft loss.

13.
Atheroscler Suppl ; 40: 68-72, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31447215

RESUMO

OBJECTIVE: In recent studies, semi-selective compared to antigen-specific immunoadsorption (IA) columns showed comparable effectiveness in anti-A/B antibody removal before incompatible living donor kidney transplantation. Semi-selective columns allow a greater number of IA treatments at lower costs. They are also capable of removing potentially harmful human leukocyte antigen alloantibodies. Nevertheless, additional plasma exchange treatments are often necessary to reach the preoperative target titer, most likely due to an inadequate anti-A/B IgM antibody depletion. METHODS: We compared the effectiveness of immunoglobulin and anti-A/B antibody reduction by different semi-selective (Therasorb Ig-flex, Therasorb Ig-omni5, Immunosorba) and antigen-specific (Glycosorb) IA columns during the desensitization of 63 ABO-incompatible living donor kidney transplant candidates with a total of 375 IA treatments. Fifty-three patients were eventually transplanted. RESULTS: Total IgM reduction during the first IA treatment was significantly greater with the Therasorb Ig-omni5 compared to the Therasorb Ig-flex (mean: -71.3 vs -41.6; p = 0.001) or Immunosorba columns (mean: -71.3 vs -42.8; p = 0.03). During a median of 5.5-6 pre-transplant IA treatments, Therasorb Ig-flex and Therasorb Ig-omni5 columns were equally effective in the reduction of total IgM while both showed superior IgM reduction compared to the Immunosorba columns (Therasorb Ig-flex, mean: -81.2 vs -72.2; p = 0.01; Therasorb Ig-omni5, mean: -88.2 vs -72.2; p = 0.02). IgG reduction was not significantly different between groups. Likewise, anti-A/B IgM antibody reduction (titer Saline) during the first IA treatment was significantly greater with the Therasorb Ig-omni5 compared to the Therasorb Ig-flex (mean titer reduction: -1.9 vs -1.1; p = 0.02) and tended to be greater than with Immunosorba or Glycosorb columns. During a median of 5-6 pre-transplant IA treatments, overall anti-A/B IgM antibody reduction was significantly greater when IA was performed with the Therasorb Ig-flex (mean titer reduction: -3.8 vs -1.3; p < 0.001) or Therasorb Ig-omni5 (mean titer reduction: -4.3 vs -1.3; p = 0.01) compared to the Immunosorba columns with no differences compared to the Glycosorb columns. Again, anti-A/B IgG antibody reduction (titer Coombs) was not significantly different between groups. CONCLUSIONS: The semi-selective Therasorb Ig-omni5 device offers potential advantages in reducing total IgM as well as anti-A/B IgM antibodies.

14.
Transpl Int ; 32(12): 1286-1296, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31322786

RESUMO

Because of the current organ shortage, ABO-incompatible (ABOi) transplantations have been increasingly performed in recent years. The results seem comparable to those of compatible transplantations, but there have also been reports of increased side effects possibly because of the desensitization therapy. To address an increase in severe infectious complications, we compared the outcomes of 48 ABOi transplant recipients to outcomes of 96 matched ABO-compatible (ABOc) controls transplanted at Heidelberg University Hospital from August 2005 to April 2018. Over a follow-up period of 8 years, ABOi transplant recipients had comparable graft and patient survival as well as graft function compared with ABOc patients. T-cell-mediated and antibody-mediated rejections were not different between groups. In ABOi transplant recipients, urosepsis (22.9% vs. 8.5%; P = 0.019) and pneumonia with opportunistic pathogens (8.3% vs. 1.0%, P = 0.025) appeared more frequently. As a consequence, a significantly higher number of deaths from infection have been observed after ABOi transplantations (6.3% vs. 0%, P = 0.010). High-titer recipients (isoagglutinin titer of ≥1:256) showed a higher incidence of BK virus replication and postoperative bleeding complications. ABO-incompatible transplantations can be performed with results that are not different from results after ABOc transplantations. However, an increased rate of serious infectious complications must be taken into account.

15.
Ann Transplant ; 24: 439-445, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31346153

RESUMO

BACKGROUND The pre-procurement pancreas suitability score (P-PASS) and the pancreas donor risk index (pDRI) are established predictive scores for graft survival and patient outcome following pancreatic transplantation. This retrospective study aimed to evaluate the predictive value of P-PASS and pDRI following simultaneous pancreas and kidney (SPK) transplantation, or pancreas after kidney (PAK) transplantation, and the clinical impact of donor-specific factors on the postoperative graft and recipient outcome at a single transplant center. MATERIAL AND METHODS The study included 105 patients who underwent SPK (n=104) or PAK (n=4) between 2000 and 2017. Donor-specific and recipient-specific parameters were recorded. Kaplan-Meier analysis and Cox regression analysis were used to assess the outcome after transplantation. RESULTS Overall, the mean 1-year and 5-year pancreas graft survival and patient survival rates were 78.7% and 93.2%, and 76.9% and 90.0%, respectively. The postoperative outcome in patients with a P-PASS score of <17 was not significantly different when compared with patients with a score of ≥17. A P-PASS score of ≥17 was significantly associated with early pancreas graft loss (p=0.04). There was no significant difference in postoperative outcome between patients with high pDRI and low pDRI. Smoking of donor (p=0.046) was a risk factor and coronary heart disease of recipient (p=0.003) had a significant effect on survival of pancreas graft. CONCLUSIONS This study showed that P-PASS and pDRI were not reliable predictors of outcome after pancreas transplantation and that specific characteristics of the donor and recipient must be evaluated when predicting the outcome of pancreas transplantation.


Assuntos
Sobrevivência de Enxerto , Transplante de Rim/mortalidade , Transplante de Pâncreas/mortalidade , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Doadores de Tecidos
16.
Surg Obes Relat Dis ; 15(8): 1319-1325, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31239098

RESUMO

BACKGROUND: Early diagnosis of kidney disease in obese patients and in such patients with type 2 diabetes (T2D) can significantly improve treatment outcome. Serum uromodulin (sUMOD) may be a sensitive parameter for early detection of nephropathy. OBJECTIVES: To analyze sUMOD and traditional markers of kidney function in a cohort study of patients with and without obesity or T2D undergoing metabolic surgery compared with blood donors. SETTING: University of Heidelberg, Germany. METHODS: Patients with obesity (body mass index >35 kg/m2) without T2D (n = 10) and T2D (n = 10) and patients with nonsevere obesity (body mass index, 25-35 kg/m2) and insulin-dependent T2D (n = 16) undergoing Roux-en-Y gastric bypass (RYGB) were enrolled. The control group consisted of 190 blood donors. sUMOD was compared with established renal markers. RESULTS: Using sUMOD, impaired kidney function at baseline was present in both groups with T2D and in none of the patients with obesity without T2D. This impairment was not detectable through traditional markers. Significant improvement of sUMOD was shown in patients with obesity and T2D 12 months postoperatively (from 130.0 ± 77.5 to 239.5 ± 179.0 ng/mL; P = .004) and in patients with nonsevere obesity and T2D 6 months after RYGB (from 140.6 ± 78.0 to 298.7 ± 154.0 ng/mL; P = .017). In patients with obesity without T2D, sUMOD remained stable (P = .375). CONCLUSIONS: sUMOD may serve as a tissue-specific biomarker in incipient diabetic nephropathy. Improvement of sUMOD after RYGB seems to profoundly restore the structural integrity of nephrons in these patients at risk for diabetic nephropathy.

17.
J Am Soc Nephrol ; 30(7): 1305-1313, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31171572

RESUMO

BACKGROUND: Levels of soluble urokinase plasminogen activator receptor (suPAR), an inflammation marker, are strongly predictive of incident kidney disease. Patients with autosomal dominant polycystic kidney disease (ADPKD) experience progressive decline in renal function, but rates of decline and outcomes vary greatly. Whether suPAR levels are predictive of declining kidney function in patients with ADPKD is unknown. METHODS: We assessed suPAR levels in 649 patients with ADPKD who underwent scheduled follow-up for at least 3 years, with repeated measurements of height-adjusted total kidney volume and creatinine-derived eGFR. We used linear mixed models for repeated measures and Cox proportional hazards to characterize associations between baseline suPAR levels and follow-up eGFR or incident ESRD. RESULTS: The median suPAR level was 2.47 ng/ml and median height-adjusted total kidney volume was 778, whereas mean eGFR was 84 ml/min per 1.73 m2. suPAR levels were associated with height-adjusted total kidney volume (ß=0.02; 95% confidence interval, 0.01 to 0.03), independent of age, sex, race, hypertension, and eGFR. Patients in the lowest suPAR tertile (<2.18 ng/ml) had a 6.8% decline in eGFR at 3 years and 22% developed CKD stage 3, whereas those in the highest tertile (suPAR>2.83 ng/ml) had a 19.4% decline in eGFR at 3 years and 68% developed CKD stage 3. suPAR levels >2.82 ng/ml had a 3.38-fold increase in the risk of incident ESRD. CONCLUSIONS: suPAR levels were associated with progressive decline in renal function and incident ESRD in patients with ADPKD, and may aid early identification of patients at high risk of disease progression.

18.
Virus Res ; 267: 36-40, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31054291

RESUMO

Host reservoir specificity of pathogens is complex and may depend on receptor variability. For pathogenic orthohantaviruses, integrin ß3 had been previously identified as entry receptor and the presence of aspartic acid residue at position 39 (D39) in human integrin ß3 was described to be a prerequisite for infection of primate cells with Hantaan virus (HTNV). However, the role of integrin ß3 in orthohantavirus infection of host animals is not completely understood. Therefore, we analyzed the nucleotide sequence of the integrin ß3 gene of Myodes glareolus and Apodemus agrarius, the hosts of Puumala virus (PUUV) and HTNV, respectively. Sequence analysis in tissue samples demonstrated that the amino acid residue D39 is not present in integrin ß3 of these natural orthohantavirus hosts. Furthermore, we analyzed the transcription and protein expression levels of integrin ß3 in the renal cell line BVK168 generated from the PUUV host, bank vole. Transcription level of integrin ß3 was 100-fold lower in BVK168 cells than in Vero E6 cells and integrin ß3 expression was not detectable in BVK168 cells. However, despite the absence of amino acid residue D39 and no detectable integrin ß3 expression, BVK168 cells are susceptible to infection with both PUUV and HTNV. These results indicate that the mechanism of orthohantaviral entry in rodent species does not correspond to the requirements that were described for the entry in primate cells in vitro.


Assuntos
Arvicolinae/virologia , Reservatórios de Doenças/veterinária , Vírus Hantaan/genética , Febre Hemorrágica com Síndrome Renal/veterinária , Especificidade de Hospedeiro , Integrina beta3/genética , Animais , Linhagem Celular , Reservatórios de Doenças/virologia , Vírus Hantaan/patogenicidade , Febre Hemorrágica com Síndrome Renal/virologia , Murinae/virologia
19.
ESC Heart Fail ; 6(2): 271-279, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30815994

RESUMO

AIMS: Each episode of acute decompensated heart failure (HF) incrementally adds to mortality. Peritoneal dialysis (PD) offers an alternative therapeutic option in refractory HF and reduces the incidence of decompensation episodes. The objective of this study was to determine the efficacy of PD, in terms of functional status, surrogate endpoints, rate of hospitalizations, and mortality. METHODS AND RESULTS: This study is based on the registry of the German Society of Nephrology, involving 159 patients receiving PD treatment due to refractory HF between January 2010 and December 2014. Body weight was reduced by PD (82.2 ± 14.9 to 78.4 ± 14.8 kg, P < 0.001), and significant improvements in New York Heart Association functional class (3.38 ± 0.55 to 2.85 ± 0.49, P < 0.001) were found already after 3 months. Left ventricular ejection fraction did not change (31.5 ± 13.8 to 34.0 ± 15.7%, P = 0.175). C-reactive protein improved with PD treatment (33.7 ± 52.6 to 17.1 ± 26.3 mg/L, P = 0.004). Blood urea nitrogen/creatinine ratio decreased significantly (148.7 ± 68.3 to 106.7 ± 44.8 mg/dL, P < 0.001). Hospitalization rates decreased significantly (total number 2.86 ± 1.88 to 1.90 ± 1.78, P = 0.001, and 39.2 ± 30.7 to 27.1 ± 25.2 days, P = 0.004). One year mortality was 39.6% in end-stage HF patients treated with PD. CONCLUSIONS: Peritoneal dialysis offers an additional therapeutic option in end-stage HF and is associated with improved New York Heart Association classification and reduced hospitalization. Although PD treatment was associated with various benefits, further studies are necessary to identify which patients benefit the most from PD.


Assuntos
Insuficiência Cardíaca/terapia , Diálise Peritoneal/métodos , Sistema de Registros , Volume Sistólico/fisiologia , Doença Aguda , Idoso , Feminino , Seguimentos , Alemanha/epidemiologia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Estudos Prospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento
20.
Am J Transplant ; 19(4): 975-983, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30768866

RESUMO

Therapeutic hypothermia, hypothermic pulsatile machine perfusion (MP), and renal-dose dopamine administered to stable brain-dead donors have shown efficacy to reduce the dialysis requirement after kidney transplantation. In a head-to-head comparison of the three major randomized controlled trials in this field, we estimated the number-needed-to-treat for each method, evaluated costs and inquired into special features regarding long-term outcomes. The MP and hypothermia trials used any dialysis requirement during the first postoperative week, whereas the dopamine trial assessed >1 dialysis session as primary endpoint. Compared to controls, the respective rates declined by 5.7% with MP, 10.9% with hypothermia, and 10.7% with dopamine. Costs to prevent one endpoint in one recipient amount to approximately $17 000 with MP but are negligible with the donor interventions. MP resulted in a borderline significant difference of 4% in 3-year graft survival, but a point of interest is that the preservation method was switched in 25 donors (4.6%) for technical reasons. Graft survival was not improved with dopamine on intention-to-treat but suggested an exposure-response relationship with infusion time. MP was less efficacious and cost-effective to prevent posttransplant dialysis. Whether the benefit on early graft dysfunction achieved with any method will improve long-term graft survival remains to be established.

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