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1.
Gastroenterologe ; 15(6): 471-476, 2020.
Artigo em Alemão | MEDLINE | ID: mdl-33173544

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has become one of the greatest global challenges of our time. It quickly became clear that coronavirus disease 2019 (COVID-19) affects not only the lungs but also other organs to varying degrees. The kidneys are particularly frequently affected. Many patients without underlying kidney diseases already show urinary abnormalities at the onset of COVID-19 and often run the risk of developing acute kidney injury.

2.
Nephrologe ; 15(4): 209, 2020.
Artigo em Alemão | MEDLINE | ID: mdl-32834854
3.
Nephrologe ; 15(4): 210-215, 2020.
Artigo em Alemão | MEDLINE | ID: mdl-32837571

RESUMO

The drastic consequences that emerging infectious diseases can have for people and society are currently being demonstrated by coronavirus disease 2019 (COVID-19). Since its initial description in December 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has dominated current scientific and public interest.

4.
Urologe A ; 58(8): 888-892, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-31161234

RESUMO

BACKGROUND: The number of organ donations in Germany decreased by 32.3% between 2010 and 2017. For this reason, more than 1500 fewer organ transplantations were performed in 2017 than in 2010. QUESTION: What are the causes of this development? METHODS: Analysis of available statistics and scientific publications. RESULTS: A decline of the organ donation potential can be ruled out as the cause of the declining organ donation figures, since the number of patients who were eligible for organ donation from a medical point of view increased during the period under consideration. Similarly, there is no indication that a change in the population's attitude towards organ donation can be held responsible for this development. The decline is rather due to a recognition and reporting deficit of potential organ donors. The extent of this deficit differs considerably between different hospitals and is not only responsible for the decline in the donor rate in recent years, but also for the low donor numbers in Germany by international standards. CONCLUSION: The low organ donation figures in Germany are due to a recognition and reporting deficit. The number of organ donations could be considerably increased by improving the internal processes in hospitals.


Assuntos
Doadores de Tecidos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Alemanha , Humanos
5.
Transplant Proc ; 50(10): 3010-3016, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577160

RESUMO

BACKGROUND: Since 2014, expected graft and recipient survival are matched by the U.S. kidney allocation system to improve organ utility. This mechanism is based on the kidney donor profile index (KDPI) and the estimated posttransplant survival score (EPTS). Here we analyzed 1. the transferability of these scores into the Eurotransplant (ET) region and 2. the extent to which the ET kidney allocation algorithm promotes utility. METHODS: We studied data of 262 kidney transplantations performed at the University Hospital Kiel between 2000 and 2009 (median follow-up, 9.94 years). RESULTS: Multivariable Cox regression analysis revealed that only the variables donor age of the KDPI and recipient's age of the EPTS have a significant value as predictors of posttransplant graft and recipient survival. The other variables showed no additional predictive value. Analyzing all kidneys allocated in the ET kidney allocation system and the European Senior Program, we found that donor and recipient's age and KDPI and EPTS were weakly correlated (rage-age = 0.5, P < .001; rKDPI-EPTS = 0.4, P < .01). If both programs were analyzed separately, no correlation between donor and recipient's age and between KDPI and EPTS was detected. CONCLUSION: The ET kidney allocation algorithm poorly matched predicted graft and recipient survival at our center. A better age-matching may improve organ utility.


Assuntos
Algoritmos , Seleção do Doador/métodos , Transplante de Rim , Doadores de Tecidos/provisão & distribuição , Adulto , Idoso , Europa (Continente) , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Estados Unidos
7.
Scand J Rheumatol ; 43(4): 307-13, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25088926

RESUMO

OBJECTIVES: Programmed death (PD)-1 is a cell death receptor that, upon stimulation, leads to apoptosis. Previous studies have shown alteration of PD-1 expression on T cells and PD-1 genes in patients with systemic lupus erythematosus (SLE). The aim of this study was to assess the expression of this receptor on effector T cells in patients with SLE. METHOD: In this study we enrolled 32 SLE patients and 31 healthy controls. T cells from peripheral blood were analysed by flow cytometry for the expression of PD-1. Interferon (IFN)-γ and interleukin (IL)-17-producing cells were investigated for the expression of this co-stimulatory marker. RESULTS: Percentages of CD4(+) T cells expressing PD-1 were significantly increased in patients with SLE compared to healthy controls. The percentage of PD-1 expression was correlated with the production of INF-γ (r = 0.83, p < 0.0001). We also investigated the production of IL-17 by PD-1(+) CD3(+) T cells. Inactive patients (3.2 ± 1.2% vs. 5.9 ± 3.5%, p = 0.002) and patients without lupus nephritis (LN) (3.2 ± 1.5% vs. 5.9 ± 3.5%, p = 0.005) showed lower levels of IL-17 compared to healthy controls. CONCLUSION: We have demonstrated increased expression of PD-1 on CD4(+) T cells in SLE patients and an association between PD-1 expression on CD4(+) T cells and IFN-γ expression on CD3(+) T cells. We have also shown that there is an altered subset of PD-1(+) T cells in inactive patients and patients without LN producing lower amounts of IL-17.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Interferon gama/metabolismo , Interleucina-17/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Adulto , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade
8.
N Engl J Med ; 368(23): 2169-81, 2013 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-23738544

RESUMO

BACKGROUND: Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. METHODS: We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2). RESULTS: A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73×10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period. CONCLUSIONS: Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic-uremic syndrome. (Funded by Alexion Pharmaceuticals; C08-002 ClinicalTrials.gov numbers, NCT00844545 [adults] and NCT00844844 [adolescents]; C08-003 ClinicalTrials.gov numbers, NCT00838513 [adults] and NCT00844428 [adolescents]).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Complemento C5/antagonistas & inibidores , Síndrome Hemolítico-Urêmica/tratamento farmacológico , Microangiopatias Trombóticas/prevenção & controle , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/sangue , Anticorpos Monoclonais Humanizados/farmacocinética , Terapia Combinada , Feminino , Síndrome Hemolítico-Urêmica/sangue , Síndrome Hemolítico-Urêmica/genética , Síndrome Hemolítico-Urêmica/terapia , Humanos , Nefropatias/tratamento farmacológico , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Mutação , Troca Plasmática , Contagem de Plaquetas , Qualidade de Vida , Adulto Jovem
10.
Scand J Immunol ; 76(3): 320-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22670785

RESUMO

Peripheral immunoregulation depends on T regulatory cell trafficking into the allograft to modulate the local alloresponse. Little is known about the relevance of trafficking receptors for Tregs after solid organ transplantation in humans. In this study, expression of the peripheral chemokine receptors CXCR3 and CCR5 on CD4⁺ FOXP3⁺ Treg cells was analysed and correlated with allograft function in renal transplant recipients. Flow cytometry analysis of peripheral blood mononuclear cells of 54 renal transplant recipients receiving a calcineurin inhibitor-based immunosuppression was performed for CD4, CD25, FOXP3, CXCR3 and CCR5 within the first 18 months post-transplantation. Correlation analysis of chemokine receptor expression and glomerular filtration rate as calculated by MDRD (eGFR) was performed. Expression of the peripheral homing receptors CXCR3 (r = 0.44, P < 0.05) and CCR5 (r = 0.45, P < 0.05) on FOXP3⁺ Tregs correlated with renal allograft function (eGFR) in patients receiving tacrolimus (n = 28), but not cyclosporine A (CsA) (n = 26). CsA but not tacrolimus reduced surface expression of CXCR3 on FOXP3⁺ Tregs in renal transplant recipients as correlated to trough levels (r = -0.42, P < 0.05). In contrast to CD4⁺ CXCR3⁺ CD25(lo) T cells, flow-sorted CD4⁺ CXCR3⁺ CD25(hi) Tregs isolated from healthy individuals did not produce IFNγ or IL-17 ex vivo and expressed high levels of GARP mRNA both at baseline as well as after TCR activation indicating functional regulatory activity. Expression of the peripheral trafficking receptors CXCR3 and CCR5 on FOXP3⁺ Tregs is associated with renal allograft function. These results suggest that Treg trafficking may also depend on the interaction of CXCR3 or CCR5 and their respective ligands.


Assuntos
Rejeição de Enxerto/imunologia , Transplante de Rim/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Antígenos CD4/biossíntese , Antígenos CD4/imunologia , Quimiotaxia de Leucócito , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/biossíntese , Fatores de Transcrição Forkhead/imunologia , Taxa de Filtração Glomerular , Rejeição de Enxerto/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real , Receptores CXCR3/biossíntese , Receptores CXCR3/imunologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Transplante Homólogo
11.
Clin Exp Immunol ; 168(2): 251-9, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22471287

RESUMO

The peripheral chemokine receptors chemokine receptor 3 (CXCR3) and CC chemokine receptor 5 (CCR5) have been reported to be associated with allograft rejection. The impact of the expression of immunosuppressive drugs on peripherally circulating CD4(+) T cell subsets after renal transplantation is unknown. Expression of CXCR3 and CCR5 was investigated by flow cytometry in 20 renal allograft recipients participating in a prospective, randomized trial (NCT00514514). Initial immunosuppression consisted of basiliximab, cyclosporin A (CsA), mycophenolate sodium and corticosteroids. After 3 months, patients were treated either with CsA, mycophenolate sodium (MPA) plus corticosteroids (n = 6), CsA and everolimus plus corticosteroids (n =8) or CsA-free (CsA(free)) receiving everolimus, MPA and corticosteroids (n = 6). After initial reduction of CD4(+) forkhead box protein 3 (FoxP3)(+) and CD4(+) CD25(hi) FoxP3(+) regulatory T cells (T(regs)) (P < 0.05; P < 0.01), 3-month post-transplant percentages of T(regs) were reconstituted in CsA(free) and CsA(lo) arms compared to CsA(reg) 12 months post transplant. Expression of CCR5 and CXCR3 on CD4(+) FoxP3(+) and CD4(+) FoxP3(-) T cells 12 months post transplant was increased in CsA(free) versus CsA(reg). Increase in CCR5(+) CXCR3(+) co-expressing CD4(+) FoxP3(-) cells between 3 and 12 months correlated negatively with the glomerular filtration rate (GFR) slope/year [modification of diet in renal disease (MDRD); r = -0.59, P < 0.01]. CsA, but not everolimus, inhibits both T(reg) development and expression of CXCR3 and CCR5 on CD4(+) T cell subsets. Increase in CCR5(+) CXCR3(+) co-expressing CD4(+) FoxP3(-) T cells is associated with early loss in allograft function.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Ciclosporina/farmacologia , Imunossupressores/farmacologia , Transplante de Rim/imunologia , Receptores de Quimiocinas/metabolismo , Sirolimo/análogos & derivados , Subpopulações de Linfócitos T/efeitos dos fármacos , Adulto , Idoso , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Basiliximab , Antagonistas dos Receptores CCR5 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Ciclosporina/uso terapêutico , Everolimo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/uso terapêutico , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Receptores CCR5/metabolismo , Receptores CXCR3/antagonistas & inibidores , Receptores CXCR3/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Proteínas Recombinantes de Fusão/uso terapêutico , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia
13.
Dtsch Med Wochenschr ; 136(5): 194-7, 2011 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-21271480

RESUMO

New guidelines of the "Kidney Disease: Improving Global Outcome" (KDIGO) working group standardize the definition of acute kidney injury (AKI) and acute kidney disease (AKD) allowing the assessment of prognosis and efficacy of prophylactic and therapeutic measures in different patient cohorts. The degree of severity and the duration of acute kidney injury are critical factors for the development of chronic kidney disease and mortality. The achievement of optimal fluid volumes is a cornerstone in the treatment during the early phase of AKI, while volume overload should be avoided in the late phase of established AKI. Recently employed biomarkers are promising for the early detection and prognosis of AKI, but cannot yet be used as routine tests. Microscopic urinalysis, a very old and cost-effective diagnostic measure, provides valuable informations about the severity and the course of AKI.


Assuntos
Injúria Renal Aguda/terapia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Creatinina/sangue , Hidratação/métodos , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Falência Renal Crônica/prevenção & controle , Testes de Função Renal/métodos , Guias de Prática Clínica como Assunto , Prognóstico , Taxa de Sobrevida , Resultado do Tratamento , Urinálise/métodos
15.
Minerva Med ; 99(2): 177-96, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18431326

RESUMO

Iodanated contrast media related nephrotoxicity is a common phenomenon, which has been known for over five decades now and is widely termed contrast media induced nephropathy (CIN). CIN is one of the most common reasons for hospital-acquired acute kidney injury. The incidence of CIN varies widely, depending on the diagnostic criteria and on the individual risk factors for CIN. CIN is associated with a significant increase in mortality. The clinical features and the histological morphology of CIN are well characterized, whereas the precise mechanisms of renal injury during CIN are not clear. Most likely a combination of different pathomechanisms is involved: contrast media induced reduction of renal perfusion, reduction of tubular flow and direct tubular toxicity leading to a decrease of glomerular filtration rate. Several risk factors for the development of CIN exist, which can be divided into patient related and non-patient related risk factors as well as in modifiable and non-modifiable risk factors. Among them pre-existing renal failure is the most critical parameter. There is no effective treatment for CIN, however, because the development of CIN is predictable, preventional strategies for CIN have been developed. They can be divided into four different categories: volume expansion before, during and after contrast media administration, pharmacological strategies to prevent reduction of renal perfusion, reduction of tubular flow and direct tubular toxicity, renal replacement therapy, and selection of contrast media. Among them, volume expansion is the most critical measure for reducing CIN and should be used in all patients undergoing contrast media procedures.


Assuntos
Meios de Contraste/efeitos adversos , Nefropatias/induzido quimicamente , Humanos , Incidência , Rim/efeitos dos fármacos , Nefropatias/epidemiologia , Nefropatias/fisiopatologia , Nefropatias/prevenção & controle , Terapia de Substituição Renal , Fatores de Risco
16.
Clin Nephrol ; 66(5): 322-30, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17140161

RESUMO

BACKGROUND: Contrast media-induced nephropathy (CIN) is an increasing cause of hospital-acquired acute kidney injury and leads to a significant increase in mortality. There is uncertainty whether the use of iso-osmolar contrast media as opposed to the use of low-osmolar contrast media would be associated with a lower incidence of CIN. Therefore, we compared the nephrotoxicity of isoosmotic contrast media iodixanol with the low-osmotic contrast media iopromid in patients receiving contrast media during coronary angiography. METHODS: In this prospective double-blind study we examined 221 patients with normal renal function who received up to 1,000 ml of contrast media during coronary angiography, and compared the effect of iodixanol and iopromid on inducing contrast media nephropathy. Patients received 800 ml fluid orally before contrast media administration and 1,000 ml saline i.v. thereafter. Creatinine clearance, serum creatinine and urine-N-acetyl-beta-D-glucosaminidase (NAG) concentration was obtained 24 h before and 48 h after contrast media administration. Decrease of 20% of the creatinine clearance, increase of 25% of serum creatinine and increase of 20% of the urine concentration of NAG was defined as CIN. RESULTS: Incidence of CIN assessed by decreased creatinine clearance was 22.2% in the iopromid group and 19.7% in the iodixanol group. CIN defined by increased serum creatinine was 6.9% in the iopromid group and 8.6% in the iodixanol group. The difference between these two groups was not significant. Subgroup analysis of the diabetic patients or the patients that received high dose of contrast media revealed no significant difference in the incidence of CIN between the two contrast media. CONCLUSION: The iso-osmolar and the low-osmolar contrast media exhibited the same incidence of CIN in our study population. If fluid administration is sufficient, the selection of either iopromid or iodixanol has no impact on the risk of developing CIN in patients with normal renal function, even when they are diabetic or receive a high dose of more than 500 ml contrast media.


Assuntos
Meios de Contraste/efeitos adversos , Iohexol/análogos & derivados , Nefropatias/induzido quimicamente , Ácidos Tri-Iodobenzoicos/efeitos adversos , Acetilglucosaminidase/urina , Distribuição de Qui-Quadrado , Meios de Contraste/administração & dosagem , Angiografia Coronária , Creatinina/metabolismo , Método Duplo-Cego , Feminino , Humanos , Incidência , Iohexol/administração & dosagem , Iohexol/efeitos adversos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Estudos Prospectivos , Fatores de Risco , Estatísticas não Paramétricas , Ácidos Tri-Iodobenzoicos/administração & dosagem
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