RESUMO
BACKGROUND: In contrast to insulin-dependent type 1 diabetes mellitus (T1DM), the indication for Simultaneous pancreas-kidney transplantation (SPK) in patients with type 2 diabetes mellitus (T2DM) is still ambiguous and wisely Eurotransplant (ET) only granted transplant-permission in a selected group of patients. However, with regard to improvement of metabolic conditions SPK might still be a considerable treatment option for lean insulin dependent type 2 diabetics suffering from renal disease. METHODS: Medical data (2001-2013) from all consecutive T1DM and T2DM patients who received a SPK or kidney transplant alone (KTA) at the University Hospital of Leipzig were analyzed. Donor, recipients and long-term endocrine, metabolic and graft outcomes were investigated for T1DM and T2DM-SPK recipients (transplanted upon a special request allocation by ET) and T2DM patients who received a KTA during the same period. RESULTS: Eighty nine T1DM and 12 T2DM patients received a SPK and 26 T2DM patients received a KTA. Patient survival at 1 and 5 years was 89.9 and 88.8% for the T1DM group, 91.7 and 83.3% for the T2DM group, and 92.3 and 69.2% for the T2DM KTA group, respectively (p < 0.01). Actuarial pancreas graft survival for SPK recipients at 1 and 5 years was 83.1 and 78.7% for the T1DM group and 91.7 and 83.3% for the T2DM group, respectively (p = 0.71). Kidney allograft survival at 5 years was 79.8% for T1DM, 83.3% for T2DM, and 65.4% for T2DM KTA (p < 0.01). Delayed graft function (DGF) rate was significantly higher in type 2 diabetics received a KTA. Surgical, immunological and infectious complications showed similar results for T1DM and T2DM recipients after SPK transplant and KTA, respectively. With regard to the lipid profile, the mean high-density lipoprotein (HDL)- cholesterol levels were significantly higher in T1DM recipients compared to T2DM patients before transplantation (p = 0.02) and remained significantly during follow up period. CONCLUSION: Our data demonstrate that with regard to metabolic function a selected group of patients with T2DM benefit from SPK transplantation. Consensus guidelines and further studies for SPK transplant indications in T2DM patients are still warranted.
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Biomarcadores/metabolismo , Diabetes Mellitus Tipo 1/cirurgia , Diabetes Mellitus Tipo 2/cirurgia , Nefropatias Diabéticas/epidemiologia , Transplante de Rim/mortalidade , Transplante de Pâncreas/mortalidade , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Aloenxertos , Glicemia/análise , Feminino , Seguimentos , Alemanha/epidemiologia , Hemoglobinas Glicadas/análise , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND/AIMS: The position of the tip of tunnelled haemodialysis (HD) catheters (THC) might influence flow characteristics during HD. In chest X-ray (CXR), carina-related landmarks may be practicable to verify the THC position, and tip-carina distance (TCD) might be useful to predict early-flow dysfunctions. METHODS: In this single-centre, retrospective study, the TCD and the angle between the distal catheter and the body vertical axis (tip-body vertical-angle [TVA]) was measured in 115 THC by post-procedure CXR with 2 investigators. The parameters were proved to be feasible by interrater-reliability and correlated with the incidence of flow-dysfunction within 10 days after insertion. RESULTS: Steep-aligned (TVA <40°, p < 0.01) and deep-ending catheters (TCD: right-sighted >1.5 cm or left-sighted >4.5 cm below the carina; p < 0.01) showed a significantly less dysfunction with a good interrater-reliability (R[TVA] = 0.8, R[TCD] = 0.9). CONCLUSIONS: Carina-related landmarks in CXR might be helpful to predict early-flow dysfunctions. However, randomized studies will be necessary to confirm this in fluoroscopic-guided placement during the insertion of THC.
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Cateteres Venosos Centrais/normas , Radiografia Torácica/métodos , Diálise Renal/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , ReologiaRESUMO
INTRODUCTION: The possible confounding influence of investigator-related preferences, available histological techniques, and healthcare systems on the frequencies and incidences of primary and secondary nephropathies was evaluated in this long-term observation. MATERIALS AND METHODS: The observation time from 1983 to 2010 was divided in regard to the political regimes: a) prior to and after German reunification: German Democratic Republic (GDR, period 1 from 1983 to 1990)/Federal Republic of Germany (FRG, period 2 from 1990 to 2010); and the two heads of the division of nephrology, b) conductor 1 (1983 - 2006) and conductor 2 (2006 - 2010). 467 kidney biopsies at the University Hospital of Leipzig were included in our analysis. RESULTS: In period 1, due to the unavailability of immunofluorescence methods, mesangioproliferative glomerulonephritis (MesP) was the most dominating nephropathy. In period 2, IgA nephropathy (IgAN) was the most common nephropathy (17%). IgAN was followed by crescentic glomerulonephritis (13%), hypertensive nephropathy (10%), minimal-change disease, and membranous glomerulonephritis (each 9%). From period 1 to period 2, MesP/IgAN (62% to 16%), membranoproliferative glomerulonephritis and postinfectious glomerulonephritis decreased significantly (p < 0.05). IgAN decreased significantly (p < 0.05) from conductor 1 to conductor 2 (21% to 6%), while diabetic nephropathy significantly increased. Focal-segmental glomerulosclerosis (FSGS) had the highest incidence rate with 1.0, followed by IgAN with 0.8 (per 100,000 per year). CONCLUSION: In a nearly ethnically identical cohort, we have demonstrated that confounding factors, e.g., healthcare systems and preferences of conductors, have a strong influence - more than 10-fold variance - on frequency and incidence on the spectrum of nephropathies.â©.
Assuntos
Atenção à Saúde , Nefropatias/epidemiologia , Política , Adulto , Biópsia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Rim/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: In this prospective study, we aimed to assess the haemodynamic changes before and after haemodialysis (HD) in cardiac healthy subjects on chronic HD by imaging methods and endocrine markers of fluid balance. METHODS: Mid-regional pro-atrial natriuretic peptide (MR-proANP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), vasopressin (AVP) and copeptin (CT-proAVP), metanephrines and normetanephrines, renin and aldosterone, standard transthoracic echocardiography and diameter of vena cava inferior (VCID) were performed in 20 patients with end stage renal disease (CKD5D) before and after HD and were stratified in residual excretion (RE, less or more 0.5 l) and ultrafiltration rate (UF, less or more 2 l). RESULTS: Copeptin was significantly higher in patients before HD. Copeptin was inversely correlated with haemodialysis treatment adequacy (KT/v), RE and UF, but was not significantly influenced by age, gender and body mass index (BMI). MR-proANP was significantly reduced by haemodialysis by 27% and was inversely correlated with KT/v, but there was a significant influence by UF, RE, age, gender and BMI. NT-proBNP was significantly higher in patients before HD and was not influenced by RE and UF. Renin, aldosterone, metanephrines and normetanephrines did not demonstrate significant differences. Echocardiographic parameters and VCID were significantly correlated with RE, UF and copeptin. CONCLUSION: Modern biomarkers will provide cardiovascular risk assessment, but elimination (UF), RE and other factors may influence the serum concentrations, e.g. in patients with renal impairment. The interpretation will be limited by altered reference ranges, and will be restricted to individual courses combined with clinical and echocardiographic data.
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Fator Natriurético Atrial/sangue , Glicopeptídeos/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Diálise Renal , Insuficiência Renal Crônica/sangue , Adulto , Aldosterona/sangue , Biomarcadores/sangue , Ecocardiografia , Feminino , Nível de Saúde , Humanos , Masculino , Metanefrina/sangue , Pessoa de Meia-Idade , Normetanefrina/sangue , Estudos Prospectivos , Diálise Renal/métodos , Insuficiência Renal Crônica/terapia , Renina/sangue , Vasopressinas/sangue , Veia Cava Inferior/diagnóstico por imagemRESUMO
A 21-year-old male patient from Borna, Saxony, in Eastern Germany, suffered from acute kidney injury (AKI) and symptoms typical for a hantavirus infection. These symptoms included nausea, vomiting, abdominal pain, diarrhea, and acute renal failure. Serological investigations by indirect IgM and IgG in-house ELISAs, commercial immunofluorescence and line assays, as well as chemiluminescence focus reduction neutralization assay confirmed an acute Dobrava-Belgrade virus (DOBV) infection of the patient. Serological and RT-PCR analyses of striped field mouse (Apodemus agrarius) trapped in a neighboring region of the residence of the patient identified an infection by DOBV, genotype Kurkino. This is the first report of an autochthonous DOBV infection in a German patient living far from the known endemic region in the north of the country. This finding has implications for the awareness of physicians in areas which are not recognized as hantavirus endemic regions but where the reservoir host of the virus is present.
Assuntos
Infecções por Hantavirus/virologia , Orthohantavírus/isolamento & purificação , Adulto , Animais , Reservatórios de Doenças/virologia , Doenças Endêmicas , Alemanha/epidemiologia , Orthohantavírus/classificação , Orthohantavírus/genética , Infecções por Hantavirus/diagnóstico , Infecções por Hantavirus/epidemiologia , Infecções por Hantavirus/transmissão , Humanos , Masculino , Camundongos , Adulto JovemRESUMO
BACKGROUND AND AIMS: Comprehensive geriatric assessments are established tools for the identification of health problems in the elderly. So far, little is known about tailoring and targeting to facilitate their application. As a starting point for a tailored assessment of patients with diabetes, a highly prevalent health condition, we aimed to assess if the Standardized Assessment of Elderly People (STEP) is able to identify relevant differences in self-reported health problems between diabetic and non-diabetic patients. PATIENTS AND METHODS: We performed a secondary analysis of a cross-sectional study including 1007 adults (aged 65 and older) from 28 German general practices, evaluating the feasibility and usefulness of the self-administered STEP version. For this exploratory study we re-analysed the data and compared patients with and without diabetes. RESULTS: Out of 940 patients included in the secondary analysis, 248 (26.4%) had diabetes. Compared to non-diabetic patients, geriatric diabetic patients reported more often problems in activities of daily living, physical problems typically associated with diabetes such as urinary incontinence, visual impairment, mood disturbances, as well as the use of medical or social services. Most of our results were stable after adjusting for age, sex and body mass index. CONCLUSION: We conclude that the self-administered version of the STEP tool may be used to screen for health problems typically associated with diabetes. Our results may guide the development of a tailored STEP-version specifically for diabetic patients. Further research might evaluate the adoption and usefulness of such a tool in every-day general practice.
Assuntos
Complicações do Diabetes/diagnóstico , Diabetes Mellitus/diagnóstico , Autoavaliação Diagnóstica , Avaliação Geriátrica , Psicometria/instrumentação , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Alemanha , Humanos , MasculinoRESUMO
PURPOSE: To assess the conservation status of, to gain information on the creation of, and to provide surface reformations of the core and the surface of the bust of the pharaoh-queen Nefertiti, considered to be one of the greatest treasures of ancient Egyptian art, with computed tomography (CT). MATERIALS AND METHODS: Multisection CT was performed with 0.6-mm section thickness. Two- and three-dimensional reformations were made to depict the core and the surface separately. RESULTS: The stucco layer on the face and the ears was very thin, a maximum of 1-2 mm thick. The rear part of the reconstructed crown showed two thick stucco layers of different attenuation values, indicating that a multistep process was used to create the sculpture. Within the stucco, a great number of air-equivalent hypoattenuating areas, filamentous fissures parallel to the surface, and an inhomogeneous bonding between the layers were delineated. Nefertiti's inner face was not anonymous, but rather delicately sculpted by the royal sculptor Thutmose. The comparison to the outer face revealed differences, including the angles of the eyelids, creases around the corners of the mouth on the limestone surface, and a slight bump on the ridge of the nose. According to the beauty ideals of the Amarna period, the differences had positive and negative effects and can be read as signs of individualization of the sculpture. The potential material-related weaknesses of the sculpture that were revealed at imaging necessitate careful handling, with the avoidance of any focal pressure and shearing forces in the crown and the shoulders. CONCLUSION: CT imaging revealed construction techniques in Nefertiti's bust that had implications for conservation, as well as for an understanding of the artistic methods used in the creation of this masterpiece of art of the 18th dynasty.
Assuntos
Pessoas Famosas , Escultura/história , Tomografia Computadorizada por Raios X/métodos , Antigo Egito , História AntigaRESUMO
OBJECTIVE: To observe and report on the pharmacokinetics of irinotecan in a patient with end-stage renal failure (ESRF) who was undergoing hemodialysis. CASE SUMMARY: A 64-year-old man with metastatic colorectal cancer who was on hemodialysis was treated with irinotecan 50 mg/m(2) weekly for 3 weeks, followed by 1 week with no treatment. As the drug was well tolerated, the dosage was increased to 80 mg/m(2) after 2 cycles. Diagnostic testing of a hepatic lesion after 2 and 6 treatment cycles showed stable disease. The carcinoembryonic antigen value decreased to 40% of its pretreatment level. Pharmacokinetically, our patient had a lower apparent clearance and a higher maximum concentration of the active metabolite SN-38 (130 L/h/m(2), maximum concentration 0.4 microg/L per mg of irinotecan) compared with published values from patients with normal renal function. Removal of irinotecan and its metabolites by hemodialysis was negligible. DISCUSSION: The reason for the unexpectedly low clearance of SN-38 in our patient remains unclear. We speculate that inhibition of the OATP1B1 transporter by uremic toxins could be an explanation. Such a mechanism would explain excessive irinotecan toxicity, as reported in previous case reports of patients undergoing hemodialysis. CONCLUSIONS: We conclude that approximately two-thirds of the standard weekly irinotecan dosage regimen should be considered in patients with ESRF.
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Antineoplásicos Fitogênicos/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/complicações , Neoplasias Colorretais/tratamento farmacológico , Glucuronatos/farmacocinética , Falência Renal Crônica/metabolismo , Camptotecina/farmacocinética , Camptotecina/uso terapêutico , Humanos , Irinotecano , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Diálise RenalRESUMO
BACKGROUND: Chronic or intercurrent alterations of the immune system in patients with end-stage renal disease (CKD) and intermittent hemodialysis (CKD5D, HD) have been attributed to an acute rejection of renal allograft. METHODS: Leukocyte subsets in flow cytometry, complement activation, and concentrations of TGFß, sCD30 (ELISA), and interleukins (CBA) of fifteen patients eligible for renal transplantation were analyzed before, during, and after a regular HD. RESULTS: Before HD, the median proportion of CD8+ effector cells, CD8+ CCR5+ effector cells, and HLA-DR+ regulatory T cells as well as the median concentration of soluble CD30 increased and naive CD8+ T cells decreased. During HD, there was a significant decrease in CD4- CD8- T cells (p < 0.001) and an increase in CD25+ T cells (p = 0.026), sCD30 (p < 0.001), HLA-DR+ regulatory T cells (p = 0.005), and regulatory T cells (p = 0.003). TGFß and sCD30 increased significantly over time. The activity of the classical complement pathway started to slightly increase after the first hour of HD and lasted until fifteen minutes after finishing dialysis. The decrease in the functional activity of the alternative pathway was only transient and was followed by a significant increase within 15 minutes after finishing the treatment. CONCLUSION: HD might interact with the allograft outcome by influencing T cell subsets and activation of the complement system in a biphasic course.
Assuntos
Transplante de Rim/efeitos adversos , Diálise Renal/efeitos adversos , Adulto , Idoso , Linfócitos T CD8-Positivos/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Interleucinas/metabolismo , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Linfócitos T/metabolismo , Adulto JovemRESUMO
Dual renin-angiotensin-aldosterone blockade (dRAASb) is purposed in the prevention of the cardiorenal syndrome (CRS). However, all attempts with dRAASb even in patients with moderate impaired chronic kidney disease (CKD) were terminated due to the typical severe adverse events (SAE), e. g., hyperkalemia and rise of serum creatinine. The aim of our study with the direct renin inhibitor aliskiren was to evaluate the effect of dRAASb with a washout phase in patients with severely advanced CKD. We have studied 45 patients (G3b to 4, A2 and >A3; median glomerular filtration rate (GFR) CKD-EPI 31 (23-40) ml/min per 1.73 m² BSA (body surface area), albumin-creatinine-ratio in urine (UACR) (0.413 (0.164 to 1.39) g/g) and proteinuria (0.5 (0.2 to 0.9) g/l) before, with and without aliskiren (150 respectively 300 mg per day) added to an angiotensin-converting enzyme inhibitor (ACEi) or an AT1-receptor blocker (ARB) over 4 ½ years. The dRAASb with aliskiren showed a significant decrease of proteinuria (0.5 to 0.38 g/l), especially in patients with an UACR≥350 mg/g and in the subgroup analysis e. g., in patients with diabetes, but proteinuria increased in the washout phase again. The blood pressure (130/80 mm Hg), serum potassium (4.9 to 5.0 mmol/l) and GFR remained nearly constant (31 to 29.5 ml/min per 1.73 m2 BSA). A more than 30% increase in serum creatinine was associated with an UACR>300 mg/g. The dRAASb has beneficial effects on proteinuria and is safe in patients with severely advanced CKD. However, in patients with high UACR (>300 mg/g) raise of creatinine and potassium have to be controlled.
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Amidas/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Fumaratos/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Insuficiência Renal Crônica/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Renina/antagonistas & inibidores , Idoso , Amidas/administração & dosagem , Amidas/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Quimioterapia Combinada , Feminino , Fumaratos/administração & dosagem , Fumaratos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/urinaRESUMO
INTRODUCTION: Endocrine disorders of the pituitary axes are frequent in patients with hemodialysis (CKD5D). The aim of this multicenter study (Leipzig (L), Quedlinburg and Blankenburg in the Harz region (Hz)) in CKD5D patients was to evaluate influences of CKD5D related factors, morphological and biochemical parameters, and serum iodine and prolactin concentrations on the pituitary-thyroid axis. PATIENTS AND METHODS: 170 patients (L n=58; Hz n=112) were included in this prospective, non-interventional, cross-sectional study. Mann-Whitney-U-test and bivariate correlation analyses with Spearman-Rho test (r correlation coefficient) were used in statistical analysis. RESULTS: TSH was higher in patients with prolactin concentrations>370 mIU/l (p=0.013), in patients with high flux membranes (p=0.0013) and in patients with longer dialysis vintage (p=0.04). Median iodine serum concentrations were slightly elevated in the Leipzig cohort (p=0.001) and correlated with fT4 (p<0.001, r=0.43) and albumin (p=0.001, r=0.245) but not with morphological signs. Albumin was correlated with fT3 (p<0.001, r=0.339) and fT4 (p<0.001, r=0.421). Prolactin was correlated with residual excretion rate (p=0.001, r=- 0.303) and thyroid volume (p=0.027, r=0.217). CONCLUSIONS: In the assessment of the thyroid status in CKD5D patients, the synopsis of the clinical and nutritional status, comorbidities, ultrasound of the thyroid gland and laboratory results is necessary for further intervention with hormone replacement. Standardized reference values of the pituitary-thyroid axis should be critically evaluated and are still lacking in CKD5D.
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Falência Renal Crônica , Hipófise/fisiopatologia , Prolactina/metabolismo , Diálise Renal , Glândula Tireoide/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Doenças Endêmicas , Feminino , Alemanha/epidemiologia , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/complicações , Doenças da Hipófise/epidemiologia , Doenças da Hipófise/metabolismo , Testes de Função Hipofisária , Hipófise/metabolismo , Diálise Renal/estatística & dados numéricos , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/metabolismo , Testes de Função Tireóidea , Glândula Tireoide/metabolismoRESUMO
Mycophenolic acid can be administered orally using mycophenolate mofetil or enteric-coated mycophenolate. In renal transplant patients on immunosuppressant combination therapy, the overall mycophenolic acid exposure after oral dosing with mycophenolate mofetil and enteric-coated mycophenolate is similar. This study compared pharmacokinetics and pharmacodynamics of mycophenolic acid after equivalent doses of enteric-coated mycophenolate (360 mg twice daily) or mycophenolate mofetil (500 mg twice daily) in 7 patients with progressive IgA nephritis (glomerular filtration rate 20-35 mL/min) using a randomized crossover design. The pharmacokinetics of mycophenolic acid concentrations and pharmacodynamics (using inosine 5'-monophosphate dehydrogenase activity as a bio-marker) were sequentially monitored for 12 hours. After enteric-coated mycophenolate treatment, the mycophenolic acid peak concentration (Cmax = 12.8 vs 6.0 microg/mL, P < .05) and the overall exposure were significantly higher (AUC = 60.9 vs 40.7 microg.h/mL, P < .05), and the apparent clearance was significantly lower (CL/F = 7.9 vs 10.7 L/h, P < .05) as compared to that after mycophenolate mofetil. Paradoxically, inosine 5'-monophosphate dehydrogenase activity was not significantly different. In conclusion, the steady-state mycophenolic acid exposure was higher during treatment with enteric-coated mycophenolate as compared to mycophenolate mofetil, which might be explained by more extensive enterohepatic recycling of mycophenolic acid after administration of enteric-coated mycophenolate, whereas inosine 5'-monophosphate dehydrogenase suppression was not different.
Assuntos
Glomerulonefrite por IGA/fisiopatologia , Imunossupressores/farmacologia , Imunossupressores/farmacocinética , Ácido Micofenólico/análogos & derivados , Pró-Fármacos/farmacologia , Pró-Fármacos/farmacocinética , Área Sob a Curva , Estudos Cross-Over , Feminino , Humanos , IMP Desidrogenase/metabolismo , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Modelos Lineares , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/farmacocinética , Ácido Micofenólico/farmacologia , Ácido Micofenólico/uso terapêutico , Pró-Fármacos/administração & dosagem , Pró-Fármacos/uso terapêutico , Insuficiência Renal/fisiopatologia , Comprimidos com Revestimento Entérico , Equivalência TerapêuticaRESUMO
HbA1c is the most accepted laboratory parameter for the long term observation of glucose control. There is still much of a debate about the use of HbA1c as a metabolic indicator in diabetic patients (DM) on haemodialysis (HD) and erythropoiesis-stimulating agent (ESA) therapy because of the altered erythrocyte turn over in patients with chronic kidney disease and haemodialysis (CKD5D). In 102 CKD5 patients with and without diabetes mellitus, we examined the dose dependent variability in HbA1c and fructosamine levels under haemodialysis and treated with epoetin α (n=48) and a new generation agent with continuous stimulation of methoxy polyethylene glycol epoetin beta (C.E.R.A.; n=54). HbA1c levels were affected by therapy with ESA treatments. ESA dose was inversely correlated with HbA1c and an escalation of 10.000 IU per week induced an estimated decrease of HbA1c of 0.6 percent. In addition, the increase of reticulocyte number as a marker for erythropoiesis was significantly inversely correlated with the increase of ΔHbA1c. ESA treatments had no such effect on the alternative metabolic parameter fructosamine. When compared, both therapeutic agents had comparable success in attaining haemoglobin (Hb) target values. C.E.R.A. showed better correlation and was more effective over a longer dose interval. Our results show that HbA1c levels in patients should be carefully interpreted based on interfering factors. Nevertheless, HbA1c is currently the most consistent parameter for use ascertaining metabolic status of patients suffering from diabetes mellitus.
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Nefropatias Diabéticas , Epoetina alfa/administração & dosagem , Eritropoetina/administração & dosagem , Frutosamina/sangue , Hemoglobinas Glicadas/metabolismo , Hematínicos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Diálise Renal , Insuficiência Renal Crônica , Adulto , Idoso , Idoso de 80 Anos ou mais , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapiaRESUMO
BACKGROUND: In progressive IgA nephropathy (IgAN), cyclophosphamide or steroids have been used to reduce the loss of renal function, but disease progression may occur after the end of treatment. The value of mycophenolic acid (MPA) maintenance therapy following initial immunosuppression in progressive IgAN is largely unknown. METHODS: In a prospective single-center trial, 20 patients with advanced IgAN (median glomerular filtration rate [GFR], 22 ml/min) and disease progression after cyclophosphamide pulse (CyP; n=18) or steroid pulse therapy (n=2) were treated with MPA for a median of 27 months. MPA dosages (initially mycophenolate mofetil 500 mg twice daily) were adjusted according to predose plasma concentrations (target concentrations 1.5 to 4 microg/mL). The course of renal function was assessed by linear regression of glomerular filtration rates. RESULTS: Median loss of renal function per month was significantly reduced from -0.8 ml/min to -0.03 ml/min per month after 6 months, to -0.05 ml/min per month after 12 months, and to -0.12 ml/min per month at the end of the study after median 27 months (p<0.05). An improved or stable GFR was observed in 16 of 20 patients during the first 12 months, and sustained in 10 patients during 24 months of follow-up. Proteinuria decreased significantly from 1.1 g/L to 0.4 g/L during MPA treatment (p=0.018). CONCLUSION: Our results indicate that MPA may be beneficial to slow down the loss of renal function in patients with progressive IgAN after previous immunosuppressive treatment.
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Ciclofosfamida/uso terapêutico , Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Feminino , Glomerulonefrite por IGA/fisiopatologia , Humanos , Rim/fisiopatologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/farmacocinética , Ácido Micofenólico/uso terapêutico , Estudos Prospectivos , Proteinúria/tratamento farmacológico , Proteinúria/fisiopatologiaRESUMO
Glucocorticoids have pleiotropic effects that are used to treat diverse diseases such as asthma, rheumatoid arthritis, systemic lupus erythematosus and acute kidney transplant rejection. The most commonly used systemic glucocorticoids are hydrocortisone, prednisolone, methylprednisolone and dexamethasone. These glucocorticoids have good oral bioavailability and are eliminated mainly by hepatic metabolism and renal excretion of the metabolites. Plasma concentrations follow a biexponential pattern. Two-compartment models are used after intravenous administration, but one-compartment models are sufficient after oral administration.The effects of glucocorticoids are mediated by genomic and possibly nongenomic mechanisms. Genomic mechanisms include activation of the cytosolic glucocorticoid receptor that leads to activation or repression of protein synthesis, including cytokines, chemokines, inflammatory enzymes and adhesion molecules. Thus, inflammation and immune response mechanisms may be modified. Nongenomic mechanisms might play an additional role in glucocorticoid pulse therapy. Clinical efficacy depends on glucocorticoid pharmacokinetics and pharmacodynamics. Pharmacokinetic parameters such as the elimination half-life, and pharmacodynamic parameters such as the concentration producing the half-maximal effect, determine the duration and intensity of glucocorticoid effects. The special contribution of either of these can be distinguished with pharmacokinetic/pharmacodynamic analysis. We performed simulations with a pharmacokinetic/pharmacodynamic model using T helper cell counts and endogenous cortisol as biomarkers for the effects of methylprednisolone. These simulations suggest that the clinical efficacy of low-dose glucocorticoid regimens might be increased with twice-daily glucocorticoid administration.
Assuntos
Glucocorticoides/farmacologia , Glucocorticoides/farmacocinética , Fatores Etários , Animais , Interações Medicamentosas , Feminino , Genômica , Glucocorticoides/efeitos adversos , Humanos , Masculino , Fatores SexuaisRESUMO
BACKGROUND: Valganciclovir is the oral prodrug of ganciclovir. The pharmacokinetics of valganciclovir in patients with renal impairment is not known. Furthermore, it is not known whether there are any pharmacokinetic differences between patients who are positive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) and healthy subjects. METHODS: A total of 44 patients were included-18 with mild, medium, or severe renal impairment; 6 with end-stage renal disease who were on long-term hemodialysis; 8 HIV/CMV-positive patients with normal renal function; and 12 healthy subjects serving as controls. Valganciclovir and ganciclovir serum concentrations were measured after oral administration of 900 mg of valganciclovir. Pharmacokinetic parameters were estimated by means of noncompartmental and compartmental methods. RESULTS: After oral administration of the prodrug valganciclovir, ganciclovir bioavailability was 60% and ganciclovir concentrations were higher (maximum concentration [C(max)], 8.5 microg/mL versus 5.8 microg/mL) and appeared later (time to maximum concentration [T(max)], 4.3 versus 2.0 hours) in patients with severe renal impairment compared with healthy subjects. The elimination half-life (t(1/2)) of ganciclovir was longer in patients with renal failure (t(1/2) of 68.1 hours in patients with end-stage renal disease compared with 3.5 hours in healthy subjects). Ganciclovir clearance was correlated with creatinine clearance (r = 0.975). Hemodialysis removed 50% of ganciclovir. We observed no differences in pharmacokinetics between HIV/CMV-positive patients and healthy subjects. A 2-compartment model with zero-order input and first-order elimination proved to be the most appropriate model for ganciclovir after oral administration of valganciclovir. CONCLUSIONS: The dosage of valganciclovir has to be adjusted to the degree of renal impairment. Dosage adjustment is not necessary for HIV/CMV-positive patients.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antivirais/farmacocinética , Infecções por Citomegalovirus/tratamento farmacológico , Ganciclovir/análogos & derivados , Ganciclovir/farmacocinética , Infecções por HIV/tratamento farmacológico , Falência Renal Crônica/complicações , Pró-Fármacos/farmacocinética , Infecções Oportunistas Relacionadas com a AIDS/complicações , Administração Oral , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/sangue , Disponibilidade Biológica , Infecções por Citomegalovirus/complicações , Esquema de Medicação , Feminino , Ganciclovir/administração & dosagem , Ganciclovir/sangue , Infecções por HIV/complicações , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Diálise Renal , ValganciclovirRESUMO
For advanced progressive primary IgA nephropathy (IgAN) no established therapy exists. We conducted a prospective, uncontrolled trial to evaluate the effect of intravenous cyclophosphamide pulse (CyP) therapy on the course of advanced progressive IgAN. Twenty-one patients (mean age 52 +/- 10 years; male/female 20/1) with biopsy-proven IgAN without crescentic extracapillary proliferation and a serum creatinine of more than 2.0 mg/dl and/or an increase more than 25% in the previous 3 months were included. Patients were treated with CyP (750 mg/m(2 )body surface area) every 4 weeks for 6 months and low dose oral prednisolone. The loss of renal function per year was significantly reduced from 16% before therapy to 4% after therapy (p < 0.001). A further increase >25% of serum creatinine after therapy was observed in 8 patients after 0.7 years (range 0.3-3.0 years), and 3 of these patients developed end-stage renal disease. Proteinuria decreased significantly during CyP therapy. A low nadir of white blood cell and platelet count was associated with a better renal outcome (p = 0.025). In conclusion, CyP therapy and low dose oral prednisolone is effective in preserving renal function in a subgroup of patients with advanced progressive IgAN.
Assuntos
Ciclofosfamida/administração & dosagem , Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/administração & dosagem , Adulto , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Creatinina/sangue , Ciclofosfamida/efeitos adversos , Progressão da Doença , Quimioterapia Combinada , Feminino , Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/fisiopatologia , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/efeitos adversos , Rim/fisiopatologia , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Estudos Prospectivos , Proteinúria/tratamento farmacológico , Pulsoterapia , Receptor Tipo 1 de Angiotensina , Análise de RegressãoRESUMO
BACKGROUND: Aim of this cross-sectional, multicentre study was to investigate associations of dialysis vintage time in haemodialysis (CKD5D) patients with oral health-related quality of life (OHRQoL) and dental and periodontal treatment need. MATERIAL AND METHODS: CKD5D patients were divided into subgroups according to dialysis vintage time in different dialysis centres in Germany. OHRQoL was assessed with oral health impact profile (OHIP-G14). Dental treatment need was classified as presence of carious lesions. Periodontal treatment need was defined as periodontal screening index score (PSI) 3-4. RESULTS: In total, 190 participants were divided into the subgroups according to the time on CKD5D: 0 - 2 (n = 29), 3 - 5 (n = 35), 6 - 8 (n = 34), 9 - 12 (n = 29), 13 - 20 (n = 34) and >20 years (n = 29). The overall treatment need in the total cohort was 92% (dental 56%, periodontal 88%) with a total OHIP-G14 sum score of 4.17 [2; 0-5] without a significant correlation. Time on CKD5D was inversely correlated with the OHIP G14 score (p < 0.01, R = -0.201). The pattern psychosocial impact was significantly associated with the dialysis duration (p < 0.01) and showed a negative correlation to the OHIP-G14 (R = -0.283, Spearman's rho test p < 0.01). For oral function also a negative correlation with OHIP-G14 was detected (Spearman's rho: -0.183). CONCLUSIONS: Patients with a prolonged dialysis vintage time show an improved OHRQoL, which might be mainly caused by the positive development of psychosocial pattern of OHRQoL. The oral health situation of HD patients seems unsatisfying, independently of dialysis vintage time and OHRQoL. Accordingly, an improvement in oral health situation of CKD5D patients is mandatory necessary. Thereby, consideration of psychosocial aspects especially at the beginning of CKD5D therapy and a sensitization regarding oral health issues with increasing vintage time might be recommendable
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Insuficiência Renal Crônica/terapia , Qualidade de Vida , Saúde Bucal , Assistência Odontológica , Estudos Transversais , Distribuição por IdadeRESUMO
BACKGROUND: Cyclophosphamide and high-dose steroids have been used as limited induction therapy in progressive IgA nephropathy (IgAN) to reduce the loss of renal function and proteinuria. We evaluated the effect of cyclophosphamide pulses (CyP) and mycophenolic acid (MPA) as sequential therapy on renal function in patients with progressive IgAN. METHODS: Twenty patients with progressive IgAN and advanced renal failure (median GFR 22 ml/min per 1.73 m2) and further disease activity (triangle downGFR -0.8 ml/min per month) after cyclophosphamide (CyP; n = 18) or steroid pulse therapy (n = 2) were treated with mycophenolate mofetil 1 g per day for a median of 27 months. RESULTS: The monthly loss of renal function was significantly reduced in linear regression analysis from -2.4 ml/min before CyP to -0.12 ml/min with CyP/MPA (p = 0.0009). Estimated renal survival time was significantly prolonged by a median of 65 months (p = 0.0014). Proteinuria decreased significantly from 1.7 to 0.4 g/l during MPA treatment (p = 0.015). In Cox regression analysis, only proteinuria >1.0 g/l was an independent risk factor for doubling of creatinine during CyP/MPA treatment (p = 0.03). CONCLUSION: A sequential therapy with CyP/MPA may arrest or slow down the loss of renal function and reduces proteinuria even in patients who passed the so called 'point of no return' with progressive IgAN.
Assuntos
Ciclofosfamida/administração & dosagem , Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/administração & dosagem , Esteroides/administração & dosagem , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/análogos & derivados , Estudos Prospectivos , Pulsoterapia , Insuficiência Renal/tratamento farmacológicoRESUMO
AIMS: To compare raloxifene pharmacokinetics between renally impaired and healthy subjects. METHODS: Raloxifene 120 mg was administered to 10 males with renal impairment (creatinine 2-4 mg dl(-1)) and to 10 healthy males. Data were analysed by two noncompartmental and one compartmental nonlinear regression methods. RESULTS: The medians (95% confidence interval) of the area under the curves (AUC) were 35.1 (25.8, 74) and 20.5 (16.8, 28.0) h ng ml(-1) per mg kg(-1), P < 0.01, and of the clearances (CL/F) were 28.5 (13.5, 38.8) and 48.8 (35.8, 59.4) l h(-1) kg(-1), P < 0.01, in renally impaired and healthy subjects, respectively. 95% Confidence intervals on the differences for AUC and CL/F were 6.5-44.1 and -35.1 to -7.9, respectively. CONCLUSION: Exposure to raloxifene was twice as high in males with renal impairment compared with healthy subjects.