RESUMO
In this longitudinal observational study, we measured urinary glucose concentration, body composition and volume status (bioimpedance spectroscopy) and plasma renin and aldosterone concentrations in n = 22 kidney transplant recipients (KTRs) initiating on SGLT2I at baseline (BL), and after 1 week and 1, 3, and 6 months. Estimated glomerular filtration rate (eGFR) decreased by -2 mL/min/1.73 m2 (IQR -10-0) after 1 week and remained stable thereafter. Urinary glucose concentration was 10 (3-24) g/g creatinine after 1 week and correlated with eGFR (r2 = 0.273; p = 0.057). SGLT2I did not affect HbA1c, fasting blood glucose, body weight, fat or lean mass. SGLT2I decreased fluid overload dependent on baseline overhydration (OH, r2 = 0.54, p = 0.0003) without occurrence of dehydration. Plasma aldosterone increased at day 7, while plasma renin did not change significantly. In conclusion, SGLT2I corrected fluid overload in patients with elevated overhydration at baseline, while in euvolemic KTRs fluid status remained stable without reduction of body water below the reference range, thus promoting the safety of SGLT2I therapy in patients following kidney transplantation. Glucosuria, together with effects of SGLT2I on blood glucose control and body weight, is attenuated in KTRs dependent on eGFR.
Assuntos
Taxa de Filtração Glomerular , Transplante de Rim , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Transplante de Rim/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Estudos Longitudinais , Adulto , Aldosterona/sangue , Idoso , Renina/sangue , Desequilíbrio Hidroeletrolítico/etiologia , Composição Corporal , Glicemia/análise , Glicemia/metabolismo , TransplantadosRESUMO
INTRODUCTION: SGLT2 inhibitors are used to reduce the risk of progression of chronic kidney disease (CKD). In patients with type 2 diabetes, they have been found to reduce extracellular volume. Given the high prevalence of extracellular volume expansion and overhydration (OH) in CKD, we investigated whether SGLT2 inhibitors might correct these disturbances in CKD patients. METHODS: CKD patients who started treatment with an SGLT2 inhibitor were investigated in this prospective observational study for 6 months. Body composition and fluid status were measured by bioimpedance spectroscopy. In addition, spot urine samples were analyzed for albuminuria, glucosuria, and urinary aprotinin-sensitive serine protease activity. RESULTS: Forty-two patients (29% with diabetic/hypertensive CKD, 31% with IgA nephropathy; 88% dapagliflozin 10 mg, 10% dapagliflozin 5 mg, 2% empagliflozin 20 mg; median eGFR 46 mL/min/1.73 m2 and albuminuria 1,911 mg/g creatinine) participated in the study. Median glucosuria increased to 14 (10-19) g/g creatinine. At baseline, patients displayed OH with +0.4 (-0.2 to 2.2) L/1.73 m2, which decreased by 0.5 (0.1-1.2) L/1.73 m2 after 6 months. Decrease of OH correlated with higher OH at BL, decrease of albuminuria, glucosuria, and urinary aprotinin-sensitive protease activity. Adipose tissue mass was not significantly reduced after 6 months. CONCLUSION: SGLT2 inhibitors reduce OH in patients with CKD, which is pronounced in the presence of high albuminuria, glucosuria, and urinary aprotinin-sensitive protease activity.
Assuntos
Compostos Benzidrílicos , Glucosídeos , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/urina , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Longitudinais , Glucosídeos/uso terapêutico , Glucosídeos/farmacologia , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/farmacologia , Estudos Prospectivos , Serina Proteases , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicaçõesRESUMO
BACKGROUND: The choice of induction therapy in kidney transplantation is often non-standardized and centre-specific. Clinicians can choose between depleting and non-depleting antibodies, which differ in their immunosuppressive capacity and the concomitant risk of infection. We herein present a standardized risk-stratified algorithm for induction therapy that might help to balance the risk of rejection and/or serious infection. METHODS: Prior to kidney transplantation, patients were stratified into low-risk, intermediate-risk or high-risk according to our protocol based on immunologic risk factors. Depending on their individual immunologic risk, patients received basiliximab (low risk), antithymocyte globulin (intermediate risk) or low-dose alemtuzumab (high risk) for induction therapy. We analysed the results after 3 years of implementation of our risk-stratified induction therapy protocol at our kidney transplant centre. RESULTS: Between 01/2017 and 05/2020, 126 patients were stratified in accordance with our protocol (low risk/intermediate risk/high risk: 69 vs. 42 vs. 15 patients). The median follow-up time was 1.9 [1.0-2.5] years. No significant difference was observed in rejection rate and allograft survival (low risk/intermediate risk/high risk: 90.07% vs. 80.81% vs. 100% after 3 years (p > 0.05)) among the groups. The median eGFR at follow-up was (low risk/intermediate risk/high risk) 47 [33-58] vs 58 [46-76] vs 44 [22-55] ml/min/1.73 m2. Although the rate of viral and bacterial infections did not differ significantly, we observed a higher rate of opportunistic fungal infections with alemtuzumab induction. CONCLUSIONS: Our strategy offers facilitated and individualized choice of induction therapy in kidney transplantation. We propose further evaluation of our algorithm in prospective trials.
Assuntos
Transplante de Rim , Humanos , Alemtuzumab/efeitos adversos , Transplante de Rim/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos Prospectivos , Quimioterapia de Indução/efeitos adversos , Imunossupressores/uso terapêutico , Rejeição de Enxerto , Sobrevivência de EnxertoRESUMO
BACKGROUND: Balancing immunosuppressive regimen to prevent rejection yet avoiding severe infectious complications remains a key challenge following renal transplantation, especially in patients sensitized after exposure to human leukocyte antigens. We herein report a late onset infection with nocardia in a sensitized renal transplant recipient. CASE PRESENTATION: A 65-year-old male patient, who had received kidney transplantation with alemtuzumab induction due to human leukocyte antigen-sensitization 3 years ago, was admitted with headache and dizziness. A cerebral magnetic resonance imaging scan showed a right parieto-occipital brain abscess. Surgical abscess drainage was performed and microbiology analysis detected Nocardia paucivorans in the abscess fluid. Laboratory results showed persistently reduced lymphocyte and T-cell counts 3 years after transplantation. We started intravenous antibiotic therapy with high dose trimethoprim/sulfamethoxazole and imipenem/cilastatin. Furthermore, immunosuppression was adapted with discontinuation of mycophenolate. After 7 weeks of intravenous antibiotic therapy, the patient was switched to an oral antibiotic regimen with amoxicillin/clavulanic acid and minocycline. In the follow-up magnetic resonance imaging scan, cerebral lesions were substantially reduced, initial symptoms completely disappeared, and allograft function remained stable. CONCLUSIONS: Induction therapy with the CD52-antibody alemtuzumab enables transplantation in highly sensitized patients but leads to lymphocyte depletion for several weeks. Our patient presented with prolonged lymphopenia and a significantly reduced T-cell count 3 years after transplantation. To our knowledge, our case is the first to describe a late-onset nocardia infection 3 years after alemtuzumab induction in a renal transplant recipient. It underlines the importance of considering this rare disease in transplant patients, especially after induction therapy with depleting antibodies.
Assuntos
Transplante de Rim , Nocardiose , Idoso , Alemtuzumab , Rejeição de Enxerto , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Masculino , Nocardiose/diagnóstico , Nocardiose/tratamento farmacológicoRESUMO
Platelets are known to be central regulators of haemostasis, inflammation and immune response. Formed by megakaryocytes in the bone marrow and the lungs, platelets express a broad range of adhesion receptors and release cytokines and platelet microparticles which enable them to interact with both immune cells and pathogens. In bacterial and viral infections, thrombophilia and thrombocytopenia are commonly seen symptoms, indicating the close relationship between haemostasis and immune defence. Indeed, platelets contribute both directly and via immune mediation to pathogen clearance. In sterile inflammation, a pathogen-free process which is often triggered by cell necrosis and autoimmune reactions, platelets are also of central importance. Recently, platelet inflammasome has been extensively studied in this context. Both sterile inflammation and infection are affected by the interactions of platelets and innate immunity, notably the complement system. Although the general elements of this interplay have been known for long, more and more insights into disease-specific mechanisms could be gained recently. This review gives an outline of the current findings in the field of platelet-immune cell interactions and points out possible implications for clinical therapy.
Assuntos
Plaquetas/imunologia , Imunidade Inata , Ativação Plaquetária , Animais , Proteínas do Sistema Complemento/imunologia , Humanos , Infecções/imunologia , Inflamação/imunologia , Neoplasias/imunologiaRESUMO
In recent years, various studies have increasingly explained platelet functions not only in their central role as a regulator in cellular hemostasis and coagulation. In fact, there is growing evidence that under specific conditions, platelets act as a mediator between the vascular system, hemostasis, and the immune system. Therefore, they are essential in many processes involved in tissue remodeling and tissue reorganization after injury or inflammatory responses. These processes include the promotion of inflammatory processes, the contribution to innate and adaptive immune responses during bacterial and viral infections, the modulation of angiogenesis, and the regulation of cell apoptosis in steady-state tissue homeostasis or after tissue breakdown. All in all platelets may contribute to the control of tissue homeostasis much more than generally assumed. This review summarizes the current knowledge of platelets as part of the tissue remodeling network and seeks to provide possible translational implications for clinical therapy.