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1.
Clin Nephrol ; 99(3): 128-140, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36633377

RESUMO

OBJECTIVE: This is a study on the demographics and clinical outcomes including the response to therapy of patients with focal segmental glomerulosclerosis (FSGS) over the past decade. MATERIALS AND METHODS: All histologically proven FSGS cases diagnosed between 2008 and 2018 were analyzed for their clinical, laboratory, and histological characteristics including treatment that could influence the disease progression and renal outcome of these patients. We used the Columbia Classification for FSGS for the renal biopsy. RESULTS: There were two subgroups of FSGS patients; those with nephrotic syndrome and those without nephrotic syndrome. Patients with FSGS with non-nephrotic syndrome had poorer survival rates compared to the nephrotic group. For those without nephrotic syndrome, the indices responsible for progression involved more tubular and blood vessel lesions in addition to glomerular pathology compared to those with nephrotic syndrome. Patients with FSGS with nephrotic syndrome responded to immunosuppressants more favorably compared to the non-nephrotic group, though both groups responded with decreasing proteinuria. The nephrotic group had a better 10-year long-term survival rate of 92 vs. 72% for the non-nephrotic group (log-rank 0.002). The 10-year survival for the whole group of FSGS patients was 64%. CONCLUSION: Our data suggest that in FSGS, one of the significant components of the disease is the vascular and tubular damage, apart from the underlying glomerular pathology, resulting in varying responses to therapy, and the difference is reflected in inherently poorer response to immunosuppressant therapy in those without nephrotic syndrome as opposed to those with nephrotic syndrome, who responded to immunosuppressant therapy (IST) with stabilization of renal function and had less blood vessel and tubular lesions.


Assuntos
Glomerulosclerose Segmentar e Focal , Nefropatias , Síndrome Nefrótica , Humanos , Glomerulosclerose Segmentar e Focal/patologia , Rim/patologia , Síndrome Nefrótica/patologia , Nefropatias/patologia , Imunossupressores
2.
Int J Immunogenet ; 50(6): 306-315, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37776087

RESUMO

Human leucocyte antigen (HLA) alleles may generate antibodies that are undetectable by routine single-antigen beads (SABs) assays if their unique epitopes are unrepresented. We aimed to describe the prevalence and explore the potential impact of unrepresented HLA alleles in standard SAB kits in our cohort. All individuals who had undergone two-field HLA typing (HLA-A/B/C/DRB1/DQA1/-DQB1/-DPA1/-DPB1) from February 2021 to July 2023 were included. Two-field HLA-DRB3/4/5 typing was imputed. Each unrepresented allele was compared with the most similar represented allele in the standard LABScreen, LABScreen ExPlex (One Lambda) and the LIFECODES (Immucor) SAB kits. Differences in eplet expression (HLA Eplet Registry) were identified. Differences in three-dimensional molecular structures were visualized using generated models (SWISS-MODEL). Two-field HLA typing was performed for 116 individuals. Overall, 16.7% of all HLA alleles, found in 36.2% of individuals, were unrepresented by all SAB test kits. Four eplets, found in 12.9% of individuals, were unrepresented in at least 1 SAB kit. Non-Chinese individuals were more likely to have unrepresented HLA alleles and eplets than Chinese individuals. There were differences in HLA allele and eplet representation amongst the different SAB test kits. Use of supplementary SAB test kits may improve HLA allele and eplet representation. Although some HLA alleles were unrepresented, most epitopes were represented in current SAB kits. However, some unrepresented alleles may contain epitopes which may generate undetectable antibodies. Further studies may be needed to investigate the potential clinical impact of these unrepresented alleles and eplets, especially in certain ethnic populations or at-risk individuals.


Assuntos
Anticorpos , Antígenos HLA , Humanos , Alelos , Estudos de Coortes , Epitopos , Teste de Histocompatibilidade
3.
Nephrology (Carlton) ; 28(5): 283-291, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36872077

RESUMO

BACKGROUND: The COVID-19 pandemic is protracted and episodic surges from viral variants continue to place significant strain on healthcare systems. COVID-19 vaccines, antiviral therapy and monoclonal antibodies have significantly reduced COVID-19 associated morbidity and mortality. Concurrently, telemedicine has gained acceptance as a model of care and a tool for remote monitoring. These advances allow us to safely transit our inpatient-based care for COVID-19 infected kidney transplant recipients (KTRs) to a hospital-at-home (HaH) model of care. METHODS: KTRs with PCR-proven COVID-19 infection were triaged by teleconsult and laboratory tests. Suitable patients were enrolled into the HaH. Remote monitoring via teleconsults were conducted daily until patients were de-isolated based on a time-based criterion. Monoclonal antibodies were administered in a dedicated clinic where indicated. RESULTS: Eighty-one KTRs with COVID-19 were enrolled into the HaH between February and June 2022, 70 (86.4%) completed HaH recovery without complications. Eleven (13.6%) patients required inpatient hospitalization for medical issues (n = 8) and weekend monoclonal antibody infusion (n = 3). Patients requiring inpatient hospitalization had longer transplant vintage (15 years vs. 10 years, p = .03), anaemia (haemoglobin 11.6 g/dL vs. 13.1 g/dL, p = .01), lower eGFR (39.8 vs. 62.9 mL/min/1.73 m2 , p < .05) and lower RBD levels (<50 AU/mL vs. 1435 AU/mL, p = .02). HaH saved 753 inpatient patient-days with no deaths observed. Hospital admission rates from the HaH programme was 13.6%. Patients who required inpatient care had direct access admission without utilization of emergency department resources. CONCLUSION: Selected KTRs with COVID-19 infection can be safely managed in a HaH programme; alleviating strain on inpatient and emergency healthcare resources.


Assuntos
COVID-19 , Transplante de Rim , Humanos , Anticorpos Monoclonais , COVID-19/epidemiologia , COVID-19/terapia , Hospitais , Pacientes Ambulatoriais
4.
Blood Purif ; 51(4): 376-382, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34198288

RESUMO

INTRODUCTION: Double-filtration plasmapheresis (DFPP) may be used for immunomodulation in kidney transplant (KTx). While DFPP reduces plasma product exposure, risk of circuit clotting merits adequate anticoagulation. Regional citrate anticoagulation (RCA) avoids the risks of systemic anticoagulation, but a protocol for RCA-DFPP is not previously widely described. METHODS: We conducted a single-center retrospective cohort study involving adult (≥21 years old) KTx recipients who underwent RCA-DFPP from 2018 to 2020 to investigate efficacy and safety for an RCA protocol during DFPP in KTx recipients. RESULTS: Fifty-one (85%) of 60 RCA-DFPP sessions in 17 patients completed without circuit clotting. Circuit clotting was associated with high post-filter ionized calcium (28 vs. 3.7%, odds ratio 10.1, 95% CI 1.1-89.4, p = 0.037). Hypo- and hypercalcemia developed in 5 (8.3%) and 8 (13.3%) sessions, respectively, but no adverse effects were noted despite severe hypocalcemia in one. There was no significant change in pre- and post-RCA-DFPP sodium, bicarbonate, albumin, and platelet levels. With regards DFPP procedure, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) was observed following 38 (64.4%) and 12 (20.3%) sessions, respectively. Severely prolonged (>1.5 × upper limit normal) PT and aPTT were recorded in 2 sessions each. Expectedly, hypofibrinogenemia developed after 31 (51.7%) sessions: including 4 (6.7%) severe hypofibrinogenemia (<0.5 g/L). Two patients developed bleeding requiring blood product transfusion. The median total volume of fluids administered per session was 1.495 (1.373-1.612) L; post-RCA-DFPP significant weight gain of 0.5 (0-1.25) kg was noted. Diuretic was commenced or dose increased following 20 (33.3%) sessions for fluid balance management. DISCUSSION/CONCLUSION: Protocol-based RCA for DFPP is feasible and safe in KTx recipients. However, DFPP-related coagulopathy can develop consequent to treatment; caution should be exercised for patients with bleeding risk. Close monitoring and management of the patients' electrolytes, especially hypocalcemia and hypomagnesemia, and fluid status is recommended.


Assuntos
Ácido Cítrico , Transplante de Rim , Adulto , Anticoagulantes/efeitos adversos , Citratos , Ácido Cítrico/efeitos adversos , Humanos , Plasmaferese/métodos , Estudos Retrospectivos , Adulto Jovem
5.
BMC Nephrol ; 23(1): 80, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-35209868

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused significant psychological distress globally. Our study assessed the prevalence of psychological distress and associated factors during COVID-19 pandemic among kidney transplant recipients and kidney donors. METHODS: A cross-sectional survey of 497 participants (325 recipients and 172 donors) was conducted from 1st May to 30th June 2020 in Singapore. The survey questionnaire assessed knowledge levels of COVID-19, socio-demographic data, health status, psychosocial impact of COVID-19, and precautionary behaviors during the pandemic. Psychological distress was defined as having anxiety, depression, or stress measured by the validated Depression, Anxiety and Stress Scale-21. Linear regression analyses were used to assess factors associated with higher psychological distress. RESULTS: The prevalence of psychological distress was 14.3% (95% confidence interval: 11.5-17.6%) in the overall population; it was 12.8% (9.79-16.6%) in recipients and 13.4% (9.08-19.6%) in donors with no significant difference (P = 0.67). Younger age (21-49 vs. ≥50 years), unmarried status, non-Singapore citizen, worse health conditions, and worrying about physical and mental health were associated with higher psychological distress. Malays (versus Chinese), taking precautionary measures (hand sanitization), and receiving enough information about COVID-19 were associated with lower psychological distress. No interactions were observed between recipients and donors. CONCLUSIONS: At least one in ten recipients and donors suffer from psychological distress during COVID-19 pandemic. Focused health education to younger adults, unmarried individuals, non-Singapore citizens, and those with poor health status could potentially prevent psychological distress in recipients and donors.


Assuntos
Ansiedade/epidemiologia , COVID-19/psicologia , Depressão/epidemiologia , Angústia Psicológica , Doadores de Tecidos/psicologia , Transplantados/psicologia , Adulto , Fatores Etários , Idoso , Ansiedade/etnologia , COVID-19/prevenção & controle , China/etnologia , Estudos Transversais , Depressão/etnologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Nível de Saúde , Humanos , Transplante de Rim , Malásia/etnologia , Masculino , Estado Civil , Pessoa de Meia-Idade , Prevalência , Escalas de Graduação Psiquiátrica , SARS-CoV-2 , Singapura/epidemiologia , Inquéritos e Questionários , Adulto Jovem
6.
Am J Transplant ; 21(5): 1944-1947, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33583132

RESUMO

Dengue virus (DENV), a mosquito-borne pathogen, causes systemic infections. There are no clear guidelines regarding the screening of donor blood is used in endemic countries to prevent blood transfusion or transplant-associated dengue. DENV has been shown to be detected in urine samples even when DENV viremia is undetectable. We describe an incident of transplant-associated dengue where the donor tested negative for DENV viremia but positive for DENV viuria resulting in the transmission of DENV to our two kidney recipients. Both recipients resolved DENV infection uneventfully, with no adverse impact on the renal graft. Our findings raise the consideration for revised screening recommendations in endemic countries to include DENV RT-PCR in the urine.


Assuntos
Vírus da Dengue , Dengue , Transplante de Órgãos , Animais , Doadores de Sangue , Dengue/diagnóstico , Humanos , Viremia
7.
J Med Virol ; 93(6): 3738-3743, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32797627

RESUMO

Early diagnosis remains key for effective prevention and treatment. Unfortunately, current screening with anti-hepatitis C virus antibody (anti-HCV Ab) test may have limited utility in the diagnosis of HCV infection and reinfection. This is of special concern to at-risk population, such as immunocompromised hosts and end-stage renal failure patients on hemodialysis. HCV antigen (Ag) could be useful in identifying the ongoing infection in such clinical scenarios. Hence, we aimed to study the utility of HCV Ag testing for the diagnosis of acute and chronic hepatitis C. Of 89 samples studied, 19 were from acute hepatitis C patients who were immunocompromised or were on hemodialysis, 43 were from active chronic hepatitis C patients and 27 were from patients treated for chronic hepatitis C. All samples were tested for HCV Ag using the Abbott ARCHITECT HCV Ag assay. HCV Ag was reactive in 19/19 samples from acute hepatitis C patients and 42/43 samples from active chronic hepatitis C patients. It was nonreactive in all samples from treated patients. The test showed a sensitivity and specificity of 98.4% and 100.0%, respectively. The positive and negative predictive values were 100.0% and 96.4%, respectively. The HCV antigen test has high clinical sensitivity and specificity and is useful for the diagnosis of acute and chronic hepatitis C infection in at-risk and immunocompromised patients. Its short turnaround time and relatively low cost are advantageous for use in patients on hemodialysis and other at-risk patients who require monitoring of HCV infection and reinfection.


Assuntos
Hepacivirus/genética , Antígenos da Hepatite C/análise , Hepatite C Crônica/diagnóstico , Hepatite C/diagnóstico , Hospedeiro Imunocomprometido , Testes Imunológicos/métodos , Adulto , Diagnóstico Precoce , Feminino , Hepacivirus/química , Hepatite C/sangue , Hepatite C/prevenção & controle , Antígenos da Hepatite C/sangue , Antígenos da Hepatite C/imunologia , Hepatite C Crônica/sangue , Hepatite C Crônica/prevenção & controle , Humanos , Testes Imunológicos/economia , Testes Imunológicos/normas , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Valor Preditivo dos Testes , RNA Viral/sangue , RNA Viral/genética , Sensibilidade e Especificidade
8.
Clin Transplant ; 35(10): e14415, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34216395

RESUMO

OBJECTIVE: We analyzed the efficacy and safety of an everolimus with reduced-exposure calcineurin inhibitor (EVR+rCNI) versus mycophenolic acid with standard-exposure CNI (MPA+sCNI) regimen in Asian patients from the TRANSFORM study. METHODS: In this 24-month, open-label study, de novo kidney transplant recipients (KTxRs) were randomized (1:1) to receive EVR+rCNI or MPA+sCNI, along with induction therapy and corticosteroids. RESULTS: Of the 2037 patients randomized in the TRANSFORM study, 293 were Asian (EVR+rCNI, N = 136; MPA+sCNI, N = 157). At month 24, EVR+rCNI was noninferior to MPA+sCNI for the binary endpoint of estimated glomerular filtration rate (eGFR) < 50 ml/min/1.73 m2 or treated biopsy-proven acute rejection (27.0% vs. 29.2%, P = .011 for a noninferiority margin of 10%). Graft loss and death were reported for one patient each in both arms. Mean eGFR was higher in EVR+rCNI versus MPA+sCNI (72.2 vs. 66.3 ml/min/1.73 m2 , P = .0414) even after adjusting for donor type and donor age (64.3 vs. 59.3 ml/min/1.73 m2 , P = .0582). Overall incidence of adverse events was comparable. BK virus (4.4% vs. 12.1%) and cytomegalovirus (4.4% vs. 13.4%) infections were significantly lower in the EVR+rCNI arm. CONCLUSION: This subgroup analysis in Asian de novo KTxRs demonstrated that the EVR+rCNI versus MPA+sCNI regimen provides comparable antirejection efficacy, better renal function, and reduced viral infections (NCT01950819).


Assuntos
Inibidores de Calcineurina , Transplante de Rim , Inibidores de Calcineurina/uso terapêutico , Everolimo/uso terapêutico , Taxa de Filtração Glomerular , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêutico , Tacrolimo
9.
Transpl Infect Dis ; 23(4): e13694, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34288307

RESUMO

Pseudomembranous colitis (PMC) is classically associated with Clostridium difficile infection. We report a rare case of cytomegalovirus (CMV)-associated PMC in a 52-year-old female patient who had undergone kidney transplantation more than 20 years ago and was on low dose prednisolone and ciclosporin. She presented with an acute history of fever, lethargy, vomiting and diarrhoea on admission. Computed tomography of the abdomen showed extensive colitis, and colonoscopy revealed extensive pseudomembrane formation. Multiple tests for Clostridium difficile and other common microbiological causes of colitis were negative. CMV DNAemia and colonic biopsies confirmed the diagnosis of CMV colitis. The patient responded to prompt CMV treatment, as demonstrated by clinical, endoscopic, and histological response. While CMV is a common pathogen in the solid organ transplant population that is familiar to most transplant physicians, it may present atypically as PMC. Here, we review the literature on CMV-associated PMC and its relevance to solid organ transplant recipients. To our knowledge, this is the first reported case of CMV-associated PMC in a kidney transplant recipient.


Assuntos
Clostridioides difficile , Colite , Infecções por Citomegalovirus , Enterocolite Pseudomembranosa , Transplante de Rim , Antivirais/uso terapêutico , Colite/diagnóstico , Citomegalovirus , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Enterocolite Pseudomembranosa/diagnóstico , Enterocolite Pseudomembranosa/tratamento farmacológico , Feminino , Humanos , Transplante de Rim/efeitos adversos , Pessoa de Meia-Idade
10.
Nephrology (Carlton) ; 26(1): 70-77, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32986301

RESUMO

AIM: Compared to Standard Criteria Donors (SCD), Expanded Criteria Donor (ECD) kidneys are associated with poorer outcomes, although pre-transplant biopsy may mitigate risks. This study assessed 5-year outcomes of deceased-donor kidney transplant recipients, comparing recipients of ECD allografts evaluated histologically to recipients of SCD and ECD kidneys assessed clinically. METHODS: This is a single-centre retrospective study. From November 2005 to December 2009 (Era 1), donors were assessed clinically for suitability for kidney donation. From December 2009 to October 2017 (Era 2), kidneys from ECDs and diabetics underwent pre-transplant biopsy and were allocated based on Remuzzi score. Outcomes of Era 1 and 2 recipients were compared. RESULTS: ECD kidney transplantation increased from 30.4% to 40.0% from Era 1 to 2. Univariable Cox regression, stratified by transplant era, found that 5-year graft loss was highest with Era 1 ECD (HR 2.5, 95% CI 1.1-5.5, P = .027) while graft loss for Era 2 ECD recipients was similar to SCD recipients. There was no difference in 5-year recipient survival. Amongst Era 1 ECD recipients, 51.2% experienced rejection compared to 30.8-41.5% for other subgroups. Five-year eGFR was higher with Era 2 ECD at 48.4 (33.3-60.7) ml/min/1.73 m2 compared to 42.2 (35.8-57.3) ml/min/1.73 m2 for Era 1 ECD. However, these differences were not statistically significant. CONCLUSION: Introduction of pre-transplant biopsy assessment may be associated with improved outcomes of ECD kidney recipients such that they are now comparable to SCD kidney recipients, with benefits persisting over 5 years.


Assuntos
Biópsia , Seleção do Doador , Rejeição de Enxerto/epidemiologia , Falência Renal Crônica , Transplante de Rim , Rim , Adulto , Biópsia/efeitos adversos , Biópsia/métodos , Seleção do Doador/métodos , Seleção do Doador/normas , Feminino , Humanos , Rim/patologia , Rim/fisiopatologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/cirurgia , Testes de Função Renal/métodos , Testes de Função Renal/estatística & dados numéricos , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Transplante de Rim/normas , Transplante de Rim/estatística & dados numéricos , Masculino , Medição de Risco/métodos , Fatores de Risco , Singapura/epidemiologia , Análise de Sobrevida , Doadores de Tecidos/estatística & dados numéricos
11.
Clin Transplant ; 33(10): e13671, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31332844

RESUMO

The evolution of trabecular bone score (TBS) and bone mineral density (BMD) over the first 5 years after renal transplantation was prospectively evaluated in 164 patients. Dual energy X-ray absorptiometry (DXA) scans were performed at 0, 6, 12, 24, and 60 months. Cumulative steroid dose, serum 25(OH)D, calcium, parathyroid hormone, and total ALP levels at these time points were checked. Incident fractures were identified from X-rays/vertebral fracture assessments. Mean (SD) age, TBS, and lumbar spine BMD at baseline were 47.11 (9.53), 1.424 (0.097), and 0.935 (0.183) gm/cm2 , respectively. Baseline TBS was lower in tertiary 1.38 (0.07) vs secondary hyperparathyroidism 1.43 (0.01) vs post-parathyroidectomy 1.46 (0.11); P = .035. Trabecular bone score and BMD significantly decreased from baseline->6 months, changes after that at consecutive time points were non-significant. 11% had incident fractures during the follow-up period, majority being metatarsal with no vertebral or hip fractures noted. This first prospective evaluation of TBS and BMD evolution at multiple time points over 5 years suggest that microarchitectural and bone density deteriorations post-renal transplantation stabilize after 6 months. Stabilization of these parameters could partially account for the absence of major fractures noted in this Asian population. Possible genetic and ethnic differences in fracture risk between Asian and Caucasian renal transplant patients have to be explored through large population-based studies.


Assuntos
Densidade Óssea , Osso Esponjoso/fisiopatologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Fraturas por Osteoporose/patologia , Medição de Risco/métodos , Absorciometria de Fóton , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/etiologia , Prognóstico , Estudos Prospectivos , Fatores de Risco
12.
Angew Chem Int Ed Engl ; 58(24): 8151-8155, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-30989779

RESUMO

Phosphorylation of (pre)biotically relevant molecules in aqueous medium has recently been demonstrated using water-soluble diamidophosphate (DAP). Questions arise relating to the prebiotic availability of DAP and other amidophosphosphorus species on the early earth. Herein, we demonstrate that DAP and other amino-derivatives of phosphates/phosphite are generated when Fe3 P (proxy for mineral schreibersite), condensed phosphates, and reduced oxidation state phosphorus compounds, which could have been available on early earth, are exposed to aqueous ammonia solutions. DAP is shown to remain in aqueous solution under conditions where phosphate is precipitated out by divalent metals. These results show that nitrogenated analogues of phosphate and reduced phosphite species can be produced and remain in solution, overcoming the thermodynamic barrier for phosphorylation in water, increasing the possibility that abiotic phosphorylation reactions occurred in aqueous environments on early earth.


Assuntos
Planeta Terra , Fosfatos/química
13.
Nephrology (Carlton) ; 22(10): 761-768, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27351105

RESUMO

AIM: Post-donation kidney function has not been well characterized in the Southeast Asian population. We studied a retrospective cohort of 174 living kidney donors at Singapore General Hospital between 1976 and 2012, evaluated patterns of change in kidney function using quantile regression analysis and investigated for predictors of low estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73m2 . Median follow-up time (range) was 7.8 (0.1-33.8) years following donor nephrectomy. RESULTS: Of the donors, 43.1% regained 75% or more of pre-nephrectomy eGFR after 5 years post-donation; 9.8% exhibited 100% recovery to pre-nephrectomy eGFR. High pre-nephrectomy eGFR was protective for risk of low post-donation eGFR, with a 6% risk reduction for each unit increase in pre-nephrectomy eGFR (odds ratio, 0.94; 95% confidence interval, 0.91-0.97; P = 0.002). This relationship was stronger in the short term (>6 months to < 5 years) than medium to long term (5 years or longer) (interaction P = 0.052). CONCLUSION: In general, kidney function is well preserved following kidney donation in Southeast Asian donors. Pre-nephrectomy eGFR is a good predictor of post-donation eGFR, especially in the short-term.


Assuntos
Taxa de Filtração Glomerular , Transplante de Rim/métodos , Rim/cirurgia , Doadores Vivos , Nefrectomia , Adulto , Povo Asiático , Feminino , Nível de Saúde , Hospitais Gerais , Humanos , Rim/fisiopatologia , Transplante de Rim/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nefrectomia/efeitos adversos , Razão de Chances , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Singapura , Fatores de Tempo , Resultado do Tratamento
14.
Orig Life Evol Biosph ; 46(4): 425-434, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27220497

RESUMO

We describe here experiments which demonstrate the selective phospho-transfer from a plausibly prebiotic condensed phosphorus (P) salt, pyrophosphite [H2P2O52-; PPi(III)], to the phosphate group of 5'-adenosine mono phosphate (5'-AMP). We show further that this P-transfer process is accelerated both by divalent metal ions (M2+) and by organic co-factors such as acetate (AcO-). In this specific case of P-transfer from PPi(III) to 5'-AMP, we show a synergistic enhancement of transfer in the combined presence of M2+ & AcO-. Isotopic labelling studies demonstrate that hydrolysis of the phosphonylated 5'-AMP, [P(III)P(V)-5'-AMP], proceeds via nuceophilic attack of water at the Pi(III) terminus.


Assuntos
Monofosfato de Adenosina/química , Cátions Bivalentes/química , Origem da Vida , Compostos de Fósforo/química , Metais
17.
Environ Microbiol ; 17(2): 257-77, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25142751

RESUMO

Since a key requirement of known life forms is available water (water activity; aw ), recent searches for signatures of past life in terrestrial and extraterrestrial environments have targeted places known to have contained significant quantities of biologically available water. However, early life on Earth inhabited high-salt environments, suggesting an ability to withstand low water-activity. The lower limit of water activity that enables cell division appears to be ∼ 0.605 which, until now, was only known to be exhibited by a single eukaryote, the sugar-tolerant, fungal xerophile Xeromyces bisporus. The first forms of life on Earth were, though, prokaryotic. Recent evidence now indicates that some halophilic Archaea and Bacteria have water-activity limits more or less equal to those of X. bisporus. We discuss water activity in relation to the limits of Earth's present-day biosphere; the possibility of microbial multiplication by utilizing water from thin, aqueous films or non-liquid sources; whether prokaryotes were the first organisms able to multiply close to the 0.605-aw limit; and whether extraterrestrial aqueous milieux of ≥ 0.605 aw can resemble fertile microbial habitats found on Earth.


Assuntos
Divisão Celular , Ecossistema , Meio Ambiente Extraterreno , Células Procarióticas/fisiologia , Microbiologia da Água , Água , Archaea/citologia , Ascomicetos/citologia , Ascomicetos/fisiologia , Bactérias/citologia , Exobiologia , Células Procarióticas/citologia , Salinidade , Cloreto de Sódio
18.
Orig Life Evol Biosph ; 45(1-2): 207-18, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25773584

RESUMO

The ubiquity of phosphorus (P) in modern biochemistry suggests that P may have participated in prebiotic chemistry prior to the emergence of life. Of the major biogenic elements, phosphorus alone lacks a substantial volatile phase and its ultimate source therefore had to have been a mineral. However, as most native P minerals are chemically un-reactive within the temperature-pressure-pH regimes of contemporary life, it begs the question as to whether the most primitive early living systems on earth had access to a more chemically reactive P-mineral inventory. The meteoritic mineral schreibersite has been proposed as an important source of reactive P on the early earth. The chemistry of schreibersite as a P source is summarized and reviewed here. Recent work has also shown that reduced oxidation state P compounds were present on the early earth; these compounds lend credence to the relevance of schreibersite as a prebiotic mineral. Ultimately, schreibersite will oxidize to phosphate, but several high-energy P intermediates may have provided the reactive material necessary for incorporating P into prebiotic molecules.


Assuntos
Evolução Química , Minerais/química , Fósforo/química , Água/química , Planeta Terra , Meteoroides , Origem da Vida , Oxirredução
19.
J Obstet Gynaecol Res ; 41(9): 1337-44, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26017543

RESUMO

AIM: Renal and obstetric outcomes in pregnancy after kidney transplantation in Singapore were last studied in 2002. A review of these outcomes in Singapore is now timely following advances in transplant and obstetric medicine. The aim was to evaluate the renal and obstetric outcomes in pregnancy after kidney transplantation in a Singapore tertiary center. METHODS: Kidney transplant recipients who underwent pregnancy after transplantation at Singapore General Hospital between January 2001 and December 2012 were identified. Data on demographics, comorbidities and clinical outcomes were collected. RESULTS: There were 10 pregnancies identified in nine recipients. The median age of recipient at childbearing was 34.6 years (IQR, 32.8-36.8) and the median interval from transplantation to conception was 69 months (IQR, 38-97). There was no difference between the median pre-pregnancy estimated glomerular filtration rate (eGFR) (47.9 mL/min/1.73 m(2); IQR, 38.4-56.8) and median eGFR at time of last post-partum follow up (43.9 mL/min/1.73 m(2); IQR, 34.5-48.7, P = 0.549). Borderline allograft rejection occurred in one recipient (10.0%) 36 days after birth due to non-adherence to immunosuppressive medication, with subsequent allograft loss 37 months after birth. No mortalities were recorded during the study period. All the 10 pregnancies (100%) ended in singleton live births. Pre-eclampsia occurred in five pregnancies (50.0%), and there were seven (70.0%) preterm deliveries. The median gestational age was 35.4 weeks (IQR, 32.6-38.2) and the median birthweight was 2353 g (IQR, 1811-2648). CONCLUSION: Post-transplantation pregnancies ended successfully with no significant worsening of allograft function, but they were associated with risks to both recipients and newborns.


Assuntos
Transplante de Rim , Rim/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Resultado da Gravidez , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Singapura
20.
Int Urol Nephrol ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649519

RESUMO

BACKGROUND: Due to the excess demand for deceased donor kidneys, risk quantification scores were developed to help with kidney allocation. The kidney donor risk index (KDRI) is used in the US kidney allocation system. We currently use expanded criteria (UNOS) and Remuzzi scoring for allocation of deceased donor kidneys and the utility of KDRI in our cohort is unknown. We aim to evaluate the association of KDRI with relation to 5 year graft and patient survival. METHODS: Retrospective cohort study of 225 adults who received a deceased donor kidney transplant between 1 Nov 2005 and 30 June 2014. Patients were followed up for 5 years or until graft-loss or death. Implant biopsies of donor kidneys were done and the Remuzzi score was calculated. RESULTS: The median age was 48 (IQR 42, 52.5) years and 50.7% were male. KDRI-USA, KDRI-THAI, and KDRI-AUST were found to have no correlation with 5 year graft survival. Donor characteristics which define an expanded criteria donor kidney, not associated with 5 year graft survival are age (p = 0.58), terminal creatinine (p = 0.71) and history of hypertension (p = 0.35). Donor cerebrovascular accident (CVA) as a cause of death (p = 0.02) and Remuzzi score were associated with graft survival at 5 years, with 75.8% with Remuzzi score ≤ 3 vs 24.2% with Remuzzi score of > 3 achieving 5 year graft survival (p = 0.001). CONCLUSION: The association of KDRI with graft and patient survival was not demonstrated in our cohort. Histological assessment of the transplant kidney remains the best method of predicting long-term survival during donor selection.

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