RESUMO
Hereditary complement C3 deficiency is associated with recurrent bacterial infections and proliferative glomerulonephritis. We describe a case of an adult with complete deficiency of complement C3 due to homozygous mutations in C3 gene: c.1811delT (Val604Glyfs*2), recurrent bacterial infections, crescentic glomerulonephritis, and end-stage renal failure. Following isolated kidney transplantation he would remain C3 deficient with a similar, or increased, risk of infections and glomerulonephritis. As C3 is predominantly synthesized in the liver, with a small proportion of C3 monocyte derived and kidney derived, he proceeded to simultaneous liver-kidney transplantation. The procedure has been successful with restoration of his circulating C3 levels, normal liver and kidney function at 26 months of follow-up. Simultaneous liver-kidney transplant is a viable option to be considered in this rare setting.
Assuntos
Glomerulonefrite , Falência Renal Crônica , Transplante de Rim , Adulto , Complemento C3/genética , Humanos , Rim , Falência Renal Crônica/cirurgia , Fígado , MasculinoRESUMO
Diaphanous (Dia)-related formins (DRFs) coordinate cytoskeletal remodeling by controlling actin nucleation and microtubule (MT) stabilization to facilitate processes such as cell polarization and migration; yet the full extent of their activities remains unknown. Here, we uncover two discrete roles and functions of DRFs during early human immunodeficiency virus type 1 (HIV-1) infection. Independent of their actin regulatory activities, Dia1 and Dia2 facilitated HIV-1-induced MT stabilization and the intracellular motility of virus particles. However, DRFs also bound in vitro assembled capsid-nucleocapsid complexes and promoted the disassembly of HIV-1 capsid (CA) shell. This process, also known as "uncoating," is among the most poorly understood stages in the viral lifecycle. Domain analysis and structure modeling revealed that regions of Dia2 that bound viral CA and mediated uncoating as well as early infection contained coiled-coil domains, and that these activities were genetically separable from effects on MT stabilization. Our findings reveal that HIV-1 exploits discrete functions of DRFs to coordinate critical steps in early infection and identifies Dia family members as regulators of the poorly understood process of HIV-1 uncoating.
Assuntos
Proteínas de Transporte/metabolismo , HIV-1/metabolismo , Desenvelopamento do Vírus , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transporte Biológico , Capsídeo/metabolismo , Proteínas de Transporte/genética , Linhagem Celular , Linhagem Celular Tumoral , Forminas , Células HEK293 , HIV-1/fisiologia , Humanos , Células Jurkat , Microscopia Confocal , Microtúbulos/metabolismo , Imagem com Lapso de Tempo/métodosRESUMO
We developed a new method for the conditional regulation of CRISPR/Cas9 activity in mammalian cells and zebrafish embryos using photochemically activated, caged guide RNAs (gRNAs). Caged gRNAs are generated by substituting four nucleobases evenly distributed throughout the 5'-protospacer region with caged nucleobases during synthesis. Caging confers complete suppression of gRNA:dsDNA-target hybridization and rapid restoration of CRISPR/Cas9 function upon optical activation. This tool offers simplicity and complete programmability in design, high spatiotemporal specificity in cells and zebrafish embryos, excellent off-to-on switching, and stability by preserving the ability to form Cas9:gRNA ribonucleoprotein complexes. Caged gRNAs are novel tools for the conditional control of gene editing, thereby enabling the investigation of spatiotemporally complex physiological events by obtaining a better understanding of dynamic gene regulation.
Assuntos
Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , RNA Guia de Cinetoplastídeos/genética , Peixe-Zebra , Animais , Linhagem Celular , Hibridização de Ácido Nucleico , Análise Espaço-Temporal , Fatores de TempoRESUMO
5-Formylcytidine (f(5)C), a previously discovered natural nucleotide in the mitochondrial tRNA of many species including human, has been recently detected as the oxidative product of 5-methylcytidine (m(5)C) through 5-hydroxymethylcytidine (hm(5)C) in total RNA of mammalian cells. The discovery indicated that these cytosine derivatives in RNA might also play important epigenetic roles similar as in DNA, which has been intensively investigated in the past few years. In this paper, we studied the base pairing specificity of f(5)C in different RNA duplex contexts. We found that the 5-formyl group could increase duplex thermal stability and enhance base pairing specificity. We present three high-resolution crystal structures of an octamer RNA duplex [5'-GUA(f(5)C)GUAC-3']2 that have been solved under three crystallization conditions with different buffers and pH values. Our results showed that the 5-formyl group is located in the same plane as the cytosine base and forms an intra-residue hydrogen bond with the amino group in the N4 position. In addition, this modification increases the base stacking between the f(5)C and the neighboring bases while not causing significant global and local structure perturbations. This work provides insights into the effects of 5-formylcytosine on RNA duplex.
Assuntos
Citosina/análogos & derivados , RNA de Cadeia Dupla/química , Pareamento de Bases , Dicroísmo Circular , Cristalografia por Raios X , Citosina/química , Conformação de Ácido Nucleico , Desnaturação de Ácido Nucleico , TermodinâmicaRESUMO
Activated platelets facilitate blood coagulation by exposing phosphatidylserine (PS) and releasing microvesicles (MVs). However, the potent physiological agonists thrombin and collagen poorly induce PS exposure when a single agonist is used. To obtain a greater procoagulant response, thrombin is commonly used in combination with glycoprotein VI agonists. However, even under these conditions, only a percentage of platelets express procoagulant activity. To date, it remains unclear why platelets poorly expose PS even when stimulated with multiple agonists and what the signaling pathways are of soluble agonist-induced platelet procoagulant activity. Here we show that physiological levels of shear present in blood significantly enhance agonist-induced platelet PS exposure and MV release, enabling low doses of a single agonist to induce full-scale platelet procoagulant activity. PS exposed on the platelet surface was immediately released as MVs, revealing a tight coupling between the 2 processes under shear. Using platelet-specific Rac1(-/-) mice, we discovered that Rac1 plays a common role in mediating the low-dose agonist-induced procoagulant response independent of platelet aggregation, secretion, and the apoptosis pathway. Platelet-specific Rac1 function was not only important for coagulation in vitro but also for fibrin accumulation in vivo following laser-induced arteriolar injury.
Assuntos
Neuropeptídeos/sangue , Ativação Plaquetária/fisiologia , Proteínas rac1 de Ligação ao GTP/sangue , Animais , Fenômenos Biomecânicos , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Micropartículas Derivadas de Células/fisiologia , Colágeno/administração & dosagem , Colágeno/fisiologia , Humanos , Camundongos , Camundongos Knockout , Neuropeptídeos/deficiência , Neuropeptídeos/genética , Fosfatidilserinas/sangue , Ativação Plaquetária/efeitos dos fármacos , Transdução de Sinais , Trombina/administração & dosagem , Trombina/fisiologia , Proteínas rac1 de Ligação ao GTP/deficiência , Proteínas rac1 de Ligação ao GTP/genéticaRESUMO
Obtaining accurate and precise results for total cyanide concentrations in wastewater samples is fraught with positive and negative interferences. Even the United States Environmental Protection Agency has acknowledged that it may be difficult or impossible to adequately mitigate all interferences. We demonstrated that a field spike of complex cyanide can be successfully used to demonstrate when sampling, preservation, pre-treatment, and analysis techniques are working adequately to retain any cyanide present in the sample without causing false positives or false negatives. For 257 industrial wastewater effluent samples collected at a wide variety of Greater Boston industries, 237 (92.2%) had usable field spike recoveries, averaging 86.2% recovery. Field spike recoveries for problematic industries that had very high or very low field spike recoveries were useful to show when alternative preservations and field dilutions were successfully preserving total cyanide. The field spike approach is general and should also work in a similar manner for raw and treated drinking water samples.
Assuntos
Cianetos/química , Resíduos Industriais/análise , Águas Residuárias/química , Poluentes Químicos da Água/química , Monitoramento Ambiental , Eliminação de Resíduos LíquidosRESUMO
Astronauts (and recently businessmen) often express a renewed sense of responsibility for taking care of the environment, after observing the overwhelming beauty of Earth from space. Despite recent attention for this "overview effect", it is unclear whether experiencing the effect directly impacts pro-environmental behaviour. Using a virtual reality experience, the current research tests in two experimental studies the direct impact of an immersive overview effect experience on both short-term and longer term subsequent pro-environmental behaviours (donating to an environmental NGO, consuming less diary and meat). Furthermore, it investigates whether the technological immersiveness of the VR experience amplifies the effect, and the mediating role of connectedness to nature. Results show no effects of the short (7 minutes) overview effect VR video on pro-environmental behaviour (Study 1). For the longer video (15 minutes, Study 2), the results showed that the most immersive experience (video featuring meditative music and voice-over) appeared to increase connection with nature and higher donation amounts to an eco-NGO, but not significantly. No effects were found for subsequent meat and dairy consumption behaviours (measured on day 2, 4, and 6). These findings contribute to a deeper understanding of the specific features determining the effectiveness of the overview effect experiences on actual pro-environmental behaviour, providing important insights to businesses and educational institutions.
Assuntos
Realidade Virtual , Humanos , Masculino , Adulto , Feminino , Planeta Terra , Astronautas/psicologia , Adulto Jovem , Meio Ambiente , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Glomerular filtration rate (GFR) is a measure of kidney function, commonly estimated using equations that adjust serum creatinine concentration for age, race, and sex. The Modification of Diet in Renal Disease (MDRD) Study equation is widely used, but underestimates GFR at higher levels. The serum creatinine-based Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI(cr)) equation generally provides more accurate estimation at GFR >60 mL/min/1.73 m(2). Newer equations have been reported using cystatin C concentration either alone (CKD-EPI(cys)) or in combination with creatinine concentration (CKD-EPI(cr-cys)). None of these equations has been well validated in older people. We tested the accuracy of these equations in people 74 years or older compared with GFR measured by a reference method. STUDY DESIGN: Diagnostic test evaluation in a prospective cohort. SETTING & PARTICIPANTS: Participants (n = 394; median age, 80 [range, 74-97] years) recruited from nephrology clinics and the community. INDEX TEST: GFR estimated using the MDRD Study, CKD-EPI(cr), CKD-EPI(cys) and CKD-EPI(cr-cys) equations. REFERENCE TEST: GFR measured using an iohexol clearance method. RESULTS: Median measured GFR was 53.4 (range, 7.2-100.9) mL/min/1.73 m(2). MDRD Study-, CKD-EPI(cr)-, and CKD-EPI(cr-cys)-estimated GFRs overestimated GFR (median differences of 3.5 [P< 0.001], 1.7 [P < 0.001], and 0.8 [P = 0.02] mL/min/1.73 m(2), respectively); the CKD-EPI(cys) equation was unbiased. Accuracy (percentage of estimates within 30% of measured GFR [P(30)]) was 81%, 83%, 86%, and 86% for the MDRD Study, CKD-EPI(cr), CKD-EPI(cys), and CKD-EPI(cr-cys) equations, respectively. Accuracy of the MDRD Study equation was inferior (P = 0.004) to the CKD-EPI(cr) equation at GFR >60 mL/min/1.73 m(2). LIMITATIONS: Those of non-European ancestry were not included. For practical reasons, only a 4-hour sampling protocol was used for iohexol clearance. CONCLUSIONS: The CKD-EPI(cr) equation appeared less biased and was more accurate than the MDRD Study equation. No equation achieved an ideal P(30) in the overall population. Our data suggest that GFR estimation is as satisfactory in older people of European ancestry as it has been reported to be in younger individuals.
Assuntos
Comportamento Alimentar , Taxa de Filtração Glomerular/fisiologia , Modelos Teóricos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Creatinina/sangue , Feminino , Humanos , Iohexol/metabolismo , Masculino , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico , Reprodutibilidade dos Testes , Fatores de Risco , População BrancaRESUMO
Abnormalities of bone mineral metabolism and vascular calcification are prevalent in patients with kidney failure. Clinical management is based on biochemical targets, in particular parathyroid hormone (PTH) concentrations, but this has many limitations including high biological variation. A possible alternative is bone-specific alkaline phosphatase (ALP); therefore, we evaluated the biological variation of this marker in patients undergoing hemodialysis. Bone ALP was measured in non-fasting serum samples taken twice a week over a 6-week period in 22 stable hemodialysis patients and 12 healthy volunteers. The within-individual coefficients of variance were calculated and used to derive the critical difference required to be certain that an observed change was significant. The coefficient of variance for bone ALP was significantly higher in hemodialysis patients compared to healthy individuals. Seven samples were required to estimate the homeostatic set point of bone ALP, within 10%, in a hemodialysis patient. The concentration of serial bone ALP measurements would need to change by 36% between any two measurements before it can be considered a significant change. Since the biological variation of bone ALP is less than half that reported for PTH, our study provides further support for the use of bone ALP as an alternative marker of bone mineral metabolism in the setting of chronic kidney disease-mineral and bone disorder.
Assuntos
Fosfatase Alcalina/sangue , Doenças Ósseas Metabólicas/diagnóstico , Remodelação Óssea , Osso e Ossos/enzimologia , Hormônio Paratireóideo/sangue , Diálise Renal , Insuficiência Renal/terapia , Adulto , Biomarcadores/sangue , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/etiologia , Estudos de Casos e Controles , Inglaterra , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Diálise Renal/efeitos adversos , Insuficiência Renal/sangue , Insuficiência Renal/complicações , Reprodutibilidade dos Testes , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Hyperphosphataemia is a primary risk factor for patients with end-stage kidney failure. Phosphate clearance by traditional thrice-weekly standard haemodialysis is inadequate for patients achieving recommended dietary protein goals. We investigated whether phosphate control was improved by adding convective clearance with haemodiafiltration. METHODS: We audited pre-midweek session calcium and phosphate levels in 5366 adult patients, 4515 treated by haemodialysis and 851 by on-line haemodiafiltration. RESULTS: The cohorts were similar for age, sex and dialysis vintage. Serum phosphate was lower in the haemodiafiltration cohort (1.42 +/- 0.61 mmol/l) compared to the haemodialysis cohort (1.53 +/- 0.53 mmol/l; P < 0.001), as was the calcium-phosphate product (3.31 +/- 1.53 vs 3.5 +/- 1.33 mmol(2)/l(2), respectively; P < 0.001) despite a shorter treatment session time (3.68 +/- 0.44 vs 3.92 +/- 0.49 h; P < 0.001). Parathyroid hormone levels were similar. CONCLUSIONS: The results of this audit suggest that haemodiafiltration offers improved phosphate control compared to standard intermittent haemodialysis.
Assuntos
Auditoria Clínica , Hemodiafiltração , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Fosfatos/sangue , Diálise Renal , Idoso , Cálcio/sangue , Feminino , Humanos , Hiperfosfatemia/epidemiologia , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Estudos Prospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Patients achieving the Kidney Disease Outcomes Quality Initiative (KDOQI) bone mineral clinical practice guidelines have been reported to have improved survival. Many factors affecting calcium and phosphate control are not modifiable; however, we wished to determine whether differences in dialysis treatment could affect achievement of KDOQI clinical guideline targets. METHODS: We audited pre-mid-week session calcium and phosphate levels in 5,324 adult patients receiving thrice weekly dialysis in the 14 Pan Thames centres: 60% male, mean age 62 ± 16 years, median dialysis vintage 29 months (14-58), 84% treated by haemodialysis, 16% by online haemodiafiltration, median session time 4.0 h (3.5-4.0). RESULTS: Patients achieving the KDOQI guidelines varied between the centres: 23.4-60% for calcium, 31.7-56.7% for phosphate, 60-87.3% for calcium-phosphate product, 17.1-46.8% for parathyroid hormone (PTH) and 1.8-10.8% for all 4 targets. Those centres which used the highest dialysate calcium concentrations (1.5 mmol/l, 3 mEq/l) had more patients above the KDOQI serum calcium and more below the PTH target, than those centres using the lowest calcium dialysates (1 mmol/l, 2 mEq/l), with χ(2) = 85.1 and χ(2) = 52.4, p < 0.001, respectively. On logistic regression analysis, serum phosphate was negatively associated with duration of dialysis session time (F = 21.4, p = 0.000) and haemodiafiltration (F = 9.6, p = 0.000), respectively. CONCLUSIONS: Although many of the factors determining calcium and phosphate control in haemodialysis patients are unmodifiable, dialysate calcium concentration, the duration of the dialysis session and haemodiafiltration all had an impact on calcium, phosphate and PTH.
Assuntos
Osso e Ossos/química , Guias de Prática Clínica como Assunto/normas , Diálise Renal/métodos , Idoso , Cálcio/sangue , Soluções para Diálise/química , Feminino , Hemodiafiltração , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Diálise Renal/normas , Fatores de Tempo , Resultado do TratamentoRESUMO
Human mitochondrial methionine transfer RNA (hmtRNA(Met)(CAU)) has a unique post-transcriptional modification, 5-formylcytidine, at the wobble position-34 (f(5)C(34)). The role of this modification in (hmtRNA(Met)(CAU)) for the decoding of AUA, as well as AUG, in both the peptidyl- and aminoacyl-sites of the ribosome in either chain initiation or chain elongation is still unknown. We report the first synthesis and analyses of the tRNA's anticodon stem and loop domain containing the 5-formylcytidine modification. The modification contributes to the tRNA's anticodon domain structure, thermodynamic properties and its ability to bind codons AUA and AUG in translational initiation and elongation.
Assuntos
Anticódon/química , Citidina/análogos & derivados , Biossíntese de Proteínas , RNA de Transferência de Metionina/química , RNA/química , Sequência de Bases , Códon/metabolismo , Citidina/química , Humanos , Dados de Sequência Molecular , Conformação de Ácido Nucleico , RNA Mitocondrial , RNA de Transferência de Metionina/síntese química , RNA de Transferência de Metionina/metabolismo , TermodinâmicaRESUMO
Silver-doped carbon nanofibers (SDCNF) are used as the base material for the selective capture of Escherichia coli in microfluidic systems. Fibers were spun in a glovebox with dry atmosphere maintained by forced dry air pumped through the closed environment. This affected the evaporation rate of the solvent during the electrospinning process and the distribution of silver particles within the fiber. Antibodies are immobilized on the surface of the silver-doped polyacrylonitrile (PAN) based carbon nanofibers via a three-step process. The negatively charged silver particles present on the surface of the nanofibers provide suitable sites for positively charged biotinylated poly-(l)-lysine-graft-poly-ethylene-glycol (PLL-g-PEG biotin) conjugate attachment. Streptavidin and a biotinylated anti-E. coli antibody were then added to create anti-E. coli surface functionalized (AESF) nanofibers. Functionalized fibers were able to immobilize up to 130 times the amount of E. coli on the fiber surface compared to neat silver doped fibers. Confocal images show E. coli remains immobilized on fiber mat surface after extensive rinsing showing the bacteria is not simply a result of non-specific binding. To demonstrate selectivity and functionalization with both gram negative and gram-positive antibodies, anti-Staphylococcus aureus surface functionalized (ASSF) nanofibers were also prepared. Experiments with AESF performed with Staphylococcus aureus (S. aureus) and ASSF with E. coli show negligible binding to the fiber surface showing the selectivity of the functionalized membranes. This surface functionalization can be done with a variety of antibodies for tunable selective pathogen capture.
RESUMO
The global outbreak of the coronavirus pandemic has led to a significant reduction of traffic and traffic-related urban air pollution. One important pollutant in this context is NO2. Sudden change in NO2 emissions related to reduction of urban traffic due to infection protection measures can be detected in Düsseldorf, Germany with continuous measurements of down-welling light with a RoX automated field-spectrometer. In comparison to a nearby reference instrument, a waveband around 590 nm was identified as significant for the retrieval in the VIS-NIR spectral range. A decision tree based on principal components which were decomposed from down-welling radiance spectra has been the most robust approach to retrieved NO2 values. Better differentiation of the NO2 value-range is achieved with a partial least square regression model. The results suggest that traffic-related changes of NOx pollution in urban air can be detected through continuous down-welling radiance measurements with inexpensive automated field-spectrometer systems.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Coronavirus , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monitoramento Ambiental , Alemanha/epidemiologia , Pandemias , Emissões de Veículos/análiseRESUMO
Biomolecule immobilization has attracted the attention of various fields such as fine chemistry and biomedicine for their use in several applications such as wastewater, immunosensors, biofuels, et cetera. The performance of immobilized biomolecules depends on the substrate and the immobilization method utilized. Electrospun nanofibers act as an excellent substrate for immobilization due to their large surface area to volume ratio and interconnectivity. While biomolecules can be immobilized using adsorption and encapsulation, covalent immobilization offers a way to permanently fix the material to the fiber surface resulting in high efficiency, good specificity, and excellent stability. This review aims to highlight the various covalent immobilization techniques being utilized and their benefits and drawbacks. These methods typically fall into two categories: (1) direct immobilization and (2) use of crosslinkers. Direct immobilization techniques are usually simple and utilize the strong electrophilic functional groups on the nanofiber. While crosslinkers are used as an intermediary between the nanofiber substrate and the biomolecule, with some crosslinkers being present in the final product and others simply facilitating the reactions. We aim to provide an explanation of each immobilization technique, biomolecules commonly paired with said technique and the benefit of immobilization over the free biomolecule.
RESUMO
BACKGROUND: Autologous stem cell transplantation (ASCT) and novel therapies have improved the prognosis for patients with multiple myeloma (MM). For those who undergo ASCT while on dialysis, a similar survival compared with the overall MM population has been reported. Therefore, for patients achieving remission following ASCT, kidney transplantation is an attractive option, offering an improved quality of life and significant economic advantage. METHOD: This case series investigates the outcome of five patients who underwent an ASCT for MM with subsequent kidney transplantation between 2006 and 2012. RESULTS: Four patients presented with end-stage renal disease (ESRD) and one progressed to ESRD shortly after diagnosis. Induction chemotherapy regimens with novel agents including thalidomide and bortezomib were utilized. Following attainment of very good partial remission or complete remission, high-dose melphalan ASCTs were performed after a median of 10 months. Kidney transplantation (living donor n = 3, deceased donor n = 2) with tacrolimus-based immunosuppression regimens was completed at a median of 27 months after ASCT. Patients 1 and 3 experienced relapse of myeloma at 6 and 16 months after kidney transplantation. Patients 2, 4 and 5 remain alive at 55 months (median) after kidney transplantation with no evidence of relapse. CONCLUSION: Forty percent of our cohort experienced a relapse in MM within 2 years of kidney transplantation. Death-censored graft survival and patient survival were 80% at 4 years. Our study adds to the growing literature supporting kidney transplantation following successful ASCT for MM and is useful when counselling patients regarding renal and haematological outcomes.
RESUMO
BACKGROUND: Circulating asymmetric dimethylarginine and symmetric dimethylarginine are increased in patients with kidney disease. Symmetric dimethylarginine is considered a good marker of glomerular filtration rate, while asymmetric dimethylarginine is a marker of cardiovascular risk. However, a link between symmetric dimethylarginine and all-cause mortality has been reported. In the present study, we evaluated both dimethylarginines as risk and glomerular filtration rate markers in a cohort of elderly white individuals, both with and without chronic kidney disease. METHODS: Glomerular filtration rate was measured in 394 individuals aged >74 years using an iohexol clearance method. Plasma asymmetric dimethylarginine, symmetric dimethylarginine and iohexol were measured simultaneously using isotope dilution tandem mass spectrometry. RESULTS: Plasma asymmetric dimethylarginine concentrations were increased ( P < 0.01) in people with glomerular filtration rate <60 mL/min/1.73 m2 compared with those with glomerular filtration rate ≥60 mL/min/1.73 m2, but did not differ ( P > 0.05) between those with glomerular filtration rate 30-59 mL/min/1.73 m2 and <30 mL/min/1.73 m2. Plasma symmetric dimethylarginine increased consistently across declining glomerular filtration rate categories ( P < 0.0001). Glomerular filtration rate had an independent effect on plasma asymmetric dimethylarginine concentration, while glomerular filtration rate, gender, body mass index and haemoglobin had independent effects on plasma symmetric dimethylarginine concentration. Participants were followed up for a median of 33 months. There were 65 deaths. High plasma asymmetric dimethylarginine ( P = 0.0412) and symmetric dimethylarginine ( P < 0.0001) concentrations were independently associated with reduced survival. CONCLUSIONS: Among elderly white individuals with a range of kidney function, symmetric dimethylarginine was a better marker of glomerular filtration rate and a stronger predictor of outcome than asymmetric dimethylarginine. Future studies should further evaluate the role of symmetric dimethylarginine as a marker of outcome and assess its potential value as a marker of glomerular filtration rate.
Assuntos
Arginina/análogos & derivados , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/mortalidade , Idoso , Idoso de 80 Anos ou mais , Arginina/sangue , Biomarcadores/sangue , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Medição de RiscoRESUMO
BACKGROUND: Clinical management of peritoneal dialysis patients includes assessments of peritoneal and renal clearances of the low-molecular-weight endogenous solutes creatinine and urea. Cystatin C is a low-molecular-weight protein used as a glomerular filtration rate marker. We investigated whether serum cystatin C concentration is related to peritoneal and renal clearances of creatinine and urea. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 119 patients undergoing peritoneal dialysis in a single dialysis unit. PREDICTOR: Peritoneal, renal, and total clearance of urea as Kt/V(urea) and creatinine as weekly creatinine clearance (C(Cr)). Residual renal function (RRF) as the average of renal clearances of urea and creatinine. OUTCOMES & MEASUREMENTS: Serum concentrations of cystatin C measured by using a particle-enhanced nephelometric immunoassay. RESULTS: Serum cystatin C concentration was related inversely to RRF (Spearman rank correlation coefficient [r(s)] = -0.65; P < 0.001), total weekly C(Cr) (r(s) = -0.52; P < 0.001), and total Kt/V(urea) (r(s) = -0.23; P = 0.01). In a multiple regression model, weight, normalized protein catabolic rate, and RRF had independent effects on serum cystatin C concentrations. Additional multiple regression models showed that only the renal components of Kt/V(urea) and weekly C(Cr) contributed to serum cystatin C concentrations. LIMITATIONS: Absence of reference GFR method. CONCLUSIONS: Serum cystatin C concentrations reflect predominantly renal, not peritoneal, clearance. Serum cystatin C measurement may be a simple and practical alternative to measurement of RRF.
Assuntos
Líquido Ascítico/metabolismo , Creatinina/metabolismo , Cistatinas/sangue , Rim/metabolismo , Diálise Peritoneal , Ureia/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Estudos de Coortes , Creatinina/urina , Estudos Transversais , Cistatina C , Feminino , Taxa de Filtração Glomerular , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Projetos de Pesquisa , Ureia/urinaRESUMO
BACKGROUND: Chronic kidney disease (CKD) is common ( approximately 30%) in non-institutionalized older people but little is known about the prevalence of CKD amongst older people living in residential care. METHODS: An observational study of older subjects [n = 250, median age 86 (range 67-100) years, 79% female, 100% Caucasian, 16% diabetic, 48% hypertensive, 5% known renal disease, mean number of medications 7] who were recruited over a 9-month period from 155 residential care homes in east Kent (total population 3811) using a randomization process. The estimated glomerular filtration rate (eGFR, ml/min/1.73 m(2)) was calculated using the Cockcroft and Gault equation corrected for the body surface area and the simplified Modification of Diet in Renal Disease (MDRD) Study equation. Serum cystatin C concentration was also measured. RESULTS: Using the MDRD equation 18% had eGFR >/=60, 39% stage 3A CKD (eGFR 45-59), 34% stage 3B CKD (eGFR 30-44) and 10% stage 4 CKD (eGFR 15-29). By the Cockcroft-Gault equation the equivalent figures were 3%, 18%, 48% and 31%, respectively. Agreement between the equations for staging of CKD was poor (kappa = 0.07). However, >80% of residents were categorized as having stage 3 CKD (>40% stage 3B) or worse whichever equation was used. Serum cystatin C concentration was increased in 92% of the population. Increasing age and higher body mass index were predictive of decreased renal function. CONCLUSION: Significant CKD is prevalent and unrecognized in this population. This may have important management implications particularly for treatment with renally excreted drugs, fracture prevention or managing cardiovascular risk.