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1.
Am J Physiol Renal Physiol ; 316(1): F90-F100, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30303711

RESUMO

Obesity, metabolic syndrome, and renal injury are considered risk factors for type 2 diabetes, as well as kidney disease. Functional and structural changes in the kidney as consequence of obesity and metabolic syndrome may lead to impaired mineral metabolism in what is known as chronic kidney disease-mineral and bone disorder. Lifestyle interventions such as physical activity are good strategies to manage these pathologies and therefore, prevent the loss of kidney functionality and related complications in mineral metabolism. In this study, we have used 40 male Zucker rats that were randomly allocated into four different experimental groups, two of them (an obese and a lean one) performed an aerobic interval training protocol, and the other two groups were sedentary. At the end of the experimental period (8 wk), urine, plasma, and femur were collected for biochemical and mineral composition analysis, whereas the kidney was processed for histological studies. The obese rats exhibited albuminuria, glomerulosclerosis, and hypertrophy in glomeruli and renal tubule in some areas, together with alterations in mineral content of plasma but not of femur. The training protocol prevented the generation of albuminuria and glomerulosclerosis, showing a significant action on plasma and bone mineral levels. Therefore, the specific training protocol used in this study was able to prevent the development of diabetic nephropathy and affected the metabolism of certain minerals.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Fêmur/metabolismo , Glomerulonefrite/prevenção & controle , Treinamento Intervalado de Alta Intensidade , Rim/fisiopatologia , Minerais/sangue , Obesidade/terapia , Albuminúria/etiologia , Albuminúria/metabolismo , Albuminúria/fisiopatologia , Albuminúria/prevenção & controle , Animais , Biomarcadores/sangue , Biomarcadores/urina , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Modelos Animais de Doenças , Glomerulonefrite/etiologia , Glomerulonefrite/metabolismo , Glomerulonefrite/fisiopatologia , Hipertrofia , Rim/patologia , Masculino , Obesidade/complicações , Obesidade/metabolismo , Obesidade/fisiopatologia , Ratos Zucker , Recuperação de Função Fisiológica , Fatores de Tempo
2.
Am J Nephrol ; 48(5): 349-356, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30408788

RESUMO

BACKGROUND: The use of L-carnitine has been proposed in haemodialysis (HD) when deficiency is present to improve anaemia resistant to erythropoietin stimulating agent, intradialytic hypotension or cardiac failure. We tested the effects of L-carnitine supplementation on parameters of chronic kidney disease-mineral bone disorder. METHODS: CARNIDIAL was a randomized, double-blinded trial having included 92 incident HD subjects for a 1-year period to receive L-carnitine versus placebo. Determinant factors of C-terminal fibroblast growth factor 23 (cFGF23) and intact FGF23 were studied including Klotho level. The L-carnitine effect on mineral metabolism was analyzed between groups by mixed linear models for repeated measurements. RESULTS: Klotho was below the lower limit of quantification (LLOQ) in 55% of the 163 samples. In multivariate analysis, cFGF23 was positively correlated with calcium and phosphate and was higher in subjects having Klotho > LLOQ. No correlation existed between Klotho and phosphate and phosphate was even higher in subjects having Klotho > LLOQ (p < 0.001). Both forms of FGF23 were not related to iron markers nor to IV iron dose. No L-carnitine effect was detected on parathyroid hormone (PTH) or FGF23 during the study period where PTH slightly decreased over time, whereas FGF23 increased. But calcium and phosphate increased more in the L-carnitine group. CONCLUSION: L-carnitine supplementation increased calcium and phosphate plasma concentrations with no detected downregulation effect on PTH and FGF23. (Clinical Trial 00322322, May 5, 2006).


Assuntos
Calcificação Fisiológica/efeitos dos fármacos , Carnitina/administração & dosagem , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/terapia , Idoso , Cálcio/sangue , Cálcio/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Método Duplo-Cego , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Glucuronidase/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Fosfatos/metabolismo , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Resultado do Tratamento
3.
Cochrane Database Syst Rev ; 8: CD006023, 2018 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-30132304

RESUMO

BACKGROUND: Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent progression of chronic kidney disease-mineral and bone disorder (CKD-MBD). This is an update of a review first published in 2011. OBJECTIVES: The aim of this review was to assess the benefits and harms of phosphate binders for people with CKD with particular reference to relevant biochemical end-points, musculoskeletal and cardiovascular morbidity, hospitalisation, and death. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 July 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs of adults with CKD of any GFR category comparing a phosphate binder to another phosphate binder, placebo or usual care to lower serum phosphate. Outcomes included all-cause and cardiovascular death, myocardial infarction, stroke, adverse events, vascular calcification and bone fracture, and surrogates for such outcomes including serum phosphate, parathyroid hormone (PTH), and FGF23. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of Bias' tool and used the GRADE process to assess evidence certainty. We estimated treatment effects using random-effects meta-analysis. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardised MD (SMD) for continuous outcomes. MAIN RESULTS: We included 104 studies involving 13,744 adults. Sixty-nine new studies were added to this 2018 update.Most placebo or usual care controlled studies were among participants with CKD G2 to G5 not requiring dialysis (15/25 studies involving 1467 participants) while most head to head studies involved participants with CKD G5D treated with dialysis (74/81 studies involving 10,364 participants). Overall, seven studies compared sevelamer with placebo or usual care (667 participants), seven compared lanthanum to placebo or usual care (515 participants), three compared iron to placebo or usual care (422 participants), and four compared calcium to placebo or usual care (278 participants). Thirty studies compared sevelamer to calcium (5424 participants), and fourteen studies compared lanthanum to calcium (1690 participants). No study compared iron-based binders to calcium. The remaining studies evaluated comparisons between sevelamer (hydrochloride or carbonate), sevelamer plus calcium, lanthanum, iron (ferric citrate, sucroferric oxyhydroxide, stabilised polynuclear iron(III)-oxyhydroxide), calcium (acetate, ketoglutarate, carbonate), bixalomer, colestilan, magnesium (carbonate), magnesium plus calcium, aluminium hydroxide, sucralfate, the inhibitor of phosphate absorption nicotinamide, placebo, or usual care without binder. In 82 studies, treatment was evaluated among adults with CKD G5D treated with haemodialysis or peritoneal dialysis, while in 22 studies, treatment was evaluated among participants with CKD G2 to G5. The duration of study follow-up ranged from 8 weeks to 36 months (median 3.7 months). The sample size ranged from 8 to 2103 participants (median 69). The mean age ranged between 42.6 and 68.9 years.Random sequence generation and allocation concealment were low risk in 25 and 15 studies, respectively. Twenty-seven studies reported low risk methods for blinding of participants, investigators, and outcome assessors. Thirty-one studies were at low risk of attrition bias and 69 studies were at low risk of selective reporting bias.In CKD G2 to G5, compared with placebo or usual care, sevelamer, lanthanum, iron and calcium-based phosphate binders had uncertain or inestimable effects on death (all causes), cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. Sevelamer may lead to constipation (RR 6.92, CI 2.24 to 21.4; low certainty) and lanthanum (RR 2.98, CI 1.21 to 7.30, moderate certainty) and iron-based binders (RR 2.66, CI 1.15 to 6.12, moderate certainty) probably increased constipation compared with placebo or usual care. Lanthanum may result in vomiting (RR 3.72, CI 1.36 to 10.18, low certainty). Iron-based binders probably result in diarrhoea (RR 2.81, CI 1.18 to 6.68, high certainty), while the risks of other adverse events for all binders were uncertain.In CKD G5D sevelamer may lead to lower death (all causes) (RR 0.53, CI 0.30 to 0.91, low certainty) and induce less hypercalcaemia (RR 0.30, CI 0.20 to 0.43, low certainty) when compared with calcium-based binders, and has uncertain or inestimable effects on cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. The finding of lower death with sevelamer compared with calcium was present when the analysis was restricted to studies at low risk of bias (RR 0.50, CI 0.32 to 0.77). In absolute terms, sevelamer may lower risk of death (all causes) from 210 per 1000 to 105 per 1000 over a follow-up of up to 36 months, compared to calcium-based binders. Compared with calcium-based binders, lanthanum had uncertain effects with respect to all-cause or cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification and probably had reduced risks of treatment-related hypercalcaemia (RR 0.16, CI 0.06 to 0.43, low certainty). There were no head-to-head studies of iron-based binders compared with calcium. The paucity of placebo-controlled studies in CKD G5D has led to uncertainty about the effects of phosphate binders on patient-important outcomes compared with placebo.It is uncertain whether the effects of binders on clinically-relevant outcomes were different for patients who were and were not treated with dialysis in subgroup analyses. AUTHORS' CONCLUSIONS: In studies of adults with CKD G5D treated with dialysis, sevelamer may lower death (all causes) compared to calcium-based binders and incur less treatment-related hypercalcaemia, while we found no clinically important benefits of any phosphate binder on cardiovascular death, myocardial infarction, stroke, fracture or coronary artery calcification. The effects of binders on patient-important outcomes compared to placebo are uncertain. In patients with CKD G2 to G5, the effects of sevelamer, lanthanum, and iron-based phosphate binders on cardiovascular, vascular calcification, and bone outcomes compared to placebo or usual care, are also uncertain and they may incur constipation, while iron-based binders may lead to diarrhoea.


Assuntos
Compostos de Cálcio/uso terapêutico , Quelantes/uso terapêutico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Fósforo/sangue , Poliaminas/uso terapêutico , Adulto , Idoso , Cálcio/sangue , Compostos de Cálcio/efeitos adversos , Causas de Morte , Quelantes/efeitos adversos , Doença Crônica , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Progressão da Doença , Humanos , Hipercalcemia/induzido quimicamente , Compostos de Ferro/efeitos adversos , Compostos de Ferro/uso terapêutico , Lantânio/efeitos adversos , Lantânio/uso terapêutico , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Poliaminas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal/estatística & dados numéricos , Sevelamer/uso terapêutico
4.
Kidney Int ; 94(1): 102-113, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29716795

RESUMO

Chronic kidney disease (CKD) causes dysregulation of mineral metabolism, vascular calcification and renal osteodystrophy, an entity called 'CKD-Mineral and Bone Disorder' (CKD-MBD). Here we determine whether metformin, an anti-diabetic drug, exerts favorable effects on progressive, severe CKD and concomitant mineral metabolism disturbances. Rats with CKD-MBD, induced by a 0.25% adenine diet for eight weeks, were treated with 200 mg/kg/day metformin or vehicle from one week after CKD induction onward. Severe, stable CKD along with marked hyperphosphatemia and hypocalcemia developed in these rats which led to arterial calcification and high bone turnover disease. Metformin protected from development toward severe CKD. Metformin-treated rats did not develop hyperphosphatemia or hypocalcemia and this prevented the development of vascular calcification and inhibited the progression toward high bone turnover disease. Kidneys of the metformin group showed significantly less cellular infiltration, fibrosis and inflammation. To study a possible direct effect of metformin on the development of vascular calcification, independent of its effect on renal function, metformin (200 mg/kg/day) or vehicle was dosed for ten weeks to rats with warfarin-induced vascular calcification. The drug did not reduce aorta or small vessel calcification in this animal model. Thus, metformin protected against the development of severe CKD and preserved calcium phosphorus homeostasis. As a result of its beneficial impact on renal function, associated comorbidities such as vascular calcification and high bone turnover disease were also prevented.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Calcificação Vascular/prevenção & controle , Adenina/toxicidade , Animais , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Modelos Animais de Doenças , Humanos , Masculino , Ratos , Ratos Wistar , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/metabolismo , Índice de Gravidade de Doença , Resultado do Tratamento , Calcificação Vascular/etiologia , Calcificação Vascular/metabolismo , Varfarina/toxicidade
5.
Ann Intern Med ; 168(6): 422-430, 2018 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-29459980

RESUMO

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a selective update of the prior CKD-MBD guideline published in 2009. The guideline update and the original publication are intended to assist practitioners caring for adults with CKD and those receiving long-term dialysis. Methods: Development of the guideline update followed an explicit process of evidence review and appraisal. The approach adopted by the Work Group and the evidence review team was based on systematic reviews of relevant trials, appraisal of the quality of the evidence, and rating of the strength of recommendations according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Searches of the English-language literature were conducted through September 2015 and were supplemented with targeted searches through February 2017. Final modification of the guidelines was informed by a public review process involving numerous stakeholders, including patients, subject matter experts, and industry and national organizations. Recommendations: The update process resulted in the revision of 15 recommendations. This synopsis focuses primarily on recommendations for diagnosis of and testing for CKD-MBD and treatment of CKD-MBD that emphasizes decreasing phosphate levels, maintaining calcium levels, and addressing elevated parathyroid hormone levels in adults with CKD stage G3a to G5 and those receiving dialysis. Key elements include basing treatment on trends in laboratory values rather than a single abnormal result and being cautious to avoid hypercalcemia when treating secondary hyperparathyroidism.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Humanos , Hipercalcemia/prevenção & controle , Hiperfosfatemia/sangue , Hiperfosfatemia/prevenção & controle , Hormônio Paratireóideo/sangue , Diálise Renal
6.
Kidney Int ; 93(1): 147-158, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28843411

RESUMO

We examined activin receptor type IIA (ActRIIA) activation in chronic kidney disease (CKD) by signal analysis and inhibition in mice with Alport syndrome using the ActRIIA ligand trap RAP-011 initiated in 75-day-old Alport mice. At 200 days of age, there was severe CKD and associated Mineral and Bone Disorder (CKD-MBD), consisting of osteodystrophy, vascular calcification, cardiac hypertrophy, hyperphosphatemia, hyperparathyroidism, elevated FGF23, and reduced klotho. The CKD-induced bone resorption and osteoblast dysfunction was reversed, and bone formation was increased by RAP-011. ActRIIA inhibition prevented the formation of calcium apatite deposits in the aortic adventitia and tunica media and significantly decreased the mean aortic calcium concentration from 0.59 in untreated to 0.36 mg/g in treated Alport mice. Aortic ActRIIA stimulation in untreated mice increased p-Smad2 levels and the transcription of sm22α and αSMA. ActRIIA inhibition reversed aortic expression of the osteoblast transition markers Runx2 and osterix. Heart weight was significantly increased by 26% in untreated mice but remained normal during RAP-011 treatment. In 150-day-old mice, GFR was significantly reduced by 55%, but only by 30% in the RAP-011-treated group. In 200-day-old mice, the mean BUN was 100 mg/dl in untreated mice compared to 60 mg/dl in the treated group. In the kidneys of 200-day-old mice, ActRIIA and p-Smad2 were induced and MCP-1, fibronectin, and interstitial fibrosis were stimulated; all were attenuated by RAP-011 treatment. Hence, the activation of ActRIIA signaling during early CKD contributes to the CKD-MBD components of osteodystrophy and cardiovascular disease and to renal fibrosis. Thus, the inhibition of ActRIIA signaling is efficacious in improving and delaying CKD-MBD in this model of Alport syndrome.


Assuntos
Receptores de Activinas Tipo II/metabolismo , Reabsorção Óssea/metabolismo , Cardiomegalia/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Nefrite Hereditária/metabolismo , Insuficiência Renal Crônica/metabolismo , Calcificação Vascular/metabolismo , Actinas/metabolismo , Receptores de Activinas Tipo II/antagonistas & inibidores , Receptores de Activinas Tipo II/genética , Animais , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patologia , Vasos Sanguíneos/fisiopatologia , Remodelação Óssea , Reabsorção Óssea/genética , Reabsorção Óssea/fisiopatologia , Reabsorção Óssea/prevenção & controle , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Osso e Ossos/fisiopatologia , Cardiomegalia/genética , Cardiomegalia/fisiopatologia , Cardiomegalia/prevenção & controle , Distúrbio Mineral e Ósseo na Doença Renal Crônica/genética , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Colágeno Tipo IV/deficiência , Colágeno Tipo IV/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Modelos Animais de Doenças , Fibrose , Taxa de Filtração Glomerular , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Camundongos Knockout , Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Nefrite Hereditária/tratamento farmacológico , Nefrite Hereditária/genética , Nefrite Hereditária/fisiopatologia , Fosforilação , Proteínas Recombinantes de Fusão/farmacologia , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/prevenção & controle , Transdução de Sinais , Proteína Smad2/metabolismo , Fator de Transcrição Sp7/metabolismo , Calcificação Vascular/genética , Calcificação Vascular/fisiopatologia , Calcificação Vascular/prevenção & controle , Remodelação Vascular , Remodelação Ventricular
7.
Nefrologia ; 37(1): 20-28, 2017.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27697413

RESUMO

Phytate, or myo-inositol 1,2,3,4,5,6-hexakis dihydrogen phosphate (InsP6), is a naturally occurring phosphorus compound that is present in many foods, mainly legumes, whole grains and nuts. Patients with chronic kidney disease (CKD) have cardiovascular disease mortality up to 30times higher than the general population. Vascular calcifications (VCs) directly contribute to overall morbidity and mortality, especially in CKD. In part, this high mortality is due to elevated levels of phosphorus in the blood. Therefore, control of dietary phosphorus is essential. Dietary phosphorus can be classified according to its structure in organic phosphorus (plant and animal) and inorganic (preservatives and additives). Plant-phosphorus (legumes and nuts), mainly associated with InsP6, is less absorbable by the human gastrointestinal tract as the bioavailability of phosphorous from plant-derived foods is very low. Recent data indicate that restriction of foods containing plant phosphates may compromise the adequate supply of nutrients that have a beneficial effect in preventing cardiovascular events, such as InsP6 or fibre found in legumes and nuts. Experimental studies in animals and observational studies in humans suggest that InsP6 can prevent lithiasis and VCs and protect from osteoporosis. In conclusion, we need prospective studies to elucidate the potential benefits and risks of phytate (InsP6) through the diet and as an intravenous drug in patients on haemodialysis.


Assuntos
Calcinose/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Hiperfosfatemia/complicações , Fosfatos/metabolismo , Fósforo na Dieta/farmacocinética , Ácido Fítico/metabolismo , Insuficiência Renal Crônica/metabolismo , Urolitíase/prevenção & controle , Animais , Antioxidantes/metabolismo , Arteriosclerose/prevenção & controle , Disponibilidade Biológica , Calcinose/etiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Cinacalcete/uso terapêutico , Estudos Transversais , Fabaceae , Humanos , Hiperfosfatemia/mortalidade , Masculino , Estrutura Molecular , Nozes , Estudos Observacionais como Assunto , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Fósforo na Dieta/administração & dosagem , Fósforo na Dieta/efeitos adversos , Ácido Fítico/farmacologia , Ácido Fítico/uso terapêutico , Estudos Prospectivos , Ratos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/dietoterapia , Urolitíase/etiologia
8.
Biomed Res Int ; 2016: 1523124, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28003998

RESUMO

Background. This study evaluated the association between achieving target chronic kidney disease-mineral and bone disorder (CKD-MBD) marker levels and mortality in Taiwanese hemodialysis (HD) patients. Target levels were based on the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Methods. We performed a retrospective medical record review of 1126 HD patients between 2009 and 2013. A logistic regression model was used to evaluate the relationship between achieving target marker levels and the risk for all-cause and cardiovascular (CV) mortality. Reference target ranges were 7.9 ≤ calcium (Ca) ≤ 9.9 mg/dL, 2.4 ≤ phosphate (P) ≤ 4.7 mg/dL, and 144 ≤ intact parathyroid hormone (iPTH) ≤ 648 pg/mL. Results. Achievement of target P levels was associated with a lower risk for all-cause mortality compared to achievement of either target Ca or iPTH levels. Achieving target P + iPTH levels (OR 1.32) was associated with a lower odds ratio for all-cause mortality compared to achieving target Ca + P (OR 1.66) and Ca + iPTH (OR 1.43) levels. Similar trends were observed for CV mortality risk. Conclusions. The present study demonstrated that achieving serum P levels within the KDIGO target range is the most important factor for lowering mortality in HD patients.


Assuntos
Cálcio/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/mortalidade , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Diálise Renal/mortalidade , Biomarcadores/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Feminino , Saúde Global , Humanos , Masculino , Pessoa de Meia-Idade , Nefrologia/normas , Guias de Prática Clínica como Assunto , Prevalência , Modelos de Riscos Proporcionais , Diálise Renal/estatística & dados numéricos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Taxa de Sobrevida , Taiwan/epidemiologia , Resultado do Tratamento
9.
Semin Dial ; 29(4): 320-2, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27075415

RESUMO

Current Kidney Disease Improving Global Outcomes guidelines for chronic kidney disease-mineral and bone disorder recommend maintaining the PTH level between 2 and 9 times the upper limit of normal. PTH levels function as a surrogate for bone turnover to differentiate forms of renal osteodystrophy. Vitamin D receptor agonists are primarily used to treat osteitis fibrosa in hemodialysis patients. However, there is concern that overtreatment may put HD patients at risk for adynamic bone disease, which has been associated with fracture and vascular calcification. This raises the issue as to whether "we use too much vitamin D in hemodialysis patients."


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Nefrologia/métodos , Diálise Renal , Vitamina D/administração & dosagem , Humanos , Vitaminas/administração & dosagem
10.
J Nephrol ; 29(6): 857-862, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27084800

RESUMO

BACKGROUND AND AIMS: Reduction of intestinal load of phosphorus is important for the prevention and treatment of chronic kidney disease (CKD)-mineral and bone disorder (MBD). However, this strategy is limited by patients' poor adherence to dietary prescription and by the existence of hidden sources of phosphorus. In addition to food containing phosphate-based additives, it was recently claimed that medications may contribute to increase the load of phosphate (P), mainly present as an excipient. To identify medications containing P as an excipient, we performed a systematic screening of medications which could potentially be prescribed for chronic oral therapies in CKD patients. METHODS: We examined 311 active pharmaceutical ingredients (APIs) and 3763 branded or generic medications, identified by the anatomical therapeutic chemical (ATC) international classification system. RESULTS: Sixty APIs (19.3 %) included at least one medication containing P as an excipient. In total, 472 medications (12.5 %) listed P as an excipient. The prevalence of medications containing phosphate as an excipient was highest for oral antidiabetic medications (23.8 %), followed by antidepressant (19.2 %), antihypertensive (17.5 %) and gastro-intestinal tract (16.4 %) medications. All other classes showed a prevalence <10 %. Within each ATC class, the APIs at risk of containing phosphate were identified as well as the prevalence of both branded and generic medications. Calcium hydrogen phosphate was the most prevalent form (77.7 %) of phosphate as an excipient. CONCLUSIONS: Our results suggest that the prevalence of phosphate-containing medications is quite low and it is possible to identify, within each drug category, the medications containing P as an excipient. Calcium phosphate, the most prevalent form, has a lower rate of intestinal absorption than sodium phosphate salts. We did not measure the actual P content, but existing data (measured or estimated) show that it is generally low, except for a few medications that can be easily identified. Thus, the extra-phosphate load from medications may be of concern only in special cases, which could be further limited when correct information and prescriptions are given. The extra-phosphate load from P-containing food and beverages remains the main concern of hidden phosphorus sources in CKD patients.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Excipientes/análise , Absorção Intestinal , Preparações Farmacêuticas/análise , Fosfatos/análise , Administração Oral , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Composição de Medicamentos , Excipientes/administração & dosagem , Excipientes/efeitos adversos , Excipientes/metabolismo , Humanos , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/metabolismo , Fosfatos/administração & dosagem , Fosfatos/efeitos adversos , Fosfatos/metabolismo , Medição de Risco , Fatores de Risco
11.
Ren Fail ; 38(5): 759-64, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27001371

RESUMO

Sclerostin is a marker of low-turnover bone disease in end stage renal disease patients. The aim of this study was to evaluate serum sclerostin in uremic patients, analyzing its behavior during a single hemodialysis session. Twenty-one adult patients on intermittent hemodialysis treatment were enrolled. Acetate Free Bio-filtration (AFB) was the technique employed. Uremic patients were characterized by higher levels of serum sclerostin when compared with values observed in healthy subjects. Sclerostin assessed in pre-dialysis samples was 1.4 ± 1.02 ng/mL, whereas, in post dialysis samples, a reduction of sclerostin values was observed (0.8 ± 0.6 ng/mL; p: 0.008). Sclerostin correlated with parameters of dialysis adequacy, such as creatinine levels and Kt/V values, and it was significantly associated with atherosclerotic disease. Receiver operating characteristics analysis revealed a good diagnostic profile in identifying atherosclerotic disease. Sclerostin, a full dialyzable substance during AFB dialysis, is closely associated with atherosclerotic disease. Its reduction obtained through AFB could represent a defensive mechanism, improving vascular disease and renal osteodystrophy.


Assuntos
Aterosclerose/metabolismo , Proteínas Morfogenéticas Ósseas/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Falência Renal Crônica/complicações , Diálise Renal/métodos , Uremia , Idoso , Aterosclerose/diagnóstico , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Remodelação Óssea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Feminino , Marcadores Genéticos , Humanos , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estatística como Assunto , Uremia/complicações , Uremia/etiologia , Uremia/metabolismo , Uremia/terapia
13.
Clin Calcium ; 25(7): 1057-62, 2015 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-26119320

RESUMO

Renal osteodystrophy is the damage of bone morphology by CKD and treatment and occurred abnormal bone metabolism through renal dysfunction. It demonstrated that the control of P and Ca improves to normalization of mineral metabolism. Protein energy wasting and malnutrition are common in patients with CKD stage 5 and has been associated with life prognosis. In CKD patients, nutritional management is a critical role of treatment. Also it may be important of nutritional management that control P and Ca and improve nutritional status in renal osteodystrophy patients.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Terapia Nutricional , Osso e Ossos/metabolismo , Cálcio/metabolismo , Colecalciferol/administração & dosagem , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Difosfonatos/administração & dosagem , Humanos , Terapia Nutricional/métodos , Estado Nutricional , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Osteoporose/prevenção & controle , Fósforo/metabolismo , Prognóstico , Desnutrição Proteico-Calórica/etiologia , Desnutrição Proteico-Calórica/prevenção & controle , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/terapia
14.
Syst Rev ; 4: 13, 2015 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-25874904

RESUMO

BACKGROUND: The prevalence of vitamin D deficiency in hemodialysis patients is high. While most hemodialysis patients are treated with activated vitamin D (1,25[OH]2D) to prevent renal osteodystrophy, clinical practices of the screening and treatment of 25(OH)2D deficiency are highly variable. It is unclear if nutritional vitamin D supplementation with D2 or D3 provides an additional clinical benefit beyond that provided by activated vitamin D treatment in this population. METHODS/DESIGN: We will conduct a systematic review of nutritional vitamin D (D2/D3) supplementation and health-related outcomes in hemodialysis patients according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary objective is to assess the impact of nutritional vitamin D supplementation on clinical outcomes relevant in hemodialysis patients, such as mortality, cardiovascular events, infections, and fractures. Secondary outcomes will include anemia, hyperparathyroidism, medication use (erythrocyte-stimulating agents, activated vitamin D), and quality of life. We will search MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov for randomized, controlled trials of nutritional vitamin D supplementation (ergocalciferol/D2 or cholecalciferol/D3) in chronic hemodialysis patients. The Cochrane Risk Assessment Tool will be used to assess the quality of eligible studies. We will perform meta-analyses using standard techniques for the outcomes listed above if pooling is deemed appropriate/sufficient. The results of this systematic review may highlight gaps in our knowledge of the relevance of nutritional vitamin D in end-stage renal disease, allowing for the informed design of clinical trials assessing the impact of nutritional vitamin D therapy in the hemodialysis population in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014013931.


Assuntos
Colecalciferol/uso terapêutico , Suplementos Nutricionais , Ergocalciferóis/uso terapêutico , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/complicações , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Protocolos Clínicos , Fraturas Ósseas/etiologia , Fraturas Ósseas/prevenção & controle , Humanos , Insuficiência Renal Crônica/mortalidade , Projetos de Pesquisa , Revisão Sistemática como Assunto , Deficiência de Vitamina D/etiologia
15.
Pediatr Nephrol ; 28(4): 537-45, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22893310

RESUMO

The treatment of the mineral and bone disorder associated with chronic kidney disease (CKD-MBD) remains a major challenge in pediatric patients. The principal aims of therapeutic measures are not only to prevent the debilitating skeletal complications and to achieve normal growth but also to preserve long-term cardiovascular health. Serum parathyroid hormone (PTH) levels are used as a surrogate parameter of bone turnover. Whereas it is generally accepted that serum calcium and phosphate levels should be kept within the range for age, current pediatric consensus guidelines differ markedly with respect to the optimal PTH target range and operate on a limited evidence base. Recently, the International Pediatric Dialysis Network (IPPN) established a global registry collecting detailed clinical and biochemical information, including data relevant to CKD-MBD in children on chronic peritoneal dialysis (PD). This review highlights the current evidence basis regarding the optimal PTH target range in pediatric CKD patients, and re-assesses the current guidelines in view of the outcome data collected by the IPPN registry. Based on a comprehensive evaluation of CKD-MBD outcome measures in this global patient cohort, a PTH target range of 1.7-3 times the upper limit of normal (i.e. 100-200 pg/ml) appears reasonable in children undergoing chronic PD.


Assuntos
Remodelação Óssea , Doenças Cardiovasculares/prevenção & controle , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Hiperparatireoidismo Secundário/prevenção & controle , Hormônio Paratireóideo/sangue , Diálise Peritoneal , Insuficiência Renal Crônica/terapia , Adolescente , Animais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Criança , Pré-Escolar , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Fidelidade a Diretrizes , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/diagnóstico , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/fisiopatologia , Lactente , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/normas , Guias de Prática Clínica como Assunto , Sistema de Registros , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Resultado do Tratamento
16.
Nephron Clin Pract ; 121(1-2): c25-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23075669

RESUMO

BACKGROUND: A phase II open-label study was conducted in hemodialysis patients evaluating the short-term safety, tolerability, and iron absorption with ferric citrate when used as a phosphate binder. METHODS: Enrollment occurred in two periods. Period 1 recruited patients taking 6-15 pills/day of binder with phosphorus of ≥2.5 mg/dl. Period 2 recruited patients taking ≥12 pills/day of binder with phosphorus of ≥3.5 mg/dl. Participants with ferritin ≥1,000 µg/l or transferrin iron saturation (TSAT) ≥50% at screening were excluded. Subjects discontinued their previous binders and started 4.5 g/day of ferric citrate (period 1) or 6 g/day (period 2) and were titrated for 4 weeks to maintain a phosphorus of 3.5-5.5 mg/dl. Chemistries and complete blood count were obtained weekly and a gastrointestinal questionnaire was administered at drug initiation and final visit. Iron therapy was permitted if the ferritin was <500 µg/l and TSAT <30%. RESULTS: Fifty-five subjects were enrolled. Four serious adverse events were reported; none were related to the study drug. Findings from the gastrointestinal questionnaire included stool discoloration (69%), constipation (15%), and bloating (7%). Mean iron parameters at the beginning of the study were ferritin 554 ± 296 µg/l, iron 68 ± 21 µg/dl, and iron saturation 30 ± 7.8%. At the end of study, mean ferritin was 609 ± 340 µg/l (p = 0.02), iron 75 ± 27 µg/dl (p = 0.04), and TSAT was 35 ± 13% (p = 0.001). Mean phosphorus and calcium levels were unchanged from baseline at the end of study. CONCLUSION: Ferric citrate was well tolerated by patients after 4 weeks with no significant clinical or biochemical adverse events related to exposure.


Assuntos
Quelantes/efeitos adversos , Compostos Férricos/efeitos adversos , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Fósforo/sangue , Adulto , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Cor , Constipação Intestinal/induzido quimicamente , Fezes , Feminino , Ferritinas/sangue , Humanos , Ferro/sangue , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Diálise Renal , Inquéritos e Questionários
17.
Duodecim ; 128(5): 465-74, 2012.
Artigo em Finlandês | MEDLINE | ID: mdl-22486062

RESUMO

Chronic renal failure results in disturbances of bone formation, degradation and mineralization and changes in bone volume. These bone changes as well as biochemical abnormalities of the blood have also been found to be associated with soft-tissue and blood vessel calcification. In fact, the patients suffer not only from skeletal problems but also from rapidly progressing arterial stiffening, which leads to early cardiovascular morbidity and mortality. Essential therapy consists of early management of hyperphosphatemia and supplementation of active vitamin D.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Hiperfosfatemia/etiologia , Hiperfosfatemia/prevenção & controle , Falência Renal Crônica/complicações , Rigidez Vascular , Vitamina D/uso terapêutico , Humanos
18.
Semin Dial ; 25(1): 50-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21967444

RESUMO

Vitamin D receptor agonists (VDRA) are currently recommended for the treatment of secondary hyperparathyroidism in stage 5 CKD. They are considered to be contraindicated in the presence of low or normal (for a dialysis patient) levels of PTH due to the risk of developing adynamic bone disease, with consequent vascular calcification. However, these recommendations are increasingly at odds with the epidemiological evidence, which consistently shows a large survival advantage for patients treated with low-dose VDRAs, regardless of plasma calcium, phosphate, or PTH. A large number of pleiotropic effects of vitamin D have been described, including inhibition of renin activity, anti-inflammation, and suppression of vascular calcification stimulators and stimulation of vascular calcification inhibitors present in the uremic milieu. Laboratory studies suggest that a normal cellular vitamin D level is necessary for normal cardiomyocyte and vascular smooth muscle function. While pharmacological doses of VDRA can be harmful, the present evidence suggests that the level of 1,25-dihydroxycholecalciferol should also be more physiological in stage 5 CKD, and that widespread use of low-dose VDRA would be beneficial. A randomized controlled trial to test this hypothesis is warranted.


Assuntos
Hiperparatireoidismo Secundário/tratamento farmacológico , Falência Renal Crônica/complicações , Diálise Renal/efeitos adversos , Vitamina D/uso terapêutico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Hormônio Paratireóideo/sangue , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Vitaminas/uso terapêutico
19.
Ann Nutr Metab ; 58(4): 315-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21986491

RESUMO

OBJECTIVES: Worldwide, incidence rates of chronic renal insufficiency have clearly increased over the past decade, especially in people of older age. Hyperphosphatemia is the strongest independent risk factor for mortality in renal patients. In order to reduce serum phosphate concentrations to recommended values, phosphate binders (P binders) are used to bind ingested phosphate in the digestive tract. Besides the traditional therapies with calcium and aluminium salts, sevelamer and lanthanum represent recent developments on the market. The purpose of the present health technology assessment (HTA) report was to compare the effectiveness and safety of different P binders in patients with chronic renal insufficiency. METHODS: Based on a systematic literature search followed by a two-part selection process with predefined criteria 18 publications were included in the assessment. RESULTS: All P binders effectively controlled serum phosphate, calcium and parathyroid hormone concentrations. The numbers of hypercalcemic episodes were higher when using calcium-containing P binders compared to sevelamer and lanthanum. Regarding mortality rate, cardiovascular calcification and bone metabolism no definite conclusions could be drawn; however, sevelamer seemed to be more effective than calcium in certain patient subgroups, such as older patients and patients with preexisting arterial calcification. CONCLUSIONS: From a medical point of view, sevelamer showed superiority over calcium-containing P binders at least for special indications.


Assuntos
Quelantes/uso terapêutico , Soluções para Hemodiálise/uso terapêutico , Lantânio/uso terapêutico , Fósforo/química , Poliaminas/uso terapêutico , Diálise Renal , Insuficiência Renal Crônica/terapia , Adulto , Idoso , Cálcio/sangue , Quelantes/efeitos adversos , Quelantes/química , Quelantes/economia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Redução de Custos , Custos de Cuidados de Saúde , Soluções para Hemodiálise/efeitos adversos , Soluções para Hemodiálise/química , Soluções para Hemodiálise/economia , Humanos , Hipercalcemia/etiologia , Hipercalcemia/prevenção & controle , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/prevenção & controle , Hiperfosfatemia/etiologia , Hiperfosfatemia/prevenção & controle , Lantânio/efeitos adversos , Lantânio/química , Lantânio/economia , Hormônio Paratireóideo/sangue , Fósforo/sangue , Poliaminas/efeitos adversos , Poliaminas/química , Poliaminas/economia , Diálise Renal/efeitos adversos , Diálise Renal/economia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/economia , Insuficiência Renal Crônica/fisiopatologia , Sevelamer , Avaliação da Tecnologia Biomédica
20.
Nefrologia ; 31(5): 528-36, 2011.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-21959719

RESUMO

During recent years, increasing recognition has been given to the endocrine action that vitamin D has on the extraskeletal system, and its deep involvement in CKD. This has meant that many vitamin D compounds (both nutritional and active) have been made available, with an important cost reduction. This review looks at the evidence available regarding the usefulness of different types of vitamin D (nutritional and active) for patients with stage 3-5 CKD and those undergoing dialysis. Emphasis is given to its usefulness to control hyperparathyroidism and its impact on morbidity and mortality. We also analysed pharmacoeconomic studies that have been published which compare active vitamin D metabolites. From this review, we are able to conclude that there is still not enough scientific evidence to be able to prefer one active vitamin D over another. In the meantime, doctors should follow the recommendations given in clinical practice guidelines, always taking into account their personal experience with patients. Furthermore, they must consider the economic impact that their treatment decisions may have.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Nefropatias/tratamento farmacológico , Vitamina D/uso terapêutico , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Doença Crônica , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/economia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/etiologia , Ensaios Clínicos como Assunto , Estudos de Coortes , Redução de Custos , Humanos , Hiperparatireoidismo Secundário/tratamento farmacológico , Hiperparatireoidismo Secundário/economia , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/prevenção & controle , Inflamação/tratamento farmacológico , Nefropatias/economia , Metanálise como Assunto , Comunicação Parácrina , Guias de Prática Clínica como Assunto , Ratos , Receptores de Calcitriol/agonistas , Vitamina D/química , Vitamina D/economia , Vitamina D/metabolismo , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/metabolismo
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