RESUMO
We have reported that a strict denosumab administration management system with oral calcium/vitamin D supplementation attenuates denosumab-induced hypocalcemia in 158 cancer patients with bone metastasis. In this report, 27.8% of the patients experienced hypocalcemia, including 0.6% with grade 2. So far, the risk factors for ≥grade 2 hypocalcemia incidence have been identified in denosumab-treated cancer patients, including patients without calcium/vitamin D supplementation. Therefore, the present study aimed to reveal the factors that affect all-grade hypocalcemia incidence with calcium/vitamin D supplementation and team medical care according to the management system. A receiver operating characteristic curve analysis suggested that the cutoff of baseline serum calcium level for all-grade hypocalcemia incidence was 9.3 mg/dL. Multivariate analysis revealed that age ≥65 years (odds ratio, 95% confidence interval: 2.57, 1.11-5.95, p = 0.03), grade 1 or higher serum alkaline phosphatase elevation (3.70, 1.71-8.00, p < 0.01), an adjusted serum calcium level of less than 9.3 mg/dL (3.21. 1.25-8.24, p = 0.02) at baseline, and co-administration of cytotoxic agents (2.33, 1.06-7.11, p = 0.03) are risk factors for the incidence of all-grade hypocalcemia. However, renal dysfunction, which has been suggested to be a risk factor in previous reports, was not a factor. In conclusion, we revealed the risk factors for all-grade hypocalcemia in calcium/vitamin D supplementation and awareness, as demonstrated by the management system. Moreover, renal dysfunction was not a risk factor in our strict denosumab administration management system. Our results support the value of early detection of hypocalcemia incidence to guide the selection of an appropriate management strategy.
Assuntos
Neoplasias Ósseas/tratamento farmacológico , Cálcio/uso terapêutico , Denosumab/efeitos adversos , Suplementos Nutricionais , Hipocalcemia/etiologia , Nefropatias/complicações , Vitamina D/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos Antineoplásicos , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/secundário , Denosumab/uso terapêutico , Feminino , Humanos , Hipocalcemia/induzido quimicamente , Hipocalcemia/prevenção & controle , Rim/patologia , Rim/fisiopatologia , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Estudos Retrospectivos , Fatores de Risco , Vitaminas/uso terapêuticoRESUMO
Trimetazidine (TMZ) is a well-known anti-ischemic agent used for the treatment of angina pectoris. In the past decades, the efficacy of this drug has been tested in a wide range of kidney injuries, including drug-induced nephrotoxicity (DIN), radio-contrast agent-induced nephropathy, and surgically induced renal ischemic injury. TMZhas renoprotective effects by attenuating oxidative stress, inflammatory cytokine release, maintaining oxygen and energy balance. Moreover, TMZ administration prevented kidney graft rejection in the porcine model by suppressing the infiltration of mononuclear cells, preserving mitochondrial functions, and maintaining Ca+ homeostasis. In DIN and diabetic kidney diseases,TMZ treatment prevents renal injury by inactivating immune cells, attenuating renal fibrosis, inflammation, apoptosis, and histological abnormalities. Interestingly, the clinical therapeutic efficacy of TMZ has also been documented in pre-existing kidney disease patients undergoing contrast exposure for diagnostic intervention. However, the mechanistic insights into the TMZ mediated renoprotective effects in other forms of renal injuries, including type-2 diabetes, drug-induced nephrotoxicity, and hypertension-induced chronic kidney diseases, remain uninvestigated and incomplete. Moreover, the clinical utility of TMZ as a renoprotective agent in radio-contrast-induced nephrotoxicity needs to be tested in a large patient population. Nevertheless, the available pieces of evidence suggest that TMZ is a promising and emerging renal therapy for the treatment and management of kidney diseases of variable etiologies. This review discusses the various pre-clinical and clinical findings and provides mechanistic insights into the TMZ mediated beneficial effects in various kidney diseases.
Assuntos
Nefropatias/tratamento farmacológico , Rim/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Trimetazidina/farmacologia , Vasodilatadores/farmacologia , Animais , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Rim/irrigação sanguínea , Rim/fisiopatologia , Nefropatias/fisiopatologia , Estresse Oxidativo , Substâncias Protetoras/uso terapêutico , Resultado do Tratamento , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêuticoRESUMO
Uremic toxins (UTs) are mainly produced by protein metabolized by the intestinal microbiota and converted in the liver or by mitochondria or other enzymes. The accumulation of UTs can damage the intestinal barrier integrity and cause vascular damage and progressive kidney damage. Together, these factors lead to metabolic imbalances, which in turn increase oxidative stress and inflammation and then produce uremia that affects many organs and causes diseases including renal fibrosis, vascular disease, and renal osteodystrophy. This article is based on the theory of the intestinal-renal axis, from bench to bedside, and it discusses nonextracorporeal therapies for UTs, which are classified into three categories: medication, diet and supplement therapy, and complementary and alternative medicine (CAM) and other therapies. The effects of medications such as AST-120 and meclofenamate are described. Diet and supplement therapies include plant-based diet, very low-protein diet, probiotics, prebiotics, synbiotics, and nutraceuticals. The research status of Chinese herbal medicine is discussed for CAM and other therapies. This review can provide some treatment recommendations for the reduction of UTs in patients with chronic kidney disease.
Assuntos
Nefropatias/tratamento farmacológico , Nefropatias/terapia , Probióticos/uso terapêutico , Uremia/induzido quimicamente , Uremia/terapia , Toxinas Urêmicas/toxicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapias Complementares/métodos , Dietoterapia/métodos , Suplementos Nutricionais , Feminino , Humanos , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Terapia de Substituição Renal/métodosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Kidney-yin deficiency (KYD) during pregnancy is common and associated with possibility of thymus hypoplasia in neonates. Zuogui Wan (ZGW) is a classic traditional medicine to treat KYD. AIM OF STUDY: The Wnt/ß-catenin signaling pathway is essential for thymic epithelial cell (TEC) viability, function and for thymus integrity. We evaluated whether maternal diets with ZGW in KYD rats ameliorates epithelial cell dysfunction in the fetal thymus, and investigated its underlying mechanism in which the Wnt/ß-catenin signaling pathway is involved. MATERIALS AND METHODS: Rats were randomly assigned to four groups (n = 8). Two experimental groups received KYD induction with or without ZGW supplementation. The other 2 vehicle groups were sham operated and administrated with normal saline or ZGW. KYD was established using periodically chronic shaken stimulus and threaten stress. Success of the model induction was evaluated by the general observation, changing of the body weight and plasma thyroxine level. Then, pregnant of vehicle and KYD rats were fed with or without ZGW-supplemented diet throughout the F1 gestation. Postnatal thymi samples were obtained after delivery for histological examination. In vitro, TECs of the newborn rats whose mother suffered KYD were isolated, and cultured using the serum containing ZGW with or without the supplement of Wnt4/ß-catenin pathway inhibitor ICG-001. Cell viability was evaluated by CCK-8 assay. Meanwhile, the thymi tissues and TECs were collected for biochemical analysis. Levels of thymosin ß4 (TMSß4) and thymosin α1 (Tα1) were detected by ELISA assay. The mRNA and protein expression of Wnt4, ß-catenin, and Foxn1 were determined by RT-qPCR and Western blot respectively. RESULTS: In vivo, KYD resulted in significantly increased apoptosis of TECs and atrophy of the thymi, especially in the medullary zone. The morphological changes observed in KYD rats were ameliorated by ZGW treatment. Meanwhile, the decreased TMSß4, Tα1, Wnt4, ß-catenin, and Foxn1 levels in KYD rats were also significantly alleviated by ZGW administration. In vitro, elevated TMSß4 and Tα1 levels accompanied with upregulated Wnt4, ß-catenin, and Foxn1 expressions in the TECs were observed after ZGW intervention, however, which were significantly downregulated by ICG-001 supplement. CONCLUSIONS: Maternal kidney-yin deficiency could result in TEC dysfunction in newborn rats. ZGW was able to improve the growth and development of TEC, potentially by regulating the Wnt/ß-catenin pathway.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Nefropatias/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , Deficiência da Energia Yin/tratamento farmacológico , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Nefropatias/fisiopatologia , Masculino , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/fisiopatologia , Ratos , Ratos Wistar , Timo/citologia , Timo/efeitos dos fármacosRESUMO
ABSTRACT: The monoterpene glycoside paeoniflorin (PF) is the principal active constituent of the traditional Chinese herbal medicines, Radix Paeoniae Alba and Radix Paeoniae Rubra, which have been used for millennia to treat cardiovascular diseases (eg, hypertension, bleeding, and atherosclerosis) and neurological ailments (eg, headaches, vertigo, dementia, and pain). Recent evidence has revealed that PF exerts inhibitory effects on inflammation, fibrosis, and apoptosis by targeting several intracellular signaling cascades. In this review, we address the current knowledge about the pharmacokinetic properties of PF and its molecular mechanisms of action. We also present results from recent preclinical studies supporting the utility of PF for the treatment of pain, cerebral ischemic injury, and neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Moreover, new evidence suggests a general protective role of PF in heart attack, diabetic kidney, and atherosclerosis. Mechanistically, PF exerts multiple anti-inflammatory actions by targeting toll-like receptor-mediated signaling in both parenchymal and immune cells (in particular, macrophages and dendritic cells). A better understanding of the molecular actions of PF may lead to the expansion of its therapeutic uses.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Glucosídeos/farmacologia , Monoterpenos/farmacologia , Animais , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Humanos , Nefropatias/fisiopatologia , Nefropatias/prevenção & controle , Doenças do Sistema Nervoso/fisiopatologia , Doenças do Sistema Nervoso/prevenção & controleRESUMO
Curcumin (Cur) has been used extensively in dietary supplement with antioxidant and anti-apoptotic properties. Although dibutyl phthalate (DBP) has adverse effects on the kidney, any association between DBP exposure and the role of Cur is unclear. We tested the hypothesis that exposure to DBP has adverse consequences on renal dysfunction in mice and the potential protective role of Cur in decreasing DBP-induced renal dysfunction via inhibiting oxidative stress and apoptosis. Kidney function, oxidative stress biomarkers, and apoptosis factors as well as Bcl-2 and Bax were investigated. The results showed a marked increase of renal dysfunction, oxidative stress and apoptosis level after DBP exposure compared to the control. While administration of Cur to DBP-treated mice may reduce these adverse biochemical changes compared with DBP-alone group. Overall, these results suggest that oxidative stress and apoptosis are involved in DBP-induced renal disorder, whereas Cur plays a protective role in inhibiting these two pathways.
Assuntos
Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Curcumina/uso terapêutico , Dibutilftalato/toxicidade , Nefropatias/induzido quimicamente , Nefropatias/fisiopatologia , Estresse Oxidativo/efeitos da radiação , Animais , Animais não Endogâmicos , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/farmacologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêuticoRESUMO
Retinoid acid (RA) is synthesized mainly in the liver and has multiple functions in development, cell differentiation and proliferation, and regulation of inflammation. RA has been used to treat multiple diseases, such as cancer and skin disorders. The kidney is a major organ for RA metabolism, which is altered in the diseased condition. RA is known to have renal-protective effects in multiple animal models of kidney disease. RA has been shown to ameliorate podocyte injury through induction of expression of differentiation markers and regeneration of podocytes from its progenitor cells in animal models of kidney disease. The effects of RA in podocytes are mediated mainly by activation of the cAMP/PKA pathway via RA receptor-α (RARα) and activation of its downstream transcription factor, Kruppel-like factor 15. Screening of RA signaling molecules in human kidney disease has revealed RAR responder protein 1 (RARRES1) as a risk gene for glomerular disease progression. RARRES1, a podocyte-specific growth arrest gene, is regulated by high doses of both RA and TNF-α. Mechanistically, RARRES1 is cleaved by matrix metalloproteinases to generate soluble RARRES1, which then induces podocyte apoptosis through interaction with intracellular RIO kinase 1. Therefore, a high dose of RA may induce podocyte toxicity through upregulation of RARRES1. Based on the current findings, to avoid potential side effects, we propose three strategies to develop future therapies of RA for glomerular disease: 1) develop RARα- and Kruppel-like factor 15-specific agonists, 2) use the combination of a low dose of RAR-α agonist with phosphodiesterase 4 inhibitors, and 3) use a combination of RARα agonist with RARRES1 inhibitors.NEW & NOTEWORTHY Retinoic acid (RA) exerts pleotropic cellular effects, including induction of cell differentiation while inhibiting proliferation and inflammation. These effects are mediated by both RA responsive element-dependent or -independent pathways. In kidneys, RA confers renoprotection by signaling through podocyte RA receptor (RAR)α and activation of cAMP/PKA/Kruppel-like factor 15 pathway to promote podocyte differentiation. Nevertheless, in kidney disease settings, RA can also promote podocyte apoptosis and loss through downstream expression of RAR responder protein 1, a recently described risk factor for glomerular disease progression. These disparate roles of RA underscore the complexity of its effects in kidney homeostasis and disease, and a need to target specific RA-mediated pathways for effective therapeutic treatments against kidney disease progression.
Assuntos
Nefropatias/metabolismo , Rim/metabolismo , Proteínas de Membrana/metabolismo , Receptores do Ácido Retinoico/metabolismo , Tretinoína/metabolismo , Animais , Diferenciação Celular , Proliferação de Células , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Nefropatias/fisiopatologia , Receptores do Ácido Retinoico/agonistas , Transdução de Sinais , Tretinoína/efeitos adversosRESUMO
BACKGROUND: Although herbal medicines (HMs) are widely used worldwide, information concerning their interactions with conventional medicines (CMs) is sparse. In particular, stroke affects a high proportion of elderly people with impaired hepatic and renal function. Stroke is often accompanied by various complications and is commonly treated via the co-administration of HMs and CMs in Asia. PURPOSE: We aimed to investigate the effects of co-administration of HMs and CMs on liver and kidney function in patients with stroke. We estimated the prevalence of drug-induced liver injury (DILI) or herb-induced liver injury (HILI) and drug-induced acute kidney injury (DIAKI) or herb-induced acute kidney injury (HIAKI) in patients co-administered HMs and CMs. STUDY DESIGN: This was a retrospective study that reviewed the electronic medical records of 401 patients with stroke in a single hospital. METHODS: The prevalence of DILI or HILI and types of liver injury was examined according to abnormal increases in liver tests. The probable causality between drug or herb administration and liver injury was assessed using the Roussel Uclaf Causality Assessment Method. In addition, the prevalence of DIAKI or HIAKI was estimated using the Kidney Disease Improving Global Outcomes acute kidney injury stage criteria and related medical records. RESULTS: Out of a total of 401 patients, only four (1.0%) developed liver injury. Two cases of DILI (0.5%) and two cases of HILI (0.5%) were reported. Moxifloxacin and ebastine were the CMs that caused hepatotoxicity. Chungpyesagan-tang and Yeoldahanso-tang were the HMs that caused liver toxicity. Even in cases showing severe liver damage, alkaline phosphatase levels remained less than five times the normal value, and liver function test values recovered within 14 days. There were no cases of DIAKI or HIAKI in this cohort. CONCLUSION: These results suggest that if appropriately prescribed by experts, the co-administration of CMs and HMs is safe and does not adversely affect liver and kidney function in patients with stroke. To support these results, further large-scale multicenter prospective studies and toxicological studies based on the interaction between HMs and CMs are warranted.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Nefropatias/induzido quimicamente , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Interações Ervas-Drogas , Humanos , Nefropatias/fisiopatologia , Testes de Função Renal , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/fisiopatologiaRESUMO
AIM: Hyperuricemia (HUA) is a metabolic disease caused by the overproduction or underexcretion of uric acid (UA). Our previous study found that treatment with Dendrobium officinalis six nostrum (DOS) led to a significant reduction in serum UA (SUA) by inhibiting UA production and promoting UA excretion in a rat model of HUA induced by potassium oxonate (PO) and high-fat sorghum feed. In this study, we aimed to further investigate the effects of DOS on UA excretion by the kidney and intestine to explore whether DOS protects against histopathological changes, and to elucidate its possible mechanisms of action in a lipid emulsion (LE)-induced rat model of HUA. METHODS: The main chemical constituents of DOS were determined to be acteoside and astilbin by high-performance liquid chromatography (HPLC). Three different doses of DOS (3.3, 6.6, and 13.2â¯g/kg/day) were given to rats daily after induction of HUA by oral administration of LE for 8 weeks. The levels of creatinine (Cr) in serum and urine and UA in serum, urine, and feces were measured by an automatic biochemical analyzer. The expression of TLR4, NF-κB and urate transport-related transporters (URAT1, ABCG2, and PDZK1) in kidney was measured by Western blot (WB). Intestinal urate transporters (ABCG2 and GLUT9) expression was assayed by IHC and WB. Serum LPS and renal inflammatory factors (IL-6, IL-8 and TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin and eosin (H&E) staining was used to assess renal histological changes. RESULTS: DOS treatment significantly reduced the SUA and SCr levels by increasing urine volume, 24â¯h urine uric acid (UUA), fecal UA (FUA), urine creatinine (UCr), and fractional excretion of UA (FEUA) levels in hyperuricemic rats. Moreover, DOS effectively regulated URAT1, PDZK1, and ABCG2 protein levels in the kidney, as well as restored protein levels of GLUT9 and ABCG2 in the intestine. DOS markedly reduced serum LPS anddown-regulated renal TLR4 and NF-κB protein levels to suppress IL-6, IL-8, and TNF-α secretion. It also improved renal inflammation in hyperuricemic rats. In addition, DOS attenuated histopathological changes in the kidneys of LE-induced rats. HPLC analysis showed levels of acteoside and astilbin of 1.39â¯mg/g and 0.72â¯mg/g in DOS, respectively. CONCLUSION: DOS has anti-hyperuricemic and anti-inflammatory effects in a rat model of HUA. The molecular mechanism appears to involve the regulation of urate transport-related transporters including renal ABCG2, URAT1, and PDZK1, and intestinal GLUT9 and ABCG2, as well as the inhibition of the LPS/TLR4/NF-κB signaling to reduce IL-6, IL-8, and TNF-α secretion in hyperuricemic rats.
Assuntos
Dendrobium/química , Hiperuricemia/prevenção & controle , Extratos Vegetais/farmacologia , Ácido Úrico/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Emulsões , Nefropatias/fisiopatologia , Nefropatias/prevenção & controle , Lipídeos/efeitos adversos , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Ratos , Ratos Sprague-DawleyRESUMO
Chinese herbal medicine is widely used globally. In many instances, it is associated with severe adverse outcomes. We report case of a Chinese herbal nephropathy occurring in a 43-year-old woman showing renal impairment, metabolic acidosis, Stokes - Adams syndrome, hypernatremia, and hypokalemia, characteristics not usually encountered in published cases.
Assuntos
Acidose/induzido quimicamente , Síndrome de Adams-Stokes/induzido quimicamente , Medicamentos de Ervas Chinesas/efeitos adversos , Fármacos para a Fertilidade Feminina/efeitos adversos , Hipernatremia/induzido quimicamente , Hipopotassemia/induzido quimicamente , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Acidose/diagnóstico , Acidose/fisiopatologia , Acidose/terapia , Síndrome de Adams-Stokes/diagnóstico , Síndrome de Adams-Stokes/fisiopatologia , Síndrome de Adams-Stokes/terapia , Adulto , Feminino , Humanos , Hipernatremia/diagnóstico , Hipernatremia/fisiopatologia , Hipernatremia/terapia , Hipopotassemia/diagnóstico , Hipopotassemia/fisiopatologia , Hipopotassemia/terapia , Rim/fisiopatologia , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Nefropatias/terapia , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Compared with hemodialysis, home peritoneal dialysis alleviates the burden of travel, facilitates independence, and is less costly. Physical, cognitive, or psychosocial factors may preclude peritoneal dialysis in otherwise eligible patients. Assisted peritoneal dialysis, where trained personnel assist with home peritoneal dialysis, may be an option, but the optimal model is unknown. The objective of this work is to characterize existing assisted peritoneal dialysis models and synthesize clinical outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A systematic review of MEDLINE, Cochrane Central Register of Controlled Trails, Cochrane Database of Systematic Reviews, Embase, PsycINFO, and CINAHL was conducted (search dates: January 1995-September 2018). A focused gray literature search was also completed, limited to developed nations. Included studies focused on home-based assisted peritoneal dialysis; studies with the assist provided exclusively by unpaid family caregivers were excluded. All outcomes were narratively synthesized; quantitative outcomes were graphically depicted. RESULTS: We included 34 studies, totaling 46,597 patients, with assisted peritoneal dialysis programs identified in 20 jurisdictions. Two categories emerged for models of assisted peritoneal dialysis on the basis of type of assistance: health care and non-health care professional assistance. Reported outcomes were heterogeneous, ranging from patient-level outcomes of survival, to resource use and transfer to hemodialysis; however, the comparative effect of assisted peritoneal dialysis was unclear. In two qualitative studies examining the patient experience, the maintenance of independence was identified as an important theme. CONCLUSIONS: Reported outcomes and quality were heterogeneous, and relative efficacy of assisted peritoneal dialysis could not be determined from included studies. Although the patient voice was under-represented, suggestions to improve assisted peritoneal dialysis included using a person-centered model of care, ensuring continuity of nurses providing the peritoneal dialysis assist, and measures to support patient independence. Although attractive elements of assisted peritoneal dialysis are identified, further evidence is needed to connect assisted peritoneal dialysis outcomes with programmatic features and their associated funding models.
Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Serviços de Assistência Domiciliar/organização & administração , Nefropatias/terapia , Modelos Organizacionais , Diálise Peritoneal , Cuidadores/organização & administração , Continuidade da Assistência ao Paciente/organização & administração , Pessoal de Saúde/organização & administração , Humanos , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Satisfação do Paciente , Assistência Centrada no Paciente/organização & administração , Diálise Peritoneal/efeitos adversos , Qualidade de Vida , Resultado do TratamentoRESUMO
Creatine supplements may transitorily rise serum creatinine levels and mimic a kidney disease. If its use is associated with a high protein diet, the resulting increase in blood urea nitrogen will increase the confusion. Since clinical laboratories usually inform the estimated glomerular filtration rate based on serum creatinine, its elevation may lead to over diagnose a chronic renal failure, with the inherent personal and public health consequences. Creatine supplements are safe and do not cause renal disease. Reports of kidney damage associated with its use are scanty. However, creatine supplements should not be used in people with chronic renal disease or using potentially nephrotoxic medications.
Assuntos
Creatina/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Rim/fisiopatologia , Creatinina/sangue , Humanos , Nefropatias/fisiopatologia , Fatores de RiscoRESUMO
In 2014/2015, tyrosine kinase inhibitors (TKIs) were introduced as a secondary treatment for refractory differentiated thyroid cancer (DTC) in Japan. While renal dysfunction is an adverse event of TKI, data on this adverse event in TKI-treated DTC remains insufficient. Here, we investigated renal function in patients undergoing TKI treatment for DTC and evaluated the efficacy of dose reduction/withdrawal for cases of renal dysfunction.A total of 73 cases of radioactive iodine-refractory DTC treated with sorafenib (nâ=â22) or lenvatinib (nâ=â51) were included. Patient data evaluated were TKI treatment period, estimated glomerular filtration rate (eGFR) before and after TKI therapy, incidence and degree (maximum value at time of TKI treatment) of proteinuria, and albumin levels before and after TKI therapy were compared.The mean ΔeGFR was -6.75% with lenvatinib and +5.90% with sorafenib. It was not significant (Pâ=â.15). The mean Δalbumin was -8.90% and -5.85% with lenvatinib and sorafenib, respectively; there was no significant difference between the lenvatinib and sorafenib groups (Pâ=â.77). According to our program of TKI dose reduction and withdrawal, all patients except 2 with diabetes were successfully continuing treatment.Overall, the present results demonstrated that renal function is negatively affected by long-term TKI treatment for RAI-refractory DTC. However, heightened proteinuria, decreased eGFR and albumin levels, and significant but apparently reversible renal dysfunction were more frequent with lenvatinib than sorafenib.
Assuntos
Taxa de Filtração Glomerular/fisiologia , Radioisótopos do Iodo/uso terapêutico , Nefropatias/etiologia , Compostos de Fenilureia/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinolinas/uso terapêutico , Sorafenibe/uso terapêutico , Neoplasias da Glândula Tireoide/terapia , Idoso , Substituição de Medicamentos , Feminino , Seguimentos , Humanos , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Tolerância a Radiação , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Up to 5% of familial Mediterranean fever (FMF) cases are unresponsive to colchicine, through resistance, side effects and toxicity. Anakinra is an alternative treatment for FMF patients whose disease remains uncontrolled with colchicine. We aimed to evaluate anti-interleukin-1 treatment regarding clinical findings, laboratory parameters and quality of life (QoL) among FMF patients presenting resistance and toxicity towards colchicine. DESIGN AND SETTING: Descriptive observational study at the rheumatology clinic, Adnan Menderes University Medical School, Aydin, Turkey. METHODS: Among the patients included, age, sex, MEFV genotypes, acute-phase reactants, hepatic/renal function tests, average colchicine dose, disease duration, attack frequency, attack duration, disease severity, proteinuria, amyloidosis and QoL were evaluated. Colchicine resistance was defined as > 6 typical episodes/year or > 3 per 4-6 months. Kolmogorov-Smirnov, Friedman and two-way analysis of variance tests were used for statistical analyses. RESULTS: Between 2015 and 2017, 14 FMF patients receiving anakinra were enrolled. The mean colchicine dose was 1.7 ± 0.3 mg/day before use of anakinra. Ten patients were attack-free after treatment, while three showed reductions of at least 50% in attack frequency, attack duration and disease severity. Proteinuria levels in all patients with renal amyloidosis decreased after treatment. QoL among patients with renal amyloidosis differed significantly from QoL among non-amyloidosis patients. Mean visual analogue scale scores significantly improved in both groups after use of anakinra. CONCLUSIONS: Use of anakinra reduced attack frequency and proteinuria and acute-phase reactant levels, and improved QoL, with only a few uncomplicated side effects among colchicine-resistant or intolerant FMF patients. Injection-site reactions of severity insufficient to require discontinuation of treatment were seen.
Assuntos
Antirreumáticos/uso terapêutico , Colchicina/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Febre Familiar do Mediterrâneo/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Interleucina-1/antagonistas & inibidores , Qualidade de Vida , Adulto , Amiloidose/tratamento farmacológico , Amiloidose/fisiopatologia , Análise de Variância , Sedimentação Sanguínea , Febre Familiar do Mediterrâneo/fisiopatologia , Feminino , Humanos , Nefropatias/tratamento farmacológico , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Proteinúria/urina , Valores de Referência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Turquia , Escala Visual AnalógicaRESUMO
Creatine supplements may transitorily rise serum creatinine levels and mimic a kidney disease. If its use is associated with a high protein diet, the resulting increase in blood urea nitrogen will increase the confusion. Since clinical laboratories usually inform the estimated glomerular filtration rate based on serum creatinine, its elevation may lead to over diagnose a chronic renal failure, with the inherent personal and public health consequences. Creatine supplements are safe and do not cause renal disease. Reports of kidney damage associated with its use are scanty. However, creatine supplements should not be used in people with chronic renal disease or using potentially nephrotoxic medications.
Assuntos
Humanos , Suplementos Nutricionais/efeitos adversos , Creatina/efeitos adversos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Nefropatias/induzido quimicamente , Fatores de Risco , Creatinina/sangue , Nefropatias/fisiopatologiaRESUMO
Fluoride is widely distributed in the environment, and excessive fluoride intake can induce cytotoxicity, DNA damage, and cell cycle changes in many tissues and organs, including the kidney. Accumulating evidence demonstrates that selenium (Se) administration ameliorates sodium fluoride (NaF)-induced kidney damage. However, the potentially beneficial effects of Se against NaF-induced cytotoxicity of the kidney and the underlying molecular mechanisms of this protection are not fully understood. At present, in this study, the normal rat kidney cell (NRK-52E) was used to investigate the potentially protective mechanism of Se against NaF-induced apoptosis, by using the methods of pathology, colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and Western blot. The experiment was designed with a control group, two NaF-treated groups (NaF, 5, 20 mg/L), two sodium selenite-treated groups (Na2SeO3, 17.1, 34.2 µg/L), and four Se + NaF-treated groups (Na2SeO3, 17.1, 34.2 µg/L; NaF, 5, 20 mg/L). The results indicate that selenium can attenuate apoptosis and AMPK phosphorylation in the NRK-52E cell induced with fluoride. These results imply that selenium is capable to modulate fluoride-induced NRK-52E cell apoptosis via regulating the expression levels of the proteins involved in mitochondrial pathway and changes in p-AMPK expressions may also be a key process in preventing fluorosis.
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Apoptose/efeitos dos fármacos , Fluoretos/metabolismo , Nefropatias/fisiopatologia , Rim/efeitos dos fármacos , Selênio/metabolismo , Selenito de Sódio/metabolismo , Proteínas Quinases Ativadas por AMP , Animais , Ciclo Celular , Fluoretos/química , Nefropatias/metabolismo , Fosforilação , Ratos , Selênio/química , Selenito de Sódio/químicaRESUMO
ABSTRACT BACKGROUND: Up to 5% of familial Mediterranean fever (FMF) cases are unresponsive to colchicine, through resistance, side effects and toxicity. Anakinra is an alternative treatment for FMF patients whose disease remains uncontrolled with colchicine. We aimed to evaluate anti-interleukin-1 treatment regarding clinical findings, laboratory parameters and quality of life (QoL) among FMF patients presenting resistance and toxicity towards colchicine. DESIGN AND SETTING: Descriptive observational study at the rheumatology clinic, Adnan Menderes University Medical School, Aydın, Turkey. METHODS: Among the patients included, age, sex, MEFV genotypes, acute-phase reactants, hepatic/renal function tests, average colchicine dose, disease duration, attack frequency, attack duration, disease severity, proteinuria, amyloidosis and QoL were evaluated. Colchicine resistance was defined as > 6 typical episodes/year or > 3 per 4-6 months. Kolmogorov-Smirnov, Friedman and two-way analysis of variance tests were used for statistical analyses. RESULTS: Between 2015 and 2017, 14 FMF patients receiving anakinra were enrolled. The mean colchicine dose was 1.7 ± 0.3 mg/day before use of anakinra. Ten patients were attack-free after treatment, while three showed reductions of at least 50% in attack frequency, attack duration and disease severity. Proteinuria levels in all patients with renal amyloidosis decreased after treatment. QoL among patients with renal amyloidosis differed significantly from QoL among non-amyloidosis patients. Mean visual analogue scale scores significantly improved in both groups after use of anakinra. CONCLUSIONS: Use of anakinra reduced attack frequency and proteinuria and acute-phase reactant levels, and improved QoL, with only a few uncomplicated side effects among colchicine-resistant or intolerant FMF patients. Injection-site reactions of severity insufficient to require discontinuation of treatment were seen.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Febre Familiar do Mediterrâneo/tratamento farmacológico , Qualidade de Vida , Resistência a Medicamentos/efeitos dos fármacos , Colchicina/uso terapêutico , Interleucina-1/antagonistas & inibidores , Antirreumáticos/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Febre Familiar do Mediterrâneo/fisiopatologia , Proteinúria/urina , Valores de Referência , Fatores de Tempo , Turquia , Índice de Gravidade de Doença , Sedimentação Sanguínea , Reprodutibilidade dos Testes , Estudos Retrospectivos , Análise de Variância , Resultado do Tratamento , Estatísticas não Paramétricas , Escala Visual Analógica , Amiloidose/fisiopatologia , Amiloidose/tratamento farmacológico , Nefropatias/fisiopatologia , Nefropatias/tratamento farmacológicoRESUMO
BACKGROUND: Systemic oxidative stress has been reported to play a central role in the pathogenesis of kidney function decline. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is one of the important endogenous antioxidant stress pathways in cells. This study aims to investigate whether shenduning granule can ameliorate oxidative stress in kidney tissues by activating the Nrf2/ARE pathway, and explores the detailed underlying mechanism. METHODS: A total of 120 male Sprague-Dawley rats were randomly assigned to the sham-operated and operation groups. Rats in the operation group underwent 5/6 nephrectomy. Two weeks later, rats in the operation group were further randomly divided into 5 groups: model group, low-dose, medium-dose and high-dose shenduning granule groups, and losartan group. Rats in each group were given the same volume of corresponding liquid orally. Serum creatinine (SCr), blood urea nitrogen (BUN), 24-h urinary protein, malondialdehyde (MDA) and superoxide dismutase (SOD), Nrf2, heme oxygenase-1 (HO-1), and γ-glutamyl-cysteine synthetase (γ-GCS) were determined. RESULTS: Shenduning granule could markedly elevate HO-1, NRF2, γ-GCS and SOD (p < 0.05), and significantly decreased MDA, 24-h urinary protein, SCr and BUN in rats (p < 0.05). CONCLUSION: Shenduning granule can improve renal antioxidative stress activity in rats, exhibiting a renoprotective effect. The potential mechanism is likely exerted by the activation of the Nrf2/ARE pathway.
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Nefropatias/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Elementos de Resposta Antioxidante/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Nefropatias/etiologia , Nefropatias/fisiopatologia , Masculino , Malondialdeído/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Plantas Medicinais/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: The aim of this registry was to evaluate the efficacy of Meriva® in subjects with temporary kidney dysfunction (TKD) and increased oxidative stress levels. TKD was a casual finding on urinary tests after reported side effects following drug consumption, a clinical event or dehydration. METHODS: Patients followed either standard management (SM) or SM plus Meriva® (Curcumin Phytosome®) supplementation (3 capsules/day, corresponding to 1.5 g of Meriva® containing 300 mg of curcumin in a bioavailable delivery form). The follow-up period lasted 4 weeks. Subjects were divided according to macroalbuminuria (>300 mg albumin on 24 hours) or microalbuminuria (<300 mg/day albuminuria). RESULTS: Albuminuria decreased in all subjects, with a statistically significant improvement in the supplement group compared with controls (P<0.05). Oxidative stress level was high in all microalbuminuria subjects at inclusion; it was significantly more reduced in the supplement group (P<0.05) after 4 weeks. During follow-up blood pressure values were controlled; all subjects were under one single antihypertensive. Blood and urinary tests at 4 weeks were normalized in all subjects. Fatigue was significantly decreased or disappeared in most supplemented subjects at 4 weeks, with better results than in controls. Compliance and tolerability to Meriva® were good. CONCLUSIONS: This registry study indicates that albuminuria - marker of TKD - is safely ameliorated with the standardized supplement Meriva®. Studies are needed to evaluate the effect of Meriva® in subjects with more significant clinical conditions (i.e. diabetics) or risk factors.
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Albuminúria/tratamento farmacológico , Curcumina/administração & dosagem , Nefropatias/tratamento farmacológico , Nefropatias/fisiopatologia , Extratos Vegetais/administração & dosagem , Adulto , Pressão Sanguínea , Suplementos Nutricionais , Feminino , Humanos , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Sistema de Registros , Insuficiência Renal/tratamento farmacológicoRESUMO
OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mLâ¢min-1â¢1.73 m-2, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) µmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mLâ¢min-1â¢1.73 m-2, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mLâ¢min-1â¢1.73 m-2 per year. CONCLUSION: Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).