BACKGROUND Kidney dysfunction and reduced filtration capacity due to chronic kidney disease(CKD)lead to a shift in the body's acid-base balance,ultimately causing metabolic acidosis(MA).Sodium bicarbonate has been...BACKGROUND Kidney dysfunction and reduced filtration capacity due to chronic kidney disease(CKD)lead to a shift in the body's acid-base balance,ultimately causing metabolic acidosis(MA).Sodium bicarbonate has been used as a supplement to alleviate the symptoms and reverse the acidosis,and it may even slow the progression of CKD.However,its safety profile and overall effectiveness are uncertain.AIM To conduct a systematic review and meta-analysis of clinical trials assessing sodium bicarbonate's safety and efficacy for treating CKD-induced MA.METHODS Medline,Scopus,EMBASE,and Cochrane Central were systematically searched from inception until May 2024 to select all relevant randomized control trials(RCTs)and non-RCT(NRCTs)evaluating the effectiveness of sodium bicarbonate in correcting MA in end-stage renal disease patients.In addition,ClinicalTrials.gov,Medrxiv.org,and Google Scholar were searched for other literature.A random-effects meta-analysis was performed to derive mean differences(MD)and risk ratios(RR)with their 95%CI for continuous and dichotomous outcomes respectively.RESULTS Following a systematic search of the databases,20 RCTs and 2 and NRCTs comprising 2932 patients were included in our study.The results revealed that sodium bicarbonate significantly increased serum bicarbonate in CKD patients(MD:2.59,95%CI:0.95-4.22;P=0.02;I2=95%).However,there was a non-significant increase in estimated glomerular filtration rate(eGFR)in patients on sodium bicarbonate therapy(MD:0.93,95%CI:-1.88-3.75;P=0.52;I2=93%).Upon assessment of the safety profile of sodium bicarbonate,no significant association was found in the outcomes of death/prolonged hospitalization(RR:1.05,95%CI:0.84-1.32;P=0.66;I2=0%),or gastrointestinal disorders(RR:1.64,95%CI:0.35-7.66;P=0.53;I2=76%),or worsening edema(RR:1.26,95%CI:0.94-1.68;P=0.12;I2=37%)when compared to control.CONCLUSION Sodium bicarbonate therapy may halt worsening kidney function by correcting serum bicarbonate levels and treating MA.Although sodium bicarbonate does not significantly improve the eGFR,it may potentially prevent CKD progression while maintaining an overall favorable safety profile.展开更多
BACKGROUND Denosumab inhibits the receptor activator of nuclear factor kappa-ligand.It markedly increases bone mineral density and has been proven to reduce the risk of fractures.However,numerous adverse effects,notab...BACKGROUND Denosumab inhibits the receptor activator of nuclear factor kappa-ligand.It markedly increases bone mineral density and has been proven to reduce the risk of fractures.However,numerous adverse effects,notably hypocalcemia,are prevalent in patients with end-stage renal disease(ESRD).AIM To analyze the incidence and predictors of hypocalcemia caused by denosumab compared to control in patients with ESRD.METHODS We conducted this study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.PubMed,Scopus,Cochrane Central,and EMBASE were systematically searched from inception through March 2024.All original studies investigating the effects of denosumab on patients with ESRD compared to control were extracted.The primary outcomes of our study were the incidence of mild,severe,and very severe hypocalcemia.Secondary outcomes included serum levels of intact parathyroid hormone,calcium,and phosphate.The results were pooled and analyzed using a random-effects model.RESULTS Seven articles comprising 3240 patients were included in our study.Patients treated with denosumab had a significantly increased incidence of mild hypocalcemia[risk ratio(RR):2.79;95%confidence interval(CI):0.99-7.91;P=0.05;I^(2)=37%]and of very severe hypocalcemia(RR:9.58;95%CI:1.58-57.98;P=0.01;I^(2)=49%).However,an increase in the occurrence of severe hypocalcemia was non-significant(RR:4.23;95%CI:0.47-38.34;P=0.20;I^(2)=96%).Alternatively,denosumab showed a significant decrease in serum intact parathyroid hormone[mean difference(MD):-433.20,95%CI:-775.12 to-91.28,I2=98%,P=0.01],while there was a non-significant decrease in phosphate(MD:-0.47,95%CI:-1.35 to 0.41,I^(2)=88%,P=0.30)and calcium levels(MD:-0.33,95%CI:-0.95 to 0.29,I^(2)=94%,P=0.29).CONCLUSION Our study demonstrated that denosumab is significantly associated with mild and very severe hypocalcemia in patients with ESRD making it necessary to detect and prevent this side effect of treatment.展开更多
文摘BACKGROUND Kidney dysfunction and reduced filtration capacity due to chronic kidney disease(CKD)lead to a shift in the body's acid-base balance,ultimately causing metabolic acidosis(MA).Sodium bicarbonate has been used as a supplement to alleviate the symptoms and reverse the acidosis,and it may even slow the progression of CKD.However,its safety profile and overall effectiveness are uncertain.AIM To conduct a systematic review and meta-analysis of clinical trials assessing sodium bicarbonate's safety and efficacy for treating CKD-induced MA.METHODS Medline,Scopus,EMBASE,and Cochrane Central were systematically searched from inception until May 2024 to select all relevant randomized control trials(RCTs)and non-RCT(NRCTs)evaluating the effectiveness of sodium bicarbonate in correcting MA in end-stage renal disease patients.In addition,ClinicalTrials.gov,Medrxiv.org,and Google Scholar were searched for other literature.A random-effects meta-analysis was performed to derive mean differences(MD)and risk ratios(RR)with their 95%CI for continuous and dichotomous outcomes respectively.RESULTS Following a systematic search of the databases,20 RCTs and 2 and NRCTs comprising 2932 patients were included in our study.The results revealed that sodium bicarbonate significantly increased serum bicarbonate in CKD patients(MD:2.59,95%CI:0.95-4.22;P=0.02;I2=95%).However,there was a non-significant increase in estimated glomerular filtration rate(eGFR)in patients on sodium bicarbonate therapy(MD:0.93,95%CI:-1.88-3.75;P=0.52;I2=93%).Upon assessment of the safety profile of sodium bicarbonate,no significant association was found in the outcomes of death/prolonged hospitalization(RR:1.05,95%CI:0.84-1.32;P=0.66;I2=0%),or gastrointestinal disorders(RR:1.64,95%CI:0.35-7.66;P=0.53;I2=76%),or worsening edema(RR:1.26,95%CI:0.94-1.68;P=0.12;I2=37%)when compared to control.CONCLUSION Sodium bicarbonate therapy may halt worsening kidney function by correcting serum bicarbonate levels and treating MA.Although sodium bicarbonate does not significantly improve the eGFR,it may potentially prevent CKD progression while maintaining an overall favorable safety profile.
文摘BACKGROUND Denosumab inhibits the receptor activator of nuclear factor kappa-ligand.It markedly increases bone mineral density and has been proven to reduce the risk of fractures.However,numerous adverse effects,notably hypocalcemia,are prevalent in patients with end-stage renal disease(ESRD).AIM To analyze the incidence and predictors of hypocalcemia caused by denosumab compared to control in patients with ESRD.METHODS We conducted this study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.PubMed,Scopus,Cochrane Central,and EMBASE were systematically searched from inception through March 2024.All original studies investigating the effects of denosumab on patients with ESRD compared to control were extracted.The primary outcomes of our study were the incidence of mild,severe,and very severe hypocalcemia.Secondary outcomes included serum levels of intact parathyroid hormone,calcium,and phosphate.The results were pooled and analyzed using a random-effects model.RESULTS Seven articles comprising 3240 patients were included in our study.Patients treated with denosumab had a significantly increased incidence of mild hypocalcemia[risk ratio(RR):2.79;95%confidence interval(CI):0.99-7.91;P=0.05;I^(2)=37%]and of very severe hypocalcemia(RR:9.58;95%CI:1.58-57.98;P=0.01;I^(2)=49%).However,an increase in the occurrence of severe hypocalcemia was non-significant(RR:4.23;95%CI:0.47-38.34;P=0.20;I^(2)=96%).Alternatively,denosumab showed a significant decrease in serum intact parathyroid hormone[mean difference(MD):-433.20,95%CI:-775.12 to-91.28,I2=98%,P=0.01],while there was a non-significant decrease in phosphate(MD:-0.47,95%CI:-1.35 to 0.41,I^(2)=88%,P=0.30)and calcium levels(MD:-0.33,95%CI:-0.95 to 0.29,I^(2)=94%,P=0.29).CONCLUSION Our study demonstrated that denosumab is significantly associated with mild and very severe hypocalcemia in patients with ESRD making it necessary to detect and prevent this side effect of treatment.