BACKGROUND Hyperphosphatemia(HP)is a common complication in an advanced stage of chronic kidney disease(CKD)and is associated with cardiovascular issues,metabolic bone abnormalities and worsening of secondary hyperpar...BACKGROUND Hyperphosphatemia(HP)is a common complication in an advanced stage of chronic kidney disease(CKD)and is associated with cardiovascular issues,metabolic bone abnormalities and worsening of secondary hyperparathyroidism.Most patients on dialysis require phosphate binders to control HP.Sucroferric oxyhydroxide(SO)(Dynulta^(TM))is a calcium-free,polynuclear iron(III)based oral phosphate binder,for the treatment of HP.In this phase IV,open-label,singlearm,multi-center,12-week,SOLO CKD study evaluated efficacy and safety of Dynulta^(TM)in Indian CKD patients undergoing hemodialysis.AIM To investigate the efficacy,safety and tolerability of SO Chewable Tablet(Dynulta^(TM))in patients with CKD on hemodialysis.METHODS Hyperphosphatemic patients on hemodialysis and fulfilling eligibility criteria were included in the study for at least 12 weeks and received SO 1500 mg chewable tablet per day.The key endpoint was change in mean serum phosphorus levels after 12 weeks.Data were analysed using analysis of variance,Paired test,Wilcoxon test,and post-hoc comparisons,with P<0.05 considered statistically significant,using Graph Pad software.RESULTS A total of 114 patients were enrolled and 94 patients completed the study.The mean±SD serum phosphorous level was reduced from 7.62 mg/dL±2.02 mg/dL at baseline to 5.13 mg/dL±1.88 mg/dL after 12 weeks of treatment.At each follow-up visit,the reduction in mean serum phosphorous levels was statistically significant(P value<0.05)compared to baseline,confirming the efficacy of SO.A total of 33.33%of patients experienced adverse events(AEs).The most frequently reported AEs were pyrexia,nasopharyngitis and headache,which were considered unlikely to be related to the study drug treatment.No serious AEs was reported during the study period and no patients discontinued treatment due to AEs.CONCLUSION This first real-world study in Indian CKD patients on hemodialysis shows SO as a safe,and effective monotherapy for HP,though its small sample size limits generalizability.展开更多
BACKGROUND Secondary hyperparathyroidism,renal osteodystrophy,and cardiovascular adverse events can occur if long-term hyperphosphatemia is not corrected,leading to the adverse prognosis of patients with chronic renal...BACKGROUND Secondary hyperparathyroidism,renal osteodystrophy,and cardiovascular adverse events can occur if long-term hyperphosphatemia is not corrected,leading to the adverse prognosis of patients with chronic renal failure.Besides the use of phosphorus binders,clinical control measures for hyperphosphatemia in these patients should also incorporate diet control.AIM To observe doctor-led intensive diet education effects on health-related quality of life in patients with chronic renal failure and hyperphosphatemia.METHODS We assessed 120 patients with hyperphosphatemia and chronic renal failure on hemodialysis admitted to our hospital(July 2018 to March 2020).The control group(n=60)was given routine nursing guidance,and the observation group(n=60)was given doctor-led intensive diet education.The changes in EQ-5D-3L scores,disease-related knowledge,and compliance scores before intervention and 3 and 6 mo after intervention in the two groups were recorded.The levels of serum parathyroid hormone(iPTH),calcium(Ca),phosphorus(P),calciumphosphorus product(Ca×P),serum creatinine(Scr),and blood urea nitrogen(BUN)before intervention and 3 and 6 mo after intervention in the two groups were assessed along with patient satisfaction.RESULTS There was no significant difference in blood iPTH,Ca,P,Ca×P,Scr,or BUN levels between the groups before intervention.After 3 and 6 mo of intervention,the blood iPTH,Ca,P,and Ca×P levels in the two groups decreased gradually(P<0.05),but there were no significant differences in Scr or BUN.The blood iPTH,Ca,P,and Ca×P levels in the observation group were lower than those in the control group(P<0.05).The satisfaction rate in the observation group after 3 mo was 93.33%and after 6,90.00%,which was high compared with the 80.00%and 71.67%,respectively,in the control group(P<0.05).There was no significant difference in EQ-5D-3L score between the two groups before intervention.After 3 and 6 mo of intervention,the visual analogue scale score of the two groups increased gradually(P<0.05);and the scores of action ability,self-care,daily activities,pain and discomfort,and anxiety and depression decreased gradually(P<0.05).The overall EQ-5D-3L score in the observation group was better than that in the control group(P<0.05).There was no significant difference in diseaserelated knowledge or compliance scores between the groups before intervention.After 3 and 6 mo of intervention,the scores of disease,diet,and medication knowledge and compliance in the two groups increased gradually(P<0.05).The scores of disease-related knowledge and compliance were higher in the observation group than in the control group(P<0.05).CONCLUSION Doctor-led intensive diet education can improve patient satisfaction and the quality of life in patients with chronic renal failure and hyperphosphatemia and promote low-phosphorus diet behavior.展开更多
AIM:To establish the frequency of hyperphosphate-mia following the administration of sodium phosphate laxatives in low-risk patients. METHODS:One hundred consecutive ASAⅠ-Ⅱindividuals aged 35-74 years,who were under...AIM:To establish the frequency of hyperphosphate-mia following the administration of sodium phosphate laxatives in low-risk patients. METHODS:One hundred consecutive ASAⅠ-Ⅱindividuals aged 35-74 years,who were undergoing colonic cleansing with oral sodium phosphate(OSP) before colonoscopy were recruited for this prospective study.Exclusion criteria:congestive heart failure, chronic kidney disease,diabetes,liver cirrhosis,intestinal obstruction,decreased bowel motility,increased bowel permeability,and hyperparathyroidism.The day before colonoscopy,all the participants entered a 24-h period of diet that consisted of 4 L of clear fluids with sugar or honey and 90 mL(60 g)of OSP in two 45-mL doses,5 h apart.Serum phosphate was measured before and after the administration of the laxative. RESULTS:The main demographic data(mean±SD) were:age,58.9±8.4 years;height,163.8±8.6 cm; weight,71±13 kg;body mass index,26±4;women, 66%.Serum phosphate increased from 3.74±0.56 to 5.58±1.1 mg/dL,which surpassed the normal value (2.5-4.5 mg/dL)in 87%of the patients.The highest serum phosphate was 9.6 mg/dL.Urea and creatinine remained within normal limits.Post-treatment OSP se-rum phosphate concentration correlated inversely with glomerular filtration rate(P<0.007,R 2=0.0755),total body water(P<0.001,R 2=0.156)and weight(P< 0.013,R 2=0.0635). CONCLUSION:In low-risk,well-hydrated patients, the standard dose of OSP-laxative-induced hyperphos-phatemia is related to body weight.展开更多
Concerned about the current situation of hemodialysis patients'awareness of the problems related to dialysis complicated with hyperphosphatemia,further analyze the existing problems and causes,give targeted and in...Concerned about the current situation of hemodialysis patients'awareness of the problems related to dialysis complicated with hyperphosphatemia,further analyze the existing problems and causes,give targeted and individualized health education,improve the compliance of diet,medication and self-management,strengthen nurse-patient communication,establish a good nurse-patient relationship,reduce and control the incidence of hyperphosphatemia,improve patients'quality of life,and improve prognosis.展开更多
Casals et al have reported an inverse correlation between serum phosphate and body weight after administration of sodium phosphate at a dose of 60 g. Our group has already described the relationship between body weigh...Casals et al have reported an inverse correlation between serum phosphate and body weight after administration of sodium phosphate at a dose of 60 g. Our group has already described the relationship between body weight and hyperphosphatemia with these preparations, although our study was not quoted by Casals. We performed a pharmacokinetic study involving 13 volunteers who were divided into two groups on the basis of body weight： group I consisting of seven women with a median weight of 60 kg and group Ⅱ consisting of five men and one woman with a median weight of 119.2 kg. Group Ⅰdeveloped higher peak phosphate levels and maintained these levels above the subjects in Group Ⅱ for a prolonged time period despite adequate hydration being ensured with frequent monitoring of weight, fluid intake and total body weight. Our studydemonstrated that adequate hydration does not protect against the secondary effects of hyperphosphatemia. In the study by Casais et al, 66% of the study subjects were women, the correlation between serum phosphate and gender in their data also appears to be important. Women are at higher risk of acute phosphate nephropathy due to a diminished volume of distribution of the high dose of ingested phosphate. Decreased volume of distribution in women is due to diminished body weight. This is further compounded by decreased creatinine clearance in females.展开更多
Tumor lysis syndrome (TLS), hyperleukocytosis, and disseminated intravascular coagulation (DIC) are representative oncological emergencies that overlap mutually at the beginning of therapy for aggressive leukemia. Lat...Tumor lysis syndrome (TLS), hyperleukocytosis, and disseminated intravascular coagulation (DIC) are representative oncological emergencies that overlap mutually at the beginning of therapy for aggressive leukemia. Lately recombinant urate oxidase (rUO) enables to control uric acid level and its crystallization, the most frequent risk factor for clinical TLS;therefore, hyperphosphatemia appears to be the main risk in the rUO era. We here report an infantile leukemia patient who developed severe hyperphosphatemia, resulting in acute renal failure and ischemic encephalopathy. A 9-month-old female baby was adynamic with a bulging anterior fontanel, and was diagnosed as infantile acute lymphoblastic leukemia with a mixed lineage leukemia gene rearrangement. A laboratory examination revealed leukocytosis, bicytopenia, hyperuricemia, a prolonged prothrombin time, activated partial thromboplastin time, and elevated lactate dehydrogenase level. Soon after a reduced dose of prednisolone was administered, she developed hypoxia caused by systemic inflammatory response syndrome and heart failure. Her white blood cell count decreased sharply, leading to acute renal failure due to hyperphosphatemia, which required continuous hemodiafiltration for 48 hours. Although renal function subsequently recovered, severe ischemic encephalopathy remained. She achieved morphological remission once, however, relapsed and passed away soon after. We have to pay attention to the progression of hyperphosphatemia, hyperkakemia and DIC, although hyperuricemia was controlled using rUO. Changes in electrolyte levels must be continuously monitored, and TLS, DIC and/or hyperleukocytosis should be promptly managed especially in patients who are sensitive to therapy.展开更多
Non-absorbed macromolecular binders as sequestrants for phosphate ions offer an effective approach to treat hyperphosphatemia in ESRD （end-stage renal disease） patients. RenaGel has been an example with remarkable s...Non-absorbed macromolecular binders as sequestrants for phosphate ions offer an effective approach to treat hyperphosphatemia in ESRD （end-stage renal disease） patients. RenaGel has been an example with remarkable success of a polymer synthesized to prevent the absorption of dietary phosphate for ESRD patients. Electrostatic interaction is the primary driving force for complexation of phosphate-based anions with these amino groups in the polymer backbone. Chitosan is a deacetylation product of chitin, which is the structural element in the exoskeleton of crustaceans and cell walls of fungi. The amino groups in the backbone give the phosphate binding ability to chitosan. This article has demonstrated that chitosan exhibited a phosphate binding effect indeed. Thus, it has potential applications in environmental management and wastewater treatment, as well as treatment of hyperphosphatemia patients.展开更多
Background Hyperphosphatemia in renal failure has been identified as a major role in the pathogenesis of hyperparathyroidism that is independent of changes in serum calcium and 1,25（OH）203. The aim of this study was...Background Hyperphosphatemia in renal failure has been identified as a major role in the pathogenesis of hyperparathyroidism that is independent of changes in serum calcium and 1,25（OH）203. The aim of this study was to evaluate the expression of parathyroid Pit-1 in hyperphosphatemia-induced secondary hyperparathyroidism （SHPT） of chronic renal failure （CRF） rats. Methods Wistar rats with CRF induced by 5/6 nephrectomy were ramdomly fed with diet containing 1.2% inorganic phosphate （Pi, high phosphate （HP） group, n=-9） or 0.2% Pi （low phosphate （LP） group, n=9） for 10 weeks starting from the fourth week after the surgery. Another 7 nephrectomy rats with HP diet were intraperitoneally injected with phosphonoformic acid （PFA, the specific inhibitor of Pit-l, HP＋PFA group） 0.15 g/kg every other day for 10 weeks starting from HP diet. Another 6 HP rats injected with the same amount of normal saline as the control of the HP＋PFA group （HP＋saline group）. At the same time, 9 rats with sham surgery received HP diet as the controls. At the 4th week and 14th week, blood was taken for measurement of serum creatinine （SCr）, serum calcium （SCa）, serum phosphorus （SPi）, 1,25（OH）2D3 and intact parathyroid hormone （iPTH）. At the 14th week, two parathroid glands （PTGs） of each rat were removed by microsurgery, one gland for immunohistochemistry analysis of proliferating cell nuclear antigen （PCNA）, the other one for detection of Pit-1 by Western blotting, and for the measurement of Pit-1 mRNA and PTH mRNA by real-time quantitative polymerase chain reaction. Results In nephrectomy rats, high dierary phosphate induced a marked increase in serum phosphate, iPTH, PTH mRNA and PCNA parathyroid cells, accompanying Pit-1 and its mRNA in parathyroid gland increased significantly. However, serum Ca and 1,25（OH）2D3 remained unchanged. PFA decreased Pit-1 and its mRNA levels to reduce intact PTH, PTH mRNA and PCNA-positive parathyroid cells. Conclusions Expression of parathyroid Pit-1 in hyperphosphatemia-induced SHPT of CRF rats was upregulated. Pit-1 may mediate the stimulation to parathyroid gland by hyperphosphatemia.展开更多
Background We require a stable model to understand the molecular mechanism by which isolated hyperphosphatemia induces hyperparathyroidism secondary to chronic renal failure. The present study established a rat model ...Background We require a stable model to understand the molecular mechanism by which isolated hyperphosphatemia induces hyperparathyroidism secondary to chronic renal failure. The present study established a rat model of hyperphosphatemia-induced secondary hyperparathyroidism in chronic renal failure. Methods Twenty-nine rats with 5/6 nephrectomy （Nx） were divided into three groups and were fed for 10 weeks on a high phosphate diet （1.2% phosphate） starting from three different post-Nx time points. Parathyroid hormone mRNA in parathyroid gland was measured by real-time PCR and parathyroid cell hyperplasia was tested by proliferating cell nuclear antigen （PCNA） assay. Results The 10 rats fed a high phosphate diet starting from the fourth week post-Nx had isolated hyperphosphatemia and excess synthesis/secretion of parathyroid hormone, and hyperplasia of the parathyroid glands were induced （r=0.86-0.97, P 〈0.001）, but the levels of serum calcium and 1,25（OH）2D3 did not change. Conclusion A rat model of hyperphosphatemia-induced secondary hyperparathyroidism in chronic renal failure was established by 5/6 Nx and 10 weeks-high phosphate diet starting from the fourth week post-Nx.展开更多
文摘BACKGROUND Hyperphosphatemia(HP)is a common complication in an advanced stage of chronic kidney disease(CKD)and is associated with cardiovascular issues,metabolic bone abnormalities and worsening of secondary hyperparathyroidism.Most patients on dialysis require phosphate binders to control HP.Sucroferric oxyhydroxide(SO)(Dynulta^(TM))is a calcium-free,polynuclear iron(III)based oral phosphate binder,for the treatment of HP.In this phase IV,open-label,singlearm,multi-center,12-week,SOLO CKD study evaluated efficacy and safety of Dynulta^(TM)in Indian CKD patients undergoing hemodialysis.AIM To investigate the efficacy,safety and tolerability of SO Chewable Tablet(Dynulta^(TM))in patients with CKD on hemodialysis.METHODS Hyperphosphatemic patients on hemodialysis and fulfilling eligibility criteria were included in the study for at least 12 weeks and received SO 1500 mg chewable tablet per day.The key endpoint was change in mean serum phosphorus levels after 12 weeks.Data were analysed using analysis of variance,Paired test,Wilcoxon test,and post-hoc comparisons,with P<0.05 considered statistically significant,using Graph Pad software.RESULTS A total of 114 patients were enrolled and 94 patients completed the study.The mean±SD serum phosphorous level was reduced from 7.62 mg/dL±2.02 mg/dL at baseline to 5.13 mg/dL±1.88 mg/dL after 12 weeks of treatment.At each follow-up visit,the reduction in mean serum phosphorous levels was statistically significant(P value<0.05)compared to baseline,confirming the efficacy of SO.A total of 33.33%of patients experienced adverse events(AEs).The most frequently reported AEs were pyrexia,nasopharyngitis and headache,which were considered unlikely to be related to the study drug treatment.No serious AEs was reported during the study period and no patients discontinued treatment due to AEs.CONCLUSION This first real-world study in Indian CKD patients on hemodialysis shows SO as a safe,and effective monotherapy for HP,though its small sample size limits generalizability.
文摘BACKGROUND Secondary hyperparathyroidism,renal osteodystrophy,and cardiovascular adverse events can occur if long-term hyperphosphatemia is not corrected,leading to the adverse prognosis of patients with chronic renal failure.Besides the use of phosphorus binders,clinical control measures for hyperphosphatemia in these patients should also incorporate diet control.AIM To observe doctor-led intensive diet education effects on health-related quality of life in patients with chronic renal failure and hyperphosphatemia.METHODS We assessed 120 patients with hyperphosphatemia and chronic renal failure on hemodialysis admitted to our hospital(July 2018 to March 2020).The control group(n=60)was given routine nursing guidance,and the observation group(n=60)was given doctor-led intensive diet education.The changes in EQ-5D-3L scores,disease-related knowledge,and compliance scores before intervention and 3 and 6 mo after intervention in the two groups were recorded.The levels of serum parathyroid hormone(iPTH),calcium(Ca),phosphorus(P),calciumphosphorus product(Ca×P),serum creatinine(Scr),and blood urea nitrogen(BUN)before intervention and 3 and 6 mo after intervention in the two groups were assessed along with patient satisfaction.RESULTS There was no significant difference in blood iPTH,Ca,P,Ca×P,Scr,or BUN levels between the groups before intervention.After 3 and 6 mo of intervention,the blood iPTH,Ca,P,and Ca×P levels in the two groups decreased gradually(P<0.05),but there were no significant differences in Scr or BUN.The blood iPTH,Ca,P,and Ca×P levels in the observation group were lower than those in the control group(P<0.05).The satisfaction rate in the observation group after 3 mo was 93.33%and after 6,90.00%,which was high compared with the 80.00%and 71.67%,respectively,in the control group(P<0.05).There was no significant difference in EQ-5D-3L score between the two groups before intervention.After 3 and 6 mo of intervention,the visual analogue scale score of the two groups increased gradually(P<0.05);and the scores of action ability,self-care,daily activities,pain and discomfort,and anxiety and depression decreased gradually(P<0.05).The overall EQ-5D-3L score in the observation group was better than that in the control group(P<0.05).There was no significant difference in diseaserelated knowledge or compliance scores between the groups before intervention.After 3 and 6 mo of intervention,the scores of disease,diet,and medication knowledge and compliance in the two groups increased gradually(P<0.05).The scores of disease-related knowledge and compliance were higher in the observation group than in the control group(P<0.05).CONCLUSION Doctor-led intensive diet education can improve patient satisfaction and the quality of life in patients with chronic renal failure and hyperphosphatemia and promote low-phosphorus diet behavior.
文摘AIM:To establish the frequency of hyperphosphate-mia following the administration of sodium phosphate laxatives in low-risk patients. METHODS:One hundred consecutive ASAⅠ-Ⅱindividuals aged 35-74 years,who were undergoing colonic cleansing with oral sodium phosphate(OSP) before colonoscopy were recruited for this prospective study.Exclusion criteria:congestive heart failure, chronic kidney disease,diabetes,liver cirrhosis,intestinal obstruction,decreased bowel motility,increased bowel permeability,and hyperparathyroidism.The day before colonoscopy,all the participants entered a 24-h period of diet that consisted of 4 L of clear fluids with sugar or honey and 90 mL(60 g)of OSP in two 45-mL doses,5 h apart.Serum phosphate was measured before and after the administration of the laxative. RESULTS:The main demographic data(mean±SD) were:age,58.9±8.4 years;height,163.8±8.6 cm; weight,71±13 kg;body mass index,26±4;women, 66%.Serum phosphate increased from 3.74±0.56 to 5.58±1.1 mg/dL,which surpassed the normal value (2.5-4.5 mg/dL)in 87%of the patients.The highest serum phosphate was 9.6 mg/dL.Urea and creatinine remained within normal limits.Post-treatment OSP se-rum phosphate concentration correlated inversely with glomerular filtration rate(P<0.007,R 2=0.0755),total body water(P<0.001,R 2=0.156)and weight(P< 0.013,R 2=0.0635). CONCLUSION:In low-risk,well-hydrated patients, the standard dose of OSP-laxative-induced hyperphos-phatemia is related to body weight.
文摘Concerned about the current situation of hemodialysis patients'awareness of the problems related to dialysis complicated with hyperphosphatemia,further analyze the existing problems and causes,give targeted and individualized health education,improve the compliance of diet,medication and self-management,strengthen nurse-patient communication,establish a good nurse-patient relationship,reduce and control the incidence of hyperphosphatemia,improve patients'quality of life,and improve prognosis.
文摘Casals et al have reported an inverse correlation between serum phosphate and body weight after administration of sodium phosphate at a dose of 60 g. Our group has already described the relationship between body weight and hyperphosphatemia with these preparations, although our study was not quoted by Casals. We performed a pharmacokinetic study involving 13 volunteers who were divided into two groups on the basis of body weight： group I consisting of seven women with a median weight of 60 kg and group Ⅱ consisting of five men and one woman with a median weight of 119.2 kg. Group Ⅰdeveloped higher peak phosphate levels and maintained these levels above the subjects in Group Ⅱ for a prolonged time period despite adequate hydration being ensured with frequent monitoring of weight, fluid intake and total body weight. Our studydemonstrated that adequate hydration does not protect against the secondary effects of hyperphosphatemia. In the study by Casais et al, 66% of the study subjects were women, the correlation between serum phosphate and gender in their data also appears to be important. Women are at higher risk of acute phosphate nephropathy due to a diminished volume of distribution of the high dose of ingested phosphate. Decreased volume of distribution in women is due to diminished body weight. This is further compounded by decreased creatinine clearance in females.
文摘Tumor lysis syndrome (TLS), hyperleukocytosis, and disseminated intravascular coagulation (DIC) are representative oncological emergencies that overlap mutually at the beginning of therapy for aggressive leukemia. Lately recombinant urate oxidase (rUO) enables to control uric acid level and its crystallization, the most frequent risk factor for clinical TLS;therefore, hyperphosphatemia appears to be the main risk in the rUO era. We here report an infantile leukemia patient who developed severe hyperphosphatemia, resulting in acute renal failure and ischemic encephalopathy. A 9-month-old female baby was adynamic with a bulging anterior fontanel, and was diagnosed as infantile acute lymphoblastic leukemia with a mixed lineage leukemia gene rearrangement. A laboratory examination revealed leukocytosis, bicytopenia, hyperuricemia, a prolonged prothrombin time, activated partial thromboplastin time, and elevated lactate dehydrogenase level. Soon after a reduced dose of prednisolone was administered, she developed hypoxia caused by systemic inflammatory response syndrome and heart failure. Her white blood cell count decreased sharply, leading to acute renal failure due to hyperphosphatemia, which required continuous hemodiafiltration for 48 hours. Although renal function subsequently recovered, severe ischemic encephalopathy remained. She achieved morphological remission once, however, relapsed and passed away soon after. We have to pay attention to the progression of hyperphosphatemia, hyperkakemia and DIC, although hyperuricemia was controlled using rUO. Changes in electrolyte levels must be continuously monitored, and TLS, DIC and/or hyperleukocytosis should be promptly managed especially in patients who are sensitive to therapy.
文摘Non-absorbed macromolecular binders as sequestrants for phosphate ions offer an effective approach to treat hyperphosphatemia in ESRD （end-stage renal disease） patients. RenaGel has been an example with remarkable success of a polymer synthesized to prevent the absorption of dietary phosphate for ESRD patients. Electrostatic interaction is the primary driving force for complexation of phosphate-based anions with these amino groups in the polymer backbone. Chitosan is a deacetylation product of chitin, which is the structural element in the exoskeleton of crustaceans and cell walls of fungi. The amino groups in the backbone give the phosphate binding ability to chitosan. This article has demonstrated that chitosan exhibited a phosphate binding effect indeed. Thus, it has potential applications in environmental management and wastewater treatment, as well as treatment of hyperphosphatemia patients.
文摘Background Hyperphosphatemia in renal failure has been identified as a major role in the pathogenesis of hyperparathyroidism that is independent of changes in serum calcium and 1,25（OH）203. The aim of this study was to evaluate the expression of parathyroid Pit-1 in hyperphosphatemia-induced secondary hyperparathyroidism （SHPT） of chronic renal failure （CRF） rats. Methods Wistar rats with CRF induced by 5/6 nephrectomy were ramdomly fed with diet containing 1.2% inorganic phosphate （Pi, high phosphate （HP） group, n=-9） or 0.2% Pi （low phosphate （LP） group, n=9） for 10 weeks starting from the fourth week after the surgery. Another 7 nephrectomy rats with HP diet were intraperitoneally injected with phosphonoformic acid （PFA, the specific inhibitor of Pit-l, HP＋PFA group） 0.15 g/kg every other day for 10 weeks starting from HP diet. Another 6 HP rats injected with the same amount of normal saline as the control of the HP＋PFA group （HP＋saline group）. At the same time, 9 rats with sham surgery received HP diet as the controls. At the 4th week and 14th week, blood was taken for measurement of serum creatinine （SCr）, serum calcium （SCa）, serum phosphorus （SPi）, 1,25（OH）2D3 and intact parathyroid hormone （iPTH）. At the 14th week, two parathroid glands （PTGs） of each rat were removed by microsurgery, one gland for immunohistochemistry analysis of proliferating cell nuclear antigen （PCNA）, the other one for detection of Pit-1 by Western blotting, and for the measurement of Pit-1 mRNA and PTH mRNA by real-time quantitative polymerase chain reaction. Results In nephrectomy rats, high dierary phosphate induced a marked increase in serum phosphate, iPTH, PTH mRNA and PCNA parathyroid cells, accompanying Pit-1 and its mRNA in parathyroid gland increased significantly. However, serum Ca and 1,25（OH）2D3 remained unchanged. PFA decreased Pit-1 and its mRNA levels to reduce intact PTH, PTH mRNA and PCNA-positive parathyroid cells. Conclusions Expression of parathyroid Pit-1 in hyperphosphatemia-induced SHPT of CRF rats was upregulated. Pit-1 may mediate the stimulation to parathyroid gland by hyperphosphatemia.
文摘Background We require a stable model to understand the molecular mechanism by which isolated hyperphosphatemia induces hyperparathyroidism secondary to chronic renal failure. The present study established a rat model of hyperphosphatemia-induced secondary hyperparathyroidism in chronic renal failure. Methods Twenty-nine rats with 5/6 nephrectomy （Nx） were divided into three groups and were fed for 10 weeks on a high phosphate diet （1.2% phosphate） starting from three different post-Nx time points. Parathyroid hormone mRNA in parathyroid gland was measured by real-time PCR and parathyroid cell hyperplasia was tested by proliferating cell nuclear antigen （PCNA） assay. Results The 10 rats fed a high phosphate diet starting from the fourth week post-Nx had isolated hyperphosphatemia and excess synthesis/secretion of parathyroid hormone, and hyperplasia of the parathyroid glands were induced （r=0.86-0.97, P 〈0.001）, but the levels of serum calcium and 1,25（OH）2D3 did not change. Conclusion A rat model of hyperphosphatemia-induced secondary hyperparathyroidism in chronic renal failure was established by 5/6 Nx and 10 weeks-high phosphate diet starting from the fourth week post-Nx.
