Background: Sickle Cell Disease (SCD) renal abnormalities commence early in childhood. The glomerular abnormalities, glomerular hyperfiltration and albuminuria are the most prevalent. However, these SCD glomerulopathi...Background: Sickle Cell Disease (SCD) renal abnormalities commence early in childhood. The glomerular abnormalities, glomerular hyperfiltration and albuminuria are the most prevalent. However, these SCD glomerulopathies have not been considered exclusively in the adolescent age group. Objective: To determine the prevalence of glomerular hyperfiltration and albuminuria as well as identify the determinants for glomerular hyperfiltration in adolescents with SCD. Patients and Methods: The electronic patient records of 153 adolescents with SCD aged 10 - <19 years, attending the Paediatrics Haematology Clinic at Evelina London Children’s Hospital, United Kingdom, were reviewed from the 10<sup>th</sup> to 23<sup>rd</sup> June 2019. Clinical information and laboratory parameters were obtained. The glomerular filtration rate was derived using the Bedside Schwartz’s method. Grouping of the adolescents was based on the presence and absence of glomerular hyperfiltration, which was defined as glomerular filtration rate > 140 ml/min/m<sup>2</sup>. The presence of albuminuria was defined as urine albumin-to-creatinine ratio > 3 mg/mmol or protein-to-creatinine ratio of >15 mg/mmol. The clinical and laboratory determinants of glomerular hyperfiltration in the total study population were investigated. Result: Prevalence of glomerular hyperfiltration was 33.3% in the adolescents studied, and that of albuminuria was 15.7% amongst the SCD adolescents studied, of which 13.7% of those with glomerular hyperfiltration also had albuminuria. On univariable analysis, the SCD adolescents with glomerular hyperfiltration had significantly lower weight (48.0 ± 18.0 versus 54.8 ± 17.0 kg;<i>p</i> = 0.02), height (155.1 ± 13.1 versus 160.6 ± 13.1 cm;<i>p</i> = 0.01), body mass index (19.4 ± 5.0 versus 21.0 ± 4.3;<i>p</i> = 0.04), haemoglobin level (88.7 ± 13.3 versus 98.1 ± 21.7 g/L;<i>p</i> = 0.001), and serum creatinine level (0.4 ± 0.1 versus 0.6 ± 0.2 mg/dl;<i>p</i> = 0.0001) as compared to those with no glomerular hyperfiltration. The SCD adolescents with glomerular hyperfiltration also had significantly higher lactate dehydrogenase levels (525.9 ± 180.3 versus 449.6 ± 170.3 IU/L;<i>p</i> = 0.01) than those with no glomerular hyperfiltration. But, multivariable analysis revealed no associations. Conclusion: This study revealed that the prevalence of glomerular hyperfiltration in SCD children in the adolescent age group is high, and the high glomerular filtration rates begin to decline toward normal values in middle adolescence.展开更多
OBJECTIVE Diabetic nephropathy(DN)has been one of the most common complications of diabetes and the leading cause of end-stage renal disease.Glomerular hyperfiltrationis central in earlystage of DN and leads to the pr...OBJECTIVE Diabetic nephropathy(DN)has been one of the most common complications of diabetes and the leading cause of end-stage renal disease.Glomerular hyperfiltrationis central in earlystage of DN and leads to the progression of renal architectonic and functional abnormalities.Salvianolic acid A(SalA)has been proved to protect diabetic complications such as hepatic fibrosis and neuropathy.The present study was designed to investigate the effects of SalA on glomerular endothelial dysfunctionand diabetic nephropathy.METHODS Primary glomerular endothelial cells were subjected to assess permeability under injury of advanced glycation end-products(AGEs).AGEs-induced changes of Rho A/ROCK pathway and cytoskeleton rearrangement were assessed bywestern blotandimmunofluorescence.The beneficial effects of SalA on diabetic nephropathy were investigated in a rat model induced by high-fat and high-glucose diet combined with low dose of streptozocin(35 mg·kg^(-1),ip).Renal function and architectonic changes were evaluated by biochemical assay and PAS staining.RESULTS SalA 3μMameliorated AGEs-induced glomerular endothelial permeability(P<0.05)and suppressed rearrangement of cytoskeleton through inhibiting AGE-RAGE-Rho A/ROCK pathway.SalA1 mg·kg^(-1)markedly reduced endothelium loss(P<0.01)and glomerular hyperfiltration(P<0.05)in diabetic kidney.Subsequently,SalA 1 mg·kg^(-1) suppressed glomerular hypertrophy and mesangial matrix expansion,eventually reduced 24 h-urinary albumin and ameliorated renal function by decreasing blood urine nitrogen(BUN),serum creatinine(Scr)and serum n-acetyl-β-d-glucosaminidase(NAG).AGEs-RAGE-Nox4-induced oxidative stress was suppressed by the treatment of SalA 1 mg·kg^(-1).CONCLUSION SalA ameliorated AGEs-induced glomerular endothelial hyperpermeability,and effectively protected against early-stage diabetic nephropathy by reducing hyperfiltration and alleviating renal structural deterioration through inhibiting AGEs and its downstream pathway.Thus,SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.展开更多
文摘Background: Sickle Cell Disease (SCD) renal abnormalities commence early in childhood. The glomerular abnormalities, glomerular hyperfiltration and albuminuria are the most prevalent. However, these SCD glomerulopathies have not been considered exclusively in the adolescent age group. Objective: To determine the prevalence of glomerular hyperfiltration and albuminuria as well as identify the determinants for glomerular hyperfiltration in adolescents with SCD. Patients and Methods: The electronic patient records of 153 adolescents with SCD aged 10 - <19 years, attending the Paediatrics Haematology Clinic at Evelina London Children’s Hospital, United Kingdom, were reviewed from the 10<sup>th</sup> to 23<sup>rd</sup> June 2019. Clinical information and laboratory parameters were obtained. The glomerular filtration rate was derived using the Bedside Schwartz’s method. Grouping of the adolescents was based on the presence and absence of glomerular hyperfiltration, which was defined as glomerular filtration rate > 140 ml/min/m<sup>2</sup>. The presence of albuminuria was defined as urine albumin-to-creatinine ratio > 3 mg/mmol or protein-to-creatinine ratio of >15 mg/mmol. The clinical and laboratory determinants of glomerular hyperfiltration in the total study population were investigated. Result: Prevalence of glomerular hyperfiltration was 33.3% in the adolescents studied, and that of albuminuria was 15.7% amongst the SCD adolescents studied, of which 13.7% of those with glomerular hyperfiltration also had albuminuria. On univariable analysis, the SCD adolescents with glomerular hyperfiltration had significantly lower weight (48.0 ± 18.0 versus 54.8 ± 17.0 kg;<i>p</i> = 0.02), height (155.1 ± 13.1 versus 160.6 ± 13.1 cm;<i>p</i> = 0.01), body mass index (19.4 ± 5.0 versus 21.0 ± 4.3;<i>p</i> = 0.04), haemoglobin level (88.7 ± 13.3 versus 98.1 ± 21.7 g/L;<i>p</i> = 0.001), and serum creatinine level (0.4 ± 0.1 versus 0.6 ± 0.2 mg/dl;<i>p</i> = 0.0001) as compared to those with no glomerular hyperfiltration. The SCD adolescents with glomerular hyperfiltration also had significantly higher lactate dehydrogenase levels (525.9 ± 180.3 versus 449.6 ± 170.3 IU/L;<i>p</i> = 0.01) than those with no glomerular hyperfiltration. But, multivariable analysis revealed no associations. Conclusion: This study revealed that the prevalence of glomerular hyperfiltration in SCD children in the adolescent age group is high, and the high glomerular filtration rates begin to decline toward normal values in middle adolescence.
基金supported by National Nature Science Foundation of China(81770847)CAMS Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-3-007,2016-I2M-1-010)National Key Research and Development Plan(2016YFC1000905)
文摘OBJECTIVE Diabetic nephropathy(DN)has been one of the most common complications of diabetes and the leading cause of end-stage renal disease.Glomerular hyperfiltrationis central in earlystage of DN and leads to the progression of renal architectonic and functional abnormalities.Salvianolic acid A(SalA)has been proved to protect diabetic complications such as hepatic fibrosis and neuropathy.The present study was designed to investigate the effects of SalA on glomerular endothelial dysfunctionand diabetic nephropathy.METHODS Primary glomerular endothelial cells were subjected to assess permeability under injury of advanced glycation end-products(AGEs).AGEs-induced changes of Rho A/ROCK pathway and cytoskeleton rearrangement were assessed bywestern blotandimmunofluorescence.The beneficial effects of SalA on diabetic nephropathy were investigated in a rat model induced by high-fat and high-glucose diet combined with low dose of streptozocin(35 mg·kg^(-1),ip).Renal function and architectonic changes were evaluated by biochemical assay and PAS staining.RESULTS SalA 3μMameliorated AGEs-induced glomerular endothelial permeability(P<0.05)and suppressed rearrangement of cytoskeleton through inhibiting AGE-RAGE-Rho A/ROCK pathway.SalA1 mg·kg^(-1)markedly reduced endothelium loss(P<0.01)and glomerular hyperfiltration(P<0.05)in diabetic kidney.Subsequently,SalA 1 mg·kg^(-1) suppressed glomerular hypertrophy and mesangial matrix expansion,eventually reduced 24 h-urinary albumin and ameliorated renal function by decreasing blood urine nitrogen(BUN),serum creatinine(Scr)and serum n-acetyl-β-d-glucosaminidase(NAG).AGEs-RAGE-Nox4-induced oxidative stress was suppressed by the treatment of SalA 1 mg·kg^(-1).CONCLUSION SalA ameliorated AGEs-induced glomerular endothelial hyperpermeability,and effectively protected against early-stage diabetic nephropathy by reducing hyperfiltration and alleviating renal structural deterioration through inhibiting AGEs and its downstream pathway.Thus,SalA might be a promising therapeutic agent for the treatment of diabetic nephropathy.
