RESUMO
BACKGROUND: Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3-5 chronic kidney disease (CKD) patients with underlying DKD. METHODS: Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2nd received allopurinol, the 3rd group received linagliptin, and the 4th received both allopurinol and linagliptin. Post-procedure follow-up for kidney functions was conducted for 2 weeks in all patients. RESULTS: 20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 (p < 0.02 and <0.03, respectively). None of the post-contrast AKI cases required dialysis. CONCLUSION: Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03470454.
Assuntos
Injúria Renal Aguda , Alopurinol , Meios de Contraste , Nefropatias Diabéticas , Linagliptina , Substâncias Protetoras , Humanos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Alopurinol/administração & dosagem , Alopurinol/uso terapêutico , Nefropatias Diabéticas/classificação , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/diagnóstico , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Linagliptina/administração & dosagem , Linagliptina/uso terapêutico , Estudos Prospectivos , Insuficiência Renal Crônica/classificação , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Meios de Contraste/efeitos adversos , Quimioprevenção/métodos , Quimioterapia Combinada , Acetilcisteína/administração & dosagem , Acetilcisteína/uso terapêutico , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/efeitos adversos , Substâncias Protetoras/uso terapêutico , Solução Salina/administração & dosagem , Solução Salina/uso terapêuticoRESUMO
BACKGROUND: Fabry's disease, an X-linked disorder of lysosomal α-galactosidase deficiency, leads to substrate accumulation in multiple organs. Migalastat, an oral pharmacologic chaperone, stabilizes specific mutant forms of α-galactosidase, increasing enzyme trafficking to lysosomes. METHODS: The initial assay of mutant α-galactosidase forms that we used to categorize 67 patients with Fabry's disease for randomization to 6 months of double-blind migalastat or placebo (stage 1), followed by open-label migalastat from 6 to 12 months (stage 2) plus an additional year, had certain limitations. Before unblinding, a new, validated assay showed that 50 of the 67 participants had mutant α-galactosidase forms suitable for targeting by migalastat. The primary end point was the percentage of patients who had a response (≥50% reduction in the number of globotriaosylceramide inclusions per kidney interstitial capillary) at 6 months. We assessed safety along with disease substrates and renal, cardiovascular, and patient-reported outcomes. RESULTS: The primary end-point analysis, involving patients with mutant α-galactosidase forms that were suitable or not suitable for migalastat therapy, did not show a significant treatment effect: 13 of 32 patients (41%) who received migalastat and 9 of 32 patients (28%) who received placebo had a response at 6 months (P=0.30). Among patients with suitable mutant α-galactosidase who received migalastat for up to 24 months, the annualized changes from baseline in the estimated glomerular filtration rate (GFR) and measured GFR were -0.30±0.66 and -1.51±1.33 ml per minute per 1.73 m(2) of body-surface area, respectively. The left-ventricular-mass index decreased significantly from baseline (-7.7 g per square meter; 95% confidence interval [CI], -15.4 to -0.01), particularly when left ventricular hypertrophy was present (-18.6 g per square meter; 95% CI, -38.2 to 1.0). The severity of diarrhea, reflux, and indigestion decreased. CONCLUSIONS: Among all randomly assigned patients (with mutant α-galactosidase forms that were suitable or not suitable for migalastat therapy), the percentage of patients who had a response at 6 months did not differ significantly between the migalastat group and the placebo group. (Funded by Amicus Therapeutics; ClinicalTrials.gov numbers, NCT00925301 [study AT1001-011] and NCT01458119 [study AT1001-041].).
Assuntos
1-Desoxinojirimicina/análogos & derivados , Doença de Fabry/tratamento farmacológico , Rim/química , Triexosilceramidas/análise , alfa-Galactosidase/antagonistas & inibidores , 1-Desoxinojirimicina/efeitos adversos , 1-Desoxinojirimicina/uso terapêutico , Adolescente , Adulto , Idoso , Diarreia/tratamento farmacológico , Diarreia/etiologia , Método Duplo-Cego , Doença de Fabry/complicações , Feminino , Taxa de Filtração Glomerular , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mutação , Triexosilceramidas/urina , Ultrassonografia , Adulto Jovem , alfa-Galactosidase/genéticaRESUMO
Low serum 25 hydroxyvitamin D (25 OH D) is common among chronic kidney disease (CKD) patients. This cross-sectional study is looking for the different factors associated with serum 25 OH D among pre-dialysis CKD. 1624 adult stage 3-5 CKD patients were studied beside 200 normal control subjects. All candidates were tested for body mass index (BMI), estimated glomerular filtration rate (eGFR), calcium (Ca), phosphorus (P), parathormone (PTH), 25 OH D, albumin, and uric acid (UA), and urine albumin/creatinine ratio (ACR). Multivariate linear regression analysis was done to determine predictors of 25 OH D. 98.6% of CKD patients have inadequate level of 25 OH D vs 48% of normal subjects. Serum 25 OH D was significantly lower in CKD patients (mean ± S.D = 16.54 ± 5.8 vs 37.79 ± 3.58 ng/mL for CKD vs control group respectively, p < .001). Serum level of 25 OH D has significant positive correlation with Ca (r = 0.337, p < .001), and significant negative correlation with P, PTH, UA, and ACR (r = -0.440, -0. 679, -0.724, and -0.781respectively, p < .001 in all). The independent predictors of 25 OH D were Ca, P, UA, PTH, and ACR (R square = 0.7, ß = -0.087, -0.226, -0.313, -0.253, and -0.33 respectively, p < .001 in all). In conclusion, pre-dialysis CKD patients frequently suffer low 25 OH D. Among the different abnormalities related to CKD, urine albumin excretion rate and UA are the most important predictors of 25 OH D in these patients.
Assuntos
Albuminúria/urina , Insuficiência Renal Crônica/complicações , Ácido Úrico/sangue , Deficiência de Vitamina D/diagnóstico , Vitamina D/análogos & derivados , Adolescente , Adulto , Albuminas/análise , Albuminúria/sangue , Albuminúria/etiologia , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/urina , Vitamina D/sangue , Deficiência de Vitamina D/etiologia , Adulto JovemRESUMO
Loin pain is frequently not associated with any urinary abnormality. Musculoskeletal abnormalities are not uncommon as alternative cause of flank pain. Osteomalacia of the ribs was infrequently encountered as the cause of flank pain. Vitamin D deficiency has been reported as a common problem worldwide with special predilection to the Middle East area. In this study, we looked for vitamin D deficiency in patients with flank pain associated with tenderness over the tips of the lowermost ribs. Out of 783 patients presenting with unilateral or bilateral flank pain to a single center over a period of 3 years, 316 did not have a definite urologic cause (group B). One hundred and eighty-seven of these patients had distinct tenderness over the costal margin (group B1) that could not be explained by history and radiology. All patients of group B were tested for serum levels of 25(OH) vitamin D. Very low serum levels of 25(OH) vitamin D was detected in all cases of group B1 and in only in only 26.4% of the remaining cases of group B (group B2). Relief of flank pain was noticed within 2 months in 55.1% of vitamin D deficient cases. In patients presenting with flank pain, the existence of tenderness of the last ribs instead of the renal angle proper should alert to a possible cause in the rib cage. Estimation of serum vitamin D level should be performed in these cases.
Assuntos
Dor no Flanco/etiologia , Deficiência de Vitamina D/complicações , Adulto , Idoso , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Adulto JovemRESUMO
Insulin resistance (IR) is very common among chronic kidney disease (CKD) patients. Disturbance in mineral and bone metabolism (MBD) seems to play a role in the pathogenesis of insulin resistance. Fibroblast growth factor-23 (FGF23) is evolving as the most important link between MBD and many pathologic sequences of CKD. The aim was to evaluate IR in pre-dialysis CKD patients looking for a possible association to mineral metabolism among CKD patients. A total of 100 stage 3-5 CKD patients were selected beside 20 normal control subjects. Homeostatic model assessment of insulin resistance (HOMA-IR) was used to assess IR in selected cases. Both groups were compared for fasting blood glucose (FBG), fasting blood insulin (FBI), HOMA-IR, estimated glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), 25 hydroxy vitamin D (25 OH vit D), parathormone (PTH), and uric acid (UA). Correlation study between HOMA_IR and different studied parameters was performed. HOMA-IR is significantly higher in CKD (8.87 ± 3.48 vs. 3.97 ± 0.34 in CKD vs. control, respectively, p < .001). In addition CKD patients have significantly higher FGF23 (235 ± 22.96 vs. 139 ± 12.3 pg/mL, p < .001), PTH (76.9 ± 15.27 vs. 47.9 ± 2.52 pg/mL, p < .001), P (4.3 ± 0.67 vs. 3.6 ± 0.23 mg/dL, p < .001), and UA (5 ± 1.22 vs. 4.85 ± 0.48 mg/dL, p < .001) and significantly lower Ca (8.2 ± 0.3 vs. 8.9 ± 0.33 mg/dL, p < .001), and 25 (OH) vit D (17 ± 5.63 vs. 37 ± 3.43 ng/mL, p < .001). Stepwise linear regression analysis revealed that BMI, GFR, Ca, P, and FGF23 were the only significant predictors of HOMA IR. Increased IR in CKD is a consequence of the uremic status and is intimately associated with disturbed phosphate metabolism and FGF23. Further studies are needed to look for an underlying mechanism.
Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Taxa de Filtração Glomerular , Resistência à Insulina , Fosfatos/metabolismo , Insuficiência Renal Crônica/metabolismo , Adulto , Glicemia , Índice de Massa Corporal , Cálcio/sangue , Cálcio/metabolismo , Estudos de Casos e Controles , Creatinina/urina , Jejum , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Masculino , Fosfatos/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/urina , Ácido Úrico/sangue , Adulto JovemRESUMO
In the last five years, the medical community was astonishingly surprised by the sequential large outcome trials that displayed the renal effects of sodium glucose co-transporter inhibitors (SGLT2Is) in type 2 diabetes mellitus (T2DM) patients with or without chronic kidney disease (CKD). This favorable effect was later disclosed in non-diabetic CKD patients. The EMPA-REG OUTCOME trial was the first trial that showed a reduction for the need for dialysis in patients suffering diabetic kidney disease (DKD) by 55%. This figure is double the score achieved by the angiotensin receptor blocker, Losartan, in RENAAL trial. The need for dialysis in DAPA-CKD trial was reduced in diabetic and non-diabetic CKD patients by 33%. The renal-specific composite outcome was reduced by 39% in EMPA-REG trial, 40% in CANVAS study, 47% in DECLARE-TIMI 58 study, 34% in CREDENCE trial, and 44% in DAPA-CKD trial. The greater surprise is the significant favorable effect of SGLT2Is on overall mortality in CKD patients with or without T2DM. Similar survival benefit was not previously encountered with any of the medications used in CKD patients with or without diabetes. In this review, we disclose the results of the DAPA-CKD trial, the CREDENCE trial and those of several cardiovascular outcome trials (CVOT) that used different SGLT2Is and showed that patients with lower eGFR levels may have greater benefit with respect to cardiovascular morbidity than patients with normal kidney function. In addition, we discuss the different mechanisms of action that explain the renal beneficial effects of SGLT2Is.
Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insuficiência Renal Crônica , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Glucose , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Sódio , Ensaios Clínicos como AssuntoRESUMO
BACKGROUND: Many of the mineral metabolite abnormalities encountered in chronic kidney disease (CKD) patients were found also associated with acute kidney injury (AKI). In the last decade, sclerostin was found to intimately affect bone mineral metabolism in CKD patients. Nothing is known about sclerostin in AKI. OBJECTIVE: We looked for serum level of sclerostin in AKI patients in comparison to normal control subjects and if there is an impact on metabolic derangement, endothelial function or clinical outcome. CASES AND METHODS: This is a cross sectional case control observational study of 219 AKI cases (group I) beside 219 age matched normal control subjects (group II). All cases of group I were in the intensive care because of sepsis; 86 had acute on CKD (group Ib), while 133 had de novo AKI (group Ia). All studied subjects underwent estimation of serum sclerostin, parathyroid hormone (PTH), 25 hydroxy vitamin D (25 OH vit D), fibroblast growth factor 23 (FGF23), C-reactive protein (CRP), interleukin 6 (IL6), Homeostatic Model Assessment for Insulin Resistance (Homa IR), beside the routine CBC, kidney and liver function tests, serum calcium, and phosphorus, and flow mediated vasodilation of brachial artery (FMD). Follow-up of group I cases was done till they recovered or passed away. RESULTS: Serum sclerostin, PTH, FGF23, phosphorus, CRP, IL6, HOMA IR, creatinine, urea, uric acid, ALT, AST and white blood cell count (WBC) were significantly higher while serum calcium, 25 OH vit D, hemoglobin, platelet count and FMD were significantly lower in group I compared to group II (P<0.001 in all). On the other hand, there was no significant difference in serum sclerostin, PTH, FGfF23, 25 OH vit D, CRP, IL6, Homa IR and FMD between group Ia and Ib. Survivors were younger in age (median 55.5 vs. 60 years, P<0.04), had lower AST (30.5 vs. 58 units, P<0.001), had higher platelet count (206 vs 162×109/L, P<0.001), otherwise, there was no significant difference in any of the other parameters between survivors and patients that were lost. Serum sclerostin had strong correlation with FGF23 in group I (r=0.99, P<0.001) and group II (r=1, P<0.001). Homa IR had positive correlation with serum sclerostin (r=0.148, P=0.014) and serum FGF23 (r=0.142, P=0.018) in group I. CONCLUSION: Sclerostin is intimately related to FGF23. Sclerostin level increases in AKI patients. Both sclerostin and FGF23 might increase insulin resistance but have no impact on FMD. Neither sclerostin nor FGF23 interfere with AKI outcome.
Assuntos
Injúria Renal Aguda , Resistência à Insulina , Insuficiência Renal Crônica , Biomarcadores , Proteína C-Reativa , Cálcio , Creatinina , Estudos Transversais , Fatores de Crescimento de Fibroblastos , Humanos , Interleucina-6 , Minerais/metabolismo , Hormônio Paratireóideo , Fósforo , Ureia , Ácido Úrico , Vitamina DRESUMO
In the last five years, the medical community was astonishingly surprised by the sequential large outcome trials that displayed the renal effects of sodium glucose co-transporter inhibitors (SGLT2Is) in type 2 diabetes mellitus (T2DM) patients with or without chronic kidney disease (CKD). This favorable effect was later disclosed in non-diabetic CKD patients. The EMPA-REG OUTCOME trial was the first trial that showed a reduction for the need for dialysis in patients suffering diabetic kidney disease (DKD) by 55%. This figure is double the score achieved by the angiotensin receptor blocker, Losartan, in RENAAL trial. The need for dialysis in DAPA-CKD trial was reduced in diabetic and non-diabetic CKD patients by 33%. The renal-specific composite outcome was reduced by 39% in EMPA-REG trial, 40% in CANVAS study, 47% in DECLARE-TIMI 58 study, 34% in CREDENCE trial, and 44% in DAPA-CKD trial. The greater surprise is the significant favorable effect of SGLT2Is on overall mortality in CKD patients with or without T2DM. Similar survival benefit was not previously encountered with any of the medications used in CKD patients with or without diabetes. In this review, we disclose the results of the DAPA-CKD trial, the CREDENCE trial and those of several cardiovascular outcome trials (CVOT) that used different SGLT2Is and showed that patients with lower eGFR levels may have greater benefit with respect to cardiovascular morbidity than patients with normal kidney function. In addition, we discuss the different mechanisms of action that explain the renal beneficial effects of SGLT2Is.
RESUMO
BACKGROUND: Recent studies have demonstrated negative associations of serum uric acid (SUA) with serum 25 hydroxy vitamin D (25 [OH] vit D) among CKD patients. OBJECTIVE: The aim of the study was to look for the impact of hypouricemic therapy using allopurinol on serum level of 25 (OH) vit D in CKD patients. CASES AND METHODS: Seventy-two CKD stage 3-5 patients were selected to this study. Patients with SUA above 7 mg/dL were allocated to hypouricemic therapy using allopurinol (group I). A control group of cases not suffering marked increase in SUA were included as control group (group II). All cases were followed up for 3 months. Serum Cr, SUA, ionized calcium (SiCa), phosphorus, 25 (OH) vitD, parathyroid hormone (PTH), and 24-h urine protein were estimated at entry and by the end of the study. RESULTS: At least 20 cases completed the study in each group. Serum 25 (OH) vit D significantly increased in group I (26.4 [14.1] vs. 39.6 [14.8] at entry vs. at end of the study, p < 0.001). In addition, SUA, PTH, and urine protein significantly decreased (11 [1.6] vs. 3.95 [0.58] mg/dL, 267.5 [97.5] vs. 225.5 [153] ng/mL, and 2.7 [1.18] vs. 1.5 [1.08] gm/day, p < 0.001, = 0.043, and <0.001 respectively). SiCa and phosphorus significantly increased (4.4 [0.3] vs. 5.2 [0.5] mg/dL and 4.25 [0.72] vs. 4.9 [0.75] mg/dL, p < 0.001 and = 0.007, respectively). CONCLUSION: This study supports a negative causal relationship between SUA and serum 25 (OH) vit D. Further studies are still needed to confirm this conclusion.
Assuntos
Alopurinol/uso terapêutico , Supressores da Gota/uso terapêutico , Falência Renal Crônica/sangue , Ácido Úrico/sangue , Vitamina D/análogos & derivados , Adulto , Alopurinol/administração & dosagem , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Feminino , Supressores da Gota/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Vitamina D/sangueRESUMO
BACKGROUND: Many of the mineral metabolite abnormalities encountered in chronic kidney disease (CKD) patients were found also associated with acute kidney injury (AKI). In the last decade, sclerostin was found to intimately affect bone mineral metabolism in CKD patients. Nothing is known about sclerostin in AKI. OBJECTIVE: We looked for serum level of sclerostin in AKI patients in comparison to normal control subjects and if there is an impact on metabolic derangement, endothelial function or clinical outcome. CASES AND METHODS: This is a cross sectional case control observational study of 219 AKI cases (group I) beside 219 age matched normal control subjects (group II). All cases of group I were in the intensive care because of sepsis; 86 had acute on CKD (group Ib), while 133 had de novo AKI (group Ia). All studied subjects underwent estimation of serum sclerostin, parathyroid hormone (PTH), 25 hydroxy vitamin D (25 OH vit D), fibroblast growth factor 23 (FGF23), C-reactive protein (CRP), interleukin 6 (IL6), Homeostatic Model Assessment for Insulin Resistance (Homa IR), beside the routine CBC, kidney and liver function tests, serum calcium, and phosphorus, and flow mediated vasodilation of brachial artery (FMD). Follow-up of group I cases was done till they recovered or passed away. RESULTS: Serum sclerostin, PTH, FGF23, phosphorus, CRP, IL6, HOMA IR, creatinine, urea, uric acid, ALT, AST and white blood cell count (WBC) were significantly higher while serum calcium, 25 OH vit D, hemoglobin, platelet count and FMD were significantly lower in group I compared to group II (P<0.001 in all). On the other hand, there was no significant difference in serum sclerostin, PTH, FGfF23, 25 OH vit D, CRP, IL6, Homa IR and FMD between group Ia and Ib. Survivors were younger in age (median 55.5 vs. 60 years, P<0.04), had lower AST (30.5 vs. 58 units, P<0.001), had higher platelet count (206 vs 162×109/L, P<0.001), otherwise, there was no significant difference in any of the other parameters between survivors and patients that were lost. Serum sclerostin had strong correlation with FGF23 in group I (r=0.99, P<0.001) and group II (r=1, P<0.001). Homa IR had positive correlation with serum sclerostin (r=0.148, P=0.014) and serum FGF23 (r=0.142, P=0.018) in group I. CONCLUSION: Sclerostin is intimately related to FGF23. Sclerostin level increases in AKI patients. Both sclerostin and FGF23 might increase insulin resistance but have no impact on FMD. Neither sclerostin nor FGF23 interfere with AKI outcome.
RESUMO
BACKGROUND: Vascular calcification has detrimental consequences on chronic kidney disease (CKD) patients, yet its pathogenesis is not fully understood. Fibroblast growth factor-23 (FGF-23) is involved in the regulation of mineral metabolism which may in turn affect vascular calcification. Data on the relationship between FGF-23 and peripheral vascular calcification, using conventional radiographs, are conflicting, and less is known about its relation to aortic calcification. We conducted this study to investigate the relationship between FGF-23 and aortic calcification in a standard haemodialysis setting. METHODS: The study included 65 haemodialysis patients (46 prevalent and 19 incident) on a three times 4-h dialysis schedule as well as 15 controls. Those with diabetes, oral anticoagulation or parathyroidectomy were excluded. Intact FGF-23, parathormone, lipids, calcium and phosphorus were measured. Aortic calcification index (ACI) was assessed by a non-contrast computerized tomography (CT) of the abdominal aorta. RESULTS: FGF-23 levels were higher among haemodialysis patients (4681.3 +/- 3906.1 pg/mL) compared to controls (98.2 +/- 51.9 pg/mL), P = 0.005. ACI was higher in haemodialysis patients (14.1 +/- 12) than controls (3.2 +/- 3.6), P = 0.009. FGF-23 (P < 0.0001) and systolic blood pressure (BP) (P < 0.0001) were independently related to ACI in stepwise multiple regression analysis of pooled analysis of haemodialysis patients, R(2) = 0.476; in subgroup analysis, the independent factors relating to ACI among prevalent dialysis patients were systolic BP (P < 0.0001), FGF-23 (P = 0.002) and age (P = 0.012), R(2)=0.48; whereas in incident patients, only FGF-23 was associated with ACI (P = 0.007), R(2) = 0.37. CONCLUSIONS: In haemodialysis patients, FGF-23 and ACI were significantly increased, and FGF-23 was independently associated with aortic calcification.
Assuntos
Doenças da Aorta/sangue , Doenças da Aorta/epidemiologia , Calcinose/sangue , Calcinose/epidemiologia , Fatores de Crescimento de Fibroblastos/sangue , Nefropatias/terapia , Diálise Renal , Adulto , Idoso , Aorta Abdominal/diagnóstico por imagem , Estudos de Casos e Controles , Doença Crônica , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Nefropatias/complicações , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Análise de Regressão , Fatores de Risco , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The impact of hepatitis virus infection on arterial calcification (AC) was not studied. OBJECTIVE: To study the prevalence, severity and distribution of AC in incident hemodialysis patients with hepatitis B and C viral infection. CASES AND METHODS: 172 stage 5 CKD adults (98 male and 74 female) were included; 58 of them were seronegative for both hepatitis B and C (SN group), 48 were positive for hepatitis B virus infection (HBV group) and 66 were hepatitis C virus positive (HCV group). Beside histopathology of the obtained arterial samples, all these cases were examined for body mass index (BMI), serum calcium (Ca), phosphorus (P), alkaline phosphatase (AP), serum albumin, uric acid (UA), alanine transaminase (ALT), parathormone (PTH), fibroblast growth factor 23(FGF23), interleukin 6 (IL6), and 25 hydroxy vitamin D (25 (OH) vit D), hemoglobin concentration, and serum ferritin. RESULTS: 86 (50%) of the cases had AC; 11 of them were in SN group (19%), 9 in HBV group (18.8%) and all the 66 HCV group (100%). In SN group, 4 had intimal calcification, 5 had medial calcification, and 2 had both intimal and medial calcification. In HBV group, 9 had intimal calcification, while no cases were encountered with either medial or both site calcifications. In HCV group, 16 had intimal calcification, 31 had medial calcification, and 19 had both intimal and medial calcification. Calcification was in the form of spots in one case in SN group, and 6 cases in HBV group, a single plaque of calcification in 5 cases of SN group, 3 cases of HBV group, and 16 cases of HCV group, multiple plaques were detected in 4 cases in SN group, and 31 cases in HCV group, and diffuse calcification in one case in SN group, and 19 cases in HCV group. In HBV group, calcification was only detected in patients with high viremia, while all patients with low or moderate viremia were devoid of calcification. In HCV group, all patients with low viremia had intimal solitary plaque of calcification, all patients with moderate viremia had multiple plaques of medial calcification, while all patients with high viremia had diffuse intimal and medial calcification. Both groups of viral hepatitis were significantly different in comparison to SN group in either distribution or calcification score (P<0.001 in all). HBV group had significantly lower serum P, CaxP and PTH in comparison to SN group (4.6±0.66 vs. 5.45±0.77mg/dL, 36.4±7.2 vs. 44.1±8.69, and 348±65.4 vs. 405.9±83.2pg/mL, P<0.001, <0.001, and 0.035 respectively). On the other hand, HCV group did not show any significant difference in any of the studied parameters compared to SN group. CONCLUSION: HCV positive patients are more prone to develop AC that is more extensive. HBV positive patients were less likely to have arterial medial calcification, probably related to lower serum phosphorus, CaxP product and PTH. HCV infection should be added as risk factor for AC among CKD patients. Further studies are needed to confirm these findings.
Assuntos
Arteriopatias Oclusivas/epidemiologia , Hepatite B/complicações , Hepatite C/complicações , Diálise Renal , Insuficiência Renal Crônica/complicações , Calcificação Vascular/epidemiologia , Viremia/complicações , Adulto , Arteriopatias Oclusivas/sangue , Arteriopatias Oclusivas/etiologia , Arteriopatias Oclusivas/patologia , Proteínas Sanguíneas/análise , Cálcio/análise , Suscetibilidade a Doenças , Feminino , Fator de Crescimento de Fibroblastos 23 , Hepatite B/sangue , Hepatite C/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fósforo/sangue , Prevalência , Artéria Radial/química , Artéria Radial/patologia , Insuficiência Renal Crônica/sangue , Fatores de Risco , Índice de Gravidade de Doença , Túnica Íntima/química , Túnica Média/química , Calcificação Vascular/sangue , Calcificação Vascular/etiologia , Calcificação Vascular/patologia , Viremia/sangue , Vitamina D/sangue , Adulto JovemRESUMO
Vascular calcification (VC) is a well-known complication in patients with chronic kidney disease (CKD). Keeping in mind, the end goal to assess the genuine effect of mineral bone disease in the pathogenesis of blood vessel calcification during the pre-dialysis course of CKD, we assessed the prevalence and extent of abdominal aortic calcification (AAC) in nondiabetic CKD patients recently starting hemodialysis (HD). Eighty-one patients with end-stage renal disease beginning HD over a one-month period were selected. They underwent a detailed clinical examination and laboratory evaluation, including serum calcium, phosphorus, parathyroid hormone, fibroblast growth factor (FGF-23), and alkaline phosphatase were measured, and spiral computed tomography was performed to evaluate AAC score. AAC was present in 64 patients (79%). There was a significant correlation between the AAC score and age (r = 0.609, P <0.001) and FGF-23 (r = 0.800, P <0.001). This study suggests that the prevalence and extent of AAC are critical in incident HD patients. Serum FGF-23 level is the sole statistically significant correlate of AAC in these patients.
Assuntos
Aorta Abdominal , Doenças da Aorta/epidemiologia , Falência Renal Crônica/terapia , Diálise Renal , Calcificação Vascular/epidemiologia , Adulto , Idoso , Aorta Abdominal/diagnóstico por imagem , Doenças da Aorta/sangue , Doenças da Aorta/diagnóstico por imagem , Aortografia/métodos , Biomarcadores/sangue , Angiografia por Tomografia Computadorizada , Egito/epidemiologia , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fósforo/sangue , Prevalência , Diálise Renal/efeitos adversos , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada Espiral , Resultado do Tratamento , Calcificação Vascular/sangue , Calcificação Vascular/diagnóstico por imagem , Adulto JovemRESUMO
INTRODUCTION: Arterial calcification (AC) is a common complication in chronic kidney disease (CKD) patients that starts to develop before these patients need renal replacement therapy. In these patients, calcification can involve tunica intima or tunica media. This study has looked for the prevalence, severity, and distribution of arterial wall calcification in incident hemodialysis patients through intraoperative arterial biopsy obtained during creation of arteriovenous vascular access for hemodialysis. METHODOLOGY: One hundred and seventy-two stage 5 CKD adults (98 male and 74 female) were included. Beside histopathology of the obtained arterial samples, all these cases were tested for serum calcium (Ca), phosphorus (P), alkaline phosphatase, uric acid, parathormone (PTH), fibroblast growth factor 23 (FGF23), and 25 hydroxy vitamin D. RESULTS: Eighty six (50%) of the cases had AC (group I); 29 (17%) as intimal (subgroup Ii), 36 (21%) as medial (subgroup Im), while 21 (12%) had both intimal and medial calcification (subgroup Iim). Eighty-six patients (50%) were devoid of calcification (group II). Apart from the significantly higher serum level of PTH in group I, statistical analysis failed to disclose significant difference in any of the other studied parameters between the 2 groups. On the other hand, there were significant differences in serum P, Ca × P product, serum PTH, and FGF23 between patients according to intensity of calcification. CONCLUSION: Half of incident hemodialysis CKD patients have developed AC mainly in tunica media. Discrepancy in serum P can have an impact on calcification intensity.
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Diálise Renal , Insuficiência Renal Crônica/complicações , Túnica Íntima/patologia , Túnica Média/patologia , Calcificação Vascular/epidemiologia , Adulto , Biópsia , Estudos de Coortes , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fósforo/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapiaRESUMO
BACKGROUND: Serum 25-hydroxyvitamin D (25(OH)D) negatively correlates with serum phosphorus level of stage 3a-5 chronic kidney disease (CKD) patients. So far, no explanation has been provided for this negative association. OBJECTIVE: To confirm this negative association and determine if this relationship is mediated through other known co-morbid factors. CASES AND METHODS: One hundred (57 male and 43 female) pre-dialysis stage 3a-5 CKD patients were selected. Estimated glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), 25(OH)D, parathyroid hormone (PTH), and intact fibroblast growth factor-23 (FGF23) were assessed. A correlation analysis between serum 25(OH)D and the different parameters studied was performed. Multivariate linear regression analysis was carried out to determine predictors of 25(OH)D. RESULTS: The negative association between serum 25(OH)D and serum P was confirmed in univariate and multivariate correlation analysis. On the other hand, we failed to detect a significant association between 25(OH)D and serum FGF23. Serum P is the most important independent predictor of 25(OH)D in these patients (partial R2=0.15, p<0.0001). CONCLUSION: Serum P is likely to have a direct negative impact on serum 25(OH)D. Further studies are needed to determine the underlying mechanism.
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Fatores de Crescimento de Fibroblastos/sangue , Insuficiência Renal Crônica/sangue , Vitamina D/análogos & derivados , Adolescente , Adulto , Correlação de Dados , Estudos Transversais , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Vitamina D/sangue , Adulto JovemRESUMO
The recent discoveries in the fields of pathogenesis and management of diabetic nephropathy have revolutionized the knowledge about this disease. Little was added to the management of diabetic nephropathy after the introduction of renin angiotensin system blockers. The ineffective role of the renin- angiotensin system blockers in primary prevention of diabetic nephropathy in type 1 diabetes mellitus necessitated the search for other early therapeutic interventions that target alternative pathogenic mechanisms. Among the different classes of oral hypoglycemic agents, recent studies highlighted the distinguished mechanisms of sodium glucose transporter 2 blockers and dipeptidyl peptidase-4 inhibitors that settle their renoprotective actions beyond the hypoglycemic effects. The introduction of antioxidant and anti-inflammatory agents to this field had also added wealth of knowledge. However, many of these agents are still waiting well-designed clinical studies in order to prove their beneficial therapeutic role. The aim of this review of literature is to highlight the recent advances in understanding the pathogenesis, diagnosis, the established and the potential renoprotective therapeutic agents that would prevent the development or the progression of diabetic nephropathy.
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The association between uric acid (UA) on one side and systemic hypertension (Htn), dyslipidemia, glucose intolerance, overweight, fatty liver, renal disease and cardiovascular disease (CVD) on the other side is well recognized. However, the causal relationship between UA and these different clinical problems is still debatable. The recent years have witnessed hundreds of experimental and clinical trials that favored the opinion that UA is a probable player in the pathogenesis of these disease entities. These studies disclosed the strong association between hyperuricemia and metabolic syndrome (MS), obesity, Htn, type 2 diabetes mellitus (DM), non-alcoholic fatty liver disease, hypertriglyceridemia, acute kidney injury, chronic kidney disease (CKD), coronary heart disease (CHD), heart failure and increased mortality among cardiac and CKD patients. The association between UA and nephrolithiasis or preeclampsia is a non-debatable association. Recent experimental trials have disclosed different changes in enzyme activities induced by UA. Nitric oxide (NO) synthase, adenosine monophosphate kinase (AMPK), adenosine monophosphate dehydrogenase (AMPD), and nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase are affected by UA. These changes in enzymatic activities can lead to the observed biochemical and pathological changes associated with UA. The recent experimental, clinical, interventional, and epidemiologic trials favor the concept of a causative role of UA in the pathogenesis of MS, renal, and CVDs.
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Systemic inflammation is a recognized feature in chronic kidney disease (CKD). The role of systemic inflammation in the pathogenesis of vascular calcification was recently settled. FGF23 was recently accused as a direct stimulus of systemic inflammation. This finding explains the strong association of FGF23 to vascular calcification and increased mortality among CKD.
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The death rate among chronic kidney disease patients is the highest compared to other chronic diseases. 60% of these fatalities are cardiovascular. Cardiovascular calcifications and chronic inflammation affect almost all chronic kidney disease patients and are associated with cardiovascular mortality. Fibroblast growth factor 23 is associated with vascular calcification. Systemic inflammation in chronic kidney disease patients is multifactorial. The role of systemic inflammation in the pathogenesis of vascular calcification was recently reappraised. Fibroblast growth factor 23 was accused as a direct stimulus of left ventricular hypertrophy, uremic inflammation, and impaired neutrophil function. This review will discuss the underlying mechanisms that underlie the link between Fibroblast growth factor 23 and increased mortality encountered among chronic kidney disease patients.
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In the last five years, the medical community was astonishingly surprised by the sequential large outcome trials that displayed the renal effects of sodium glucose co-transporter inhibitors (SGLT2Is) in type 2 diabetes mellitus (T2DM) patients with or without chronic kidney disease (CKD). This favorable effect was later disclosed in non-diabetic CKD patients. The EMPA-REG OUTCOME trial was the first trial that showed a reduction for the need for dialysis in patients suffering diabetic kidney disease (DKD) by 55%. This figure is double the score achieved by the angiotensin receptor blocker, Losartan, in RENAAL trial. The need for dialysis in DAPA-CKD trial was reduced in diabetic and non-diabetic CKD patients by 33%. The renal-specific composite outcome was reduced by 39% in EMPA-REG trial, 40% in CANVAS study, 47% in DECLARE-TIMI 58 study, 34% in CREDENCE trial, and 44% in DAPA-CKD trial. The greater surprise is the significant favorable effect of SGLT2Is on overall mortality in CKD patients with or without T2DM. Similar survival benefit was not previously encountered with any of the medications used in CKD patients with or without diabetes. In this review, we disclose the results of the DAPA-CKD trial, the CREDENCE trial and those of several cardiovascular outcome trials (CVOT) that used different SGLT2Is and showed that patients with lower eGFR levels may have greater benefit with respect to cardiovascular morbidity than patients with normal kidney function. In addition, we discuss the different mechanisms of action that explain the renal beneficial effects of SGLT2Is. (AU)
Durante los últimos cinco años la comunidad médica se ha visto sorprendida por los grandes ensayos de resultados secuenciales que mostraron los efectos renales de los inhibidores del cotransportador de sodio y glucosa (SGLT2I) en pacientes con diabetes mellitus de tipo 2 (DMT2), con o sin enfermedad renal crónica (ERC). Este efecto favorable se descubrió posteriormente en pacientes no diabéticos con ERC. El ensayo EMPA-REG OUTCOME fue el primero que mostró una disminución del 55% de la necesidad de diálisis en pacientes con enfermedad renal diabética (ERD). Esta cifra duplica la puntuación obtenida por el antagonista de los receptores de la angiotensina (losartán) en el ensayo RENAAL. La necesidad de diálisis en el ensayo DAPA-CKD se redujo en un 33% en los pacientes con ERC diabéticos y no diabéticos. El criterio de valoración compuesto específico renal se redujo en un 39% en el ensayo EMPA-REG, un 40% en el estudio CANVAS, un 47% en el estudio DECLARE-TIMI 58, un 34% en el ensayo CREDENCE y un 44% en el ensayo DAPA-CKD. La mayor sorpresa es el significativo efecto favorable de los SGLT2I en la mortalidad global de los pacientes con ERC con o sin DMT2. No se había encontrado con anterioridad un beneficio de supervivencia similar con ninguno de los medicamentos utilizados en pacientes con ERC diabéticos y no diabéticos. En esta revisión presentamos los resultados del ensayo DAPA-CKD, el ensayo CREDENCE y varios ensayos de resultados cardiovasculares (CVOT) que utilizaron diferentes SGLT2I y mostraron que los pacientes con niveles más bajos de tasa de filtración glomerular estimada (TFGe) pueden gozar de un mayor beneficio con respecto a la morbilidad cardiovascular que los pacientes con función renal normal. Además, se abordan los diferentes mecanismos de acción que explican los efectos renales beneficiosos de los SGLT2I. (AU)