The correlation between sclerostin and bone mineral density in renal transplant recipients / Correlación entre la esclerostina y la densidad mineral ósea en receptores de trasplante renal

INTRODUCTION: Sclerostin is an anti-anabolic protein synthesized by osteocytes that may cause osteoporosis by inhibiting bone formation. The aim of our study was to investigate the correlation between sclerostin and bone mineral density (BMD) reduction in renal transplant recipients (RTRs) with more than 1 year after transplantation. MATERIAL AND METHODS: This cross-sectional study was conducted on 80 patients (38 (47.5%) male/42 (52.5%) female) RTRs with a mean age of 44.68±10.39 years. Patients were compared with an age and sex-matched control group of 40 healthy individuals. BMD was measured by dual-energy X-ray absorptiometry. The levels of sclerostin were determined using enzyme-linked immunosorbent assay. RESULTS: The mean sclerostin was 3.77±0.3pg/mL in patients and 3.81±0.21pg/mL in healthy individuals. The mean T score of femoral trochanter (FT) (FT-T), femoral neck (FN) (FN-T), lumbar vertebrae (L1-4) (L1-4-T) were −0.81±0.86, −1.08±1.09 and −0.8±1.2, respectively. The mean Z score of FT (FT-Z), FN (FN-Z), L1-4 (L1-4-Z) were −0.6±0.73, −0.32±0.9 and −0.54±1.13, respectively. FT-Z and L1-4-Z were lower in patients than healthy subjects (p = 0.009, p = 0.021 respectively). Serum creatinine (p < 0.001), intact parathyroid hormone (p < 0.001) were higher and phosphate (p < 0.001), was lower in patients than healthy subjects. Patients with a log10 sclerostin of >3.84pg/mL had higher FT-T (p = 0.040), FT-Z, FN-T (p = 0.018), FN-Z (p = 0.006) than those with a log10 sclerostin of ≤3.84pg/mL. There was a significant correlation between log10 sclerostin and FN-T (r=−0.296, p = 0.009) and FN-Z (r=−0.269, p = 0.019). In linear regression analysis, high sclerostin was found to be correlated with male gender, lower FN-T and lower FN-Z independently of other risk factors. CONCLUSION: The levels of sclerostin can predict reduction of proximal femur BMD and development of mineral and bone disorder in RTRs. There was no difference in sclerostin levels between RTRs and healthy individuals

INTRODUCCIÓN: La esclerostina es una proteína con efecto antianabólico sintetizada por los osteocitos que puede causar osteoporosis al inhibir la formación de hueso. El objetivo de nuestro estudio fue investigar la correlación entre la esclerostina y la reducción de la densidad mineral ósea (DMO) en receptores de trasplante renal (RTR) más de un año después del trasplante. MATERIALES Y MÉTODOS: Este estudio transversal se realizó en 80 pacientes (38 [47,5%] varones/42 [52,5%] mujeres) RTR con una edad media de 44,68±10,39 años. Se comparó a los pacientes con un grupo de comparación emparejado por edad y sexo de 40 individuos sanos. La DMO se midió mediante absorciometría de rayos X de doble energía. Los niveles de esclerostina se determinaron utilizando un enzimoinmunoanálisis de adsorción. RESULTADOS: El nivel medio de esclerostina fue de 3,77±0,3pg/ml en pacientes y 3,81±0,21pg/ml en individuos sanos. La puntuación T media del trocánter femoral (TF) (T-TF), del cuello femoral (CF) (T-CF), las vértebras lumbares (L1-4) (T-L1-4) fue de −0,81±0,86, −1,08±1,09 y −0,8±1,2, respectivamente. La puntuación Z media del TF (Z-TF), CF (Z-CF), L1-4 (Z-L1-4) fue de -0,6±0,73, −0,32±0,9 y −0,54±1,13, respectivamente. Las puntuaciones Z-TF y Z-L1-4 fueron inferiores en los pacientes que en los sujetos sanos (p = 0,009 y p = 0,021, respectivamente). Los niveles de creatinina sérica (p < 0,001) y hormona paratiroidea intacta (p < 0,001) fueron superiores en los pacientes que en los sujetos sanos, y los niveles de fosfato (p < 0,001) fueron inferiores. Los pacientes con un log10 esclerostina >3,84pg/ml tuvieron puntuaciones T-TF (p = 0,040), Z-TF, T-CF (p = 0,018), Z-CF (p = 0,006) superiores a las de los pacientes con un log10 esclerostina ≤3,84pg/ml. Se observó una correlación significativa entre log10 esclerostina y T-CF (r=−0,296, p = 0,009) y Z-CF (r=−0,269, p = 0,019). En el análisis de regresión lineal, se observó que los niveles elevados de esclerostina estaban correlacionados con el sexo masculino, una puntuación T-CF inferior y una puntuación Z-CF inferior independientemente de otros factores de riesgo. CONCLUSIÓN: Los niveles de esclerostina pueden predecir la reducción de la DMO del fémur proximal y el desarrollo de un trastorno mineral y óseo en RTR. No se observaron diferencias en los niveles de esclerostina entre los RTR y los individuos sanos

The correlation between sclerostin and bone mineral density in renal transplant recipients.

INTRODUCTION: Sclerostin is an anti-anabolic protein synthesized by osteocytes that may cause osteoporosis by inhibiting bone formation. The aim of our study was to investigate the correlation between sclerostin and bone mineral density (BMD) reduction in renal transplant recipients (RTRs) with more than 1 year after transplantation. MATERIAL AND METHODS: This cross-sectional study was conducted on 80 patients (38 (47.5%) male/42 (52.5%) female) RTRs with a mean age of 44.68±10.39 years. Patients were compared with an age and sex-matched control group of 40 healthy individuals. BMD was measured by dual-energy X-ray absorptiometry. The levels of sclerostin were determined using enzyme-linked immunosorbent assay. RESULTS: The mean sclerostin was 3.77±0.3pg/mL in patients and 3.81±0.21pg/mL in healthy individuals. The mean T score of femoral trochanter (FT) (FT-T), femoral neck (FN) (FN-T), lumbar vertebrae (L1-4) (L1-4-T) were -0.81±0.86, -1.08±1.09 and -0.8±1.2, respectively. The mean Z score of FT (FT-Z), FN (FN-Z), L1-4 (L1-4-Z) were -0.6±0.73, -0.32±0.9 and -0.54±1.13, respectively. FT-Z and L1-4-Z were lower in patients than healthy subjects (p=0.009, p=0.021 respectively). Serum creatinine (p<0.001), intact parathyroid hormone (p<0.001) were higher and phosphate (p<0.001), was lower in patients than healthy subjects. Patients with a log10 sclerostin of >3.84pg/mL had higher FT-T (p=0.040), FT-Z, FN-T (p=0.018), FN-Z (p=0.006) than those with a log10 sclerostin of ≤3.84pg/mL. There was a significant correlation between log10 sclerostin and FN-T (r=-0.296, p=0.009) and FN-Z (r=-0.269, p=0.019). In linear regression analysis, high sclerostin was found to be correlated with male gender, lower FN-T and lower FN-Z independently of other risk factors. CONCLUSION: The levels of sclerostin can predict reduction of proximal femur BMD and development of mineral and bone disorder in RTRs. There was no difference in sclerostin levels between RTRs and healthy individuals.

Echocardiographic assessment of right ventricular function in peritoneal dialysis patients.

OBJECTIVE: Cardiovascular disease is the leading cause of mortality in patients undergoing dialysis. Most of the available studies focus on left ventricular (LV) function in peritoneal dialysis (PD) patients; data about the effect of PD on right ventricular (RV) function are scarce. The aim of this study was to evaluate echocardiographic parameters of the RV in patients with end-stage renal disease (ESRD) undergoing PD. METHODS: A total of 73 individuals were grouped as follows: PD patients (n=36) and healthy controls (n=37). Echocardiography of the RV was performed in all of the patients using tissue Doppler imaging (TDI). RESULTS: The LV mass index (LVMI), left atrial (LA) diameter, posterior wall, and interventricular septum thicknesses were significantly greater in the PD group. The LV peak late diastolic atrial contraction (A) velocity was higher, and the peak early diastolic (E) velocity and the early diastolic velocity of the lateral mitral annulus (Em) were lower in the PD group compared with the control group. The right atrial (RA) diameter, RA area, RV fractional area change, RV myocardial performance index, and pulmonary vascular resistance values were similar in both groups, whereas the tricuspid annular plane systolic excursion (TAPSE) value was lower in the PD patients. The RV E; early diastolic (Ea), late diastolic (Aa), and systolic (Sa) velocities; deceleration time; and tricuspid regurgitation velocity were also similar in the 2 groups. Only the RV A velocity and the Ea/Aa ratio were significantly higher in the PD group, and the E/A ratio was lower in the PD group than in the control group. CONCLUSION: The results of conventional and TDI echocardiography indicated that RV systolic and diastolic functions were preserved in PD patients.

The Association of Fibroblast Growth Factor 23 with Arterial Stiffness and Atherosclerosis in Patients with Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND/AIMS: In patients with autosomal dominant polycystic kidney disease (ADPKD), cardiovascular events are the most frequent cause of mortality and morbidity. The aim of our study is to investigate the association between serum fibroblast growth factor-23 (FGF-23) and arterial stiffness (AS) as determined with brachial-ankle pulse wave velocity (baPWV) and atherosclerosis development as determined with carotid artery intima-media thickness (CA- IMT). METHODS: This cross-sectional study was conducted with totally 86 ADPKD patients, 50 (58.1%) female and 36 (41.9%) male, with a mean age of 49.5 ± 13.9 years. Patients were compared with healthy control group with similar distribution of age and gender. AS was assessed with baPWW, and atherosclerosis development was assessed with CA-IMT. CA-IMT > 9 mm was considered as increased atherosclerosis. Serum FGF-23 and soluble klotho (s-KL) levels were measured with enzyme-linked immunosorbent assay. Due to skewed distribution of variables, statistical calculations of FGF-23 and s-KL were performed with log10. RESULTS: According to the CKD stages, 46 (53.5%) patients had stage 1-2, 32 (37.2%) had stage 3-4, and 8 (9.3%) had predialysis stage 5 disease. Mean log10FGF-23 was 2.43 ± 0.41 pg/mL, and mean log10s-KL was 1.28 ± 0.09 ng/mL. Mean baPWV was 7.48 ± 1.68 m/sec, and mean CA-IMT was 0.63 ± 0.14 mm. Among patients at various stages of CKD, systolic blood pressure (SBP) (p = 0.003), diastolic blood pressure (DBP) (p = 0.002), creatinine, 1.25hydroxy(OH)2VitaminD3, log10FGF-23, baPWV, CA-IMT were higher (p < 0.001)andlog10s-KL were lower (p < 0.001) in comparison to healthy individuals. FGF-23 was positively correlated with creatinine, 1.25(OH)2VitD3 (p < 0.001), baPWV (p = 0.002) and CA-IMT (p = 0.005), and negatively correlated with eGFR (p < 0.001). CONCLUSION: In patients with ADPKD, as the disease stage advanced, serum FGF-23 levels increased while s-KL decreased. In ADPKD patients, AS and atherosclerosis development increased as compared to healthy subjects, and as CKD advanced. In ADPKD patients, the effect of serum FGF-23 on the development of AS and atherosclerosis in peripheral vessels is independent of s-KL.

The association of serum angiogenic growth factors with renal structure and function in patients with adult autosomal dominant polycystic kidney disease.

PURPOSE: Autosomal dominant polycystic kidney disease (ADPKD) is a common congenital chronic kidney disease (CKD). We report here the relationship of serum angiopoietin-1 (Ang-1), Ang-2, and vascular endothelial growth factor (VEGF) with total kidney volume (TKV), total cyst volume (TCV), and renal failure in adult ADPKD patients at various stages of CKD. METHODS: This cross-sectional study was conducted with 50 patients diagnosed with ADPKD and a control group of 45 age-matched healthy volunteers. In patient group, TKV and TCV were determined with upper abdominal magnetic resonance imaging, whereas in controls, TKV was determined with ultrasonography according to ellipsoid formula. Renal function was assessed with serum creatinine, estimated glomerular filtration rate (eGFR), and spot urinary protein/creatinine ratio (UPCR). Ang-1, Ang-2, and VEGF were measured using enzyme-linked immunosorbent assay. RESULTS: Patients with ADPKD had significantly higher TKV (p < 0.001) and UPCR (p < 0.001), and lower eGFR (p ≤ 0.001) compared to the controls. Log10Ang-2 was found to be higher in ADPKD patients at all CKD stages. Multiple linear regression analysis showed that there was no association between log10Ang-1, log10Ang-2, or log10VEGF and creatinine, eGFR, UPCR, log10TKV (p > 0.05). CONCLUSION: There was no association of serum angiogenic growth factors with TKV or renal failure in ADPKD patients. Increased serum Ang-2 observed in stages 1-2 CKD suggests that angiogenesis plays a role in the progression of early stage ADPKD, but not at later stages of the disease. This may be explained by possible cessation of angiogenesis in advanced stages of CKD due to the increased number of sclerotic glomeruli.

Functional bowel disorders and associated risk factors in hemodialysis patients in Turkey.

BACKGROUND/AIMS: Functional bowel disorders (FBDs) impair the quality of life in patients with end-stage renal disease (ESRD). The aim of our study was to determine the prevalence and distribution of the subtypes of FBDs in hemodialysis (HD) patients. MATERIALS AND METHODS: This prospective, cross-sectional study included 80 patients who received HD for more than 3 months (patient group) and 80 healthy controls (control group). FBDs were diagnosed according to the Rome II diagnostic criteria by excluding organic pathologies. RESULTS: Forty-six (57.5%) patients were males, and their average age was 62.13±12.92 (23-90) years. The mean duration of dialysis was 57.48±59.23 (3-312) months, and the mean Kt/V (K: dialyzer clearance of urea, t: dialysis time, V: volume of distrubition of urea) value was 1.53±0.31. The rate of FBDs was significantly higher in the patient group than in the control group (p=0.01). In total, 7.5% of the patients had irritable bowel syndrome, 3.8% had functional bloating, and 16.3% had functional constipation. FBDs were significantly higher in women (p=0.004). While there was no statistically significant difference between patients with and those without FBDs in terms of the presence of additional diseases, smoking, alcohol use, educational level, marital status, and resi- dential areas (p>0.05), serum phosphorus (P) levels were significantly higher in the patients with FBDs (p=0.03). CONCLUSION: FBDs and their functional constipation subtype are more common in HD patients than in the healthy population in Turkey. FBDs are most frequently observed in females and housewives with high serum P levels.

Soluble Klotho and fibroblast growth factor 23 levels in diabetic nephropathy with different stages of albuminuria.

The relationship between soluble Klotho (s-Klotho) levels, fibroblast growth factor 23 (FGF23) levels, and albuminuria in patients with diabetic chronic kidney disease (CKD) remains unclear. A total of 109 patients with type 2 diabetes (mean age 61.63±9.77 years), at the outpatient clinic of the Antalya Research and Training Hospital Nephrology Unit between January and June 2014, as well as 32 healthy controls (mean age 49.53±7.32 years) were enrolled for this cross-sectional study. Patients were classified into three groups according to their urinary albumin creatinine ratio (UACR), normoalbuminuria (UACR<30 mg/g), microalbuminuria (UACR 30-300 mg/g), and macroalbuminuria (UACR>300 mg/g). The blood was analyzed for FGF23, s-Klotho, parathyroid hormone (PTH), P, Ca, creatinine, and 25-hydroxyvitamin D3 (25hD) levels. Creatinine, s-Klotho, FGF23, and PTH levels were significantly higher and 25hD levels were significantly lower in the patient group than in the healthy controls (p<0.001). Between the groups according to UACR, 1-way analysis of variance revealed statistically significant differences for creatinine (p<0.001), 25hD (p<0.001), PTH (p=0.002), Ca (p=0.002), and albumin levels (p<0.001). A statistically significant positive correlation was found between s-Klotho and FGF23 (r=0.768; p=0.001), and between FGF23 levels and UACR (r=0.768; p=0.001). In conclusion, the results of the present study suggest that s-Klotho levels are significantly elevated in patients with diabetes and s-Klotho levels decreased with increasing albumin excretion in our patients despite a reduction in estimated glomerular filtration rate.

Bone mineral density and biochemical markers of bone metabolism in predialysis patients with chronic kidney disease.

The aim of the study was to evaluate the usefulness of serum bone turnover markers (BTM) and bone mineral density (BMD) determined by dual-energy X-ray absorptiometry (DEXA) in predialysis patients with chronic kidney disease (CKD). We enrolled 83 patients with CKD, 41 (49.4%) males, 42 (50.6%) females, with mean estimated glomerular filtration rate (eGFR) 23.90 ± 12 (range = 6.0-56.0). BMD of the lumbar spine (LS) (anteroposterior, L2 through L4), femoral neck (FN) and femoral trochanter (FT) were measured by DEXA. Biochemical BTM, including calcium (Ca), phosphorus (P), intact parathyroid hormone (PTH), serum specific alkaline phosphatase (serum AP), bone-specific AP (BSAP), plasma bicarbonate and 25-hydroxy-vitamin D (25hD) were used for the prediction of BMD loss. T score results of LS and FN were worse than FT. BMD levels were lower in females than in males (all p < 0.05). According to different BMD T score levels, patients with age ≥ 65 years and patients in menopause were significantly more osteopenic (p = 0.026) and there was no relation between different BMD T scores and presence of diabetes (p = 0.654). A positive correlation was identified between the BMD of FN T-Z scores (r = 0.270, p = 0.029, r = 0.306, p = 0.012), FT T-Z scores (r = 0.220, p = 0.076, r:0.250, p = 0.043) and serum HCO3, while the correlation with serum alkaline phosphatase (AP) and BSAP was considered to be negative. No statistically significant association was found between BMD of all the measured skeletal sites and eGFR. Loss of BMD was identified mostly in females over ≥ 65 years of age and after menopause. Higher serum levels of BSAP and AP can be determined in the advanced stages of renal failure and they reflect fracture risk of the femur, but not spine. Measurements of BMD by DEXA are useful to demonstrate bone loss, but not technical enough to distinguish the quantity of bone loss between different stages of CKD.

Effect of steroid and cyclosporine in membranous nephropathy that is resistant to steroid and/or cytotoxic treatment.

Membranous Nephropathy (MN) is a glomerular disease characterized by proteinuria. The etiology is unknown in many cases, while in some patients MN may be secondary to infection, to other diseases, or to exposure to drugs and toxic substances. The prognosis of the disease is variable, 1/3 of patients can have spontaneous remission; patients with nephrotic proteinuria, those with advanced tubulointerstitial changes and those with increased serum creatinine at presentation have a poorer prognosis. Although MN is one of the most common causes of adult-onset Nephrotic Syndrome (NS), its management is still controversial. Corticosteroids have been used for many years as the basic treatment, though with controversial results. Controversial results have been obtained with cytotoxic agents. Cyclosporine has been shown to be effective in the treatment of this disease. We have evaluated the results of 23 patients (14 males, 9 females aged between 26-53) diagnosed with Idiopathic MN (IMN) who have received cyclosporine because of the relapse or persistence after steroid and/or cytotoxic treatment. At the end of a 12-month follow-up, 8 patients had (34.8%) complete remission, 8 (34.8%) had partial remission, 2 (8.7%) had persistent proteinuria and 5 patients (21.7%) had no response to the treatment. There was a significant decrease in proteinuria throughout the study. There was no significant difference in total protein, albumin and creatinine levels between before and after the treatment. Our results indicate that patients with MN who do not respond well or have-relapse after steroid and/or cytotoxic therapy, should be offered cyclosporine. We think that in the future; long-term studies which are prospective and randomized with an extensive number of patients will be effective on the treatment of MN.

Montelukast is as effective as penicillin in treatment of acute otitis media: an experimental rat study.

BACKGROUND: Leukotrienes are the major factors in the formation of edema and mucus, as well as development of tuba Eustachii dysfunction in acute otitis media. We developed an experimental acute suppurative otitis media model and compared the responses of rats to penicillin and combinations of leukotriene antagonist with respect to histopathological observations conducted in early and late phases. MATERIAL AND METHODS: A total of 83 ears from 56 Wistar rats were used in this study. Pneumococcus suspension was injected trans-tympanically into all rats. Subjects were classified into 4 different groups with 14 rats in each. In Group A, intramuscular penicillin G was injected for a period of 5 days. In Group B, intraperitoneal montelukast was injected for 21 days in addition to penicillin. In Group C, intraperitoneal montelukast isotonic NaCl in Group D was injected into rats for 21 days. RESULTS: No significant difference was found between the groups, except for mucosal vascularization with respect to mucosal and TM parameters in early phases. Furthermore, considerable deviations were observed for the recuperation of TM and mucosal inflammation for groups in which subjects were injected with montelukast as compared to other groups of the study in the late phases. CONCLUSIONS: When the parameters of inflammation in the rat middle ear were compared with each other, most of these parameters did not show any statistically significant beneficial effects in montelukast and penicillin groups.