No abstract
Hyperphosphatemia is a common and serious complication of chronic kidney disease, contributing to the increased cardiovascular mortality seen in this patient group. The sodium phosphate (P) cotransporters system is involved in intestinal P absorption and is regulated by several factors. We investigate the effect of diets with distinct concentrations of P in the regulation of cotransporters NaPIIb and PiT1 in the intestine of rats. Male Wistar rats (n=66) were used, 33 of which were submitted to nephrectomy 5/6 (Nx) and the others were used as controls (C). The animals received a standard (ST) diet (20% protein and 0.54% P) for 30 days, after they were divided into 2 sets of 3 groups in accordance with the concentration of P in the diet (0.2%, 0.54% or 0.9%) and fed for 2 days. Blood samples, 24h urine, and intestine (duodenum, ileum and jejunum) were accordingly collected. Immunofluorescence, Western blot or ELISA were used to analyze the expressions of the cotransporters and qRT‐PCR to evaluate the gene expression of NaPIIb and PiT1. The concentrations of Cr, Pi, FGF23, PTH and Albu were higher in Nx animals. Pu decreased in Nx animals and some of these parameters were modified by the concentration of dietary P. There were significant differences in the expression of PiT1 in jejunum and ileum of Nx animals in diet 0.2% P relative to their respective controls, normalized to B‐actin (p=0.01 and p=0.02, respectively). The results demonstrate alteration in P homeostasis in Nx animals impaired upregulation of cotransporters in the P low diet and downregulation in the P high diet differently of the controls, as observed in PCR and immunofluorescence for PiT and NaPi in duodenum, respectively. Grant Funding Source: Supported by FAPESP
Subendocardial perfusion was lower in patients with BMD, reflecting higher cardiovascular risk in this population. Whether early parathyroidectomy in the course of kidney disease could modify such results still deserves further investigation.
Introduction and Aims: High-resolution peripheral quantitative computed tomography (HR-pQCT) is a noninvasive imaging technique that assesses trabecular and cortical bone microarchitecture in vivo. The purpose of our study is to evaluate, for the first time, the correlation between HR-pQCT measures and transiliac bone biopsy (Bx) in chronic kidney disease (CKD) patients. Methods:We measured bone mineral desnsity (BMD) by HR-pQCT and dual energy x-ray absorptiometry (DXA) in 31 CKD stage 5D patients. Biopsies were analyzed by 2D quantitative histomorphometry, where both total and mineralized trabecular bone volume (2D BV/TV and 2D Md.V/TV, respectively) were measured. Results: Patients (19 males) were 41 ± 11 years old, with a dialysis vintage of 28 months, BMI of 24 kg/m², serum Ca of 8.4 ± 0.6 mg/dl; P of 3.4±1.5 mg/dl; alkaline phosphatase 93 (71 -145) U/L; PTH 463 ± 343 pg/ml; 25-vitamin D 25 (18 -32) ng/ml and sclerostin 1.03 (0.51 -1.83) ng/ml. 2D BV/TV correlated significantly with height; lumbar spine (r = 0.70) and total femur (r = 0.59) DXA; and modestly with HR-pQCT BV/TV at the radius (r = 0.42; p< 0.05) but not at the tibia. 2D Md.V/TV correlated significantly with age; height; lumbar spine (r = 0.67) and total femur (r = 0.63) DXA; and HR-pQCT BV/TV (r = 0.50; p<0.05) only at the radius. Conversely, a strong correlation was found between 2D cortical porosity (Ct.Po) and HR-pQCT cortical bone density (Dcomp) both at radius and tibia (r = -0.60 and -0.64, respectively; p <0.05). We found significant negative correlations between cortical density measured by HR-pQCT, and age, time on dialysis, PTH and alkaline phosphatase in the distal radius and tibia. The trabecular density and BV/TV, as measured by HR-pQCT, correlated with the age at the distal tibia and radius, and sex hormones, only at the radio.Conclusions: There was a good correlation between HR-pQCT and transiliac bone biopsy with respect to cortical compartment. On the other hand, in trabecular bone, despite being statistically significant and greater than that described for the general population, the correlations between both methods were modest, indicating that HR-pQCT cannot be used to predict 2D BV/TV. Further, larger studies are needed as well as studies to determine if these noninvasive measures can predict fracture.
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