Iron-based phosphorus chelator: Risk of iron deposition and action on bone metabolism in uremic rats.

Phosphate chelators are frequently used in patients with chronic kidney disease (CKD). New iron-based chelators remain understudied and offer a promising therapeutic option for the control of bone and mineral disorders of chronic kidney disease (BMD-CKD). We assessed the effect of the phosphorus chelator, chitosan-iron III (CH-FeCl), compared to calcium carbonate (CaCO3) in BMD-CKD and the potential iron overload in uremic rats. Thirty-two animals were divided into four groups, namely the control, CKD, CKD/CH-FeCl, and CKD/CaCO3 groups. CKD was induced by adding 0.75% (4 weeks) and 0.1% (3 weeks) adenine to the diet. The chelators were administered from week 3 through week 7. The renal function, BMD-CKD markers, and histomorphometry of the femur were assessed at week 7. The CKD group showed a significant increase in creatinine (83.9 ± 18.6 vs. 41.5 ± 22.1 µmol/L; P = 0.001), phosphate (3.5 ± 0.8 vs. 2.2 ± 0.2 mmol/L; P = 0.001), fractional excretion of phosphorus (FEP) (0.71 ± 0.2 vs. 0.2 ± 0.17; P = 0.0001), and FGF23 (81.36 ± 37.16 pg/mL vs. 7.42 ± 1.96; P = 0.011) compared to the control group. There was no accumulation of serum or bone iron after the use of CH-FeCl. The use of chelators reduced the FEP (control: 0.71 ± 0.20; CKD/CH-FeCl: 0.40 ± 0.16; CKD/CaCO3 0.34 ± 0.15; P = 0.001), without changes in the serum FGF23 and parathyroid hormone levels. Histomorphometry revealed the presence of bone disease with high remodeling in the uremic animals without changes with the use of chelators. The CH-FeCl chelator was efficient in reducing the FEP without iron accumulation, thereby paving the way for the use of this class of chelators in clinical settings in the future.

Chitosan-Fe (III) Complex as a Phosphate Chelator in Uraemic Rats: A Novel Treatment Option.

Phosphate retention and hyperphosphataemia are associated with increased mortality in patients with chronic kidney disease (CKD). We tested the use of cross-linked iron chitosan III (CH-FeCl) as a potential phosphate chelator in rats with CKD. We evaluated 96 animals, divided equally into four groups (control, CKD, CH-FeCl and CKD/CH-FeCl), over 7 weeks. We induced CKD by feeding animals an adenine-enriched diet (0.75% in the first 4 weeks and 0.1% in the following 3 weeks). We administered 30 mg/kg daily of the test polymer, by gavage, from the third week until the end of the study. All animals received a diet supplemented with 1% phosphorus. Uraemia was confirmed by the increase in serum creatinine in week 4 (36.24 ± 18.56 versus 144.98 ± 22.1 µmol/L; p = 0.0001) and week 7 (41.55 ± 22.1 versus 83.98 ± 18.56 µmol/L; p = 0.001) in CKD animals. Rats from the CKD group treated with CH-FeCl had a 54.5% reduction in serum phosphate (6.10 ± 2.23 versus 2.78 ± 0.55 mmol/L) compared to a reduction of 25.6% in the untreated CKD group (4.75 ± 1.45 versus 3.52 ± 0.74 mmol/L, p = 0.021), between week 4 and week 7. At week 7, renal function in both CKD groups was similar (serum creatinine: 83.98 ± 18.56 versus 83.10 ± 23.87 µmol/L, p = 0.888); however, the CH-FeCl-treated rats had a reduction in phosphate overload measured by fractional phosphate excretion (FEPi) (0.71 ± 0.2 versus 0.4 ± 0.16, p = 0.006) compared to the untreated CKD group. Our study demonstrated that CH-FeCl had an efficient chelating action on phosphate.

Are Kidney Transplant Patients Receiving Chronic Kidney Disease Treatment? A Comparative Study to Predialysis Patients in a Multidisciplinary Setting.

OBJECTIVES: Kidney transplant recipients present with treatable complications related to chronic kidney disease, similarly to predialysis patients. The role of multidisciplinary clinics in the management of these complications in kidney transplant recipients is not fully understood. The objective of the present study was to compare the availability of specific treatments for chronic kidney disease-related complications between predialysis patients and kidney transplant recipients, both followed by a multidisciplinary team. MATERIALS AND METHODS: In a cross-sectional study, we compared the prevalence of chronic kidney disease-related complications and the presence or absence of treatment for those complications, when clinically indicated, in 133 kidney transplant recipients and 114 predialysis patients, all followed by a multidisciplinary team of nephrologists, nurses, dieticians, social workers, and psychologists. RESULTS: Kidney transplant recipients were younger, had better kidney function, and lower prevalence of hypertension, proteinuria, diabetes, obesity, cardiovascular disease, anemia, hyperuricemia, hypocalcemia, and hyperphosphatemia. However, the availability of treatment for anemia (odds ratio of 0.58; 95% confidence interval, 0.2-1.6; P = .31), dyslipidemia (odds ratio of 0.9; 95% confidence interval, 0.3-2.4; P = .84), metabolic acidosis (odds ratio of 3.75; 95% confidence interval, 0.8-18.2; P = .101), hyperphosphatemia (odds ratio of 1.89; 95% confidence interval, 0.3-10.8; P = .47), and hyperuricemia (odds ratio of 1.3; 95% confidence interval, 0.3-6.2; P = .73) was similar between the groups. CONCLUSIONS: Despite clinical and demographic differences, the comparable treatment directed to chronic kidney disease-related complications for both predialysis patients and kidney transplant recipients suggests that a multidisciplinary approach could be appropriate for better clinical management of chronic kidney disease in kidney transplant recipients.

Low-level laser therapy decreases renal interstitial fibrosis.

OBJECTIVE: the purpose of this study was to investigate the effect of low-level laser therapy (LLLT) on chronic kidney disease (CKD) in a model of unilateral ureteral obstruction (UUO). BACKGROUND DATA: Regardless of the etiology, CKD involves progressive widespread tissue fibrosis, tubular atrophy, and loss of kidney function. This process also occurs in kidney allograft. At present, effective therapies for this condition are lacking. We investigated the effects of LLLT on the interstitial fibrosis that occurs after experimental UUO in rats. METHODS: The occluded kidney of half of the 32 Wistar rats that underwent UUO received a single intraoperative dose of LLLT (AlGaAs laser, 780 nm, 22.5 J/cm(2), 30 mW, 0.75 W/cm(2), 30 sec on each of nine points). After 14 days, renal fibrosis was assessed by Sirius red staining under polarized light. Immunohistochemical analyses quantitated the renal tissue cells that expressed fibroblast (FSP-1) and myofibroblast (α-SMA) markers. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the mRNA expression of interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1), transforming growth factor (TGF)-ß1 and Smad3. RESULTS: The UUO and LLLT animals had less fibrosis than the UUO animals, as well having decreased expression inflammatory and pro-fibrotic markers. CONCLUSIONS: For the first time, we showed that LLLT had a protective effect regarding renal interstitial fibrosis. It is conceivable that by attenuating inflammation, LLLT can prevent tubular activation and transdifferentiation, which are the two processes that mainly drive the renal fibrosis of the UUO model.