losartan-potassium and Hyperphosphatemia

Although patients with either β-thalassemia or chronic kidney disease (CKD) clinically correlate with severe osteoporosis, the mechanism by which CKD exposed to high phosphate affects bone turnover has not been characterized in β-thalassemia. We aimed to determine the effects of renal insufficiency on high phosphate intake induced changes in bone metabolism after 5/6th nephrectomy in hemizygous β-globin knockout (BKO) mice. Male BKO mice manifested severe anemia and osteopenia. Nephrectomy induced renal fibrosis and reduced renal function as assessed by increased serum urea nitrogen levels. Moreover, nephrectomy increased bone turnover leading to bone loss in wild type (WT) but not BKO mice. In nephrectomized BKO, PBS in drinking water induced hyperphosphatemia, and hypercalcemia along with osteopenia in both cancellous and cortical bone. Histomorphometric analysis confirmed reduced cancellous bone volume due to decreased bone formation rate, osteoblast number and osteoclast number. The mRNA levels for Alpl, Sp7, Kl, Tnfsf11, and Tnfsf11/Tnfrsf11b were decreased in nephrectomized BKO mice drinking PBS. Interestingly, Fgf23, a bone-derived hormone produced by osteocytes and osteoblasts in response to hyperphosphatemia, were remarkably increased in nephrectomized BKO mice following PBS intake. Serum FGF23 and erythropoietin levels were markedly elevated in BKO mice. Nephrectomy decreased serum erythropoietin but not FGF23 levels. Hyperphosphatemia in BKO mice increased serum erythropoietin, FGF23, and PTH levels, nominating these factors as candidate mediators of bone loss in thalassemic mice with CKD during phosphate retention.

Topics: Animals; beta-Thalassemia; Bone Diseases, Metabolic; Erythropoietin; Fibroblast Growth Factors; Humans; Hyperphosphatemia; Male; Mice; Phosphates; Renal Insufficiency, Chronic

Anemia of chronic kidney disease (CKD) is, in part, caused by hepcidin-mediated impaired iron absorption. However, phosphate binder, ferric citrate (FC) overcomes the CKD-induced impairment of iron absorption and increases serum iron, transferrin saturation, and iron stores and reduces erythropoietin requirements in CKD/ESRD patients. The mechanism and sites of intestinal absorption of iron contained in FC were explored here.. Eight-week old rats were randomized to sham-operated or 5/6 nephrectomized (CKD) groups and fed either regular rat chow or rat chow containing 4% FC for 6 weeks. They were then euthanized, and tissues were processed for histological and biochemical analysis using Prussian blue staining, Western blot analysis to quantify intestinal epithelial tight junction proteins and real-time PCR to measure Fatty Acid receptors 2 (FFA2) and 3 (FFA3) expressions.. CKD rats exhibited hypertension, anemia, azotemia, and hyperphosphatemia. FC-treated CKD rats showed significant reductions in blood pressure, serum urea, phosphate and creatinine levels and higher serum iron and blood hemoglobin levels. This was associated with marked increase in iron content of the epithelial and subepithelial wall of the descending colon and modest iron deposits in the proximal tubular epithelial cells of their remnant kidneys. No significant difference was found in hepatic tissue iron content between untreated and FC-treated CKD or control groups. Distal colon's epithelial tight Junction proteins, Occludin, JAM-1 and ZO-1 were markedly reduced in the CKD groups. The FFA2 expression in the jejunum and FFA3 expression in the distal colon were significantly reduced in the CKD rats and markedly increased with FC administration.. Iron contained in the phosphate binder, FC, is absorbed by the distal colon of the CKD animals via disrupted colonic epithelial barrier and upregulation of short chain fatty acid transporters.

Topics: Animals; Colon; Erythropoietin; Ferric Compounds; Hyperphosphatemia; Intestinal Absorption; Iron; Male; Phosphates; Rats; Rats, Sprague-Dawley; Renal Insufficiency, Chronic; Tissue Distribution

In children with chronic kidney disease (CKD) anemia and calcium-phosphate disturbances are already present at early stages of the disease and require a comprehensive treatment. The aim of this study was to evaluate the efficacy of the treatment of biochemical disturbances, depending on the severity of CKD in children.. The study included 71 children (44 boys, 27 girls) with CKD stage 1-5. Mean age was 11 ± 5 years, mean height: 135.7 ± 28 cm and mean eGFR 32 ml/min/1.73 m2. The serum hemoglobin, urea, creatinine, cystatin C, calcium, phosphorus and parathyroid hormone (PTH) levels were measured. eGFR was calculated according to Schwartz and Filler formulas, employing creatinine and cystatin C as markers. Patients were divided into groups depending on the stage of CKD [group 1: CKD stage 1+2 (GFR > 60), group 2: CKD stage 3 (GFR = 30-59) Group 3: CKD stage 4 (GFR = 15-29 ml/min/1.73 m2), group 4 - dialyzed children].. The concentration of he- moglobin depending on the stage of CKD (group 1 vs. group 2 vs. group 3 vs group 4) was 12.95 vs. 12.68 vs. 12.47 vs. 11.3 g/dI, respectively. The concentration of total and ionized calcium was significantly lower in children on dialysis compared to patients treated conservatively. With the progression of CKD the concentration of phosphorus (1.39 vs. 1.4 vs. 1.49 vs. 1.82 mmolI) and PTH (21.7 vs 48.6 vs 99.9 vs. 219 pg/ml) significantly increased. Treatment with erythropoietin was used in 48% of children, calcium carbonate in 55% and alphacalcidol in 56% of patients.. Despite the use of regular treatment, with the progression of CKD a progression of anemia, increased serum phosphate and parathyroid hormone and a decrease in calcium levels in studied children was observed. The severity of metabolic disorders in dialyzed children indicates the need for administration of new and more effective drugs, to prevent early enough complications of CKD in the form of mineral bone disease and cardiovascular complications.

Topics: Adolescent; Anemia; Calcium Carbonate; Child; Disease Progression; Erythropoietin; Female; Humans; Hydroxycholecalciferols; Hyperphosphatemia; Hypocalcemia; Male; Parathyroid Hormone; Renal Insufficiency, Chronic; Treatment Outcome

Hyperphosphatemia, secondary hyperparathyroidism (SHPT) and anemia are common secondary complications in hemodialysis patients with end-stage renal disease (ESRD). Compared with conventional hemodialysis (CHD), short daily hemodialysis (sDHD) has been found to be more effective in patients with ESRD. The objective of this study was to determine whether sDHD could improve hyperphosphatemia, SHPT and anemia in patients with ESRD.. Twenty-seven patients (11 women and 16 men, 46.8 ± 13.4 years old) were switched from CHD to sDHD. All hematologic parameters were measured prior to the switch (baseline), at 3 months after the switch (sDHD(1)) and at 6 months after the switch (sDHD(2)).. The serum phosphate decreased from 2.54 ± 0.32 mmol/L at baseline to 2.15 ± 0.36 mmol/L (p < 0.001) at sDHD(1) and 1.97 ± 0.33 mmol/L (p < 0.001) at sDHD(2). Calcium-phosphate product decreased from 5.18 ± 1.24 mmol(2)/L(2) at baseline to 4.20 ± 0.71 mmol(2)/L(2) (p < 0.001) at sDHD(1) and 4.02 ± 0.83 mmol(2)/L(2) (p < 0.001) at sDHD(2). The serum PTH levels decreased from 223.9 ± 124.7 pmol/L at baseline to 196.3 ± 101.3 pmol/L (p < 0.05) at sDHD(2). The hemoglobin concentration increased significantly from CHD to sDHD. However, the requirement for erythropoietin (EPO) dose decreased from 6847.8 ± 1057.3 u/week at baseline to 5869.6 ± 1094.6 u/week (p < 0.05) at sDHD(2).. sDHD may decrease serum phosphate, calcium-phosphate product and PTH, increase hemoglobin levels and decrease exogenous EPO dose requirements compared with CHD in hemodialysis patients.

Topics: Adult; Aged; Anemia; Calcium Phosphates; Erythropoietin; Female; Health Status; Hemoglobins; Humans; Hyperparathyroidism, Secondary; Hyperphosphatemia; Kidney Failure, Chronic; Male; Mental Health; Middle Aged; Parathyroid Hormone; Quality of Life; Renal Dialysis

Published studies suggest that longer hemodialysis (HD) sessions are associated with improved morbidity and mortality, but few centers offer long sessions. The Western Infirmary renal unit has offered long overnight hemodialysis (LOH) (6 to 7 h) thrice weekly since 1998. The aim of this study was to describe patients who chose LOH and compare outcomes with patients on conventional hours (4 to 5 h) HD.. Patients who ever had LOH for three or more consecutive sessions were identified (n = 146). Indices of urea reduction ratio (URR), anemia, hyperphosphatemia, and predialysis BP (BP) control in a subgroup of all patients on LOH for at least 1 yr since 2004 were compared with age, sex, and diabetes-matched controls undergoing conventional duration HD.. The mean age at the time of starting LOH was 51.8 yr and 74.7% started with a functioning arteriovenous fistula. Median duration of continuous LOH was 1.6 yr. Of those no longer on LOH, only 33.3% reverted to conventional hours HD (mean duration LOH 2.2 yr). When comparing LOH and conventional HD cohorts, there was increased URR and mean hemoglobin with a trend toward lower mean erythropoietin index. There was a trend toward fewer phosphate binder tablets but no difference in mean serum phosphate, BP, or number of prescribed antihypertensive medicines.. LOH is a well tolerated hemodialysis option, associated with improved URR and better control of anemia.

Topics: Adult; Aged; Anemia; Blood Pressure; Case-Control Studies; Erythropoietin; Female; Hemoglobins; Humans; Hyperphosphatemia; Kidney Failure, Chronic; Male; Middle Aged; Night Care; Patient Satisfaction; Phosphates; Renal Dialysis; Urea