Calcium-based phosphate binders and bone mineral density in patients undergoing hemodialysis: a retrospective cohort study.

BACKGROUND: Calcium supplements are commonly prescribed to prevent fractures in patients with osteoporosis. Nonetheless, they are generally eschewed in hemodialysis patients because they increase vascular calcification and induce cardiovascular disease. This retrospective cohort study aimed to investigate the effect of calcium-based phosphate binders (CBPB) on bone mineral density (BMD) in hemodialysis patients. METHODS: Outpatients on dialysis who underwent BMD measurement from January to December 2017, whose data on BMD trends and CBPB administration were recorded over the next 4 years, were enrolled. Patients receiving anti-osteoporotic medications were excluded. The association between the presence and duration of CBPB administration and changes in BMD was evaluated. RESULTS: The femoral neck's BMD decreased from 0.836 g/cm2 (0.702-0.952) to 0.764 g/cm2 (0.636-0.896) (P < 0.001) in the non-CBPB group (patients who never received CBPB over 4 years, n = 32). The CBPB group (n = 56) exhibited only a minute decrease from 0.833 g/cm2 (0.736-0.965) to 0.824 g/cm2 (0.706-0.939) (P = 0.004). Multivariate linear regression analysis revealed better BMD maintenance in the CBPB group [ß-coefficient (95% CI): 0.033 (0.001-0.065); P = 0.046] than in the non-CBPB group. Additionally, the prolonged-CBPB administration group showed superior BMD preservation [ß-coefficient (95% CI): 0.038 (0.001-0.076); P = 0.042]. CONCLUSION: CBPB administration may be associated with BMD maintenance.

A Case of Hypokalemia Caused by Left Native Renal Artery Stenosis in a Kidney Transplant Recipient.

A 39-year-old woman with end-stage renal failure of unknown origin was on peritoneal dialysis for 10 years. One year ago, she underwent ABO-incompatible living-donor kidney transplantation from her husband. After the kidney transplantation, her serum creatinine level remained around 0.7 mg/dL, but her serum potassium level remained low at around 3.5 mEq/L despite potassium supplementation and spironolactone. The patient's plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were markedly elevated (20 ng/mL/h and 868 pg/mL, respectively). A CT angiogram of the abdomen performed 1 year previously suggested stenosis of the left native renal artery, which was considered responsible for the hypokalemia. Renal venous sampling was done on both the native kidneys and the transplanted kidney. Since renin secretion from the left native kidney was significantly elevated, a laparoscopic left nephrectomy was performed. Postoperatively, the renin-angiotensin-aldosterone system was markedly improved (PRA: 6.4 ng/mL/h, PAC: 147.3 pg/mL), and the serum potassium levels also improved. Pathological examination of the removed kidney showed many atubular glomeruli and hyperplasia of the juxtaglomerular apparatus (JGA) in residual glomeruli. In addition, renin staining showed strong positivity in the JGA of these glomeruli. Here, we report a case of hypokalemia caused by left native renal artery stenosis in a kidney transplant recipient. This valuable case study provides histological confirmation of maintained renin secretion in an abandoned native kidney after kidney transplantation.

Long-term Clinical Course after Living Kidney Donation by a Patient with Gitelman Syndrome Harboring a Compound Heterozygous Mutation of the SLC12A3 Gene.

The eligibility for kidney donation and long-term post-donation renal prognosis of patients with Gitelman syndrome (GS) are unknown. We herein report a 44-year-old woman with GS who donated her kidney for transplant. A gene sequence analysis revealed compound heterozygous mutations of T180K and L858H in the SLC12A3 gene. Since transplantation, the renal function and serum potassium and magnesium levels of the donor and recipient have remained stable for seven years with careful monitoring and supplementation. Patients with asymptomatic GS who have no complications can be considered eligible to donate their kidney for transplant with proper monitoring after transplantation.

Severe chronic kidney disease environment reduced calcium-sensing receptor expression in parathyroid glands of adenine-induced rats even without high phosphorus diet.

BACKGROUND: Chronic kidney disease (CKD) disrupts mineral homeostasis and its main underlying cause is secondary hyperparathyroidism (SHPT). We previously reported that calcium-sensing receptor (CaSR) mRNA and protein expression in parathyroid glands (PTGs) significantly decreased in a CKD rat model induced by a 5/6 nephrectomy that were fed a high phosphorus diet. However, there was a significant difference in the severity of CKD between high phosphorus and adequate phosphorus diet groups. Thus, it was unclear whether CKD environment or the high phosphorus diet influenced CaSR expression, and the underlying mechanism remains largely unknown. METHODS: CKD was induced in rats with 0.75% adenine-containing diet. CKD and control rats were maintained for 5 days and 2 weeks on diets with 0.7% or 1.3% phosphorus. For gene expression analysis, quantitative real-time polymerase chain reaction was performed with TaqMan probes. Protein expression was analyzed by immunohistochemistry. RESULTS: PTG CaSR expression significantly decreased in the presence of a severe CKD environment, even without the high phosphate load. Ki67 expressing cells in PTGs were significantly higher only in the CKD rats fed a high phosphorus diet. Furthermore, among the many genes that could affect CaSR expression, only vitamin D receptor (VDR) and glial cells missing 2 (Gcm2) showed significant changes. Moreover, Gcm2 was significantly reduced at an early stage without significant changes in serum calcium, phosphorus and 1,25(OH)2 vitamin D, and there was no significant reduction in CaSR and VDR expressions. Then, significantly elevated Ki67-positive cell numbers were also only observed in the early CKD PTGs with high-phosphorus diets. CONCLUSIONS: Our data suggest that the cause of the decreased PTG CaSR expression is the reduction in VDR and Gcm2 expression; Gcm2 may play a role in the onset and progression of SHPT.

Effect of adipose-derived mesenchymal stem cell transplantation on vascular calcification in rats with adenine-induced kidney disease.

Previous studies have investigated the use of mesenchymal stem cells (MSCs) to treat damaged kidneys. However, the effect of adipose-derived MSCs (ASCs) on vascular calcification in chronic kidney disease (CKD) is still poorly understood. In the present study, we explored the potential of ASCs for the treatment of CKD and vascular calcification. CKD was induced in male Sprague-Dawley rats by feeding them a diet containing 0.75% adenine for 4 weeks. ASCs transplantation significantly reduced serum inorganic phosphorus (Pi) as compared to that in the control. The histopathology of the kidneys showed a greater dilation of tubular lumens and interstitial fibrosis in the control group. Calcium and Pi contents of the aorta in the ASCs transplantation group were lower than those in the control group. Von Kossa staining of the thoracic aorta media revealed that ASCs transplantation suppressed vascular calcification. Thus, this study revealed that autogenic ASCs transplantation inhibits kidney damage and suppresses the progression of vascular calcification in the CKD rat model, suggesting that autogenic ASCs transplantation is a novel approach for preventing the progression of CKD and vascular calcification.

Cinacalcet for hemodialyzed patients with or without a high PTH level to control serum calcium and phosphorus: ECO (evaluation of cinacalcet HCl outcome) study.

BACKGROUND: We investigated the influence of cinacalcet on serum Ca and P in hemodialyzed patients with or without a high PTH level, according to K/DOQI guideline, to control serum Ca and P levels. METHODS: We recruited 130 patients in this prospective cohort study and classified them into Group A (iPTH > 300 pg/ml), Group B (iPTH = 181 - 300 pg/ml), and Group C (iPTH ≤ 180 pg/ml). After 24 weeks on cinacalcet, serum Ca, P and iPTH were measured. RESULTS: The achievement rate of the target iPTH level in JSDT guideline was significantly higher in Group B compared with Group A. The achievement rate of serum Ca and P target levels in the Japanese Society for Dialysis Therapy (JSDT) guideline was higher in Group C. In Group A and Group C, the simultaneous achievement rates (Ca, P, and iPTH) in KDOQI guideline increased after treatment with cinacalcet (p < 0.01). There was no difference in the reduction of Ca and P among the groups, while the iPTH reduction was significantly lower in groups B and C compared with that in A. CONCLUSION: Administration of cinacalcet to patients with or without high PTH levels, according to the K/DOQI guideline, facilitates the control of Ca and P levels.

Serum soluble α-klotho in hemodialysis patients.

BACKGROUND: The extracellular domain of klotho is cleaved and released into various extracellular fluids, such as blood, urine, and cerebrospinal fluid, as soluble α-klotho (sαKl). METHODS: We measured sαKl in 53 hemodialysis patients and 20 healthy controls to examine its role in mineral metabolism. RESULTS: The sαKl level of the hemodialysis patients was 430 pg/ml (386 - 540 pg/ml, which was lower than that of healthy controls 740 pg/ml (550 - 913 pg/ml, p < 0.01). The serum sαKl level showed a positive correlation with serum phosphorus (P) (σ = 0.33, p = 0.014), while serum corrected Ca tended to be negatively correlated with sαKl (σ = -0.26, p = 0.06). Both parameters showed the same trends in healthy subjects. However, there was no significant association between serum sαKl and age (σ= 0.21, p = 0.14), intact PTH (σ = -0.08, p= 0.55), whole PTH (σ = -0.08, p = 0.59), or FGF23 (σ = -0.07, p = 0.62). Multiple regression analysis showed that P was independently associated with the serum sαKl levels (total adjusted R2 = 0.18, p = 0.02). CONCLUSIONS: The sαKl level was lower in hemodialysis patients than in healthy persons. Serum P level was independently associated with the serum sαKl level.

Metanephros transplantation inhibits the progression of vascular calcification in rats with adenine-induced renal failure.

BACKGROUND/AIM: Recent research has shown that transplanted metanephroi form primitive vascularized kidneys with histologically recognizable renal features. The aim of the present study was to determine the metabolic function of transplanted metanephroi in rats with chronic renal failure (CRF), with particular reference to secondary hyperparathyroidism and vascular calcification. METHODS: CRF was induced in 11-week-old male Wistar rats by maintaining them on a 0.75% adenine diet for 4 weeks, followed by normal diet for an additional 2 weeks. At the end of adenine loading, whole metanephroi from embryonic day 15 rats were transplanted into the omentum and epididymis of the transplantation group. Vascular calcification was evaluated 2 weeks after metanephroi transplantation. RESULTS: Metanephros transplantation significantly reduced vascular calcium and phosphorus content and suppressed the progression of vascular calcification as indicated by von Kossa staining of the media of the thoracic aorta. However, no significant differences between the adenine-fed control and transplantation groups were found regarding the serum levels of 1,25(OH)2D3, calcium or phosphorus or the calcium × phosphorus product. CONCLUSION: The present study has shown that transplantation of metanephroi suppresses the progression of vascular calcification via a mechanism that is independent of calcium-phosphorus dynamics.

The negative Ca(2+) balance is involved in the stimulation of PTH secretion.

The low calcium (Ca(2+)) dialysate have been developed to diminish the risk of hypercalcemia with the administration of active vitamin D and Ca(2+) carbonate as phosphate binder. Today, increasing numbers of hemodialysis (HD) patients have been on the low Ca(2+) dialysate (Ca(2+) = 2.5 mEq/l). However, the clinical consequences of a negative calcium net-balance which may be induced by the use of low Ca dialysate are not well evaluated. In the present study, we explored the effects of low Ca(2+) dialysate on the calcium balance and the PTH secretion. Eighty one chronic HD patients (male/female: 47/34; mean age: 60.2 +/- 1.5 years; mean HD periods: 11.1 +/- 0.8 years) who had been dialyzed with 3.0 mEq/l Ca(2+) dialysate were studied. All patients were transferred to the low Ca dialysate, which actually brought about a negative net-balance in Ca (mean: -94.5 mg) and an increase in serum intact PTH levels (mean: +23.7%: p = 0.03) during a single HD session. However, no changes in serum ionized Ca(2+) were found in spite of negative Ca(2+) balance. One month after change to the low Ca(2+) dialysate (total 12 sessions in each case), serum intact PTH levels increased significantly (186.7 +/- 19.5 vs. 216.2 +/- 21.9 pg/ml: p = 0.01) in spite of the fact that no changes were found in serum ionized Ca(2+), Pi and Mg. This result indicates that the negative Ca(2+) balance during low-Ca(2+) hemodialysis-stimulated PTH secretion, which offset the decrease of serum Ca(2+); a trade-off phenomenon between negative Ca balance and PTH. This suggests that low Ca(2+) dialysate may exaggerate the progression of secondary hyperparathyroidism.