Association of serum sodium levels with fractures and mortality in patients undergoing maintenance hemodialysis.

BACKGROUND: Hyponatremia is implicated in pathological bone resorption and has been identified as a risk factor for bone fracture in the general population. However, there are limited data on the association between serum sodium levels and fracture risk in patients undergoing hemodialysis (HD). METHODS: We analyzed a historical cohort of 2220 maintenance HD patients to examine the association between serum sodium levels and the risk of fracture and mortality. We also examined the association between serum sodium levels and osteoporosis, based on metacarpal bone mineral density, in a subcohort of 455 patients with available data. In addition, we examined the association between serum sodium levels and bone turnover markers in a separate cross-sectional cohort of 654 maintenance HD patients. RESULTS: During a median follow-up of 5.4 years, 712 patients died, 113 experienced clinical fractures, and 64 experienced asymptomatic vertebral fractures. Lower serum sodium levels were associated with an increased risk of mortality (HR 1.06 per 1 mEq/L decrease; 95% CI 1.03-1.09) but not with the risk of clinical fracture (HR 1.04 per 1 mEq/L decrease; 95% CI 0.97-1.11). A similar lack of association was observed for asymptomatic vertebral fracture and any fracture. Serum sodium levels were also not associated with osteoporosis in a subcohort with available data (n = 455) or with bone alkaline phosphatase or tartrate-resistant acid phosphatase-5b in a separate cross-sectional cohort. CONCLUSION: Serum sodium levels were associated with mortality but not with fracture risk, osteoporosis, or bone turnover markers in maintenance HD patients.

Evaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patients.

Two-thirds of urate is excreted via the renal pathway and the remaining one-third via the extra-renal pathway, the latter mainly via the intestine in healthy individuals. ABCG2, a urate exporter, is expressed in various tissues including the kidney and intestine, and its dysfunction leads to hyperuricemia and gout. ABCG2 is regarded as being responsible for most of the extra-renal urate excretion. However, the extra-renal urate excretion capacity via ABCG2 remains undefined in end-stage kidney diseases. Therefore, we evaluated the capacity of extra-renal ABCG2 using 123 anuric hemodialysis patients whose urate excretion depended on only the extra-renal pathway. ABCG2 function in each participant was estimated based on ABCG2 dysfunctional variants. We computed the uric acid pool (PoolUA) from bodyweight and serum urate level (SUA) using previously reported radio-isotopic data, and we analyzed the association between ABCG2 function and the PoolUA. SUA and PoolUA increased significantly with ABCG2 dysfunction, and extra-renal ABCG2 could excrete up to approximately 60% of the daily uric acid turnover in hemodialysis patients. Our findings indicate that the extra-renal urate excretion capacity can expand with renal function decline and highlight that the extra-renal pathway is particularly important in the uric acid homeostasis for patients with renal dysfunction.

Serum Sclerostin Levels and Mortality in Hemodialysis Patients: An 8-Year Prospective Study.

INTRODUCTION: Sclerostin is an osteocyte-derived inhibitor of bone formation and is increased in kidney failure. Sclerostin might be involved in the pathogenesis of vascular calcification, but few studies have examined the association between sclerostin and mortality in hemodialysis patients. METHODS: We analyzed a prospective cohort of 654 patients undergoing maintenance hemodialysis. The primary exposure variable was the baseline serum sclerostin level measured at study enrollment. The primary outcome was 8-year all-cause mortality. Mortality risk was assessed using Cox regression models adjusted for potential confounders. RESULTS: During a median follow-up of 7.6 years (interquartile range, 4.1-8.0 years), 229 of the 654 participants died. In a univariate analysis, serum sclerostin levels were not associated with mortality (HR per doubling, 0.94; 95% CI, 0.76-1.17). This result was unchanged after adjustment for age, sex, dialysis vintage, diabetes, prior cardiovascular disease, and body mass index (HR per doubling, 0.92; 95% CI, 0.72-1.17). Similar results were obtained for cardiovascular mortality. CONCLUSION: Serum sclerostin levels were not associated with mortality in maintenance hemodialysis patients. Further research is required to determine the role of sclerostin in vascular calcification and cardiovascular disease in kidney failure.

Interrelationships Between Sclerostin, Secondary Hyperparathyroidism, and Bone Metabolism in Patients on Hemodialysis.

CONTEXT: Sclerostin is an osteocyte-derived inhibitor of bone formation and is increased in kidney failure, but its role in the pathogenesis of renal bone disease remains unknown. OBJECTIVE: We aimed to explore the association of serum sclerostin with bone metabolism in patients undergoing hemodialysis, with a particular focus on parathyroid hormone (PTH)-dependent and PTH-independent pathways. METHODS: This cross-sectional and prospective cohort study included 654 patients undergoing hemodialysis at 10 facilities in Japan. We employed multivariable linear regression to explore whether sclerostin levels were associated with metacarpal bone mineral density (BMD), intact PTH, bone alkaline phosphatase (BAP), and tartrate-resistant acid phosphatase-5b (TRACP-5b). We employed mediation analyses to explore whether and to what extent the association of PTH with bone turnover markers is mediated by sclerostin. We also compared sclerostin levels between patients with and without previous or incident fractures. RESULTS: The median sclerostin level in hemodialysis patients was 3- to 4-fold higher than that in healthy individuals. Higher sclerostin levels were associated with higher metacarpal BMD and lower levels of intact PTH, BAP, and TRACP-5b. However, the relationships of sclerostin with bone turnover markers were substantially attenuated after adjustment for PTH. Mediation analysis suggested that the effects of PTH on bone turnover markers were mainly direct rather than mediated by sclerostin. Sclerostin levels were not associated with previous or incident fractures. CONCLUSION: These findings suggest that in patients undergoing dialysis, sclerostin has only a limited role in bone metabolism and may not mediate the effect of PTH on bone turnover.

A disposable, ultra-fine endoscope for non-invasive, close examination of the intraluminal surface of the peritoneal dialysis catheter and peritoneal cavity.

The ability to visualize intraluminal surface of peritoneal dialysis (PD) catheter and peritoneal cavity could allow elucidation of the cases of outflow problems, and provide information on changes to the peritoneal membrane leading to encapsulating peritoneal sclerosis. A non-invasive examination that allows those monitoring in need is desirable. We have developed a disposable ultra-fine endoscope that can be inserted into the lumen of the existing PD catheter, allowing observation of the luminal side of the catheter and peritoneal cavity from the tip of the PD catheter, with minimum invasion in practice. In a pre-clinical study in pigs and a clinical study in 10 PD patients, the device provided detailed images, enabling safe, easy observation of the intraluminal side of the entire catheter, and of the morphology and status of the peritoneal surface in the abdominal cavity under dwelling PD solution. Since this device can be used repeatedly during PD therapy, clinical application of this device could contribute to improved management of clinical issues in current PD therapy, positioning PD as a safer, more reliable treatment modality for end-stage renal disease.

Metacarpal bone mineral density by radiographic absorptiometry predicts fracture risk in patients undergoing maintenance hemodialysis.

The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guideline update suggests bone mineral density testing to assess fracture risk in patients with chronic kidney disease, but dual-energy X-ray absorptiometry is not available in most dialysis facilities. Radiographic absorptiometry is an inexpensive and quick method for evaluating bone mineral density. Therefore, we analyzed a historical cohort of 456 maintenance hemodialysis patients to determine whether metacarpal bone mineral density measured by digital image processing, a computer-assisted radiographic absorptiometry technique, predicts fracture risk. At baseline, the median metacarpal bone mineral density T-score was -2.05 (interquartile range, -3.35 to -0.99). During a mean follow-up of 5.3 years, there were 16 clinical fractures and 11 asymptomatic vertebral fractures as estimated by height loss. Metacarpal bone mineral density T-score was significantly lower in patients who sustained a clinical fracture than in those remaining event-free. Decreasing metacarpal bone mineral density T-score was significantly associated with increased risk of clinical fracture (hazard ratio, 1.41 per 1 standard deviation decrease in bone mineral density T-score [95% confidence interval, 1.09 to 1.83]; the hazard ratio for lowest versus highest tertile was 4.86 [1.03 to 22.92]. Similar associations were observed between metacarpal bone mineral density T-score and vertebral fracture or any fracture. The results were robust to different analysis strategies and were consistent across different subgroups. Thus, radiographic absorptiometry could be a useful tool for primary screening of hemodialysis patients at high risk for fracture. Additional studies are required to determine the predictive ability of radiographic absorptiometry techniques compared to dual-energy X-ray absorptiometry or other established methods.

Parathyroid hormone-producing cells exist in adipose tissues surrounding the parathyroid glands in hemodialysis patients with secondary hyperparathyroidism.

Possible ectopic parathyroid hormone (PTH) production in adipose tissues surrounding hyperplastic parathyroid glands was examined in patients with secondary hyperparathyroidism (SHPT). In vitro culture of adipose tissues from 31 patients excised during parathyroidectomy showed PTH secretion in 23 (74.2%) patients. In vitro PTH secretion was detected in adipose tissues adhered to the parathyroid glands from 22 (71.0%) patients, in not-adhered adipose from 11 (35.5%) and in the thymus from four (28.6%) patients. Immunohistochemistry revealed colonies of PTH- and GCM2-positive cells intricately intertwined with adipocytes in excised adipose tissues prior to culture. When pieces of parathyroid parenchyma from SHPT patients were transplanted into the thyroid of immunodeficient nude rats with induced SHPT, the transplants secreted human PTH for one to three-and-half months after transplantation and expressed adipocyte markers, PPARγ2 and perilipin A, that the transplants did not express prior to transplantation. These findings indicate the importance of thoroughly removing adipose tissues surrounding the parathyroid glands when performing parathyroidectomy. We speculate that these ectopic PTH-producing cells are parathyroid parenchymal cells pushed out from the glands along with adipocyte progenitors during nodular growth of hyperplastic parenchymal cells and that these cells proliferate in SHPT, forming colonies PTH-producing cells intricately intertwined with adipocytes.

Glucocorticoid Receptor Antagonist Administration Prevents Adrenal Gland Atrophy in an ACTH-Independent Cushing's Syndrome Rat Model.

ACTH-independent Cushing's syndrome (CS) is mainly caused by cortisol-secreting adrenocortical tumours. It is well known that secondary adrenal insufficiency occurs after surgical resection of these tumours. In this regard, impaired adrenocortical function is likely induced by atrophy of the residual adrenal tissue as a result of chronic suppression by the low ACTH levels of the hypercortisolism state. Therefore, we considered the prevention of adrenal atrophy as a method for preventing postoperative adrenal insufficiency. On the basis of these findings, we hypothesized that the use of a glucocorticoid receptor (GR) antagonist before surgery in ACTH-independent CS would rapidly activate the hypothalamic-pituitary-adrenal (HPA) axis and residual adrenal function. We thus examined adrenal function in a dexamethasone- (DEX-) induced CS rat model with or without mifepristone (MIF). In this study, MIF-treated rats had elevated plasma ACTH levels and increased adrenal weights. In addition, we confirmed that there were fewer atrophic changes, as measured by the pathological findings and mRNA expression levels of corticosterone synthase CYP11B1 in the adrenal glands, in MIF-treated rats. These results indicate that MIF treatment prevents the suppression of the HPA axis and the atrophy of the residual adrenal tissue. Therefore, our study suggests that preoperative GR antagonist administration may improve residual adrenal function and prevent postoperative adrenal insufficiency in ACTH-independent CS.

Nutritional status and survival of maintenance hemodialysis patients receiving lanthanum carbonate.

Background: Hyperphosphatemia and poor nutritional status are associated with increased mortality. Lanthanum carbonate is an effective, calcium-free phosphate binder, but little is known about the long-term impact on mineral metabolism, nutritional status and survival. Methods: We extended the follow-up period of a historical cohort of 2292 maintenance hemodialysis patients that was formed in late 2008. We examined 7-year all-cause mortality according to the serum phosphate levels and nutritional indicators in the entire cohort and then compared the mortality rate of the 562 patients who initiated lanthanum with that of the 562 propensity score-matched patients who were not treated with lanthanum. Results: During a mean ± SD follow-up of 4.9 ± 2.3 years, 679 patients died in the entire cohort. Higher serum phosphorus levels and lower nutritional indicators (body mass index, albumin and creatinine) were each independently associated with an increased risk of death. In the propensity score-matched analysis, patients who initiated lanthanum had a 23% lower risk for mortality compared with the matched controls. During the follow-up period, the serum phosphorus levels tended to decrease comparably in both groups, but the lanthanum group maintained a better nutritional status than the control group. The survival benefit associated with lanthanum was unchanged after adjustment for time-varying phosphorus or other mineral metabolism parameters, but was attenuated by adjustments for time-varying indicators of nutritional status. Conclusions: Treatment with lanthanum is associated with improved survival in hemodialysis patients. This effect may be partially mediated by relaxation of dietary phosphate restriction and improved nutritional status.

A Retrospective Study on Erythropoiesis Stimulating Agent Dose Reducing Potential of an Anti-Platelet Activation Membrane Dialyzer in Hemodialysis Patients.

Our previous small-scale trial demonstrated an erythropoiesis stimulating agent (ESA)-sparing potential of the TORAYLIGHT NV (NV) dialyzer in hemodialysis patients with high interleukin-6 levels. We now retrospectively explored this ESA-sparing potential of the NV dialyzer in 122 and 129 prevalent dialysis patients who were on the NV and conventional polysulfone (PS) dialyzers, respectively, for 12 months. ESA resistance index (ERI) increased with the PS dialyzers whereas neither ERI nor ESA dose changed with the NV dialyzer. Analyses of baseline ERI or ESA dose-based subgroups revealed a decrease in ERI and ESA dose with the NV dialyzer in patients with a baseline ERI ≥12 IU·dL/week·kg·g Hb (P < 0.05) and in those with a baseline ESA dose >6000 IU/week (P < 0.001), respectively. Neither ERI nor ESA dose improved in the corresponding subgroups on the PS dialyzers. These findings suggest that NV dialyzer can improve ESA responsiveness in hemodialysis patients with advanced ESA resistance.

Critical Governance Issue of Parathyroid Hormone Assays and its Selection in the Management of Chronic Kidney Disease Mineral and Bone Disorders.

Measurement of circulating parathyroid hormone (PTH) levels is essential for optimal management of mineral and bone disorders (MBD) in chronic kidney disease (CKD) patients. There are two major types of PTH assays currently in use: intact parathyroid hormone (i-PTH) and whole PTH (w-PTH) assays. The i-PTH assay is the current standard, and considerable information regarding the management of CKD-MBD has been obtained with this method. However, several limitations have been found with the i-PTH assay. One limitation is that i-PTH assay also measures fragments other than full-length PTH (1-84). Another limitation is the existence of multiple readout methods of the i-PTH assay. The w-PTH assay is theoretically ideal because it exclusively detects full-length PTH (1-84). However, clinical data proving the advantages of w-PTH measurement are not sufficient. For uremic patients, Kidney Disease Improving Global Outcomes suggest that PTH levels should be maintained within approximately two to nine times the upper normal limit of the i-PTH assays. The most critical issue in the evaluation of PTH levels is the lack of definitive PTH assay method. Evidence-based recommendations on clinical management goals of PTH are warranted.

En Bloc Cadaver Kidney Transplantation From a 9-Month-Old Donor to an Adult Recipient: Maturation of Glomerular Size and Podocyte in the Recipient.

BACKGROUND: Favorable outcomes of en bloc pediatric donor kidney transplantation to adult recipients are attributed primarily to grafting of twice the nephron mass of a single kidney. METHODS: The kidneys of a 9-month-old male infant were transplanted en bloc in a 56-year-old man. Biopsies were performed 1 hour postreperfusion, 6 months and 3.5 years posttransplant. RESULTS: Warm and cold ischemia times were 21 and 426 minutes, respectively. The recipient was released from hemodialysis 10 days posttransplant and discharged 91 days posttransplant when serum creatinine was 0.9 mg/dL. At 4 years and 9 months posttransplant, serum creatinine was 1.0 mg/dL, and estimated glomerular filtration rate was 58.0 mL/min per 1.73 m2. The grafts increased in size until they reached adult size by 3 months posttransplant. The glomerular area and volume, respectively, increased from 5.9 × 103 µm2 and 0.34 × 106 µm3 at 1 hour postreperfusion to 14.9 × 103 µm2 and 1.27 × 106 µm3 at 3.5 years posttransplant, both of which were less than half of adult size. At 1 hour postreperfusion, podocytes were structurally immature. At 6 months posttransplant, podocyte immaturity was still evident. At 3.5 years posttransplant, podocytes were mature. CONCLUSIONS: These findings suggest that podocytes and glomerular size of pediatric donor kidneys can continue to mature in adult recipients at rates appropriate for donor age when transplanted en bloc. The maturational levels of podocytes and glomeruli may also be a factor involved in favorable outcomes of en bloc pediatric donor kidney transplantation.

Management of secondary hyperparathyroidism: how and why?

Secondary hyperparathyroidism (SHPT) is a common complication in chronic kidney disease. Currently, various treatment options are available, including vitamin D receptor activators, cinacalcet hydrochloride, and parathyroidectomy. These treatment options have contributed to the successful control of SHPT, and recent clinical studies have provided evidence suggesting that effective treatment of SHPT leads to improved survival. Although bone disease is the most widely recognized consequence of SHPT and remains a major target for treatment of SHPT, there is increasing evidence that parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23), both of which are markedly elevated in SHPT, have multiple adverse effects on extraskeletal tissues. These actions may lead to the pathological development of left ventricular hypertrophy, renal anemia, immune dysfunction, inflammation, wasting, muscle atrophy, and urate accumulation. Given that treatment of SHPT leads to decreases in both PTH and FGF23, these data provide an additional rationale for treating SHPT. However, definitive evidence is still lacking, and future research should focus on whether treatment of SHPT prevents the adverse effects of PTH and FGF23.

Vitamin D receptor agonist VS-105 directly modulates parathyroid hormone expression in human parathyroid cells and in 5/6 nephrectomized rats.

Vitamin D receptor (VDR) agonists (VDRAs) are commonly used to treat secondary hyperparathyroidism (SHPT) associated with chronic kidney disease (CKD). Current VDRA therapy often causes hypercalcemia, which is a critical risk for vascular calcification. Previously we have shown that a novel VDRA, VS-105, effectively suppresses serum parathyroid hormone (PTH) without affecting serum calcium levels in 5/6 nephrectomized (NX) uremic rats. However, it is not known whether VS-105 directly regulates PTH gene expression. To study the direct effect of VS-105 on modulating PTH, we tested VS-105 and paricalcitol in the spheroid culture of parathyroid cells from human SHPT patients, and examined the time-dependent effect of the compounds on regulating serum PTH in 5/6 NX uremic rats (i.p. 3x/week for 14days). In human parathyroid cells, VS-105 (100nM) down-regulated PTH mRNA expression (to 3.6% of control) and reduced secreted PTH (to 43.9% of control); paricalcitol was less effective. VS-105 effectively up-regulated the expression of VDR (1.9-fold of control) and CaSR (1.8-fold of control) in spheroids; paricalcitol was also less effective. In 5/6 NX rats, one single dose of 0.05-0.2µg/kg of VS-105 or 0.02-0.04µg/kg of paricalcitol effectively reduced serum PTH by >40% on Day 2. Serum PTH remained suppressed during the dosing period, but tended to rebound in the paricalcitol groups. These data indicate that VS-105 exerts a rapid effect on suppressing serum PTH, directly down-regulates the PTH gene, and modulates PTH, VDR and CaSR gene expression more effectively than paricalcitol.

Feasibility of photodynamic therapy for secondary hyperparathyroidism in chronic renal failure rats.

BACKGROUND: Feasibility of photodynamic therapy (PDT) for secondary hyperparathyroidism (SHPT) was examined in a rat model of SHPT. METHODS: A photosensitizer, 5-aminolevulinic acid (5-ALA), was injected intraperitoneally, and the parathyroid glands were irradiated either after surgical exposure with 385-nm light or transdermally with 630-nm light from a light-emitting diode (LED) lamp. RESULTS: PDT with high 5-ALA and irradiation doses caused severe hypoparathyroidism in SHPT rats within two days. Low-dose invasive PDT reduced intact parathyroid hormone (iPTH) levels in all rats from 748.9 ± 462.6 pg/mL at baseline to 138.7 ± 117.5 pg/mL at week 6, followed by a further decrease to 80.5 ± 54.0 pg/mL at week 9 in 60 % of rats or an increase to 970.0 ± 215.6 pg/mL at week 9 in 40 % of rats. Low-dose noninvasive PDT reduced iPTH levels from 1612.5 ± 607.8 pg/mL at baseline to 591.9 ± 480.1 pg/mL at week 4 in all rats. Thereafter, iPTH levels remained low in 43 % of rats and were 233.7 ± 51.6 pg/mL at week 9, whereas 57 % showed an increase, reaching 3305.9 ± 107.3 pg/mL at week 9. Control SHPT rats had iPTH levels of 2487.8 ± 350.9 and 2974.6 ± 372.1 pg/mL at week 4 and 9, respectively. The parathyroid glands of the rats with low iPTH levels were atrophied and had few parathyroid cells surrounded by fibrotic materials and no recognizable blood vessels. Those of the rats with high iPTH levels showed well-preserved gland structure, clusters of parathyroid cells, and blood vessels. CONCLUSION: These results demonstrate that 5-ALA-mediated PDT for SHPT is feasible.

Effect of Scavenging Circulating Reactive Carbonyls by Oral Pyridoxamine in Uremic Rats on Peritoneal Dialysis.

Pyridoxamine, a reactive carbonyl (RCO) scavenger, can ameliorate peritoneal deterioration in uremic peritoneal dialysis (PD) rats when given via dialysate. We examined the effects of scavenging circulating RCOs by oral pyridoxamine. Rats underwent nephrectomy and 3 weeks of twice daily PD either alone or with once daily oral pyridoxamine. PD solution was supplemented with methylglyoxal, a major glucose-derived RCO, to quench intraperitoneal pyridoxamine. Oral pyridoxamine achieved comparable blood and dialysate pyridoxamine concentrations, suppressed pentosidine accumulation in the blood but not in the mesenterium or dialysate, and reduced the increases in small solute transport and mesenteric vessel densities, with no effects on submesothelial matrix layer thickening or serum creatinine. Thus, reducing circulating RCOs by giving oral pyridoxamine with PD provides limited peritoneal protection. However, orally given pyridoxamine efficiently reaches the peritoneal cavity and would eliminate intraperitoneal RCOs. Oral pyridoxamine is more clinically favorable and may be as protective as intraperitoneal administration.

A Case of Encapsulating Peritoneal Sclerosis Complicated by Malignant Peritoneal Mesothelioma.

We report a case of peritoneal mesothelioma discovered in a patient during peritoneal dialysis. The patient was a 55-year-old woman who had no history of asbestos exposure. Owing to end-stage kidney failure, she had been undergoing peritoneal dialysis for over 8 years, and she had been diagnosed with encapsulating peritoneal sclerosis. She was admitted to the hospital for intestinal obstruction. Three months later, she noticed an enlarging mass in the epigastric region. Computed tomography showed a 10-cm mass originating in the abdominal wall that had invaded the liver. It was diagnosed as malignant mesothelioma via biopsy. Cases of sarcoma-like mass-forming peritoneal mesothelioma are rare, and there are no prior reports of encapsulating peritoneal sclerosis complicated by malignant peritoneal mesothelioma. Thus, this unique case of peritoneal mesothelioma can provide us with important knowledge about this rare entity.

A Prospective Multicenter Randomized Controlled Study on Interleukin-6 Removal and Induction by a new Hemodialyzer With Improved Biocompatibility in Hemodialysis Patients: A Pilot Study.

We compared interleukin-6 (IL-6) removal and induction between conventional polysulfone (Con) and TORAYLIGHT NV (NV) dialyzers in hemodialysis patients. Twenty patients on Con with high IL-6 concentrations (2.7-8.5 pg/mL) were randomized to Con or NV group. Dialyzer performance was determined in NV group while patients were on Con and after being switched onto NV. Erythropoiesis-stimulating agent (ESA) response index (ERI) was assessed every 4 months for one year. IL-6 clearance was comparable between Con and NV. IL-6 removal rates were comparable for the first 1 h, but were higher with NV for the entire session (P = 0.03). Before-to-during-dialysis IL-6 concentration ratios were lower with NV on the venous side after the session (P = 0.03). During the one-year study, hemoglobin was lower in Con group than in NV group at month 8 (P = 0.046). ERI decreased in NV and increased in Con group, with a significant difference between the groups (P = 0.002). NV and Con are comparable in removing IL-6 and both induce IL-6. However, the data suggest that NV induces less IL-6, which may reduce the risk of ESA hyporesponsiveness.

Association between Asymmetric Dimethylarginine and Pentosidine in Dialysis Effluent of Peritoneal Dialysis Patients -A possible intraperitoneal crosstalk between asymmetric dimethylarginine and advanced glycation end products in peritoneal dialysis patients.

OBJECTIVE: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase. Elevated serum ADMA concentration is associated with impaired vascular endothelial function. We examined the relationships of ADMA with pentosidine, a representative advanced glycation end product, cytokines and the markers of peritoneal inflammation, damage and repair in dialysate effluent of peritoneal dialysis patients. METHODS: Study design was cross-sectional. Twenty-eight peritoneal dialysis patients who were ≥ 18 years of age, had been on peritoneal dialysis for at least 3 months and had no history of renal transplantation were enrolled. Dialysis effluent and blood were sampled after 8 hours of peritoneal dialysis. Concentrations of ADMA, pentosidine, cytokines and the markers of peritoneal inflammation, damage and repair were determined in dialysis effluent. Blood samples were analyzed for routine laboratory parameters. RESULTS: The effluent ADMA level had a significant correlation with effluent pentosidine concentration (R=0.511, P=0.005), but not with interleukin-6, interleukin-8, transforming growth factor-α, hyaluronic acid, cancer antigen 125 or fibrinogen/fibrin degradation products. CONCLUSION: In the light of available evidence, our results suggest that AGEs generated during dialysate dwelling alters ADMA metabolism in the peritoneal tissues, leading to ADMA accumulation in the peritoneal cavity.

Evaluation of Parathyroidectomy for Secondary and Tertiary Hyperparathyroidism by the Parathyroid Surgeons' Society of Japan.

Secondary hyperparathyroidism (SHPT) remains a serious complication in patients with chronic kidney disease, and some patients require parathyroidectomy. The Parathyroid Surgeons' Society of Japan (PSSJ) evaluated parathyroidectomy for SHPT and tertiary hyperparathyroidism (THPT) in Japan. The annual numbers of parathyroidectomies between 2004 and 2013 were evaluated using questionnaires. Since 2010, the PSSJ has registered the patients. In total, 826 patients from 42 institutions were registered. The annual number of parathyroidectomies for SHPT and THPT in Japan increased from 2004 to 2007 and then decreased markedly after 2007, with 296 operations performed in 2013. The number of women and men was almost equal (397/427). Median (interquartile range) age of these patients was 59.0 (24-87) years, the duration of hemodialysis before parathyroidectomy was 10.83 (0.0-38.7) years, and diabetic nephropathy was 87/826 (10.5%). Of these patients 59.6% were treated with cinacalcet at undergoing parathyroidectomy. In 75.3% of patients, a total parathyroidectomy with forearm autograft was performed. In 77.7% of patients, four or more parathyroid glands were removed during the initial operation. The incidences of husky voice and wound hemorrhage were 2.9% and 1.1%, respectively. The number of parathyroidectomies for SHPT in Japan decreased markedly after the introduction of cinacalcet. Based on the evaluation of registered patients, parathyroidectomies have been successfully performed at the institutions participating in the PSSJ.