Naoki Tsuboniwa

Glycemic control and survival of diabetic hemodialysis patients—Importance of lower hemoglobin A1C levels

AIMS The significance of hemoglobin A1C (HbA1C) on the survival of diabetic hemodialysis patients still remains controversial. We investigated the impact of HbA1C on the survival. METHODS A total of 122 diabetic patients on maintenance hemodialysis (age, 59.9+/-11.9 years [mean+/-SD]; hemodialysis duration: 53+/-38 months) were surveyed (survey period: 46+/-19 months). RESULTS The cumulative survival of the poor glycemic control group (mean HbA1C of 3-month period > or =6.3%, n=62) was significantly lower than that of the good group (HbA1C<6.3%, n=60), as determined by Kaplan-Meier estimation (P=0.0084, log-rank test). Kaplan-Meier analysis also demonstrated that both cardiovascular and non-cardiovascular mortalities were higher in the poor group than in the good group (P=0.0545 and P=0.0453, respectively). In a multivariate Cox proportional hazard model, the mean HbA1C was a significant predictor of survival (OR 1.260 per 1.0%, 95% CI 1.020-0.579, P=0.0325). CONCLUSIONS Poor glycemic control is an independent predictor of poor prognosis in diabetic hemodialysis patients. HbA1C is a clinically useful parameter for identifying the risk for mortality, both for cardiovascular and non-cardiovascular mortality, and that careful management of glycemic control by use of HbA1C is important.

Significant inverse relationship between serum undercarboxylated osteocalcin and glycemic control in maintenance hemodialysis patients.

SummaryIncreased levels of serum undercarboxylated osteocalcin, which were associated with bone metabolism markers, correlated inversely with indices of glucose metabolism (plasma glucose, hemoglobin A1C, and glycated albumin) in hemodialysis patients with abnormalities of bone metabolism.IntroductionUndercarboxylated osteocalcin (ucOC), a possible marker of bone metabolism and one of the osteoblast-specific secreted proteins, has recently been reported to be associated with glucose metabolism. We tested the hypothesis that ucOC levels are associated with indices of glucose metabolism in chronic hemodialysis patients with abnormalities of bone metabolism.MethodsSerum ucOC, bone alkaline phosphatase (BAP, a bone formation marker), and tartrate-resistant acid phosphatase-5b (TRACP-5b, a bone resorption marker) were measured in 189 maintenance hemodialysis patients (96 diabetics and 93 non-diabetics), and their relationships with glucose metabolism were examined.ResultsucOC correlated positively with BAP (ρ = 0.489, p < 0.0001), TRACP-5b (ρ = 0.585, p < 0.0001) and intact parathyroid hormone (iPTH; ρ = 0.621, p < 0.0001). Serum ucOC levels in the diabetic patients were lower than those of non-diabetic patients (p < 0.001), although there were no significant differences in serum BAP or TRACP-5b between diabetic and non-diabetic patients. Serum ucOC correlated negatively with plasma glucose (ρ = −0.303, p < 0.0001), hemoglobin A1C (ρ = −0.214, p < 0.01), and glycated albumin (ρ = −0.271, p < 0.001), although serum BAP or TRACP-5b did not. In multiple linear regression analysis, log [plasma glucose], log [hemoglobin A1C], and log [glycated albumin] were associated significantly with log [ucOC] after adjustment for age, gender, hemodialysis duration, and body mass index but were not associated with log [BAP], log [TRACP-5b], or log [intact PTH].ConclusionIncreased levels of serum ucOC, which were associated with bone metabolism markers, were inversely associated with indices of glucose metabolism in hemodialysis patients.

Decreases in parathyroid gland volume after cinacalcet treatment in hemodialysis patients with secondary hyperparathyroidism.

Background/Aim: Cinacalcet, an allosteric modulator of the calcium-sensing receptor, effectively reduces serum parathyroid hormone (PTH). It was examined whether a regression of parathyroid glands in hemodialysis patients with secondary hyperparathyroidism was induced by cinacalcet treatment. Methods: Ultrasonography of the parathyroid glands was performed to examine the changes in the parathyroid gland volumes after cinacalcet treatment in 58 patients. Results: After cinacalcet treatment, serum calcium, phosphate, alkaline phosphatase, and intact PTH significantly decreased (p < 0.0001). The total volumes of the parathyroid glands were significantly decreased 6 months after cinacalcet treatment (942 ± 747 vs. 708 ± 550 mm3, p < 0.0005). There was a significant positive correlation between the parathyroid gland volumes at the start of cinacalcet treatment and the volume reduction in parathyroid glands (r = 0.716, p < 0.0001). Of the 58 patients, the total parathyroid gland volume was decreased in 42 patients and increased in 16 although the doses of cinacalcet, phosphate binders or vitamin D were not significantly different. In both groups, the intact PTH serum levels were significantly decreased after cinacalcet treatment. Conclusion: Cinacalcet treatment in patients with secondary hyperparathyroidism significantly reduced the total parathyroid gland volume in a short 6-month period. This study suggests that cinacalcet treatment may postpone parathyroidectomy and/or reduce cases.

Relationship between Fat Mass and Serum High-Sensitivity C-Reactive Protein Levels in Prevalent Hemodialysis Patients

Background/Aims: Little is known about the relationship between fat mass distribution and chronic inflammation in dialysis patients, in whom chronic inflammation is related to morbidity and mortality. Methods: The fat and lean masses (truncal and nontruncal) of 452 hemodialysis patients (age: 64 ± 11 years; hemodialysis duration: 89 ± 77 months; 37% diabetics) were measured by dual X-ray absorptiometry and their association with high-sensitivity C-reactive protein (hsCRP) was examined. Results: The fat mass of the high hsCRP group (n = 106) was significantly higher than that of the normal hsCRP group (n = 346; p < 0.05); there were no significant differences in lean mass between the two groups. Truncal fat mass of the former group was significantly greater than that of the latter (p < 0.05), but there was no significant difference in nontruncal fat mass between the two groups. In multiple regression analysis, truncal fat mass (β = 0.227, p < 0.01) was significantly and independently associated with serum hsCRP levels after adjustment for age, gender and serum albumin (R2 = 0.137, p < 0.01), whereas nontruncal fat mass was not. Conclusion: Fat mass, particularly truncal fat mass, but not lean body mass, was significantly associated with serum hsCRP levels. The results suggest that truncal fat mass exhibits a distinct effect on chronic inflammation in hemodialysis patients.

Effect of cinacalcet on bone mineral density of the radius in hemodialysis patients with secondary hyperparathyroidism.

BACKGROUND/AIM Cinacalcet, an allosteric modulator of the calcium sensing receptor, effectively reduces serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. It is not well known whether bone mineral density (BMD) of hemodialysis patients with secondary hyperparathyroidism is altered after cinacalcet treatment. METHODS The BMD in the distal 1/3 of the radius and in the ultradistal radius, which are enriched with cortical and cancellous bone, respectively, was examined by dual X-ray absorptiometry, 1 year prior to, at the start, and 1 year after cinacalcet treatment, in 61 patients. RESULTS The BMD of both the distal 1/3 and ultradistal radius decreased significantly in the year prior to cinacalcet treatment (p < 0.01). However, the BMD at either site did not change significantly in the year after cinacalcet treatment. The annual changes in the BMD of the distal 1/3 radius increased significantly from -0.023 ± 0.029 g/cm2/year to -0.002 ± 0.033 g/cm2/year, prior to and after cinacalcet treatment, respectively; however, the annual changes in the BMD of the ultradistal radius did not change significantly prior to and after cinacalcet treatment. CONCLUSION There was a significant association between cinacalcet treatment and reduction in BMD loss in patients with secondary hyperparathyroidism. Cortical bone, rather than cancellous bone, was particularly affected by cinacalcet treatment.

Significant Positive Association Between Parathyroid Hormone and Fat Mass and Lean Mass in Chronic Hemodialysis Patients

BACKGROUND It has been reported that there is a significant positive relationship between PTH and body weight or body mass index in the general population. However, little is known about this relationship in dialysis patients in whom PTH levels are higher. It is also not known whether fat mass or lean mass is associated with serum PTH among these patients. In the present study, we examined the association of intact PTH with fat mass and lean mass in hemodialysis patients. METHODS Serum intact PTH, calcium, and phosphate were measured in 590 hemodialysis patients (age, 60.2 ± 12.2 y; median hemodialysis duration, 59.6 mo; 343 males and 247 females; diabetics, 27.7%). Fat mass and lean mass were measured by dual-energy x-ray absorptiometry. RESULTS Intact PTH correlated significantly and positively with body weight and body mass index in all patients. Intact PTH correlated significantly and positively with fat mass and lean mass in males (P < .01), and tended to correlate positively with fat mass and lean mass in females (P < .1). In multiple regression analyses after adjustment for age, gender, hemodialysis duration, calcium, phosphate, vitamin D use, and phosphate binder use, intact PTH was associated significantly with body weight (β = .190; P < .0001), body mass index (β = .177; P < .0001), fat mass (β = .142; P < .0005), and lean mass (β = .192; P < .01). Furthermore, intact PTH was associated significantly and independently with both fat mass and lean mass after adjustment (R(2) = .206; P < .0001). CONCLUSION Serum intact PTH in chronic hemodialysis patients is associated significantly and positively with body composition of fat mass and lean mass.