Association of serum mineral parameters with mortality in hemodialysis patients: Data from the Korean end-stage renal disease registry

BACKGROUND: We investigated the associations between mineral metabolism parameters and mortality to identify optimal targets in Korean hemodialysis patients. METHODS: Among hemodialysis patients registered in the end-stage renal disease registry of the Korean Society of Nephrology between March 2012 and June 2017, those with serum calcium, phosphorus, and intact parathyroid hormone (iPTH) measured at enrollment were included. Association of serum levels of calcium, phosphorus, and iPTH with all-cause mortality was analyzed. RESULTS: Among 21,433 enrolled patients, 3,135 (14.6%) died during 24.8 ± 14.5 months of follow-up. After multivariable adjustment, patients in the first quintile of corrected calcium were associated with lower mortality (hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.71–0.99; P = 0.003), while those in the fifth quintile were associated with higher mortality (HR, 1.39; 95% CI, 1.20–1.61; P < 0.001) compared with those in the third quintile. For phosphorus, only the lowest quintile was significantly associated with increased mortality (HR, 1.24; 95% CI, 1.08–1.43; P = 0.003). The lowest (HR, 1.18; 95% CI, 1.02–1.36; P = 0.026) and highest quintiles of iPTH (HR, 1.24; 95% CI, 1.05–1.46; P = 0.013) were associated with increased mortality. For target counts achieved according to the Kidney Disease Outcomes Quality Initiative guideline, patients who did not achieve any mineral parameter targets hadhigher mortality than those who achieved all three targets (HR, 1.37; 95% CI, 1.12–1.67; P = 0.003). CONCLUSION: In Korean hemodialysis patients, high serum calcium, low phosphorus, and high and low iPTH levels were associated with increased all-cause mortality.

Stabilization of serum alkaline phosphatase in hemodialysis patients by implementation of local chronic kidney disease-mineral bone disorder management strategy: A quality improvement study

BACKGROUND: The aim of this study is to narrow the gap between global guidelines and local practices, we recently established domestic recommendations by adapting the international guidelines for management of chronic kidney disease-mineral bone disorder (CKD-MBD) in patients on maintenance hemodialysis (MHD). This study was undertaken to determine whether application of this guideline adaptation was associated with improved serum mineral profiles in patients with CKD-MBD. METHODS: A total of 355 patients on MHD were enrolled from seven dialysis units. After adhering to our strategy for one year, serum phosphorus, calcium, intact parathyroid hormone (iPTH), and alkaline phosphatase (AP) levels were compared with the baseline. The endpoint was improvement in the proportion of patients with serum mineral levels at target recommendations. RESULTS: The median serum phosphorus level and proportion of patients with serum phosphorus within the target range were not changed. Although the median serum calcium level was significantly increased, the proportion of patients with serum calcium within the target range was not significantly affected. The proportion of patients with serum iPTH at the target level was not altered, although the median serum iPTH was significantly decreased. However, both median serum AP and the proportion of patients with serum AP at the target level (70.4% vs. 89.6%, P < 0.001) were improved. CONCLUSION: In our patients with MHD, serum mineral profiles were altered and the serum AP level stabilized after implementing our recommendations. Long-term follow-up evaluations are necessary to determine whether uremic bone disease and cardiovascular calcifications are affected by these recommendations.

Predicting postoperative total calcium requirements after parathyroidectomy in secondary hyperparathyroidism

BACKGROUND/AIMS: To prevent hypocalcemia after parathyroidectomy (PTX), parenteral calcium is required in addition to oral calcitriol and calcium. After switching to oral calcium, patients can be discharged from the hospital. The aim of this study was to analyze the clinical characteristics and outcomes of PTX performed at a single Korean center and to investigate the associated laboratory factors used to analyze the total amount of postoperative calcium required. METHODS: We enrolled 91 hemodialysis patients undergoing PTX from November 2003 to December 2011. We collected clinical and laboratory data preoperatively, 12 and 48 hours postoperatively, at discharge, and 3 and 6 months postoperatively. RESULTS: In total, 59 patients underwent PTX with autotransplantation (AT), 6 underwent total PTX without AT, 11 underwent subtotal PTX, and 15 underwent limited PTX. Total PTX without AT showed the lowest recurrence rate. At all postoperative time points, the mean levels of serum calcium, phosphorus, and intact parathyroid hormone (iPTH) decreased significantly, compared with preoperative levels; however, alkaline phosphatase (ALP) increased significantly from 48 hours postoperatively to discharge (p < 0.001). On multiple linear regression analysis, the total amount of injected calcium during hospitalization showed a significant correlation with preoperative ALP (p < 0.001), preoperative iPTH (p = 0.037), and Deltaphosphorus at 48 hours (p < 0.001). We developed an equation for estimating the total calcium requirement after PTX. CONCLUSIONS: Preoperative ALP, preoperative iPTH, and Deltaphosphorus at 48 hours may be significant factors in estimating the postoperative calcium requirement. The formula for postoperative calcium requirement after PTX may help to predict the duration of postoperative hospitalization.

Management of chronic kidney disease-mineral and bone disorder: Korean working group recommendations

For Korean dialysis patients, chronic kidney disease-mineral bone disorder is a serious burden because of cardiovascular calcification and mortality. However, recent epidemiologic data have demonstrated that many patients undergoing maintenance hemodialysis are out of the target ranges of serum calcium, phosphorus, and intact parathyroid hormone. Thus, we felt the necessity for the development of practical recommendations to treat abnormal serum phosphorus, calcium, and iPTH in dialysis patients. In this paper, we briefly comment on the measurement of serum calcium, phosphorus, iPTH, dialysate calcium concentration, dietary phosphorus restriction, use of phosphate binders, and medical and surgical options to correct secondary hyperparathyroidism. In particular, for the optimal management of secondary hyperparathyroidism, we suggest a simplified medication adjustment according to certain ranges of serum phosphorus and calcium. Large-scale, well-designed clinical studies are required to support our strategies to control chronic kidney disease-mineral bone disorder in this country. Based on such data, our practice guidelines could be established and better long-term outcomes should be anticipated in our dialysis patients.

Serum calcium and phosphorus levels in patients undergoing maintenance hemodialysis: A multicentre study in Korea

BACKGROUND: In many countries, nephrologists follow clinical practice guidelines for mineral bone disorders to control secondary hyperparathyroidism (SHPT) associated with abnormal serum calcium (Ca) and phosphorus (P) levels in patients undergoing maintenance hemodialysis (MHD). The Kidney Disease Outcomes Quality Initiative (KDOQI) Guidelines have long been used in Korea, and this study was undertaken to investigate the current status of serum Ca and P control in MHD patients. METHODS: Data were collected from a total of 1,018 patients undergoing MHD without intercurrent illness, in 17 hemodialysis centers throughout the country. Serum levels of Ca, P, and intact parathyroid hormone (iPTH) were measured over 1 year, and the average values were retrospectively analyzed. RESULTS: Serum levels of Ca, P, and the CaxP product were 9.1+/-0.7mg/dL, 5.3+/-1.4mg/dL, and 48.0+/-13.6mg2/dL2, respectively. However, the percentages of patients with Ca, P, and Ca x P product levels within the KDOQI guideline ranges were 58.7%, 51.0%, and 70.7%, respectively. Of the 1,018 patients, 270 (26.5%) had iPTH >300pg/mL (uncontrolled SHPT), whereas 435 patients (42.7%) showed iPTH <150pg/mL. Patients with uncontrolled SHPT had significantly higher values of serum Ca, P, and CaxP product than those with iPTH < or =300pg/mL. CONCLUSION: Despite the current clinical practice guidelines, SHPT seems to be inadequately controlled in many MHD patients. Uncontrolled SHPT was associated with higher levels of serum Ca, P, and Ca x P product, suggestive of the importance of SHPT management.

Efficacy of Hemocontrol Biofeedback System in Intradialytic Hypotension-Prone Hemodialysis Patients

We conducted a study to determine whether the hemocontrol biofeedback system (HBS) can improve intradialytic hypotension (IDH) in hypotension-prone hemodialysis (HD) patients compared with conventional HD. In this multicenter prospective crossover study, 60 hypotension-prone patients were serially treated by conventional HD for 8 weeks (period A), by HD with hemoscan blood volume monitoring for 2 weeks (period B0), and by HBS HD for 8 weeks (period B1). The number of sessions complicated by symptomatic IDH during 24 HD sessions (14.9+/-5.8 sessions, 62.1% in period A vs 9.2+/-7.2 sessions, 38.4% in period B1, P<0.001) and the number of IDH-related nursing interventions in a session (0.96+/-0.66 in period A vs 0.56+/-0.54 in period B1, P<0.001) significantly decreased in period B1 than in period A. Recovery time from fatigue after dialysis was significantly shorter in period B1 than in period A. The patients with higher post-dialysis blood pressure, lower difference between pre- and post-dialysis blood pressure, less frequent IDH, and higher pre- and post-dialysis body weight in period A responded better to HBS in period B1 in regard to the reduction of IDH. In conclusion, HBS may improve the patient tolerability to HD by reducing the IDH frequency and promoting faster recovery from fatigue after dialysis.

25-Hydroxyvitamin D Status in Patients with Chronic Kidney Disease in a Single Center / 대한신장학회지

PURPOSE: We checked the levels of serum 25-hydroxyvitmain D (25OHD) in the patients with chronic kidney disease (CKD) to survey the status of vitamin D levels, to see the seasonal variations of 25OHD, and to evaluate the relationships among the levels of intact PTH, corrected calcium, and phosphorus. METHODS: We defined vitamin D insufficiency and vitamin D deficiency as serum 25-hydroxyvitamin D levels between 20 and 30 ng/mL and below 20 ng/mL, respectively. 185 patients in a single center were enlisted who categorized into 3 groups, CKD2-3, CKD4, and CKD5 by eGFR using MDRD7 equation. To see the seasonal differences of the levels of 25OHD, we collected laboratory data two times per each patient during summer division (April to September) and winter division (October to March). RESULTS: Prevalences of hypovitaminosis D were 42.8% (CKD2-3), 66.1% (CKD4), 92.8% (CKD5) in summer division and 48.7% (CKD2-3), 73.1% (CKD4), 92.8% (CKD5) in winter division. Seasonal difference of the levels of 25OHD was evident only in CKD stage 2-3 (p=0.018). Negative correlations were recognized between 25OHD and intact PTH (r=-0.2048, p<0.001), phosphorus (r=-0.1711, p=0.0011). CONCLUSION: Hypovitaminosis D is prevalent even in patients with early stages of CKD. The levels of 25OHD decreased significantly in winter division in patients with CKD stages 2-3. The levels of 25OHD were inversely correlated with those of intact PTH, phosphorus, respectively.

Mandibular Enlargement, Metastatic Pulmonary Calcification and Gastric Mucosal Calcinosis in a Patient with Chronic Kidney Disease-mineral Bone Disorder / 대한신장학회지

Secondary hyperparathyroidism is one of the most common complications of patients with chronic kidney disease (CKD). Mandibular enlargement, metastatic pulmonary calcification, and gastric mucosal calcinosis are rare complications in these patients. The defect of calcium and phosphorus metabolism may precipitate pathologic calcification at diverse organs and soft tissue, and change bone architecture. In case of involving periarticular area, patients usually present with localized swelling, pain, and reduced mobility in affected sites. However, in case of organ involvement, except in an advanced stage of disease, there are no specific symptoms. Among these patients, treatment strategies include tight control of calcium and phosphate levels, parathyroidectomy for hyperparathyroidism, renal transplantation, and local excision of calcific lesions. We report a case of mandibular enlargement, metastatic pulmonary calcification, and gastric mucosal calcinosis due to CKD with improvement 3 months after medical and surgical treatment.

The change of serum level of total antioxidant status and cytokine, and in-stent restenosis after supplementation of antioxidant / 대한내과학회지

BACKGROUND: Oxidative stress might be a role in atherosclerosis and increased intake of antioxidant appear to be protective and modify neointimal formation. An antioxidant and probucol prevents endothelial dysfunction and low density lipoprotein oxidation and also inhibits the secretion of cytokine by macrophages. We aimed 1) to study the effects of antioxidant (Vitamin C, E and probucol) supplementation on serum level of antioxidant status (TAS), P-selectin, MCP-1, IL-6 and IL-10 and 2) to investigate the effects of antioxidant intake on in-stent restenosis. METHODS: Total 90 patients were assigned to control or antioxidant group (probucol; 500 mg, vitamin C; 1,000 mg, vitamin E; 400 mg). We performed follow up coronary angiography in 35 patients of antioxidant group and 36 patients of control group after 6 months of coronary bare metal stent implantation. We counted the stenotic lesions more than 50% of implanted stent lumen as a restenosis by quantitative coronary angiography. The serum levels of total antioxidant status, P-selectin, MCP-1, IL-6 and IL-10 were measured. RESULTS: The serum levels of total antioxidant status was not elevated in antioxidant group. Antioxidant supplementation did not change the serum levels of P-selectin, MCP-1, IL-6 and IL-10. The 6-month angiographic in-stent restenosis rate was 27% versus 30% (p=NS) with an associated late loss of 0.76+/-1.01 mm versus 0.91+/-1.00 mm (p=NS) for antioxidant group and control group. The serum levels of total antioxidant status did not correlate with the restenosis or late loss after stent implantation. CONCLUSIONS: Vitamin C, E and probucol did not elevate the serum level of antioxidant status and could not prevent in-stent restenosis after bare metal stent implantation.

A Case of Hypernatremia by Folk Remedies in a CRF Patient / 대한신장학회잡지

We report a case of chronic hypernatremia caused by excessive salt intake as folk remedies for three months. The patient had chronic tubulointerstitial nephritis (CTIN), but without documented cognitive or psychiatric disorders. She presented with severe hypernatremia 189 mmol/L and general weakness. Fluid therapy was done initially with isotonic and then with 0.45% hypotonic saline until serum sodium level reached to 157 mmol/L. Finally hemodialysis was supplemented to achieve normal serum sodium level, and she recovered without any sequelae. This report might be the first case of chronic hypernatremia due to voluntary ingestion of excessive salt in an adult patient with CTIN but without cognitive or psychiatric disorders.

Responsiveness of Recombinant Human Erythropoietin in Chronic Renal Failure Patients Undergoing Maintenance Hemodialysis / 대한신장학회잡지

BACKGROUND: Hyporesponsiveness to erythropoietin is an important issue in the treatment of the anemia of chronic renal failure. We tried to identify the factors of erythropoietin responsiveness in chronic renal failure patients undergoing maintenance hemodialysis for the effective treatment of anemia. METHODS: Seventy hemodialysis patients with hemoglobin increment over 2.0 g/dL during erythropoietin treatment were divided into two groups by median erythropoietin dose, 120 IU/kg/week (the low-dose group vs. the high-dose group). We compared age, gender, cause of renal failure, duration of hemodialyis, use of angiotensin-converting enzyme inhibitor, hemoglobin, hematocrit, serum iron, TIBC, transferrin saturation, ferritin, albumin, cholesterol, parathyroid hormone (iPTH), CRP, CO2 content, BUN, creatinine and Kt/V between the two groups. RESULTS: The low-dose group had significantly shorter duration of hemodialysis (40.9 months vs. 66.1 months, p=0.036), higher serum albumin level (3.93 g/dL vs. 3.72 g/dL, p=0.011) and lower iPTH level (94.97 pg/mL vs. 218.52 pg/mL, p=0.013) compared with the high-dose group. Serum creatinine level and Kt/V showed a tendency to be higher in the low-dose group but there were no significant differences (10.53 mg/dL vs. 9.40 mg/dL, p=0.053 and 1.69 vs. 1.38, p=0.080). Other clinical and laboratory parameters were not different between the two groups. CONCLUSION: Adequate nutritional support and prevention of secondary hyperparathyroidism may be helpful to enhance the responsiveness of erythropoietin in chronic renal failure patients undergoing maintenance hemodialysis.

Evaluation of Left Ventricular Function using New Index in Echocardiography

BACKGROUND: Systolic and diastolic dysfunction frequently coexist in heart failure. The purpose of this study is to evaluate combined systolic and diastolic function in heart failure using new index presented by Dr. Tei. A new index: [(ICT+IRT)/ET] defined as the sum of isovolemic contraction time(ICT) and isovolemic relaxation time(IRT) divided by ejection time(ET). METHOD: Study patients consisted of 71 subjects. 20 normals, 23 patients in NYHA class II, 22 patients in NYHA class III and 6 patients in NYHA class IV. Left ventricular end-systolic and end-diastolic dimension, FS(fractional shortening) were measured by conventional echocardiography. ICT, IRT, ET, ICT/ET, deceleration time of mitral E wave and E/A of mitral flow were also measured.(ICT+IRT)/ET was easily obtained by subtracting ET from the interval between cessation and onset of the mitral inflow to give the sum of ICT and IRT. Cardiac output was calculated by left ventriculography in 10 normals and 19 patients. RESULTS: The mean value of (ICT+IRT)/ET was significantly different between group IV(0.88 +/-0.03) and group I(0.50+/-0.04) and II(0.50+/-0.03)(p<0.01). also, was significant between group IV and group III(0.63+/-0.04)(p<0.05). FS and deceleration time of mitral E wave were also significant between group III and group IV(p<0.05). Cardiac output calculated by left ventriculography was significantly correlated with(ICT+IRT)/ET(n=29, r=-0.463, p<0.05). CONCLUSION: (ICT+IRT)/ET is a new and simple Doppler index of combined systolic and diastolic left ventricular function in patient with heart failure.

Effects of Nifedipine on Left Ventricular Diastolic Function in Hypertensive Patients by Assessment with Doppler Echocardiography

It is well known that hypertension is associated with left ventricular diastolic dysfunction which frequently precede systolic dysfunction. To determine whether nifedipine could improve left ventricular diastolic function in hypertensive patients, we studied 15 hypertensive patients and 15 normotensive subjects matched for sex, age with Doppler echocardiography. After oral administration of 10mg of nifedipine, there were no significant changes in Doppler-derived transmitral diastolic filling indexes of normotensive subjects. On the other hand, although peak flow velocity in atrial systole(PFVA), time velocity integral in atrial systole(TVIA) did not change significantly after nifedipine, nifedipine significantly increased peak flow velocity in early diastole(PFVE) from 40.2+/-6.4cm/sec to 46.5+/-10.9cm/sec(p<0.005), time velocity integral in early diastole(TVIE) from 5.24+/-1.2cm to 5.97+/-1.43cm(p<0.001), the ratio of PFVE/PFVA from 0.69+/-0.11 to 0.76+/-0.12(p<0.05), the ratio of TVIE/TVIA from 1.18+/-0.21 to 1.29+/-0.24(p<0.05), deceleration slope(DS) from 244.9+/-51.9cm/sec2 to 289.9+/-49.1cm/sec2 (p<0.001) and decreased isovolumic relaxation time(IVRT) from 132.3+/-10.3msec to 117.2+/-13.5msec(p<0.001), deceleration time(DT) from 168.8+/-30.3msec to 154.9+/-29.8msec(p<0.05) in hypertensive patients. These fimdings indicated that nifedipine improves Doppler-derived early diastolic filling indexes in hypertensive patients and may be related to improvement of active relaxation of left ventricle in early diastole.

Apexcardiogram in Hyperthyroidism: With Particular Reference to Fractional Systolic and Diastolic Time Intervals

For the non-invasive evaluation of cardiac performance in hyperthyroidism, fractional systolic and diastolic time intervals were determined in 96 female patients with hyperthyroidism from the mechanocardiograms which included apexcardiograms together with electrocardiograms, phonocardiograms and carotid arterial pulse tracings. The observed values of the time intervals inversely related to heart rate, i.e., ejection period, mechanical systole, isovolumic relaxation time and active ventricular filling period, were significantly shortened in proportion to the severity of the disease in general, as determined by the rate of the radioactive iodine uptake of the thyroid glands. However, these values were not significantly different from those of the predicted for heart rate, except for one of mechanical systoles which is a time interval from the onset of the systolic upstroke in the apexcardiogram to the second aortic sound. This suggests that the shortening of these observed values is promarily due to tachycardia associated with hyperthyroidism. One the other hand, the observed values of the time intervals unrelated to heart rate, i.e., electromechanical delay, isovolumic contraction time together with one of its components, namely ventricular pressure elevation time, and rapid ventricular filling period, were significantly shorter than those in the controls, although the degree of the shortening was not related to the degree of the radioactive iodine uptake of the thyroid gland. It appears that the shortening of these time intervals is related to the altered cardiac function caused by hyperthyroidism and, in particular, that of the isovolumic contraction time and ventricular pressure elevation time reflects enhancemet by the thyrotoxic myocardial contractility.