Variability in calcium, phosphorus, and parathyroid hormone in patients on hemodialysis

Calcium, phosphorus, and parathyroid hormone (PTH) levels are routinely measured in patients undergoing chronic hemodialysis. Medications, diet, and dialytic therapies are modified based upon these lab values to achieve specific goal values in the hope of improving outcomes. However, the variability of these values in patients undergoing chronic hemodialysis has only been rarely studied.
We prospectively investigated the variability of these measures in 35 patients undergoing chronic hemodialysis as well as the impact of this variability on clinical decision-making in a prospective manner over a month. There is significant session-to-session variability in phosphorus and PTH values (mean coefficient of variations [CV] of 0.19 and 0.31, respectively). Calcium variability is much lower (mean CV of 0.05). Not surprisingly, the CV for all values is increased during the long interdialytic interval. The impact of this variability on clinical decision-making was analyzed. The variability in calcium, phosphorus, and PTH values would lead to a different clinical decision in 23.6%, 41.2%, and 39.7% of different session lab values. We also investigated the variability of these lab measures over a year in these patients and found that the session-to-session variability was very similar to the month-to-month variability.
The high degree of variability of these parameters has important implications for clinical decision-making and for implementation of pay-for-performance measures.     

Switch from calcitriol to paricalcitol in secondary hyperparathyroidism of hemodialysis patients: Responsiveness is related to parathyroid gland size

Paricalcitol is more effective than calcitriol in hemodialysis patients (HD) with secondary hyperparathyroidism (SHPT), but it is not effective in some of them. We have investigated the relationship between paricalcitol responsiveness and parathyroid gland (PTG) size. Thirty HD with SHPT treated previously with calcitriol for at least 6 months were switched to paricalcitol (1:4 conversion ratio). Parathyroid gland number and size (maximum longitudinal diameter [MLD] of largest PTG) was measured by ultrasonography. Patients were divided into 2 groups: group A (MLD ≤9.0 mm [17 HD]); and group B (MLD >9.0 mm [13 HD]). They were defined responder if both the last 2 monthly determinations of inhibit parathyroid hormone (iPTH) were within the target (<300 pg/mL) according to National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommendations. Twenty‐six and 20 HD completed 6‐month and 12‐month paricalcitol therapy, respectively. After 6 months of paricalcitol treatment, 23.5% HD of group A and 7.7% of group B were responders. At 12 months, 41.2 % of group A and 7.7% of group B were responders. Throughout paricalcitol therapy, serum calcium and phosphorus concentrations slightly increased in all HD but more significantly in group B. The baseline iPTH and MLD of the largest PTG were significantly correlated with final iPTH levels. Paricalcitol is more effective than calcitriol in SHPT, but the responsiveness to paricalcitol and hypercalcemia are related to PTG size. The measurement of MLD by ultrasonography may be useful for predicting responsiveness to paricalcitol, avoiding an unnecessary and expensive therapy.     

Parathyroidectomized patients have impaired capacity of peripheral vascular constriction during hemodialysis

Parathyroidectomy (PTx) seems to improve cardiovascular outcomes and reduce blood pressure levels. However, the effect of PTx on hemodynamic changes during hemodialysis (HD) is still overlooked. This was a prospective cohort design. Patients with end‐stage renal disease on maintenance HD were included. Diabetes and nonsinusal rhythm were exclusion criteria. History of PTx was recorded. Finometer monitor was used to access parameters immediately pre‐ and post‐HD sessions. Cardiac index (CI) variation (ΔCI) and peripheral arterial resistance variation (ΔPAR) were the variables of interest. Biochemical and echocardiographic data were also obtained. PTx patients (n = 11) were matched to non‐PTx patients (n = 20). ΔPAR was lower in PTx group in comparison with non‐PTx group (P = 0.039), which was independent of parathyroid hormone (PTH) levels. Multiple regression analysis showed that PTx, ΔCI, and dialysate calcium remained independently associated with PAR variation and even adjusted for ultrafiltration rate (adjusted r² = 0.64). In conclusion, parathyroidectomized patients have impaired capacity of vasoconstriction in response to ultrafiltration, an effect independent of serum PTH levels. Further studies are needed to elucidate mechanisms explaining the interaction between PTx and systemic vascular tonus.     

Intradialytic changes in reflective properties of the arterial system during a single hemodialysis session

Increased aortic stiffness-measured as aortic augmentation index (AIx), a global stiffness marker-has emerged as a powerful predictor of survival in hemodialysis (HD). A single HD session is known to produce considerable improvement in aortic stiffness. We set out, for the first time, to examine the relative contributions to the post-HD drastic improvement in aortic stiffness of ultrafiltration rate and volume, or blood pressure (BP) changes. Aortic AIx (difference between the first and the second systolic peak of the aortic pressure waveform divided by pulse wave height) was determined hourly and recorded by applanation tonometry using a SphygmoCor device in 20 chronic HD patients (9 males, age 55.1 years). The other parameters recorded were: weight pre- and post-HD, ultrafiltration volume (UFV), hemoglobin, albumin, creatinine, urea reduction rate (URR), calcium and PTH, and BP. The dialysis significantly decreased AIx from 24.2+/-11.27% to 15.57+/-12.58% (p<0.05). In a univariate analysis, the intradialytic decrease in AIx (AIx 0-4) did not correlate with UFV, URR or with any of the biochemical markers. Significant correlations for AIx 0-4 were age (p=0.018), systolic blood pressure (SBP) at the beginning of HD (p=0.049), the intradialytic decrease in the SBP (p=0.001), and in pulse pressure (PP) (p=0.009). Multivariate stepwise regression showed that the decrease in SBP, PP, and intradialytic percentage reduction in weight explained 64.9% of the total variation in AIx 0-4. The decrease in SBP was the most important factor influencing the AIx variation (b=1.54, p=0.007). The most significant reduction in AIx was from the beginning of HD to the third hour (p=0.039), and correlated with the reduction in SBP (p=0.006) and PP (p=0.025) between the same moments. A single HD session produces a drastic improvement in aortic stiffness. The effect is not explained by the UFV depletion but is highly correlated with the decrease in SBP and PP. Further work is now needed to explore a potential role for endothelin and nitric oxide metabolism.     

Factors associated with serum magnesium and vascular stiffness in maintenance hemodialysis patients

Introduction : We evaluated the associated factors of serum magnesium in patients on maintenance hemodialysis (MHD). Furthermore, we evaluated the relationship between low serum magnesium and arteriosclerosis in these patients. Methods : In 129 patients on MHD, we evaluated the blood levels of magnesium, brachial‐ankle pulse wave velocity (ba‐PWV), ankle‐brachial index (ABI), and intima‐media thickness of the common carotid artery (IMT). Findings : In MHD patients, the serum level of magnesium was significantly correlated with age, calcium, TNF‐α, albumin, and ba‐PWV but not with ABI or IMT. In the multiple regression analysis, albumin (P = 0.0001, β = 0.31) and calcium (P = 0.029, β = 0.18) were selected as significant predictors of the magnesium level in MHD patients. Furthermore, the serum level of magnesium, as well as systolic blood pressure (P = 0.0001, β = 0.32) and age (P = 0.005, β = 0.25), were selected as significant (P = 0.012, β = ?0.22) predictors of ba‐PWV in MHD patients. Discussion : In MHD patients, the serum magnesium level was associated with the serum levels of calcium and albumin. Furthermore, a low serum magnesium level in MHD patients was associated with the index of vascular stiffness.     

Inadvertently high dialysate magnesium causing weakness and nausea in hemodialysis patients

As maintenance hemodialysis patients are exposed to large quantities of dialysis water, any contamination of it might be reflected in plasma levels. We present a series of cases due to such a contamination. Six maintenance hemodialysis patients dialyzing at the same peripheral hemodialysis facility presented to us over a short period of time with symptoms mimicking inadequate dialysis. Their blood urea and creatinine levels were not very high, but all the patients had hypermagnesemia [serum Mg levels = 1.8 (±0.3) mmol/L]. Except for one patient who had cardiac arrest at presentation, all patients improved after undergoing hemodialysis at our center [serum Mg at discharge = 0.86 (±0.01) mmol/L]. The origin of hypermagnesemia was traced to dialysis water contamination with magnesium due to inadequate maintenance of the water treatment system. Corrective measures improved the quality of water, and no further cases were reported from that center. Proper maintenance and periodic checks of the quality of water are central to the outcomes of maintenance hemodialysis patients.     

Efficacy and safety of Cinacalcet on secondary hyperparathyroidism in Chinese chronic kidney disease patients receiving hemodialysis

Introduction Secondary hyperparathyroidism (SHPT) develops in patients with chronic renal failure. Cinacalcet hydrochloride has been used successfully in U.S., Europe, and Japan in the treatment of SHPT, while maintaining serum levels of calcium and phosphorus. The efficacy and safety profile of Cinacalcet treatment vs. conventional treatments has been of great interest in clinical practice. In this recent phase III study conducted in China, efficacy and safety of a calcimimetic agent, Cinacalcet (Kyowa Hakko Kirin Co., Ltd.), were assessed for SHPT treatment in stable chronic renal disease patients on hemodialysis. Methods In this double‐blind, multicenter, placebo‐controlled, randomized phase III study, 238 subjects were enrolled in 12 centers and randomly divided into a Cinacalcet group and a placebo group. The percentage of patients achieving a serum parathyroid hormone (PTH) level ≤250 pg/mL was the primary efficacy end point. Serum calcium and phosphorus levels were measured. Adverse events and serious adverse events were recorded, and causal analysis performed. Findings In primary analysis, 25.4% of the Cinacalcet group and 3.5% of the placebo group achieved the primary end point (PTH ≤250 pg/mL). Calcium and phosphorus levels and calcium–phosphorus product were lower in the Cinacalcet group compared with the placebo group. Eleven serious adverse events were reported and considered to be not related to study drugs. Mild to moderate hypocalcemia and reduced calcium levels were reported and considered to be Cinacalcet related. Discussion This phase III study demonstrated that Cinacalcet is effective and well tolerated in treating SHPT in Chinese chronic kidney disease patients on hemodialysis, and in a patient population with much higher baseline PTH levels.     

The effects of nocturnal compared with conventional hemodialysis on mineral metabolism: A randomized‐controlled trial

Hyperphosphatemia is common among patients receiving dialysis and is associated with increased mortality. Nocturnal hemodialysis (NHD) is a long, slow dialytic modality that may improve hyperphosphatemia and disorders of mineral metabolism. We performed a randomized‐controlled trial of NHD compared with conventional hemodialysis (CvHD); in this paper, we report detailed results of mineral metabolism outcomes. Prevalent patients were randomized to receive NHD 5 to 6 nights per week for 6to 10 hours per night or to continue CvHD thrice weekly for 6 months. Oral phosphate binders and vitamin D analogs were adjusted to maintain phosphate, calcium and parathyroid hormone (PTH) levels within recommended targets. Compared with CvHD patients, patients in the NHD group had a significant decrease in serum phosphate over the course of the study (0.49 mmol/L, 95% confidence interval 0.24–0.74; P=0.002) despite a significant reduction in the use of phosphate binders. Sixty‐one percent of patients in the NHD group compared with 20% in the CvHD group had a decline in intact PTH (P=0.003). Nocturnal hemodialysis lowers serum phosphate, calcium‐phosphate product and requirement for phosphate binders. The effects of NHD on PTH are variable. The impact of these changes on long‐term cardiovascular and bone‐related outcomes requires further investigation.     

Effects of secondary amyloidosis on arteriovenous hemodialysis fistula outcomes and intradialytic hypotension: a case-control study

Amyloid fibrils can affect vascular structure through deposition and by causing nitric oxide depletion and increase of asymmetric dimethyl arginine. Patients with amyloidosis are prone to development of hypotension. Hypotension may also affect the maturation of arteriovenous fistula (AVF) and may set the stage for formation of thrombosis and fistula failure. Thus, we aimed to evaluate effects of secondary amyloidosis on AVF outcomes and intradialytic hypotension. This is a case‐control study which included 20 hemodialysis patients with amyloidosis and 20 hemodialysis patients without amyloidosis as control group. All patients underwent Doppler ultrasound of AVF. A thorough fistula history and baseline laboratory values along with episodes of intradialytic hypotension and blood pressure measurements were recorded. There was no difference between the groups regarding age, gender, body mass index, presence of comorbidities, hypertension, and drug use. Systolic and diastolic blood pressures were similar (119 ± 28/75 ± 17 and 120 ± 14/75 ± 10 mmHg for patients with and without amyloidosis, respectively). Intradialytic hypotension episodes were also similar. Patients with amyloidosis had significantly lower serum albumin and higher C‐reactive protein values compared to control hemodialysis patients. AVF sites and total number of created fistulas were similar in both groups. Flow rates of current functional AVFs were not different between the groups (1084 ± 875 and 845 ± 466 mL/minute for patients with and without amyloidosis, respectively, p:0.67). Patency duration of first AVF was not different between the groups. Clinical fistula outcomes and rate of intradialytic hypotension episodes were not significantly different between patients with and without secondary systemic amyloidosis.     

Assessment of subjective and hemodynamic tolerance of different high‐ and low‐flux dialysis membranes in patients undergoing chronic intermittent hemodialysis: A randomized controlled trial

Clinical experience and experimental data suggest that intradialytic hemodynamic profiles could be influenced by the characteristics of the dialysis membranes. Even within the worldwide used polysulfone family, intolerance to specific membranes was occasionally evoked. The aim of this study was to compare hemodynamically some of the commonly used polysulfone dialyzers in Switzerland. We performed an open‐label, randomized, cross‐over trial, including 25 hemodialysis patients. Four polysulfone dialyzers, A (Revaclear high‐flux, Gambro, Stockholm, Sweden), B (Helixone high‐flux, Fresenius), C (Xevonta high‐flux, BBraun, Melsungen, Germany), and D (Helixone low‐flux, Fresenius, Bad Homburg vor der Höhe, Germany), were compared. The hemodynamic profile was assessed and patients were asked to provide tolerance feedback. The mean score (±SD) subjectively assigned to dialysis quality on a 1–10 scale was A 8.4 ± 1.3, B 8.6 ± 1.3, C 8.5 ± 1.6, D 8.5 ± 1.5. Kt/V was A 1.58 ± 0.30, B 1.67 ± 0.33, C 1.62 ± 0.32, D 1.45 ± 0.31. The low‐ compared with the high‐flux membranes, correlated to higher systolic (128.1 ± 13.1 vs. 125.6 ± 12.1 mmHg, P < 0.01) and diastolic (76.8 ± 8.7 vs. 75.3 ± 9.0 mmHg; P < 0.05) pressures, higher peripheral resistance (1.44 ± 0.19 vs. 1.40 ± 0.18 s × mmHg/mL; P < 0.05) and lower cardiac output (3.76 ± 0.62 vs. 3.82 ± 0.59 L/min; P < 0.05). Hypotension events (decrease in systolic blood pressure by >20 mmHg) were 70 with A, 87 with B, 73 with C, and 75 with D (P < 0.01 B vs. A, 0.05 B vs. C and 0.07 B vs. D). The low‐flux membrane correlated to higher blood pressure levels compared with the high‐flux ones. The Helixone high‐flux membrane ensured the best efficiency. Unfortunately, the very same dialyzer correlated to a higher incidence of hypotensive episodes.     

Erythrocyte folate status and serum iron levels in patients undergoing hemodialysis

The present study was aimed to evaluate erythrocyte folate and the iron levels in diabetes and hypertension patients treated with/without hemodialysis. The effects of erythropoietin and iron treatment as well as vitamin supplementation on measured parameters were considered. The 67 controls consisted of healthy subjects (n = 22), hypertensive subjects (n = 22), and diabetic subjects (n = 23) without any renal disorder. According to primary renal disorders, the patients undergoing hemodialysis (n = 68) were classified into four groups as diabetic nephropathy, hypertensive nephropathy, reflux nephropathy or interstitial nephritis, and renal insufficiency depending on other causative factors. The mean value of erythrocyte folate levels of all patients undergoing hemodialysis was higher than the healthy control group (P < 0.05). Erythrocyte folate levels in hypertensive and diabetic nephropathy patients were higher than their own hypertensive or diabetic controls and also healthy controls (both, P < 0.05). Serum iron levels of all subgroups in hemodialysis patients were found to be similar with healthy controls (all, P > 0.05). The only significance observed within the subgroups was between diabetic controls and diabetic nephropathy patients (P < 0.05). None of the treatment or supplementation of erythropoietin, iron and vitamin affected erythrocyte folate levels (all, P > 0.05). The increase in erythrocyte folate status of patients with end stage renal diseases might be the result of sum or individual effects of causative factors such as renal pathology, compensation mechanism against renal anemia, or routine folate supplementation.     

Effects of flaxseed consumption on systemic inflammation and serum lipid profile in hemodialysis patients with lipid abnormalities

Inflammation and lipid abnormalities are two important risk factors for cardiovascular disease in hemodialysis (HD) patients. The present study was designed to investigate the effects of flaxseed consumption on systemic inflammation and serum lipid profile in HD patients with lipid abnormalities. This was an unblinded, randomized clinical trial. Thirty HD patients with dyslipidemia (triglyceride >200 mg/dL and/or high‐density lipoprotein‐cholesterol (HDL‐C) <40 mg/dL) were randomly assigned to either a flaxseed or control group. Patients in the flaxseed group received 40 g/day ground flaxseed for 8 weeks, whereas patients in the control group received their usual diet, without any flaxseed. At baseline and at the end of week 8, 7 mL of blood was collected after a 12‐ to 14‐hour fast and serum concentrations of triglyceride, total cholesterol, low‐density lipoprotein‐cholesterol (LDL‐C), HDL‐C, and C‐reactive protein (CRP) were measured. Serum concentrations of triglyceride (P < 0.01), total cholesterol (P < 0.01), LDL‐C (P < 0.01), and CRP (P < 0.05) decreased significantly in the flaxseed group at the end of week 8 compared with baseline, whereas serum HDL‐C showed a significant increase (P < 0.01). These changes in the flaxseed group were significant in comparison with the control group. The study indicates that flaxseed consumption improves lipid abnormalities and reduces systemic inflammation in HD patients with lipid abnormalities.