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.     

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.     

Intradialytic changes of serum magnesium and their relation to hypotensive episodes in hemodialysis patients on different dialysates

Magnesium is a crucial mineral, involved in many important physiological processes. Magnesium plays a role of maintaining myocardial electrical stability in hemodialysis patients. Intradialytic hypotension is a common complication of dialysis and it is more common with acetate dialysate. The significance of the intradialytic changes of magnesium and their relation to parathyroid hormone (PTH) level and calcium changes during dialysis, and their relation to hypotensive episodes during dialysis are interesting. The aim of this work is to investigate the intradialytic changes of serum magnesium in chronic hemodialysis patients with different hemodialysis modalities and the relation to other electrolytes and to PTH, and also the relation to intradialytic hypotension. The present study was conducted on 20 chronic renal failure patients. All patients were on regular hemodialysis thrice weekly 4 hr each using acetate dialysate (group I). To study the effect of an acetate-based dialysate vs. a bicarbonate-based dialysate on acute changes of magnesium, calcium, phosphorus, and PTH during a hemodialysis session, the same patients were shifted to bicarbonate dialysis (group II). All patients were subjected to full history and clinical examination, predialysis laboratory assessment of blood urea nitrogen (BUN), serum creatinine, albumin, and hemoglobin, serial assessment of magnesium, calcium, phosphorus, and parathyroid hormone at the start of the hemodialysis session, 2 hr later, and at the end of the session, blood pH, and electrocardiogram (ECG) presession and postsession. All patients were urged to fix their dry weight, diet, and current medications. None of the patients had diabetes, neoplasia, liver disease, or cachexia, nor had they been recently on magnesium-containing drugs or previously parathyroidectomized. Hemodialysis sessions were performed by volumetric dialysis machines using the same electrolyte composition. Magnesium level significantly increased in the bicarbonate group at the end of dialysis (0 hr: 2.73+/-0.87, 2 hr: 3.21+/-1.1, and at 4 hr: 5.73+/-1.45 mg/dL, p value <0.01), while it significantly decreased in the acetate group (0 hr: 3.00+/-0.58, 2 hr: 2.26+/-0.39, 4 hr: 1.97+/-0.33 mg/dL, p value <0.01). Calcium level significantly increased in the bicarbonate group (p=0.024) but not in the acetate group. Phosphorus level significantly decreased in both acetate and bicarbonate groups. PTH level did not significantly change in either group, p value > or =0.05. Blood pH significantly increased, changing from acidic to alkaline pH, with both modalities of hemodialysis. ECG showed no significant changes during sessions with either type of dialysate. Hypotension was significantly higher in group I compared with group II (p=0.01), and this hypotension was positively correlated with a decrease in serum magnesium level in group I. Intradialytic changes in serum magnesium have no correlation with intradialytic changes in serum calcium or with PTH level. However, it was significantly correlated with hypotension during the dialysis session, especially with acetate dialysate. Further investigations are needed to determine whether or not this is true in patients using bicarbonate dialysis.     

Looking at calcimimetics impact on hypercalcemia of immobilization: hypotheses and a case study

For the treatment of secondary hyperparathyroidism (HPTH-II) in dialysis patients and hypercalcemia in patients with parathyroid carcinoma. Calcimimetics are a new class of drugs approved in the European Community and the United States by the Food and Drug Administration that were designed to suppress parathyroid hormone (PTH) levels with a simultaneous reduction in serum calcium and phosphorus levels, and calcium phosphorus product (Ca x P). Hypocalcemia is a frequent finding during the correction phase of the HPTH-II with calcimimetics. By contrast, the appearance of a hypercalcemia has yet to be described. In this paper, we report a case of severe hypercalcemia of immobilization in a 40-year-old hemodialyzed woman treated by cinacalcet HCl for a severe HPTH-II (PTH>1,000 pg/mL). A kidney transplantation recipient 1983 to 1995, she was diagnosed with Charcot-Marie Tooth disease in 1991. She had multiple orthopedic interventions for kidney-related osteoarticular problems probably favored by the kidney graft and the immunosuppressive treatment. While she was receiving the maximum dose of 180 mg/day of cinacalcet HCl and PTH at 443 pg/mL, she needed to be hospitalized for a right hip prothesis. Two weeks after the intervention she developed a symptomatic hypercalcemia of 3.57 mmol/L which was resistant to several measures including lowering the calcium concentration in the dialysate, withdrawing all vitamin D and calcium supplementation and the administration of calcitonin. Her serum calcium level was finally stabilized in the 2.37-2.95 mmol/L by administration of a single intravenous dose of pamidronate. This observation illustrates that the pharmacological activation of the parathyroid CaR and other putative CaR on bone cells by calcimimetics did not protect against the occurrence of hypercalcemia of immobilization favored by a severe HPTH-II in a hemodialysis patient.     

Use of 3‐hour daily hemodialysis and paricalcitol in patients with severe secondary hyperparathyroidism: A case series

Patients with poor metabolic control receiving conventional hemodialysis are at risk for developing severe secondary hyperparathyroidism. We postulated that daily hemodialysis may be effective at controlling parathyroid hormone (PTH) in the setting of severe secondary hyperparathyroidism by improving the control of hyperphosphatemia and allowing increased use of vitamin D analogs. We present 5 patients with severe secondary hyperparathyroidism (median iPTH=1783 pg/mL) who were treated with 3‐hour daily hemodialysis (3 hours × 6 times a week). Daily hemodialysis, at 1 year, was associated with a 70.4% reduction in median PTH (1783 pg/mL [interquartile range: 1321–1983]–472 pg/mL [334, 704], P<0.001). Additionally, there was an increase in paricalcitol dose from 0 mcg/d to 10.8 (2.00, 11.7) mcg/d, a 39% reduction in calcium × phosphorus product (80.3 ± 26.8–48.9 ± 14.0, P<0.01), a 52% reduction in serum phosphorus (9.90 ± 2.34–4.75 ± 0.79 mg/dL, P<0.0001), and a 17.6% increase in serum calcium (8.18 ± 2.04–9.62 ± 0.93 mg/dL, P<0.01). Three‐hour daily hemodialysis with the use of high‐dose paricalcitol is associated with improved control of severe secondary hyperparathyroidism.     

Calcium‐phosphate and parathyroid intradialytic profiles: A potential aid for tailoring the dialysate calcium content of patients on different hemodialysis schedules

Severe hyperparathyroidism is a challenge on hemodialysis. The definition of dialysate calcium (Ca) is a pending issue with renewed importance in cases of individualized dialysis schedules and of portable home dialysis machines with low‐flow dialysate. Direct measurement of calcium mass transfer is complex and is imprecisely reflected by differences in start‐to‐end of dialysis Ca levels. The study was performed in a dialysis unit dedicated to home hemodialysis and to critical patients with wide use of daily and tailored schedules. The Ca‐phosphate (P)‐parathyroid hormone (PTH) profile includes creatinine, urea, total and ionized Ca, albumin, sodium, potassium, P, PTH levels at start, mid, and end of dialysis. “Severe” secondary hyperparathyroidism was defined as PTH > 300 pg/mL for ≥3 months. Four schedules were tested: conventional dialysis (polysulfone dialyzer 1.8–2.1 m²), with dialysate Ca 1.5 or 1.75 mmol/L, NxStage (Ca 1.5 mmol/L), and NxStage plus intradialytic Ca infusion. Dosages of vitamin D, calcium, phosphate binders, and Ca mimetic agents were adjusted monthly. Eighty Ca‐P‐PTH profiles were collected in 12 patients. Serum phosphate was efficiently reduced by all techniques. No differences in start‐to‐end PTH and Ca levels on dialysis were observed in patients with PTH levels < 300 pg/mL. Conversely, Ca levels in “severe” secondary hyperparathyroid patients significantly increased and PTH decreased during dialysis on all schedules except on Nxstage (P < 0.05). Our data support the need for tailored dialysate Ca content, even on “low‐flow” daily home dialysis, in “severe” secondary hyperparathyroid patients in order to increase the therapeutic potentials of the new dialysis techniques.     

Rationale and study design of a three‐period, 58‐week trial of ferric citrate as a phosphate binder in patients with ESRD on dialysis

Chronic kidney disease associated mineral and bone disorders arise as a result of aberrant bone mineral metabolism in patients with advancing levels of renal dysfunction and end‐stage renal disease. One of the cornerstones of treatment is the use of phosphate‐binding agents. We describe the rationale and study design for a clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder. This trial is a three‐period, international, multicenter, randomized, controlled clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder, consisting of a 2‐week washout period, a 52‐week safety assessment period in which subjects are randomized to ferric citrate or active control, and a 4‐week efficacy assessment period in which subjects randomized to ferric citrate in the safety assessment period are randomized to ferric citrate or placebo. Eligible subjects include end‐stage renal disease patients who have been treated with thrice‐weekly hemodialysis or peritoneal dialysis for at least 3 months in dialysis clinics in the United States and Israel. Primary outcome measure will be the effect of ferric citrate vs. placebo on the change in serum phosphorus. Safety assessments will be performed by monitoring adverse events, concomitant medication use, and sequential blood chemistries (including iron parameters, phosphorus, and calcium). This three‐period trial will assess the efficacy of ferric citrate as a phosphate binder. If proven safe and efficacious, ferric citrate will likely provide an additional phosphate binder to treat chronic kidney disease associated mineral and bone disorders.     

Achieving targets for bone and mineral metabolism: the impact of cinacalcet HCl in clinical practice

Achieving the K/DOQI targets for bone and mineral metabolism has proven difficult with the use of vitamin D analogues and phosphate binders. The introduction of cinacalcet HCl provided a new tool with a novel therapeutic mechanism of action. The purpose of this study was to evaluate the effect of the introduction of combination algorithm for managing secondary hyperparathyroidism (SHPT) on phosphorus, calcium, and biointact parathyroid hormone (PTH). The 61 patients who dialyzed in the facility from January 2004 (baseline) and who remained in the facility as of April 2005 (follow-up) were included in the study. In the baseline period, 37 (61%) of the patients received paricalcitol at some time during the 3-month observation period. In the follow-up period, 19% or 31% of the patients received cinacalcet HCl. Of those not receiving cinacalcet HCl, 67% had PTH at or below target, 17% were felt to be noncompliant with oral meds, 7% had low calcium, and 10% either could not get the medication or were not switched to the combination pathway. Compared with the baseline period, the percent of patients who met the PTH target increased from 19.7% to 37.7%, p<0.05. The percent of patients meeting all 4 targets increased from 14.8% to 24.6%, although this did not reach statistical significance. The introduction of cinacalcet HCl into a treatment algorithm for management of SHPT resulted in a significant increase in the percentage of patients achieving the PTH target while maintaining the other mineral metabolism targets.     

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.     

Intensive In-Center Hemodialysis for Children: A Case for Longer Dialysis Duration

Background:  Children with renal failure need their dialysis time optimized. Although traditional surrogate markers of outcome in pediatric patients have been growth and development, increasing attention is being focused on cardiovascular risk factors, such as hypertension, volume overload, malnutrition, and elevated calcium (Ca) and phosphorus (P) levels. We have previously shown catch-up growth without growth hormone, in children undergoing long intermittent hemodialysis. Recently we analyzed retrospectively cardiovascular risk factors in patients treated with this regimen.
Methods:  Patients starting dialysis between 1997 and 2001 and on dialysis at least 6 months were evaluated. Charts were reviewed for Ca, P, parathyroid hormone (PTH), albumin, hemoglobin and blood pressure levels, Ca intake, blood pressure medications, dialysis time, and clearance and ultrafiltration rates. Means were calculated for 6- month intervals, up to 36 months.
Results:  Mean equilibrated dialyzer Kt/V _urea ranged from 1.9 to 2.1, and mean weekly dialysis time for oliguric patients varied from 14.8 to 16.3 hr, with average hourly ultrafiltration rates from 0.3 to 0.4 L. Mean values for P and Ca × P were below 1.8 mM and 4.4 mmol   ² /L ² , respectively. Mean hemoglobin levels were 115 to 126 g/L, albumin 39 to 41 g/L, and PTH 156 to 231 pg/mL. Most patients had normal predialysis blood pressures.
Conclusions:  In this pediatric cohort, intensive center hemodialysis was associated with excellent growth, nutrition, Ca, P, and anemia control and reasonable blood pressure values. Large multicenter studies are needed to better determine optimal dialysis therapy for children.     

Clinical epidemiology of parathyroidectomy in hemodialysis patients: the USRDS waves 1, 3, and 4 study

Despite advances in the medical management of secondary hyperparathyroidism, parathyroidectomy remains necessary in some end-stage renal disease patients. Observational studies may help with the design of intervention trials. We linked the retrospective Waves 1, 3, and 4 Dialysis Morbidity and Mortality Study datasets to Medicare claims data to identify incident parathyroidectomy in 10,588 Medicare patients receiving hemodialysis in the United States on December 31, 1993. The mean age was 60.0 years, and the mean follow-up 3.6 years. De novo parathyroidectomy incidence was 14.2/1000 patient-years. Considered as quintiles (Q), higher levels of standard bone metabolism variables were associated (p<0.0001) with parathyroidectomy stepwise, such that adjusted hazards ratios (AHR) for Q5 (vs. Q1) were, for calcium (>10.3 mg/dL), 5.09 (3.64-7.10); for phosphorus (>7.5 mg/dL), 2.92 (2.06-4.15); for calcium-phosphorus product (>71 mg2/dL2), 3.32 (2.27-4.85); and for parathyroid hormone (PTH; >480 pg/mL), 13.81 (7.47-25.55). Other antecedent associations included younger age, lower hemoglobin, and longer dialysis vintage, while transplantation, as a time-dependent covariate, was associated with lower hazards ratios. Using interval Poisson analysis, parathyroidectomy was associated with higher mortality risk ratios in the first year, and progressively lower risk ratios subsequently. Demographic variables may modify the risk of parathyroidectomy. Younger patients on long-term hemodialysis may be at a special risk. Parathyroidectomy risk increases stepwise with alterations in bone metabolism variables, suggesting that a single-threshold management approach may not be ideal.     

Association of mineral metabolism factors with all-cause and cardiovascular mortality in hemodialysis patients: the Japan dialysis outcomes and practice patterns study

Abnormalities in mineral metabolism have been linked to mortality in hemodialysis (HD) patients. We postulated that these abnormalities would have a particularly large deleterious impact on deaths due to cardiovascular causes in Japan. This study describes the recent status of abnormal mineral metabolism, significant predictors, and potential consequences in the Dialysis Outcomes and Practice Patterns Study (DOPPS), Phases 1 and 2, in Japan. Major predictor variables were patient demographics, comorbidities, and laboratory markers of mineral metabolism such as albumin-adjusted serum calcium (calciumAlb), phosphorus, and intact PTH (iPTH). In a cross section of 3973 Japanese HD patients in DOPPS I and II, a large faction had laboratory values outside of the recommended Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline range for serum concentrations of phosphorus (51% of patients above upper target range), calciumAlb (43.7% above), calcium-phosphorus (Ca x P) product (41.1% above), and iPTH (18.6% above). All-cause mortality was significantly and independently associated with calciumAlb (relative risk [RR]=1.22 per 1 mg/dL, p=0.0005) and iPTH (RR=1.04 per 100 pg/mL, p=0.04). Cardiovascular mortality was significantly associated with calciumAlb (RR=1.28, p=0.02), phosphorus (RR=1.13 per 1 mg/dL, p=0.008), Ca x P product (RR=1.07 per 2 mg(2)/dL(2), p=0.002), and PTH (RR=1.08, p=0.0001). This study expands our understanding of the relationship between altered mineral metabolism and mortality outcomes, showing slightly stronger associations with cardiovascular causes than observed for all-cause mortality. These findings have important therapeutic implications for Japanese HD patients.     

Effect of serum FGF‐23, MGP and fetuin‐A on calcium‐phosphate metabolism in maintenance hemodialysis patients

This study was aimed to explore the role of serum fibroblast growth factor (FGF)‐23, matrix Gla protein (MGP) and fetuin‐A in the calcium‐phosphate metabolism and their predicting value in coronary artery calcification in maintenance hemodialysis (MHD) patients. This study included 64 patients who receive hemodialysis in our hospital. The serum FGF‐23, MGP and fetuin‐A were analyzed by enzyme‐linked immunosorbent assay (ELlSA). Coronary artery calcification score (CACS) was evaluated by coronary artery computed tomography scan. The 64 patients (30 males, 34 females, 60.6 ± 11.3 years of age) received an average dialysis vintage of 6.88 ± 2.94 years. We divided the CACS into three levels, and 13 (20.31%), 16 (25%), and 35 (54.69%) exhibited a CACS of 0–100, 100–400, and >400, respectively. Dialysis vintage, serum FGF‐23, fetuin‐A, phosphorus and high‐density lipoprotein‐C levels were identified as independent variables of CACS by stepwise multiple regression analysis. The area under receiver operating characteristic curve indicated that serum FGF‐23 and fetuin‐A were useful for identifying CAC in MHD patients. The cut‐off value corresponding to the highest Youden's index was serum FGF‐23 ≥ 256 pg/mL and fetuin‐A ≤ 85 μg/mL, which was defined as the optimal predictors of CAC. Different combinations of serum FGF‐23 and fetuin‐A in parallel or in series effectively boosted the identification of CAC. The incidence of CAC is high in MHD patients. Serum FGF‐23 and fetuin‐A levels are closely correlated with CAC.     

Cirrhosis Ameliorates Renal Osteodystrophy in Patients on Regular Hemodialysis

Cirrhosis (Cir) is often associated with chronic renal failure (CRF) in Egyptian patients on regular hemodialysis (RHD). This is largely attributed to hepatosplenic schistosomiasis and concomitant Hepatitis C viral infection. As the liver has a major role in vitamin D3 activation, we designed this study to envisage the impact of Cir on renal osteodystrophy (ROD). It included 130 consecutive age‐ and gender‐matched subjects in 4 categories. Group I: 39 patients (34 male and 5 female; mean age 48.8 years) with Cir normal renal function; group II: 37 patients (30 male and 7 female; mean age 49.0 years) with CRF and normal liver function, on RHD for a mean duration of 6 ± 3.9 years; group III: 41 patients (30 male and 11 female; mean age 50.7 years) with CRF and concomitant Cir, stable on RHD for a mean duration of 7.0 ± 4.0 years; and group IV: 16 normal volunteers (13 male and 3 female; mean age 46.3 years). The prevalence of diabetes as well as previous infection with schistosomiasis was similar in all patient groups and that of HCV infection was alike in groups I and III. In all subjects, conventional parameters of liver and renal function were tested; in addition to measurement of serum total protein, albumin, calcium, phosphate, total and bone‐specific alkaline phosphatase (B‐ALP), parathormone (PTH), 5‐hydroxycholecalciferol (5HD), 1,25‐dihydroxycholecalciferol (1,25HD), Cross Laps (CXL) as a marker of bone resorption, and aminoterminal propeptide of type I procollagen (PINP) as a measure of bone formation. Bone mineral density (BMD) was measured by either Dual Energy X‐ray Absorptiometry (DEXA) or Computerized Tomography (CT). Group II patients displayed the typical CRF profile comprising hypocalcemia, hyperphosphatemia, increased total and bone‐specific alkaline phosphatases, high PTH and 25HD, low 1,25HD, increased PINP as well as CXL, and generally decreased BMD. Cir (Group III) significantly (p value at least <0.5) modified this profile in several aspects: it checked hypocalcemia (mean 8.8 vs. 7.9 mg/dL in groups II and III, respectively), hyperphosphatemia (5.15 vs. 4.9 mg/dL), and the elevation of B‐ALP (62 vs. 30.5 μg/L) and PTH (89 vs. 78 pg/mL). It lowered the serum level of 25HD (18.7 vs. 13.7 ng/mL), augmented the deficiency of 1,25HD (13.4 vs. 8.0 pg/mL), did not appreciably affect the increase in bone formation (PINP 77.9 vs. 75.5 ng/mL), but ameliorated its excessive resorption (CXL 21 860 vs. 30 328 pmol/L) noticed in group II. This was associated with amelioration of the dialysis‐associated osteopenia (70 vs. 33.5%) and increased incidence of osteosclerosis (30 vs. 61%), as measured by bone mineral density. Conclusion: Our data indicate that Cir ameliorates ROD through decreased bone resorption. This is associated with better tolerance to 1,25HD deficiency, which initiates the cascade of hypocalcemia, hyperparathyroidism, and increased bone resorption in CRF. Such tolerance may reflect upregulation of vitamin D receptors as a consequence of the humoral perturbation supervening in Cir, involving IGF‐1, estrogens, or other vitamin D metabolites as 24,25 HD.     

Severe hypercalcemia caused by Milk‐Alkali syndrome requiring urgent hemodialysis – Tums by the ton

An increased frequency of the Milk‐Alkali syndrome in the last several years has been noticed related to increasing use of calcium carbonate as a phosphate binder in CKD patients, as an antacid or as calcium supplementation. We present a case of severe hypercalcemia secondary to Milk‐Alkali syndrome that precipitated acute renal failure requiring urgent hemodialysis. A 59-year‐old male with history of hypertension, diabetes mellitus, and acid reflux presented to the ER with confusion, lethargy, nausea, vomiting, and diarrhea. His family relayed a history of recent indigestion and relief with Tums. He was taking several tablets at short intervals to self‐treat the indigestion. At the time of presentation, patient was confused and noted to be dehydrated. Lab findings were significant for elevated BUN/Cr‐ 121 mg/dl/11.1 mg/dl (baseline Cr 1.1 mg/dl few months ago), bicarbonate 38 mg/dl, calcium 16.7 mg/dl, ionized Ca of 1.76 mmol/L, iPTH 10 pg/ml, PTHrP 0.7 pg/ml. Medical management with intravenous fluids and furosemide showed no improvement in renal failure, or calcium level. Patient was then started on hemodialysis with 2.0 mmol/L calcium in the dialysate the next day. There was gradual improvement in patient's mental status, calcium values, and renal failure over the ensuing 2 weeks.
Discussion and Conclusions:  The diagnosis of Milk‐Alkali syndrome is made on the basis of history. Metabolic abnormalities involved in this syndrome are hypercalcemia with low to normal PTH and Vit. D levels, renal failure, and metabolic alkalosis. Failed medical management required acute dialysis in this patient. Acute hemodialysis in such a case could be life saving. Due to increasing use of calcium carbonate for dyspepsia and osteoporosis, patients should be made aware of these severe, potentially life-threatening adverse effects.     

Bone‐specific alkaline phosphatase and bone turnover in African American hemodialysis patients

Introduction: Noninvasive measures of bone activity include intact parathyroid hormone (iPTH) and bone‐specific alkaline phosphatase (BSAP). Whether BSAP measurement alone or in combination with other biochemical data provides more reliable information about bone turnover than iPTH alone in African Americans on hemodialysis is unknown. Methods: This cross‐sectional study aimed to determine the optimal predictor and cutoff points for BSAP, iPTH, calcium and phosphorus in classifying bone biopsy findings. Forty‐three African American hemodialysis patients were available for analysis. Biochemical data on the day of biopsy across a spectrum of qualitative histologic bone features were compared. Classification and regression tree analysis was used to determine both the optimal predictor and cutoff points for BSAP, iPTH, calcium and phosphorus in identifying bone turnover status. Findings: Seven subjects had adynamic disease, 31 had mild/moderate hyperparathyroid bone features, and five had severe hyperparathyroid bone disease. BSAP was the optimal predictor of bone biopsy with a cutoff point of 22 ng/mL. Calcium and phosphorus had no predictive value. At BSAP ≤ 22 ng/mL, subjects had either adynamic bone disease or mild/moderate hyperparathyroid bone disease but iPTH was not useful in further classifying biopsy findings. When BSAP was >22 ng/mL, subjects had either mild/moderate or severe hyperparathyroid bone disease, and iPTH was useful in further classifying biopsy findings. With BSAP > 22 ng/mL and iPTH < 726 pg/mL, all subjects had mild/moderate bone turnover features. Discussion: Compared to iPTH, BSAP was shown to be the optimal predictor of biopsy findings with an optimal cutoff at 22 ng/mL.