Trends of elevated parathormone serum titers in hemodialysis patients on intensive therapy for bone disease: a multicenter study.

To determine the prevalence of controlled parathyroid hormone (PTH) serum levels with intensified therapy for chronic kidney disease mineral and bone disorder (CKD-MBD) in the dialysis population, we studied 563 chronic hemodialysis patients recruited from three different dialysis centers from three different major cities in the Kingdom of Saudi Arabia. The trend of the routine monthly chemistries related to CKD-MBD was evaluated besides the whole-molecule PTH serum levels over 28 months (January 2011 to April 2013). The cost ratios of the medications to the estimated dialysis total cost were calculated. There were 323 (57.4%) males in the study, and the mean age of the patients was 50.2±15.2 years; 371 (65.9%) patients were initiated on dialysis before 2011. The causes of the original kidney disease included diabetes mellitus in 163 (29%) patients. Parathyroidectomy was performed in 23 (4.1%) patients and only six (23%) patients underwent the operation during the study period; most of the parathyroidectomies (69%) were performed before 2011. The trend of the medians of monthly serum levels of calcium, phosphorus, albumin, bicarbonate, alkaline phosphatase, serum levels of PTH and vitamin D25 assays showed better control of the levels with time. The added cost of cinacalcet was more significant than the other drugs, including vitamin D and phosphate binders, but the cost was minimal in comparison with the whole dialysis bill. The ratios of the discontinuation rates to the total patient-months of treatment for the different drugs were in the range of 3-4% and mostly due to transient overdosing of medications. We conclude that the trends of the median serum levels of PTH and related minerals in the CKD patients in our dialysis patients suggested a good inclination toward control and prevention of the vascular calcifications prevalent in the CKD-MBD. The popularity of use of new drugs such as cinacalcet is promising and does not seem to add much to the current out-patient cost of chronic dialysis.

Intravenous alfacalcidol once versus twice or thrice weekly in hemodialysis patients.

Secondary hyperparathyroidism remains a serious problem in hemodialysis patients. The use of vitamin D analogs still constitutes a basis for its treatment. This study was carried out to evaluate the efficacy of intravenous administration of alfacalcidol once versus twice or thrice weekly in hemodialysis patients with secondary hyperparathyroidism. Twenty-nine end-stage renal disease patients maintained on hemodialysis for more than one year were included in this prospective study after signing the consent. These patients with secondary hyperparathyroidism had been on intravenous alfacalcidol twice or thrice per week and were followed up to 4 months (stage 1). Then they were shifted to intravenous alfacalcidol once weekly starting with the last total weekly intravenous dose for another 4 months (stage 2). The dose of alfacalcidol was adjusted according to intact parathyroid hormone, serum calcium and phosphorus levels, and calcium-phosphorus product. Intact parathyroid hormone, calcium, phosphorus, calcium-phosphorus product were measured monthly. Parathyroid ultrasound was done as a baseline and then repeated at the end of stage 1 and stage 2. The intact parathyroid hormone was reduced from 49.72 ± 2.72 pmol/L (mean ± standard error of the mean [SEM] during stage 1 to 42.13 ± 2.15 pmol/L during stage 2 (P = 0.005). Dose of alfacalcidol was reduced from 18.80 ± 1.15 µg/month (mean ± SEM) in stage 1 to 15.18 ± 1.27 µg/month in stage 2 (P = 0.008), and consequently the cost of alfacalcidol was reduced from 21.05 ± 1.25 US$/month (mean ± SEM) during stage 1 to 16.87 ± 1.40 US$/month during stage 2 (P = 0.008). Although the phosphorus level increased from 1.56 ± 0.36 mmol/L (mean ± SD) in stage 1 to 1.70 ± 0.46 mmol/ L in stage 2 (P = 0.003), and calcium-phosphorus product increased from 3.48 ± 0.82 mmol(2)/L(2) (mean ± SD) in stage 1 to 3.76 ± 1.00 mmol(2) /L(2) in stage 2 (P = 0.017), they remained in the target levels recommended by the Kidney Disease Outcomes Quality Initiative guidelines. No serious effects were observed during stage 1 and stage 2, respectively. Intravenous alfacalcidol once weekly is effective, safe and less costly in suppressing intact parathyroid hormone compared to twice or thrice weekly administration in chronic hemodialysis patients.

Appropriateness of anemia management in hemodialysis patients.

UNLABELLED: The anemia of end stage renal disease (ESRD) is common and often severe complication that can be managed successfully by erythropoiesis-stimulating agents (ESA) administration. AIMS: To investigate current practice of anemia management in hemodialysis patients and to assess the appropriateness of anemia management by comparing observed practice to the Kidney Disease Outcomes Quality Initiative (KDOQI) guideline recommendations. SETTINGS AND DESIGN: The study was conducted at two hemodialysis centers in Riyadh, Saudi Arabia. Data on anemia parameters, comorbidities, ESA dosing and iron supplementation were collected. The data were collected for 7 months retrospectively from April to the end of May 2008 and prospectively from June to October 2008. Patients who were over 18 years of age with ESRD undergoing hemodialysis were included. Patients were excluded if they have cancer or receiving chemotherapy or radiotherapy. RESULTS: Data were collected from 87 patients. Mean Hgb value for those patients was 11.16 ± 0.97 g/dL. Thirty-nine patients (45%) had mean Hgb values between 11.0 and 12.0 g/dL the target range recommended by KDOQI guideline. The mean weekly prescribed dose of erythropoietin was 8099 ± 5946 IU/Week (135 ± 99 IU/kg/Week). Information on ferritin concentrations was available for 48 (55%) patients. The mean serum ferritin concentration for those patients was 693 ± 420.5 ng/mL. Fifty-two patients had transferrin saturation (TSAT) values recorded. The mean TSAT value was 38.5 ± 19.7%. CONCLUSIONS: There is an opportunity to improve anemia management in hemodialysis patients particularly thorough evaluation of causes of inadequate response rate and better monitoring and management of iron status.

Cinacalcet hydrochloride therapy for secondary hyperparathyroidism in hemodialysis patients.

This study compared the efficacy of a cinacalcet-based regimen with unrestricted conventional therapy (vitamin D and phosphate binders) for achieving Kidney Disease Outcome Quality Initiative (K/DOQI) targets for dialysis patients. In this multicenter, prospective study, hemodialysis patients with poorly controlled secondary hyperparathyroidism (SHPT) were randomized to receive a cinacalcet-based regimen (n=55) or a conventional therapy (n=27). Doses of cinacalcet, vitamin D sterols, and phosphate binders were adjusted during a 12-week dose-titration phase to achieve intact parathyroid hormone (iPTH) levels ≤ 31.8 pmol/L. The primary end point was the percentage of patients with values in this range during a 24-week efficacy-assessment phase. The clinical response to 36-week cinacalcet treatment was evaluated. A dual energy X-ray absorptiometry was performed before and after 36 weeks of cinacalcet therapy. Fifty-eight percent of the cinacalcet group reached the primary end point, as compared with 19% of the conventional therapy group (P=0.001). A higher percentage of patients receiving the cinacalcet-based regimen versus conventional therapy achieved the targets for calcium, phosphorus and Ca×P. Achievement of targets was greatest in patients with less severe disease (intact PTH range, 31.8 to 53 pmol/L). Cinacalcet therapy increased proximal femur bone mineral density (BMD), but did not affect the lumbar spine. Itching intensity decreased significantly. Cinacalcet based treatment facilitates achievement of the K/DOQI targets for iPTH and bone mineral metabolism compared with conventional therapy in hemodialysis patients. Suppression of iPTH with cinacalcet reverses bone loss in the proximal femur. Cinacalcet alleviated itching.

Cinacalcet effect on severe hyperparathyroidism.

To determine the efficacy and safety of cinacalcet, a calcimimetic drug that suppress parathyroid hormone (PTH) production, we studied its effect on 20 patients (13 males) on maintenance hemodialysis (HD), 80% of them have persistent high PTH levels (i.e. more than 80 pmol/L), the remaining patients had PTH levels more than 60 pmol/L. Five of 20 (25%) patients dropped out from the study (2 because of severe GIT upset, one showed severe myalgia and arthralgia, one patient due to non compliance and one died at home due to cardiac arrest). The remaining 15 patients (10 males) had a mean age of 40 ± 12.86 years and dialysis duration of 29.13 ± 18.27 months. The follow-up period on cinacalcet was 4 months with a single daily oral dose started with 30 mg/day and increased gradually according to the PTH levels. Nine (60%) patients were on concomitant active vitamin D during the study period with a mean dose of 7.33 ± 3.39 µg/week. There was a significant decrease in the serum PTH levels at the end the study compared to that at the start (46.4 ± 4.7 pmol/L versus 93.3 ± 25.6 pmol/L, respectively, P< 0.000), and the target PTH level (< 31.6 pmol/L) was achieved in 54% of patients. No significant changes in serum Ca and phosphorous levels were observed. We conclude that cinacalcet is an effective therapy to suppress the serum PTH levels and allows favorable management of the serum calcium and phosphorus levels in HD patients. The drug was well tolerated; however, GIT discomfort is a significant side effect that may necessitate drug withdrawal in some patients.

The role of oral L-carnitine therapy in chronic hemodialysis patients.

To evaluate the effects of L-carnitine oral supplementation on anemia and cardiac function in patients on maintenance hemodialysis (HD), we studied 55 adult chronic HD patients at our center during the period from January 2006 to June 2006 and divided them into two groups; a group of 20 patients who received 1500 mg/day oral L-carnitine and a control group of 35 patients. Both groups were on erythropoietin therapy. Echogardiographic studies were performed before and at the end of the study. The mean hemoglobin levels were comparable in the L-carnitine group and the control group at the start and after 6 months of therapy (8.63 +/- 1.77 and 9.39 +/- 2.02 gm/dL, P = 0.18; 10.49 +/- 1.65 and 10.92 +/- 2.48 gm/dL, P = 0.76, respectively). The mean weekly maintenance dose of erythropoietin was not statistically significantly different in L-carnitine group (80.16 +/- 35.61 units/kg) and the control group (91.9 +/- 38.21 units/kg, P = 0.20). In addition no significant improvement could be observed in the echogardiographic findings in the L-carnitine group after therapy. We conclude that our study revealed no significant improvement in hemoglobin, erythropoietin dose and echocardiographic findings after six months of therapy. Long-term studies including larger number of patients are required to clarify the questionable role of L-carnitine in the HD patients.

Colchicine vs. omega-3 fatty acids for prevention of chronic cyclosporine nephrotoxicity in Sprague Dawley rats: an experimental animal model.

BACKGROUND: In view of the high cost of the new immunosuppressive drugs, which represents a challenge for both patients and governmental resources especially in developing countries, trials to prevent side effects of the first calcineurin inhibitor discovered (cyclosporine, Cs) are of particular interest. METHODS: In this prospective randomized experimental study, 60 male Sprague Dawley rats were enrolled. Group 1 served as negative control group and received olive oil. Group 2 received Cs orally 100 mg/kg for 80 days and served as positive control group. Group 3 was given daily colchicine (30 microg/kg/day) in addition to Cs. Group 4 was given omega-3 fatty acids (100 mg/kg/day) in addition to Cs. Animals were subjected every other week to laboratory assessment for serum creatinine, sodium, potassium, and Cs whole-blood through levels. At the end point, the animals were sacrificed, and kidney tissue was examined for histopathological changes. RESULTS: There were no significant differences in serum creatinine, creatinine clearance, and serum sodium and potassium in all groups. Histopathological examination of kidney tissues showed focal tubular atrophy and interstitial fibrosis in inner medulla and inner strip of the outer medulla in all Cs-treated animals. Morphological changes were significantly less in colchicine-treated rats compared to omega-3 fatty acid-treated rats and absent in the negative control group. Furthermore, immunostaining showed positive reactions for vimentin in Cs-treated animals only. CONCLUSIONS: Colchicine and omega-3 fatty acids are protective for the kidney against cyclosporine-induced nephropathy; however, colchicine is more protective than omega-3 fatty acid.