Sevelamer reduces calcium load and maintains a low calcium-phosphorus ion product in dialysis patients.

BACKGROUND: Sevelamer HCl, a non-aluminum, non-calcium containing hydrogel, has proved an effective phosphate binder in North American hemodialysis patients. This single-center, open-label, dose titration study assessed the efficacy of sevelamer in a cohort of European hemodialysis patients with different dietary habits, in particular with lower phosphate intake. The aim of the study was to obtain a calcium x phosphate product lower than 60 mg2/dL2 in all patients. METHODS: Administration of calcium- or aluminum-based phosphate binders was discontinued during a two-week washout period. Nineteen patients whose serum phosphate level at the end of washout was greater than 5.5 mg/dL (1.78 mmol/L) qualified to receive sevelamer for six weeks. Based on the degree of hyperphosphatemia during washout, patients were started on 403 mg sevelamer capsules with a dose schedule different from previous studies. Only one capsule was administered at breakfast, and the rest of the phosphate binder was divided equally at the two main meals. Sevelamer could be increased by two capsules per day every two weeks, if necessary. A second two-week washout period followed. RESULTS: Mean serum phosphorus rose from a baseline of 5.3 +/- 1.0 to 7.4 +/- 1.4 mg/dL at the end of washout, then declined to 5.4 +/- 0.8 mg/dL (p < 0.001) by the end of the six-week treatment period and rebounded significantly to 7.1 +/- 1.1 mg/dL after the second two-week washout. Calcium x phosphate product showed a similar pattern, decreasing significantly from 64.1 +/- 14.1 to 46.9 +/- 7.4 mg2/dL2 (p < 0.001) after six weeks of sevelamer. A level of less than 50 mg2/dL2 was reached by 68% of patients, and 95% had less than 60 mg2/dL2. The mean dose of sevelamer at the end of treatment was 3.1 +/- 0.6 g per day. As expected, calcium declined from 9.2 +/- 0.5 to 8.7 mg/dL (p < 0.01) during the initial washout after stopping calcium-based phosphate binders, but remained stable thereafter. Ionized calcium did not change significantly throughout the washout and sevelamer treatment. However, interruption of calcium salts led to a 81% reduction of total calcium intake. CONCLUSIONS: We confirmed in an European sample of hemodialysis patients that sevelamer can reduce phosphate levels without inducing hypercalcemia. The drug can also be successfully used to reduce mean calcium x phosphate levels below 50 mg2/dL2, closer to normal values. Although similar results can be obtained with other phosphate binders, a concomitant accumulation of aluminum, calcium or magnesium could be detrimental to patients.

Twice versus thrice weekly administration of intravenous calcitriol in dialysis patients: a randomized prospective trial. Gruppo Italiano di Studio dell'Osteodistrofia Renale.

BACKGROUND: Administration of intravenous (i.v.) calcitriol three times weekly effectively controls the synthesis and secretion of PTH in most uremic patients. Administration of a single dose of 1.25(OH)2D3 reduces synthesis of PTH-mRNA for 6 days in rats. Moreover, it can lower PTH levels for up to 4 days in chronic hemodialysis patients. Therefore, a good response to the administration of i.v. calcitriol two times weekly can be expected. We studied - in a multicenter randomized study in patients with moderate to severe secondary hyperparathyroidism - the effects of the same doses of intravenous calcitriol, administered two or three times weekly. METHODS: Twenty-two hemodialysis patients were randomized into two frequencies of treatment groups: two times (G-2/w) and three times weekly (G-3/w). Both groups were treated with increasing doses of intravenous calcitriol for 3 months (first month 3 microg, second month 4 microg, third month 6 microg weekly). RESULTS: After 12 weeks of therapy with intravenous calcitriol the G-2/w group showed a significant reduction in serum PTH levels (from 821 +/- 392 to 350 +/- 246 pg/ml; mean reduction = 57.4%) comparable to the decrease observed in the G-3/w group (from 632 +/- 116 to 246 +/- 190 pg/ml; mean reduction = 61.2%). Ionized calcium (G-2/w from 1.13 +/-0.10 to 1.14 +/- 0.08 and G-3/w 1.21 +/- 0.13 to 1.26 +/- 0.18 mmol/l) and phosphate levels (G-2/w from 4.99 +/- 1.01 to 5.99 +/- 1.78 and G-3/w 5.31 +/- 0.73 to 5.81 +/- 1.18 mg/dl) did not change significantly and phosphate binders were not modified during the study. CONCLUSION: This study confirms that intravenous calcitriol is an effective therapy for moderate to severe secondary hyperparathyroidism. The administration of two doses per week of intravenous calcitriol is as efficacious as three doses per week in suppressing PTH secretion.

Cardiac and pulmonary calcification in a hemodialysis patient: partial regression 4 years after parathyroidectomy.

AIMS: The reversibility of extraskeletal calcifications in dialysis patients is an important and unresolved issue. Although periarticular calcifications have been shown to be reversible, little data are available on vascular or parenchymal calcifications. CASE HISTORY: A patient on maintenance hemodialysis with severe hyperparathyroidism, hypercalcemia and hyperphosphatemia was admitted to undergo parathyroidectomy. A preoperative total body bone scintigraphy was performed to better evaluate a lytic lesion in the pelvis, the histology of which proved to be a "brown tumor". The scan showed the typical findings of renal osteodystrophy, but also a diffuse extra-skeletal uptake of bone tracer in the lungs, kidneys, femoral arteries and myocardium. After surgery, good control of serum calcium, phosphate (Ca x P product < 50 mg2/dl2) and PTH levels was maintained during 4 years of follow-up. Bone scans were repeated after 2 and 4 years, showing marked improvement of periarticular uptake at the ends of long bones. Extraosseous calcium deposition was still markedly evident, but progressively decreased (at 4 years: heart -36%, lungs -18%). CONCLUSION: In this dialysis patient, extraskeletal calcification of visceral organs (particularly in the heart and the lungs) due to prolonged hypercalcemia and hyperphosphatemia was partially reversible by parathyroidectomy followed by good long-term control of serum phosphate and calcium.

Acute tubulo-interstitial nephritis requiring dialysis associated with intermittent rifampicin use: case report.

Rifampicin is one of the most effective antibiotics used for the treatment of tuberculosis and severe staphylococcal infections. Intermittent administration of high doses of rifampicin has been associated with frequent adverse reactions, including hepatotoxicity and nephrotoxicity, sometimes resulting in acute renal failure. We describe a case of rifampicin-associated acute renal failure, with biopsy findings of tubulointerstitial nephritis; inflammatory cells were characterized by immunohistochemistry, which showed immunoreactivity for CD3 and CD5 (T lymphocytes) and for CD68 (macrophages). The patient presented with a very rapid systemic reaction to the offending drug and rapid deterioration of renal function, which required dialysis treatment. The response to rifampicin discontinuation was excellent: no further therapy was required, as renal function began to improve within several days and returned to normal values (serum creatinine 1.17 mg/dl) seven months after the onset of symptoms. When prescribing rifampicin the physician should investigate previous use of the drug, because re-exposure is a critical factor in predicting the possibility of drug-induced acute renal failure.

Potassium-based dilutional method to measure hemodialysis access recirculation.

BACKGROUND: Assessment of access recirculation (AR) is crucial to dialysis efficiency and there is thus a need for a method yielding a highly accurate, fast, easy and economical measurement that can be applied in any busy dialysis clinic. Non-urea based dilutional methods are more accurate than urea based methods and avoid problems with cardiopulmonary recirculation, but they require expensive specialized devices, which limit their applicability. METHODS: We developed a simple dilutional method of AR which does not require any specific device, based on the determination of serum potassium [K+] in two samples. Briefly, a basal sample is drawn at the time of needle insertion (basal [K+]); needles are connected to blood lines and blood flow rate is quickly increased to 300 ml/mm; a second sample (arterial [K+]) is drawn from the arterial line port within 5 to 10 seconds, to avoid errors due to cardiopulmonary recirculation of the normal saline entering the blood stream. At this time, if recirculation is present, part of the normal saline will enter the arterial line and dilute the serum [K+]. The AR formula is: AR (%) = 100 x [1 - arterial K+/basal K+]. We compared our method with the two-needle urea and ultrasound velocity dilution methods. RESULTS: AR values by the ultrasound method > 10% were hypothesized as gold standard for AR, against which values obtained with the potassium method were compared. The potassium based method showed: sensitivity (100%,); specificity (95%); predictive value, positive (91%); predictive value, negative (100%). In addition, the potassium based method appears to be more reliable than the two-needle urea based method. CONCLUSION: Our method, similar to other dilutional methods, is not influenced by cardiopulmonary recirculation or veno-venous disequilibrium and is fast and accurate. Moreover it is very simple, economical, and can easily be performed in any dialysis unit.

[Mechanism of uremic osteodystrophy and prevention of hyperparathyroidism in the uremic patient]. / Meccanismi dell'osteodistrofia uremica e prevenzione dell'iperparatiroidismo del soggetto uremico.

The management of secondary hyperparathyroidism is of crucial importance in the treatment of end stage renal disease (ESRD) patients. In particular, hypercalcemia, hyperphosphatemia, and elevated calcium x phosphate (Ca x P) product should be taken into consideration during administration of vitamin D metabolites for the control of PTH secretion. During the last 10 years, many authors have been studying the efficacy of new non-calcemic vitamin D analogs on suppressing secondary hyperparathyroidism in ESRD patients. In this brief review, we analyzed three new vitamin D analogs: 22-oxacalcitriol (Maxacalcitriol), 19-nor-1a, 25(OH)2D2 (Paracalcitriol), and 1a (OH)2D2 (Doxacalciferol). In addition, calcimimetic agents may represent a new pharmacologic choice to the treatment of secondary hyperparathyroidism, binding parathyroid calcium sensing receptors (CaSR) and reducing PTH secretion. These compounds may represent an important tool for the treatment of both secondary hyperparathyroidism and soft tissue calcifications in ESRD patients. In conclusion, a combined use of non calcemic phosphate binders, new vitamin D analogs and calcimimetics should be seriously considered to further improve the already known therapy of secondary hyperparathyroidism in ESRD patients.

[HFR vs HDF-ON line: plasmatic amino acids loss evaluation]. / HFR vs HDF on-line: valutazione della perdita aminoacidica plasmatica.

PURPOSE: The high convection dialytic techniques, such as hemodiafiltration (HDF), can cause the loss of important molecules such as growth factors, vitamins and amino acids. Hemodiafiltration reinfusion (HFR) is an HDF on-line process, using a sipping cartridge, able to remove uremic toxins and give back a "repaired" ultra-filtrate to the patient. We aimed to establish the plasmatic amino acid levels before and after dialysis in HFR vs. HDF on-line, with scrupulous attention to branched chain amino acids (BCAA) such as isoleucine, leucine and valine. These amino acids, often present with low plasmatic levels in hemodialyzed patients, seem to be related to a picture of malnourishment. METHODS: Eleven male patients on bicarbonate dialysis, for at least 1 yr, were evaluated (average dialytic age = 88 months, /average age = 67 yrs), with good dialytic efficiency and body mass levels, randomized in HFR or HDF on-line (filter PAN AN 69) for 1 week of treatment, respectively. The different results of each method were controlled for the same patient. Blood samples were taken before and after dialysis in each 2nd hemodialytic weekly session. Total amino acids, essential, non-essential and BCAA were determined by gas-chromatography. RESULTS: There was no difference detected in pre-dialytic plasmatic levels of analyzed amino acids between the two groups. In post-dialysis, HDF patients demonstrated a total essential, non-essential amino acid and BCAA higher loss rate, compared to HFR patients. Post-dialysis amino acid level averages were: total amino acids in HDF 1852 +/- 302.6 micromol/L, in HFR 2395 +/- 492.8 micromol/L (p = 0.018); essential amino acids in HDF 428.8 +/- 118.2 micromol/L, in HFR 510.3 +/- 129.3 micromol/L (p = 0.022); non-essential amino acids in HDF 1176 +/- 213 micromol/L, in HFR 1546 +/- 339.2 micromol/L (p = 0.01); BCAA in HDF 242.7 +/- 83.42 micromol/L, and in HFR 286.7 +/- 89.9 micromol/L (p = 0.03). CONCLUSIONS: Since low plasmatic BCAA levels are related to anorexia and malnourishment, the loss of these amino acids can be important in the dialytic technique choice. HFR can offer an outstanding advantage, combining a high convection treatment with medium molecule removal, without compromising physiologic molecule loss.