losartan-potassium and Hyperparathyroidism--Secondary

Topics: Aluminum; Anemia; Angiotensin-Converting Enzyme Inhibitors; Carnitine; Chronic Disease; Drug Resistance; Erythropoietin; Humans; Hyperparathyroidism, Secondary; Inflammation; Iron Deficiencies; Kidney Failure, Chronic; Malnutrition; Recombinant Proteins; Renal Dialysis

Anemia management programs typically strive to maintain hemoglobin (Hb) levels in the target range of 11 to 12 g/dL recommended by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI). Although nephrology clinicians are constantly alert for conditions that cause hyporesponse to Epoetin alfa therapy, management protocols generally focus on assessing and managing acute disorders that affect the production of red blood cells. A more difficult clinical challenge is how to systematically manage patients with conditions that chronically affect the erythropoietic response and are intractable to routine therapies. This article addresses the etiology and management of chronic conditions that require a specialized anemia management approach to ensure that patients can achieve targeted Hb levels and associated clinical and quality of life benefits. Examples include chronic inflammatory disorders, severe secondary hyperparathyroidism, malignancies, human immunodeficiency virus (HIV), and kidney transplant failure.

Topics: Aged; Anemia; Chronic Disease; Erythropoiesis; Erythropoietin; Female; HIV Infections; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Neoplasms

Hyperparathyroidism is usually listed among the possible reasons for impaired response to recombinant human erythropoietin (rHuEPO) in patients with renal disease. However, its relevance in the context of other causes of renal anaemia, and the mechanisms by which it may worsen anaemia, are not entirely clear. Possible pathogenic links between anaemia and parathyroid hormone (PTH) include reduced erythropoiesis due to calcitrol deficiency, and direct or indirect effects of PTH on erythropoietin release, red blood cell (RBC) production, survival, and loss. Studies of these mechanisms have produced disparate results, possibly because secondary hyperparathyroidism may have only a relatively minor role in anaemia that may be masked by the confounding effects of other factors with greater impact. Variations in medical treatment or study methodology may also have affected study results. Severe parathyroid overfunction may contribute to the severity of anaemia in uraemic patients and diminish rHuEPO responsiveness in a minority of patients. However, overall, the importance of hyperparathyroidism appears to be minor compared with other factors such as iron deficiency or inflammation.

Topics: Anemia; Drug Resistance; Erythropoietin; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Osmotic Fragility; Parathyroid Hormone; Parathyroidectomy; Treatment Failure

Topics: Aluminum; Anemia; Erythropoietin; Humans; Hyperparathyroidism, Secondary; Iron Deficiencies; Recombinant Proteins; Renal Dialysis

Topics: Erythropoietin; Female; Hormones; Humans; Hyperparathyroidism, Secondary; Kidney; Kidney Failure, Chronic; Male; Pancreatic Hormones; Pituitary-Adrenal System; Prostaglandins; Renin-Angiotensin System; Testosterone

PTH may participate in the genesis of the anemia of uremia through at least three pathways. These include inhibition of erythropoiesis, shortening survival of RBCs and inducing fibrosis of bone marrow cavity. A possible fourth mechanism through which PTH may contribute to the anemia of uremia is its effect on platelets. PTH inhibits platelet aggregation [53] and, as such, may play an important role in the genesis of the bleeding tendencies and the consequent blood loss in uremia.

Topics: Anemia; Anemia, Hypochromic; Anemia, Sideroblastic; Animals; Colony-Forming Units Assay; Erythrocyte Aging; Erythropoiesis; Erythropoietin; Folic Acid Deficiency; Hematopoietic Stem Cells; Hemolysis; Hemorrhage; Humans; Hyperparathyroidism, Secondary; In Vitro Techniques; Mice; Parathyroid Hormone; Uremia

Topics: Adult; Anemia; Cytokines; Erythropoietin; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Parathyroidectomy; Prospective Studies; Renal Dialysis

In cases with severe hyperparathyroidism, anaemia improves after parathyroidectomy. The objective of this study was to investigate the influence of treatment with intravenous calcitriol on anaemia in 28 haemodialysis patients. The patients showed moderate to severe hyperparathyroidism (mean parathyroid hormone level 811.6 +/- 327 pg/ml) and were treated with calcitriol (2 microg i.v.) after haemodialysis. The follow-up period was 12 months. 21 out of the 28 patients had been receiving erythropoietin (EPO) prior to calcitriol administration; the remaining 7 did not receive EPO. 24 patients received oral or intravenous iron. The doses of EPO and iron were modified throughout the study period to maintain a haematocrit equal to or higher than 30% and ferritin levels above 150 ng/ml, respectively. EPO needs were evaluated according to the relation EPO dose/haematocrit. We found a significant rise in haematocrit and haemoglobin at 3 and 12 months on calcitriol therapy, with no modification of the EPO dose nor ferritin levels. This improvement in anaemia was observed both in those patients who received EPO initially (p < 0.01) and in those who did not (p < 0.05). Upon dividing the patients according to the response of hyperparathyroidism to the intravenous calcitriol treatment, we observed in the responding patients (n = 19) significant increases in haematocrit (from 31.7 +/- 4.2 to 36.3 +/- 4.9%) and haemoglobin(from 10.6 +/- 1.5 to 12.2 +/- 1.5 g/dl; p < 0.001) at 12 months on intravenous calcitriol therapy, while this was not true of the non-responding patients. The EPO needs diminished in the group of responding patients and increased in the non-responders, although these changes were not statistically significant. We found no direct correlation between the decrease of parathyroid hormone and EPO needs in the group of responding patients. However, an inverse correlation between parathyroid hormone levels and EPO needs (r = -0.799, p < 0.05) was seen in the group of non-responding patients. Treatment with intravenous calcitriol in patients on haemodialysis controls secondary hyperparathyroidism, improves anaemia, and decreases the need for EPO. Studies including a larger number of patients are necessary to clarify the mechanisms underlying the improvement of anaemia upon control of secondary hyperparathyroidism with intravenous calcitriol treatment and to confirm our findings.

Topics: Alkaline Phosphatase; Anemia; Calcitriol; Erythropoietin; Female; Humans; Hyperparathyroidism, Secondary; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Recombinant Proteins; Renal Dialysis; Time Factors

Topics: Adolescent; Adult; Aged; Anemia; Erythropoietin; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Topics: Acetates; Analysis of Variance; Anemia; Calcium; Calcium Carbonate; Drug Administration Routes; Erythropoietin; Female; Follow-Up Studies; Humans; Hyperparathyroidism, Secondary; Male; Parathyroid Hormone; Prospective Studies; Renal Dialysis; Uremia

Primary as well as secondary hyperparathyroidism may be associated with anemia, and parathyroidectomy (PTx) may improve or even heal it. The precise link between the two conditions is still matter of discussion. The purpose of the present study was to investigate possible effects of PTx on serum immunoreactive erythropoietin (iEPO) in secondary (group I, n = 23), and primary (group II, n = 16) hyperparathyroidism patients, and in 3 patients undergoing cervicotomy for thyroid mass removal (group III). In group I patients, circulating iEPO levels rose from 23.1 +/- 4.8 mU/ml before PTx to 28.2 +/- 5.0 and 245 +/- 125 mU/ml (mean +/- SEM) at day 7 (p = NS) and 14 after PTx (p less than 0.003), respectively. Reticulocyte count increased 2 weeks after PTx: from 61,000 +/- 13,317 to 86,533 +/- 13,462/mm3 (p less than 0.05, n = 23). In 4 of these patients serum iEPO levels could be measured again 12-24 months after PTx. They were slightly higher than those determined before PTx: 37.0 +/- 8.4 versus 31.8 +/- 13.5 mU/ml. Their hematocrits were also higher than before PTx: 12.8 +/- 0.9 versus 11.0 +/- 0.9 g/dl. In group II patients, serum iEPO levels remained unchanged after PTx: 17.5 +/- 2.0 mU/ml before PTx and 20.0 +/- 3.0 mU/ml 14 days PTx. The reticulocyte count, however, increased significantly 2 weeks after PTx: from 25,103 +/- 3,000 to 40,827 +/- 4,080/mm3 (p less than 0.01). In group III patients, serum iEPO, reticulocyte count, and hemoglobin remained stable after surgery. Since all group I patients had received vitamin D supplementation after PTx, we studied an additional group of 14 chronic dialysis patients (group IV) who received either calcitriol (1 micrograms/day, n = 7) or placebo (n = 7) during 14 days. The patients on calcitriol treatment, but not those on placebo, had a significant decrease of serum iEPO: 18.6 +/- 4.9 versus 16.0 +/- 4.2 mU/ml (p less than 0.03). In conclusion, PTx led to a striking increase of serum iEPO and blood reticulocytes in uremic patients with secondary hyperparathyroidism, and an increase of reticulocyte count, but not of iEPO, in patients with primary hyperparathyroidism. Marked changes of circulating PTH, extra-or intracellular calcium and phosphorus concentrations as well as of tissue sensitivity to EPO after PTx could all be responsible. In contrast, the surgical procedure and the therapeutic increase in plasma calcitriol do not appear to be involved.

Topics: Calcitriol; Erythropoiesis; Erythropoietin; Female; Humans; Hyperparathyroidism; Hyperparathyroidism, Secondary; Male; Middle Aged; Parathyroid Hormone; Parathyroidectomy

Hyperphosphatemia, secondary hyperparathyroidism (SHPT) and anemia are common secondary complications in hemodialysis patients with end-stage renal disease (ESRD). Compared with conventional hemodialysis (CHD), short daily hemodialysis (sDHD) has been found to be more effective in patients with ESRD. The objective of this study was to determine whether sDHD could improve hyperphosphatemia, SHPT and anemia in patients with ESRD.. Twenty-seven patients (11 women and 16 men, 46.8 ± 13.4 years old) were switched from CHD to sDHD. All hematologic parameters were measured prior to the switch (baseline), at 3 months after the switch (sDHD(1)) and at 6 months after the switch (sDHD(2)).. The serum phosphate decreased from 2.54 ± 0.32 mmol/L at baseline to 2.15 ± 0.36 mmol/L (p < 0.001) at sDHD(1) and 1.97 ± 0.33 mmol/L (p < 0.001) at sDHD(2). Calcium-phosphate product decreased from 5.18 ± 1.24 mmol(2)/L(2) at baseline to 4.20 ± 0.71 mmol(2)/L(2) (p < 0.001) at sDHD(1) and 4.02 ± 0.83 mmol(2)/L(2) (p < 0.001) at sDHD(2). The serum PTH levels decreased from 223.9 ± 124.7 pmol/L at baseline to 196.3 ± 101.3 pmol/L (p < 0.05) at sDHD(2). The hemoglobin concentration increased significantly from CHD to sDHD. However, the requirement for erythropoietin (EPO) dose decreased from 6847.8 ± 1057.3 u/week at baseline to 5869.6 ± 1094.6 u/week (p < 0.05) at sDHD(2).. sDHD may decrease serum phosphate, calcium-phosphate product and PTH, increase hemoglobin levels and decrease exogenous EPO dose requirements compared with CHD in hemodialysis patients.

Topics: Adult; Aged; Anemia; Calcium Phosphates; Erythropoietin; Female; Health Status; Hemoglobins; Humans; Hyperparathyroidism, Secondary; Hyperphosphatemia; Kidney Failure, Chronic; Male; Mental Health; Middle Aged; Parathyroid Hormone; Quality of Life; Renal Dialysis

Secondary hyperparathyroidism (SHPT), known complication of chronic renal failure, in addition to effects on bone and cardiovascular systems, is associated with reduced response to erythropoietin (EPO). Calcimimetics such as cinacalcet are the latest generation of drugs used in the treatment of SHPT. Few studies have evaluated the effect of cinacalcet on anemia associated with SHPT in dialysis patients, while no study has compared this cinacalcet effect with that of vitamin D analogs such as paricalcitol.. Using a retrospective chart-based review of dialysis patients' records to identify patients being treated with either cinacalcet or paricalcitol alone, matched for the same EPO treatment, which had been followed for 1 year, we have evaluated the effect of cinacalcet on anemia compared to that of paricalcitol.. Ten patient records were found that fit the criteria, five treated with cinacalcet (Group 1) and five treated with paricalcitol (Group 2), all treated with the same dose of darbepoetin. Darbepoetin dosage was the only parameter that significantly changed between groups, decreasing in Group 1 (-33%, p = 0.009) while remaining unchanged in Group 2. PTH-level reduction, which was significant versus baseline in both groups, although not statistically different between groups, was higher with cinacalcet.. The combination of lower EPO dose in cinacalcet-treated patients compared with paricalcitol-treated patients, along with good SHPT control is a novel information and might have considerable benefits in dialysis patients not only preventing bone (fractures) and cardiovascular system (calcifications) damages but also in terms of cost savings via a reduction of EPO dosage.

Topics: Aged; Cinacalcet; Darbepoetin alfa; Drug Interactions; Erythropoietin; Female; Hematinics; Humans; Hyperparathyroidism, Secondary; Male; Naphthalenes; Renal Dialysis; Retrospective Studies

It has been suggested that parathyroidectomy for hyperparathyroidism (HPT) in end-stage renal disease (ESRD) may result in improvement in anemia and the response to erythropoiesis-stimulating drugs. This study examines the effect parathyroidectomy had on erythropoietin (EPO) dosing requirements and anemia in ESRD.. A retrospective review was conducted. Patients were included if pre-operative and 12 month postoperative hemoglobin (Hg) and hematocrit (Hct) levels were available and they did not receive a kidney transplant or have failure of parathyroidectomy during the follow-up. Erythropoietin (EPO) dose and serum levels of calcium, phosphorus, alkaline phosphatase, albumin, and parathyroid hormone (PTH) were also obtained. Other data collections were at 1 and 2 mos. postoperatively.. Thirty-seven patients met inclusion criteria. Parathyroidectomy resulted in decreased PTH from 1,871 +/- 236 (mean +/- SEM) to 172 +/- 29 pg/mL (P < .001) at 1 year. EPO dosing requirement showed a profound decrease from 10,086 +/- 1,721 to 3,514 +/- 620 units/week (P < .05). Hb and Hct levels followed an upward trend at 12 mos (11.4 +/- 0.3 to 12.1 +/- 0.2 g/dL and 35.7 +/- 1.0 to 37.1 +/- 0.6%, respectively).. In ESRD, parathyroidectomy for HPT improves anemia and decreases requirements for exogenous erythropoietin suggesting either increased endogenous EPO production or improved response. As a result, we propose refractory ESRD-associated anemia as a secondary indication for parathyroidectomy resection in this population.

Topics: Adult; Aged; Anemia; Drug Dosage Calculations; Erythropoietin; Female; Hematinics; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Parathyroidectomy; Retrospective Studies; Young Adult

In patients on chronic hemodialysis (CHD), hyperparathyroidism (HPTH) is associated with anemia and resistance to erythropoietin (EPO). In the last few years, calcitriol intravenously (IV) has been used with success in the treatment of the HPTH, secondary to chronic renal failure. However, the effects of calcitriol on the hematological parameters of these patients have never been well evaluated. This study included 11 elderly CHD patients (f = 6, m = 5; mean age = 73.6 years, mean time on CHD = 42.8 months) with HPTH under EPO therapy (IV). They were treated for 12 months with calcitriol IV (mean dose = 2.33 mcg/pt/week). Patients with iron deficiency anemia (ferritin < 200 ng/ml) were excluded. The patients were compared before and after 12 months of calcitriol treatment, with respect to several laboratory parameters and with respect to EPO dose. A paired t-test was used. After treatment, we found a decrease of PTH (634 vs. 418 pg/ml, P = 0.029); the serum calcium increased (8.8 vs. 9.9 mg/dl, P = 0.002); no differences were noted in the plasma levels of alkaline phosphatase, phosphorous, BUN, creatinine, Na and K. Mean levels of Hb (10.2 vs. 11.4 g/dl, P = 0.004) and the Hct (30 vs. 34.3, P = 0.004) increased after 12 months of calcitriol; the levels of serum iron (70 vs. 78 microg/dl, P = ns) and ferritin (531 vs. 785 ng/ml, P = ns) and the EPO dose (105 vs. 100 U/kg/week, P = ns) were similar before and after treatment. Our data show that the treatment of HPTH in CHD elderly patients with calcitriol can increase Hb level without increasing EPO dose.

Topics: Aged; Calcitriol; Calcium Channel Agonists; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Hyperparathyroidism, Secondary; Infusions, Intravenous; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis

The available literature is still controversial and shows that surgical (parathyroidectomy, PTX) or medical (calcitriol) treatment actually improved or even corrected the rhEPO-resistant anemia of ESRD patients with severe SHP. The aims of this study were to 1) assess the influence of SHP on hematological parameters in ESRD patients, 2) evaluate whether or not calcitriol could improve anemia and reduce the need of erythropoietin in dialysis patients, and 3) investigate the longitudinal effect of a parathyroidectomy for 6 months on regarding any improvements in calcitriol-refractory ESRD patients.. 37 chronic hemodialysis patients in Chang Gung Memorial Hospital Dialysis Unit were divided into two groups: patients with SHP (iPTH>300 pg/mL) and patients without SHP (ipTH<300 pg/mL) before calcitriol therapy was applied. Sixteen patients remain with a status of hyperparathyroidism and were considered candidates for calcitriol therapy. Furthermore, we divided the patients according to the response of HPT to calcitriol into responding patients and nonresponding patients. Among nonresponder groups, three patients agreed to accept surgical intervention to treat their hyperparathyroidism status.. The phosphate levels and serum alkaline phosphatase levels in patients with SHP were significantly higher when compared with those without SHP (P<0.05). As for the hematological data, hematocrit for patients with SHP was significantly higher than those without SHP (10.5 +/- 0.6 vs. 8.9 +/- 0.8, p<0.05). Other hematological parameters such as transferrin saturation and serum ferritin were not significantly different. We found a significant difference in alkaline phosphate levels in responding and nonresponding patients at 6 months on calcitriol therapy. Concomitantly, the hematocrit level is significantly higher in responding group when compared to those in nonresponding group (10.63 +/- 0.72 vs. 8.96 +/- 1.21, p<0.01). As for the dose of EPO requirement, significant difference between groups was also found after 6-month treatment (3617 +/- 2011 vs. 5416 +/- 1947, p<0.05). As for rhEPO dose requirement, positive effects of PTX were significantly found. The rhEPO doses needed to maintain patients in the hematocrit target range of 30-33% decreased gradually by 29% from 5323 +/- 1326 micro to 3774 +/- 2145 micro per week. The hematocrit level showed a significant increase at 3 months after PTX (p<0.05). This effect lasted until 6 months after PTX. The serum ferritin level was constantly around 350 to 400 pg/mL. While the transferrin saturation decreased 3 months after PTX (p<0.05) and recovered at 6 months.. ESRD patients with SHP, usually associated with more severe anemia show resistance to rhEPO. In this case, investigation of SHP is strongly recommended with measurement of serum PTH, phosphate and alkaline phosphatase level. Treatment of calcitriol has a beneficial effect on renal anemia in ESRD patients with SHP. In addition, PTX could also provide another choosing therapy in improving renal anemia when medical treatment fails.

Topics: Anemia; Calcitriol; Case-Control Studies; Erythropoietin; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Parathyroidectomy; Recombinant Proteins; Renal Dialysis

Secondary hyperparathyroidism is a common complication of renal failure. The exact prevalence in chronic hemodialysis patients in not known. We evaluated 122 patients who were receiving maintenance hemodialysis for at least 12 months in 2 dialysis centers in mid Michigan. Seventy-eight percent of the patients had iPTH above 200 pg/mL (mean 481 pg/mL), 19% had iPTH within the accepted normal range (mean 155 pg/mL), while 3% had level below 100 (mean 53 pg/mL). Phosphate, calcium, calcium phosphate product, age and time on dialysis are the important factors correlating with elevated iPTH. There was no significant difference in iPTH between diabetic and nondiabetic patients with mean iPTH of 403 pg/mL and 407 pg/mL respectively. Black patients had a statistically significant elevated iPTH compared with white patients with a mean iPTH of 438 pg/mL and 283 pg/mL respectively (p < or = 0.004). Factors that predict the response to vitamin D therapy need to be evaluated to help reduce the high prevalence of secondary hyperparathyroidism. The patterns of bone disease in black patients need to be evaluated to further define the accepted normal iPTH range for this population.

Topics: Adult; Age Factors; Calcium Phosphates; Diabetes Complications; Diabetes Mellitus; Erythropoietin; Female; Humans; Hyperparathyroidism, Secondary; Hypertension; Kidney Failure, Chronic; Male; Michigan; Middle Aged; Parathyroid Hormone; Prevalence; Racial Groups; Recombinant Proteins; Renal Dialysis; Statistics as Topic; Time Factors; Urea

Paricalcitol [Zemplar: Abbott Laboratories, Abbott Park, IL, U.S.A.] is efficient for treating secondary hyperparathyroidism in patients on maintenance hemodialysis (HD). Zemplar is thought to be more potent than calcitriol and has been reported to cause less hypercalcemia and hyperphosphatemia. Here, we report a 1-year follow-up on patients from one inner-city dialysis unit. We reviewed the charts of 100 patients and collected data for 1 year. Patients were stratified into four groups depending upon their intact parathormone (iPTH) levels. Hemoglobin (Hb) and erythropoietin (EPO) doses were determined. More than 50% of patients had iPTH levels greater than 300 pg/mL. Mean Ca and PO4 levels were not significantly different, but Zemplar doses were significantly different in all groups. None of the patients had symptomatic bone disease. Seven patients were changed to low-Ca dialysate (1.0 mEq/L) secondary to hypercalcemia (Ca > 11.5 mg/dL) and severe secondary hyperparathyroidism. Interestingly, patients with low iPTH (< 100 pg/microL) showed relative EPO resistance, and patients with high iPTH (> 600 pg/microL) required smaller EPO doses. An inverse relationship was observed between Zemplar and EPO dose. The effect of Zemplar on EPO responsiveness needs to be confirmed in a larger study. Our data suggest that severe secondary hyperparathyroidism is frequent despite aggressive paricalcitol therapy in our inner-city HD population. To control severe secondary hyperparathyroidism in these patients, dietary and medication compliance may need to be supplemented with more effective non-calcium phosphate binders or calcimimetic agents, or both.

Topics: Adult; Aged; Aged, 80 and over; Calcium; Ergocalciferols; Erythropoietin; Hemoglobins; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Middle Aged; Parathyroid Hormone; Renal Dialysis

Secondary hyperparathyroidism (2-HPT) has an adverse effect on renal anemia and may cause a hyporesponsiveness to recombinant human erythropoietin (rHuEpo) in patients with chronic renal failure. The early effects of parathyroidectomy (PTx) on renal anemia, erythropoietin production, and nutritional state were examined.. Twenty-nine patients under hemodialysis therapy received a PTx for 2-HPT. They were prospectively studied regarding hematological parameters, rHuEpo use, plasma erythropoietin levels, and nutritional condition until 12 months after PTx.. The hemoglobin level showed a significant increase from 3 months after PTx (10.2% +/- 1.5% to 11.2% +/- 1.3%; P <0.01), associated with a consistent increase of the reticulocyte count. These changes lasted until 12 months after PTx. The plasma erythropoietin level showed a gradual increase of up to about 5 times the level of the preoperative value, until 12 months after PTx (22.6 +/- 10.1 to 106.3 +/- 112.1 mU/mL; P <0.001). The weekly dose of rHuEpo administration decreased after 3 months. The serum levels of albumin and total protein also significantly and gradually improved until 12 months after PTx.. PTx caused a significant early improvement in renal anemia in patients with secondary hyperparathyroidism. This effect may be caused by an enhanced erythropoietin production and may also be partially due to the improved nutritional state after PTx.

Topics: Adult; Aged; Drug Resistance; Erythropoietin; Female; Humans; Hyperparathyroidism, Secondary; Linear Models; Male; Middle Aged; Parathyroidectomy; Prospective Studies; Recurrence; Renal Dialysis; Reoperation; Treatment Outcome; Uremia

To identify the factors determining a high recombinant human erythropoietin (rHuEPO) dose requirement and associated side effects in children undergoing hemodialysis.. We retrospectively analyzed the clinical data of 23 children (aged 5-20 years) undergoing long-term hemodialysis. All subjects received intravenous rHuEPO to maintain hemoglobin levels > or = 10 g/dL and had iron supplement. Subjects were divided into 2 groups: those receiving high-dose rHuEPO (> or = 450 U/kg/wk) and those receiving an average dose (< 450 U/kg/wk). We compared the specific variables between both groups by using Mann-Whitney, Fisher exact, and linear regression tests; a P value < .05 was considered significant.. Four of 23 subjects (17%) received high-dose rHuEPO despite iron repletion. These subjects were small and young and had frequent bacterial infections, high ferritin levels, and severe hyperparathyroidism. Two patients with human immunodeficiency virus infection required high-dose rHuEPO. The main adverse effect of high-dose rHuEPO was an increase in the heparin requirement during hemodialysis.. Age, body weight, inflammatory status, and severity of hyperparathyroidism should be taken into account when adjusting rHuEPO dose for children undergoing hemodialysis. Furthermore, we suggest that high rHuEPO doses are related to an increase in the heparin requirement in these children.

Topics: Age Factors; Anemia, Iron-Deficiency; Body Weight; Child; Erythropoietin; Female; Ferritins; Humans; Hyperparathyroidism, Secondary; Injections, Intravenous; Kidney Failure, Chronic; Linear Models; Male; Parathyroid Hormone; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Secondary hyperparathyroidism is a frequent condition of dialysis patients. Endocrine derangements, with disturbance of calcium metabolism are complex, involving bone, heart (left ventricular hypertrophy-dilatation), bone marrow (anemia and erythropoietin resistance), muscle (increase of body fat mass) and insulin resistance. Aim of the study was to assess how these conditions are inter-correlated in the same patients. 45 patients (m 20, f 25; years 61.8 +/- 11.6) in maintenance bicarbonate three-weekly hemodialysis since > 3 years were studied. Cardiac function was assessed by echocardiography (EF%: left ventricular ejection fraction), which showed an inverse correlation both with parathormone (iPTH vs EF%: r = -0.64; p < 0.001) and with erythropoietin (rHu-EPO vs EF%: r = -0.62; p < 0.001). This suggests the possibility of a multi-endocrine resistance in dialysis patients with chronic renal failure, secondary to the degree of malnutrition. Lower lean mass is correlated with hyperparathyroidism (iPTH vs fat mass%: r = 0.37; p < 0.01), with lower left ventricular systolic function (EF% vs fat mass%: r = -0.41; p < 0.005) and with rHu-EPO resistance. Moreover, patients with higher iPTH show a hypercatabolic disposition, assessed as protein catabolic rate (PCR/kg vs iPTH r = 0.54; p < 0.001). This pattern can be a consequence of chronic renal failure, but bio-compatibility of materials can be involved as well.

Topics: Body Mass Index; Drug Resistance; Erythropoietin; Female; Hemoglobin A; Humans; Hyperparathyroidism, Secondary; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Contraction; Nutrition Disorders; Parathyroid Hormone; Recombinant Proteins; Renal Dialysis; Stroke Volume; Systole

Topics: Anemia; Erythropoietin; Follow-Up Studies; Hemoglobins; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Parathyroidectomy; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Treatment Outcome

In long-term haemodialysis patients suffering from secondary hyperparathyroidism Se iPTH could be suppressed by an intravenous calcitriol therapy. As the Se iPTH level became reduced, lower doses of Rh-EPO were already sufficient for the maintenance of the target haematocrit, while in two patients not requiring Rh-EPO treatment an improvement of their moderate anaemia could be observed. These data corroborate the view that calcitriol is an effective drug in secondary hyperparathyroidism. The results suggest that in the improvement of renal anaemia of dialysed patients the reduction of the Se-PTH level also plays a role.

Topics: Adult; Aged; Anemia; Calcitriol; Erythropoietin; Hematocrit; Humans; Hyperparathyroidism, Secondary; Middle Aged; Parathyroid Hormone; Recombinant Proteins; Renal Dialysis

Topics: Adult; Anemia; Dose-Response Relationship, Drug; Drug Resistance; Erythropoietin; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Parathyroid Hormone; Parathyroidectomy; Recombinant Proteins; Renal Dialysis

We examined the effect of total parathyroidectomy (PTX) on renal anemia in 20 dialysis patients with secondary hyperparathyroidism. We obtained the following results. (1) Before PTX, 13 of these patients were not treated with erythropoietin (EPO) while the remaining 7 patients received EPO therapy. (2) In 8 out of 13 cases without recombinant human EPO treatment before PTX, a 10% increase in RBC was observed after PTX. (3) In 7 of the patients who were treated with EPO before PTX, anemia was improved after PTX despite discontinuation of EPO therapy in 2, a reduced dose of EPO in 3 and the same dose of EPO in 2. Our data is consistent with the notion that elevated blood levels of PTH in patients with chronic renal failure participate in the genesis of anemia of renal failure.

Topics: Adult; Anemia; Erythropoietin; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Parathyroidectomy; Recombinant Proteins; Renal Dialysis

The effects of recombinant human erythropoietin (rHuEPO) treatment on parathyroid function in patients on maintenance hemodialysis (HD) with secondary hyperparathyroidism (HPT) is poorly understood. We compared the levels of serum intact parathyroid hormone (PTH) and the suppressibility of PTH by intravenous calcium infusion before and after 12 weeks of rHuEPO treatment in 8 HD patients with secondary HPT. The suppressibility of PTH by calcium infusion in HD patients was also compared with that of normal subjects. After rHuEPO treatment, in HD patients hematocrit and hemoglobin levels increased significantly from 20.1 +/- 1.3% and 6.65 +/- 0.46 g/dl to 28.7 +/- 1.0% and 9.68 +/- 0.39 g/dl, respectively. The serum intact PTH levels did not change significantly (541.9 +/- 65.3 pg/ml before versus 572.9 +/- 75.3 pg/ml after rHuEPO treatment), nor did serum ionized calcium, phosphate, magnesium, aluminum, alkaline phosphatase, and 1.25(OH)2D levels. Calcium infusion significantly increased serum ionized calcium and suppressed serum PTH levels. However, the increment in serum calcium levels and the percent decrement of serum PTH showed no significant differences before and after rHuEPO treatment in HD patients. Elevations in serum calcium levels during calcium infusions were not significantly different between normal subjects and HD patients. However, the percent maximal decrement in serum PTH level was less in HD patients both before and after rHuEPO treatment than in normal subjects (-75.4 +/- 3.9 and -76.4 +/- 4.1% versus -91.4 +/- 1.4%). We conclude that rHuEPO treatment has no influence on parathyroid function in maintenance HD patients with secondary HPT. In addition, PTH secretion is less suppressed by calcium infusion in the same group of patients.

Topics: Adult; Alkaline Phosphatase; Aluminum; Blood Urea Nitrogen; Calcifediol; Calcium; Creatinine; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Hyperparathyroidism, Secondary; Injections, Intravenous; Magnesium; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Recombinant Proteins; Renal Dialysis; Renal Insufficiency; Time Factors

Topics: Adult; Drug Resistance; Erythropoietin; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Parathyroidectomy

Anemia is common in patients with chronic renal insufficiency and secondary hyperparathyroidism. Erythropoietin therapy is effective, but the dose required varies greatly. One possible determinant of the efficacy of erythropoietin therapy is the extent of marrow fibrosis caused by hyperparathyroidism. We examined the relation between the erythropoietic response to erythropoietin and hyperparathyroidism in a cross-sectional study of 18 patients undergoing hemodialysis who had received erythropoietin therapy for one to three years. In 7 patients (the poor-response group), the dose of intravenous erythropoietin needed to maintain a mean (+/- SD) target hematocrit of 35 +/- 3 percent was > 100 units per kilogram of body weight three times a week, and in 11 patients (the good-response group) it was < or = 100 units per kilogram. In all patients, indexes of the adequacy of dialysis and the extent of hyperparathyroidism and aluminum toxicity were determined monthly, and bone histomorphometry was performed.. The mean (+/- SD) dose of erythropoietin required to maintain the target hematocrit was 174 +/- 33 units per kilogram three times a week in the poor-response group and 56 +/- 18 units per kilogram in the good-response group. The mean ages, duration and adequacy of dialysis, increment in hematocrit, iron requirements, and serum concentrations of calcium, phosphate, and aluminum were similar in the two groups. The percentages of osteoid volume and surface, the osteoid thickness, and the stainable aluminum content of bone were similar in the two groups. In contrast, the mean serum parathyroid hormone concentration, the percentages of osteoclastic and eroded bone surfaces, and the degree of marrow fibrosis were greater in the poor-response group than in the good-response group (P = 0.03, P = 0.04, P = 0.009, and P = 0.009, respectively).. In patients with uremia, the dose of erythropoietin needed to achieve an adequate hematocrit response may depend on the severity of secondary hyperparathyroidism and the extent of bone marrow fibrosis.

Topics: Adult; Aged; Anemia; Cross-Sectional Studies; Erythropoietin; Female; Hematocrit; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Primary Myelofibrosis; Prospective Studies; Renal Dialysis; Uremia

After successful subtotal parathyroidectomy (PTX) in 10 chronic haemodialysis patients, significant elevation of Epo was observed, from 48.4 +/- 17.8 mU/ml(M +/- SEM) at preoperative state to 103.3 +/- 34.7 mU/ml at 6 h and 163.4 +/- 50.2 mU/ml at 12 h after PTX. Significant reductions in both PTH-m and ionized calcium (iCa) were confirmed. Since Epo did not increase in the cases with an inadequate PTX and ovariectomy, an abrupt reduction in PTH with a decrease in iCa may play some role in the elevation of Epo.

Topics: Adult; Aged; Anemia; Erythropoietin; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Middle Aged; Ovariectomy; Parathyroidectomy; Renal Dialysis

The administration of recombinant human erythropoietin (rHuEPO) to anemic hemodialysis patients is usually followed by a rapid increase in hemoglobin. Initial 'nonresponders' may either respond to higher doses of rHuEPO or rarely may remain totally unresponsive. Schematically, one can distinguish between a state of relative and absolute resistance to the action of the hormone. The most common causes of resistance are iron deficiency, aluminium overload, episodes of infection or other inflammatory processes, probably severe hyperparathyroidism, acute or chronic hemolytic conditions, acute or chronic blood loss, folate deficiency, and hemoglobinopathies in exceptional instances. Antibody formation against rHuEPO or marrow fibrosis secondary to rHuEPO treatment can be discarded as potential causes of resistance.

Topics: Aluminum; Anemia; Drug Resistance; Erythropoietin; Hemoglobins; Humans; Hyperparathyroidism, Secondary; Inflammation; Iron Deficiencies; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis