Effects of a parathyroidectomy on the immune system and nutritional condition in chronic dialysis patients with secondary hyperparathyroidism

Effects of a Parathyroidectomy on the Immune System and Nutritional Condition in Chronic Dialysis Patients with Secondary Hyperparathyroidism Chikao Yasunaga, MD, Masahiko Nakamoto, MD, Kenzo Matsuo, MD, Gakusen Nishihara, MD, Tetsuhiko Yoshida, MD, Tadanobu Goya, MD, Kitakyushu, Japan

BACKGROUND: Parathyroid hormone (PTH) has an adverse effect on the immune system and may cause immunologic disorders in patients with chronic renal failure. The in vivo effects of a parathyroidectomy on the immunologic parameters was examined. METHODS: Thirty-four patients under dialysis therapy received a parathyroidectomy (PTx) for secondary hyperparathyroidism (HPT). They were prospectively studied regarding serum immunoglobulins, complements, CD markers, and serum soluble IL-2 receptor (sIL-2R) until 12 months after PTx. RESULTS: The serum levels of IgG, IgA and IgM showed significant increase until 12 months after PTx (P <0.001, respectively). C3, C4, and CH50 also indicated significant increase at 12 months after PTx. In cellular immunity, only serum sIL-2R showed significant increase 2 weeks after PTx (P ⴝ 0.028). The hematocrit and serum albumin also improved significantly at 12 months. CONCLUSIONS: PTx showed beneficial effects on humoral immunological markers. The effects are probably due to the remarkable PTH reduction and partly improved nutritional state after PTx. Am J Surg. 1999;178:332–336. © 1999 by Excerpta Medica, Inc.

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atients with chronic renal failure (CRF) have an impaired immune system and an increased risk of infection.1–5 The underlying mechanisms for such immunological disturbances have not yet been fully delineated in either uremic or chronically dialyzed patients. Parathyroid hormone (PTH), as an uremic toxin, has been shown to adversely affect the immune system and may thus play a role in the development of immunological disorders in chronic renal failure.6 Previous studies of PTH on the

From the Kidney Center, Saiseikai Yahata Hospital, Kitakyushu, Japan. This work was supported in part by the Baxter PD Research Foundation. Requests for reprints should be addressed to Chikao Yasunaga, MD, The Kidney Center, Saiseikai Yahata Hospital, 5-9-27 Harunomachi, Yahata-Higashiku, Kitakyushu 805, Japan. Manuscript submitted February 5, 1999, and accepted in revised form August 17, 1999.

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immune system were largely performed using either a human in vitro assay7–9 or using a CRF animal model10,11 for cellular7,8,10 and humoral immunity.9,11 Parathyroidectomy for secondary hyperparathyroidism is a good model to observe the effects of PTH on uremic abnormalities in CRF patients, since this operation causes a drastic reduction of PTH. However, an immunodeficiency in CRF patients has not yet been shown to improve after a parathyroidectomy. The main purpose of the present study was to investigate the in vivo effects of PTH reduction on both the humoral and cellular immunity. We therefore studied the following immunological parameters: (1) the serum levels of immunoglobulins and complements as markers for humoral immunity12,13; (2) the serum soluble IL-2 receptor (sIL-2R) and IL-2R positive T-cells as markers for T-cell activation14 –17; and (3) anemia and nutritional condition that could alter the immune responses.3,18 We attempted to establish the immunological improvement for a long-term period after a parathyroidectomy. This is the first prospective in vivo study that observed the effects of a parathyroidectomy on the humoral and cellular immune system in chronic hemodialysis patients with secondary hyperparathyroidism.

METHODS Patients From 1990 to 1997, 116 uremic patients undergoing dialysis therapy underwent a parathyroidectomy (PTx) for severe, uncontrolled hyperparathyroidism (HPT) at the Kidney Center, Saiseikai Yahata Hospital. The center consists of the surgeons (CY, KM, TG) and the nephrologists (MN, GN, TY). Thirty-four patients among them received PTx from February 1995 to November 1997, who had been referred from 19 different dialysis clinics. They were all prospectively studied for immunologic parameters for 1 year after PTx. The patients (13 men and 21 women), aged from 21 to 68 years (48.2 ⫾ 10.3 [mean ⫾ SD]), had all undergone dialysis for 13.9 ⫾ 4.5 years (33 hemodialysis and 1 continuous ambulatory peritoneal dialysis). The patients suffered from chronic renal failure due to chronic glomerulonephritis in 32 cases, and polycystic disease and diabetes mellitus in 1 each, respectively. They were free from underlying autoimmune diseases. The 33 patients underwent regular hemodialysis for between 4 and 5 hours, three times a week with the following dialysis membranes without reuse. The types of dialysis membranes used were unsubstituted cellulose (cuprophane) for 4, modified cellulose (2 cellulose acetate and 14 cellulose triacetate) for 16, 0002-9610/99/$–see front matter PII S0002-9610(99)00194-4

PARATHYROIDECTOMY EFFECTS ON IMMUNITY IN CHRONIC RENAL FAILURE/YASUNAGA ET AL

TABLE I Changes in the Immunological Markers during the 12 Months after Parathyroidectomy (Mean ⴞ SD)

IgG (mg/dL); n ⫽ 34 IgM (mg/dL), n ⫽ 34 IgA (mg/dL), n ⫽ 34 C3 (mg/dL), n ⫽ 34 C4 (mg/dL), n ⫽ 34 CH50 (U/mL), n ⫽ 34 Lymphocyte (%), n ⫽ 11 CD3 (%), n ⫽ 11 CD4/CD8, n ⫽ 11 CD25 (%), n ⫽ 11 sIL2R (U/mL), n ⫽ 11

Postoperative Term

Normal Range

Preoperative

2 Weeks

1 Month

3 Months

6 Months

12 Months

800–1800 49–305 100–400 74–155 12–38 30–40 25–45 70.7 ⫾ 15.4 0.8–2.7 3.7 ⫾ 4.0 494 ⫾ 253

1,290 ⫾ 369 93 ⫾ 57 215 ⫾ 116 82 ⫾ 15 25.3 ⫾ 11.0 35.3 ⫾ 7.4 26.7 ⫾ 8.3 74.1 ⫾ 13.0 1.57 ⫾ 0.50 4.6 ⫾ 4.0 1,330 ⫾ 462

1,249 ⫾ 349 93 ⫾ 47 223 ⫾ 120 84 ⫾ 18 24.9 ⫾ 5.5 35.8 ⫾ 5.1 28.7 ⫾ 8.8 72.2 ⫾ 11.6 1.45 ⫾ 0.44 2.9 ⫾ 1.5 1,692 ⫾ 518*

1,425 ⫾ 426‡ 110 ⫾ 59† 237 ⫾ 128† 84 ⫾ 15 26.5 ⫾ 7.2† 37.5 ⫾ 6.7 28.0 ⫾ 5.5 76.4 ⫾ 9.7 1.51 ⫾ 0.37 4.4 ⫾ 2.0 1,411 ⫾ 410

1,475 ⫾ 384‡ 112 ⫾ 61‡ 244 ⫾ 145† 86 ⫾ 17 26.5 ⫾ 8.8* 37.1 ⫾ 7.0 28.1 ⫾ 5.3 75.9 ⫾ 9.6 1.57 ⫾ 0.38 4.1 ⫾ 2.6 1,566 ⫾ 607

1,507 ⫾ 396‡ 114 ⫾ 65‡ 251 ⫾ 141† 85 ⫾ 14 26.4 ⫾ 6.7* 38.2 ⫾ 5.8* 25.4 ⫾ 5.3 74.2 ⫾ 10.8 1.52 ⫾ 0.39 3.6 ⫾ 1.7 1,523 ⫾ 509

1,429 ⫾ 349‡ 109 ⫾ 57‡ 268 ⫾ 146‡ 89 ⫾ 17‡ 28.7 ⫾ 11.2† 38.0 ⫾ 5.6‡ 28.3 ⫾ 6.6 75.8 ⫾ 10.9 1.50 ⫾ 0.37 6.0 ⫾ 2.8 1,518 ⫾ 321

* P ⬍0.05 compared with preoperative value. † P ⬍0.01 compared with preoperative value. ‡ P ⬍0.001 compared with preoperative value. sIL2R ⫽ serum soluble IL-2 receptor.

and synthetic membranes (6 polysulfone, 2 polymethyl methacrylate, 2 ethylenevinylalcohol copolymer, and polyacrylonitrile, biorex, polyester polymer alloy in 1 each) for 13 patients. These dialysis membranes were not changed during the study. Ten patients were positive for HCV antibody, and 2 patients were positive for HBs antigen. In addition, the presence of malignancy, active infection, and immunosuppressive drug administration were ruled out in all patients. Preoperatively, all patients were clinically symptomatic for such symptoms as osteoarticular pain, skin itching, muscle weakness, and irritability, and had associated elevated levels of immunoreactive parathyroid hormone and roentgenographic findings of secondary HPT. Operative Procedures and Postoperative Management Thirty patients first underwent a total parathyroidectomy and autotransplantation of about 100 mg parathyroid tissue into the forearm muscle (PTx-A).19,20 The remaining 4 patients received reoperations for recurrence. PTx was performed by the author (CY) in all cases. The parathyroid glands were elucidated with the use of intraoperative methylene blue injection.21 Postoperatively, all patients exhibited a significant reduction in both the PTH and calcium levels. When the serum calcium levels became lower than 7.0 mg/dL or hypocalcemic symptoms appeared, a calcium supplement was administered using calcium gluconate intravenously and orally with 1␣-OH-vitamin D3 3.0 ␮g per day. The target serum calcium level was thus controlled at between 9.0 and 10.0 mg/dL. Laboratory Investigation After discharge, the patients were followed up in the outpatient clinic of our hospital and underwent the following examinations at 2 weeks, 1 month, 3 months, 6 months, and 1 year after PTx-A, and the findings were then compared with the preoperative values. A complete blood cell count and other routine serum examinations were also carried out. Blood samples were collected on the day after undergoing dialysis.

Evaluation of Parathyroid Hormone and Bone Mineral Content and Body Composition A radioimmunoassay for intact-PTH (1-84PTH; Allegro PTH assay kit; Nichols Institute Diagnostics, San Juan Capistrano, California), normal range 10 to 60 pg/mL, and mid-region PTH (44-68 PTH; HS-PTH; Highly Sensitive PTH RIA kit; Yamasa, Tokyo, Japan), normal range 150 to 500 pg/mL, were used to evaluate the postoperative parathyroid levels. The latter was used because of its stability regardless of calcium and vitamin D administration just before assay and the blood collection site related to autotransplantation.22,23 The bone Gla-protein (osteocalcin) was also measured using a radioimmunoassay (Yamasa, Tokyo, Japan), normal range 3.5 to 13.7 ng/mL. Serum levels of total calcium, ionized calcium (normal range 2.27 to 2.63 mEq/L), phosphorus and alkaline phosphatase were also regularly measured. Dual energy X-ray absorptiometry (DEXA) was performed, and the bone mineral density of the lumbar spine (L2-4 BMD) and the ratio of the total bone mineral content to lean body mass (%TBMC/LBM) were measured using the XR-26HS Dual X-ray Bone Densitometer (Norland, Fort Atkinson, Wisconsin). L2-4 BMD was expressed by percent age-matched value, which was calculated using the data based on a gender- and age-matched normal Japanese population. LBM was also used to evaluate the nutritional condition of the patients.24 Immunologic Parameters The immunologic markers for humoral immunity included the serum immunoglobulins (IgG, IgM, and IgA) and complements (C3, C4, CH50), which were examined for all patients. For cellular immunity, a flow cytometry analysis of T cell subsets was done for CD 3, 4, 8, and 25 (IL-2 receptor positive T-cells); Mitsubishi Yuka Bio-Clinical Laboratories, Inc., Tokyo, Japan). The control values in Table I were calculated based on 50 normal subjects. The serum soluble IL-2 receptor (sIL-2R) concentration was also measured using an enzyme-linked immunosorbent assay (T Cell Sciences, Cambridge, Massachusetts), normal

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TABLE II Changes of Mean Parathyroid Hormone, Osteocalcin, and Calcium Levels during 12 Months after Parathyroidectomy (Mean ⴞ SD; n ⴝ 11) Normal Range Intact-PTH (pg/mL) HS-PTH (pg/mL) Osteocalcin (ng/mL) Total Ca (mg/dL) Ionized Ca (mEq/L) Vitamin D supply (␮g/day)

10–60

Postoperative Term Preoperative

1 Day

2 Weeks

805.5 ⫾ 509.1 26.4 ⫾ 19.5‡ 34.4 ⫾ 40.8‡

150–500 88,682 ⫾ 24,906 3.5–13.7

375 ⫾ 253.8

9.0–11.4

10.4 ⫾ 0.6

2.27–2.63

2.52 ⫾ 0.12

—

0.18 ⫾ 0.28

ND

1 Month

3 Months

6 Months

12 Months

ND

ND

246.2 ⫾ 438.0*

59.0 ⫾ 74.9‡

2,181 ⫾ 1,553‡ 2,598 ⫾ 2,682‡ 3,079 ⫾ 2,834‡ 3,467 ⫾ 3,930‡ 3,066 ⫾ 2,825‡

ND

371 ⫾ 78.0

177 ⫾ 96.0

83 ⫾ 71.5†

8.6 ⫾ 0.6‡

9.6 ⫾ 1.2

9.8 ⫾ 1.1

9.5 ⫾ 0.8*

10.2 ⫾ 1.2

9.7 ⫾ 0.7†

ND

ND

2.56 ⫾ 0.34

2.44 ⫾ 0.21

2.6 ⫾ 1.6

1.5 ⫾ 1.2

1.1 ⫾ 1.0

0.6 ⫾ 0.5

2.24 ⫾ 0.13‡ 2.42 ⫾ 0.18* 1.1 ⫾ 1.4

3.0 ⫾ 0.0

56 ⫾ 31.9†

40 ⫾ 14.7†

These data were calculated based on the 11 patients operated on between February 1995 and October 1995. * P ⬍0.05 compared with preoperative value. † P ⬍0.01 compared with preoperative value. ‡ P ⬍0.001 compared with preoperative value. HS-PTH ⫽ highly sensitive parathyroid hormone (mid-region PTH); ND ⫽ not determined; vitamin D ⫽ 1␣-OH-vitamin D3.

values 246 to 742 U/mL. The examinations for cellular immunity were performed for the first 11 patients operated on from February 1995 to October 1995. The tests for cellular immunity were originally planned to continue for the following patients; however, PTx seemed to have no apparent effect on cellular immunity after 10 cases, and therefore the tests were only performed for the first 11 patients. Statistical Analysis The results are expressed as the mean ⫾ SD. A statistical analysis was performed with the Student’s paired t test to compare the biochemical and immunological data. A P value of ⬍0.05 was considered to be significant. All calculations were performed using SPSS for windows, Release 6.1.3J (SPSS Japan Inc., Tokyo, Japan).

RESULTS Effects of Parathyroidectomy on Parathyroid Hormone and Bone Condition The PTx was associated with a remarkable improvement in such clinical symptoms as osteoarticular pain and skin itching, and there were rapid and significant decreases in PTH levels measured by intact-PTH and HS-PTH at 2 weeks after PTx and later. The mean osteocalcin levels showed more gradual reduction (Table II). The ionized calcium level significantly decreased 1 day after PTx (2.52 ⫾ 0.12 to 2.24 ⫾ 0.13 mEq/L; P ⬍0.001), and vitamin D and calcium supplement were started mostly within 48 hours after the operation. The ionized calcium levels were not significantly different after 6 months, compared with before PTx. The vitamin D supply was started with a 3 ␮g daily dose and then gradually decreased during the study (Table II). A dual X-ray bone densitometer study showed a significant increase in the mean percent agematched L2-4 BMD (92.4% ⫾ 15.5% to 100.9% ⫾ 24.0% 334

and 106.4% ⫾ 16.6%; P ⬍0.001, respectively) and %TBMC/LBM (4.70% ⫾ 0.84% to 5.14% ⫾ 1.18% and 5.33% ⫾ 0.63%; P ⬍0.001, respectively) at 6 and 12 months after PTx (Table III). Effects of PTx on Immunological Markers There were significant increase of serum levels of IgG (1,289 ⫾ 369 to 1,425 ⫾ 426 mg/dL; P ⬍0.001), IgA (215 ⫾ 116 to 237 ⫾ 128 mg/dL; P ⫽ 0.01), and IgM (93 ⫾ 57 to 110 ⫾ 59 mg/dL; P ⫽ 0.003) at 1 month after PTx. As shown in Table I, these significant changes continued until 12 months after PTx. CH50 showed significant increase at 6 and 12 months (P ⫽ 0.011 and P ⬍0.001, respectively). C3 (82.0 ⫾ 14.7 to 89.1 ⫾ 16.7 mg/dL; P ⫽ 0.02) and C4 (25.3 ⫾ 11.0 to 28.7 ⫾ 11.2 mg/dL; P ⫽ 0.05) levels also showed significant increase at 12 months (Table I). In contrast, there were no significant differences in the CD3 count (74.1% ⫾ 13.0% to 75.8% ⫾ 10.9%; P ⫽ 0.294), CD4/CD8 ratio (1.57 ⫾ 0.50 to 1.50 ⫾ 0.37; P ⫽ 0.62), and CD25 count (4.6% ⫾ 4.0% to 6.0% ⫾ 2.8%; P ⫽ 0.337) at 12 months after PTx. The serum sIL-2R level significantly increased only at 2 weeks after PTx (1,330 ⫾ 462 to 1,692 ⫾ 518 U/mL; P ⫽ 0.028); however, it was not significantly different at times later than 1 month after PTx (Table I). Effects of PTx on Anemia and Nutritional Status The hematocrit value significantly dropped at 2 weeks and gradually increased until 12 months after PTx (32.7% ⫾ 4.4% to 35.9% ⫾ 4.8%; P ⬍0.001 at 12 months), whereas the dose of erythropoietin administration did not significantly increase (1,773 ⫾ 1,788 to 1,091 ⫾ 1,819 units a week; P ⫽ 0.096). The nutritional status was assessed by serum albumin, total protein, standard body weight before HD, and the lean body mass measured by

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TABLE III Changes in Nutritional Condition and Bone Mineral Content Measured by Dual Energy X-ray Absorptiometry (Mean ⴞ SD; n ⴝ 34) Postoperative Term Normal Range Hct (%) Epo use (U/wk) Alb (g/dL) TP (g/dL) LBM (g) DBW (Kg) L2-4BMD (%) %TBMC/LBM

25–40 — 3.9–5.5 6.5–8.0 — — 100 —

Preoperative

2 Weeks

1 Month

3 Months

6 Months

12 Months

32.7 ⫾ 4.4 27.9 ⫾ 3.4‡ 31.4 ⫾ 5.0‡ 33.8 ⫾ 7.3‡ 35.5 ⫾ 4.7‡ 35.9 ⫾ 4.8‡ 1,773 ⫾ 1,788 1,773 ⫾ 1,788 2,182 ⫾ 1,850 2,591 ⫾ 1,819 1,091 ⫾ 1,819 1,295 ⫾ 1,754 3.9 ⫾ 0.3 3.7 ⫾ 0.3 4.2 ⫾ 0.3‡ 4.2 ⫾ 0.8‡ 4.3 ⫾ 0.3* 4.4 ⫾ 0.3‡ 6.7 ⫾ 0.5 6.5 ⫾ 0.4 7.2 ⫾ 0.6‡ 7.3 ⫾ 1.4‡ 7.5 ⫾ 0.5† 7.5 ⫾ 0.5‡ 3,4334 ⫾ 7,952 ND ND ND 35,708 ⫾ 7,444 35,537 ⫾ 8,157 50.2 ⫾ 7.5 49.6 ⫾ 7.6 49.5 ⫾ 7.5* 49.4 ⫾ 7.3* 50.0 ⫾ 6.9 51.4 ⫾ 7.6* 92.4 ⫾ 15.5 ND ND ND 100.9 ⫾ 24.0‡ 106.4 ⫾ 16.6‡ 4.70 ⫾ 0.84 ND ND ND 5.14 ⫾ 1.18‡ 5.33 ⫾ 0.63‡

* P ⬍0.05 compared with preoperative value. † P ⬍0.01 compared with preoperative value. ‡ P ⬍0.001 compared with the preoperative value. Hct ⫽ hematocrit; Epo ⫽ erythropoietin; Alb ⫽ serum albumin; TP ⫽ serum total protein; LBM ⫽ lean body mass; DBW ⫽ dried body weight; L2-4 BMD ⫽ bone mineral density of the lumbar spine; TBMC/LBM ⫽ ratio of the total bone mineral content to lean body mass; ND ⫽ not determined; L2-4BMD ⫽ gender- and age-matched normal Japanese controls, expressed by %.

DEXA. The serum levels of albumin and the total protein significantly and gradually improved until 12 months. The standard body weight showed a significant increase at 12 months (50.2 ⫾ 7.5 to 51.4 ⫾ 7.6 kg; P ⫽ 0.033), whereas the lean body mass did not show a significant increase (34,334 ⫾ 7,952 to 35,537 ⫾ 8,157 g; P ⫽ 0.167) at 12 months after PTx (Table III).

COMMENTS The immune system is impaired in uremic patients, and at least two factors have been implicated in the underlying mechanisms: (1) the metabolic and toxic consequences of uremia, and (2) the associated abnormalities in nutrition.25 These factors may be corrected in part by adequate dialysis therapy; however, they continue to be present to some extent. Excess blood levels of PTH may play a role in the pathogenesis of the impairment of immune response in chronic dialysis patients.6 We thus studied the effects of parathyroidectomy for secondary hyperparathyroidism on humoral and cellular immunological parameters in association with a drastic reduction of PTH. The present study revealed that the parameters for humoral immunity, represented by immunoglobulins and complements, significantly improved after a parathyroidectomy. Actually, 15 of 34 patients (44%) showed less than normal values for some humoral markers, preoperatively. After PTx, 11 of 15 cases (73%) returned to normal by 12 months. When the 15 patients with below normal values and the remaining 19 patients with normal levels before PTx are considered separately, both groups still showed a statistically significant increase in humoral markers, such as immunoglobulins and CH50. The 4 patients who did not demonstrate normal values after PTx also showed an increase in the markers. These results are compatible with the suppressive effects of PTH on T-cell independent Bcell proliferation26 and immunoglobulin production9,27 using an in vitro assay. Malnutrition has been recognized as a relatively common complication in chronic dialysis patients and may accentuate this immunodeficiency.3,18 The nutritional condition, as evaluated by the serum levels of

albumin and total protein, anemia (hematocrit) and dry weight, improved significantly after a parathyroidectomy (Table III). These nutritional improvements may be caused by the correction of hypercalcemia and hyperparathyroidism, which can decrease gastric acid secretion.28,29 Patients with secondary hyperparathyroidism were catabolic and also had increased rates of glucose and fat turnover.30 In addition, the increased daily activity, as a result of a reduced osteoarticular pain, may have also helped to improve their appetites. Regarding cellular immunity, Angelini et al31 reported the elevated levels of PTH to be associated with a reduction in the total number of T cells, and increased levels of CD8 count, soluble CD8 and serum I1-2R in 54 hemodialysis patients. The addition of PTH in a human lymphocyte culture, from healthy donors, caused a significant decrease in the CD4/CD8 ratio of T-cells.8 T cells from dialysis patients showed lower responses in the PHA and IL-2 induced proliferation with and without PTH compared with those from normal subjects.32 These in vitro studies were conducted in short-term cultures such as for 72 hours8 or 5 days32 and might thus be different from the dialysis patients who are chronically exposed to markedly elevated blood levels of PTH. We measured the CD3 count, CD4/CD8 ratio, CD25 count, and serum level of sIL-2R to assess T-cell activation,13–17 however, only a transient increase of sIL-2R was observed after a parathyroidectomy (Table II). These parameters were static to evaluate the cellular immunity, and the function might have also changed, such as IL-2 production and lectininduced transformation of T-cells,7,8 and natural killer cell cytotoxicity.33 The serum levels of 1,25-(OH)2-vitamin D3 have been shown to have some immunomodulating effects on the delayed hypersensitivity response, natural killer cell activity, and polymorphonuclear leukocyte (PMNL) function.33–35 The oral dosage of 1␣-OH-vitamin D3 was increased up to 3.0 ␮g per day after the parathyroidectomy in our study and might thus have affected the immunological parameters after PTx. The resting levels of [Ca2⫹]i in the

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T-cells and PMNLs from dialysis patients were significantly higher than in the T-cells from normal subjects. The chronic exposure to excess PTH may also be responsible for the rise in the resting levels of [Ca2⫹]i and may have thus induced a reduction in the calcium signal transduction.32 The decreased levels of ionized calcium right after a parathyroidectomy might also have directly affected on the primary immune system. The clinical significance of increased levels of immunoglobulins and complements should be demonstrated by a prophylactic effect on infective diseases. To prove this, a larger controlled study of secondary hyperparathyroidism with and without PTx is thus called for. The beneficial effects of PTx on humoral immunity are probably due to the remarkable reduction of PTH in the blood, which directly affects the B-cells. In addition, the improved nutritional status after PTx is also considered to be, at least partly, responsible for the increased production of immunoglobulins and complements.

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THE AMERICAN JOURNAL OF SURGERY® VOLUME 178 OCTOBER 1999