Chronic Maintenance Research Articles

Medical and Surgical Treatment for Secondary and Tertiary Hyperparathyroidism

Prevention and treatment of secondary hyperparathyroidism (SHPT) in patients on chronic maintenance hemodialysis and of tertiary hyperparathyroidism (THPT) in patients after kidney transplantation is a challenge for the nephrologist and for the surgeon. Indication and results of medical and surgical therapy for SHPT and THPT have remained under discussion during the last decades. This review resumes the current medical and surgical strategies for patients with SHPT and THPT.

Bone Biopsy as a Diagnostic Tool in the Assessment of Renal Osteodystrophy

When renal disease develops, mineral and vitamin D homeostasis is disrupted, resulting in diverse modifications in bone cells, bone structure and the rate of bone turnover. In end stage renal failure (ESRF) when patients require chronic maintenance dialysis, nearly all of them have abnormal bone histology known as renal osteodystrophy (ROD). Moreover, survival rates of patients on dialysis have increased because of therapeutic improvement and the resultant increase in duration of dialysis has led to a further rise in renal osteodystrophy. Because metabolic bone disease can produce fractures, bone pain, and deformities late in the course of the disease, prevention and early treatment are essential. Serum PTH and various bone markers are commonly used to assess bone changes in ESRF patients, but the diagnosis of underlying bone disease is still rather uncertain. To date, bone biopsy is the most powerful and informative diagnostic tool to provide precise information on the type and severity of renal osteodystrophy, and on the presence and amount of aluminum and strontium deposited in the bone. Bone biopsy is not only useful in clinical settings but also in research to assess the effects of therapies on bone. Although considered an invasive procedure, bone biopsy has been proven to be safe and free from major complications, but the operator's experience and skill is important in further minimizing morbidity. Alternatives to bone biopsy continue to be sought, but the non-invasive bone markers have not been proven to be sufficient in diagnostic performance related to bone turnover, mineralization process and bone cell abnormality. Hence, transiliac bone biopsy remains the gold standard for the diagnosis of renal osteodystrophy.

A clinical assessment of the relationship between bone scintigraphy and serum biochemical markers in hemodialysis patients

Renal osteodystrophy is a metabolic bone disease and a common complication of end-stage chronic renal failure and maintenance dialysis treatment. In this study, we examined the correlation between quantifying bone scintigraphy and serum biochemical markers in hemodialysis patients. Bone scintigraphy with technetium-99m-hydroxy-methylene-diphosphonate (99mTc-HMDP) was performed on 28 patients on maintenance hemodialysis. Bone scintigraphy was performed using a standard protocol and was quantified by setting regions of interest (ROIs) over selected regions. The bone-to-soft-tissue ratio (B/ST ratio) at each region was calculated in all patients. The B/ST ratios were then compared with serum biochemical markers. The B/ST ratio for the skull correlated well with serum bone-specific alkaline phosphatase (BAP) (r = 0.735, p < 0.001), serum deoxypyridinoline (DPD) (r = 0.806, p < 0.001) and intact parathyroid hormone (intact PTH) (r = 0.701, p < 0.001). The B/ST ratio for the lumbar spine correlated with intact PTH (r = 0.387, p < 0.05) but not with serum BAP or serum DPD. The B/ST ratio for the femoral neck correlated with serum DPD (r = 0.431, p < 0.05) and intact PTH (r = 0.449, p < 0.05) but not with serum BAP. Our data suggest that quantitative bone scintigraphy is a sensitive and useful method for evaluating bone metabolism in hemodialysis patients. The B/ST ratio for the skull may reflect changes of bone metabolism in hemodialysis patients.

The pharmacokinetics and hemodynamics of sildenafil citrate in male hemodialysis patients

Erectile dysfunction (ED) is highly prevalent in men with renal disease. The clearance of sildenafil citrate, a highly effective oral treatment for ED, is decreased in men with severe renal insufficiency, but the pharmacokinetic and hemodynamic profiles during maintenance hemodialysis in men with end-stage renal disease have not been studied. Fifteen men undergoing chronic outpatient maintenance hemodialysis received a single 50-mg oral dose of sildenafil on 2 occasions, once 2 hours before, and once 2 hours after hemodialysis, with randomized assignment to sequence. Blood and dialysate samples were collected, and hemodynamic measurements were made. Hemodialysis did not significantly clear either sildenafil or its primary metabolite, UK-103,320. Administration after hemodialysis was associated with a 17% higher peak plasma concentration and earlier time to peak, which were not clinically meaningful, whereas the overall extent of absorption and the elimination half-life were not affected. The average extent of drug bound to plasma protein was approximately 96% in hemodialysis patients. Intradialytic hypotension was not observed more frequently when sildenafil was administered before hemodialysis. Systolic blood pressure tended to decrease less during hemodialysis when subjects were treated with sildenafil before dialysis. The present study demonstrates that sildenafil is not cleared by hemodialysis, and the pharmacokinetic profile resembles more closely that observed in normal volunteers than that observed in patients with severe renal insufficiency. In addition, we found that sildenafil does not promote intradialytic hypotension.

Antihypertensive Effects of Long-Acting Calcium Channel Blockers on Hemodialysis Days – A Randomized Crossover Trial between Benidipine and Nifedipine CR

Background/Aims: Since antihypertensive effects of most calcium channel blockers largely depend on their plasma concentrations, a rapid increase in blood pressure may occur as circulating levels of such blockers decrease after hemodialysis. Thus, the effects of benidipine and nifedipine CR (extended-release coated tablets, Adalat CR^®), which are long-acting calcium channel blockers, on post-hemodialytic blood pressures were investigated. Methods: A randomized crossover trial was carried out with 10 hypertensive patients on chronic maintenance hemodialysis. Patients were assigned to receive benidipine (4–8 mg/day) or nifedipine CR (20–40 mg/day), and after 4 weeks, 24-hour ambulatory blood pressure monitoring was performed on the day of hemodialysis and blood samples were obtained before and after hemodialysis to measure plasma concentrations of the blockers. The calcium channel blockers were then exchanged in each patient and the same protocol was repeated. Results: The pattern of fluctuation of blood pressure differed markedly between the treatment with benidipine and nifedipine CR. Under treatment with nifedipine CR, rapid increase in blood pressure was observed after hemodialysis, while blood pressure remained at favorable levels with benidipine. Plasma concentrations of the blockers were significantly decreased by hemodialysis. Conclusion: Benidipine exerts more sustained antihypertensive effects than expected from its disposition in plasma. The stable depressor effects of benidipine even after hemodialysis may contribute to favorable control of blood pressure in this population.

Relationship of predialytic intact parathyroid hormone on secondary hyperparathyroidism in chronic maintenance haemodialysis patients.

In order to clarify the predialytic factors influencing the onset of secondary hyperparathyroidism (SHPT) in patients on chronic maintenance haemodialysis, the time-course changes of serum levels of intact-PTH (i-PTH) during haemodialysis for 5 years were investigated. The subjects were 69 non-diabetic patients who had a serum aluminium level of less than 1.85 nmol/L at the end of observation. Patients were divided into two groups based on i-PTH levels obtained at the start of dialysis; the high group (H group) consisted of patients whose i-PTH levels were more than 22.00 pmol/L, the low group (L group) had levels less than 22.00 pmol/L. In the H group, i-PTH was 41.46 +/- 2.87 pmol/L at the start of dialysis (vs L group, P < 0.0001) and 15.82 +/- 2.85 pmol/L after haemodialysis initiation. In the L group, i-PTH levels did not significantly change and was 11.69 +/- 2.50 pmol/L 12 months after the start of dialysis (at the 12th month). However, at the 60th month, the i-PTH level was 33.24 +/- 5.30 pmol/L in the H group, and 9.85 +/- 2.13 pmol/L in the L group (P < 0.005). It is suggested that control of i-PTH levels in the predialytic period may be important to suppress SHPT throughout haemodialysis.

Chronic food restriction increases d-1 dopamine receptor agonist-induced phosphorylation of extracellular signal-regulated kinase 1/2 and cyclic AMP response element-binding protein in caudate-putamen and nucleus accumbens

Results of behavioral and c-fos immunohistochemical studies have suggested that chronic food restriction and maintenance of animals at 75–80% of free-feeding body weight may increase d-1 dopamine (DA) receptor function. The purpose of the present study was to determine whether d-1 DA receptor binding and/or mitogen-activated protein kinase (MAPK) signaling in caudate-putamen (CPu) and nucleus accumbens (NAc) are increased in food-restricted subjects. In the first experiment, saturation binding of the d-1 DA receptor antagonist [ 3H]SCH-23390 indicated no difference between food-restricted and ad libitum fed rats with regard to density or affinity of d-1 binding sites in CPu or NAc. In the second experiment, activation of extracellular signal-regulated kinases (ERK1/2) and cyclic AMP response element-binding protein (CREB) by i.c.v. injection of the d-1 DA receptor agonist SKF-82958 (20 μg) were markedly greater in food-restricted than ad libitum fed rats. Given a prior finding that SKF-82958 does not differentially stimulate adenylyl cyclase in CPu or NAc of food-restricted versus ad libitum fed subjects, the present results suggest that increased d-1 DA receptor-mediated ERK1/2 MAP kinase signaling may mediate the enhanced downstream activation of CREB, c-fos, and behavioral responses in food-restricted subjects. It is of interest that food restriction also increased the activation of c-Jun N-terminal protein kinase/stress-activated protein kinase, but this effect was no greater in rats injected with SKF-82958 than in those injected with saline vehicle. This represents additional evidence of increased striatal cell signaling in food-restricted subjects, presumably in response to the i.c.v. injection procedure, although the underlying receptor mechanisms remain to be determined. There were no differences between feeding groups in protein levels of the major phosphatases, MKP-2 and PP1. The upregulation of striatal MAP kinase signaling in food-restricted animals may adaptively serve to facilitate associative learning but, at the same time, increase vulnerability to the rewarding and addictive properties of abused drugs.

Development of an Expert System Knowledge Base: A Novel Approach to Promote Guideline Congruent Asthma Care

Existing guidelines for the clinical management of asthma provide a good framework for such tasks as diagnosing asthma, determining severity, and prescribing pharmacological treatment. Guidance is less explicit, however, about establishing a patient‐provider partnership and overcoming barriers to asthma management by patients in a way that can be easily adopted in clinical practice. We report herein the first developmental phase of the “Stop Asthma” expert system. We describe the establishment of a knowledge base related to both the clinical management of asthma and the enhancement of patient and family self‐management (including environmental management). The resultant knowledge base comprises 142 multilayered decision rules that describe clinical and behavioral management in three domains: 1) determination of asthma severity and control; 2) pharmacotherapy, including prescription of medicine for chronic maintenance, acute exacerbation, exercise pretreatment, and rhinitis relief; and 3) patient self‐management, including the process of intervening to facilitate the patient's asthma medication management, environmental control, and well‐visit scheduling. The knowledge base provides a systematic and accessible approach for intervening with family asthma‐related behaviors.

The Effects of Exercise on Markers of Lipid Peroxidation in Renal Dialysis Patients Compared with Control Subjects

The purpose of this study was to compare the susceptibility to exercise-induced lipid peroxidation of patients on chronic maintenance dialysis (CMD) and non-CMD control subjects. Cross-sectional comparison of exercise-induced changes in breath ethane and pentane flux between patients on CMD (group A) and an age-, gender-, medical diagnosis-, smoking-, and ethanol consumption-matched comparison group (group B). Breath ethane and pentane were measured at rest before exercise, during cardiopulmonary exercise stress testing (CPX) at lactic acidosis threshold (Vo2lat), and 5 minutes after CPX. Group comparisons of clinical characteristics reveal that the groups were similar in terms of age, ethnicity, comorbid diagnoses, prevalence of medication use, BMI, measurements of aerobic exercise capacity, cigarette smoking and ethanol consumption behaviors. All subjects successfully completed the CPX protocol achieving Vo2lat. There were significant differences in breath ethane flux between group A and B subjects, with greater pre-exercise, Vo2lat, and postexercise ethane levels in group A compared with group B subjects, and significant group differences, with lower breath ethane/pentane flux ratios at rest, Vo2lat, and recovery with lower ratios in group B than group A subjects. This study shows that patients on CMD have greater lipid peroxidation compared with control subjects at rest and during and after physical exercise. In addition, compared with control subjects, patients on CMD preferentially peroxidize n-3 polyunsaturated fatty acids at rest and during physical exercise and recovery. The lipid peroxidation profile may result in an unfavorable endoperoxide shift and should be evaluated further, along with modalities to reduce oxidative stress among patients on CMD.

Effect of Vitamin E Dialyzer Membrane on Anemia in Hemodialysis Patients

Red blood cell (RBC) survival in patients on chronic maintenance hemodialysis (HD) has been reported to be shortened due to the oxidative damage of RBC membrane. The use of antioxidants might help in the control of anemia and reduce the erythropoietin (EPO) dose needed.Objective: The objective was to determine the effects of vitamin E‐bonded dialyzer membrane (VEM) on anemia and EPO requirements in chronic HD patients.Patients and methods: We prospectively studied 19 stable patients on HD (8 males, age 58.47, range 31–76 years) who were shifted from other dialyzer membranes to VEM for 6 months. At baseline they were given a mean dose of EPO of 90.6 ± 51 U kg–1 BW–1 week–1. Clinical data, dry body weight corrected pre‐dialysis RBC, hemoglobin, reticulocytes, serum iron and ferritin, complete biochemistry, iPTH, and CRP were studied at 3 and 6 months, while therapy scheme was reevaluated monthly.Results: A significant rise, compared to the baseline, was found in hemoglobin and in RBC at 3 months of treatment (12.44 ± 1.16 g/dL vs. 11.2 ± 1.2 g/dL, p = 0.002; and 4.01 ± 0.53 × 106/μL vs. 3.64 ± 0.5 × 106/μL, p &lt; 0.05) and at the end of follow‐up (12.17 ± 1.33 g/dL vs. 11.2 ± 1.2 g/dL, p &lt; 0.05; and 4.03 ± 0.53 × 106/μL vs. 3.64 ± 0.5 × 106/μL, p &lt; 0.05). No significant change in serum iron and ferritin, reticulocytes, EPO dose used, iPTH, Kt/V, or CRP was found at the end of follow‐up compared to the baseline (68.8 ± 17 mg/dL vs. 67.9 ± 18 mg/dL, p = NS; 421 ± 296 mg/dL vs. 478 ± 359 mg/dL, p = NS; 3.76 ± 0.89 × 104/μL vs. 3.82 ± 0.78 × 104/μL, p = NS; 90.2 ± 53 U kg–1 BW–1 week–1 vs. 90.6 ± 51 U kg–1 BW–1 week–1, p = NS; 157 ± 43 pg/dL vs. 148 ± 56 pg/dL, p = NS; 1.21 ± 0.22 vs. 1.2 ± 0.17, p = NS; 7.15 ± 5.42 mg/L vs. 15.38 ± 29.8 mg/L, p = NS, respectively).Conclusions: Despite the small number of patients and the short time interval of treatment, an antioxidant effect of VEM apparently achieved early a better control of anemia in HD patients.

Metabolic acidosis in maintenance dialysis patients: Clinical considerations

Metabolic acidosis in maintenance dialysis patients: Clinical considerations. Metabolic acidosis is a common consequence of advanced chronic renal failure (CRF) and maintenance dialysis (MD) therapies are not infrequently unable to completely correct the base deficit. In MD patients, severe metabolic acidosis is associated with an increased relative risk for death. The chronic metabolic acidosis of the severity commonly encountered in patients with advanced CRF has two well-recognized major systemic consequences. First, metabolic acidosis induces net negative nitrogen and total body protein balance, which improves upon bicarbonate supplementation. The data suggest that metabolic acidosis is both catabolic and antianabolic. Emerging data also indicate that metabolic acidosis may be one of the triggers for chronic inflammation, which may in turn promote protein catabolism among MD patients. In contrast to these findings, metabolic acidosis may be associated with a decrease in hyperleptinemia associated with CRF. Several studies have shown that correction of metabolic acidosis among MD patients is associated with modest improvements in the nutritional status. Second, metabolic acidosis has several effects on bone, causing physicochemical dissolution of bone and cell-mediated bone resorption (inhibition of osteoblast and stimulation of osteoclast function). Metabolic acidosis is probably also associated with worsening of secondary hyperparathyroidism. Data on the effect of correction of metabolic acidosis on renal osteodystrophy, however, are limited. Preliminary evidence suggest that metabolic acidosis may play a role in beta2-microglobulin accumulation, as well as the hypertriglyceridemia seen in renal failure. Given the body of evidence pointing to the several systemic consequences of metabolic acidosis, a more aggressive approach to the correction of metabolic acidosis is proposed.

Malnutrition and nutritional therapy of chronic kidney disease in developing countries: the asian perspective

There is a paucity of data regarding the prevalence and clinical consequences of protein-energy malnutrition (PEM) in the chronic renal failure, maintenance dialysis, and renal transplant population in developing countries. Malnutrition, which is reported to be present in 42% to 77% of the end-stage renal disease population in developing countries, is strongly associated with morbidity and mortality. Many religious practices in developing countries promote abstinence from meat, fish, and eggs. Both a vegetarian dietary pattern, which is being adopted by an increasing number of people, and ingestion of inadequate protein and calories in the diet to arrest the progression of chronic renal failure, may lead to malnutrition. The attendant complications of PEM, malaise, wasting, anemia, and decreased immunity, may predispose these patients to infections. This is commonly seen in both the maintenance hemodialysis and peritoneal dialysis population and may decrease their survival. There is an urgent need for nutritional counseling by a dietitian to contain the damage of malnutrition and to provide important nutritional information to the patient. Consultation with a dietitian should take place at least 3 times yearly and, in malnourished patients, more often, as needed. Dietetic documentation should include reports of food intake, subjective global assessment, anthropometric measurements, estimation of the nPNA, serum albumin, and prealbumin, the serum lipid profile, sodium and potassium intake, calcium and phosphorus status, and any changes in body weight.

Metabolic effects of a corticosteroid-free immunosuppressive regimen in recipients of pancreatic transplant.

A corticosteroid (CS)-free immunosuppressive regimen may be considered less diabetogenic than treatments including CSs principally after pancreas transplantation. To test whether a CS-free immunosuppressive treatment is metabolically superior to a regimen including CSs, we prospectively studied 19 CS-free simultaneous pancreas and kidney (SPK) transplant recipients (body mass index=22+/-1 kg/m2; cyclosporine dose=400+/-19 mg/kg/day; azathioprine dose=77+/-8 mg/day; basal plasma C-peptide=1.3+/-0.12 ng/mL) and 12 matched CS-treated SPK transplant recipients (prednisone dose=9+/-1 mg/day; basal C-peptide=2.2+/-0.2 ng/mL) by means of the 6,6-2H(2)-glucose infusion and the euglycemic insulin clamp (1 mU/kg/min, insulin infusion rate). In addition, six renal transplant recipients receiving a CS-free regimen were also studied as a control group. In the postabsorptive state, CS-treated SPK transplant recipients demonstrated comparable plasma glucose levels but higher plasma insulin levels than CS-free SPK transplant recipients. Plasma triglyceride levels were significantly higher in CS-treated SPK patients than in CS-free SPK patients (1.16+/-0.16 mg/dL vs. 0.88+/-0.08; P<0.05). High-density lipoprotein and apoprotein A(1) levels were similar in both groups. No difference was observed in pyruvate, lactate, beta-OH-butyrate, and basal endogenous glucose production in all three groups of patients studied. During euglycemic hyperinsulinemia, the inhibition of endogenous glucose production and the stimulation of tissue glucose disposal were not statistically different among the three groups. SPK recipients receiving chronic low-dose CS maintenance therapy do not present a lower glucose disposal than CS-free recipients. Nonetheless, this is obtained at the expense of a higher endogenous insulin secretion, which can cause an alteration of the triglyceride profile.

Controlling the plaque biofilm

To examine the effect of supragingival plaque removal in conjunction with different periodontal therapies on subgingival plaque composition in different subject populations. Four different studies are presented which examined the effect of repeated removal of supragingival plaque performed by professionals or by tooth brushing on subgingival plaque composition. The studies were performed in different populations including chronic periodontitis, periodontal maintenance and refractory subjects. For all studies, each subject was examined for clinical parameters at up to 168 sites and subgingival plaque samples were taken from the mesial aspect of each tooth and examined for their content of specific bacterial species using checkerboard DNA-DNA hybridisation techniques. Repeated supragingival plaque removal used in conjunction with scaling and root planing only or combined with other periodontal therapies resulted in improvements in clinical parameters as well as significant decreases in the counts of subgingival species, including those associated with periodontal disease aetiology. Meticulous tooth brushing provided similar clinical and microbial improvements. Meticulous removal of supragingival plaque has beneficial effects on clinical parameters of periodontal disease and on the nature of the microbiota that colonises both above and below the gingival margin and appropriately has been a major focus in the prevention and control of dental diseases, particularly periodontal disease.

Hypoalbuminemia is a marker of overhydration in chronic maintenance patients on dialysis.

Hypoalbuminemia is an important risk factor for increased morbidity and mortality in patients on dialysis. Hypoalbuminemia is usually attributed to malnutrition or a state of chronic inflammation. However, hypoalbuminemia could result from hemodilution caused by chronic volume expansion. We prospectively evaluated 142 patients on chronic dialysis for 12 consecutive months (mean age: 62 +/- 14 years; 41% women, 37% African American, 43% diabetic, 27% peritoneal dialysis). Intracellular (ICW) and extracellular (ECW) water content was estimated using single frequency bioelectrical impedance. Values in each albumin grouping (group 1, < 3.5 g/dl; group 2, 3.5-4.0 g/dl; group 3, > 4.1 g/dl) are expressed as annual mean +/- SEM. Group 1 patients had lower body weight, body mass index, blood urea nitrogen, serum creatinine, dietary protein intake, and ICW content than those in groups 2 and 3. ECW was significantly increased in group 1 when compared with groups 2 and 3 (p < 0.001). A significant correlation was found between ECW and serum albumin concentration (R = 0.2230; p < 0.0001). Resistance and reactance were decreased in group 1 when compared with groups 2 and 3 (p < 0.05 and 0.001, respectively), causing the resultant bioimpedance vector to move away from the normal population range into the overhydration boundaries. We conclude that, in addition to malnutrition and chronic inflammation, overhydration is a contributor to hypoalbuminemia in patients on chronic dialysis.

Transient neuronal but persistent astroglial activation of ERK/MAP kinase after focal brain injury in mice.

Astrogliosis is a nearly ubiquitous response to a variety of insults to the central nervous system (CNS). This reaction is triggered rapidly, but can persist for years after the initial trauma. Little is known about the signaling mechanisms responsible for this activation and its chronic maintenance. Extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) activation is implicated in several functions important to the reactive glial phenotype such as cellular proliferation and motility. Here we utilize immunohistochemistry with a phosphorylation state-specific antibody (pERK) to characterize the temporal and spatial pattern of ERK/MAPK activation in neurons and glia following a forebrain stab lesion (FSL) in mice. Early activation (1 h) was primarily in perilesional neuronal elements, particularly of the hippocampus. Occasional perilesional glia were also positive for pERK. Additionally, ependymal cells bilaterally stained prominently for pERK. These patterns of pERK immunoreactivity at 1 h were abolished by pretreatment with the selective MEK inhibitor, SL327. ERK/MAPK activation at later time points between 1 day (d) and 30 d was primarily restricted to perilesional astrocytes with maximum labeling at 3 d. However, pERK-positive astrocytes represented only a subset of total GFAP-positive cells and were found more proximal to the lesion suggesting specific functional activation of these cells. Finally, immunostaining for the phosphorylated form of cAMP response element-binding (CREB) protein, a downstream target of the ERK/MAPK cascade, was increased in perilesional glia 7 d after FSL. Sustained activation of the ERK/MAPK signaling pathway in perilesional reactive glia suggests a critical role for this cascade in astrogliosis.

Body composition analysis by bioelectrical impedance in chronic maintenance dialysis patients: Comparisons to the National Health and Nutrition Examination Survey III

Objective: To compare bioelectrical impedance analysis derived parameters in chronic maintenance dialysis patients to those obtained in National Health and Nutrition Examination Survey (NHANES) III. Design: Cross-sectional nutritional surveillance study. Setting: Hospital-based, not-for-profit chronic maintenance dialysis center. Patients: A total of 913 chronic maintenance dialysis patients and a subset of 10,263 subjects from NHANES III who underwent bioelectrical impedance analysis. Independent (Predictor) Variables: Bioelectrical impedance parameters including resistance, reactance, phase angle, and total body capacitance. Main Outcome Measures: Total body water, intracellular and extracellular water, body cell mass, fat free mass, fat mass. Results: Relative to NHANES III, end-stage renal disease patients have lower resistance (3%), reactance (26%), phase angle (28%); and intracellular water (9%) values, whereas extracellular water content is 17% higher (P <.001). In addition, body cell mass, fat free mass, and fat mass were lower in end-stage renal disease patients when compared with NHANES III subjects (9%, 3%, and 12%, respectively; P <.001). Conclusions: End-stage renal disease patients have a lower tissue mass than the general population and remain in a state of overhydration while on chronic maintenance dialysis therapy. © 2003 by the National Kidney Foundation, Inc.

Efficacy of Hepatitis B Immunization in HIV-Infected Patients on Hemodialysis (HD)

Patients on HD are at a high risk of hepatitis B infection. Therefore hepatitis B vaccination is recommended for all HD patients, although compared with adults with normal immune status, the protective antibody response is lower and ranges from 34–88%. We hypothesized that HIV infected patients on HD are likely to have even lower antibody responses to hepatitis B vaccination. We therefore reviewed the immunization history of 16 HIV-infected dialysis patients who received chronic maintenance HD at our dialysis units. The mean age of the patients was 43 ± 11 (mean ± SD). Of the 16 patients the majority were black males (13). The mean CD 4 count of these patients was 261 ± 206 (mean ± SD, range: 18–668 cells/μL). The mean viral load was 96727 ± 184084 (range 50–650846 copies/ml). Six patients had undetectable plasma viral loads. Of the 16 patients, 10 had protective antibodies (HBs Ab ≥ 10 mIU/ml). Of these 10 patients, 3 had positive Hepatitis core antibody suggesting previous viral exposure, another 3 were negative for HBcAb and in the remaining 4 HBcAb was unavailable. Five of the 10 patients with protective antibody received vaccination after starting dialysis. Pearson product moment correlation showed negative correlation of HBsAb with viral load, r = − 0.45, p value = 0.07. No correlation was found between CD4 count and response to vaccination. We conclude that HIV-infected HD patients develop protective antibodies at a rate similar to HIV-negative HD patients.

Baboons undergoing orthotopic concordant cardiac xenotransplantation surviving more than 300 days: Effect of immunosuppressive regimen

Objective: We reviewed long-term survival among hosts in 3 consecutive series of a rhesus monkey-baboon orthotopic cardiac xenotransplantation model with reference to host immune response, including the effectiveness in preventing rejection and limiting toxicity concerning infection, to evaluate specific immunosuppressive regimens for long-term outcomes. Methods: Six juvenile baboons surviving more than 300 days after transplantation were reviewed. Regimen A consisted of splenectomy, FK506, methotrexate, and antilymphocyte globulin. Regimen B consisted of pretransplantation and chronic maintenance with cyclosporine A (INN: ciclosporin), methotrexate, and antithymocyte globulin. Regimen C was the same as regimen B plus pretransplantation total lymphoid irradiation and intraoperative donor bone marrow cell infusion. Rejections were detected by means of echocardiography. Results: Long-term survivors in 3 groups were followed for a range of 332 to 515 days (mean, 436 days). Rejection frequency in regimens A, B, and C was 0.35, 0.58, and 0.18 per month, and rescue therapy days were 23 (4.8%), 123 (9.5%), and 20 (2.4%), respectively (P <.0001). Infection frequency was 0.58, 0.56, and 0.19 per month, and therapy days were 192 (38.2%), 164 (12.6%), and 7 (0.9%), respectively (P <.0001). Concerning the host immune response, interleukin 2-activated T cells of all groups during rejection-free periods showed lower numbers compared with those of control animals (P <.0005), and regimen C was the lowest among 3 groups (P <.01). The production of xenoantibody was sufficiently attenuated in all groups. Conclusion: Regimen C leads to long-term survival with fewer rejection and infection episodes by means of suppression of the interleukin 2 pathway and xenoantibody production.J Thorac Cardiovasc Surg 2003;125:60-70

The health and productivity cost burden of the "top 10" physical and mental health conditions affecting six large U.S. employers in 1999.

A multi-employer database that links medical, prescription drug, absence, and short term disability data at the patient level was analyzed to uncover the most costly physical and mental health conditions affecting American businesses. A unique methodology was developed involving the creation of patient episodes of care that incorporated employee productivity measures of absence and disability. Data for 374,799 employees from six large employers were analyzed. Absence and disability losses constituted 29% of the total health and productivity related expenditures for physical health conditions, and 47% for all of the mental health conditions examined. The top-10 most costly physical health conditions were: angina pectoris; essential hypertension; diabetes mellitus; mechanical low back pain; acute myocardial infarction; chronic obstructive pulmonary disease; back disorders not specified as low back; trauma to spine and spinal cord; sinusitis; and diseases of the ear, nose and throat or mastoid process. The most costly mental health disorders were: bipolar disorder, chronic maintenance; depression; depressive episode in bipolar disease; neurotic, personality and non-psychotic disorders; alcoholism;, anxiety disorders; schizophrenia, acute phase; bipolar disorders, severe mania; nonspecific neurotic, personality and non-psychotic disorders; and psychoses. Implications for employers and health plans in examining the health and productivity consequences of common health conditions are discussed.