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Pedro Aljama

Publications and source records attributed to Pedro Aljama.

At least 19 recordsLinked to original sources
PubMed2006

A prospective multicentre study of the role of anaemia as a risk factor in haemodialysis patients: the MAR Study.

BACKGROUND: Retrospective studies have shown hospitalization and mortality rates during haemodialysis (HD) to be associated with anaemia. METHODS: The prospective, multicentre Morbidity-and-mortality Anaemia Renal (MAR) study was designed to establish the burden of anaemia by controlling for other risk factors. Charlson index was used for comorbid adjustment. Finally, 1428 patients from 119 centres (60% men, aged 64.4 years, time on HD 15.3 months, Charlson comorbidity index 6.5 +/- 2.3) completed follow-up. They had hypertension (75.8%), diabetes mellitus (25.9%), heart failure (13.9%) and coronary disease (16.7%). Of the total patients, 94.8% were receiving erythropoietin (111.6 +/- 70.6 U/kg/week) and 76.7% i.v. iron, and haemoglobin (Hb) at inclusion was 11.7 +/- 1.5 g/dl. RESULTS: Hospitalization rate was 1.1 admissions/patient/year. Yearly mortality was 12% [35% cardiovascular (CV)]. The relative risk and confidence interval (CI) for hospitalization and death were 0.86 (0.81-0.91) and 0.82 (0.73-0.91), respectively, per 1 g/dl increase in initial Hb after adjustment for comorbidity, vintage, aetiology, access type, albumin and Kt/V. The probability of remaining free from hospitalization (CI) was 0.34 (0.27-0.41) for initial Hb <10 g/dl, 0.47 (0.41-0.53) for Hb 10-11 g/dl, 0.54 (0.49-0.59) for Hb 11-12 g/dl, and 0.63 (0.59-0.67) for Hb >12 g/dl. Same analysis for patient survival was 0.77 (0.71-0.83) for Hb <10 g/dl vs 0.82 (0.77-0.87) for Hb 10-11 vs 0.89 (0.86-0.92) for Hb 11-12 vs 0.92 (0.90-0.94) for Hb > 12 g/dl, P < 0.001. The Cox regression model for hospitalization-free survival included the risk factors initial Hb (relative risk 0.86 per 1 g/dl increase, P < 0.001) Charlson, albumin and prior CV event. CONCLUSION: Hb level predicted 1-year-survival and hospitalization. This effect persisted after adjustment for comorbidity and other prognostic factors.

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PubMed2006

On-line hemodiafiltration reduces the proinflammatory CD14+CD16+ monocyte-derived dendritic cells: A prospective, crossover study.

It is not known whether high convective transport may have a role in modulating the chronic inflammation of hemodialysis (HD) patients. The aim of this study was to evaluate the effect of on-line hemodiafiltration (OL-HDF) on proinflammatory peripheral monocytes: Percentage of CD14+CD16+ cells and their telomere length and spontaneous or bacterial DNA-induced production of cytokines (TNF-alpha and IL-6). In a prospective, crossover study, 31 patients who were on high-flux HD (HF-HD) were evaluated. Patients underwent the following sequence of treatments (4 mo each): HF-HD (basal), OL-HDF (period 1), HF-HD (period 2), OL-HDF (period 3), and HF-HD (period 4). The dialysis characteristics were similar in the two modalities; the only difference was a higher convective transport in the OL-HDF than in the HF-HD. All patients who were on OL-HDF periods showed a significantly lower number of CD14+CD16+ cells than on HF-HD (18.5 +/- 2.3 basal versus 13.6 +/- 2.9 period 1 and 13.9 +/- 2.3 period 3; P = 0.001). By contrast, HF-HD restored the number of CD14+CD16+ cells to the basal values (19.2 +/- 2.8 and 18.6 +/- 1.4, periods 2 and 4, respectively; NS). During OL-HDF periods, the reduction of CD14+CD16+ was paralleled by a decreased number of short telomere cells. Spontaneous or bacterial DNA-induced production of cytokines (TNF-alpha and IL-6) was increased in HF-HD as compared with OL-HDF. In conclusion, these results demonstrate that as compared with HF-HD, OL-HDF markedly reduces the number of proinflammatory CD14+CD16+ cells and the production of TNF-alpha and IL-6. Future studies are needed to assess the possible therapeutic effect of convective transport on chronic inflammation that is associated with HD.

Adult↗
PubMed2006

Microinflammation in hemodialysis is related to a preactivated subset of monocytes.

Increased percentage of monocytes with low CD14 expression and that co-express CD16 (CD14+/CD16+) have been reported in hemodialysis (HD) patients. We sought to determine whether CD14+/CD16+ monocytes in HD therapy are sensibilized cells to a proinflammatory activity. Cells from 32 HD patients, and from 9 Systemic Lupus Erythematosus (SLE), 9 individuals with human immunodeficiency virus (HIV)-1- and 15 healthy controls were studied. Cells were analyzed by means of flow cytometry for CD14/CD16 expression and immune function (cytokine, chemokines, and sialoadhesin expression), and phagocytosis. Increased percentage of CD14+/CD16+ monocytes was observed in HD patients. Compared with CD14++ monocytes, the CD14+/CD16+ monocytes exhibited increased expression of proinflammatory cytokines and markers of differentiated cells. In addition, these monocytes showed an increased phagocytic activity. Similarly, CD14+/CD16+ monocytes from SLE and HIV patients showed increased inflammatory activity as compared with CD14++ cells. These results support that CD14+/CD16+ monocytes from HD patients evidence characteristics of primed prestimulated proinflammatory cells, similar to data observed in SLE and HIV.

Adult↗
PubMed2005

Cytometric bead array (CBA) for the measurement of cytokines in urine and plasma of patients undergoing renal rejection.

Renal rejection is associated with an active immune response regulated by cytokines and in which immunocompetent cells are involved. Previous studies have measured high levels of cytokines in the urine and plasma in various renal dysfunction states. However, some methods used to measured cytokines hinder their use as a diagnostic tool in renal rejection. In this report, cytokine levels were determined in the plasma and urine of kidney transplant patients, with renal rejection and without it, using a cytometric bead array (CBA) technique. Concentrations of six human cytokines (IL-2, IL-4, IL-5, IL-10, TNF-alpha and INF-gamma) were established. Results show that patients who develop renal rejection presented high levels of IL-10 and IFN-gamma cytokines in plasma and urine compared to patients without renal rejection. The CBA technique displayed greater sensitivity in the determination of cytokines in urine than the conventional ELISA technique. Finally, when standard cytokines in plasma and in urine were compared, it was observed that, in plasma, levels of IL-4, IL-5, IL-10, TNF-alpha and IFN-gamma were detected, whereas in urine the levels detected were of IL-4, IL-5, IL-10 and IFN-gamma. These results indicate that the CBA assay is a sensitive method to measure cytokines in urine. In kidney transplant patients undergoing acute renal rejection, the presence of cytokines in urine reflects renal damage and could be a useful method in the diagnosis of renal rejection.

Adult↗
PubMed2005

Pathochemical toxicity of perfluorocarbon-5070, a liquid test performance fluid previously used in dialyzer manufacturing, confirmed in animal experiment.

In the light of clustered deaths in late 2001 associated with hemodialysis (HD), this article analyzes the pathochemical toxicity of the perfluorocarbon-5070 (PF-5070), a liquid used as test performance fluid for detecting capillary leaks during dialyzer manufacturing. Residual PF-5070 in some Athane dialyzers of the involved brands was infused in the injured patients during hemodialysis. The clinical presentation was in contrast with other previously described severe reactions to HD. Foam material was discovered in the right ventricle and caval vein of the patients who underwent postmortem examination. Deaths were attributed to gas embolism without the external causes identified. To explore the pathochemical toxicity of the inert liquid PF-5070, an animal model was developed. In a rabbit model, single slug intravenous injections as bolus of increasing doses of PF-5070 were performed. In a first set of experiments, three groups of three rabbits were administered increasing doses of PF-5070 at 4, 40, or 160 microl/kg. After intravenous injection, the animals were observed for clinical signs of adverse effects and underwent autopsy after death. Doses were normalized to animal body weight to allow comparison with supposed patient exposure. Five of nine rabbits died soon after PF-5070 dosing: One rabbit died within 4 h in the 4 microl/kg group, one rabbit died within 30 min in the 40 microl/kg group, and three rabbits died within 30 min in the 160 mul/kg group. In a second set of experiments, six rabbits were injected with a lethal dose of PF-5070 to analyze clinical symptoms and pathophysiology. All rabbits died on the day of dosing and displayed neurologic disorders (paralysis, nystagmus, rigidity, convulsions), then breathing abnormalities (rapid breathing, salivation, dark mucous membrane), and fatal collapse. Autopsy of rabbits showed evidence of gas retention in the lung tissue and gas bubbles in the right cardiac cavities. Histologic findings included alveolar hemorrhage with pulmonary edema, cerebellum, and cortex patchy areas of infarction. Single-dose intravenous administration of PF-5070 reproduced in a rabbit model the pathophysiologic effects observed in the hemodialysis patients. Severity of the symptoms observed in the animals was dose-dependent. Clinical and pathologic findings can be explained by the capacity of perfluorocarbon to emulsify blood at body temperature, to increase partial pressure in the pulmonary capillary bed, and to form bubbles in the pulmonary capillary circulation, thus blocking lung and visceral perfusion. Such experimental findings indicate the toxicity of PF-5070 administered intravenously and make the pathochemical toxicity link with the hemodialysis-related deaths caused by the presence of residues of PF-5070 in the Althane dialyzers. We conclude, in light of this outbreak and the subsequent investigations, that liquid PF-5070 is a highly toxic compound when administered intravenously because of its emulsifying properties. The use of PF-5070 or any liquid fluorocarbon compounds in medical devices with blood contact and particularly in the dialyzer manufacturing should be considered with caution.

Animals↗
PubMed2005

Lymphocyte apoptosis: role of uremia and permeability of dialysis membrane.

BACKGROUND: Uremia is associated to host defense mechanism disorders. Lymphocyte apoptosis, which may cause alteration of the immune system, is increased in uremic patients. The aim of the present study was to determine if, in addition to uremia, dialysis membranes with different biocompatibility and permeability have an effect on lymphocyte apoptosis. METHODS: Cell apoptosis and Fas expression were assessed using flow cytometry in four groups of patients: (1) uremic non-dialyzed (Non-D) patients; (2) hemodialysis (HD) patients on hemophan; (3) low-flux polysulfone, and (4) high-flux polysulfone membrane. Ten healthy volunteers were used as controls. RESULTS: At baseline, lymphocytes from patients on hemophan showed an increase in apoptosis (18.4 +/- 6.9%) as compared with Non-D (7.2 +/- 2.8%; p < 0.001), low-flux (6.4 +/- 2.4%; p < 0.001), high-flux (2.6 +/- 1.2%; p < 0.001) and controls (2.0 +/- 1.0%; p < 0.001). Fas expression was similar in lymphocytes from Non-D and hemophan dialyzed patients (40.5 +/- 5% vs. 40.4 +/- 6%), and in both groups it was greater than low-flux (30%+/-7%; p < 0.001), high-flux (11 +/- 4%; p < 0.001) and controls (12.6 +/- 3%; p < 0.001). When lymphocytes were cultured for 48 h, apoptosis was similar in Non-D and hemophan (27.0 +/- 4.3% vs. 27.1 +/- 6.9%); apoptosis of lymphocyte from patients on low-flux (14.1 +/- 3.5%) was greater than on high-flux polysulfone membrane (7.0 +/- 2.0%; p < 0.001). CONCLUSION: These findings suggest that in dialysis patients lymphocyte apoptosis is influenced not only by the biocompatibility but also by the permeability of the dialysis membrane.

Adult↗
PubMed2005

Stress-induced premature senescence in mononuclear cells from patients on long-term hemodialysis.

BACKGROUND: Repeatedly stimulated mononuclear cells may become senescent prematurely as a result of frequent activation-induced replication. In hemodialysis patients, mononuclear cells are activated repeatedly with each hemodialysis procedure. Characteristics of senescent mononuclear cells include telomere length shortening, increased p53 expression, CD14dim/CD16bright expression, and interleukin overproduction. METHODS: Peripheral mononuclear cells from 15 hemodialysis patients and 15 age-matched controls were evaluated. Telomere length was assessed by means of fluorescence in situ hybridization in flow cytometry. Expression of p53, CD14/CD16, and intracellular cytokine production (interleukin-1beta [IL-1beta], IL-6, and IL-4) was evaluated by means of flow cytometry using specific antibodies. RESULTS: Features of senescence were found in a subpopulation of mononuclear cells: (1) accelerated telomere shortening, (2) increased p53 expression, (3) CD14dim/CD16bright expression, and (4) cytokine overproduction (IL-1beta, IL-6, and IL-4). Telomere length shortening was present in 40% +/- 6% of cells from hemodialysis patients compared with less than 5% from age-matched controls. Percentage of cells with short telomeres correlated positively with serum C-reactive protein level, which reflects inflammation. p53 expression was increased in mononuclear cells from hemodialysis patients. Mononuclear cells from hemodialysis patients with decreased telomere length mainly showed the CD14dim/CD16bright phenotype; conversely, cells with normal telomeres presented the CD14bright/CD16dim phenotype. Finally, mononuclear cells from hemodialysis patients, but not controls, spontaneously produced the proinflammatory cytokines IL-1beta and IL-6. CONCLUSION: This study shows the presence of a prematurely senescent subpopulation of peripheral mononuclear cells in hemodialysis patients. These senescent cells probably result from repeated activation and may have a pathophysiological role in the chronic inflammation described in hemodialysis patients.

Adult↗
PubMed2005

Mild hyperphosphatemia and mortality in hemodialysis patients.

BACKGROUND: Severe hyperphosphatemia (serum phosphate level > 6.5 mg/dL [>2.10 mmol/L]) has been associated directly with increased overall and cardiovascular mortality in hemodialysis (HD) patients. Currently, clinical guidelines recommend maintaining phosphate levels within normal range (3.0 to 5.0 mg/dL [0.97 to 1.61 mmol/L]). However, mild hyperphosphatemia (phosphate, 5.01 to 6.5 mg/dL [1.62 to 2.10 mmol/L]) is still to be addressed as an independent mortality risk factor in HD patients. METHODS: The association between serum phosphate level and survival in maintenance HD patients was explored prospectively in 385 incident patients from 1990 to 2001. Cox regression was performed using phosphate level as: (1) a continuous variable; (2) stratified as low phosphate level (<3 mg/dL [<0.97 mmol/L]), normal phosphate level (3.0 to 5.0 mg/dL [0.97 to 1.61 mmol/L]), mild hyperphosphatemia (phosphate, 5.01 to 6.5 mg/dL [1.62 to 2.10 mmol/L]), or severe hyperphosphatemia (phosphate > 6.5 mg/dL [>2.10 mmol/L]); and (3) phosphate level greater or less than 5.0 mg/dL (> or <1.61 mmol/L). RESULTS: As a continuous variable, relative risk (RR) for mortality for serum phosphate level was 1.26 (confidence interval [CI], 1.09 to 1.47) after adjusting for age, sex, diabetes, Kt/V, albumin level, hemoglobin level, serum calcium level, normalized protein catabolic rate, and parathyroid hormone level. Compared with a normal phosphate level, mild hyperphosphatemia showed an adjusted mortality RR of 1.94 (CI, 1.17 to 3.19), and severe hyperphosphatemia, an RR of 2.02 (CI, 1.10 to 3.73). Patients with a phosphate level cutoff value greater than 5.0 mg/dL (>1.61 mmol/L) showed a 2-fold increase in adjusted RR for mortality compared with those with a phosphate level of 5.0 mg/dL or less (< or =1.61 mmol/L; RR, 2.11; CI, 1.44 to 3.08). CONCLUSION: A serum phosphate level greater than 5.0 mg/dL (>1.61 mmol/L) is independently associated with an increased risk for death in HD patients.

Aged↗
PubMed2005

Necrotizing glomerulonephritis and pulmonary hemorrhage associated with carbimazole therapy.

Methimazole, carbimazole, and propylthiouracil (PTU) are the mainstays of antithyroid drug therapy. Adverse effects of these drugs have been documented in less than 15% of patients undergoing treatment for hyperthyroidism. Common problems include fever, skin rash, urticaria, arthralgias, and arthritis. Vasculitis associated with antineutrophil anticytoplasmic antibodies (ANCA) has been reported on several occasions following treatment with PTU. However, vasculitis rarely appears to be associated with carbimazole. We report the clinical history of a woman with a necrotizing glomerulonephritis and pulmonary hemorrhage associated with carbimazole therapy.

Antithyroid Agents↗
PubMed2005

Antibody-mediated pure red cell aplasia (PRCA): ensuring future progress by collecting data from a registry.

The recent emergence of antibody (Ab)-mediated pure red cell aplasia (PRCA) resulting from administration of certain erythropoiesis-stimulating agents (ESAs) has heightened awareness of the potential for this disorder in patients receiving ESAs for anaemia associated with chronic kidney disease (CKD). The Spanish Society of Nephrology sponsored an independent registry for analysis of patients who developed epoetin-induced, Ab-mediated PRCA in Spain. Twelve patients from 11 regional hospitals were included in the Spanish PRCA registry from November 2000 to December 2002 that met the criteria for Ab-mediated PRCA. Patients were reported using a standardized form specifically developed for PRCA, and serum samples were analysed in a central laboratory at Reina Sofia University Hospital in Cordoba, Spain. The characteristics of these patients, their serological and haematological results, and the outcomes of immunosuppressive therapies are presented. The Spanish PRCA registry serves as a model for establishing an independent global PRCA registry sponsored by the various nephrology societies in European Union countries, and elsewhere and coordinated by key investigators from the respective countries.

Adult↗
PubMed2005

Replicative senescence in patients with chronic kidney failure.

BACKGROUND: Chronic activation of immunocompetent cells may lead to stress-induced premature senescence (SIPS); these senescent cells are characterized by a decrease in telomere length. The present study evaluates SIPS in circulating immunocompetent cells from predialysis patients, patients on hemodialysis, and in renal transplant patients with normal renal function. METHODS: Determination of telomere length by flow-fluorescence in situ hybridization (FISH), expression of surface molecules, and evaluation of apoptosis was performed by flow cytometry. RESULTS: In uremic predialysis patients, we observed a subpopulation of lymphocytes with short telomeres. However, in this population of patients we did not observe SIPS mononuclear cells. In hemodialysis patients, we found a subpopulation of SIPS mononuclear cells that also showed phenotypic changes of proinflammatory activity. Finally, transplant patients with normal renal function also exhibited a subpopulation of SIPS lymphocytes, which can be attributed to chronic lymphocyte activation induced by the major histocompatibility complex. CONCLUSION: In chronic kidney disease patients, immunocompetent cells undergo SIPS, a process associated with chronic cell activation and induced by numerous stimuli including uremia, hemodialysis membranes, and bacterial products. Because SIPS immunocompetent cells are activated cells with proinflammatory features and live longer in peripheral blood, it is likely that SIPS cells contribute significantly to the chronic inflammatory state of patients with advanced renal failure.

Apoptosis↗
PubMed2005

Monocytes from dialysis patients exhibit characteristics of senescent cells: does it really mean inflammation?

Hemodialysis treatment induces mononuclear cell activation particularly if cellulosic hemodialysis membrane is used. In normal cells, repeated activation induce a process of accelerate cellular senescence. The aim of the present study was to evaluate whether the mononuclear cell activation associated to hemodialysis with cellulosic membranes favors a process of accelerate senescence in mononuclear cells. Our results show that mononuclear cells from patients dialyzed with cellulosic membranes, exhibit: decrease telomere length, increase percentage of cells CD14dim/CD16bright and increase production of IL-1beta, IL1Ra and IL6 cytokines. After culture in vitro, these cells shown increase susceptibility to undergoing spontaneous apoptosis, that is enhanced by IL-4 and prevented by IL-1beta or LPS. All of these characteristics have been reported associated to senescence of monocytes, and not are observed in cells from controls subjects or patients dialyzed with non-cellulosic membranes, suggesting that hemodialysis with cellulosic membranes induce a process of senescence in mononuclear cells.

Adult↗
PubMed2004

Marked reduction in the prevalence of hepatitis C virus infection in hemodialysis patients: causes and consequences.

BACKGROUND: The prevalence of hepatitis C virus (HCV) infection in hemodialysis (HD) patients has decreased significantly in the course of the past decade in most HD units. The objective of this study is to analyze the causes of this reduction and obtain additional information for the near future that could be of use for health services planning. METHODS: All patients who underwent HD in the Province of Cordoba, Spain, between January 1992 and December 2002 were studied. We analyzed annual exclusions from the HD program of HCV-positive patients (deaths and kidney transplantations) and inclusions (predialysis patients, patients with chronic graft rejection, and HD patients with acute HCV infection). The trend in the time series of measurements was calculated by means of exponential smoothing with 2 parameters. RESULTS: In December 1992, the prevalence of antibody to HCV (anti-HCV) was 24% (N = 54), whereas by December 2002, it had decreased to 9.2% (N = 35). Of 657 predialysis patients included in the maintenance HD program, 2.8% (n = 19) were positive for anti-HCV. Annual mean incidence of acute HCV infection was 0.5%, and the median was 0.32%. Mean crude annual mortality rates were 12.2% for anti-HCV-positive patients versus 9.9% for anti-HCV-negative patients. The trend in this time series suggests that by 2006, the prevalence of anti-HCV in HD patients will be approximately 2.5%. CONCLUSION: Causes implicated in the reduction in prevalence of HCV infection in HD patients are a greater mortality rate, stabilization of the incidence of acute HCV infection, and a low percentage of HCV infection in predialysis patients. By the end of 2006, the rate of HCV infection in HD patients will be very close to that of the predialysis population.

Adult↗
PubMed2004

The impact of donor age on the results of renal transplantation.

BACKGROUND: The use of elderly donors is becoming more frequent. An increase in the donor's age is associated with a greater incidence of delayed graft function (DGF), chronic allograft nephropathy (CAN) and worse graft survival. Poor renal graft function is a risk factor for cardiovascular (CV) complications and, finally, for mortality of the patients. METHODS: A total of 3365 adult patients transplanted in 1990 (n = 824), 1994 (n = 1075) and 1998 (n = 1466) with a functioning graft after the first year were included. The impact of donor age on renal function, DGF, acute rejection and other clinical factors was evaluated according to two donor and recipient age categories: young (< 60 years old) and elderly (> or =60 years old). Additionally, donor age was categorized by decades for the analysis of patient and graft survival, acute rejection and CV mortality. RESULTS: Donor mean age significantly increased during the three transplantation periods. A total of 478 out of 3365 donors were older than 60 years. Elderly donors showed an increased risk of DGF (38.9 vs 28.8%) and CAN (56.8 vs 46.2%). Mean serum creatinine at 3 and 12 months and proteinuria were significantly higher in the old donor group. Incidence and severity of acute rejection were similar in both groups. Graft and patient survival were significantly lower in the old donor group. Also, risk of mortality due to CV events was also significantly higher. A linear increase in risk of graft loss, patient death or CV mortality was observed when donor age was divided into 10 year increase subsets. CONCLUSIONS: Donor age is a strong predictor of CAN and graft loss. Patient survival is also affected by donor age, particularly by a higher risk of CV mortality.

Adult↗
PubMed2004

The imbalance in the ratio of Th1 and Th2 helper lymphocytes in uraemia is mediated by an increased apoptosis of Th1 subset.

BACKGROUND: In uraemia there is a reduction in the total number of T lymphocytes and an imbalance in the ratio of Th1/Th2 T-helper (Th) lymphocytes. A higher rate of apoptosis in T lymphocytes has been reported in haemodialysis patients. The aims of the present study were to assess the Th1/Th2 pattern in uraemia and to evaluate whether a relative increase in Th1 apoptosis may explain the Th1/Th2 imbalance observed in uraemic patients. METHODS: Seventeen non-dialysed uraemic patients were evaluated; eight healthy volunteers served as controls. Intracellular interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were measured by direct intracellular immunofluorescence and flow cytometry. Apoptosis was determined by flow cytometry using annexin V or TUNEL. Mechanisms of apoptosis were assessed by determination of Fas and Bcl-2 expression. RESULTS: Cell production of cytokines is significantly higher in uraemic patients than in controls. In addition, in uraemic patients only 5.1+/-2.1% of the T lymphocytes contained IFN-gamma (Th1 cells) while 61.9 +/- 14.8% contained IL-4 (Th2 cells) (P < 0.0001). The percentage of apoptosis was 29.6 +/- 6.3% and 4.7 +/- 1.6% in Th1 and Th2 lymphocytes, respectively (P < 0.001). Fas expression was higher in Th1 than in Th2 cells and the expression of Bcl-2 was lower in Th1 than in Th2 cells. The apoptosis induced by anti-Fas antibodies was similar in both types of lymphocytes. CONCLUSIONS: In uraemia there is a reduction in the proportion of Th1 lymphocytes due to a higher rate of apoptosis in this subset of lymphocytes. Th1 from uraemic patients show a higher expression of Fas and a lower expression of Bcl-2 than Th2. This makes uraemic Th1 cells more susceptible to apoptosis. The Th1/Th2 imbalance may contribute to alterations in cellular immunity observed in chronic kidney disease patients.

Adult↗
PubMed2003

Dynamics of PTH secretion in hemodialysis patients as determined by the intact and whole PTH assays.

BACKGROUND: Renal hyperparathyroidism is assessed by measurement of parathyroid hormone (PTH) levels. The intact PTH assay (I-PTH) not only reacts with 1-84 PTH but also with large, truncated fragments of non-1-84 PTH. Because the whole PTH assay (W-PTH) is specific for 1-84 PTH, non-1-84 PTH is determined by subtracting W-PTH from I-PTH values. These large circulating PTH fragments may exert a hypocalcemic effect by contributing to skeletal resistance to 1-84 PTH. METHODS: The dynamic secretion of both 1-84 PTH and non-1-84 PTH was evaluated during the induction of hypo- and hypercalcemia in eight hemodialysis patients. RESULTS: The basal ionized calcium concentration was 1.23 +/- 0.03 mmol/L at which time I-PTH, W-PTH, and non-1-84 PTH values were 276 +/- 78 pg/mL, 164 +/- 48 pg/mL, and 102 +/- 28 pg/mL, respectively. The induction of hypo- and hypercalcemic changes resulted in a sigmoidal response for all three PTH moieties, I-PTH, W-PTH, and non-1-84 PTH. During hypocalcemia, maximal values of W-PTH were greater than those of non-1-84 PTH. But during hypercalcemia, minimal values of W-PTH and non-1-84 PTH were similar. Neither the set points nor the basal/maximal ratios for W-PTH, I-PTH, and non-1-84 PTH were different. At the baseline ionized calcium concentration, the W-PTH (1-84 PTH)/non-1-84 PTH ratio was 1.53 +/- 0.15. Changes in ionized calcium resulted in a sigmoidal relationship with hypocalcemia, increasing this ratio to a maximum of 2.01 +/- 0.30 and hypercalcemia decreasing this ratio to a minimum of 1.18 +/- 0.15 (P < 0.01 vs baseline for both hypo- and hypercalcemia). CONCLUSION: Although acute changes in serum calcium produce similar secretory responses in 1-84 PTH and non-1-84 PTH, the secretory responses are not proportional for these PTH moieties. Changes in the serum calcium concentration modulate the ratio of 1-84 PTH/non-1-84 PTH in a sigmoidal pattern with hypocalcemia maximizing this ratio. Whether changes in the 1-84 PTH/non-1-84 PTH ratio specifically modulate the calcemic action and other biologic effects of 1-84 PTH remain to be determined.

Aged↗