[Consensus guidelines for managing diabetic nephropathy: are they really valid?].
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Biomedical subjects
Publications and source records attributed to F de Alvaro.
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BACKGROUND: In the Irbesartan Diabetic Nephropathy Trial (IDNT), treatment with irbesartan demonstrated 23% and 20% reductions in the combined endpoint of doubling of serum creatinine (DSC), end-stage renal disease (ESRD) or death in patients with hypertension, type 2 diabetes and overt nephropathy compared to amlodipine and control respectively. A simulation model was developed to project long-term cost consequences of the IDNT in the Spanish setting. METHODS: A Markov model simulated progression from nephropathy to DSC, ESRD and death in patients with hypertension, type 2 diabetes and overt nephropathy. Treatment-specific probabilities were derived from IDNT. Country-specific ESRD-related data were retrieved from published sources. Delay in onset of ESRD, life expectancy and mean lifetime costs were calculated for patients with baseline age 59 years. Future costs were discounted at 6% per annum, and clinical benefits were discounted at 0% and 6% per annum. Extensive sensitivity analyses were performed. RESULTS: Onset of ESRD was delayed with irbesartan by 1.41 and 1.35 years versus amlodipine and control respectively. When a 25-year (lifetime) horizon was considered, delay in ESRD onset led to anticipated improvements in life expectancy (discounted at 6% shown in brackets) of 0.46 (0.21) years versus amlodipine and 0.75 (0.37) years versus control. Irbesartan was associated with cost savings of 13,673 Euro and 7,632 Euro patient versus amlodipine and control respectively. The results were robust under a wide range of plausible assumptions. CONCLUSIONS: Treating patients with hypertension, type 2 diabetes and overt nephropathy using irbesartan was both cost- and life-saving compared to amlodipine and control in the Spanish setting.
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Henoch-Schönlein purpura (HSP) is a necrotizing vasculitis affecting small vessels characterized by nontrombocytopenic purpura. The most characteristic clinical manifestations are purpura, arthritis, abdominal pain, abdominal bleeding and nephritis. Lung hemorrhage is a rare symptom associated with the HSP. Although the subclinical alterations of pulmonary function are frequent in patients with PSH without clinical lung manifestations, the presence of lung hemorrhage is an unusual symptom. We report a case of a patient with hemoptysis and HSP previously asymptomatic.
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Assessment of healthcare technology and economics can be used to assess the access to healthcare, its quality and efficacy as well as its cost and cost efficiency. This report addresses these issues for the provision of care for end-stage renal disease (ESRD) patients. An international comparison of access to ESRD treatment modalities was made with reference to the healthcare provider structure in a range of industrial countries. The countries were grouped into 'public' (Beveridge model), 'mixed' (Bismarck model) and 'private' (Private Insurance model). In 'public' provider countries, 20-52% of dialysis patients are treated with home therapies (haemodialysis and peritoneal dialysis), and the number of patients with renal transplants is 45-81% of all ESRD patients. In 'mixed' provider countries, only 9 17% of all dialysis patients are treated with home therapies, and 20-48% of ESRD patients have renal transplants. In 'private' provider countries, 17% of US and 6% Japanese dialysis patients are treated with home therapies. Japan has 0.3% and the US has 26% of ESRD patients who receive renal transplants. It thus seems that provider structure influences access to and choice of ESRD treatment. With a growing elderly population and longer life expectancy, there will be an increased requirement for ESRD treatments in all industrial countries. Equal access to, and quality of ESRD care in the future will require adequate funding and reimbursement strategies in a cost-constrained healthcare environment. growing elderly population, new and innovative healthcare technologies, increasing expectations of the population and the dilemma of economic constraints. Therefore, new disciplines such as health technology assessment and healthcare economics are developing to support the needs of health policy decision makers. Their main objective is to create a balance between the three key factors of a healthcare system: access to healthcare (equity for all), quality of healthcare (efficacy) and finally the cost or cost efficiency of healthcare provision [1; see also Lameire et al., this issue]. This report will assess access to healthcare in a very specific and very costly area that of end-stage renal disease (ESRD). An international comparison of access to ESRD treatment for patients from a series of industrial countries will be used as a means for evaluation of this access.
Long-term therapy with recombinant human erythropoietin (rhEPO) in uremic male patients undergoing hemodialysis has been followed by an increase in plasma levels of testosterone and a decrease in baseline levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The aim of the present study was to assess the effect of acutely administered rhEPO on FSH and LH responses to gonadotropin-releasing hormone (GnRH) in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Sixteen clinically stable male patients (age, mean+/-SEM, 45.3+/-3.9 years) with chronic renal insufficiency and 12 healthy volunteers with a normal renal function, matched for age and body mass index, were studied. All patients were on CAPD therapy for at least 3 months, and none of them received rhEPO therapy. Patients were moderately anemic (hemoglobin 11.0+/-0.3 g/dl) and showed testosterone levels significantly lower than those found in control subjects (3.47+/-0.37 vs. 6.91+/-0.49 ng/ml, p < 0.001). Each subject was tested with GnRH (100 microg i.v. as bolus) and with GnRH plus rhEPO (40 U/kg at a constant infusion rate for 30 min, starting 15 min before GnRH injection) on different days. Blood samples for FSH and LH were obtained between -30 and 120 min. In uremic patients the baseline FSH levels were higher than those found in control subjects (18.88+/-5.41 vs. 6.41+/-1.10 mU/ml, p < 0.05). After GnRH administration FSH values reached a maximum of 25.50+/-6.19 mU/ml in patients and of 12.50+/-2.02 mU/ml in controls (p < 0.05). rhEPO infusion produced a significant (p < 0.01) decrease in the area above the baseline value of FSH in uremic patients, with no other change in FSH responses to GnRH both in patients and controls. Baseline LH concentrations were significantly higher in patients than in controls (15.56+/-3.41 vs. 2.58+/-0.36 mU/ml, p < 0.001). LH peak and area under the curve of LH secretion after GnRH were significantly higher in patients than in controls (45.25+/-6.28 vs. 26.83+/-4.62 mU/ml, p < 0.05, and 77.02+/-11.30 vs. 34.40+/-5.22 mU x h/ml, p < 0.005, respectively). When GnRH was injected during the rhEPO infusion, a significant (p < 0.02) reduction in LH concentrations at 60, 90, and 120 min was found in uremic patients. Accordingly, the LH area under the curve was significantly reduced in patients (65.99+/-11.44 mU x h/ml, p < 0.05). rhEPO had no effect on GnRH-induced LH release in control subjects. These results suggest that acute rhEPO administration might reduce the exaggerated LH response to GnRH stimulation found in uremic male patients on CAPD.
Long-term complications of Insulin Dependent Diabetes Mellitus (IDDM) have been associated with several risk factors, particularly the degree of metabolic control and evolution time of the disease. A study was conducted with 219 randomly selected patients with IDDM at our clinic; evolutive, clinical and analytical parameters were assessed and conventional or multiple insulin therapy was evaluated. The classification of glycated hemoglobin (Hb A1c) in quartiles demonstrated a relatively higher incidence of diabetic retinopathy and nephropathy in the upper quartiles versus the lower quartile (p < 0.05). Likewise, patients with multiple insulin therapy had lower retinopathy (24.5% vs. 50.6, p < 0.001) and nephropathy rates (12.9% vs. 26.6%, p < 0.05) compared with those following a conventional insulin therapy. The multivariate analysis showed a statistically significant regression model (p < 0.001) for microalbuminuria level in patients with no established nephropathy; in these patients, the evolution time of IDDM and their Hb A1c level showed a positive independent association, and the use of multiple insulin therapy was a protective factor. The regression analysis of microalbuminuria levels compared with glycated hemoglobin in patients with no established nephropathy showed a value for Hb A1c of 9% as a break-point; from this point upwards microalbuminuria levels increased more markedly. The multivariate analysis here presented can help identify the presence of microalbuminuria in the pathological range in patients with IDDM followed at a hospital clinic from feasible clinical variables (evolution time, glycated hemoglobin level, program of insulin therapy used) establishing a metabolic objective which helps prevent the development of this complication.
The aim of this study was to evaluate the role of pulse oral calcitriol in the control of secondary hyperparathyroidism in peritoneal dialysis (PD) patients, addressing the effects after withdrawal. We studied 15 patients with intact parathyroid hormone (iPTH) plasma levels above 250 pg/mL. The initial calcitriol dose was 8 or 4 micrograms/week, administered in two doses, according to whether the iPTH plasma levels were above or below 400 pg/mL. This dose was modified during the follow-up according to the response. Serum iPTH levels decreased in all patients after the first month (559 +/- 243 to 212 +/- 94 pg/mL, p < 0.001). Serum calcium levels significantly increased during therapy, while serum phosphorus levels did not change. The mean duration of the treatment was 95 +/- 57 days. Nine patients reached the target iPTH levels without complications, and in 6 patients the treatment was interrupted because of hypercalcemia. One month after finishing pulse therapy, a significant decrease in serum calcium levels and an increase in iPTH levels were observed. These values were similar to baseline data and were significantly higher than those found during the pulse calcitriol period. Pulse oral calcitriol administration seems to be a short-term, efficient therapy for secondary hyper-parathyroidism in PD patients. However, after the end of pulse therapy, iPTH serum levels return to baseline values, suggesting long-term therapeutic failure.
Lactate (L)-containing dialysate has a low pH, responsible for its poor biocompatibility. Dial-ysate-containing bicarbonate (B) with a physiological pH is available. We compare the peritoneal functional effects of these two solutions. Eight patients were studied two weeks apart using two consecutive peritoneal kinetic tests to determine convective and diffusive mass transfer coefficient (MTC) capacities for different solutes. Both L and B solutions were identical, except for pH and buffer content. Peritoneal equilibration values at four-hour dwell time were similar for all solutes, except for urea (B: 0.91 +/- 0.05 vs L: 0.87 +/- 0.06, p < 0.05). Peritoneal MTC (B vs L) values for urea (19.6 +/- 6.6 vs 18.2 +/- 4.5), creatinine (8.8 +/- 4.8 vs 7.8 +/- 3.5), phosphate (7.7 +/- 4.6 vs 6.0 +/- 2.2), and potassium (13.3 +/- 5.6 vs 11.7 +/- 5.0) were slightly higher for B (NS). Glucose-MTC was slightly lower for B (6.2 +/- 3.3 vs 7.5 +/- 3.2, NS). Ultrafiltration (UF) was lower for B (drained volume: 2120 +/- 204 vs 2443 +/- 285 mL after 4 hr, p < 0.05). Higher transperitoneal calcium [11 +/- 22 L vs -3.1 +/- 11.0 (positive balance) mg, p < 0.05] and sodium (48 +/- 30 L vs 13 +/- 20 mEq) removal were evident. With L, the loss of 43.0 +/- 6.3 mEq of bicarbonate appeared. The linear regression analysis of MTC values showed higher r coefficients for the bicarbonate solution. These results suggest that bicarbonate dial-ysate improves the diffusion capacity of the peritoneum with respect to lactate.
To evaluate circulating burst-forming unit-erythroid (BFU-E) cells after erythropoietin (EPO) treatment, 7 female continuous ambulatory peritoneal dialysis patients were studied [baseline hemoglobin (HB): 7-10.5 g/dL)]. EPO (4000 U subcutaneously) was administered twice weekly for two months. The control group consisted of 7 healthy women with similar demographic characteristics. Mononuclear cells (MC) (5 x 10(5)) were added to 1 mL of culture medium, supplemented with 30% fetal bovine serum, 2 U/mL of EPO, 1% bovine serum albumin, and 0.3% agar. To enumerate colonies derived from each circulating BFU-E, plates were examined by inverse light microscopy, identifying BFU-E as large aggregates with more than 100 hemoglobinized cells (HC). A remarkable individual response was observed, with Hb values ranging 8.4-13.6 g/dL at week 4 and 8.8-16.5 g/dL at week 8. Baseline levels of BFU-E in patients ranged 0-100/5 x 10(5) MC (0-358 mL of whole blood), and in controls they ranged 6-24/5 x 10(5) MC (29.6-101.3/mL) (NS). Hemoglobin levels after four and eight weeks of EPO showed a significant relationship with circulating BFU-E at baseline (r = -0.873, r = -0.928, respectively). The increment in Hb after eight weeks showed a significant relationship with baseline BFU-E (r = 0.812). Hemoglobin levels at the fourth to eighth week, and the increment in Hb after eight weeks, showed a significant, direct relationship with the increments in circulating BFU-E registered after one to two weeks of treatment. We conclude that, after the first week of EPO treatment, its effect on hemoglobin may be predieted by the increment in circulating BFU-E. Thus; a new tool to measure the earliest EPO effects has become available.
OBJECTIVE: To study the relationship between peritoneal effluent cells and infection rate and to relate this population with functional characteristics. DESIGN: Prospective, longitudinal, and comparative study. SETTING: Outpatient continuous ambulatory peritoneal dialysis (CAPD) unit of a university medical center. PARTICIPANTS: Seventy-one uninfected patients, treated for 0-156 months on CAPD, in stable condition were studied (33 female, 38 male). INTERVENTIONS: Nocturnal peritoneal effluent (NPE) was drained with EDTA (2.5 mmol/L) at 37 degrees C and centrifuged at 2500 rpm for 9 minutes. MEASUREMENTS: Accumulated peritoneal inflammation days/year and ultrafiltration/diffusion (mass transfer coefficients (MTCs) for small molecules) capacities were recorded. Cellular count (cells/night) was performed using a Neubauer chamber. Macrophage function was assessed by cytochemical (lysosomal enzyme content: ANAE, beta-glucuronidase, acid phosphatase) and immunohistochemical procedures (expression of membrane antigens, CD4, 11b, 11c, 14, 16, 25, 35, and 71). RESULTS: The macrophage is the most frequently appearing cell in the NPE. Cell count decreases over time on CAPD (from 20 x 10(6) to 5 x 10(6) after the first year). Intrapatient variability was low, but interpatient differences were marked. Mesothelial cell count remained stable over time (0.25-0.5 x 10(6)). Four of our patients showed a "transforming" change in these cells. Previous incidence of peritonitis and values of functional measurements did not correlate with cell count or expressions of macrophage function (lysosome enzyme content and percentage of cells expressing different membrane antigens). CONCLUSION: There is difficulty interpreting the results on peritoneal effluent cells and their relationship with the incidence of peritonitis and functional characteristics of the peritoneum. No definite conclusions can be drawn other than the great interpatient and intrapatient variability. The presence of abnormal peritoneal cells with undetermined origin and function suggests the need for periodic studies of peritoneal effluent cells on long-term CAPD patients.
A decrease in the peritonitis rate and the incidence of catheter exit-site/tunnel (E/T) infection are the most important factors affecting the permanent peritoneal catheter in continuous ambulatory peritoneal dialysis (CAPD) patients. Moncrief et al. have introduced a novel methodology (two phases) for peritoneal catheter placement (7.8). The most relevant characteristic is that the external portion remains buried on the subcutaneous tissue (sterile environment) during the healing process. After four to six weeks, the catheter is brought out through a small incision (0.5 cm) distal 2 cm from the subcutaneous cuff, and peritoneal dialysis may be initiated. The data available, presented by Moncrief et al., show a lower incidence of peritonitis rate and E/T infection with this implantation technique, when compared with a classic technique. The aim of this study is to learn if the placement of a peritoneal catheter with Moncrief's methodology decreases the incidence of complications related to peritoneal catheters. We treated 29 patients (group C) with the conventional procedure and 25 patients (group M) with the Moncrief technique. Follow-up was similar for both groups (C = 12.2 +/- 7.9 months vs M = 11.1 +/- 6.1 months, NS). The time buried was 3.23 +/- 0.9 weeks (2-5). Eleven patients completed four weeks with the catheter buried subcutaneously (group M-4). The incidence of E/T infection was similar for groups C and M, and lower in group M-4 (p < 0.05). The number of catheters free of infection was less in group C (31%) than in group M (46%) and M-4 (67%) (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Ultrafiltration failure (UFF) is one of the most frequent causes of continuous ambulatory peritoneal dialysis (CAPD) dropout and is a common consequence of peritoneal hyperpermeability secondary to inappropriate regeneration of mesothelial cells. In this paper we present the results of 25 peritoneal resting periods of 4 weeks in 16 patients who showed UFF. The mean duration of CAPD was 44 +/- 22 months. All patients had been free of peritonitis for at least 3 months when included in the peritoneal resting trial. UFF was always defined as a long-lasting decrease of UF capacity such that dry weight could no longer be achieved by CAPD. The former incidence of peritonitis was 3.9 +/- 2.3 episodes. Results compared to the preresting data: urea MTC (mass transfer coefficient) decreased from 24.9 +/- 6.8 to 21.0 +/- 6.1 (p < 0.05), creatinine MTC from 16.5 +/- 6.0 to 13.8 +/- 4.0 (p < 0.05), and UF increased from 493.8 +/- 278.0 to 881.3 +/- 388.1 (p < 0.001). The response in terms of UF in patients with low permeability ultrafiltration (creat MTC less than 13) was heterogeneous and lower than in patients with criteria of hyperpermeability (greater than 13): 720 +/- 396 to 1150 +/- 533 (NS) versus 491 +/- 310 to 808 +/- 205, respectively. Simultaneously, creatinine MTC did not change in the former group (10.2), while hyperpermeability patients showed a remarkable decrease (19 +/- 5 to 15 +/- 2, p < 0.05). In conclusion, peritoneal resting is a useful tool in the management of ultrafiltration failure in CAPD patients, primarily in those with peritoneal hyperpermeability.