[Fibrate-induced deterioration of renal function]. / Deterioro de la función renal inducido por fibratos.

INTRODUCTION: Fibrates represent one of the medications used to treat patients with hyperlipemia. Deterioration in renal function is not a very known adverse effect of fibric acid derivates. In the last 26 months we have detected thirteen patients with acute renal failure associated to fibrates in our outpatients' clinic. SUBJECTS AND METHODS: The aim of our study is to analyze our experience in deterioration in renal function associated to fibrates use. This is a retrospective charts review. RESULTS: From the thirteen patients (8 males/5 females) with mean age of 65.5 +/- 12.2 years, ten received Fenofibrate (FN), one Bezafibrate (BZ) and two Gemfibrozil (GF). Six cases had previously normal renal function and the seven remaining had mild chronic renal failure (CRF). The increase of serum Creatinine (Crs) value was higher than 74%. Acute renal failure was reversible in 9 patients (group 1), but the other 4 did not recover their previous renal function (group 2). The average of Crs before fibrate treatment was 1.33 +/- 0.36 mg/dl (Creatinine clearance 63.2 +/- 26.6 ml/min) and the highest average of Crs during the treatment was 2.22 +/- 0.49 mg/d (Creatinine clearance 37.3 +/- 11.9 ml/min). The average time until acute renal failure diagnosis was 6.7 +/- 5.8 months and the recovery of renal function was delayed an average of 3.8 +/- 3.5 months after fibrates withdrawn. Group 2 patients had a higuer Crs and longer time with fibrates than group 1 patients. CPK values were normal in all cases. In two patients renal biopsy was performed and no significant lesions were detected. CONCLUSION: The fibrate treatment can induce an acute renal failure. Four patients (30.8%) did not recover their basal renal function. When fibrate treatment begins a renal function should be monitored specially in patients with CRF.

Deterioro de la función renal inducido por fibratos / No disponible

Introducción: Los fibratos representan uno de los grupos de fármacos indicados para el tratamiento de la hiperlipidemia. Uno de sus efectos secundarios, aún poco conocido, es el deterioro agudo de la función renal. En los últimos 26 meses hemos objetivado en nuestra consulta externa de Nefrología un total de13 pacientes con deterioro de la función renal asociado al uso de fibratos. Material y métodos: El objetivo de nuestro estudio es evaluar nuestra experiencia en el incremento de Creatinina sérica (Crs) inducido por fibratos. Se trata de una revisión retrospectiva de una serie de casos. Resultados: De los 13 pacientes (8 hombres/5 mujeres) con edad media de 65,5 ± 12,2 años, diez fueron tratados con fenofibrato, uno con bezafibrato y dos con gemfibrozilo. Seis pacientes partían de una función renal normal y los otros siete presentaban una Insuficiencia Renal Crónica (IRC) leve-moderada previamente al inicio del tratamiento. El incremento de creatinina con respecto a la basal expresado en porcentaje fue superior al 74%. En nueve de los pacientes el deterioro de función renal fue completamente reversible (grupo 1), mientras que en cuatro de ellos la recuperación fue parcial (grupo 2). La media de creatinina antes de recibir tratamiento con fibratos fue de 1,33 ± 0,36 mg/dl (aclaramiento de creatinina 63,2 ± 26,6 ml/min) y la media de la creatinina máxima durante el tratamiento fue de 2,22± 0,49 mg/dl (aclaramiento de creatinina 33,4 ± 8,1 ml/min). El tiempo medio de evolución hasta objetivarse el incremento de creatinina fue de 6,7 ± 5,8 meses y la recuperación de la función renal ocurrió a los 3,8 ± 3,5 meses de la suspensión del tratamiento con fibratos. En los pacientes del grupo 2 se objetivó un mayor incremento de Crs y un tiempo de tratamiento confibratos más prolongado. En los pacientes en los que se obtuvieron niveles de CPK, éstos fueron normales. En dos de nuestros (..) (AU)

Introduction: Fibrates represent one of the medications used to treat patients with hyperlipemia. Deterioration in renal function is not a very known adverse effect of fibric acid derivates . In the last 26 months we have detected thirteen patient s with acute renal failure associated to fibrates in our outpatients’ clinic. Subjects and methods : The aim of our study is to analyze our experience in deterioration in renal function associated to fibrates use. This is a retrospective char t s review. Results: From the thirteen patients (8 males/5 females) with mean age of 65.5 ± 12.2 year s , ten received Fenofibrate (FN) , one Beza fibrate (BZ) and two Gemfibrozil (GF). Six cases had previously normal renal function and the seven remaining had mi ld chronicrenal failure (CRF) . The increase of serum Creatinine (Cr s ) value was higher than 74%. (..) (AU)

[Analysis of evaluation process of research projects submitted to the Fondo de Investigación Sanitaria, Spain]. / Análisis del proceso evaluador de los proyectos de investigación en el Fondo de Investigación Sanitaria.

BACKGROUND: At the present time it seems very clear that research improvement is both an unquestionable fact and the right way to develop technological innovation, services and patents. However, such improvement and corresponding finances needs to be done under fine and rigorous evaluation process as an assessment tool under which all the research projects applying to a public or private call for proposals should be submitted to assure a coherence point according to the investment to be made. At this end, the main target of this work has been focused to analysis and study the evaluation process traditionally made by Fondo de Investigación Sanitaria (FIS) as well as to propose most adequate modifications. MATERIAL AND METHOD: A sample of 431 research projects corresponding to year 1998 proposal was analysed. The evaluation from FIS and ANEP (National Evaluation and Prospective Agency) was evaluated and scored (evaluation quality) in its main contents by 3 independent evaluators, the showed results submitted to a comparative frame between these agencies at indoor (FIS) and outdoor (FIS/ANEP) level. RESULTS: FIS evaluation had 20 commissions or areas of knowledge. The analysis indoor (FIS) clearly showed that evaluation quality was correlated to the assigned commission (F = 3.71; p < 0.001) and to the time last of the researched proposal (F = 3.42; p < 0.05) but no related to the evaluator. On the other hand, the quality of ANEP evaluation showed a correlated dependency of the three mentioned facts. In all terms, the ANEP evaluation was better than FIS for the three years time projects, but in did not show significant differences in one or two years time projects. In all cases, the evaluation with final results as negative (financing denied) showed an average quality higher than positive evaluation. CONCLUSIONS: The obtained results advice about the convenience of making some changes in the evaluative structure and to review the sort of FIS technical commissions focusing an improvement of the evaluation process.

Remission of lupus nephritis with cyclophosphamide and late relapses following therapy withdrawal.

We describe the long-term follow-up of severe lupus nephritis treated with cyclophosphamide, with emphasis on the incidence of relapses after therapy withdrawal. From a cohort of SLE patients followed over a period of twelve years, we review the charts of the eleven with histologic evidence of class IV nephritis who reached complete remission with cyclophosphamide and who were followed for more than four years after the discontinuation. In all patients, cyclophosphamide was maintained for longer than two years after complete remission. Four patients relapsed following therapy withdrawal (36%). Sequential biopsies were taken in eight patients after remission or relapse and show a good histologic correlation with clinical renal data. Clinical remission with re-induction therapy could not be achieved in two patients after relapse. We conclude that relapse is frequently observed following cyclophosphamide withdrawal in lupus patients with diffuse proliferative glomerulonephritis initially responsive to this therapy. Studies are needed to determine the influence of different regimes of maintenance therapy on the rate of relapses.

Effects of angiotensin converting enzyme inhibitors on the progression of renal failure and proteinuria in humans.

We studied the long-term effect of an angiotensin converting enzyme (ACE) inhibitor, captopril, on the progression of chronic renal failure and on the rate of urinary protein excretion. When compared with standard triple therapy, captopril slowed the progression of renal failure. Captopril was also able to reduce the proteinuria of non-diabetic glomerular origin. This reduction was not dependent on the presence or absence of arterial hypertension but was limited by the presence of low serum albumin levels, and only occurred in patients with proteinuria in excess of 3 g/24 h.

Hematuria due to hypercalciuria and hyperuricosuria in adult patients.

We have prospectively studied 37 adult patients (15 males, 22 females; age 31 +/- 10.6 years) with previously undiagnosed isolated hematuria in which hypercalciuria or hyperuricosuria was found. Eighteen of them had had episodes of gross hematuria. Isolated hypercalciuria (4.4 to 10.4, X 5.6 +/- 1.9 mg/kg/24 hr) was found in nine patients (Group I), isolated hyperuricosuria (784 to 1500, X 1088 +/- 228 mg/24 hr) in 11 (Group II), and both hypercalciuria (4 to 8, X 4.9 +/- 1 mg/kg/24 hr) and hyperuricosuria (752 to 1476, X 1042 +/- 181 mg/24 hr) in 17 patients (Group III). Thiazide treatment for patients with hypercalciuria and allopurinol for those with hyperuricosuria were administered; calciuria and uricosuria became normal by the first month of therapy in every case. In 22 (59.4%) cases (Responder patients) hematuria resolved completely as soon as calciuria and uricosuria became normal. In the remaining 15 cases (Nonresponder patients) hematuria persisted despite the normal calcium and uric acid excretions. Several disorders that explained hematuria were diagnosed later in most of Nonresponder patients. Responder patients persisted without hematuria on the follow-up; only in three patients a transient relapse of hematuria was seen associated with a sudden increase of calciuria and uricosuria because of treatment withdrawal. There were no differences in age, male/female ratio nor in the basal values of calciuria and uricosuria between Responder and Nonresponder patients. A familial history of urolithiasis was found more frequently in Responder patients (64%) than in Nonresponders (20%) (P less than 0.05). We conclude that hypercalciuria and hyperuricosuria are definable and potentially reversible causes of hematuria in adult patients.

Implications of hypervitaminosis A on the calcium-phosphate metabolism and on blood lipids in hemodialysis.

Serum levels of vitamin A (VA) were measured in 71 hemodialysis (HD) patients and in 30 normal controls. 65 of the 71 patients were taking multivitamin preparations (MP) containing VA. The HD patients had significantly greater values: 7.81 +/- 2.86 mumol/l (224 +/- 82 micrograms/dl) versus 3.97 +/- 0.97 mumol/l (114 +/- 28 micrograms/dl; p less than 0.0005); those taking MP with large doses of VA showed the highest levels. Patients were divided as having normal (group I, n = 21) or elevated (group II, n = 50) serum levels of VA. Patients of group II had higher levels of serum calcium (Ca) and lower of serum phosphate (P) and PTH than those of group I. Four months after the withdrawal of oral VA, the serum levels of VA and Ca fell significantly in group II, while the serum P increased. On the contrary, in group I serum levels of VA, Ca and P remained unchanged. Serum triglycerides (TG) were significantly higher in group II but did not change after the withdrawal of VA. No differences between both groups of patients were observed for age, time on HD, residual diuresis, residual renal function, serum levels of cholesterol (CL) or anemia. A retrospective study of 18 hepatic biopsies of HD patients disclosed hyperplasia of Ito cells (VA-storaging cells) in 7 of them. These 7 biopsies belonged to patients who had taken large amounts of oral VA. Our data indicate that prolonged VA intake in HD patients is followed by an increase of serum CA, a decrease of serum P and PTH and a hepatic accumulation of VA.(ABSTRACT TRUNCATED AT 250 WORDS)

Focal glomerulosclerosis and proteinuria in patients with solitary kidneys.

We have studied ten normotensive patients (nine male and one female, aged between 28 and 51 years) who each had a solitary functioning kidney and proteinuria. Six had undergone unilateral nephrectomy, and four unilateral renal agenesis. In each case, intravenous pyelography revealed only one functioning kidney with compensating hypertrophy. Mild to moderate chronic renal failure was present in six, and microhematuria in two. Proteinuria ranged from 1.10 to 4.10 g/24 hr, being in the nephrotic range in three patients. In seven patients, a renal biopsy showed focal glomerulosclerosis. Immunofluorescence studies demonstrated granular deposits of IgM in three and C3 in six cases, over the sclerotic areas. We suggest that the appearance of proteinuria and focal glomerulosclerosis in a patient with a solitary kidney could be due to chronic glomerular hyperfiltration.

Acute worsening of renal function during episodes of macroscopic hematuria in IgA nephropathy.

The appearance of renal failure during episodes of macroscopic hematuria (EMH) in IgA nephropathy (IgAN) has been described as very unusual. The results of a prospective investigation on the effect of EMH on renal function in IgAN are presented. During a 3-year period, 29 episodes of EMH occurring in 21 patients with IgAN have been studied. A derangement of renal function (increase of serum creatinine by more than 0.5 mg/dl) was observed in 11 episodes (37.9%) with peak creatinine values ranging from 1.2 to 6.7 mg/dl. The worsening of renal function was accompanied by a longer duration of EMH (4.8 +/- 1.3 vs. 3.5 +/- 1.5 days; P less than 0.05) but not by arterial hypertension or edema. A complete recovery of renal function was observed in every patient 1 to 2 months after the start of EMH. The histological survey disclosed that the decrease of renal function correlated closely with the presence of red blood cell casts in as much as 50% of the tubular lumen and with findings of tubular necrosis. We conclude that a worsening of renal function can be observed frequently during the EMH. Tubular damage and obstruction by red blood cell casts may play a significant role in the pathogenesis of this complication.