[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was 6.7 +/- 5.8 months and the recovery of renal function was delayed an average of 3.8 +/- 3.5 months after fibrates withdrawn.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.

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.

[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.

[Hypertensive crisis. Clinical and therapeutic study of 130 cases (author's transl)]. / Crisis hipertensivas. Estudio clínico y terapéutico de 130 casos.

The clinical aspects and response to therapy of 130 hypertensive emergencies are reviewed in this report. According to the main features of the clinical picture, the patients were divided into neurologic, cardiac or mixed emergencies. The patients were evaluated with clinical examination, fundoscopy, routine biochemistry, ECG, and chest radiograms. According to the response of the blood pressure to the administration of hypotensive drugs, the patients were divided into two groups: group I, with good response to a single drug associated to frusemide, and group II, with good response to two or more drugs associated to frusemide. Neurologic emergencies appeared in 55 patients (42% of total), and cardiac emergencies in 45 (34%), the initial blood pressure beeing higher in the first group (p less than 0.005). The fundus showed hypertensive retinopathy degrees III-IV in 55% of the patients. Patients in group I had less elevation of the initial blood pressure, showed a better response to therapy, and had only mild side effects from the administered drugs. Group II had a mortality of 11% and, as expected, showed more complications due to side effects. The frequency of appearance of toxic side effects from the drugs given is reviewed, and a therapeutic schedule is proposed.

[Low dose clofibrate in the treatment of hypertriglyceridemia in hemodialysis patients (author's transl)]. / Clofibrato a dosis bajas en el tratamiento de la hipertrigliceridemia de los enfermos en hemodiálisis.

Sixteen patients on regular hemodialysis were treated with clofibrate, 500 mg three times a week for six weeks. A sustained and significant reduction of serum triglycerides occurred in thirteen patients. Serum cholesterol was also significantly reduced, although to a lesser degree. Predialysis levels of blood urea nitrogen, creatinine, and uric acid were significantly elevated during the treatment period and returned to previous levels after withdrawal of the drug. The incidence of side-effects was elevated. Five patients complained of nausea and upper abdominal discomfort, while four patients had muscle pain. Several muscle enzymes were elevated in a high percentage of patients, returning to basal values after discontinuation of the drug. It is concluded that clofibrate, although it is effective in lowering serum triglycerides in patients on hemodialysis, should not be used in such patients.

[Familial and hereditary mesangial glomerulonephritis with IgA deposits (author's transl)]. / Glomerulonefritis mesangial con depósitos de IgA, familiar y hereditaria.

Idiopathic mesangial glomerulonephritis with IgA deposits was observed in two relatives, father and son, in a family of 5 members. In the father the disease started at age 43 with relapsing macroscopic hematuria, proteinuria, renal failure and hypertension, with a progressive course in the ensuing four years. The affected son, the oldest of three brothers, developed relapsing macroscopic hematuria at age 16; two years later renal function was normal and there was no hypertension, but microhematuria persisted without proteinuria. The mother and the other two brothers had no clinical or biological signs of renal disease. Serum immunoglobulins (IgG, IgA, and IgM) and complement (C3, C4, C3 proactivator) were normal in the patients and their relatives. Histocompatibility typing demonstrated the presence of HLA-Bw35 in the father and the two unaffected sons, being negative in the mother and the affected son. The analysis of HLA-Bw35 in 23 patients with IgA mesangial glomerulonephritis gave positive results in 30% of them, while the control group had a positivity of 15% (p non significant with the X2 test). The present observations suggest that IgA mesangial glomerulonephritis is a potentially familial and hereditary renal disease. HLA-Bw35 antigen appears not to be a genetic marker of the disease in our geographical area.

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.

Detection of immediate hypersensitivity in rabbits by direct basophil degranulation.

The direct in vitro antigen-induced degranulation of rabbit basophils based on a simplified one-step method for the staining of these cells is reported. Degranulation was assessed by counting the number of basophils before and after exposure to antigen at 37 degrees C in the presence of Ca++. The degranulation was IgE-mediated, as shown by its passive transfer to nonimmunized rabbits by IgE-containing serum; also, the reaction was dependent on the presence of Ca++ ions and normal cell metabolism. The technique allowed the detection of serum factors capable of blocking the degranulation. It provided a means for following IgE sensitization at the cellular level, which is a better index of immediate hypersensitivity than the presence of circulating specific IgE.

Evidence for the involvement of IgE-basophil system in acute serum sickness.

The role of the basophils in acute serum sickness of rabbits was examined by monitoring daily the absolute number of basophils before, during and after the disease period. After antigen (bovine serum albumin, BSA) elimination, levels of serum IgE and in vitro basophil degranulation in the presence of BSA were determined. The results showed that the onset of glomerular lesions depends upon the simultaneous occurrence of circulating immune complexes greater than 19 S and of an in vivo basophil depletion--probably equivalent to degranulation--reaching 70% of the pre-disease number. Post-disease antigen-dependent in vitro degranulation of the basophils and levels of serum IgE anti BSA did not prove to be good indexes of basophil sensitization. Our data suggest that basophils are instrumental at early stages of the deposition of immune complexes, most probably through their sensitization by membrane-bound IgE antibodies.

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.

Pathology of the kidney in "toxic oil epidemic syndrome".

In May 1981, a massive intoxication of people who had ingested adulterated cooking oil took place in Madrid and nearby provinces. Although the patients presented, in the first phase of the disease, with acute respiratory illness, later on thromboembolic complications, severe neuromuscular involvement, and scleroderma-like cutaneous lesions appeared. Kidneys were apparently spared; however, 4 out of 842 admitted patients developed glomerulonephritis; kidney biopsies revealed glomerular, vascular, tubular, and interstitial changes. Cases 1 and 3 had diffuse proliferative endocapillary glomerulonephritis; case 2 had diffuse membranoproliferative glomerulonephritis; and case 4 had diffuse extracapillary glomerulonephritis. Three cases had vascular lesions characterized by degenerative and proliferative endothelial changes, intimal foamy macrophages, and partial or complete obliteration of the vascular lumen by concentric myxoid fibrosis. There were signs of necrosis of tubular epithelium along with edema and lymphocytic and eosinophilic interstitial infiltration. Two out of 22 autopsies had segmentary glomerulonephritis, and 17 out of 22 autopsies showed renal vascular lesions.