Nephropathy associated with antiphospholipid antibodies in patients with systemic lupus erythematosus.

BACKGROUND: Nephropathy associated with antiphospholipid antibodies (aPL) has been proposed as a risk factor of worse renal prognosis in patients with systemic lupus erythematosus (SLE). The purpose of the current study was to evaluate the prevalence of aPL-associated nephropathy (aPLN) among patients with lupus nephritis and to describe their functional renal outcome. METHODS: A total of 79 renal biopsies from 77 patients followed at the Hospital Clinic, Spain were analysed. Each renal biopsy was evaluated by a pathologist who was blinded to the aPL status. Thrombotic microangiopathy (TMA), fibrous intimal hyperplasia (FIH), fibrocellular arterial occlusion (FAO), focal cortical atrophy (FCA), and tubular thyroidization as lesions suggestive of aPLN were identified. RESULTS: aPLN was found in nine (11.4%) biopsies. TMA was found in three (33.3%) cases whereas chronic aPLN, represented by FIH and FCA, was found in four (44.4%) and three (33.3%) cases, respectively. A significant association between the presence of aPL and aPLN was found (p = 0.003). Patients with lupus anticoagulant (LA) plus IgG anticardiolipin antibodies (aCL) showed an increased prevalence of aPLN (OR: 3.61, 95% CI 1.28-5.14; p = 0.002). Creatinine levels were significantly increased in patients with aPLN compared with those with aPL without aPLN (p = 0.038). However, no significant difference in complete remission, partial remission, not response, and established renal damage between groups was observed at the end of follow-up. CONCLUSIONS: The aPL have an important role in the pathogenesis of renal lesions in SLE patients. Prospective studies are needed to address the role of aPLN in the long-term outcome of SLE patients with positive aPL.

Does medicine still show an unresolved discrimination against women? Experience in two European university hospitals.

Have invisible barriers for women been broken in 2007, or do we still have to break through medicine's glass ceiling? Data from two of the most prestigious university hospitals in Barcelona with 700-800 beds, Hospital Clínic (HC) and Hospital de la Santa Creu i Sant Pau (HSCSP) address this issue. In the HSCSP, 87% of the department chairs are men and 85% of the department unit chiefs are also men. With respect to women, only 5 (13%) are in the top position (department chair) and 4 (15%) are department unit chiefs. Similar statistics are also found at the HC: 87% of the department chairs and 89% of the department unit chiefs are men. Currently, only 6 women (13%) are in the top position and 6 (11%) are department unit chiefs. Analysis of the 2002 data of internal promotions in HC showed that for the first level (senior specialist) sex distribution was similar. Nevertheless, for the second level (consultant) only 25% were women, and for the top level (senior consultant) only 8% were women. These proportions have not changed in 2007 in spite of a 10% increase in leadership positions during this period. Similar proportions were found in HSCSP where 68% of the top promotions were held by men. The data obtained from these two different medical institutions in Barcelona are probably representative of other hospitals in Spain. It would be ethically desirable to have males and females in leadership positions in the medical profession.

[Institute for clinical management of nephro-urological diseases: the benefits of a quality care programme]. / Instituto de gestión clínica para las enfermedades nefrourológicas: utilidad de un programa de calidad asistencial.

The Clinic Institute of Nefro and Urology (ICNU) was formed in Clinic Hospital of Barcelona in 1999. It grouped together services of Nephrology, Urology and Renal Transplant. At the same time, in order to ensure Quality in this process of change, we designed a specific quality program. In this program, we defined objectives to improve the quality of these services in one year and we defined different quality indicators in order to maintain and monitor health quality. The indicators referred to technical quality and perceived quality and we periodically evaluated their evolution. The results of the last five years indicate that the majority of the indicators have improved, except those concerning infections surgery and the response to complaints. This has helped the consolidation and recognition of the work of this innovatory project in the health management of the nephrologic and urinary systems that locate the patient in the center of the organization and recognize the health professionals as the true managers of this model.

[Renal involvement in benign monoclonal gammopathies: an underdiagnosed condition]. / Afectación renal en las gammpatías monoclonales benignas: una entidad infradiagnosticada?

Renal involvement is observed frequently in association with malignant gammopathies, mainly those related to light chain deposition, although has also been described in non-malignant monoclonal gammopathy. This study reports the clinicopathological findings and outcome in 9 patients with nephropaty secondary to monoclonal immunoglobulin deposit in absence of malignancy. They were three men and six women and they were 59.2+/-12 years old. All patients presented proteinuria and different levels of renal insufficiency (mean creatinin = 315+/-187 micromol/L) at the moment of diagnostic. Two patients required dialysis at the time of renal biopsy. The pathology studies revealed a nodular sclerosing glomerulopathy in four cases, mesangiocapilary glomerulonephritis in three cases, only tubular lesions in one and mesangial lesions in the other one. The treatment applied was: Prednisone alone (two cases), with chemotherapy associated (melfalan in two, clorambucil in one and ciclophosphamide in another one). One patient received plasmapheresis and mycophenolate and another patient undergone a bone marrow authotransplant associated to mycophenolate and prednisone. One of the two patients who required dialysis at the moment of presentation was not treated. After a follow-up of more than 4 years (4.89 +/-DE: 3.69) renal function improved or remained stable in three patients and proteinuria was disappeared in more than 50% of patients. Four patients had a worsening of renal function and they required dialysis during the time of follow-up (in 2,4 years +/- DE: 4,3). In any case malignitation was observed. Chemotherapy stabilized or improved renal function in 3 of nine patients (33%) with non-malignant monoclonal gammopathy. Non-malignant monoclonal gammopathy could go unnoticed. Appearance of abnormalities in renal routine tests deserves more in-depth diagnostic procedures, including renal biopsy. Evolution to end stage renal disease could probably be avoided or reduced in severity with early detection and treatment of this entity.

Renal expression of ICAM-1 and VCAM-1 in ANCA-associated glomerulonephritis--are there differences among serologic subgroups?

BACKGROUND: Antineutrophil cytoplasmic autoantibodies (ANCA) play a role in the expression of adhesion molecules. Differences in ANCA test results in ANCA-associated vasculitis may provide differences in their renal expression. PATIENTS AND METHODS: We assessed the renal expression of ICAM-1 and VCAM-1 with monoclonal antibodies in 19 patients with ANCA-vasculitis: 7 microscopic polyangiitis, 5 Wegener's granulomatosis, 4 renal-limited vasculitis and 3 Churg-Strauss disease. Immunofluorescence and ELISA for myeloperoxidase (MPO) and proteinase 3 (PR3) were performed for ANCA-testing. 10 normal renal tissues were used as controls. RESULTS: The ANCA staining pattern was perinuclear in 14 patients, with MPO-ANCA 31 - 220 EU/ml, and cytoplasmic in 5, with PR3-ANCA 37 - 144 EU/ml. Abnormal tubular expression of ICAM-1 and VCAM-1 was seen in more than 80% of biopsies and abnormal expression of VCAM-1 in glomerular tuft was seen in 60%. Glomerular tuft stains of ++ or +++ for VCAM-1 were observed in 10% of renal biopsies from MPO-ANCA-GN patients, but in 60% of biopsies from PR3-ANCA-GN patients (Fi = 8.538, p = 0.03). IN CONCLUSION: De novo expression of VCAM-1 on glomerular tuft suggests that the endothelial cells play a role in ANCA-GN. De novo glomerular expression of VCAM-1 is associated more with ANCA directed against PR3 than with ANCA directed against MPO. Upregulated glomerular expression of VCAM-1 may reflect a higher histological activity in patients with PR3-ANCA, and supports the existence of specific immune activation mechanisms in the different serologic subgroups in ANCA-GN. The de novo tubular expression of ICAM-1 and VCAM-1 suggests that the epithelial cells may participate in adhesive interactions in ANCA-GN.

Renal expression of intercellular adhesion molecule-1 in immunoglobulin A nephropathy: tubulointerstitial injury and prognosis.

In immunoglobulin A nephropathy (IgAN), the abnormal expression of intercellular adhesion molecule-1 (ICAM-1) on proximal tubule epithelium is associated with the glomerular and interstitial infiltration of leucocytes, but its clinical significance remains uncertain. We analysed the relationship between the ICAM-1 (CD54) expression in tubular epithelial cells and interstitial leucocytes, macrophages (CD14) and T lymphocytes (CD3) with the histologic features, proteinuria and serum creatinine at the time of renal biopsy and after 2.42 years in 45 patients with IgAN and after 1.8+/-1.5 years in 29 patients with non-glomerulonephritis (non-GN). In IgAN, ICAM-1+ tubule epithelium was 0.1+/-0.18 (x+/-SD), and this was associated with extracapillary proliferation (up to 20% of Bowman's space), glomerular sclerosis involving less than 50% of glomerular area, interstitial cellular infiltration, tubular atrophy and proteinuria level. ICAM-1+ interstitial leucocytes were correlated with glomerular sclerosis involving less than 50% of glomerular area, glomerular sclerosis involving more than 50% of glomerular area, tubular atrophy, interstitial fibrosis and serum creatinine level. In patients with an increase of 50% in serum creatinine, ICAM-1+, CD14+ and CD3+, interstitial leucocytes were significantly outnumbered than in patients with stable serum creatinine. In non-GN, ICAM-1+ tubule epithelium was 0.02+/-0.04 (U=344, P<0.05, vs IgAN), and this was inversely correlated with the percentage of the normal glomeruli and associated with glomerular sclerosis covering more than 50% of glomerular area, tubular atrophy and serum creatinine level. The association between tubular ICAM-1 and proteinuria and the association between interstitial ICAM-1+, CD14+ and CD3+, leucocytes and renal failure at presentation and the deterioration in IgAN in contrast with non-GN suggest that tubular and interstitial expression of ICAM-1 may be a marker of tubulointerstitial disturbance in IgAN.

Leukocyte infiltration and intercellular adhesion molecule-1-mediated cell interactions in immunoglobulin A nephropathy.

BACKGROUND: Mononuclear leukocytes have a role in immunoglobulin (Ig) A nephropathy. Renal leukocyte recruitment is mediated by adhesive interactions between leukocytes and their ligands on renal cells. METHODS: We assessed interstitial and glomerular leukocytes using an avidin-biotin-peroxidase method with monoclonal antibodies (MAbs) against leukocytes (CD45), beta2-integrin (CD18), macrophages (CD14), T cells (CD3) and T-cell subsets (CD4, CD8), intercellular adhesion molecule-1 (ICAM-1) (CD54), and HLA class II antigens. We analyzed their relation with the abnormal expression of ICAM-1 on proximal tubular epithelium in sequential renal sections from 57 patients with IgA nephropathy stratified by degrees of interstitial cellular infiltration as seen by light microscopy. RESULTS: In IgA nephropathy without infiltration (n = 15) and with interstitial cellular infiltration of 1+ by light microscopy (n = 11), ICAM-1 expression on vascular endothelium was unchanged with respect to that observed in the normal kidney; the proximal tubular epithelium was negative for this stain. Moreover, in IgA nephropathy with interstitial cellular infiltration greater than or equal to 2+ by light microscopy (n = 31), ICAM-1+ stain was seen on proximal tubular epithelium. The value of ICAM-1+ tubule staining was significantly (P = .0004) higher in the biopsies with a higher degree of interstitial cellular infiltration seen by light microscopy. The tubular ICAM-1+ stain was significantly associated with the number of interstitial leukocytes identified by the MAbs tested and correlated (P < .05) with CD45+ (r = 0.59), CD14+ (r = 0.54), and CD3+ (r = 0.51) interstitial leukocytes in IgA nephropathy with interstitial cellular infiltration by light microscopy. Interstitial ICAM-1+ cells and interstitial CD18+ leukocytes were correlated (r = 0.85, P < .001). Correlation was found between the value of ICAM-1+ tubule staining and the number of CD45+ (r = 0.87, P < .01), CD14+ (0.58, P < .05), and CD8+ (r = 0.68, P < .05) glomerular leukocytes. CONCLUSIONS: Our results suggest that tubular and interstitial ICAM-1+ cells may participate in adhesive interactions with interstitial leukocytes. Epithelial tubular cells expressing ICAM-1 may be a marker of tubulointerstitial disturbance upregulated by interstitial and glomerular infiltration of macrophages and T cells in IgA nephropathy.

[Anti-glomerular basement membrane antibody mediated disease: revision of 32 cases and follow-up at one year of the diagnosis]. / Enfermedad por Ac anti-MBG: revisión de 32 casos y seguimiento al año del diagnóstico.

Anti-basement membrane antibody mediated disease is an unfrequent entity but with a high mortality and morbidity. We present a revision of 32 patients diagnosed of anti-basement membrane antibody mediated disease between 1983 and 1997, and their evolution at one year of the diagnosis. The clinical pattern of presentation was as a Goodpasture's syndrome (glomerulonephritis and lung haemorrhage) in 15 patients and glomerulonephritis without lung involvement in 17. We reviewed retrospectively the features at the clinical presentation, the different treatments, and the delay of the starting of it since the beginning of the symptoms, in order to evaluate a prognosis dats of the disease. After the retrospective study we deduce that anti-basement membrane antibody mediated disease has a high mortality although the different regimes of treatment applied (25%), and the need of renal replacement therapy at one year of diagnosis is also high (70.8%). The renal survival at one year of the diagnosis is low and the response to therapy depends on the serum creatinine value at the diagnosis. The contribution of immunocompetent leucocytes to renal hypercellularity suggests that both humoral and cell-mediated immunity play a role in this disease.

[Intravenous calcitriol in the treatment of the refractory secondary hyperparathyroidism of terminal chronic kidney failure]. / El calcitriol por vía intravenosa en el tratamiento del hiperparatiroidismo secundario refractario de la insuficiencia renal crónica terminal.

BACKGROUND: In advanced cases of secondary hyperparathyroidism (HPT) in terminal chronic renal failure, the oral treatment of calcitriol is not possible due to the development of hypercalcemia. It has been demonstrated that calcitriol directly inhibits the secretion of parathormone (PTH), independently of calcium. Therefore the intravenous administration of high and intermittent doses of calcitriol (ivVD) has been proposed as an alternative treatment for resistant HPT. METHODS: The response of PTHi to treatment over 6 months with ivVD was evaluated in 18 patients with moderate-severe HPT resistant to the classical schedules. RESULTS: An important decrease was observed in the PTHi values (basal: 698 +/- 277 pg/ml, end of treatment: 272 +/- 200; p < 0.05). Alkaline phosphatase values followed a parallel course (basal: 476 +/- 286 U/l, end of treatment: 301 +/- 276 U/l, p < 0.05). Fifty-five percent of the patients presented hypercalcemia at some time (Ca > or = 11.5 mg/dl) being controlled by a decrease in the doses of calcitriol or calcium in dialysis fluid. No response was observed in 3 patients (17%) with treatment being discontinued due to presentation of uncontrollable hypercalcemia. CONCLUSIONS: The administration of intravenous calcitriol at high and intermittent doses is effective in a considerable number of patients with hyperparathyroidism resistant to the classical oral schedules. Its use may avoid surgical parathyroidectomy in some cases.

[Renal expression of intercellular adhesion molecule-1 (ICAM-1) in IgA deposit mesangial nephropathy. A tubulointerstitial lesion marker]. / Expresión renal de la molécula de adhesión intercelular-1 (ICAM-1) en la nefropatía mesangial por depósitos de IgA. Un marcador de lesión tubulointersticial.

BACKGROUND: The aim of this study was to determine the significance of the renal expression of ICAM-1 in IgA nephropathy (IgAN). PATIENTS AND METHOD: First, we identified ICAM-1 (CD54) expression in tubular epithelial cells and interstitial leucocytes in renal biopsies from 45 patients with IgAN and 29 patients with non-glomerulonephritis nephropathy (non-GN). We then analysed the relationship between this expression and both histological and clinical data at the time of renal biopsy and after 2.4 (2) (X [SD]) years in IgAN, and 1.8 (1.5) years in non-GN. RESULTS: In IgAN, tubular ICAM-1 positive staining was seen in 25 (55%) biopsies; it was associated with extracapillary proliferation, glomerulosclerosis involving less than 50% of glomerular area, interstitial cell infiltration and tubular atrophy. ICAM-1 positive interstitial leucocytes were 234 (307)/mm2; this expression correlated with glomerulosclerosis, tubular atrophy, interstitial fibrosis and serum creatinine (Cr) level. In patients with 50% increase in Cr level, ICAM-1 positive interstitial leucocytes were 516 (360)/mm2 as compared with 66 (87.8)/mm2 (U = 16; p < 0.005) in patients with stable Cr. In non-GN, tubular ICAM-1 expression was observed in 7 (24%) biopsies. CONCLUSIONS: Tubular and Interstitial expression of ICAM-1 can be a marker of tubulointerstitial damage in IgAN. Interstitial ICAM-1, rather than tubular ICAM-1, may predict the progression of this disease.

Professional recognition of female and male doctors.

PRECEDENTS AND AIM: The awards for the excellence of the Official College of Physicians of Barcelona (COMB) were instituted in 2004 to recognize the excellence of the professional exercise. The winners are yearly chosen by juries appointed by the board of government, whose members propose for the award doctors who, in their opinion, have an exemplary professional and human behaviour. SUBJECTS AND METHODS: The number of male and female doctors who have obtained this recognition has been analysed in relation with the sex distribution in the juries. Likewise it has been compared the ratios men-to-women of those who have been rewarded and this ratio among physicians of more than 45 years. RESULTS: Between the awarded physicians the ratio men-to-women was of 2.7/1 (range, from 1.2/1 for awardees in primary care to 6/1 in research). The men-to-women ratio among those who were awarded was in parallel to the man-to-women ratios of the juries. The ratio between men and women among members of the COMB of more than 45 years was 1.4/1, whereas in those who were awarded it was of 2.7/1. The increase in the proportion of women in the juries in the last four years has been followed by an increase in the number of female physicians awarded. CONCLUSION: This data demonstrates that the predominance of male doctors among those who were awarded does not depend so much on the age factor, but basically on the proportion of male and female doctors in the juries.

Renal expression of adhesion molecules in anca-associated disease.

INTRODUCTION: Anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated disease among other manifestations can underlie rapidly progressive glomerulonephritis (RPGN), with crescentic and necrotizing GN. Differences in pathogenic immune mechanisms in RPGN may provide differences in the renal expression of adhesion molecules mediating these lesions. METHODS: Renal intercellular adhesion molecule 1 (ICAM-1; CD54) and vascular cell adhesion molecule 1 (VCAM-1; CD106) were assessed in 40 patients with type I RPGN (anti-glomerular basement membrane antibodies, n = 4), type II (immune complexes, n = 17), and type III (ANCA, n = 19). Enzyme-linked immunosorbent assay (ELISA) for detection of immunoglobulin G antibodies against the Goodpasture's antigen and indirect immunofluorescence and ELISA for myeloperoxidase (MPO) and proteinase 3 (PR3) were performed for ANCA testing. Ten normal renal tissues were used as controls. Relationships between ICAM-1 and VCAM-1, histopathologic features, and CD18, CD14, and CD3 cells were analyzed. RESULTS: Abnormal ICAM-1 and VCAM-1 in tubule was seen in >80% of biopsies with RPGN. Abnormal VCAM-1 in glomerular tuft was seen in >60% of biopsies with RPGN. Glomerular ICAM-1 was associated with less glomerulosclerosis (chi (2) = 6.719, p = 0.01), less interstitial fibrosis (chi (2) = 4.322, p < 0.05), and less tubular atrophy (chi (2) = 8.547, p < 0.005). Glomerular VCAM-1 was associated with glomerular leukocyte infiltration (chi (2) = 4.698, p < 0.05). Glomerular tuft stains of ++/+++ for VCAM-1 was observed in 10% from MPO-ANCA-GN patients but in 60% from PR3-ANCA-GN (Fi = 8.538, p = 0.03). CONCLUSIONS: The following conclusions can be made from this study. (1) The renal expression of ICAM-1 and VCAM-1 is upregulated in RPGN, and this is associated with the histological activity. (2) De novo expression of VCAM-1 on glomerular tuft suggests that endothelial cells play a role in RPGN. (3) De novo tubular expression of ICAM-1 and VCAM-1 suggests that epithelial cells may participate in adhesive interactions in RPGN. (4) De novo expression of VCAM-1 at the glomerular tuft in PR3-ANCA positive patients seems greater than in MPO-ANCA positive patients, which suggests that testing specific immune activation mechanisms may play a role in ANCA-associated GN.