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.

[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.

Henoch-Schönlein IgA glomerulonephritis complicating myeloma kidneys: case report.

Myeloma kidney is the principal pathological substrate of rapidly progressive renal failure in multiple myeloma. We report the unusual case of a 72-year-old male diagnosed with kappa Bence Jones myeloma with renal failure which needed dialysis. After treatment with vincristine, doxorubicin (Adriamycin), dexamethasone (VAD), and plasmapheresis, the renal function was recovered until serum creatinine level was <2 mg/dl. Six months later, the pathological counterpart of rapidly progressive renal failure was crescentic IgA proliferative glomerulonephritis as a manifestation of Henoch-Schönlein syndrome associated with sepsis caused by coagulase-negative staphylococci. This case suggests that mesangial IgA deposition should be considered within the spectrum of consequent glomerular lesion-associated chemotherapy occurring in multiple myeloma.

Focal segmental glomerular sclerosis in two patients with Addison's disease: any more than fortuitous development of glomerular disease?

Adjustment of the mineralocorticoid activity under substitution therapy is of primary importance in Addison's disease. We report the clinical and biological conditions of 2 patients with Addison's disease who developed nephrotic proteinuria during their deficient mineralocorticoid state. Renal biopsy was performed and the specimens processed using conventional histochemistry, Congo red staining, and indirect immunofluorescence. The renal biopsy specimens showed focal segmental glomerular sclerosis and nodular deposits of IgM and C3. Negative for Congo red staining. Serum complement, circulating immune complexes, and anti-DNA and hepatitis B and C and human immunodeficiency virus antibodies were all normal or negative. Absence of vesicoureteral reflux was assessed by X-ray studies. Our observations suggest that deficiency in mineralocorticoid substitution therapy inducing a status of hyperreninemia could play a role in the development of focal segmental glomerulosclerosis in patients with Addison's disease.

[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.

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.

Circulating soluble adhesion molecules in ANCA-associated vasculitis.

BACKGROUND: To evaluate whether changes in concentrations of soluble (s) E-selectin, sP-selectin, sL-selectin, intercellular adhesion molecule 1 (sICAM-1), and vascular cell adhesion molecule 1 (sVCAM-1) reflect disease activity in patients with ANCA-associated vasculitis and whether serum levels of these adhesion molecules are related to the degree of renal failure in patients with chronic renal failure (CRF). SUBJECTS AND METHODS: A sandwich ELISA was used to measure these soluble adhesion molecules in (i) sera from 20 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (10 patients with Wegener's granulomatosis (WG) and 10 patients with microscopic polyangiitis (MPA)), obtained at the time of diagnosis and during the remission period; (ii) sera from 40 patients with CRF not undergoing haemodialysis. RESULTS: At the time of diagnosis, serum levels of sE-selectin, sICAM-1 and sVCAM-1 (88+/-42 ng/ml, 437+/-184 ng/ml, 1720+/-1174 ng/ml respectively) were significantly higher in patients with ANCA-associated vasculitis than in healthy controls (P<0.0001, P=0.002 and P=0.001 respectively). Serum sP-selectin values did not differ from those obtained in normal donors. In contrast, sL-selectin levels (940+/-349 ng/ml) were significantly lower in patients than those recorded in healthy controls (P<0.0001). A significant decrease in concentrations of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 was observed between active and remission phases (P<0.0001, P=0.002, P=0.001 and P=0.001 respectively). No significant differences were observed in sL-selectin levels between active and remission phases. sL-selectin concentrations (802+/-306 ng/ml) during the remission phase remained lower than those observed in healthy controls (P<0.0001). No correlation was observed between serum creatinine and sE-selectin, sP-selectin, sICAM-1 and sVCAM-1 in patients of the CRF group. A slight negative correlation was established between creatinine and sL-selectin concentration. CONCLUSIONS: Increased serum levels of sE-selectin, sICAM-1, and sVCAM-1 and decreased levels of sL-selectin in active ANCA-associated vasculitis, and the normalization of sE-selectin, sICAM-1, and sVCAM-1 during the remission phase suggest that the concentration of soluble levels of these adhesion molecules reflects disease activity. The decrease in sP-selectin levels between active and inactive phases also suggest that this receptor may reflect clinical activity. The lack of correlation between serum levels of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 and the degree of renal failure in patients with CRF suggests that the mechanism of clearance of these molecules is not renal.

Cellular immunity analysis using monoclonal antibodies in human glomerulonephritis.

Monoclonal antibodies against class II antigens of the human major histocompatibility complex (MHC) (Edu 1), von Willebrand factor-related antigen marker of endothelial cell, T cells (Cris 1), helper/inducer T cells (T4) and cytotoxic/suppressor T cells (T8) by indirect immunofluorescence, and stain for nonspecific esterase characterizing monocytes-macrophages (Mo-Ma) were applied in 64 renal biopsies--54 glomerulonephritis (GN), 10 non-GN- and in 14 normal kidneys. Class II antigens were expressed on the endothelium of renal microvasculature in all specimens. Intraglomerular T cells and Mo-Ma were only present in GN. Mo-Ma appeared associated with endo- and extracapillary proliferation (Xc2 = 4.68; p less than 0.05), C3 (X2 = 4.21; p less than 0.05), and fibrinogen (X2 = 3.84; p less than 0.05) deposition; and those were most numerous in biopsies with intraglomerular T cells. Interstitial MHC-class II+ cells (Xc2 = 5.5; p less than 0.02), T cells (F = 3.37; p less than 0.005) and Mo-Ma (F = 2.45; p less than 0.05) were significantly higher in GN with endo- or extracapillary proliferation than in the remaining. In GN, correlations were seen between T cells and MHC-class II+ cells (r = 0.63; p less than 0.001), and Mo-Ma (r = 0.38; p less than 0.02), infiltrating the interstitium. Our results suggest that both humoral and cellular immunity contribute to macrophage glomerular infiltration in the human GN. Mononuclear cells, and no intrinsic renal cells, would be implicated in the cellular immune interactions in situ.

Plasmapheresis induced recovery from renal failure in mesangiocapillary glomerulonephritis of acute onset.

Plasmapheresis (PE) was used in the treatment of three patients with biopsy proven mesangiocapillary glomerulonephritis (MCGN) of acute onset and renal failure. The percent of glomeruli with extracapillary proliferation varied from 40 to 90 per cent. Following PE, there were reductions in serum creatinine of 66 per cent, 61 per cent and 82 per cent in patients, one, two and three respectively. Plasmapheresis proved effective in a second episode of renal failure in patient three. After the completion of PE, renal function has remained stable in all patients for periods ranging from two to 12 months. However, haematuria and heavy proteinuria persist in every case. PE appears to facilitate recovery from renal failure in MCGN of acute onset, possibly by removing circulating mediators of acute inflammatory glomerular damage.