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1.
Hum Pathol ; 38(12): 1798-809, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17714761

ABSTRACT

We retrospectively reviewed the clinicopathological features of a series of 68 renal AA amyloidosis observations collected between 1990 and 2005. The amyloidogenic disease was a chronic infection (40.8%), a chronic inflammation (38%), a tumor (9.9%), a hereditary disease (9.9%), or was undetermined in 1.4% of cases. Nephrotic syndrome and renal insufficiency were noted in 63.1% and 75% of patients, respectively. The distribution pattern of glomerular amyloid deposits was mesangial segmental (14.7%), mesangial nodular (26.5%), mesangiocapillary (32.3%), and hilar (26.5%). Glomerular form was observed in 80.9% of cases and vascular form in 19.1%. AA amyloidosis-related inflammation was noted in 30 patients (44.1%) and appeared as a multinucleated giant cell reaction (27.9%) or a glomerular inflammatory infiltrate (25%), including glomerular crescents (17.6%). At the end of follow-up, 26 patients (38.2%) showed end-stage renal disease. The clinical presentation of glomerular and vascular forms was distinct with a clear predominance of proteinuria in glomerular form. Inflammatory reaction was preferentially observed in biopsies with a codeposition of immunoglobulin chains and/or complement factors in AA amyloid deposits. The distribution pattern of glomerular amyloid deposits and glomerular inflammatory reaction were independent factors influencing proteinuria level. Tubular atrophy, abundance, and distribution pattern of glomerular amyloid deposits at the time of biopsy were independent predictors of renal outcome. In conclusion, the glomerular involvement appeared as the determining histological factor for clinical manifestations and outcome of renal AA amyloidosis. AA amyloidosis-related inflammation could partly result from an immune response directed against AA fibrils and could induce amyloid resolution and crescents.


Subject(s)
Amyloidosis/pathology , Inflammation/pathology , Kidney Diseases/metabolism , Kidney Diseases/pathology , Serum Amyloid A Protein/metabolism , Adult , Aged , Amyloidosis/metabolism , Female , Hematuria/etiology , Humans , Hypertension/etiology , Inflammation/metabolism , Kidney Diseases/complications , Male , Middle Aged , Proteinuria/etiology , Retrospective Studies
2.
Nephrol Dial Transplant ; 20(7): 1392-9, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15855209

ABSTRACT

BACKGROUND: Pauci-immune renal vasculitis with focal glomerular necrosis and crescent formation is usually associated with anti-neutrophil cytoplasmic antibodies (ANCAs). However, ANCA's are absent in up to 10% of cases, which constitutes a rarely studied variant of renal vasculitis. METHODS: This retrospective multicentre cohort study analyzed the presenting features, renal histology and outcome in 20 patients with pauci-immune crescentic necrotizing renal vasculitis in whom indirect immunofluorescence did not detect ANCA. RESULTS: Renal histology revealed a high percentage of active glomerular lesions (50%), mainly cellular crescents, 28% of them with glomerular necrosis. Chronic tissue damage with glomerulosclerosis (21%) and diffuse interstitial fibrosis (40%) was already present at diagnosis, more prominent than in historical PR3-positive patients. Infiltrates of polymorphonuclear neutrophils in glomerular capillary loops were observed in 40% of all biopsies, mainly in necrotic lesions. The subsets of interstitially infiltrating leukocytes similar to ANCA-associated disease. Microscopic polyangiitis was diagnosed in 17 patients, Wegener's granulomatosis in two and renal-limited vasculitis in one. The patients median disease extent index (DEI) of 5 (range 4-11) reflected a systemic vasculitis. ANCA-negative vasculitis was not associated with infection or malignancy. Renal outcome was correlated to DEI (P = 0.032) and serum creatinine at diagnosis (P = 0.04). The mortality rate was high (35%) and closely related to age above 65 years at diagnosis (P = 0.014). Conclusions. The histological findings and prognosis in ANCA-negative renal vasculitis are comparable with those of ANCA-positive disease. Our data underline the importance of the exact diagnosis in an active vasculitic disease process even in the absence of ANCAs.


Subject(s)
Glomerulonephritis/pathology , Vasculitis/pathology , Adult , Aged , Aged, 80 and over , Antibodies, Antineutrophil Cytoplasmic/blood , Cohort Studies , Creatinine/blood , Female , Glomerulonephritis/blood , Glomerulonephritis/complications , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Prognosis , Retrospective Studies , Severity of Illness Index , Vasculitis/blood , Vasculitis/complications
5.
Nephrol Dial Transplant ; 19(2): 386-90, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14736963

ABSTRACT

BACKGROUND: Adefovir (ADV), an orally administered nucleotide analogue active against hepadnaviruses, retroviruses and herpes viruses was shown to be effective in HIV-infected patients, but the prevalence of nephrotoxicity with doses of 60-120 mg/day was considered unacceptable. Recently, lower doses of ADV were shown to be effective for the treatment of HIV-1 patients with chronic lamivudine (LAM)-resistant hepatitis B. METHODS: In a cohort of 35 patients infected with both HIV-1 and LAM-resistant hepatitis B virus, we investigated the renal tolerance of a once-daily dose of ADV 10 mg over 52 weeks. Their mean baseline creatinine clearance was within the normal range (105 +/- 3 ml/min/1.73 m(2)). No patient had significant changes in renal function or electrolyte balance secondary to ADV treatment. RESULTS: Transient increases in serum creatinine, which resolved by the end of the study were noted in two patients and three developed proteinuria, which was felt to be unrelated to ADV treatment. The cohort's mean serum phosphate level, 2.45 +/- 0.09 mg/dl at baseline, did not change significantly under treatment (2.66 +/- 0.12 mg/dl at week 52, P = NS). CONCLUSIONS: Our study shows that ADV dosed at 10 mg/day for the treatment of LAM-resistant chronic hepatitis B in patients co-infected with HIV is not associated with renal tubular dysfunction or a significant change in renal function.


Subject(s)
Adenine/analogs & derivatives , Adenine/administration & dosage , HIV Infections/complications , HIV Infections/drug therapy , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/drug therapy , Kidney/drug effects , Organophosphonates , Administration, Oral , Adult , Cohort Studies , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Resistance, Viral , Female , Follow-Up Studies , HIV Infections/diagnosis , Hepatitis B, Chronic/diagnosis , Humans , Kidney Function Tests , Lamivudine/administration & dosage , Male , Maximum Tolerated Dose , Middle Aged , Prospective Studies , Risk Assessment , Treatment Outcome
6.
Hum Pathol ; 34(12): 1350-4, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14691923

ABSTRACT

Morphological examination of 2 renal biopsy specimens obtained from a 69-year-old woman with a nephrotic syndrome, high blood pressure, and a reduced glomerular filtration rate revealed, in ultrastructural study, a type of a glomerulonephritis with fibrillar deposits in a subendothelial position which were unusual in their immunoglobulin components (mainly IgM). The fibrillar components were of irregular size, 13 to 18 nm in diameter and presented a very particular "barbed wire" morphological aspect, not hitherto described. Diffraction studies and image analysis, revealed spiraled fibrils with regular alternating elements that we suggest may correspond to IgM molecules. The clinical (isolated renal symptoms) and laboratory (traces of 3 monoclonal components in the serum and 2 normal bone marrow biopsy specimens) data provided no evidence of hematopoietic malignancy, viral hepatitis or cryoglobulinemia.


Subject(s)
Glomerulonephritis/pathology , Immunoglobulin M/ultrastructure , Kidney Glomerulus/ultrastructure , Aged , Female , Glomerulonephritis/immunology , Glomerulonephritis/physiopathology , Humans , Image Processing, Computer-Assisted , Kidney Glomerulus/pathology , Microscopy, Electron , Microscopy, Fluorescence , X-Ray Diffraction
8.
Am J Kidney Dis ; 41(6): 1205-11, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12776272

ABSTRACT

BACKGROUND: The association of thrombotic events and/or pregnancy complications with circulating antiphospholipid antibodies defines antiphospholipid syndrome (APS). In previous reports, renal involvement in APS consisted mainly of thrombotic vascular complications involving large vessels or intrarenal small-sized vessels (APS nephropathy). We report 9 cases of glomerulonephritis associated with APS. These cases are characterized by predominant pathological features distinct from vascular APS nephropathy. METHODS: We reviewed consecutive renal biopsies examined in 2 French university hospitals between 1980 and 2002 and identified renal biopsies performed in patients with primary APS. RESULTS: We identified 29 biopsies performed in patients with APS. Twenty biopsies showed characteristic features of APS nephropathy. In 9 cases, predominant pathological features distinct from vascular APS nephropathy were noted: membranous nephropathy (3 cases), minimal change disease/focal segmental glomerulosclerosis (3 cases), mesangial C3 nephropathy (2 cases), and pauci-immune crescentic glomerulonephritis (1 case). In 7 cases, the presentation of renal symptoms was subacute or chronic. Two patients experienced episodes of acute renal failure. At referral, median creatinine clearance was 50 mL/min (0.83 mL/s) (range, 18 to 117 mL/min [0.30 to 1.95 mL/s]). Proteinuria was noted in all cases (range, 1.5 to 15 g/d), with nephrotic syndrome in 4 cases. Lupus anticoagulant was present in all cases, and anticardiolipin antibodies, in 8 cases. Anti-DNA antibodies repeatedly were negative in all cases. Treatment consisted of antihypertensive therapy (6 cases), anticoagulant drugs (5 cases), steroids (4 cases), and antiplatelet drugs (3 cases). At last follow-up, renal function remained stable in 7 patients. Of 2 patients presenting with acute renal failure, 1 patient recovered normal renal function, whereas the other patient progressed to end-stage renal failure. CONCLUSION: The cases reported here represent a new aspect of the expanding spectrum of renal diseases encountered in association with APS.


Subject(s)
Antiphospholipid Syndrome/complications , Autoimmune Diseases/complications , Kidney Diseases/etiology , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Anticoagulants/therapeutic use , Antihypertensive Agents/therapeutic use , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/drug therapy , Autoantibodies/analysis , Autoimmune Diseases/blood , Autoimmune Diseases/drug therapy , Biopsy , Blood Proteins/analysis , Female , France/epidemiology , Glomerulonephritis/epidemiology , Glomerulonephritis/etiology , Glomerulonephritis, Membranoproliferative/epidemiology , Glomerulonephritis, Membranoproliferative/etiology , Glomerulonephritis, Membranous/epidemiology , Glomerulonephritis, Membranous/etiology , Glomerulosclerosis, Focal Segmental/epidemiology , Glomerulosclerosis, Focal Segmental/etiology , Humans , Hypertension/drug therapy , Hypertension/etiology , Kidney/pathology , Kidney Diseases/drug therapy , Kidney Diseases/epidemiology , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/etiology , Male , Nephrosis, Lipoid/epidemiology , Nephrosis, Lipoid/etiology , Nephrotic Syndrome/epidemiology , Nephrotic Syndrome/etiology , Platelet Aggregation Inhibitors/therapeutic use , Retrospective Studies , Thrombophilia/drug therapy , Thrombophilia/etiology
9.
J Am Soc Nephrol ; 13(12): 2962-8, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12444215

ABSTRACT

Cyclosporine (CsA), a widely used immunosuppressive drug, is an effective treatment of sight-threatening posterior idiopathic uveitis. CsA's main side effect is nephrotoxicity. The aim of this single-center prospective cohort study (conducted in a tertiary care teaching hospital in Paris, France) was to assess the long-term renal tolerance of a low-dose CsA treatment in patients with previously healthy kidneys on clinical, biologic, and pathologic criteria. Forty-one patients treated with 4.3 +/- 1.6 mg/kg body wt per day CsA for 44.9 +/- 3.6 mo were included. Mean follow-up was 55.4 +/- 0.2 mo. BP, CsA trough level, and renal function were prospectively monitored together with blood urea, creatinine clearance, GFR, and effective renal plasma flow. Eleven patients underwent serial kidney biopsies before and after 2 yr of a 4 +/- 0.9 mg/kg daily CsA treatment. Sustained low-dose CsA treatment induced a significant increase in plasma creatinine (P < 0.0001), a significant decrease in creatinine clearance (P < 0.0001), and isotopic GFR (P < 0.0001) over time. The highest dose induced more severe alterations in any of the renal parameters than the lowest dose. Prevalence of hypertension was particularly high. Histopathologic data showed significant interstitial fibrosis (P < 0.003) and tubular atrophy (P < 0.003) after 2 yr. Low-dose long-term CsA treatment induces significant renal impairment and a high incidence of hypertension. Our study suggests that lowering daily dosage may prevent CsA-induced nephrotoxicity if a daily dose of < or =3 mg/kg is used. Whether once established it is reversible is still prospective, although the occurrence of interstitial fibrosis in the kidney would argue against reversibility.


Subject(s)
Cyclosporine/administration & dosage , Immunosuppressive Agents/administration & dosage , Kidney/drug effects , Uveitis/drug therapy , Adult , Atrophy , Cohort Studies , Creatinine/blood , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Fibrosis , Follow-Up Studies , Glomerular Filtration Rate/drug effects , Humans , Hypertension/chemically induced , Kidney/pathology , Kidney Tubules/drug effects , Kidney Tubules/pathology , Male , Middle Aged , Prospective Studies
10.
Gastroenterology ; 123(5): 1436-40, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12404216

ABSTRACT

BACKGROUND & AIMS: In Crohn's disease, cases of interstitial nephritis with renal failure have been reported in connection with the use of mesalamine. METHODS: We observed 4 patients with severe interstitial nephritis proven by examination of kidney biopsy specimens. Renal failure was discovered before or simultaneously with the diagnosis of Crohn's disease, and patients were not treated with mesalamine. Impairment of renal function progressed to end-stage renal failure in 3 of the 4 patients. RESULTS: Our results show that the kidney can be an extraintestinal target of Crohn's disease. CONCLUSIONS: Several unanswered questions remain concerning the frequency of interstitial nephritis in patients with Crohn's disease, as well as the exact role of mesalamine in the development of chronic interstitial nephritis.


Subject(s)
Crohn Disease/complications , Nephritis, Interstitial/etiology , Adult , Disease Progression , Female , Humans , Kidney Failure, Chronic/etiology , Male
11.
Nephron ; 91(3): 416-23, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12119471

ABSTRACT

BACKGROUND: Idiopathic collapsing glomerulopathy (ICG) and HIV-associated nephropathy (HIV-AN) are characterized by severe nephrotic syndrome, collapse and sclerosis of the glomerular tuft with prominent podocyte alterations and extensive tubulointerstitial lesions. We previously showed phenotypic changes in podocytes from patients with diffuse mesangial sclerosis, a severe glomerulopathy sharing several morphological features with collapsing glomerulopathy. The aim of this study was to analyze the podocyte phenotype in ICG and HIV-AN. METHODS: Using immunohistochemical techniques, we studied the podocyte expression of the transcription factor WT1 and its target PAX2, GLEPP1, synaptopodin and vimentin as markers of podocyte maturity and of proliferating cell nuclear antigen (PCNA) as a marker of proliferation. Apoptosis was analyzed by the TUNEL method. Results from renal biopsies of ICG and HIV-AN were compared with those obtained from normal kidney, minimal change nephrotic syndrome (MCNS), focal and segmental glomerulosclerosis (FSGS) and membranous glomerulonephritis (MGN). RESULTS: Abnormal distribution of WT1 and PAX2 and extensive loss of podocyte markers were observed in ICG and HIV-AN; this dysregulation was associated with podocyte proliferation without detectable apoptosis. In contrast, no podocyte changes were detected in MCNS or MGN. In FSGS, phenotypic changes, without proliferation, were restricted to podocytes surrounding focal and segmental glomerular lesions. Increased PCNA expression and apoptosis were observed in ICG and HIV-AN tubular cells. CONCLUSION: Dysregulation of podocyte phenotype and proliferation are present in both ICG and HIV-AN. This suggests that, whatever their etiology, both types of collapsing glomerulopathy share a common pathogenic pathway. Upregulation of cell proliferation and apoptosis observed in tubular epithelial cells is probably involved in the occurrence of severe tubulointerstitial lesions in collapsing glomerulonephritis.


Subject(s)
AIDS-Associated Nephropathy/pathology , Epithelial Cells/metabolism , Glomerulosclerosis, Focal Segmental/pathology , Kidney Glomerulus/metabolism , AIDS-Associated Nephropathy/metabolism , Adolescent , Adult , Apoptosis/physiology , Biomarkers , Biopsy , Cell Division/physiology , Child , Child, Preschool , DNA-Binding Proteins/metabolism , Epithelial Cells/cytology , Female , Glomerulonephritis, Membranous/metabolism , Glomerulonephritis, Membranous/pathology , Glomerulosclerosis, Focal Segmental/metabolism , Humans , In Situ Nick-End Labeling , Kidney Glomerulus/cytology , Male , Membrane Proteins/metabolism , Microfilament Proteins/metabolism , Nephrosis, Lipoid/metabolism , Nephrosis, Lipoid/pathology , PAX2 Transcription Factor , Phenotype , Proliferating Cell Nuclear Antigen/metabolism , Protein Tyrosine Phosphatases/metabolism , Receptor-Like Protein Tyrosine Phosphatases, Class 3 , Transcription Factors/metabolism , Vimentin/metabolism , WT1 Proteins/metabolism
12.
J Am Soc Nephrol ; 13(1): 42-52, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11752020

ABSTRACT

In the course of the antiphospholipid syndrome (APS), the existence of vaso-occlusive lesions capable of affecting numerous organs is now well established. The renal involvement attributable to primary APS, APS nephropathy (APSN), corresponds to vaso-occlusive lesions of the intrarenal vessels, associating side-by-side, acute thromboses with chronic arterial and arteriolar lesions, leading to zones of cortical ischemic atrophy. A retrospective study of 114 lupus patients undergoing renal biopsy was undertaken to determine the following: (1) if APSN can be found in the course of systemic lupus erythematosus (SLE); (2) if certain clinical and biologic factors can permit the prediction of the presence of APSN; and (3) if APSN is a superadded renal morbidity factor in lupus patients. This study shows the following: (1) APSN occurs in SLE (32% of patients with renal biopsies) in addition to, and independently of, lupus nephritis; (2) APSN is statistically associated with lupus anticoagulant but not with anticardiolipin antibodies; (3) APSN is associated with extrarenal APS, mainly arterial thromboses and obstetrical fetal loss, but not with the venous thromboses of APS; (4) APSN is an independent risk factor, over and above lupus nephritis, that contributes to an elevated prevalence of hypertension, elevated serum creatinine, and increased interstitial fibrosis. Thus, it seems likely that, because of its associations with hypertension, elevated serum creatinine, and increased interstitial fibrosis, APSN may worsen the prognosis in these patients. APSN may also have therapeutic significance in that its recognition should permit a better balance between immunosuppressor and antithrombotic and/or vasoprotective therapy. Finally, this study suggests that APSN should be considered as an element to be included in the classification criteria of APS.


Subject(s)
Antiphospholipid Syndrome/etiology , Kidney Diseases/etiology , Lupus Erythematosus, Systemic/complications , Adolescent , Adult , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/complications , Creatinine/blood , Female , Genital Diseases, Female/etiology , Humans , Hypertension/etiology , Kidney Glomerulus , Lupus Coagulation Inhibitor/analysis , Lupus Nephritis/etiology , Male , Middle Aged , Prognosis , Retrospective Studies , Thrombosis/etiology
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