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1.
Transpl Immunol ; 20(1-2): 61-7, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18929659

ABSTRACT

To assess the significance of antibodies detected by complement-dependent cytotoxicity (CDC), solid phase (SPA) and flow cytometry (FC) assays we compared their predictive value in 354 consecutive cases of deceased-donor kidney transplantation. Pre-transplantation screening of anti-HLA class I and class II antibodies was performed by CDC and SPA. The direct crossmatch between recipients' sera and donors' T and B cells was performed by CDC followed by FC and SPA ("virtual cross-match"). The past history of antibodies displayed by the recipient was not considered a contraindication for transplantation even when it showed DSA. A side-by-side comparison of the correlation between graft loss, history of DSA and cross-match results indicated that sensitivity was 5%, 16% and 17% while specificity was 99%, 93% and 86% in CDC, SPA, FC crossmatches respectively. There was no significant difference between the 3 year survival of primary and secondary kidney allografts. We conclude that screening and cross-matching the sera by CDC provides reliable results and optimizes the patient's chances to receive a transplant. SPA and FC, however, are of great importance for identifying patients which require close monitoring by biopsy and serology for early diagnosis and treatment of acute antibody mediated rejection (AAMR).


Subject(s)
Graft Rejection/immunology , Histocompatibility Antigens Class II/immunology , Histocompatibility Antigens Class I/immunology , Histocompatibility Testing/methods , Isoantibodies/blood , Kidney Transplantation/immunology , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Cadaver , Cytotoxicity Tests, Immunologic , Female , Flow Cytometry , Graft Rejection/drug therapy , Graft Rejection/mortality , Graft Survival/immunology , Humans , Immunosuppression Therapy , Kidney Transplantation/mortality , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Predictive Value of Tests , Sensitivity and Specificity , Tacrolimus/administration & dosage , Tacrolimus/therapeutic use
2.
Kidney Int ; 73(8): 909-10, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18379527

ABSTRACT

The worldwide prevalence of obesity continues to rise. Obesity has been shown to increase the risk of both the development and the progression of renal failure, even after correction for other comorbid conditions. The ability of nephrologists to intervene will require greater understanding of obesity's renal physiologic effects. Kidney biopsies and functional studies performed on morbidly obese patients without overt renal disease who presented for bariatric surgery have helped to elucidate the earliest obesity-related structural and functional responses.


Subject(s)
Kidney Glomerulus/pathology , Obesity, Morbid/pathology , Humans
8.
Kidney Int ; 71(6): 491-5, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17264872

ABSTRACT

The 2003 International Society of Nephrology (ISN)/Renal Pathology Society (RPS) Classification of lupus nephritis (LN) was designed to eliminate ambiguities and standardize definitions. Major changes from the 1982 Modified WHO Classification include the elimination of the normal biopsy category and the subcategories of membranous Class V, the introduction of sharper distinctions between the classes, and the addition of subcategories within diffuse LN (class IV) for predominantly segmental (LN IV-S) and global (LN IV-G) lesions. It stipulates that sclerotic glomeruli owing to scarred LN should be taken into account when assessing the percentage of glomeruli affected by LN. Since its publication, the ISN/RPS classification has been used successfully in a number of clinical-pathologic studies. Several studies addressing the relationship between LN IV-S and LN IV-G have failed to identify a significantly worse outcome in IV-S than IV-G, although there were some differences in presenting clinical and pathologic features. Importantly, the ISN/RPS classification has achieved its goal of improved interobserver reproducibility. Its use has increased the percentage of LN biopsies meeting criteria for class IV. As it gains widespread acceptance, the ISN/RPS classification is already providing a standardized approach to renal biopsy interpretation needed to compare outcome data across centers.


Subject(s)
Kidney Glomerulus/pathology , Lupus Nephritis/classification , Biopsy , Humans , Observer Variation , Reproducibility of Results , Sclerosis/pathology , Societies, Medical
11.
Transplant Proc ; 38(10): 3384-7, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17175278

ABSTRACT

INTRODUCTION: Our center has recently observed foreign carbohydrate-appearing particles (FP) on transplant postreperfusion biopsy specimens: (PRBx). METHODS: To further characterize FPs, we reviewed all renal transplant RBx (30-45 minutes) performed between September 1, 2004 and December 3, 2005. Donor, preservation, and outcome variables were collected among patients with FP. RESULTS: A total of 135 PRBx were performed (45 deceased donors [DD] and 90 live donors [LD]). Fifteen PRBx demonstrated FP. All 15 cases were DD kidneys that underwent machine perfusion (MP) on the Waters RM3 (Waters Medical Systems, Rochester, Minn, United States) with Belzer MP solution (Trans Med, Elk River, Minn, United States). Donor age was 39.8 +/- 15.7 years. Terminal creatinine level was 1.45 +/- 0.8 mg/dL. Two of 15 were flushed in situ with HTK solution (no starch). Cold ischemia time was 28.8 +/- 9.1 hours with 14.3 +/- 5.1 hours of MP. In 13 of 15 patients, perfusion parameters were excellent (flow > 100 mL; resistance < .35). CHARACTERISTICS OF FP: Particles were 10-30 mu and globular in shape. FP were not visible on hematoxylin and eosin stain, but stained strongly periodic acid-Schiff-(PAS) positive and were refractile under polarized light. FP were seen segmentally within glomerular capillaries in all cases and in peritubular capillaries in 3. In 11 of the 15 cases with FP, focal glomerular fibrin thrombi or intracapillary neutrophil margination was seen. Ten of 15 patients with FP had a biopsy within the first week with no identifiable FP. OUTCOMES: Recipient age was 45.3 +/- 11.6 years. Eight patients (53.3%) had delayed graft function. Biopsy-proven rejection occurred in 3 patients (20%). Three-month creatinine level was 1.59 +/- 0.35 mg/dL. One graft was lost to early thrombosis in a patient with a hypercoagulable state and 1 patient died of sepsis at 2 months. All remaining 13 patients are alive with excellent graft function at a median follow-up of 6.7 months (range, 3-17 months). CONCLUSIONS: Microscopic intrarenal particles may be seen on DD kidney PRBx after MP. These FPs likely originate from surgical gloves. FPs are too small to be captured by standard filters but clear spontaneously and do not have deleterious effects on renal function or outcomes.


Subject(s)
Kidney Transplantation/pathology , Organ Preservation/methods , Adult , Biopsy , Cadaver , Carbohydrates/analysis , Creatinine/blood , Follow-Up Studies , Foreign Bodies/pathology , Humans , Kidney Glomerulus/cytology , Kidney Glomerulus/ultrastructure , Kidney Transplantation/physiology , Living Donors , Middle Aged , Time Factors , Tissue Donors , Treatment Outcome
13.
Kidney Int ; 70(12): 2148-51, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17063172

ABSTRACT

Direct immunofluorescence (IF) on frozen tissue is the method of choice for the study of medical renal diseases. When no glomeruli are available, IF can be performed on the formalin-fixed paraffin-embedded tissue allocated for light microscopy after antigen retrieval with proteases. In this study, the results of IF on frozen tissue (IF-F) and on deparaffinized, pronase-treated tissue (IF-P) were compared in 71 renal biopsies representing 12 major renal diseases. Using IF-P, diagnostic findings were obtained in 100% of cases of lupus nephritis, acute post-infectious glomerulonephritis, cryoglobulinemic glomerulonephritis, fibrillary glomerulonephritis, primary amyloidosis, myeloma cast nephropathy, and light-chain Fanconi syndrome (LCFS), 88% of cases of immunoglobulin (Ig)A nephropathy, 80% of cases of light-chain deposition disease, 60% of cases of membranoproliferative glomerulonephritis type 1, 50% of cases of idiopathic membranous glomerulopathy (MGN) and 20% of cases of anti-glomerular basement membrane (GBM) disease. IF-P was less sensitive than IF-F for the detection of C3 in all disease categories and for the detection of IgG in cases of MGN and anti-GBM disease. The diagnostic kappa light-chain staining was demonstrated in 100% of cases of LCFS by IF-P versus 40% by IF-F. We conclude that IF-P is a valuable salvage immunohistochemical technique for renal biopsies lacking adequate cortical sampling for IF-F, and is superior to IF-F for the diagnosis of LCFS.


Subject(s)
Fluorescent Antibody Technique/methods , Kidney Diseases/pathology , Kidney/pathology , Paraffin Embedding , Pronase , Antigen-Antibody Complex , Biopsy , Frozen Sections , Humans , Immunoglobulin G , Immunoglobulin kappa-Chains , Kidney/immunology , Kidney Diseases/immunology , Sensitivity and Specificity
14.
Kidney Int ; 70(10): 1783-92, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17021605

ABSTRACT

Five pathologic variants of idiopathic focal segmental glomerulosclerosis (FSGS) are recognized: collapsing (COLL), cellular (CELL), glomerular tip lesion (GTL), perihilar, and not otherwise specified (NOS). The prognostic significance of CELL FSGS has not been determined. We compared the presenting clinical and pathologic characteristics in 225 patients with CELL (N=22), COLL (N=56), GTL (N=60), and NOS (N=87) variants of idiopathic FSGS. CELL, COLL, and tip lesion all showed greater frequency and severity of nephrotic syndrome, and shorter time to biopsy compared to NOS. Predictors of end-stage renal disease (ESRD) for all FSGS patients included initial serum creatinine, % global sclerosis, % COLL lesions, chronic tubulo-interstitial injury score, and lack of remission response. COLL FSGS had the highest rate of renal insufficiency at presentation, most extensive glomerular involvement and chronic tubulo-interstitial disease, fewest remissions (13.2%), and highest rate of ESRD (65.3%). GTL patients were older and showed the highest remission rate (75.8%) and lowest rate of ESRD (5.7%). CELL variant showed intermediate rates of remission (44.5%) and ESRD (27.8%) compared to COLL and tip lesion. CELL variant may include cases of unsampled tip or COLL lesion, underscoring the importance of adequate sampling. Our data support the view that CELL and COLL FSGS are not equivalent and validates an approach to pathologic classification that distinguishes between COLL, CELL, and tip lesion variants of FSGS.


Subject(s)
Glomerulosclerosis, Focal Segmental/classification , Glomerulosclerosis, Focal Segmental/pathology , Kidney Glomerulus/pathology , Podocytes/pathology , Adolescent , Adult , Age Factors , Child , Cohort Studies , Creatinine/blood , Female , Glomerulosclerosis, Focal Segmental/complications , Glomerulosclerosis, Focal Segmental/therapy , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/physiopathology , Kidney Glomerulus/physiopathology , Male , Middle Aged , Predictive Value of Tests , Renal Insufficiency/pathology , Renal Insufficiency/physiopathology , Retrospective Studies , Sclerosis , Severity of Illness Index , Treatment Outcome
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