Luis F. Arias

Glomerular diseases in a Hispanic population: review of a regional renal biopsy database

CONTEXT AND OBJECTIVE Epidemiological data provide useful information for clinical practice and investigations. This study aimed to determine glomerular disease frequencies in a region of Colombia and it represents the basis for future studies. DESIGN AND SETTING Single-center retrospective analysis at the University of Antioquia, Colombia. METHODS All native renal biopsies (July 1998 to December 2007) were reviewed, but only glomerular diseases were analyzed. The diagnosis of each case was based on histological, immunopathological and clinical features. RESULTS A total of 1,040 biopsies were included. In 302 cases (29.0%), the patients age was <or= 15 years. Primary glomerular diseases were diagnosed in 828 biopsies (79.6%) and secondary in 212 (20.4%). The most common primary diseases were focal and segmental glomerulosclerosis (FSGS) (34.8%), immunoglobulin A (IgA) nephropathy (IgAN) (11.8%), membranous glomerulonephritis (MGN) (10.6%), minimal change disease (MCD) (10.6%), crescentic glomerulonephritis (GN) (5.6%), and non-IgA mesangial proliferative GN (5.6%). Postinfectious GN represented 10.7% of the diagnoses if included as primary GN. Lupus nephritis corresponded to 17.8% of the entire series. In adults, the order of the most frequent primary diseases was: FSGS, IgAN, MGN, crescentic GN and MCD. In children (<or= 15 years), the most frequent were: FSGS, postinfectious GN, MCD, non-IgA mesangial proliferative GN, endocapillary diffuse GN and IgAN. CONCLUSIONS As among Afro-Americans, FSGS is the most frequent type of glomerulopathy in our population, but in our group, there are more cases of IgAN. The reasons for these findings are unclear. This information is an important contribution towards understanding the prevalence of renal diseases in Latin America.

C4D Immunostaining in Surveillance Endomyocardial Biopsies From Well-Functioning Heart Allografts

OBJECTIVE The meaning of biopsy C4d detection in heart allografts without dysfunction or morphologic changes suggesting antibody-mediated rejection (AMR) is not clear. The aim of this study was to search for an association between C4d detection in allograft biopsies of well-functioning hearts without changes suggestive of AMR, and clinical outcomes. METHODS Endomyocardial protocol biopsies from 44 heart transplant patients with well-functioning grafts and without changes suggesting AMR were performed at 1 month and 1 year after transplantation and analyze the presence of C4d deposition using immunohistochemistry. Two-year follow-up was based on clinical parameters and echocardiographic information. Heart graft function was categorized as good vs. poor. The presence of C4d, using diverse schemes to graduate the extension of the deposition, was correlated with clinical graft outcomes. RESULTS C4d deposition was observed in the capillary walls of 33 biopsies (37.5%; n = 25 patients; 56.8%). No biopsy had diffuse (>50%) immunostaining. Six patients presented with multifocal capillary C4d immunostaining in at least 1 biopsy. Capillary positivity for C4d (if focal or multifocal) showed no statistical association with cellular rejection or graft function. Perimyocytic C4d detection was neither associated with rejection nor graft outcome. CONCLUSION Our work failed to demonstrate an association between C4d detection in protocol biopsies of heart grafts and clinical outcomes. The clinical utility of C4d staining in solid organ transplantation may vary by organ. Our results suggest that C4d did not have clinical utility in surveillance biopsies of well-functioning heart grafts without morphological changes suggesting AMR.

Características inmunofenotípicas y clínicas del carcinoma renal mucinoso tubular y de células fusiformes

IMMUNOHISTOCHEMICAL PROFILE AND CLINICAL FEATURES OF MUCINOUS TUBULAR AND SPINDLE RENAL CELL CARCINOMA Introduction: We present the immunohistochemical (IHC) analyses of a series of four kidney tumors currently classified as mucinous tubular and spindle renal cell carcinoma (WHO), a tumor with uncertain histogenesis and differentiation. Our aims were to determine an immunoprofile and to add clinical and morphological information about this rare renal carcinoma. Material and methods: The four tumors were found between 415 renal carcinomas at our center (0.89%). IHC was carried out with a panel of antibodies in these four cases. Morphogical and clinical information was collected and analyzed. Results: All tumors were well circumscribed and confined to the kidney. Immunoreactivity for cytokeratin (CK)7 was intense and diffuse. Immunostaining was variable for EMA, vimentin, S-100, Ulex europaeus antigen, high-molecular-weight CK, CK 8, CK18, and CK 19. The tumors were homogeneously negative for CEA, CD15, CD10, CD34, desmin, actin, CK10, CK20, and HMB45. Proliferative index (Ki67) was <1% en all cases. The immu- noreactivity was similar in cuboidal and spindle cells. Conclusions: The present tumor shows a variable immunophenotype and there is not a precise cell type diffe- rentiation. The immunostaining in cuboidal and spindle cells suggests a similar differentiation and histogenesis.

T cell receptor beta chain (TCR-Vβ) repertoire of circulating CD4+ CD25−, CD4+ CD25low and CD4+ CD25high T cells in patients with long-term renal allograft survival

The mechanisms underlying maintenance of renal allografts in humans under minimal or conventional immunosuppression are poorly understood. There is evidence that CD4+ CD25+ regulatory T cells and clonal deletion, among other mechanisms of tolerance, could play a key role in clinical allograft survival. Twenty‐four TCR‐Vβ families were assessed in CD4+ CD25−, CD4+ CD25low and CD4+ CD25high T cells from patients with long‐term renal allograft survival (LTS), patients exhibiting chronic rejection (ChrRx), patients on dialysis (Dial) and healthy controls (HC) by flow cytometry. LTS patients presented a higher variability in their TCR‐Vβ repertoire, such decreased percentage of Vβ2+, Vβ8a+ and Vβ13+ in CD4+ CD25low and high compared with CD4+ CD25− subset and increased Vβ4 and Vβ7 families in CD4+ CD25high T cells exclusively. Additionally, LTS patients, particularly those that were not receiving calcineurin inhibitors (CNI), had increased percentages of CD4+ CD25high T cells when compared with Dial (P < 0.05) and ChrRx (P < 0.05) patients. Our results suggest that a differential expression of particular TCR‐Vβ families and high levels of circulating CD4+ CD25high T cells in long‐term surviving renal transplant patients could contribute to an active and specific state of immunologic suppression. However, the increase in this T cell subset with regulatory phenotype can be affected by CNI.

Tip variant of focal segmental glomerulosclerosis: outcome and comparison to ‘not otherwise specified’ variant

BACKGROUND The clinical significance of focal segmental glomerulosclerosis (FSGS) tip variant remains unclear. With the aim to determine its clinical and histological features, and natural history, we studied our cases of patients with this glomerular lesion. METHODS This is a retrospective analysis. All native renal biopsies from patients diagnosed as FSGS, between 1998 and 2006, were revised for cases with tip variant. Glomerulosclerosis (GS), segmental lesions and interstitial fibrosis (IF) were quantified. We analysed clinical and follow-up data and compared with cases of FSGS not otherwise specified (NOS). RESULTS In 248 primary FSGS cases, 37 corresponded to tip variant (14.9%). Median age was 17 years (range 1-65); 13 (35.1%) patients were <15 years old, and 56.8% were males. All patients had nephrotic proteinuria. At diagnosis, there were no significant differences for age, renal function and proteinuria between cases with NOS and tip variant. IF, GS and percentage of glomeruli with segmental lesions were higher in NOS than GTL (P < 0.01). At follow-up (n = 25), 15 patients received steroids alone, and 10 steroids and a cytotoxic agent. At a median follow-up of 48.7 months (24.3-86.7), 7 patients (28.0%) progressed to chronic kidney disease (CKD), 4 (16.0%) developed end-stage renal disease (ESRD) and 9 (36.0%) had complete remission. In NOS patients (n = 93), 48 (51.6%) developed CKD (P = 0.04), 20 (21.5%) developed ESRD (P = 0.54%) and 13 (14.0%) had complete remission (P = 0.02). CONCLUSIONS Our work does not demonstrate a clearly favourable prognosis in a group of patients with FSGS tip variant. Although in the tip variant there are less chronic renal tissue damage and CKD, and more frequent complete remission of the nephrotic syndrome, there is an important percentage of patients who develop CKD and ESRD.

Histologic variants of primary focal segmental glomerulosclerosis: presentation and outcome

INTRODUCTION The clinical significance of histologic variants of primary focal segmental glomerulosclerosis (FSGS) remains unclear. With the aim to determine presentation and outcome of the variants of FSGS in a hispanic population, we studied our cases of this glomerulopathy. METHODS In this retrospective study, all renal biopsies with FSGS (1998-2009), were classified according to the Columbias classification. We analyzed histological, clinical and follow-up data and compared among variants. RESULTS Among 291 cases, 224 (77.0%) corresponded to NOS variant, 40 cases (13.7%) to tip variant (TIP), 14 cases (4.8%) to perihilar (PH), 10 cases (3.4%) to collapsing (COLL) and three cases (1.0%) to cellular variant (CELL). Median age: 26 years (range 1 to 79); 74 patients (25.4%) were < 15 years of age. Hypertension and renal dysfunction were more frequent in PH and COLL cases. PH presented frequently as nonnephrotic proteinuria. There were fewer histologic chronic lesions in TIP cases. There was remission in 23.5% of patients with NOS, 57.7% of patients with TIP, 22.2% of patients with COLL and 0 patients with PH (p < 0.01). Chronic kidney disease (CKD) was less frequent in TIP than in the other variants (p = 0.03). There were not statistical differences for end-stage renal disease among variants. CONCLUSIONS Glomerular histological appearance is not a good indicator of outcome. COLL is a disease with many differences to the other variants and bad prognosis; PH is a variant mainly of adults, with frequent evolution to CKD. TIP appears as a less aggressive, although not benign, variant.

Varicella-zoster virus (VZV) and alpha 1 antitrypsin: a fatal outcome in a patient affected by endemic pemphigus foliaceus

Background  Herpes virus infections are well known infectious complications of pemphigus and bullous pemphigoid. We describe pathologic findings utilizing autopsy tissue from several organs from a patient affected by a new variant of endemic pemphigus in El Bagre, Colombia, South America.

Memory phenotype and polyfunctional T cells in kidney transplant patients

Allospecific memory T cells are a barrier against long-term graft survival. Production of multiple cytokines by a single T cell is considered a sign of an active ongoing immune response, the presence of these polyfunctional cells has not been addressed in transplanted patients accordingly to graft outcome. Memory phenotype, based on the expression of CD45RO and CD27, and polyfunctional T cells were evaluated in long-term graft survival patients (LTS), short-term survival patients (STS), chronic rejection patients (ChrRx), dialysis patients (DIAL) and healthy controls (Ctrls). Memory T cells were quantified ex vivo, after allogeneic and anti-CD3 plus anti-CD28 stimulation, in cells proliferating or not to these stimuli. The percentages of cells producing IFNγ, IL-2 and/or TNFα after allogeneic stimulation and the memory phenotype of single cytokine producing cells were evaluated. Ex vivo CD8+CD45RO-CD27- effector cells were decreased in transplanted patients compared to non-transplanted individuals. After allogeneic stimulation, CD4+CD45RO+CD27+, central memory cells in LTS and CD4+CD45RO-CD27- effector cells in Dial were augmented compared to Ctrls and ChrRx, and CD8+CD45RO-CD27- effector cells were increased in ChrRx. There were no differences in the percentage of single cytokine producing cells among the groups. IFNγ+TNFα+CD4 and CD8 cells were detected in Ctrls, STS and ChrRx and no cells positive for the three cytokines were found. The phenotype of cytokine producing cells was mainly effector memory. Interestingly, in LTS there was an increase in effector cells producing IFNγ and IL-2. Changes in subpopulation distribution in patients with different outcomes may be a reflection of the graft acceptance or rejection status.

Estudios auxiliares en el diagnóstico diferencial de tumores epiteliales renales con células granulares

ANCILLARY STUDIES IN THE DIFFERENTIAL DIAGNOSIS OF EPITHELIAL RENAL CELL TUMORS WITH GRANULAR CELLS Introduction and objectives: Differential diagnosis of renal neoplasms with granular cells may pose difficulties and implications on ontogeny and prognosis. Our aims are to characterize the pattern of immunostaining and to search for a useful diagnosis panel. Methods: We studied with colloidal iron staining (Mowrys modified method) and 22 commonly used immunomarkers 22 conventional carcinomas (CC), 37 chromophobe carcinomas (CPC), 8 oncocytomas (OC), and 7 collecting duct carci- nomas (CDC) with granular cells. Cases with not entirely clear diagnosis were excluded. Results: Colloidal iron staining was diffuse, strong, reticular, and cytoplasmic in 32 CPC cases, the diffuse and strong pattern was not observed in other tumors. The more useful diagnostic panel was cytokeratin 7 (CK7)/CD10/vimentine (vim). The 8 OC were negative for the three antibodies. The most common profile for CC was CK7-/CD10+/vim+, the CPC profile was CK7+/CD10-/vim-, and CDC did not show a particular profile. With these three antibodies specificity was >90% for the differential diagnosis. Adding colloidal iron staining specificity was 100%. Conclusions: Morphologic features, colloidal iron staining (modified Mowrys method), and immunostaining with CK7/CD10/vim permit the final diagnosis with high specificity. However, a 100% specific marker does not exist at the present time.INTRODUCTION AND OBJECTIVES Differential diagnosis of renal neoplasms with granular cells may pose difficulties and implications on ontogeny and prognosis. Our aims are to characterize the pattern of immunostaining and to search for a useful diagnosis panel. METHODS We studied with colloidal iron staining (Mowrys modified method) and 22 commonly used immunomarkers 22 conventional carcinomas (CC), 37 chromophobe carcinomas (CPC), 8 oncocytomas (OC), and 7 collecting duct carcinomas (CDC) with granular cells. Cases with not entirely clear diagnosis were excluded. RESULTS Colloidal iron staining was diffuse, strong, reticular, and cytoplasmic in 32 CPC cases, the diffuse and strong pattern was not observed in other tumors. The more useful diagnostic panel was cytokeratin 7 (CK7)/CD10/vimentine (vim). The 8 OC were negative for the three antibodies. The most common profile for CC was CK7-/CD10+/vim+, the CPC profile was CK7+/CD10-/vim-, and CDC did not show a particular profile. With these three antibodies specificity was >90% for the differential diagnosis. Adding colloidal iron staining specificity was 100%. CONCLUSIONS Morphologic features, colloidal iron staining (modified Mowrys method), and immunostaining with CK7/CD10/vim permit the final diagnosis with high specificity. However, a 100% specific marker does not exist at the present time.

Ureteritis por citomegalovirus en receptor de trasplante renal: Informe de un caso con presentación inusual

Resumen La infeccion por citomegalovirus (CMV) es la infeccion viral mas frecuente en pacientes trasplantados, pero es muy inusual el compromiso del tracto urinario. Solo se han informado unos pocos casos de uretritis por CMV en trasplantados renales. En los informes previos la presentacion clinica mas habitual es nefropatia obstructiva, a menudo en ausencia de enfermedad sistemica, o, algunas veces, puede simular un episodio de rechazo con minimos sintomas obstructivos. Nosotros describimos un caso mas de uretritis por CMV en un paciente trasplantado renal con ureterostomia y una presentacion muy inusual caracterizada por sintomas de infeccion de vias urinarias y ulceracion en la boca de la ureterostomia. El numero incrementado de informes de ureteritis por CMV en trasplantados renales plantea la posibilidad de un aumento en la incidencia de esta complicacion post-trasplante