Cephotaxime-associated allergic interstitial nephritis and MPO-ANCA positive vasculitis.

We report a case of reversible acute renal failure after cephotaxime treatment in a patient affected by non-Hodgkin lymphoma. Renal biopsy showed necrotizing vasculitis associated with eosinophil-rich interstitial inflammatory infiltrates and patchy infiltrates of CD20+ lymphoid cells. High serum p-ANCA titers were also detected. Drug withdrawal was closely related with recovery of renal function and disappearance of ANCA. Acute renal failure therefore represented a consequence of ANCA-mediated renal vasculitis and acute interstitial nephritis related to cephotaxime treatment

Preimplantation biopsy predicts delayed graft function, glomerular filtration rate and long-term graft survival of transplanted kidneys

Background The predictive value of preimplantation biopsies for long-term graft function is often limited by conflicting results. The aim of this study was to evaluate the influence of time-zero graft biopsy histological scores on early and late graft function, graft survival and patient survival, at different time points. Methods We retrospectively analyzed 284 preimplantation biopsies at a single center, in a cohort of recipients with grafts from live and deceased donors (standard and nonstandard), and their impact in posttransplant renal function after a mean follow-up of 7 years (range 1–16). Implantation biopsy score (IBS), a combination score derived from 4 histopathological aspects, was determined from each sample. The correlation with incidence of delayed graft function (DGF), creatinine clearance (1st, 3rd and 5th posttransplant year) and graft and patient survival at 1 and 5 years were evaluated. Results Preimplantation biopsies provided somewhat of a prognostic index of early function and outcome of the transplanted kidney in the short and long term. In the immediate posttransplantation period, the degree of arteriolosclerosis and interstitial fibrosis correlated better with the presence of DGF. IBS values between 4 and 6 were predictive of worst renal function at 1st and 3rd years posttransplant and 5-year graft survival. The most important histological finding, in effectively transplanted grafts, was the grade of interstitial fibrosis. Patient survival was not influenced by IBS. Conclusions Higher preimplantation biopsy scores predicted an increased risk of early graft losses, especially primary nonfunction. Graft survival (at 1st and 5th years after transplant) but not patient survival was predicted by IBS

Decreased C-Src Expression Enhances Osteoblast Differentiation and Bone Formation

c-src deletion in mice leads to osteopetrosis as a result of reduced bone resorption due to an alteration of the osteoclast. We report that deletion/reduction of Src expression enhances osteoblast differentiation and bone formation, contributing to the increase in bone mass. Bone histomorphometry showed that bone formation was increased in Src null compared with wild-type mice. In vitro, alkaline phosphatase (ALP) activity and nodule mineralization were increased in primary calvarial cells and in SV40-immortalized osteoblasts from Src−/− relative to Src+/+ mice. Src-antisense oligodeoxynucleotides (AS-src) reduced Src levels by ∼60% and caused a similar increase in ALP activity and nodule mineralization in primary osteoblasts in vitro. Reduction in cell proliferation was observed in primary and immortalized Src−/− osteoblasts and in normal osteoblasts incubated with the AS-src. Semiquantitative reverse transcriptase-PCR revealed upregulation of ALP, Osf2/Cbfa1 transcription factor, PTH/PTHrP receptor, osteocalcin, and pro-alpha 2(I) collagen in Src-deficient osteoblasts. The expression of the bone matrix protein osteopontin remained unchanged. Based on these results, we conclude that the reduction of Src expression not only inhibits bone resorption, but also stimulates osteoblast differentiation and bone formation, suggesting that the osteogenic cells may contribute to the development of the osteopetrotic phenotype in Src-deficient mice

Histopathology of Lupus Nephritis

The spectrum of morphologic changes in lupus nephritis, either microscopic, ultrastructural, or immunohistological, closely reflects the great variety of immune complexes that are produced in the course of the disease. Every tissue component of the kidney can be affected, but glomeruli are the target structure in most patients. Several attempts have been made to correlate the clinical severity and the outcome of the nephritis with the pathologic features; the current classification and the six classes that resulted from an international study group are entirely based on glomerular changes. Major criteria of classification include the focal or diffuse involvement of the glomerulus, the site of hypercellularity, the site of immune complex deposition and the presence of active and/or sclerotic lesions. Even if less thoroughly investigated than the glomerulus, the interstitial compartment has revealed many interesting features as are vascular lesions, a common and often underestimated feature. Typing of subpopulation of lymphoid infiltrates supports the emerging evidence indicating that B cells are promoting autoimmunity in mechanisms other than autoAb secretion. Many aspects are still debated and/or poorly understood, such as the interpretation of the so-called "full house nephropathy" that closely mimic lupus nephritis in seronegative patients

Glomerulosclerosis: pathogenetic mechanisms and possibility of regression

Glomerular sclerosis means an increase in the extracellular matrix of the glomerulus. It is a complex, heterogeneous phenomenon with multiple cellular and biochemical mechanisms and different morphological patterns, depending on a variety of local and systemic factors. The term as such does not indicate the quantity nor the type of components of the deposited matrix. The amount of extracellular matrix increases in three types of events: - matrix deposition in areas that were destroyed by a necrotizing process (scars following glomerular necrosis); - matrix deposition in glomerular regions where matrix is normally found (mesangium, glomerular basement membranes) as seen in diabetic nephropathy; - matrix deposition inside or around collapsing capillaries involving the entire glomerulus or a segment of it (focal segmental glomerular sclerosis with nephrotic syndrome). Knowledge of the diverse morphological patterns producing glomerular sclerosis and the cellular and molecular mechanisms involved is essential for obvious reasons: they represent the rationale for any therapy aimed at preventing or reducing the progression of sclerosis and can provide a starting point to determine which forms are, at least potentially, reversible

The renal pathology in light chain deposition disease

Light Chain Deposition Disease (LCDD) is a relatively frequent renal disease associated with dysproteinemia. Although the light chain deposits can be widespread, the kidney is the most frequently involved organ, and renal involvement can dominate the clinical condition. The morphological features of LCDD can be recognized by light microscopy; however, the diagnosis can be made certain only by immunofluorescence microscopy, using antisera to kappa and lambda chains, and by electron microscop

NODAL PERIPHERAL T -CELL LYMPHOMA ASSOCIATED WITH WARTHIN'S TUMOR

Warthin’s tumour (cystadenoma ‘lymphomatosum’ papilliferum) of the salivary glands can also be observed in upper cervical lymph nodes. Both in the salivary glands (mainly the parotid gland) and in the neighbouring lymph nodes, Warthin’s tumour may be associated with different lymphoproliferative disorders, the most common being follicular lymphomas and Hodgkin’s lymphoma, that may develop from the reactive lymphoid component of this benign epithelial tumour. To the best of our knowledge no well-documented cases of association of Warthin’s tumour and T-cell lymphoma in the same site have been described so far. We report the case of a 66-year-old male patient who underwent a lymph node biopsy in January 2004 due to upper right cervical lymphadenopathy. The lymphnode biopsy discovered the presence of a Warthin’s tumour, mainly composed of cystic spaces with the typical bilayered oxyphilic epithelium. Our report indicates that the association of a T-cell lymphoma with a salivary gland-type Warthin’s tumour does exist, although extremely rare. This may be explained by the overall low incidence of T-cell lymphoproliferative diseases, and in particular of (nodal) peripheral T-cell lymphoma, NOS (<5% of all lymphoma cases). Thus, T-cell lymphomas have to be considered in the spectrum of lymphoproliferative disorders that may be associated with a Warthin’s tumour in the same site

Juvenile nephropathy in a Boxer dog resembling the human nephronophthisis-medullary cystic kidney disease complex

A juvenile nephropathy in a 4-year-old male Boxer dog, closely resembling the Nephronophthisis (NPHP)-Medullary Cystic Kidney Disease Complex (MCKD) in humans is described. Gross examination of the kidneys revealed several multiple cysts at the corticomedullary junction and in the medulla. Histological examination was characterized by a widespread tubular atrophy and dilatation, with a marked thickening of the tubular basement membrane, interstitial lymphocytic infiltration and fibrosis. Ultrastructural studies revealed dilated tubules with irregular basement membrane thickening and splitting. Lectin histochemistry investigation revealed that the cysts originated in the distal convoluted tubule and collecting duct. Having excluded all other known cystic diseases of the kidney, and based on the lectin histochemistry results, the macroscopic and histological findings of our case are highly compatible with a diagnosis of the NPHP-MCKD complex. To our knowledge, this is the first report describing this particular lesion

Aberrantly glycosylated IgA1 in glomerular immune deposits of IgA nephropathy

In IgA nephropathy, abnormal O-glycosylation of IgA1 molecules contributes to mesangial IgA1 deposition and the development of glomerular injury; however, direct in situ demonstration of aberrantly O-glycosylated IgA1 within glomerular immune deposits has not been reported. This study investigated the presence of abnormally glycosylated IgA1 in situ and its spatial relationship with complement within the immune deposits and correlated these features with glomerular lesion severity. Immunofluorescence and confocal microscopy were used to evaluate 19 consecutive renal biopsies, and the severity of glomerular lesions were also scored. Aberrantly glycosylated IgA was observed within the immune deposits, and its amount was found to correlate with both the severity of glomerular lesions and the amount of C3c on the surface of the deposits. These results demonstrate that qualitative and quantitative evaluation of aberrantly glycosylated IgA can be performed on routine renal biopsy samples. Its presence in immune deposits likely influences the spatial organization of IgA and C3c, thereby contributing to the glomerular inflammatory response in IgA nephropathy