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Poster presentada en el 50th ERA-EDTA Congress (European Renal Association - European Dialysis Transplant Association), celebrado del 18 al 21 de mayo de 2013 en Estambul (Turquia)

Lupus nephritis results from an acute inflammatory and immunological response to renal immune complex deposition. The acute response is characterized by activation of circulating leukocytes and renal parenchymal cells, triggering the production of pro-inflammatory cytokines and growth factors. In all too many cases, this response is followed by a chronic response, which is characterized by excessive deposition of collagen and other extracellular matrix macromolecules and the development of end-stage renal disease. Mechanisms underlying this chronic response in progressive renal disease are not adequately defined. In this overview, potential roles of reactive oxygen species (ROS) generation and transforming growth factor-β (TGF-β) production in the pathogenesis of lupus nephritis are considered. ROS and TGF-β may be key elements of a pathway leading to persistent and excessive matrix deposition in progressive lupus nephritis. Further studies to define the role of this pathway in lupus nephritis may lead to the development of additional, more specific therapeutic targets to prevent progression of renal disease.

We present an unusual case of metastatic renal cell carcinoma (RCC) mimicking diverticulitis in a 76-year-old man with a 16-year history of chronic lymphocytic leukaemia (CLL) and a 2 cm left renal mass. The patient presented with severe abdominal pain and lower gastrointestinal bleeding with anticoagulation from recent pulmonary embolism. His clinical course was troubled by recurrent hospitalisations and complications that delayed investigations and potential treatments. Radiographic findings revealed stable CLL, mild sigmoid diverticulitis and a small renal mass. Small renal masses (less than 4 cm) are considered low risk for metastasising and are, thus, often observed or ablated, rather than resected. Furthermore, gastrointestinal metastases from RCC are rare. This case adds new perspective to the unpredictable nature of RCC and how synchronous malignancies may be masked in patients with long-standing CLL.

IgA nephropathy (IgAN) is now recognized as the most common primary glomerulonephritis worldwide. Although the clinical course is variable, many patients develop slowly progressive renal disease, culminating in end-stage renal disease 10-20 years after diagnosis. Some recent randomized clinical trials have suggested that dietary fish oil supplementation may be a relatively safe long-term therapeutic option for preventing the development of progressive renal disease in patients with IgAN. However, other studies have failed to demonstrate a protective effect of dietary fish oil supplementation in treatment of IgAN. Although in vitro studies have provided a theoretical basis for the use of dietary fish oil supplementation, potential mechanisms underlying the protective effect of fish oil have not been well defined. In this overview, recent clinical and experimental data providing a basis for the use of dietary fish oil supplementation in treatment of IgAN and other progressive renal diseases are reviewed.

It was reported previously that dietary fish oil supplementation retarded the progression of renal disease in patients with IgA nephropathy in a multicenter, placebo-controlled, randomized, 2-yr clinical trial. The aim of this study was to determine the long-term influence of fish oil treatment on renal progression in observations on the study cohort of 106 patients extending beyond the 2-yr trial. Renal function was assessed by serial serum creatinine and 24-h urine protein measurements. Vital, end-stage renal disease (ESRD), and BP status and treatment beyond completion of the 2-yr trial were determined. As in the trial, the primary end point was an increase of 50% or more in the serum creatinine, and the secondary end point was ESRD. After a mean follow-up of 6.4 yr, 46 patients-17 in the fish oil group versus 29 in the placebo group-reached the primary end point (P = 0.002), and 27 patients-eight in the fish oil group versus 19 in the placebo group-developed ESRD (P = 0.009). At the end of the 2-yr trial, 75 patients (45 fish oil, 30 placebo) remained at risk for the primary end point. This is also when the double-blind part of the trial ended, allowing physicians to stop supplements, switch original placebo-assigned patients to fish oil, and continue fish oil in original fish oil-assigned patients. A significantly greater number of nonsupplemented placebo patients developed the primary end point (P = 0.02) and ESRD (P = 0.003) compared with long-term supplemented fish oil patients. Conversely, more fish oil-supplemented patients had stable renal function than nonsupplemented patients (P = 0.02). By intention, BP control, primarily treated with angiotensin-converting enzyme inhibition, was equal in the fish oil and placebo groups. Proteinuria was modestly reduced in both groups. It is concluded that early and prolonged treatment with fish oil slows renal progression for high-risk patients with IgA nephropathy.

Renal biopsy can be extremely valuable in the management of patients with lupus nephritis. It is remarkably common to find pathological evidence of substantial nephron loss in patients with low grade laboratory abnormalities. This is due to compensatory hypertrophy and hemodynamic adjustments within the less diseased nephron mass. It has been shown that the decision to institute immunosuppressive therapy is highly informed by the results of renal biopsy and offers the prospect of achieving more favorable renal outcomes. Kidney biopsies should be evaluated by dedicated renal pathology services experienced in diagnostic light, immunofluorescence and electron microscopy. Biopsies should be classified according to the World Health Organization (WHO) system and specific lesions semiquantitatively scored against a checklist of features comprising activity (reversible) and chronicity (irreversible damage) indices. The renal biopsy findings should be reviewed jointly by pathologists and the clinicians caring for patients with lupus nephritis.

Tissue factor (TF), the cellular initiator of the protease blood coagulation cascade, has been shown to be expressed in a variety of solid tumors, particularly those of epithelial origin. However, the mechanisms that mediate TF expression in tumors, as well as the clinical implications of this expression, remain largely unknown. In this study, we examined the cytological distribution of TF in normal human breast tissue and breast carcinomas. Epithelial cells exhibited TF immunoreactivity with little obvious correlation with malignant progression from in situ lesions to invasive cancer. However, there was a strong correlation between progression to invasive cancer and the expression of TF antigen in cellular components of the stroma. TF-positive cells were particularly abundant in close proximity to infiltrating tumor cells and included both macrophages and myofibroblasts, as determined by double-immunofluorescent staining for TF and cell type-specific marker proteins. Double-immunofluorescent staining for TF and transforming growth factor beta (TGF-beta) revealed TGF-beta immunoreactivity both in tumor cells and in the extracellular matrix surrounding TF-positive stromal cells. To test the role of carcinoma cell-derived growth factors in the regulation of stromal cell TF activity, we examined the ability of conditioned media (CM) from breast carcinoma cell lines to stimulate TF activity in myofibroblast-like cells in vitro. Extracts from myofibroblasts exposed to CM displayed strong TF procoagulant activity. However, extracts from cells exposed to unconditioned media or CM pretreated with anti-TGF-beta antibodies did not. The induction of TF activity was also observed upon treatment of indicator cells with recombinant TGF-beta isoforms. Collectively, these data indicate that the recruitment and/or activation of TF-expressing stromal cells is an early event in progression to invasive breast cancer and likely occurs, in part, as a paracrine response to tumor cell-derived members of the TGF-beta family of growth factors.

To investigate the frequency of membranous nephropathy associated with nonsteroidal anti-inflammatory drug (NSAID) use and identify associated clinical characteristics.Retrospective chart review.A large group practice that staffs 2 large teaching hospitals.All patients diagnosed as having stage I or early stage II membranous nephropathy by renal biopsy between January 1975 and May 1995.Nephrotic syndrome was said to be associated with NSAID use if patients developed nephrotic syndrome while taking an NSAID and if other causes of membranous nephropathy were excluded and a rapid remission of the nephrotic syndrome followed withdrawal of the drug.Of 125 patients identified with early membranous nephropathy, 29 were taking NSAIDs at the time symptoms of nephrotic syndrome developed. Thirteen of these patients met the criteria for NSAID-associated membranous nephropathy. None of these patients had any evidence of renal insufficiency or significant proteinuria after follow-up periods ranging from 5 months to 13 years. In addition to diclofenac and fenoprofen, which have previously been implicated, ibuprofen, nabumetone, naproxen, and tolmetin were found to be associated.Nephrotic syndrome due to membranous nephropathy should be recognized as an idiosyncratic drug reaction to many NSAIDS. Because withdrawal of the drug may result in prompt and complete recovery of normal renal function, a history of NSAID intake should be sought in patients with membranous nephropathy.

The gene PKD I, which is mutated in type I autosomal dominant polycystic kidney disease (ADPKD 1), encodes a large protein of novel structure and unknown function and distribution that has been named polycystin. To gain better insight into polycystin function, we raised a panel of antisera against synthetic peptide antigens derived from the unique portion of the predicted polycystin sequence. Antisera were used to immunolocalize the protein in a variety of normal human fetal, childhood, and adult tissues as well as kidney and liver tissue from individuals with ADPKD 1, the genetically distinct ADPKD 2, and acquired renal cystic disease (ARCD). Subcellular localization studies were carried out on human cultured cell lines of renal epithelial origin. In normal tissues, polycystin expression was noted in renal tubular epithelial cells from 20 weeks gestation to 4 years postpartum, and in hepatocytes and biliary epithelium up to 4 years, but not in adult kidney or liver. Expression also was present in fetal and childhood pancreas, myocardium, bowel, and adrenal medulla. In cell lines of renal epithelial origin, immunofluorescence and immunoelectron-microscopical studies showed localization of polycystin epitopes to the peripheral cytoplasm. Kidney and liver from four unrelated adults with known ADPKD 1 showed strong staining, which was not seen in kidney and liver from one adult with ADPKD 2 or in kidney from three patients with ARCD. We conclude that polycystin is expressed in renal tubular epithelial cells as well as a variety of other cell types during development and growth but is absent or weakly expressed in adult kidney and liver. Overexpression of polycystin epitopes within affected tissue may be a specific feature of some or all cases of ADPKD 1.

Lipopolysaccharide, a potent pro-inflammatory constituent of bacterial cell walls, is capable of promoting glomerular inflammation, by both activating circulating inflammatory cells and local interactions with renal parenchymal cells. We sought to determine whether lipopolysaccharide was capable of promoting glomerular inflammation by directly stimulating mesangial cell production of monocyte chemoattractant protein 1, a recently described cytokine capable of eliciting recruitment of mononuclear phagocytes into inflammatory foci. Northern hybridization analysis revealed dose and time-dependent induction of mRNA coding for monocyte chemoattractant protein 1 in quiescent rat mesangial cells treated with lipopolysaccharide. Lipopolysaccharide-elicited induction of monocyte chemoattractant protein mRNA was detectable after 1 hour and persisted for at least 30 hours. Media isolated from rat mesangial cell cultures stimulated by lipopolysaccharide possessed monocyte chemotactic activity that was detectable at 8 hours and peaked at 24 hours; an antimonocyte chemoattractant protein antibody blocked 87% of this chemotactic activity. We suggest that lipopolysaccharide, released from bacterial cell walls, promotes glomerular inflammation by stimulating mesangial cell production of monocyte chemoattractant protein 1.

Immune hemolytic anemia in patients after organ transplantation has been reported generally to be graft-cell-derived due to elaboration by the donor's "passenger" lymphocytes of the antibodies directed against the recipient's red cell antigens. In contrast, this report presents a case that illustrates postoperative red cell alloantibody production by the recipient of an orthotopic liver transplant. Anti-Jka, -c, and -S, detected in the recipient's serum 9 days after transplantation, resulted in significant hemolysis. These alloantibodies had not been present in the recipient's serum before transplantation or in the sera of the liver or blood donors. In addition, anti-Jka and -c were eluted from posttransfusion red cells. The patient was transfused during surgery with crossmatch-compatible blood, that carried the alloantigens Jka, c, and S. The liver donor's red cells also carried the Jka, c, and S antigens. The recipient's pretransplantation red cell phenotyping was Jk(a-), c-, S-. The recipient had received only one transfusion 10 years prior to this operation, after which time he was noted to have anti-K. Immunosuppression initially consisted of cyclosporine, azathioprine, and prednisolone. This is believed to be the first report of delayed immune hemolysis due to non-ABO antibodies in a liver transplant patient treated with cyclosporine.

Arteries respond to long-term changes in flow rate by alterations in caliber that tend to restore wall shear stress to normal baseline levels. Changes in radius, pressure, or geometric configuration elicit changes in structure and composition of the media in keeping with the altered level and distribution of tensile stresses. Similar stabilizing adaptations occur in the presence of conditions that induce the formation of atherosclerotic plaques, but the ultimate effectiveness of these reactions is variable. Several recent experiments provide information on the possible effects of hyperlipidemia on the smooth muscle cell (SMC) response to normal or increased levels of mechanical stress: (a) Normolipemic serum increases collagen synthesis by SMCs grown on purified elastin membranes compared to synthesis in serum-free medium, but synthesis is not further enhanced by cyclic stretching of the cells. Collagen production increase is less marked in hyperlipemic serum, but cyclic stretching raises synthesis to a degree comparable to that noted for serum-free medium. (b) The increase in artery diameter in response to increased flow rate and the elaboration of media components in relation to the increase in diameter are not hampered by hyperlipidemia. (c) The compensatory enlargement of arteries in response to plaque formation is not prevented by hyperlipidemia even in the presence of hypertension. (d) The healing of a transmural necrotizing injury of the media is, however, retarded and incomplete in the presence of hyperlipidemia. These findings indicate that hyperlipidemia per se does not necessarily interfere with the SMC response to mechanical stimuli. The usual adaptive reactions remain intact.(ABSTRACT TRUNCATED AT 250 WORDS)

Among 28 autopsied patients with aortoenteric fistulas, the mean age was 67 years (range, 19 to 91 years) and 23 (82%) were men. The most common causes were aortobifemoral bypass grafts (16 cases [57%]) and gastrointestinal carcinomas (6 cases [21%]). Fistulas developed at proximal anastomosis sites in 15 of 16 patients with grafts and were associated with radiation injury in 3 of 6 patients with carcinomas. Aortoenteric fistulas involved the duodenum in 16 (57%), esophagus in 9 (32%), and other gastrointestinal sites in 3 patients (11%). They involved the abdominal aorta in 20 cases (71%) and descending thoracic aorta in 8 cases (29%). Exsanguination from aortoenteric fistulas was the cause of death in 23 cases (82%). Major risk factors for aortoenteric fistulas are aortic bypass grafts and gastrointestinal carcinomas.