Granulomatous reactions caused by foreign bodies have been described in drug abusers, in subjects exposed to occupational pollutants, and more rarely, in association with the use of prosthetic devices. We describe a 62-year-old patient with multiorgan parenchymal granulomatosis caused by inorganic debris of unknown origin. The patient presented with fever, hepatosplenomegaly, progressive cholestasis, and acute renal failure. Liver and kidney biopsies showed the presence of noncaseating epithelioid giant-cell granulomas containing scattered polarizable particles. Similar particles were also present in stools. Studies by innovative scanning electron microscopy and energy-dispersive microanalytical techniques showed that the particles isolated in liver, kidney, and stools were made by feldspars, the main component of porcelain. No occupational or environmental exposure to these materials could be identified in this patient and the only reliable source of the porcelain debris turned out to be constituted by 2 dental bridges evidently worn because of a possible inappropriate construction, malocclusion, and bruxism. The porcelain of the dental prostheses had the same elemental spectrum of the particles isolated from stool specimens and liver-kidney granuloma. After identification of the dental prostheses as the most likely source of ceramic debris, and after their removal, the particles from stool specimens disappeared. The patient was then treated with steroids leading to a remission of the clinical symptoms and a decrease in granulomatous inflammatory reaction in both liver and kidney. This is the first report suggesting that a foreign body systemic granulomatosis can be associated with worn dental prostheses.

During the past 10 years the type of vascular access for haemodialysis procedures have changed markedly in our centre: more elbow AV fistulae and more central venous catheters are now used. Nevertheless, early referral to nephrologists and availability of central venous catheters and peritoneal dialysis allow elderly people to be admitted for dialysis treatment. Since vascular access for haemodialysis plays a key role in patient well-being, it is mandatory to apply quality assurance criteria to vascular access for haemodialysis surgery. Based on the results of a national survey, in Italy this policy is still in its early stages: monitoring of vascular access differs amongst centres, interventional radiology is used in a differing way, planning of vascular access for haemodialysis in pre-dialysis patients often remains an unsolved problem. According to our initial experience, we propose the use and validation of a quality-index [(minimum success rate) in elective vascular access for haemodialysis surgery], allowing accreditation of a department and a single surgeon for access management. Prevalence of central venous catheters at first dialysis of chronic renal failure patients is also proposed to evaluate the efficiency in access planning. Better knowledge of vascular access management by different teams could eventually lead to definition of guidelines for this 'Cinderella of dialysis'.

One hundred and nine unselected patients with Acute Renal Failure (ARF) of medical aetiology were hospitalized at the Nephrological Unit of Policlinico University Hospital (Modena) during a 30-month period. ARF was considered as a rapid increase of serum creatinine > 2mg/dl over the baseline level or the doubling of pre-existing value in chronic renal failure. Mean age of patients was 67+/-17 years and median age was 72; 64.2% needing dialytic treatment. Four main causes of ARF were identified: 33 patients had reduced renal perfusion by dehydration, hypotension etc.; 20 multifactorial aetiology; 14 biopsy-investigated renal parenchymal diseases and 39 had drug-related acute renal failure (D-ARF). The clinical outcome was significantly worse in elderly patients as regard mortality (P < 0.02), chronic dialytic treatment (P < 0.04) and complete recovery (P < 0.004). The mean age of D-ARF patients was significantly greater than remaining ARF patients (72.6+/-12.8 vs 63.2+/-18.5: P < 0.004. Nonsteroidal antiinflammatory drugs (NSAIDs) and ACE-inhibitors (Ace-i) caused ARF in 24 and 8 patients respectively. Elderly age, vascular disease and monoclonal gammopathy represented the main risk factors and were significantly more frequent in D-ARF patients (P<001, <0.01, <0.04 respectively). Our data confirm the high susceptibility of ageing kidneys to nephrotoxic damage caused by drugs affecting glomerular autoregulation by microvascular mechanisms. Greater attention to renal changes in ageing and an increased dissemination of preventative measures among nephrologists, could reduce the incidence of these serious and potentially lethal diseases.

The effect of the urinary calcium concentration (CaU) on erythrocyte morphology was studied by incubating erythrocytes in urine with prefixed CaUs of 5, 10, 20 and 40 mmol/l by addition of CaCl2. The same experiment was carried out on erythrocytes preincubated with levo-verapamil (l-V) at 10, 100 and 200 mumol/l. Phase contrast microscopy observations were performed at 0, 30, 60, 120, and 240 min by 2 experienced investigators. At 0 min the erythrocytes showed a clear extraglomerular pattern. At 60 min marked morphological and volumetric alterations were evident when the CaU was > or = 10 mmol/l. On the contrary, no change was found when red cells were treated with > or = 100 mumol/l l-V, independent of the CaU. Dysmorphic erythrocyturia has been related to transglomerular passage even if it was sporadically observed in hypercalciuric or lithiasic patients. This work suggests a role for a high CaU in causing the formation of microcytic and warped erythrocytes. In our opinion, in hypercalciuric urine the appearance of dysmorphic or mixed hematuria does not necessarily indicate transglomerular passage.

Lipid peroxidation, as measured by the thiobarbituric acid test, has been reported to have increased in hemodialysis (HD) patients, even though the test has low specificity in vivo. Conjugated diene fatty acid (CDFA) hydroperoxides are formed during lipid peroxidation, but not all conjugated dienes (CD) detected in humans originate from lipid peroxidation: octadeca-9,11-dienoic acid, a nonhydroperoxide CD derivative of linoleic acid (CDLA), has a dietary origin. We evaluated CDFA hydroperoxides, CDLA and linoleic acid, using high-performance liquid chromatography, in lipids extracted from plasma, adipose tissue and RBC membranes obtained from 25 patients treated with HD, 16 patients treated with hemodiafiltration (HDF) and 29 controls. No differences in the levels of CDFA hydroperoxides and linoleic acid were seen in any of the groups. Concentrations of CDLA were found to be significantly high in the adipose tissue and low in the RBC membranes of HD patients. HDF-treated patients showed the same results as HD patients. No direct evidence of increased lipid peroxidation was found in HD patients. This does not exclude the possibility that lipid peroxidation is increased and escapes direct detection due to the body's homeostatic control eliminating the increased production of hydroperoxides. Both HD- and HDF-treated patients showed a significant change in CDLA concentrations, either in the adipose tissue, or in the RBC membranes. These dietary CD may be mistaken for markers of lipid peroxidation by conventional methodologies.

The expression and distribution pattern of beta 1 (alpha 1-alpha 6) and alpha v beta 3 integrins and ICAM-1 and VCAM-1 counter receptors were evaluated by an immunohistochemical technique on eight renal samples from patients affected by rapidly progressive glomerulonephritis (RPGN) of different aetiologies. In all cases integrins and counterreceptors displayed similar patterns. On tubular cells of renal cortex, a marked upregulation of alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha v beta 3 integrins and VCAM-1 was observed with as many as 60-90% of tubular cross-sections labelled, while a strong ICAM-1 reactivity was limited to the luminal surface. The same adhesion molecules were also uniformly expressed on crescentic cells. In glomeruli, integrin upregulation occurred only on apparently preserved capillary tufts, i.e. in an early stage of lesion, while collapsed and sclerotic tufts showed a reduced integrin expression. In addition a morphometric study of extracellular matrix (EM) proteins cellular fibronectin and tenascin showed a 9.56 +/- 1.9-fold and 3.35 +/- 0.6-fold increase respectively in these proteins, as compared to normal kidney (P < 0.001). The upregulation of alpha v beta 3 on podocytes might play a role in the adhesion of crescentic cells. An increased production of cytokines, in particular transforming growth factor-beta, might induce augmented deposition of EM proteins and upregulation of beta 1 and beta 3 integrins in RPGN.

The localization of the alpha 2, alpha 3 and alpha 6 subunits of the beta 1 integrin family on different cells of the glomerular capillary wall and on juxta-capillary mesangium was investigated using an immunoelectron microscopic technique on freshly harvested normal human glomeruli. Alpha 2 beta 1, alpha 3 beta 1 and alpha 6 beta 1 were weakly expressed on both luminal and abluminal surfaces of glomerular endothelial cells; alpha 2 beta 1 and alpha 3 beta 1 were also found on the mesangium of the juxta-capillary areas. Alpha 3 beta 1 was regularly present in great density on the basal and lateral surface of podocyte foot processes, confirming alpha 3 beta 1 as the unique beta 1 integrin on glomerular epithelial cells. None of these integrins was strictly polarized along the glomerular basement membrane, thus suggesting, in agreement with recent literature, that these molecules perform other biological functions in addition to adhesivity.

The expression of alpha 2; alpha 3; alpha 5; alpha 6-subunits of the beta 1 [very late activation (VLA)] integrin family was studied in kidney specimens using an immunofluorescent technique. 6 specimens from normal kidney were compared with 10 specimens from patients affected by various glomerulopathies [minimal change nephropathy (MCN), membranous nephropathy (MN) and systemic lupus erythematosus nephritis (SLEN)]. On normal glomeruli, alpha 3 was the dominant integrin, being mainly present on podocytes and showing a linear fluorescent pattern codistributed with laminin. In MCN and SLEN, alpha 3 presented a normal pattern. In MN, alpha 3 revealed a trabecular picture on thickened glomerular basement membranes. Moreover, in stage-III MN, a segmental loss of alpha 3-integrin was detected. In our opinion, VLA-3 may offer an interesting approach to the study of the relationships between podocytes and their substrate.