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We report another case of acute interstitial nephritis with uveitis (TINU syndrome) in a 35-year-old woman. About thirty cases were described since the first ones 20 years ago. We discuss the assessment needed to reach the diagnosis. The evolution is unusually favourable with steroid therapy.

The EDTA (European Dialysis and Transplantation Association) statistic data on kidney diseases in ageing population point out vascular and/or metabolic origins. We report here a case of a rare cause of renal insufficiency, a Gougerot-Sjögren primary syndrome, diagnosed in an old patient. Renal and salivary gland biopsies were performed. The invasive investigation allowed an accurate diagnosis and an etiologic treatment.

A 40-year-old plumber was admitted to the emergency room of our hospital in October, 2003, with bilateral backache for 1 week. He had no other complaints. He had no previous medical history and was not on any treatment. On examination, his temperature (36 ·5°C), heart rate (80 beats per min), and blood pressure (140/70 mm Hg) were normal. There was no rash and no lympha-denopathy. Lungs were clear and heart sounds were normal. There was no oedema and he was passing urine normally. Abdomen was unremarkable except for tenderness of both costovertebral angles. Laboratory tests showed normal blood-cell counts but a severe renal failure: serum creatinine 390 µmol/L (normal: 35-106), with raised uric acid (2268 µmol/L: 200-500). Urinalysis showed microscopic haematuria and moderate proteinuria (600 mg/L). Neither crystals nor amorphous material was detected in the urinary sediment. Abdominal ultrasound showed enlarged kidneys (14 cm in length). A renal biopsy was done and haemodialysis started. The biopsy specimen showed a massive interstitial tumour infiltrate (figure, A) composed of a monomorphous population of small to medium-sized cells with round to oval nuclei, very fine chromatin, and scanty cytoplasm (figure, B). The widened interstitium compressed the tubular luminae but neither urate crystals nor tubular necrosis were seen; there were some mitotic figures. Immunohistochemical studies identified these cells as precursor T lymphoblasts because they were positive for several T-cell antigens, including CD2, CD3, and CD5, as well as for terminal deoxynucleotidyltransferase (TdT) (figure, C and D). The diagnosis of precursor T-lymphoblastic lymphoma was then made. Cytological examination of a bone-marrow aspirate showed massive lymphoblastic involvement, indicative of acute lymphoblastic leukaemia. A positron emission transaxial tomography (PET) scan showed increased metabolic activity in all bone-marrow areas, liver, spleen, and kidneys (figure, E). High doses of corticosteroids (intravenous methylprednisolone, 80 mg twice a day for 1 week) led up to a rapid return to normal of renal function. Tumour lysis secondary to corticosteroids could have been responsible for worsening of hyperuricaemia. Rasburicase (0·2 mg/kg/day for 1 week) was given. Once the final diagnosis was established, standard chemotherapy was started. As of October, 2004, he is on maintenance treatment, feels well, is in complete remission, and his serum creatinine is normal. Severe acute renal failure is a rare presentation of malignant haemopathies. There are two pathophysiological mechanisms. Hyperuricaemia due to increased nucleic-acid catabolism is the most frequent. Uric-acid nephropathy is characterised by tubular necrosis due to uric-acid crystallisation in the tubular lumen. In this setting, urate crystals are easily detectable by light microscopy, the size of the kidneys is within normal range, and patients are usually oliguric.

Chronic renal failure (CRF) in the elderly is a cause of multiple endocrine dysfunctions. The three most common pituitary axes involved are the thyrotrope, lactotrope and gonadotrope axes. Thyroid dysfunction may be the consequence of thyroid or pituitary failure. Hyperprolactinemia results in gonadal failure and is present in 30% of patients. Early presentation of menopause and andropause are common in patients with CRF. Sexual hormonal replacement is controversial and must be individually tailored. We propose a systematic screening in the elderly with CRF: determination of TSH, TPO antibodies and cervical palpation, measures of PRL, LH, FSH and testosterone to explore lactotrope and gonadotrope axis.

We report another case of acute interstitial nephritis with uveitis (TINU syndrome) in a 35-year-old woman. About thirty cases were described since the first ones 20 years ago. We discuss the assessment needed to reach the diagnosis. The evolution is unusually favourable with steroid therapy.

The incidences of clinical and biological markers of atopy were investigated in 16 children with IgA nephropathy (IgAN) (group A) and in 22 with Henoch-Schönlein purpura nephritis (HSPN) (group B). The incidence of increased plasma IgE levels according to age-matched normal values was significantly higher in group B (17/22, 77%) than in group A (7/16, 44%) (P

Two cases of interstitial nephritis in sarcoidosis with improvable renal failure, using methylprednisolone, are described. The effectiveness of such a therapy is discussed.

Glomerular and tubular epithelial cells from salt-loaded normal and glomerulonephritic rats and from salt-depleted normal rats were cultured in 199 medium. Supernatants from cultures after 3, 7, 17 and 23 days provided molecular weight fractions similar to those previously found to contain natriuretic activity in plasma and urine. When tested in a bioassay system, extracts isolated from culture supernatants from normal ‘salt-loaded’ tubular cells produced a significant natriuretic effect but did not modify overall glomerular filtration rate and renal plasma flow. No natriuretic activity was observed with supernatants removed from culture of the epithelial cells prepared in the other conditions.

1. 1. The biosynthesis of basement membrane polypeptides by confluent cultures of normal rat glomerular epithelial or mesangial cells has been studied by immunological and biochemical techniques. 2. 2. The epithelial cells synthesize and secrete GBM polypeptides, sharing some antigenic determinants with type IV collagen, into the culture medium. 3. 3. On the contrary, the mesangial cells synthesize and secrete GBM polypeptides different from type IV collagen into the culture medium.

A proliferative, non-crescentic, glomerulonephritis (GN) was induced in rats preimmunized with rabbit IgG by injecting a sub-nephrotoxic dose of rabbit anti-GBM IgG. Control rats either received anti-GBM IgG only, or were totally irradiated (800 rads, kidneys protected) 2 days before the second injection. All the GN rats developed a severe proteinuria within 2–4 days after the injection of anti-GBM IgG, contrarily to the control rats. At the same time, many mononuclear cells, of predominantly extra-renal origin, infiltrated the glomeruli. Glomeruli were isolated from GN, normal and control rats and were cultivated in RPMI medium. In normal and control rat cultures, epithelial and mesangial cells were observed. In GN rat cultures, not only epithelial and mesangial cells, but also endothelial and macrophagic cells were identified; the outgrowth capacity of the mesangial cells was enhanced. These data were particularly evident in cultures of GN glomeruli isolated within 2–4 days after the induction of the renal disease, exactly when the glomeruli were infiltrated by a large number of mononuclear phagocytes. It is suggested that the mononuclear phagocytes infiltrating the glomeruli of rats with this model of GN stimulate the proliferation of endothelial and mesangial cells in vitro.

The properties of follitropin receptors in immature porcine testis were determined using highly purified porcine follitropin. 1. The characteristics of follitropin binding to a subcellular fraction rich in plasma membranes were studied using a 125I-labelled follitropin with high specific activity (75-100 Ci/g) and high binding activity. The binding is dependent on time, temperature and pH. It is specific to follitropin as demonstrated by the very low binding activity of the follitropin alpha and beta subunits and of the other glycoprotein hormones. Scatchard analysis of binding data indicated an equilibrium association constant of 2 x 10(10) M-1 and a concentration of high affinity binding sites of 500 fmol/mg membrane proteins. 2. A sensitive radio-ligand receptor assay was developed. Fifty percent inhibition of binding was obtained with as little as 2 ng of porcine follitropin. Ovine and bovine follitropins and pregnant mare serum gonadotropin gave binding inhibition curves parallel to that given by porcine follitropin. With equine and human follitropin, significantly different slopes were recorded. 3. Kinetics of dissociation of labelled follitropin from its testis receptors showed the presence of at least two compartments with fast and slow dissociation rate constants. The ratio between the sizes of the slow and fast compartments appeared dependent upon preincubation time. 4. A temporal correlation was observed between binding of follitropin to testis receptors and activation of membrane bound adenylate cyclase.

The adhesion of normal rat peritoneal macrophages to normal rat glomerular epithelial or mesangial cells has been studied in vitro after a 60 min incubation at 37 degree C. After washing, the cell preparations were examined by phase contrast or scanning electron microscopy. Quantitative studies were also performed using macrophages labelled with 99mTc tin colloids. Peritoneal macrophages predominantly adhered to the cultured mesangial cells. The percent-age of labelled macrophages adhering to these cells was about 10 times higher than that of labelled macrophages adhering to the cultured epithelial cells. This percentage increased proportionally to the number of labelled macrophages added, and was strongly reduced by the prior incubation of macrophagic cells with aggregated IgG, with anti-fibronectin IgG, or with F(ab')2 fragments of anti-fibronectin IgG. Furthermore, the macrophage-mesangial cell interaction was significantly reduced by the prior incubation of mesangial cells with anti-fibronectin IgG or with F(ab')2 fragments of anti-fibronectin IgG. The data demonstrate that normal rat peritoneal macrophages preferentially adhere in vitro to normal rat glomerular mesangial cells, and that this binding may be modulated, at least, by: (a) the Fc receptor binding activity of macrophages; (b) the fibronectin molecules available at the surface of macrophages and of mesangial cells.

A proliferative glomerulonephritis was induced in rats preimmunised with rabbit IgG by injecting a sub-nephrotoxic dose of rabbit anti-rat GBM IgG. All the rats developed a severe proteinuria within 2-5 days after the injection of anti-GBM IgG. At the same time, many mononuclear phagocytes infiltrated the glomeruli, the colloidal iron staining of the glomerular filtration barrier was altered, and the urinary excretion of laminin and of neutral proteinase strongly increased. However, the pattern and intensity of staining of different collagenous and non-collagenous BM glycoproteins were not modified, as shown by indirect immunofluorescence microscopy. The existence of a direct significant correlation between the proteinuria and the laminin urinary excretion, and between the latter and the urinary neutral proteinase activity suggests that lysosomal proteinase of mononuclear phagocytes may be involved in the damage of the GBM during the course of this experimental glomerulonephritis.

Electronegative charges of the glomerular filtration barrier play probably an important role in its impermeability to anionic proteins 1–9. Sialic acid 10 (present in laminin) and glycosaminoglycans 11 seem to be the major molecules responsible for this propriety. Neutral proteinases synthetized either by mesangial cells or by monocytes and neutrophils, infiltrating glomeruli in some pathologic states, are able to degrade GBM glycoproteins in vitro 12–14.

The perfusion of polymeric or secretory IgA-Concanavalin A complexes into the aorta of rats led to a mannose-dependent binding of both IgA and lectin to the glomerular capillary wall, as shown by double immunolocalization experiments, by quantitative analysis of the amount of radiolabelled complexes bound per g of kidney, and by blocking experiments with the corresponding carbohydrate. Rats injected with amounts of those complexes as low as 500 micrograms developed, one hour later, a focal and segmental proliferative glomerulonephritis characterized by the deposition of injected complexes and of rat C3 and rat fibrin/fibrinogen in most glomeruli; focal thrombosis and small areas of necrosis in 10 to 15% of glomeruli, confined to the periphery of a single lobule of the tuft and segmental infiltration of these glomeruli by polymorphonuclear leucocytes and platelets. At the same time, many mesangial cells exhibited a hyperactive appearance, and red blood cells were noted in tubular lumens. In contrast, rats similarly injected with either monomeric IgA-ConA complexes, multimeric or secretory IgA-peanut agglutinin complexes or polymeric or monomeric IgA aggregates of comparable apparent molecular weight did not develop obvious glomerular lesions within one hour. The data indicate that performed polymeric IgA-ConA complexes can specifically bind to glomerular structures in vivo and trigger acute glomerular lesions locally, analogous to those observed in some glomerular diseases associated with a cryoglobulinaemia.

This case of congenital nephrotic syndrome is not easy to classify. Treatment with usually effective doses of cyclophosphamide and prednisolone was unsuccessful, whereas a treatment with gammaglobulin was concomitant with a decrease in the frequency of infections, improvement of the nephrotic syndrome, growth, psychomotor development and bone maturation. Electron microscopy shows basal membrane abnormalities not yet described.

Confluent cultures of renal glomerular or tubular epithelial cells were incubated with [14C] proline and [3H] lysine. The incorporation rate of both radioactive precursors was found to be linear for up to 12 h. The synthesis and secretion of basement membrane collagenous polypeptides was demonstrated by the presence in the culture media of non-dialyzable 4-hydroxy [14C] proline and hydroxy [3H] lysine. After gel filtration of the culture media on Sephadex G-100 columns, glomerular and tubular basement membrane polypeptides were identified in the chromatographic fractions by radioimmunoassay. They were further purified by affinity chromatography, using Sepharose cyanogen-bromide coupled with specific rabbit anti-human glomerular or tubular basement membrane antibodies. Absorbed labelled membrane polypeptides were eluted from the Sepharose by acidic medium at 4 degrees C. This membrane material represented 3-4% of the total proteins synthesized by glomerular and tubular cells. The glomerular and tubular basement membrane polypeptides purified by affinity chromatography exhibited a molecular weight of approximately 140,000; 80% of the total hydroxy [3H] lysine was recovered as glucosyl-galactosyl-hydroxy [3H] lysine. Analysis of the carbohydrate content of labelled basement membrane polypeptide chains originating from glomerular or tubular cells incubated with [14C] glucose of [14C glucosamine indicated the presence of glucose, galactose, mannose, glucosamine, and galactosamine. No fucose, mannosamine or sialic acid were detectable. The data demonstrate that glomerular and tubular epithelial cells are able to synthesize basement membrane collagenous polypeptides in culture. This property might provide a useful tool for the study of the biosynthesis of similar material by diseased kidneys.

The perfusion of polymeric IgA (pIgA)--or secretory IgA (sIgA)--Concanavalin A (ConA) non-immune complexes (apparent Mol.Wt greater than 10(3) Kd) into the aorta of rats led to a dose-dependent and a mannose-dependent deposition of both IgA and lectin into the glomeruli. Rats injected with amounts of those complexes as low as 500 micrograms developed, one hour later, a focal and segmental proliferative glomerulonephritis characterized by: a) the deposition in the mesangial area of most glomeruli of injected complexes and of rat C3; b) small areas of fibrinoïd necrosis in 10 to 15% of glomeruli, confined to the periphery of a single lobule of the tuft; c) a segmental infiltration of those glomeruli by polymorphonuclear leucocytes, mononuclear phagocytes and platelets; d) a hyperactive aspect of mesangial cells; e) the presence of red blood cells in tubular lumens. By contrast, no glomerular lesions were obvious in rats similarly injected either with monomeric IgA (mIgA)-ConA, pIgA-peanut agglutinin (PNA) or sIgA-PNA complexes or with heat-aggregated pIgA or mIgA. The data indicate that preformed polymeric IgA-ConA complexes can specifically bind to glomerular structures in vivo and locally trigger, as antigen-antibody complexes, an acute inflammatory reaction resulting in glomerular lesions similar to those observed in Henoch-Schönlein purpura nephritis.

Glomerular tufts were isolated from normal rat kidneys and were cultivated in RPMI1640 medium supplemented with 15% fetal bovine serum. Studies on DNA synthesis demonstrated two peaks (A and B) of cell division. The cells of peak A grew as a monolayer until confluency, exhibited many junctional complexes and microvilli. They were very susceptible to the aminonucleoside of puromycin, as glomerular epithelial cells in vivo. They did not contain many bundles of intracellular microfilaments and were not stained by an anti-factor VIII serum. The cells of peak B formed both monolayered sheets and multilayered bands, exhibited no junctional complexes, but contained large bundles of intracellular fibrillar structures, which were strongly stained by an antimyosin antiserum. They were not stained by an anti-factor VIII antiserum. The B cells exhibited a contractile activity in response to 10-9M angiotensin II and were very susceptible to mitomycin C treatment, as glomerular mesangial cells in vivo. They synthesized large amounts of prostaglandins (mainly PGE2). The data suggest that the A cells are visceral epithelial cells, and that the B cells are smooth muscle-like cells derived from the glomerular mesangium.

1. The biosynthesis of basement membrane polypeptides by confluent cultures of normal rat glomerular epithelial or mesangial cells has been studied by immunological and biochemical techniques. 2. The epithelial cells synthesize and secrete GBM polypeptides, sharing some antigenic determinants with type IV collagen, into the culture medium. 3. On the contrary, the mesangial cells synthesize and secrete GBM polypeptides different from type IV collagen into the culture medium.

A boy presenting with a severe congenital nephrotic syndrome diagnosed by histological analysis at the age of 3 weeks was biopsied again 7 years later. The ultrastructural glomerular basement membrane abnormalities depicted in the first biopsy were no longer present in the second one. The number of completely hyalinized glomeruli was not significantly decreased. The GFR remained normal, but a moderate persistent, non-selective proteinuria (800 mg/24 h) was noted without oedema. The patient however developed a progressive perceptive deficit of hearing.