IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23.

End-stage renal disease (ESRD) is a major public health problem, affecting 1 in 1,000 individuals and with an annual death rate of 20% despite dialysis treatment. IgA nephropathy (IgAN) is the most common form of glomerulonephritis, a principal cause of ESRD worldwide; it affects up to 1.3% of the population and its pathogenesis is unknown. Kidneys of people with IgAN show deposits of IgA-containing immune complexes with proliferation of the glomerular mesangium (Fig. 1). Typical clinical features include onset before age 40 with haematuria and proteinuria (blood and protein in the urine), and episodes of gross haematuria following mucosal infections are common; 30% of patients develop progressive renal failure. Although not generally considered a hereditary disease, striking ethnic variation in prevalence and familial clustering, along with subclinical renal abnormalities among relatives of IgAN cases, have suggested a heretofore undefined genetic component. By genome-wide analysis of linkage in 30 multiplex IgAN kindreds, we demonstrate linkage of IgAN to 6q22-23 under a dominant model of transmission with incomplete penetrance, with a lod score of 5.6 and 60% of kindreds linked. These findings for the first time indicate the existence of a locus with large effect on development of IgAN and identify the chromosomal location of this disease gene.

Macular cherry-red spot and myoclonus syndrome. Juvenile form of sialidosis.

Macular cherry-red spot, myoclonus and progressive mental deterioration are described in a man of 16 years. Morphological examination of the liver, bone marrow and fibroblasts showed numerous vacuoles containing storage material in the cytoplasm of the cells. Twelve different oligosaccharides were isolated from urine and their structures were determined. All have N-acetylglucosamine in a reducing end and (2--3) and 2--6) neuraminic acid in the terminal position. This abnormal urinary oligosaccharide excretion is due to absence of (2--6) neuraminidase which was not detected in fibroblast culture. This case is discussed in relationship to other cases with macular cherry-red spot, myoclonus and oligosaccharide urinary excretion.

Acute renal failure due to idiopathic tubulo-intestinal nephritis and uveitis: "TINU syndrome". Case report and review of the literature.

Acute renal failure due to idiopathic tubulo-interstitial nephritis associated with bilateral uveitis (TINU syndrome) is a rare clinical event, contracted mainly by girls or women. Here we report the clinical follow-up regarding a 22-year-old woman with acute renal failure (creat. clearance 13.5 ml/min) due to idiopathic tubulo-interstitial nephritis documented by renal biopsy, after bilateral uveitis which healed with local prednisone. The clinical history and the clinical follow-up of our patient were typical of the TINU syndrome. We were able to exclude all diseases causing acute tubulo-interstitial nephritis such as systemic infection, hypersensitivity to drugs, Behcet's disease, Sjogren syndrome, sarcoidosis, systemic lupus or vasculitides. The patient recovered after systemic prednisone.

Autosomal recessive and dominant polycystic kidney diseases.

It is possible to identify renal cysts in several subjects by ultrasonography imaging techniques. Among the inherited polycystic kidney diseases we include autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic diseases such as von Hippel-Lindau disease, tuberous sclerosis complex (TSC1 and TSC2), and autosomal dominant polycystic kidney disease (ADPKD). ARPKD is a rare disease, related to PKHD1 gene, located on chromosome 6p21, that encodes a protein named polyductin/fibrocystin. Pathoanatomical features are bilateral kidney involvement with multiple microcysts, and invariably liver involvement with portal and interlobular fibrosis. A single genetic defect leads to different degrees of renal and hepatic involvement with very different phenotypes and different clinical outcome, in the same family too. ARPKD clinically may show 4 different forms: perinatal, neonatal, infantile, and juvenile. ADPKD is much more frequent (1: 400-1000 live births), and can arise from mutations in 2 different genes, named PKD1 located on chromosome 16p13.3, and PKD2 located on chromosome 4q21-23. The proteins encoded by the PKD1 and PKD2 genes are named polycystins which play crucial roles in several biologic processes. To explain the focal lesions that affected different organs and tissues the "double hit" theory has been proposed (germinal mutation plus somatic mutation on PKD1 or PKD2). Recently, biologic evidence documented the crucial role of the renal primary cilia on the formation of polycystins to induce cystogenesis. ADPKD may be clinically characterized by abdominal pain, hypertension, episodes of gross hematuria, headache, renal stones, aortic and cerebral aneurysms, mitral valve prolapse, and polycystic liver disease. ADPKD is slowly progressive disease responsible for up 10% of end stage renal failure (ESRF) in every country of the world. Male sex, PKD1 gene, episodes of gross hematuria, and the precocity and severity of hypertension play an important role in the progression of renal disease to ESRF.

Evolution of renal pathology in Fabry disease.

UNLABELLED: Fabry disease is a rare lysosomal storage disorder which results from deficient activity of the enzyme alpha-galactosidase A. The resultant deposition and progressive accumulation of glycosphingolipids in all types of body tissue leads to severe clinical manifestations involving the heart, CNS and kidney. Renal manifestations are observed relatively early in the course of the disease, and progression to end-stage renal failure is common in hemizygous males in the third to fifth decades of life. Renal biopsy specimens reveal evidence of diffuse intracytoplasmic glycosphingolipid accumulation, mainly affecting podocytes and epithelial cells of distal tubules, which are strikingly enlarged and vacuolated. On electron microscopy the deposits appear as typical osmiophilic inclusion bodies in the cytoplasm of all kinds of renal cells, and show a characteristic 'onion skin' or 'zebra' appearance. These pathological features are also evident in heterozygous females. Deposits occur before the development of renal impairment. As patients age, the disease progresses in cells throughout the kidney, and is associated with increasing glycosphingolipid accumulation. CONCLUSION: The age-related evolution of renal pathology in Fabry disease is closely correlated with progressive intracellular deposition of glycosphingolipid and ultimately leads to end-stage renal failure.

Nosocomial outbreak of Aspergillus fumigatus infection among patients in a renal unit?

Aspergillus fumigatus is present in the environment worldwide and it is only able to infect debilitated or immunodepressed subjects. Nosocomial outbreaks of A. fumigatus infection have been associated with hospital reconstruction. Spores are released into the environment and are inhaled by immunodepressed patients housed in nearby Medical Units. Specific clinical syndromes are allergic bronchopulmonary aspergillosis and invasive pulmonary aspergillosis with characteristic radiological features. Invasive A. fumigatus infection is commonly fatal, even if promptly diagnosed and treated. Three consecutive cases of A. fumigatus infection occurred in debilitated patients housed in our Renal Unit while building renovation near the Unit was being performed. Two of these patients died and pulmonary and diffuse aspergillosis was found on postmortem examination. The third patient, highly suspected to be infected with Aspergillus, was aggressively and successfully treated with liposomal amphotericin B. Our experience suggests that fungal infections have gained increasing prominence in clinical medicine and they must be considered in chronic debilitated patients including dialysis patients, and that liposomal amphotericin B represents an important advance in the treatment of aspergillosis.

Inhibition of rat lens aldose reductase by bendazac-L-lysine salt.

Authors describe the in vitro effect of bendazac-L-lysine salt on the activity of enzyme aldose reductase from rat lens. In the presence of bendazac the activity of the tested enzyme was inhibited. Lineweaver-Burk plot demonstrated that the inhibition was noncompetitive. The possible curative effects on diabetic cataract together with a better way of administration are pointed out.

Two brothers with idiopathic membranous nephropathy and familial sensorineural deafness.

Genetic factors could play an important role in the pathogenesis of idiopathic membranous nephropathy, and a few cases of familial membranous nephropathy have been described: an increased incidence of some HLA antigens as DR3 and others has been reported. We present two brothers with idiopathic membranous nephropathy and sensorineural deafness. HLA typing was performed in the two patients and in the members of the family, and it showed the absence of linkage of an HLA antigen with the renal disease in the family.

IgA mesangial nephropathy associated with renal cell carcinoma.

The authors report the occurrence of proliferative glomerulonephritis with mesangial IgA deposits in a 47-year-old man, heavy smoker, affected with renal cell carcinoma at stage I. The relationship between neoplastic diseases and IgA glomerulonephritis is unresolved. It is possible that IgA mesangial nephropathy may occur as a paraneoplastic disease, but in this patient its association with renal cell carcinoma may be merely fortuitous.

Variability of clinical phenotype in a large Alport family with Gly 1143 Ser change of collagen alpha 5(IV)-chain.

In a large Italian family with adult-onset Alport syndrome, molecular analysis of the COL4A5 gene, which encodes the alpha 5(IV)-chain of glomerular basement membrane collagen, revealed a GGC-->AGC change in exon 38, resulting in substitution of a serine for a glycine in position 1143 of the polypeptide chain, between interruptions 19 and 20 of the triple helical domain. The mutation leads to loss of a restriction site for the enzyme Msp I, and could thus be easily recognized in several female and male relatives. Among relatives of both sexes who carried the same mutation, the clinical phenotype of Alport syndrome was variable as for the onset of renal failure and the presence of associated ear and eye abnormalities.

Renal pathological changes in Fabry disease.

Fabry disease is a rare X-linked disorder, characterized by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to systemic accumulation of the glycosphingolipid globotriaosylceramide (Gb3) in all body tissues and organs, including the kidney. Renal manifestations are less evident in female heterozygotes than in male hemizygotes, according to the Lyon hypothesis. Accumulation of Gb3 occurs mainly in the epithelial cells of Henle's loop and distal tubule, inducing early impairment in renal concentrating ability; involvement of the proximal tubule induces Fanconi syndrome. All types of glomerular cells are involved, especially podocytes, and glomerular proteinuria may occur at a young age. The evolution of renal Fabry disease is characterized by progressive deterioration of renal function to end-stage renal failure (ESRF). Ultrastructural study of kidney biopsies reveals typical bodies in the cytoplasm of all types of renal cells, characterized by concentric lamellation of clear and dark layers with a periodicity of 35-50 A. Management of progressive renal disease requires dietetic and therapeutic strategies, usually indicated in developing chronic renal failure, with dialysis and renal transplantation required for patients with ESRF. The recent development of enzyme replacement therapy, however, should make it possible to prevent or reverse the progressive renal dysfunction associated with Fabry disease.

Renal transplantation from living donor parents in two brothers with Alport syndrome. Can asymptomatic female carriers of the Alport gene be accepted as kidney donors?

Renal transplantation from living donor parents was performed in two brothers with end-stage renal failure due to Alport syndrome (AS). Two years later, the patient receiving the kidney graft from the mother, obligate carrier of AS, presented persistent microhematuria and proteinuria with normal renal function. The histological study demonstrated ultrastructural glomerular lesions consistent with AS. The authors conclude that: (1) Alport patients should not be deprived of renal transplantation from living donors, since anti-GBM nephritis is a rare complication; (2) an oligosymptomatic female carrier of the Alport gene may be considered as living renal donor, although a longer follow-up is needed in order to draw definitive conclusions.

Effect of topical glucocorticoid administration on the protein and nonprotein sulfhydryl groups of the rabbit lens.

The effects of topical administration of glucocorticoids on rabbit lenses are described. Animals were divided into three groups. The first group (A) served as control, the second (B) and the third (C) group were treated with betamethasone and fluorometholone, respectively. After 40 days of treatment there was a significant fall in the levels of nonprotein sulfhydryl (-SH) groups (group A: 3.82 +/- 0.21; group B: 2.61 +/- 0.11; group C: 1.93 +/- 0.13 mumol/lens) and of protein -SH groups (group A: 8.215 +/- 1.023; group B: 4.120 +/- 0.631; group C: 4.068 +/- 0.538 mumol/lens). Also ascorbic acid levels showed a significant decrease both in lens and in aqueous humor. No differences were noted in the reduced glutathione content in aqueous humor. The fall in nonprotein and protein -SH could be the first event in the well-known biochemical changes that occur in steroid-induced cataract. The mechanism underlying steroid-induced damage could be due to a conformational change of lens crystallins which results in an unmasking of -SH groups with a consequent increased susceptibility to oxidation. The decrease of ascorbic acid should represent an effect of the fall in the glutathione system. Lastly, it is hypothesized that the protective effect exerted by some substances, such as vitamin E and ascorbic acid, occurs by counteracting this oxidation.

Quantification and measurement of human lens opacities using the lens opacity meter.

Lens opacity was quantified in 85 cataractous patients, using a new instrument: the lens opacity meter 701 (LOM; Interzeag, Schlieren, Switzerland). Cataracts were classified as nuclear, cortical, subcapsular and mixed forms. Sensitivity, specificity and reproducibility of the results were evaluated by statistical analysis. Visual acuity was correlated with LOM values in patients with nuclear and mixed cataracts. Moreover, the instrument gave a good degree of reproducibility only in patients who presented these forms of lens opacities. Our findings demonstrate that the LOM 701 is able to detect and to measure only lens opacities which affect the central area of the lens.

Behçet's disease: an unusual case with bilateral obliterating retinal panarteritis and ischemic optic atrophy.

Report of an unusual case of Behçet's disease with bilateral obliterating retinal panarteritis and ischemic optic atrophy. The rarity of the primary optic nerve involvement and chiefly the exceptional full acute bilateral occlusion of the retinal arteries are emphasized. This ophthalmoscopic picture is further clinical evidence for the major importance of the vascular involvement in the pathogenesis of Behçet's disease.

Hypocomplementemic type II membranoproliferative glomerulonephritis in a male patient with familial lecithin-cholesterol acyltransferase deficiency due to two different allelic mutations.

Patients with familial lecithin-cholesterol acyltransferase (LCAT) deficiency very often show progressive glomerulosclerosis with evolution to end-stage disease. High levels of an abnormal lipoprotein (lipoprotein X) cause glomerular capillary endothelial damage. The ultrastructural study of renal biopsy specimens shows characteristic glomerular deposits of membrane-like, cross-striated structures and vacuole structures. The gene encoding for LCAT has been mapped to chromosome 16q22.1, and several mutations of this gene cause LCAT deficiency which is inherited as an autosomal recessive trait and which is characterized by corneal opacities, normochromic normocytic anemia, and renal dysfunction. Herein we report clinical features and renal histological findings concerning a 24-year-old male patient with classical familial LCAT deficiency due to two different allelic mutations: a nonsense mutation inherited from the father and a missense mutation inherited from the mother. Moreover, the patient showed glomerular histological lesions and an immunofluorescent glomerular pattern typical of hypocomplementemic membranoproliferative type II glomerulonephritis (dense-deposit disease). The nature of electron-dense material that characterizes dense-deposit disease is still unknown, but there are suggestions that some chemical modifications might occur in the renal basement membranes. Therefore, this clinical case might induce to consider possible relations between disorders of the lipoprotein metabolism and renal dense-deposit disease.

Systemic and ocular effects of alpha 2-adrenergic stimulating and beta 2-blocking agents.

The effects of alpha 2-adrenergic stimulating agents (clonidine and guanabenz) and beta-adrenolytic agents (atenolol and propranolol) on the systemic arterial pressure, heart-rate, blood glucose level and intraocular pressure, as well as on the concentrations of glucose, Na+, K+ and Ca++ in the lens and aqueous and vitreous humours, are evaluated in the rabbit. alpha 2-adrenergic stimulating agents cause a significant increase of the glucose concentration in the blood, lens, aqueous and vitreous humours; whereas the beta-adrenolytic agents cause insignificant effects. Neither of the two drugs alters the concentration of Na+, K+ and Ca++ in the lens and aqueous and vitreous humours.