HMGB-1 and TGFß-1 highlight immuno-inflammatory and fibrotic processes before proteinuria onset in pediatric patients with Alport syndrome.

INTRODUCTION: Alport syndrome (ALP) is a rare genetic condition characterized by progressive involvement of the basal membranes and renal dysfunction. The purpose of the study was to evaluate urinary (u) and serum (s) levels of tumor growth factor (TGF)-beta(ß) and high mobility group box (HMGB)-1 in ALP patients with normal renal function, albuminuria and proteinuria. METHODS: A prospective, single-center study was performed with a follow-up period of 12 months, enrolling 11 pediatric ALP patients and 10 healthy subjects (HS). Normal values of serum creatinine, albuminuria and proteinuria, as well as unaltered estimated glomerular filtration rate (eGFR) were required at enrollment. RESULTS: ALP patients had significantly higher levels of serum and urinary HMGB1 compared to HS. The same trend was observed for TGF-ß1, with higher values in ALP patients than in HS. HMGB1 and TGF-ß1 correlated with each other and with markers of renal function and damage. Urinary biomarkers did not correlate with eGFR, whereas sHMGB1 and sTGF-ß1 were negatively related to filtration rate (r: - 0.66; p = 0.02, r: - 0.96; p < 0.0001, respectively). Using proteinuria as a dependent variable in a multiple regression model, only the association with sTGF-ß1 (ß = 0.91, p < 0.0001) remained significant. CONCLUSIONS: High levels of HMGB1 and TGF-ß1 characterized ALP patients with normal renal function, highlighting the subclinical pro-fibrotic and inflammatory mechanisms triggered before the onset of proteinuria. Further studies are needed to evaluate the role of HMGB1 and TGFß-1 in ALP patients.

[Management of hyperphosphatemia in patients with chronic kidney disease]. / Il controllo della fosforemia nell'insufficienza renale cronica.

Hyperphosphatemia is a common finding in patients with chronic kidney disease (CKD) undergoing hemodialysis or receiving conservative treatment. Recent papers have reported a link between hyperphosphatemia, soft tissue calcifications, and cardiovascular events responsible for high morbidity and mortality in these patients. Our group identified in salivary phosphate secretion a method to study the phosphate balance in CKD. Moreover, we found that CKD patients on hemodialysis usually drink beverages with a high phosphate content that may increase their serum phosphorus levels. Hyperphosphatemia is currently treated with diet, phosphate-binding drugs, and drugs acting on bone metabolism. Despite such treatment, only half of the patients with end-stage renal disease fall within the K/DOQI guidelines range for serum phosphorus levels. This paper reports positive results obtained with the use of the polymer chitosan as a phosphatebinding chewing gum in CKD patients undergoing periodic hemodialysis.

A new approach to the evaluation of hyperphosphatemia in chronic kidney disease.

AIMS: Hyperphosphoremia, main contributor to cardiovascular calcifications, has a major impact on the morbidity and mortality of chronic renal failure (CRF) patients. Phosphate binders and dietary phosphate limitation are not effective enough to abolish hyperphosphoremia-induced cardiovascular abnormalities, therefore, the identification of other and more timely approaches for serum phosphorous reduction is necessary. Salivary fluid contains phosphate which, if related to the daily salivary secretion (1,000 - 1,800 ml), deserves attention as a marker for an earlier start of pharmacologic treatment for phosphorous removal. In ESRD patients under dialysis we have shown increased salivary phosphate closely to be related with serum phosphorous and interpreted as compensatory. This study evaluates salivary phosphate secretion in 77 nondialyzed CRF compared with healthy subjects and its relationship with renal function. METHODS: Saxon's test confirmed normal salivary function in patients and controls. Serum phosphorous, creatinine and GFR were also measured. RESULTS: Salivary phosphorous was significantly higher in CRF patients compared with controls: 38.60 mg/dl (range 12.20 - 95.60) vs 16.30 (10.30 - 27.10), p < 0.0001; serum phosphate was also significantly higher: 3.70 (2.10 - 6.80) vs 3.50 (2.3 4.6), p = 0.013. In CRF patients, salivary phosphorous positively correlated with serum phosphorous (r - 0.45, p < 0.0001) and with serum creatinine (r = 0.72, p < 0.0001), while negatively correlated with GFR (r = -0.72, p < 0.0001). CONCLUSIONS: The results of our study show also in CRF patients increased salivary phosphate secretion, which is related with renal function. On this basis the use of salivary phosphate secretion as a marker for an earlier start of the abnormal phosphate, metabolism pharmacologic treatment could be proposed.

Seminal vesicle cysts with unilateral renal agenesis and contralateral ureteral stenosis in a beta-thalassemic patient: an unknown association by incomplete development of the mesonephric duct.

We report the case of a 13-year-old male patient with beta-thalassemic trait who presented for a colic pain. An ultrasound of the abdomen revealed absence of the right kidney with a complex hypoechogenic pelvic mass causing mild pressure on the posterior bladder wall. Urography showed hypertrophy of the left kidney with moderate ureteral enlargement of the distal third due to an insertion defect in the bladder suggestive of a primary segmental nonobstructing megaureter. MR studies showed right multilocular seminal vesicle cysts. One year later an MR examination of the pelvis showed an increase in size of seminal vesicle cysts and open surgery was performed to remove the cystic retrovesical mass. Our case represents a very rare association of seminal vesicle cysts, unilateral renal agenesis and alteration in contralateral ureteral insertion in a patient with beta-thalassemic trait.

[The status of peritoneal dialysis in Piedmont by 12/31/1997]. / La situazione della dialisi peritoneale in Piemonte al 31/12/1997.

BACKGROUND: The aim of the study is to examine the situation of chronic uremia substitutive treatment by means of peritoneal dialysis in Piedmont on December 31, 1997 using data from the Piedmont regional dialysis and transplant register. METHODS: Starting from the year 1981, data are reported (absolute, per million population, and according to different patient's anagraphic ages) about peritoneal dialysis prevalence and incidence; about basic nephropathies; drop-out from treatment; patient's rehabilitation; complications incidence, particularly peritonitis; patient's survival compared with survival of patients treated, during the same years with extracorporeal techniques. RESULTS: The data demonstrate, during these years, an increase of peritoneal dialysis incidence and prevalence; patients' survival curves, compared with those of patients treated with extracorporeal techniques, are very similar during the first years of treatment and worse afterwards, but never reaching statistical significance. CONCLUSIONS: They support Peritoneal Dialysis as a very good kind of substitutive treatment for some years, but this opinion deserves further examination and investigation on a longer period of time.

A sampling of the yeast proteome.

In this study, we examined yeast proteins by two-dimensional (2D) gel electrophoresis and gathered quantitative information from about 1,400 spots. We found that there is an enormous range of protein abundance and, for identified spots, a good correlation between protein abundance, mRNA abundance, and codon bias. For each molecule of well-translated mRNA, there were about 4,000 molecules of protein. The relative abundance of proteins was measured in glucose and ethanol media. Protein turnover was examined and found to be insignificant for abundant proteins. Some phosphoproteins were identified. The behavior of proteins in differential centrifugation experiments was examined. Such experiments with 2D gels can give a global view of the yeast proteome.

A Saccharomyces cerevisiae Internet protein resource now available.

The QUEST Protein Database Center is now making available two Saccharomyces cerevisiae protein databases via the Internet. The yeast electrophoretic protein database (YEPD) is a database of approximately one hundred protein identifications on two-dimensional gels. The yeast protein database (YPD) is a database of gene names and properties of over 3500 yeast proteins of known sequence. These databases can be accessed via a World-Wide Web (WWW) server (URL http:@siva.cshl.org). YPD is available via public ftp (isis.cshl.org) as well, in a spreadsheet format, and in ASCII format. When accessed via WWW, both of these databases have hypertext links to other biological data, such as the SWISS-PROT protein sequence database and the Saccharomyces Genome Database (SacchDB), and to each other.

Subcutaneous low doses of recombinant human erythropoietin in predialysis patients do not interfere with the progression of renal failure.

This paper reports a study on the treatment of predialysis patients with recombinant human erythropoietin (r-HuEPO). The haematocrit, haemoglobin, reticulocyte and platelet values as well as creatinine and creatinine clearance evaluated by standard and radio-isotopic methods before, during and after r-HuEPO treatment were determined. The slope of the inverse creatinine versus time curves was studied too. The authors did not observe any variation of the renal function parameters during and after study and suggest their protocol of r-HuEPO administration for predialysis patients.

REF52 on Global Gel Navigator: an internet-accessible two-dimensional gel electrophoresis database.

Until recently, the REF52 2-D gel database of experiments with rat cell lines was accessible only with special software. This database has now been made available to all investigators with access to the Internet, using the World Wide Web (WWW) technology. The package which delivers the database through the WWW has been named the Global Gel Navigator and can be used to explore the data by several methods, including the direct selection of proteins in the displayed gel using the mouse.

A distributed system for two-dimensional gel analysis.

The Quest II system is a new two-dimensional (2D) gel analysis software system for the construction and analysis of 2D gel protein databases. A new architectural approach to 2D gel software systems has been utilized. This architecture is based on a tightly coupled client/server model. There are three layers to the system architecture: (i) a database layer consisting of three database servers, (ii) a compute layer consisting of three compute servers and (iii) an extensible user interface layer currently consisting of user interface tools for linearization and merging of scanned images, the segmentation and detection of protein spots on the images, matching, editing, and analysis of gels. The ability to store and retrieve the large volume of spot data inherent in 2D gel analysis while utilizing database technology is demonstrated.

Renal function evaluation in an adult female with cat-eye syndrome.

Cat-eye syndrome is a rare congenital anomaly involving the kidney. It is rarely reported in literature, while renal function has never been studied up to now. Shown here are the morphofunctional renal alterations observed in a female patient affected by cat-eye syndrome.