Idiopathic Calcium Oxalate Nephrolithiasis: A Cellular Disease

Physico-chemical, metabolic and hormonal theories regarding the pathogenesis of calcium oxalate nephrolithiasis do not sufficiently explain many features of this disease. The recent findings of an abnormally faster oxalate self-exchange and higher phosphorylation of band 3 in erythrocytes of idiopathic calcium oxalate stone formers suggest the hypothesis that nephrolithiasis may be a cellular disease, characterized by a defect in the function of the anion-exchange. The cellular anomaly seems genetically controlled. Band 3 anion exchanger function seems to be biochemically regulated through modulation of band 3 phosphorylation, which depends on cyclic AMP- and phospholipid-sensitive Ca2+ independent protein kinases. In this light, a reduced glycosaminoglycan concentration in the erythrocyte membranes of stone formers might play a role, as these molecules exert a strong inhibitory effects on band 3 phosphorylation and anion transport in vitro and in vivo. An in vivo trial was performed in which stone formers were administered glycosaminoglycans orally. A reduction in oxalate excretion, and oxalate renal clearance, and a simultaneous correction of the abnormal RBC oxalate flux and band 3 phosphorylation were observed. These data suggest the existence of a link between the erythrocyte abnormality and oxalate transport by the kidney and gut

Discovering predictive temporal patterns for Acute Kidney Injury from critical care data

Acute Kidney Injury is a severe clinical condition with a high risk of multi-organs complications and mortality. For this reason, early recognition is crucial. Our proposal based on a 3-window framework discovers all hidden regularities, called Approximate Predictive Functional Dependencies, with the aim to enable early recognition of high-risk patients during hospitalization in the Intensive Care Unit (ICU). We evaluated the different severity stages according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines, building different pathological state patterns, from admission to the discharge from ICU. According to the clinical practice, for each patient, we examined various characteristics expressed as a temporal history of events that may predict a pathological state pattern. We evaluated our proposal exploiting the MIMIC-IV dataset, a collection of Electronic Medical Records from ICU. The obtained results showed promising possibilities to use this type of dependency to support clinical practice

Heparanase: A Multitasking Protein Involved in Extracellular Matrix (ECM) Remodeling and Intracellular Events

Heparanase (HPSE) has been defined as a multitasking protein that exhibits a peculiar enzymatic activity towards HS chains but which simultaneously performs other non-enzymatic functions. Through its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans, thus contributing to the remodeling of the extracellular matrix and of the basal membranes. Furthermore, thanks to this activity, HPSE also promotes the release and diffusion of various HS-linked molecules like growth factors, cytokines and enzymes. In addition to being an enzyme, HPSE has been shown to possess the ability to trigger different signaling pathways by interacting with transmembrane proteins. In normal tissue and in physiological conditions, HPSE exhibits only low levels of expression restricted only to keratinocytes, trophoblast, platelets and mast cells and leukocytes. On the contrary, in pathological conditions, such as in tumor progression and metastasis, inflammation and fibrosis, it is overexpressed. With this brief review, we intend to provide an update on the current knowledge about the different role of HPSE protein exerted by its enzymatic and non-enzymatic activity

Nephroprotective action of glycosaminoglycans: why the pharmacological properties of sulodexide might be reconsidered

A relatively large body of evidence supports the notion that glomerular capillary wall and mesangial alterations in diabetic nephropathy involve biochemical alterations of glycoproteins in these structures. Evidence in experimental animals rendered diabetic reveals that the administration of heparin and other anionic glycoproteins can effectively prevent the biochemical alterations that promote albuminuria. Moreover, angiotensin II inhibits heparan sulfate synthesis, while heparins modulate angiotensin II signaling in glomerular cells, inhibiting aldosterone synthesis and lowering proteinuria in diabetes patients. Sulodexide, a mixture of heparin and dermatan sulfate, appears to be a promising treatment for diabetic proteinuria partially resistant to renin–angiotensin system blocking agents. Sulodexide prevents heparan sulfate degradation, thus allowing reconstruction of heparan sulfate content and restoration of glomerular basement membrane ionic permselectivity. The antiproteinuric effect appears to be mainly related to the basal proteinuria and consequently to the duration of treatment in a relatively large number of small clinical trials. On the other hand, several sulodexide pharmacodynamic properties could improve the prognosis of chronic kidney disease patients, also independently from its antiproteinuric effect. However, sulodexide development as an antiproteinuric drug needs to be continued, in order to define which kind of patients could better respond to this treatment

Low level exposure to cadmium increases the risk of chronic kidney disease: analysis of the NHANES 1999-2006

BACKGROUND: Environmental factors have been associated with the outbreak of chronic kidney disease (CKD). We evaluated the association of Cadmium (Cd) exposure with the risk of CKD in U.S. adults who participated in the 1999-2006 National Health and Nutrition Examination Surveys (NHANES). METHODS: 5426 subjects > or = 20 years were stratified for values of urinary and blood Cd and a multivariate logistic regression was performed to test the association between blood and urinary Cd, CKD and albuminuria (ALB) after adjustment for age, gender, race/ethnicity, body mass index and smoking habits. RESULTS: Subjects with urinary Cd > 1 mcg/g and subjects with blood Cd > 1 mcg/L showed a higher association with ALB (OR 1.63, 95% CI 1.23, 2.16; P = 0.001). Subjects with blood Cd > 1 mcg/L showed a higher association with both CKD (OR 1.48, 95% CI 1.01, 2.17; P = 0.046) and ALB (OR 1.41, 95% CI 1.10, 1.82; P = 0.007). An interaction effect on ALB was found for high levels of urinary and blood Cd (P = 0.014). CONCLUSIONS: Moderately high levels of urinary and blood Cd are associated with a higher proportion of CKD and ALB in the United States population

Heparanase and Renal Fibrosis

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Improvement of Urinary Stones Analysis Combining Morphological Analysis and Infrared Spectroscopy

Daudon et al. have developed a complex morphoconstitutional classification of renal stone in six different morphological types and several subtypes. According to this classification, a precise correspondence exists between causes of renal stones and subtypes with a great clinical relevance and can be considering a sort of shortcut for the metabolic diagnosis in renal stone patients. Now the diagnosis of causes of renal stones generally requires repeated biochemical investigations on urine and blood samples and usually remains presumptive. We analyzed 150 urinary stones both by stereoscopic microscopy and Fourier transform infrared spectroscopy. The comparison of 150 stones did not reveal any disagreement. We have only 20 partial agreement, and clinicians agreed that the imprecise information obtained with morphological analysis alone would have missed an important clinical finding only in 3 cases. In conclusion, in our opinion, the analysis of urinary stone must combine two different analytical techniques: morphological analysis by stereomicroscope and biochemical analysis with the FT-IR