Coronary artery calcification is more prevalent in dialysis patients than in patients without kidney disease and this is associated with high serum phosphorus. In this study, we evaluate the effect of calcium carbonate or sevelamer treatments on the progression of calcification in 90 predialysis patients. Inclusion criteria were stable serum calcium, phosphorus, parathyroid hormone, and a similar baseline total calcium score (TCS). These patients were not treated by phosphate binder, vitamin D, or statin. They were given low-phosphorus diets without or with daily calcium carbonate or sevelamer throughout the study that averaged 2 years. Baseline demographic or clinical characteristics along with biochemical parameters were not different among the three groups. The TCS significantly increased in patients on the low-phosphorus diet alone, to a lesser extent in calcium carbonate-treated patients, and not at all in sevelamer-treated patients. The progression of coronary calcification paralleled that of the calcium score. Our study shows that sevelamer treatment should not be restricted to dialysis patients; however, a larger study should be undertaken to confirm these results.

The recent characterization of the prokaryotic Cys2His2 zinc-finger domain, identified in Ros protein from Agrobacterium tumefaciens, has demonstrated that, although possessing a similar zinc coordination sphere, this domain is structurally very different from its eukaryotic counterpart. A search in the databases has identified Ϸ300 homologues with a high sequence identity to the Ros protein, including the amino acids that form the extensive hydrophobic core in Ros. Surprisingly, the Cys2His2 zinc coordination sphere is generally poorly conserved in the Ros homologues, raising the question of whether the zinc ion is always preserved in these proteins. Here, we present a functional and structural study of a point mutant of Ros protein, Ros56-142C82D, in which the second coordinating cysteine is replaced by an aspartate, 5 previously-uncharacterized representative Ros homologues from Mesorhizobium loti, and 2 mutants of the homologues. Our results indicate that the prokaryotic zinc-finger domain, which in Ros protein tetrahedrally coordinates Zn(II) through the typical Cys2His2 coordination, in Ros homologues can either exploit a CysAspHis2 coordination sphere, previously never described in DNA binding zinc finger domains to our knowledge, or lose the metal, while still preserving the DNA-binding activity. We demonstrate that this class of prokaryotic zinc-finger domains is structurally very adaptable, and surprisingly single mutations can transform a zinc-binding domain into a nonzinc-binding domain and vice versa, without affecting the DNA-binding ability. In light of our findings an evolutionary link between the prokaryotic and eukaryotic zinc-finger domains, based on bacteria-to-eukaryota horizontal gene transfer, is discussed.Cys2His2 zinc finger ͉ DNA binding proteins ͉ metal binding proteins ͉ Ros protein I n eukaryotic organisms the abundant Cys 2 His 2 zinc-finger domain, involved in relevant protein-nucleic acid and proteinprotein interactions, consists of Ͻ30 aa and a zinc ion, tetrahedrally coordinated by 2 histidine nitrogens and 2 cysteine sulfurs and essential for stabilizing the ␤␤␣ fold (1-5). In prokaryotic organisms, the first Cys 2 His 2 zinc-finger domain has been identified only recently in the transcriptional regulator Ros from Agrobacterium tumefaciens (6). The Ros zinc-binding domain contains 2 cysteines occupying the first 2 coordinating positions and 3 histidines (His-92, His-96, and His-97; see Fig. 1). We (7) demonstrated that in the Ros protein the histidines involved in zinc coordination are His-92, acting as the third coordinating residue, and His-97 as the fourth; when His-97 is mutated in Ala, the protein is still able to bind zinc and DNA with His-96 acting as the fourth coordinating residue. The NMR structure of Ros DNA-binding domain ) has shown that the prokaryotic Cys 2 His 2 zinc-finger domain, although having a similar zinc coordination sphere, possesses a novel protein fold, which is very different from that of the eukaryotic counterpart (8). In particular, Ros 56 -142 gl...

According to the recent definition proposed by the Consensus conference on Acute Dialysis Quality Initiative Group, the term cardio-renal syndrome (CRS) has been used to define different clinical conditions in which heart and kidney dysfunction overlap. Type 1 CRS (acute cardio- renal syndrome) is characterized by acute worsening of cardiac function leading to AKI (5, 6) in the setting of active cardiac disease such as ADHF, while type - 2 CRS occurs in a setting of chronic heart disease. Type 3 CRS is closely link to acute kidney injury (AKI), while type 4 represent cardiovascular involvement in chronic kidney disese (CKD) patients. Type 5 CRS represent cardiac and renal involvement in several diseases such as sepsis, hepato - renal syndrome and immune - mediated diseases.

The first putative prokaryotic Cys2His2 zinc-finger domain has been identified in the transcriptional regulator Ros from Agrobacterium tumefaciens, indicating that the Cys2His2 zinc-finger domain, originally thought to be confined to the eukaryotic kingdom, could be widespread throughout the living kingdom from eukaryotic, both animal and plant, to prokaryotic. In this article we report the NMR solution structure of Ros DNA-binding domain (Ros87), providing 79 structural characterization of a prokaryotic Cys2His2 zinc-finger domain. The NMR structure of Ros87 shows that the putative prokaryotic Cys2His2 zinc-finger sequence is indeed part of a significantly larger zinc-binding globular domain that possesses a novel protein fold very different from the classical fold reported for the eukaryotic classical zinc-finger. The Ros87 globular domain consists of 58 aa (residues 9 -66), is arranged in a ␤␤␤␣␣ topology, and is stabilized by an extensive 15-residue hydrophobic core. A backbone dynamics study of Ros87, based on 15 N R1, 15 N R2, and heteronuclear 15 N-{ 1 H}-NOE measurements, has further confirmed that the globular domain is uniformly rigid and flanked by two flexible tails. Mapping of the amino acids necessary for the DNA binding onto Ros87 structure reveals the protein surface involved in the DNA recognition mechanism of this new zinc-binding protein domain.DNA binding proteins ͉ NMR spectroscopy ͉ Ros protein

We tested for the presence of coronary calcifications in patients with chronic renal disease not on dialysis and studied its progression in 181 consecutive non-dialyzed patients who were followed for a median of 745 days. Coronary calcifications (calcium score) were tallied in Agatston units by computed tomography, and the patients were stratified into two groups by their baseline calcium score (100 U or less and over 100 U). Survival was measured by baseline calcium score and its progression. Cardiac death and myocardial infarction occurred in 29 patients and were significantly more frequent in those patients with calcium scores over 100 U (hazard ratio of 4.11). With a calcium score of 100 U or less, the hazard ratio for cardiac events was 0.41 and 3.26 in patients with absent and accelerated progression, respectively. Thus, in non-dialyzed patients, the extent of coronary calcifications was associated to cardiac events, and progression was an independent predictive factor of cardiac events mainly in less calcified patients. Hence, assessment of coronary calcifications and progression might be useful for earlier management of risk factors and guiding decisions for prevention of cardiac events in this patient population.