Showing papers in "Kidney & Blood Pressure Research in 2007"
TL;DR: Serum creatinine level, the presence of diabetes, and the duration of the PCI may affect serum NGAL values and kidney function following a PCI procedure.
Abstract: The value of neutrophil-gelatinase-associated lipocalin (NGAL) was highlighted as a novel biomarker for the detection of acute renal failure. We tested the hypothesis whether NGAL could represent an early biomarker of contrast-induced nephropathy (CIN) in 100 patients with normal serum creatinine values undergoing percutaneous coronary interventions (PCI). In addition, we assessed serum and urinary NGAL in relation to cystatin C, estimated glomerular filtration rate, and serum and urinary creatinine in these patients. We measured urinary and serum NGAL values before and 2, 4, 8, 24, and 48 h after the PCI. We found a significant rise in serum NGAL levels 2, 4, and 8 h after the PCI and in urinary NGAL values 4, 8, and 24 h after a PCI procedure. Cystatin C rose significantly 24 h after the procedure. The prevalence of CIN was 11%. The NGAL levels were significantly higher 2 h after the PCI (serum NGAL) or 4 h after the PCI (urinary NGAL), whereas the cystatin C values were higher only 8 and 24 h after a PCI procedure in patients with CIN. In multivariate analysis, only serum creatinine was a predictor of serum NGAL before a PCI. NGAL may represent a sensitive early biomarker of renal impairment after PCI. Serum creatinine level, the presence of diabetes, and the duration of the PCI may affect serum NGAL values and kidney function following a PCI procedure.
108 citations
TL;DR: The inhibitory effect of everolimus appears to represent a class effect of mTOR inhibitors in Han:SPRD rats, and the number of 5-bromo-2-deoxyuridine-labeled nuclei in cyst epithelia was markedly reduced.
Abstract: Background/Aims: Rapamycin inhibits cyst growth in polycystic kidney disease by targeting the mammalian target of rapamycin (mTOR) To determine if this is a class effect of the mTO
106 citations
TL;DR: The aim of this review is to summarize the current knowledge dealing with a possible role of hepcidin in iron metabolism and its regulation, particularly in kidney disease.
Abstract: Maintaining the correct iron balance is crucial for health. Our understanding of the molecular control of iron metabolism has increased dramatically over the past 5 years due to the discovery of hepcidin. This is a circulating antimicrobial peptide mainly synthesized in the liver, which has been recently proposed as a factor regulating the uptake of dietary iron and its mobilization from macrophages and hepatic stores. Inflammation causes an increase of production of hepcidin, which is a potent mediator of anemia of chronic diseases. Anemia in chronic kidney disease is mainly due to erythropoietin deficiency but these patients often have a chronic inflammatory state. The aim of this review is to summarize the current knowledge dealing with a possible role of hepcidin in iron metabolism and its regulation, particularly in kidney disease. In addition, current methods of determination of hepcidin are reviewed.
103 citations
TL;DR: The authors review briefly the main pathophysiological mechanisms leading to reduced arterial compliance and the potential therapeutic interventions – mainly the use of certain antihypertensive drugs and reduction of vascular calcification – are discussed.
Abstract: Cardiovascular (CV) morbidity and mortality is greatly enhanced in patients with chronic kidney disease, compared to the non-renal population. One key element of this high CV burden appears to be arte
92 citations
TL;DR: The exercise-induced reduction of BP, which is mediated by improved endothelial function, is independent of pulse pressure, and physical exercise is a helpful adjunct to control BP even in old hypertensives with markedly increased arterial stiffness.
Abstract: Background: Hypertension in the elderly is commonly characterized by an elevation of pulse pressure. With regard to advanced arteriosclerosis and limited physical fitness, doubt was
88 citations
TL;DR: Cyst formation is a key event in the genesis of hypertension while the sympathetic nervous system is important in the maintenance of hypertension in this model of ARPKD.
Abstract: Background/Methods: We have examined the hypothesis that cyst formation is key in the pathogenesis of cardiovascular disease in a Lewis polycystic kidney (LPK) model of autosomal-re
84 citations
TL;DR: Although biosimilars will likely lower the cost of modern therapies there are issues which have to be discussed at this stage among physicians regarding in particular the differences between biosimilar and generics of the classical chemical drugs, need for appropriate regulations as well as identification of potential problems with biosimilARS.
Abstract: Biotechnological drugs have become an essential part of modern pharmacotherapy and are expected to reach a 50% share in the pharmaceutical market in the next few years. The expiry of patent protection for many original biotechnological medicines has led to the development of what are called biosimilars or follow-on biologics. Biosimilars attempt to copy the original technology leading to the production of innovative biotechnological medicines to obtain a product which is similar to the original one. The first two biosimilars have recently been approved in the European Union and one application was rejected. Many more biosimilars will likely see approval in the near future. Our experience with biosimilars has been very limited to date and long-term safety data including immunogenicity are not available. Although biosimilars will likely lower the cost of modern therapies there are issues which have to be discussed at this stage among physicians regarding in particular the differences between biosimilars and generics of the classical chemical drugs, need for appropriate regulations as well as identification of potential problems with biosimilars. Other specific problems which will also be addressed in this review are safety of biosimilars, pharmacovigilance, automatic substitution, naming and labeling/prescription rules.
76 citations
TL;DR: The AURORA trial is the first large-scale international trial to assess the effects of statins on cardiovascular outcomes in patients with ESRD on chronic haemodialysis and results will impact on the current guidelines and use of statin in this patient population.
Abstract: Background: Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD). Aims: AURORA (A study to evaluate the Use
57 citations
TL;DR: How the RA- and NO-generating systems may underpin key aspects of gender differences in normal renal function and renal disease is examined.
Abstract: Female gender is associated with better renal function and resistance to renal injury, suggesting that an oestrogen-based effect or increased androgenic effects are responsible. Studies in rodents have confirmed a biological basis for this, based on the differential effects of androgens and oestrogens on the normal and diseased kidney. Many researchers in the field believe that the pre-menopausal levels of oestrogen are key to the protection observed in females. The key pressor effects of the renin-angiotensin (RA) system are due to both direct vasoconstrictory properties and alterations in renal control of extracellular fluid volume. Additionally, the RA has been shown to promote diverse aspects of renal injury. RA activity is positively modulated by androgens and antagonized by oestrogens. Nitric oxide (NO) is a potent vasorelaxant with a key role in renal control of extracellular fluid homeostasis. NO can variously have both protective and deleterious effects on renal injury. Endogenous oestrogen has an anti-hypertensive effect as well as protective effects against cell and organ damage, many of which are mediated via increases in NO generation. We examine how the RA- and NO-generating systems may underpin key aspects of gender differences in normal renal function and renal disease.
47 citations
TL;DR: Renoprotection conferred byLosartan combined with pioglitazone is superior to that conferred by losartan alone in subjects with type 2 diabetic nephropathy and the combination is generally well tolerated.
Abstract: Aim: This study was performed to ascertain whether losartan combined with pioglitazone is superior to losartan alone in delaying the progression of chronic renal failure in patients with type 2 diabetic nephropathy. Methods: Sixty patients with type 2 diabetic nephropathy (stage 3 or 4 chronic kidney disease) were enrolled in a randomized, controlled trial. Thirty patients received losartan (100 mg/day) and pioglitazone (30 mg/day), and 30 patients received losartan only (100 mg/day). The patients were assessed at baseline and at 3-month intervals for 24-hour urinary protein excretion, serum creatinine, creatinine clearance, and fasting blood glucose values. The glomerular filtration rate was measured by means of a 99mTc-diethylenetriamine penta-acetic renogram at baseline and after 12 months. Results: As compared with therapy with losartan alone, the losartan-pioglitazone combination therapy resulted in significantly lower serum creatinine and fasting glucose values at 12 months and in significantly lower degrees of proteinuria at 6 and 12 months. The declines in creatinine clearance and glomerular filtration rate below baseline measurements at stages 3 and 4 of chronic kidney disease were significantly slower for the losartan-pioglitazone group as compared with the losartan-only group. Conclusions: Renoprotection conferred by losartan combined with pioglitazone is superior to that conferred by losartan alone in subjects with type 2 diabetic nephropathy. The combination is generally well tolerated.
41 citations
TL;DR: This review aims at summarizing available techniques for podocyte cell cultures from both the past and present, with special attention to the currently used methods.
Abstract: Podocytes (glomerular visceral epithelial cells) cover the exterior surface of the glomerular capillaries and contribute to the glomerular filtration membrane. Failure of podocyte function is involved in the progression of chronic glomerular disease; accordingly, research interest into podocyte biology is driven by the need for better protection and perhaps recovery of these cells in renal diseases. This review aims at summarizing available techniques for podocyte cell cultures from both the past and present, with special attention to the currently used methods. The establishment of classical primary cultures is based on isolation of glomeruli by differential sieving. Plating of glomeruli onto a collagen surface is followed by an outgrowth of cobblestone-like cells that, after replating, differentiate into arborized, mature podocytes. Currently, the majority of research studies use immortalized podocytic cell lines most often derived from transgenic mice bearing a conditional immortalizing gene. The podocytes can also be collected and cultured from healthy or diseased animal or patient urine. The urinary podocytes obtained from subjects with active glomerulopathies display higher proliferation potential and viability in vitro, perhaps due to disease-induced transdifferentiation. Finally, a list of phenotypic markers useful for identification and characterization of the cultured podocytic elements is provided.
TL;DR: The role of the kidney in the metabolism and/or the removal of PAPP-A and sRAGE is demonstrated and, on the contrary, early chronic vascular changes in the kidney TX are associated with elevation of their serum levels.
Abstract: Background: Pregnancy-associated plasma protein A (PAPP-A) and soluble receptor for advanced glycation end products (sRAGE) are new markers related to vascular damage. Meth
TL;DR: A graded independent relation between lower level of FT3 and the risk of nondipping is demonstrated, even if the mechanisms of the findings remain incompletely understood.
Abstract: Currently, the pathogenesis of nondipper hypertension remains largely unclear in patients without any renal or endocrine pathology. It is well known that overt hypothyroidism is strongly associated wi
TL;DR: The effects of recombinant human erythropoietin, a drug widely used in patients on dialysis, on the pulmonary circulation were studied to maintain or induce a reduction in pulmonary arterial pressure.
Abstract: Numerous uremic patients on hemodialysis have pulmonary hypertension attributable to the presence of arteriovenous fistulas, vascular calcification, and endothelial dysfunction due to alterations in the balance between vasoconstrictive and vasodilatory substances. For these reasons, the effects of recombinant human erythropoietin, a drug widely used in patients on dialysis, on the pulmonary circulation were studied. Some authors maintain that recombinant human erythropoietin has an antihypertensive effect, while others have observed that this hormone induces a reduction in pulmonary arterial pressure due to its vasoactive and stimulatory effects on endothelial and smooth muscle cell precursors.
TL;DR: The IFN-upregulated negative costimulatory molecule PD-L1 on TEC may play a protective role to limit tissue injury during renal parenchymal immune responses.
Abstract: Background/Aims: MHC molecules are upregulated on renal proximal tubular epithelial cells (TEC) under inflammatory conditions. This allows TEC to act as ‘non-professional’ antigen-p
TL;DR: Beneficial BP-independent HMR1766 effects on kidney structure and urinary albumin excretion in a noninflammatory model of renal failure and may argue for a novel therapeutic principle.
Abstract: Nitric oxide formation is impaired in chronic renal failure. The renoprotective effects of a nonhypotensive dose of HMR1766, a direct activator of the heme enzyme soluble guanylyl cyclase was studied in comparison to an ACE-i in the remnant kidney model. Male Sprague-Dawley rats were subtotally nephrectomized (SNX) or sham operated (sham) and left untreated or started on treatment with HMR1766 or ACE-i in non-hypotensive doses. BP, albumin excretion and parameters of renal damage were analyzed. After a 12-week study, urinary albumin excretion was significantly higher in untreated SNX than in sham; this increase was prevented by ACE-i and ameliorated by HMR1766. Relative kidney and left ventricular weight were significantly higher in untreated SNX compared to sham; these changes were completely prevented by HMR1766. In untreated SNX, glomerulosclerosis (1.02 ± 0.13) was significantly higher than in sham (0.12 ± 0.04), SNX+HMR1766 (0.27 ± 0.04) and SNX+ACE-i (0.46 ± 0.06). Tubulointerstitial changes went in parallel. Increased glomerular cell number after SNX (71.5 ± 14 vs. 60 ± 7.3 in sham) was prevented by HMR1766 (55.7 ± 7.3), but not by ACE-i (66.6 ± 9). The results document beneficial BP-independent HMR1766 effects on kidney structure and urinary albumin excretion in a noninflammatory model of renal failure and may argue for a novel therapeutic principle.
TL;DR: Treatment with indapamide was followed by a significant decrease of plasma adiponectin concentration, which may participate in the pathogenesis of carbohydrate metabolism disturbances often found in patients treated with thiazide-type diuretics.
Abstract: Background/Aim: Adiponectin is an adipose tissue-specific protein with antiatherogenic and insulin-sensitizing properties. In patients with essential hypertension, plasma adiponecti
TL;DR: The prevalence of BEN remains stable over time in Vreoci village and in persons with proteinuria but not enough criteria for BEN, tubular disorders and hypertension were frequently found.
Abstract: Background/Aims: Thirty-one years after the first cross-sectional study, the population of Vreoci, a Balkan endemic nephropathy (BEN) village, was reinvestigated in order to determi
TL;DR: CsA might be an appropriate and a less toxic alternative drug for LN both as a first-choice and rescue therapy and led to significant improvement in proteinuria and stabilization of renal function.
Abstract: Background: The optimal therapy for lupus nephritis (LN), including the role of cyclosporine (CsA), still lacks scientifically valid clinical experience We evaluated the efficacy of CsA in the induction and maintenance treatment of patients with biopsy-proven LN Patients and Methods: A total of 31 patients (25 women, 6 men, mean age 295 years) were enrolled in the study The majority had proliferative LN The mean follow-up was 856 ± 247 months Results: CsA was used as first-line treatment in 387% of patients and as second-line treatment in 613% of patients Complete remission was achieved in 935% of patients The relapse rate was 452% The mean disease-free interval was 33 months At the end of follow-up, a total of 679% of the patients were in remission The treatment led to significant improvement in proteinuria (p = 0001) and stabilization of renal function Conclusion: CsA might be an appropriate and a less toxic alternative drug for LN both as a first-choice and rescue therapy
TL;DR: Mildly impaired kidney function is common in nondiabetic adults among whom MS prevails, and in men it is mainly associated with IR but not with central obesity and MS-related dyslipidemia, and the quadratic GFR equation enables an acceptable estimation of GFR in a general population.
Abstract: Aims: The association of mild renal dysfunction (estimated glomerular filtration rate [eGFR] 60–89.9 ml/min/1.73 m2) with insulin resistance (IR) or metabolic syndrome (MS) needs be investigated in a population in which MS prevails. Methods: After excluding subjects with diabetes mellitus, 1,678 subjects from a representative cohort (median age 52 years) were studied cross-sectionally. eGFR was based on serum creatinine concentrations using the quadratic GFR equation and categorized by 90 and 60 ml/min/1.73 m2 as limits. MS was identified using the modified criteria of the Adult Treatment Panel-III. Results: In men, whereas MS was not significantly associated with a reduced eGFR category when controlled for homeostatic model assessment (HOMA), HOMA adjusted for MS or for its components was significantly associated with the likelihood of a reduced eGFR. This likelihood was increased by 14% with a doubling of HOMA in men. Age was the dominant correlate of reduced eGFR in women, whereby an association with HOMA was not significant. Conclusion: Mildly impaired kidney function is common in nondiabetic adults among whom MS prevails, and in men it is mainly associated with IR but not with central obesity and MS-related dyslipidemia. The quadratic GFR equation enables an acceptable estimation of GFR in a general population.
TL;DR: The data suggest that IL6, while having no effect on blood pressure, impairs regulation of epoxygenase producing Cyp2c, which could contribute to the development of renal injury in angiotensin salt-sensitive hypertension.
Abstract: Impaired cytochrome P450 epoxygenase enzyme (Cyp2c) regulation contributes to renal damage in angiotensin salt-sensitive hypertension (ANG/HS). We hypothesized that interleukin-6 null mice (IL6–/–) wo
TL;DR: Classic therapeutic combination melphalan and prednisone has been supplemented with drugs with different mechanisms of action in this group of patients, which leads to the better survival and prognosis in the majority of patients.
Abstract: Primary (AL amyloidosis) is a systemic disease characterized by an amyloid deposition process in many organs, with unsatisfactory survival of patients. The monoclonal light chains form the fibrils that deposit and accumulate in tissues. Renal involvement is very frequent in AL amyloidosis and could lead to development of nephrotic syndrome followed by the renal failure in many cases. Classic therapeutic combination melphalan and prednisone has been supplemented with drugs with different mechanisms of action in this group of patients: high-dose dexamethasone, high-dose dexamethasone with melphalan, combination of vincristine, doxorubicin, and dexamethasone or newly high-dose melphalan supported by peripheral blood stem cell transplantation. This progressive therapy leads to the better survival and prognosis in the majority of patients. Alternative therapeutic approaches include thalidomide (alone or in combination with cyclophosphamide), lenalidomide, iododoxorubicin, etanercept and rituximab. The development of immunotherapy is expected in the near future.
TL;DR: Female TGR develop hypertension more rapidly and the salt-sensitive component of hypertension is more pronounced in female than in male TGR.
Abstract: Background: In the present study we evaluated plasma and kidney angiotensin II (ANG II) levels in female and male Ren-2 transgenic rats (TGR) in comparison to age-matched female and
TL;DR: In this article, Proinflammatory cytokines are thought to play an important role in various kidney graft diseases resulting in interstitial fibrosis and tubular atrophy frequently found in cas.
Abstract: Aims: Proinflammatory cytokines are thought to play an important role in various kidney graft diseases resulting in interstitial fibrosis and tubular atrophy frequently found in cas
TL;DR: The prevalence of anemia in patients after transplantation was 32.1%, and the most common cause of the anemia is insufficient graft function development.
Abstract: Background/Aim: Although anemia is a common complication after renal transplantation (RT), data concerning endogenous erythropoietin (EPO) levels in long-term RT recipients are rare
TL;DR: The mechanisms of DNA damage are reviewed, focusing on the role of advanced glycation end products (AGEs) which accumulate markedly in renal insufficiency, and a significant role of AGEs in DNA damage and the potential development of cancer is assumed.
Abstract: In end-stage renal disease (ESRD) there is not only excessive morbidity and mortality due to cardiovascular disease but also an enhanced occurrence of various types of cancer. Both are characterized by oxidative stress and inflammation as two of the central underlying causes of the disease states. In cancer, genomic damage has been demonstrated to be of high pathogenetic relevance. DNA lesions may induce mutations of oncogenes and tumor-suppressor genes which, in the long-run, may lead to malignancies if mutagenicity is not mitigated by repair mechanisms. A high incidence of genomic damage in ESRD patients has been validated by various biomarkers of DNA lesions. We reviewed the mechanisms of DNA damage, focusing in particular on the role of advanced glycation end products (AGEs) which accumulate markedly in renal insufficiency. Considering the in vitro and in vivo findings to date, one has to assume a significant role of AGEs in DNA damage and the potential development of cancer.
TL;DR: The data reveal that A1R mediate glomerular vascular resistance whether or not TGF is activated, that additive effects of CAI and KW3902 on salt excretion occur, in part, because KW 3902 inhibits reabsorption downstream from the macula densa, and that Kw3902 likely inhibits proximal re absorption by interfering with apical sodium-hydrogen exchange.
Abstract: Background: Carbonic anhydrase inhibitors (CAI) reduce proximal reabsorption, activating tubuloglomerular feedback (TGF) and reducing glomerular filtration rate (GFR). Adenosine A
TL;DR: Diastolic dysfunction occurred progressively as renal function deteriorates in patients with ADPKD and this effect is independently related to age and blood pressure.
Abstract: Background: This study evaluates the prevalence of diastolic dysfunction (DD) in several stages of chronic kidney disease (CKD) in patients with autosomal dominant polycystic kidney
TL;DR: In this paper, the intrarenal protein expression was investigated in hypertensive Ren-2 transgenic rats (TGR) and in normotensive Hannover Sprague-Dawley (HanSD) rats.
Abstract: Background: The present study was performed in hypertensive Ren-2 transgenic rats (TGR) and in normotensive Hannover Sprague-Dawley (HanSD) rats. First, the intrarenal protein expre
TL;DR: The increase in AOPP levels was higher than what is expected in this degree of renal failure (glomerular filtration rate in the AA-RA group corresponding to chronic kidney disease stage III), and may have been partly explained by the diminished renal clearance.
Abstract: Background: The aim of the study was to assess the contribution of carbonyl and oxidative stresses to the development of amyloidosis in patients suffering from chronic rheumatic diseases, and the potential influence of renal function to their concentrations was considered. Methods: We investigated 17 patients with chronic rheumatological diseases and histologically proven diagnosis of AA amyloidosis (group AA-RA), 26 patients suffering from rheumatoid arthritis without any signs of AA amyloidosis (group nonAA-RA) and 20 healthy volunteers (Co). In all patients, advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), pregnancy-associated plasma protein A (PAPP-A) and other selected proinflammatory markers were measured. Results: An increase in serum levels of AOPP and AGEs was found in the AA-RA group in comparison with nonAA-RA patients and also with Co (p Conclusions: Increased plasma levels of AGEs and AOPP in the group of patients with AA-RA may have been partly explained by the diminished renal clearance. However, the increase in AOPP levels was higher than what is expected in this degree of renal failure (glomerular filtration rate in the AA-RA group corresponding to chronic kidney disease stage III).