Impairments of functional exercise capacity, muscle strength, balance and kinesiophobia in patients with chronic kidney disease: a cross-sectional study.

BACKGROUND: Muscle weakness, balance, and functional capacity are affected in patients with chronic kidney disease (CKD) in dialysis. However, studies about kinesiophobia, peripheral and respiratory muscle strength, balance, exercise capacity, fatigue, and physical activity level in patients with CKD 3-4 are limited. The study aimed to compare the functional exercise capacity, peripheral and respiratory muscle strength, pulmonary function, balance, kinesiophobia, physical activity, fatigue, and dyspnea between patients with CKD 3-4 and controls. METHODS: This cross-sectional study included 43 patients and 45 controls. Functional exercise capacity [6-Minute Walking Test (6MWT)], peripheral and respiratory muscle strength, pulmonary function, dyspnea, fatigue, physical activity, balance [Berg Balance Scale (BBS)], and kinesiophobia were evaluated. RESULTS: Demographic characteristics were similar in patients [53(50-57) y, 26 M/17F] and controls [51(4.506-55) y, 33 M/12F] (p > 0.05). The 6MWT, respiratory and peripheral muscle strength, pulmonary function, physical activity, and BBS were significantly lower, and the level of dyspnea and kinesiophobia were higher in patients compared with controls (p < 0.05). CONCLUSIONS: Patients had impaired functional exercise capacity, upper and lower extremity muscle strength, respiratory muscle strength, pulmonary function, and balance, increased perception of dyspnea and kinesiophobia, and reduced physical activity level compared with controls. Patients should be directed to cardiopulmonary rehabilitation programs.

Effects of different inspiratory muscle training protocols on functional exercise capacity and respiratory and peripheral muscle strength in patients with chronic kidney disease: a randomized study.

BACKGROUND: Pathological changes were observed in the diaphragm due to abnormal renal function in chronic kidney disease (CKD). Inspiratory muscle training (IMT) has been suggested for patients with CKD; however, the most appropriate intensity for IMT has not been determined. Therefore, this study aimed to investigate the effects of different IMT protocols on respiratory muscle strength, quadriceps femoris muscle strength (QMS), handgrip muscle strength (HGS), functional exercise capacity, quality of life (QoL), pulmonary function, dyspnoea, fatigue, balance, and physical activity (PA) levels in patients with CKD. METHODS: This randomized, controlled, single-blind study included 47 patients and they were divided into three groups: Group 1 (n = 15, IMT with 10% maximal inspiratory pressure (MIP)), Group 2 (n = 16, IMT with 30% MIP), and Group 3(n = 16; IMT with 60% MIP). MIP, maximal expiratory pressure (MEP), 6-min walking test (6-MWT), QMS, HGS, QoL, pulmonary function, dyspnoea, fatigue, balance, and PA levels were assessed before and after eight weeks of IMT. RESULTS: Increases in MIP, %MIP, 6-MWT distance, and %6-MWT were significantly higher in Groups 2 and 3 than in Group 1 after IMT (p < 0.05). MEP, %MEP, FEF25-75%, QMS, HGS, and QoL significantly increased; dyspnoea and fatigue decreased in all groups (p < 0.05). FVC, PEF, and PA improved only in Group 2, and balance improved in Groups 1 and 2 (p < 0.05). CONCLUSIONS: IMT with 30% and 60% MIP similarly improves inspiratory muscle strength and functional exercise capacity. IMT with 30% is more effective in increasing PA. IMT is a beneficial method to enhance peripheral and expiratory muscle strength, respiratory function, QoL and balance, and reduce dyspnoea and fatigue. IMT with %30 could be an option for patients with CKD who do not tolerate higher intensities. TRIAL REGISTRATION: This study was retrospectively registered (NCT06401135, 06/05/2024).

Association of serum lncRNA H19 expression with inflammatory and oxidative stress markers and routine biochemical parameters in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a disorder that affects millions worldwide, and current treatment options aiming at inhibiting the progression of kidney damage are limited. Long noncoding RNA (lncRNA) H19 is one of the first explored lncRNAs and its deregulation is associated with renal pathologies, such as renal cell injury and nephrotic syndrome. However, there is still no research investigating the connection between serum lncRNA H19 expressions and clinical outcomes in CKD patients. Therefore, we investigated the relation of serum lncRNA H19 expressions with routine biochemical parameters, inflammatory cytokines, oxidative stress and mineralization markers in advanced CKD patients. METHODS: lncRNA H19 serum levels from 56 CKD patients and 20 healthy controls were analyzed with reverse-transcription quantitative polymerase chain reaction method. Serum tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and osteocalcin (OC) levels were measured with enzyme linked-immunosorbent assay. Total antioxidant status (TAS) and total oxidative status (TOS) levels were evaluated by the routine measurement method. RESULTS: We found that lncRNA H19 expressions were upregulated in patients with CKD compared to the controls. Furthermore, lncRNA H19 relative expression levels showed a negative relationship with glomerular filtration rate (GFR) while it was positively correlated with ferritin, phosphorus, parathyroid hormone, TNF-α, IL-6, OC, TAS and TOS levels. CONCLUSION: lncRNA H19 expressions were increased in CKD stage 3-5 and HD patients, and elevated lncRNA H19 expressions were associated with decreased glomerular filtration rate, inflammation, and mineralization markers in these patients.

Assessment of corneal topographic, tomographic, densitometric, and biomechanical properties of Fabry patients with ocular manifestations.

PURPOSE: To investigate whether cornea verticillata affects corneal topography, tomography, densitometry, or biomechanics of Fabry patients with ocular manifestations and to compare these results with those obtained from healthy subjects. METHODS: This prospective, cross-sectional study included 23 Fabry patients (Fabry group) with cornea verticillata and the 37 age- and sex-matched healthy subjects (control group). After comprehensive ophthalmological examinations, corneal topography, tomography, and densitometry measurements were taken using Pentacam HR and corneal biomechanics were captured via Corvis ST for all participants. RESULTS: All the investigated topographic and tomographic values were similar in the eyes with Fabry disease (FD) and the controls (P > 0.05). The corneal densitometry values of patients with FD were statistically significantly higher in all the concentric zones and layers, except posterior 0-2 mm and posterior 2-6 mm zones, compared to the controls (P < 0.05). The mean values of A1 velocity, A2 velocity, deformation amplitude ratio, Corvis biomechanical index, tomographic and biomechanical index, and Stiffness parameter at the first applanation in the Fabry group were statistically significantly different compared to control group (P < 0.05). However, the mean values of A1 length, A2 length, and the biomechanically corrected intraocular pressure were similar between the groups (P = 0.317, P = 0.819, and P = 0.468; respectively). CONCLUSION: Although cornea verticillata associated with FD is not considered to affect vision, it is associated with increased light backscattering and reduced corneal transparency as well as altered corneal biomechanical properties.

Retinal Microcirculation in Predicting Diabetic Nephropathy in Type 2 Diabetic Patients without Retinopathy.

PURPOSE: To evaluate retinal thicknesses and retinal microcirculation in healthy controls and in diabetic patients with or without microalbuminuria. METHODS: Eighty-six diabetic patients without diabetic retinopathy (DR) (44 normoalbuminuric, 42 microalbuminuric) and 51 healthy controls were enrolled in this cross-sectional, prospective study. Optical coherence tomography (OCT) and OCT angiography (OCTA) were performed. Correlations between OCTA parameters with mean urinary albumin levels were evaluated. RESULTS: The mean vessel densities of superficial capillary plexus (SCP), whole disc, and peripapillary area were significantly decreased in patients with microalbuminuria compared to patients with normoalbuminuria and controls (p < 0.05 for all). The mean vessel density of deep capillary plexus was significantly reduced in patients with microalbuminuria compared to controls (p < 0.05 for all). There were no significant differences in retinal thickness between groups (p > 0.05). Both duration of diabetes and urinary albumin levels were significantly and moderately correlated with mean vessel density of whole SCP in diabetic patients (r = 0.330, p = 0.021; r = 0.356, p = 0.017, respectively). CONCLUSION: Diabetic eyes without clinically detectable DR show impaired retinal microcirculation. Microalbuminuria is associated with alterations of retinal microcirculation in diabetic patients without DR. Evaluation of retinal microcirculation is likely useful for detecting early changes related to microvascular complications in type 2 diabetic patients.

Optical coherence tomography angiography analysis of fabry disease.

PURPOSE: Fabry disease (FD) is characterized by a deficiency in α-galactosidase A activity that leads to the cumulative deposition of unmetabolized glycosphingolipids within organs, including the vascular endothelium and the eyes. The purpose of this study was to assess the effects of FD on the retinal microvasculature, foveal avascular zone (FAZ), macular thickness and retinal nerve fiber layer (RNFL) using optical coherence tomography angiography (OCT-A). METHODS: Twenty-five patients (14 female and 11 male; mean age 33.16 ± 11.44) with genetically verified FD were compared with 37 age- and sex-matched healthy controls (mean age 32.36 ± 15.54). The vessel density (VD) values of the superficial and deep capillary plexuses (SCP and DCP), the area of the FAZ, the density of radial peripapillary capillaries (RPC), the macular thickness and the retinal nerve fiber layer thickness were measured by OCT-A examination. RESULTS: The patients showed significantly lower VD values than controls in the foveal regions of both SCP and the DCP (21.15 ± 5.56 vs. 23.79 ± 4.64 (p = 0.048), 37.92 ± 6.78 vs. 41.11 ± 5.59 (p = 0.048), respectively). The FAZ was significantly larger in the FD group than in the control group (0.3 ± 0.1 vs. 0.24 ± 0.08 (p = 0.011)). No significant difference was identified in measurements of RPC density, peripapillary RNFL thickness or macular thickness between the two groups (p > 0.05 for all). CONCLUSION: Decreased VD and an enlarged foveal avascular area suggest possible changes in the retinal microvasculature of patients with FD. OCT-A can serve as a useful, noninvasive, quantitative tool for diagnosing FD and monitoring its progression.

The association between methylation levels of targeted genes and albuminuria in patients with early diabetic kidney disease.

OBJECTIVE: The incidence of diabetes and its complications are greatly increasing world-wide. Diabeticnephropathy (DN) is the main cause of end-stage renal disease and is associated with high morbidity and mortality. It is important to predict patients with high risk for DN in the early stage. We selected the genes which have an important role on diabetic kidney disease. We aimed to investigate the association between DNA methylation levels of targeted genes and albuminuria in patients with early DN. METHODS: We collected the clinical data of patients with type 2 diabetes mellitus. We measured spot urine albumin creatinine ratio to calculate albuminuria level. We divided patients into two groups based on albumin excretion as patients with (n = 69) and without DN (n = 27). We performed methylation profiling after bisulfite conversion by pyrosequencing method. The mean value of percent methylation level of each gene was calculated. RESULTS: We compared targeted genes (TIMP-2, AKR1B1, MMP-2, MMP-9, MYL9, SCL2A4, SCL2A1, SCL4A3) methylation levels and albuminuria. We found significant negative correlation between TIMP-2 and AKR1B1 gene methylation levels and albuminuria levels. CONCLUSIONS: The present study provided evidence that hypomethylation of TIMP-2 and AKR1B1 genes can be associated with albuminuria in patients with early DN. We may speculate that the hypomethylation of TIMP-2 and AKR1B1 genes may be an early surrogate marker of DN.

The Prevalence of Fabry Disease in Patients with Chronic Kidney Disease in Turkey: The TURKFAB Study.

BACKGROUND/AIMS: Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of α-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. METHODS: This prospective study assessed α-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. RESULTS: Three (all males) of 313 CKD patients (0.95%) were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%), tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%), heat intolerance (71%), and abdominal pain (57%). The most frequent manifestations in female patients were fatigue and cornea verticillata (50%), and tinnitus, vertigo and angiokeratoma (25%). Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. CONCLUSIONS: The prevalence of Fabry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin.

Higher Serum Bisphenol A Levels in Diabetic Hemodialysis Patients.

BACKGROUND: Bisphenol A (BPA) has been implicated as an 'endocrine disruptor'. We aimed at exploring the association between serum BPA levels and patient characteristics, particularly the presence of diabetes mellitus, and laboratory parameters in hemodialysis patients. METHODS: This study included 47 chronic hemodialysis patients. Patient characteristics were recorded. Blood was drawn before and after hemodialysis session. Serum BPA levels were measured by the high-performance-liquid-chromatography and laboratory parameters were measured by using standard methods. RESULTS: In hemodialysis patients, postdialysis serum BPA levels were significantly higher than predialysis after a single hemodialysis session (5.57 ± 1.2 vs. 4.06 ± 0.73, p < 0.0001). Predialysis serum BPA levels were significantly higher in patients with diabetes than non-diabetics (4.4 ± 0.6 vs. 3.9 ± 0.7, p = 0.025). No association was found between serum BPA levels and patient characteristics, and particularly laboratory parameters. CONCLUSION: Serum BPA levels were rising significantly after a single dialysis session. Diabetic hemodialysis patients had higher predialysis serum BPA levels.

Thiol/disulfide homeostasis as a new oxidative stress marker in patients with Fabry disease.

This is the first study to show both dynamic thiol-disulfide balance and oxidative stress levels in patients with Fabry disease (FD). This prospective study consists of 30 FD patients and 30 healthy controls. Thiol and disulfide values of the study groups were evaluated using a new, cost-effective and fully automatic colorimetric method. A total of 60 subjects were included in the study. A statistically significant difference was found between the patient and control groups for native and total thiol levels (p < 0.001). In addition, disulfide levels were significantly higher in FD patients compared with the control group (p < 0.003). Native thiol levels showed significantly negative correlation with lysosomal globotriaosylceramide, total oxidant status (TOS), and oxidative stress index (OSI) levels. In addition, a positive correlation was found between disulfide/natural thiol and disulfide/total thiol ratios and TOS, OSI, and blood urea nitrogen. We found total antioxidant status levels were lower in the patient group compared to the control group, while TOS and OSI levels were higher and were statistically significant. This study highlights for the first time a novel, cost-effective and fully automated measurement of thiol-disulfide levels in patients with FD. Determination of thiol levels can make important contributions to understand the etiopathogenesis and follow-up of the disease in FD patients.

Acute Kidney Injury: Medical Causes and Pathogenesis.

Acute kidney injury (AKI) is a common clinical syndrome characterized by a sudden decline in or loss of kidney function. AKI is not only associated with substantial morbidity and mortality but also with increased risk of chronic kidney disease (CKD). AKI is classically defined and staged based on serum creatinine concentration and urine output rates. The etiology of AKI is conceptually classified into three general categories: prerenal, intrarenal, and postrenal. Although this classification may be useful for establishing a differential diagnosis, AKI has mostly multifactorial, and pathophysiologic features that can be divided into different categories. Acute tubular necrosis, caused by either ischemia or nephrotoxicity, is common in the setting of AKI. The timely and accurate identification of AKI and a better understanding of the pathophysiological mechanisms that cause kidney dysfunction are essential. In this review, we consider various medical causes of AKI and summarize the most recent updates in the pathogenesis of AKI.

Serum uric acid level and endothelial dysfunction in patients with nondiabetic chronic kidney disease.

BACKGROUND: An elevated serum uric acid level is strongly associated with endothelial dysfunction and inflammation, both of which are common in chronic kidney disease (CKD). We hypothesized that endothelial dysfunction in subjects with CKD would correlate with uric acid levels. MATERIALS AND METHODS: We evaluated the association between serum uric acid level and ultrasonographic flow-mediated dilatation (FMD) in 263 of 486 patients with recently diagnosed CKD (stage 3-5) (48% male, age 52 ± 12 years). To minimize confounding, 233 patients were excluded because they were diabetic, had established cardiovascular complications or were taking drugs (renin-angiotensin system blockers, statins) interfering with vascular function. RESULTS: Serum uric acid level was significantly increased in all stages of CKD and strongly correlated with estimated glomerular filtration rate (eGFR-MDRD); FMD was inversely associated with serum uric acid (r = -0.49, p < 0.001). The association of serum uric acid with FMD remained after adjustment for age, gender, smoking, LDL cholesterol, eGFR, high-sensitivity C-reactive protein, systolic blood pressure, proteinuria, and homeostatic model assessment index (ß = -0.27, p < 0.001). CONCLUSION: Increased serum uric acid is an independent predictor of endothelial dysfunction in subjects with CKD.

Long-term morbidity and mortality related to falls in hemodialysis patients: role of age and gender - a pilot study.

BACKGROUND: Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are prone to falls. In this pilot study, we aimed to determine the incidence of falls in a cohort of HD patients during a 1-year period, to identify any specific risk factors that may predict falls in this cohort, and to assess whether falls can independently predict hospitalization, nursing home admissions and/or mortality over an additional 2 years. MATERIALS AND METHODS: Baseline assessments followed by documentation of falls prospectively during a 1-year period were done on 76 HD patients. Patients were followed for an additional 2 years and four outcomes were recorded: all-cause death, nursing home admission, the number and duration of all hospitalizations. RESULTS: 20 patients (26.3%) fell over a 12-month period. Elderly and females had a higher risk of falls than the younger and male population (p = 0.034 and 0.006 respectively). During the 2-year follow-up, compared to non-fallers, fallers had a 2.13-fold increase in risk of death, a 3.5-fold increase in risk of nursing home admission, and nearly a 2-fold increase in the number and duration of hospitalizations. CONCLUSIONS: Falls are common in HD patients, with a higher incidence in females and elderly, and are associated with worse outcomes, more so in recurrent fallers.

Screening for depression in elderly hemodialysis patients.

BACKGROUND: Depression is common and associated with increased morbidity and mortality in elderly (≥65 years) hemodialysis patients. Beck's Depression Inventory (BDI) and the Geriatric Depression Scale (GDS) have been used in different cohorts to screen for depression. OBJECTIVES: We aimed to evaluate the 15-item GDS (GDS-15) as such a tool in elderly hemodialysis patients and compare it with BDI, a previously validated tool in younger hemodialysis patients. DESIGN: Cross-sectional study. SETTING: Four out-patient hemodialysis units; 1 based in a university hospital and 3 based in the community. PARTICIPANTS: Hemodialysis patients aged 65 years and older. INTERVENTION: Both tools were administered to all participants, and a geriatric psychiatrist blinded to the results evaluated them for depression by the gold standard psychiatric interview. MEASUREMENTS: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for both tools were assessed against the psychiatric interview (n = 62). RESULTS: Patients who were depressed according to the psychiatric interview had significantly higher GDS-15 and BDI scores compared to those not depressed (p < 0.01 both). ROC curves showed high predictive accuracy of the GDS-15 and BDI (area under the curve: 0.808 and 0.729) versus the psychiatric interview. The GDS-15 cutoff with the best diagnostic accuracy was 5 with a sensitivity of 63%, specificity of 82%, PPV of 60% and NPV of 83%. The BDI cutoff with the best diagnostic accuracy was 10 with a sensitivity of 68%, specificity of 77%, PPV of 57% and NPV of 85%. CONCLUSION: These results provide evidence that the GDS-15 shows validity in comparison to a gold standard and can be used to screen for depression in the elderly hemodialysis population.

Determination of Serum Perfluorooctanoic Acid and Perfluorooctanesulfonic Acid Levels with Different Stages of Chronic Kidney Disease.

The aim of this study is to investigate the perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) levels in patients with different stages of chronic kidney disease (CKD). Sixty-one CKD stage 1-4 patients who applied to the nephrology outpatient clinic were recruited. A control group consisting of 26 age- and sex-matched healthy controls were also included in the study. Concentrations of PFOA and PFOS were determined by comparing their peak areas with their standard curves. All samples were analyzed three times. The average values of blank samples were subtracted from the detected PFOA and PFOS values. PFOA and PFOS levels were significantly higher in CKD group than the controls (11.4 ± 7.47, 0.45 ± 0.55; 0.13 ± 0. 17, 0.19 ± 0.4 ng/mL, respectively) (P = 0.001). Hemoglobin, serum albumin, and estimated glomerular filtration rate (eGFR) levels were significantly lower and potassium and uric acid levels were higher in the CKD group than the controls. PFOA and PFOS levels were significantly higher in all stages of CKD patients than healthy controls. However, there was no correlation between eGFR, and PFOS and PFOA. We have demonstrated significantly increased PFOA and PFOS concentrations in different stages of CKD patients. We could not find an association between eGFR, age, and serum PFOS and PFOA concentrations.

Corneal endothelial cell density and microvascular changes of retina and optic disc in autosomal dominant polycystic kidney disease.

Purpose: Vascular endothelial dysfunction in autosomal dominant polycystic kidney disease (ADPKD) may affect the retinal vascular parameters due to structural similarities of kidney and retina. We aimed to evaluate the microvascular changes of retina and optic disc and also corneal endothelial cell density in patients with ADPKD. Methods: Forty-six eyes of 23 patients with ADPKD (Group 1), and 46 eyes of 23 sex- and age-matched healthy controls (Group 2) were included in this cross-sectional study. Demographic and ophthalmic findings of participants were collected. Corneal endothelial cell density (CECD) measurements were obtained by noncontact specular microscopy. Foveal retinal thickness, peripapillary retinal nerve fiber layer (RNFL) thickness, vessel density in different sections of the retina and optic nerve head were analyzed by optical coherence tomography angiography. Results: The mean ages were 41 ± 11 years for Group 1 and 39 ± 10 years for Group 2 (P = 0.313). CECD values were significantly lower in group 1 when compared to group 2 (2653 ± 306 cells/mm2 and 2864 ± 244 cells/mm2, respectively, P < 0.001). The foveal retinal thickness and RNFL thickness were similar, but superior quadrant thickness of RNFL was significantly lower in Group 1 than Group 2 (126 ± 14 µm vs. 135 ± 15 µm, P = 0.003). In Group 1, whole image of optic disc radial peripapillary capillary densities were significantly lower compared to Group 2 (49.4 ± 2.04%, and 50.0 ± 2.2%, respectively, P = 0.043). There was no significant difference regarding superficial, deep retinal vessel densities, foveal avascular zone and flow areas between the groups (P > 0.05 for all). Conclusion: Lower CECD values and decreased superior quadrant RNFL thickness, and microvascular densities of optic disc were revealed in patients with ADPKD. Evaluation of CECD and retinal microvasculature may be helpful in the management of these patients.

Determinants of Outcomes of Acute Kidney Injury: Clinical Predictors and Beyond.

Acute kidney injury (AKI) is a common clinical syndrome characterized by rapid impairment of kidney function. The incidence of AKI and its severe form AKI requiring dialysis (AKI-D) has been increasing over the years. AKI etiology may be multifactorial and is substantially associated with increased morbidity and mortality. The outcome of AKI-D can vary from partial or complete recovery to transitioning to chronic kidney disease, end stage kidney disease, or even death. Predicting outcomes of patients with AKI is crucial as it may allow clinicians to guide policy regarding adequate management of this problem and offer the best long-term options to their patients in advance. In this manuscript, we will review the current evidence regarding the determinants of AKI outcomes, focusing on AKI-D.

Potential new therapeutic agents for diabetic kidney disease.

Diabetic nephropathy is the leading cause of end-stage renal disease, and both the incidence and prevalence of diabetic nephropathy continue to increase. Currently, various treatment regimens and combinations of therapies provide only partial renoprotection. It is obvious that new approaches are desperately needed to retard the progression of diabetic nephropathy. Recently, a number of new agents have been described that have the potential to delay the progression of diabetic kidney disease and minimize the growing burden of end-stage renal disease. These include inhibitors and breakers of advanced glycation end products, receptor antagonists for advanced glycation end products, protein kinase C inhibitors, NADPH (reduced nicotinamide adenine dinucleotide phosphate) oxidase inhibitors, glycosaminoglycans, endothelin receptor antagonists, antifibrotic agents, and growth factor inhibitors. This review addresses these promising new therapeutic agents for delaying the progression of diabetic kidney disease.

Vascular calcification in chronic kidney disease.

VC (vascular calcification) is highly prevalent in patients with CKD (chronic kidney disease), but its mechanism is multifactorial and incompletely understood. In addition to increased traditional risk factors, CKD patients also have a number of non-traditional cardiovascular risk factors, which may play a prominent role in the pathogenesis of arterial calcification, such as duration of dialysis and disorders of mineral metabolism. The transformation of vascular smooth muscle cells into chondrocytes or osteoblast-like cells seems to be a key element in VC pathogenesis, in the context of passive calcium and phosphate deposition due to abnormal bone metabolism and impaired renal excretion. The process may be favoured by the low levels of circulating and locally produced VC inhibitors. VC determines increased arterial stiffness, left ventricular hypertrophy, a decrease in coronary artery perfusion, myocardial ischaemia and increased cardiovascular morbidity and mortality. Although current therapeutic strategies focus on the correction of phosphate, calcium, parathyroid hormone or vitamin D, a better understanding of the mechanisms of abnormal tissue calcification may lead to development of new therapeutic agents, which could reduce VC and improve cardiovascular outcome in CKD patients. The present review summarizes the following aspects: (i) the pathophysiological mechanism responsible for VC and its promoters and inhibitors, (ii) the methods for detection of VC in patients with CKD, including evaluation of arterial stiffness, and (iii) the management of VC in CKD patients.

Magnesium in chronic kidney disease: challenges and opportunities.

Cardiovascular disease is the leading cause of mortality and morbidity in patients with chronic kidney disease, which is partly explained by the fact that 40-70% of patients receiving dialysis have significant coronary artery disease. Recent clinical studies have shown that lower serum magnesium (Mg) levels are associated with vascular calcification and cardiovascular mortality among patients with end-stage renal disease (ESRD). On the other hand, hypermagnesemia inhibits parathyroid hormone secretion, which is considered an important independent risk factor for vascular calcification, left ventricular hypertrophy and mortality in ESRD patients. Finally, increasing evidence points towards a link between Mg and cardiovascular disease, even in subjects without chronic kidney disease. The purpose of this review was to critically review the current literature examining the effects of plasma Mg levels on cardiovascular disease and parathyroid hormone homeostasis in ESRD, and renal transplant patients.