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Background. The degree of renal scarring in kidney biopsy is an important prognostic factor in patients with chronic kidney diseases. We hypothesize that gene expression in the urinary sediment reflects the degree of renal damage. Methods. We studied 29 patients with chronic kidney disease who underwent kidney biopsy (12 immunoglobulin-A nephropathy and 17 glomerulosclerosis) and 10 healthy controls. The mRNA expressions of a panel of target genes in urinary sediment were measured by real-time quantitative polymerase chain reaction. The results were compared with the degree of histological damage and renal function decline. Results. There were significant differences in the urinary expression of transforming growth factor-b (TGF-b), monocyte chemotactic protein-1 (MCP-1) and collagen IV between disease groups and controls. Urinary TGF-b mRNA expression correlated significantly with estimated glomerular filtration rate (r ¼ � 0.412, P ¼ 0.029) and the degree of tubulointerstitial scarring (r ¼ 0.418, P ¼ 0.024). Urinary MCP-1 expression correlated with the degree of glomerulosclerosis (r ¼ 0.450, P ¼ 0.014), but not tubulointerstitial scarring. Urinary MCP-1 expression correlated with its corresponding level by enzyme-linked immunosorbent assay (ELISA) (r ¼ 0.650, P

Angiotensin-converting enzyme inhibitors are the drugs of choice in renal hypertension. The efficacy and safety of ramipril in adults has been proved; however, data on effectiveness of ramipril in children are few. The aim of the present study was to investigate the effect of ramipril on blood pressure (BP) and proteinuria in children with chronic kidney diseases.A total of 31 children (median age 11.3 years, range 1.9-19.8 years) with various chronic nephropathies and hypertension or proteinuria were prospectively treated with ramipril for 6 months. Blood pressure was evaluated using ambulatory BP monitoring and hypertension was defined as mean BP equal to or greater than the 95th percentile for healthy children. Proteinuria was defined as protein excretionor =100 mg/m(2)/24 h. The starting dose of ramipril was 1.5 mg/m(2)/24 h once daily. In 27 children it was given as monotherapy.The median decrease in ambulatory BP was 11 mm Hg for daytime systolic, 10 mm Hg for daytime and nighttime diastolic, and 8 mm Hg for nighttime systolic BP. Hypertension normalized in 55% of the children. Proteinuria decreased in 84% of the children with pathologic proteinuria; the median decrease was 51%. A positive correlation was found between initial proteinuria and change of proteinuria (r = 0.95, P.001). Glomerular filtration rate and serum potassium level did not change significantly. One child developed a cough that was believed to be related to ramipril.Ramipril is an effective and safe drug in children with chronic kidney diseases associated with hypertension, proteinuria, or both.

The effects of an oral adsorbent, AST-120, in chronic kidney disease (CKD) patients was evaluated by the 24-month dialysis-free rate and 50% dialysis-free period. This study retrospectively analyzed 193 patients admitted to the Osaka Medical College Hospital between January 1994 and December 2001 because of CKD and who later started dialysis. The propensity score on multiple factors was used to match two groups of patients (AST-120 group, n = 78; non-AST-120 group, n = 78). Then, the proportion of patients remaining dialysis-free and the 50% dialysis-free period during the 24 months after starting treatment with or without AST-120 were analyzed. The impact of AST-120 on the risk of dialysis initiation was also determined by multivariate analysis. There were no significant differences in the clinical background and laboratory values after matching the two groups using the propensity score. The 50% dialysis-free period was significantly prolonged in the AST-120 group compared to the non-AST-120 group for all patients analyzed, as well as for the subgroup with diabetic or non-diabetic renal disease. When AST-120 treatment was started at a serum creatinine level below 3 mg/dL, the dialysis-free period was longer than 24 months in the AST-120 group, compared with 16.2 months in the non-AST-120 group. The 24-month dialysis-free rate was higher in the AST-120 group in every patient category. The risk of dialysis initiation was increased 3.48-fold in patients who were not administered AST-120. These results show that AST-120 delays the initiation of dialysis in CKD patients. Thus, AST-120 is an effective supplementary therapy to prevent the initiation of dialysis in CKD patients.

The signaling pathways involved in the progression of chronic renal diseases remain poorly understood. Recent works have shown that epidermal growth factor receptor (EGFR) may act as a central transducer of heterologous signaling systems, such as angiotensin II, endothelin-1 and proteinuria, leading to renal damage. The molecular mechanisms of EGFR transactivation involve processing of transmembrane growth factor by metalloproteases. Transactivation of EGFR triggers molecular and cellular events that promote cell proliferation, matrix synthesis and vascular remodeling. Elucidation of elements and regulatory pathways implicated in EGFR transactivation should contribute to the development of novel therapeutic strategies for preventing the progression of chronic kidney disease.

Background. The aim of our study was to assess the subgingival profile of 9 periodontal pathogens, by means of real-time PCR, in a group of predialysis chronic kidney disease patients with and without periodontal disease and to identify the risk factors associated with periodontal disease in these patients.Material and Methods. This is a single centre cross-sectional cohort study performed on 70 CKD patients. Patients received a full-mouth periodontal examination and the following parameters were assessed: periodontal pocket depth (PPD), clinical attachment level, bleeding on probing, and plaque index; subgingival biofilm samples were collected from the deepest periodontal pocket of each quadrant and were pooled in one transporting unit. Clinical data were drawn from the medical file of the patients.Results.T. denticola(P=0.001),T. forsythia(P<0.001), andP. micros(P=0.003) are significantly associated with periodontal disease in CKD subjects but in a multivariate model only age andT. forsythiaremain independent risk factors for periodontal disease in patients with CKD.Conclusions. In our cohort, age andT. forsythiaare independently associated with periodontitis in CKD patients. Within the limits of this study, CKD was not significantly associated with a particular subgingival periodontal pathogens profile in periodontitis patients.

Arterial hypertension is the important reason of the morbidity and mortality of the patients with chronic kidney disease. The aim of this study was to estimate the feature of the arterial hypertension, vasomotor form endothelial dysfunction and level of VCAM1 at patients with chronic kidney disease at groups with achievement and not achievement target arterial pressure. At the moment of the survey the target arterial pressure was achieved at 70 (1 group) and not achieved at 31 patients (2 group). During investigation it was applied the complex of biochemical, immune-enzyme and instrumental methods. The vasomotor form of endothelial dysfunction was detected at all of patients. The improvement of endothelium-dependent vasodilatation was defined at patients with achieved target arterial pressure. The VCAM1 concentration was elevated only at the patients 2 group. This group was differ from the 1 group with more high arterial pressure, left ventricular hypertrophy, atrium enlargement, complex intima-media enlargement, decrease glomerular filtration rate. It was made the conclusion that achievement target arterial pressure facilitate the correction of vasomotor form of endothelial dysfunction.

The benefit of the add-on angiotensin II receptor blocker candesartan to angiotensin-converting enzyme (ACE) inhibitors in inhibition of progression of nephropathy in hypertensive patient with nondiabetic renal disease compared with monotherapy with ACE inhibitors remains controversial. All patients were previously treated with ACE inhibitors. Urinary protein excretion of patients exceeded 1.0 g/d despite treatment with ACE inhibitors. Ninety hypertensive patients with chronic renal insufficiency were randomly assigned to one of two groups. One group received ACE inhibitor plus candesartan (2 to 12 mg/d), and a control group received only ACE inhibitor. The target BP was < or = 130/80 mmHg. The primary outcome was the changes in serum creatinine and the reduction of proteinuria. The mean duration of follow-up was 3.1 +/- 0.4 yr. At years 2 and 3, systolic and diastolic BP were reduced from 140 +/- 3/84 +/- 2 to 129 +/- 1/78 +/- 2 mmHg (candesartan group) and from 135 +/- 2/85 +/- 2 to 130 +/- 2/80 +/- 2 mmHg (ACE inhibitors group). In both groups, both systolic and diastolic BP decreased significantly from the beginning to the end of the study (P < 0.01). The serum creatinine concentration increased from 3.02 +/- 0.27 to 3.38 +/- 0.49 mg/dl (candesartan plus ACE inhibitor group) versus 3.00 +/- 0.37 to 4.48 +/- 0.57 mg/dl (ACE inhibitor group; P < 0.01) at year 3. Although the level of proteinuria significantly declined in each group (P < 0.05), the degree of reductions in proteinuria was greater in the candesartan group than in the ACE inhibitors group (P < 0.01). In the patients who were treated with candesartan and ACE inhibitor or ACE inhibitor alone, pretreatment proteinuria correlated significantly with decline of renal function, whereas reduction of proteinuria negatively correlated with decline in renal function in the patients who were treated with candesartan. Candesartan with an ACE inhibitor is effective in slowing the progression of renal insufficiency in hypertensive patients with nondiabetic renal disease through reduction of proteinuria.

Magnetic resonance imaging (MRI) of normal and diseased kidneys shows great promise because of the combined value of anatomical and functional information provided, as well as of specific contrast patterns that can be observed non-invasively. Multicontrast MRI is able to show infiltrative kidney disorders. Diffusion-weighted imaging can assess alterations in renal function and can suggest obstruction or inflammation when present. Due to the low nephrotoxicity, contrast-enhanced MR studies using serial dynamic enhancement with non-specific gadolinium chelates are able to provide information on glomerular filtration. Furthermore, contrast agents such as ultrasmall particles of iron oxide, specific of inflammation, should be used in the near future to detect active from quiescent involvement, both in native kidneys and renal allografts. Early results should indicate that these compounds might differentiate acute tubular necrosis from other acute nephropathies, as well as active proliferative nephropathies from chronic ones. Ongoing studies will obviously demonstrate the value of the combination of these various MRI sequences in the diagnosis of acute renal failure and chronic kidney disease.

Background. Diabetic patients with chronic kidney disease (CKD) suffer from low quality of life (QOL). We aim to assess the effectiveness of auricular acupressure for QOL improvement in these patients.Materials and Methods. Sixty-two participants were randomly assigned to an auricular or a control arm in a randomized controlled trial. Participants in the auricular arm were instructed to perform auricular acupressure 3–5 times per day for 3 months, when they were receiving conventional treatments. Participants in the control arm received conventional treatments only. The primary outcome was the summarized score of Kidney Disease and Quality of Life Short-Form (KDQOL-SF) at 3 months after randomization. The secondary outcomes included the 36-Item Short Form Health Survey (SF-36), glycosylated hemoglobin (HbA1c), and estimated glomerular filtration rate (eGFR).Results. The summarized KDQOL differed significantly between the acupressure (76.6, 95% CI, 72.2 to 81.0) and the control group (61.8, 95% CI, 57.7 to 65.9). Similar results were found in the SF-36 scores. HbA1c and eGFR were not found to be significantly different between the arms and neither were the adverse events.Conclusion. Auricular acupressure was well tolerated in diabetic patients with chronic kidney diseases receiving hemodialysis. Future research is needed to confirm these results.

Background Tacrolimus is a CYP3A4 inhibitor and can alter colchicine metabolism. In this study, we aimed to evaluate plasma colchicine levels in different stages of kidney disease as well as in kidney transplant (KTx) recipients using tacrolimus. Method This study included six familial Mediterranean fever (FMF) patients with normal glomerular filtration rate (GFR) as controls, three patients with low GFR, six FMF patients on hemodialysis (HD), and six FMF patients who were KTx recipients using tacrolimus. After a three-d washout period, plasma colchicine levels were measured at 0 (pre-dose), one, two, four, eight, and 24 h post-dose of 1 mg oral colchicine. Area under the curve 0–24 h (AUC0–24) and maximum concentration (Cmax) were evaluated and compared between the groups. Results Colchicine AUC0–24 was six-fold higher in HD (p

In 2008 the World Health Assembly endorsed the Global Noncommunicable Disease (NCD) Action Plan, based on growing evidence that NCDs have replaced communicable diseases as the most common cause of premature mortality worldwide.[1] Priority was given to cardiovascular disease, cancer, diabetes and chronic respiratory disease since together they accounted for the major portion of global burden of NCDs and were the leading causes of death. The International Society of Nephrology (ISN), however, welcomed the Declaration of the High Level Meeting on NCDs a few years later in September 2011 stating that “the UN General Assembly recognizes that renal diseases pose a major health threat for many countries and share common risk factors and can benefi t from common responses to noncommunicable diseases. [2] ISN saw this important statement as a fi rst step toward proper recognition of chronic kidney disease as a major NCD.[3] That kidney disease constitutes a public health priority is also underlined by the fact that recent fi ndings from the Global Burden of Disease (GBD) 2010 study have documented an ever-increasing rate of CKD mortality globally.[4] In 2010, CKD ranked 18th among global causes of mortality, in comparison to its ranking of 27th in 1990.[4] Of note, in the last two decades the number of deaths from CKD has risen by 82%, the third largest increase among the top 25 causes of death, behind HIV/AIDS and diabetes.[4] CKD occurs in approximately 10% of the population. However, it must not be assumed that CKD is entirely contained within the cardiovascular risk envelope. Health strategies for prevention, detection, and early treatment of diabetes and cardiovascular disease do not avoid the need to address separately the burden of kidney disease. In the industrialized world up to 40% of those identifi ed with CKD in screening programs have neither diabetes nor cardiovascular disease.[5,6] Such patients are often young, and the health and social costs of the progression of their disease are high and prolonged. Thus, early detection and treatment programs for CKD are also required. Because the risk factors are not the same worldwide, targeting of populations in all regions only on the basis of previously described risk factors—namely hypertension, diabetes mellitus and obesity—might miss groups at risk of CKD where these factors are not the most common causes. Thus, region-specifi c highrisk populations should be screened, such as those exposed to harmful herbal preparations or environmental factors.[7] Herbal medicines are widely used by rural populations in Africa and Asia.[8] Toxic herbs can cause kidney injury, tubular dysfunction, electrolyte disturbances, hypertension, renal papillary necrosis, urolithiasis, CKD and urothelial cancer.[9] In countries where traditional medicines are popular and pharmaceutical medicines are frequently substituted or supplemented by products that include herbs containing aristolochic acid, herbal causes should be considered in cases of unexplained kidney disease.[10] Epidemiologic data from Taiwan and China show an association between use of herbs containing aristolochic acid and CKD.[11,12] Similarly, Balkan-endemic nephropathy, which affects people living along the tributaries of the Danube river in Europe, is now considered to be a form of aristolochic acid-related kidney disease.[13] Clusters of cases of CKD of uncertain etiology (CKDu) have been reported more recently in Sri Lanka and India. An apparently new form of CKD, which cannot be attributed to diabetes, hypertension or other known causes, has emerged in Sri Lanka, with a point prevalence ranging from 2–16% among those aged >18 years. [14–16] Case–control and cross-sectional studies have provided some insights into associations with the condition. Results show chronic exposure of people in the endemic area to low levels of cadmium through the food chain and also to pesticides. They may also be exposed to lead and arsenic through the food chain. Urine concentrations of cadmium and arsenic acid in individuals with CKDu were at levels known to cause kidney damage, and the levels of cadmium positively correlated with CKD stage.[14] This fi nding led the Sri Lankan Ministry of Health, together with WHO representatives who coordinated the research, to suggest that cadmium contamination could be a risk factor for pathogenesis of this hitherto undetermined CKD in the country. (There could be, however, additional genetic susceptibility predisposing to renal injury where individuals are exposed to the toxin.) Notably, this achievement was the result of combined efforts by several stakeholders and organizations, including ISN, which was invited to be part of the International Advisory Board, based on the fact that ISN is the only nongovernmental organization dealing with renal health care in a formal relationship with WHO. Other population clusters have recently received attention because of CKDs that await etiologic characterization, especially in poor communities in developing countries. The clinical presentation resembles that of interstitial nephritis. Histology shows interstitial fi brosis, tubular atrophy and interstitial infl ammatory cell infi ltration. As in Sri Lanka, contamination of water, food or both by heavy metals, fertilizers and pesticides has been suspected. [17] In two studies in India partially funded by the ISN Research and Prevention Committee, no excess of heavy metals was found in the water in the Srikakulam district (MS Ravishankar, Sevenhills Hospital, Mumbai, India, personal communication), while contamination of ground water used for drinking purposes with trace elements such as silica was suspected of causing CKDu described in rural villages in Prakasham and Nellore districts in the state of Andrapradesh (G. Taduri, Nizams Institute of Medical Sciences, Hyderabad, India, personal communication). In the latter case, a program for changing drinking water source was adopted by the communities and strict monitoring of the population for CKD was established.

Nonthyroidal illness syndrome (NTIS) is widely found in the patients with chronic kidney disease (CKD) or critical illness. However, the exact pathogenesis and reasonable treatment remain unclear. To identify suitable studies for inclusion in present review, a search for articles using PubMed search engine with combined terms: (thyroid OR hypothyroidism OR hyperthyroidism OR triiodothyronine) AND (glomerulonephritis OR chronic kidney disease OR chronic renal failure OR end stage renal disease OR hemodialysis OR peritoneal dialysis OR kidney transplantation OR renal transplantation) was performed. The bibliographies of relevant articles were also hand searched. The search was updated on November 8, 2013. Mechanisms for the alternations of thyroid hormone concentrations in NTIS are complicated. Inflammatory cytokines and oxidative stress may play pivotal roles in the pathogenesis of NTIS in patients with CKD. It was controversial whether CKD patients with NTIS should be treated with thyroid hormone replacement. N-Acetyl cysteine or sodium bicarbonate may negatively regulate the progress of micro-inflammation in CKD. Large-scale, multi-centered randomized controlled trials should be conducted to verify the NTIS hypothesis in CKD patients.

Background. Numbers of drugs are required to manage patients with chronic kidney disease (CKD). Drug adherence is relatively poor in this population. Methods. In 36 CKD patients with hypertension and dyslipidemia, who were prescribing amlodipine 5 mg and atorvastatin 10 mg daily, the influences of exchanging to a combination drug containing equivalent doses of amlodipine and atorvastatin were observed for 6 months. Results. At the baseline, flow-mediated dilation (FMD) was reduced (2.4 ± 0.3%), and proteinuria was significantly contributed to decrements of FMD (, , df (6,29), and ). Six months later from exchanging to combination drug, total cholesterol (TC, 197 ± 5 to 183 ± 3 mg/dL, ) and triglycerides (142 ± 14 to 129 ± 10 mg/dL, ) were decreased, but high density lipoprotein cholesterol (53 ± 3 to 56 ± 3 mg/dL, ) was increased. FMD was slightly albeit significantly improved to 2.7 ± 0.3% (). No serious adverse effects were seen by the combination drug. Subanalysis for the patients with considerable reductions of TC demonstrated that the combination drug decreased proteinuria and high sensitive CRP ( for both). Conclusion. Our data indicate that proteinuria constitutes a determinant of a reduced FMD. The present results implicate that combination drug is useful to improve adherence and suggest that atorvastatin refines endothelium function as well as lipid profiles in CKD patients.

In both human and veterinary medicine, diagnosing and staging renal disease can be difficult. Measurement of glomerular filtration rate is considered the gold standard for assessing renal function but methods for its assessment can be technically challenging and impractical. The main parameters used to diagnose acute and chronic kidney disease include circulating creatinine and urea concentrations, and urine-specific gravity. However, these parameters can be insensitive. Therefore, there is a need for better methods to diagnose and monitor patients with renal disease. The use of renal biomarkers is increasing in human and veterinary medicine for the diagnosis and monitoring of acute and chronic kidney diseases. An ideal biomarker would identify site and severity of injury, and correlate with renal function, among other qualities. This article will review the advantages and limitations of renal biomarkers that have been used in dogs and cats, as well as some markers used in humans that may be adapted for veterinary use. In the future, measuring a combination of biomarkers will likely be a useful approach in the diagnosis of kidney disorders.

Study Objective This study was designed to prospectively evaluate the in vivo activities of drug transporters, metabolizing enzymes, and pharmacokinetics in patients with chronic kidney diseases (CKD) caused by glomerulonephritis and nonglomerular etiologies. Design A prospective study design. Participants Eighteen adults with CKD. Setting General Clinical Research Center at the University of North Carolina and University of Pittsburgh. Measurement and Main Results Blood and urine were collected and assayed for fexofenadine (transporter function) as well as flurbiprofen and 4-hydroxyflurbiprofen (CYP2C9 function). CYP3A4 activity was assessed by the erythromycin breath test. In patients with glomerulonephritis, the apparent oral clearance of fexofenadine (representing transporter activity) was 58.8 ± 34.4 L/hour, documenting a 40% reduction compared with previous data in healthy controls. The CYP2C9 pathway (4-hydroxyflurbiprofen formation clearance) was similar in all the patients with CKD and was concordant with previous reports of patients with end-stage renal disease (ESRD) and healthy controls. For flurbiprofen, patients with glomerulonephritis had higher oral clearance than those with nonglomerular CKD, suggesting higher unbound fraction and enhanced metabolism through other (non-CYP2C9) routes. No statistically significant differences in CYP3A4 activity were observed in either group of patients or when compared with results from previous studies of patients with ESRD or healthy controls. Conclusions The current study suggests no statistically significant differences in the in vivo activity of CYP2C9 and CYP3A4 in patients with either glomerulonephritis or nonglomerular CKD. However, there are clinical differences in transporter function as defined by at least a 25% reduction in activity in glomerulonephritis as opposed to healthy controls. A similarity in the in vivo function between patients with glomerulonephritis and ESRD, and between patients with glomerulonephritis and nonglomerular CKD was present despite significant differences in kidney function. Further in vivo and in vitro studies are necessary to fully understand the physiologic and disease-specific nuances that contribute to alterations in drug disposition in patients with kidney diseases.

Traditional Chinese herbal medications (TCHMs) are frequently used in conjunction with western pharmacotherapy for treatment of chronic kidney diseases (CKD) in China and many other Asian countries. The practice of traditional Chinese medicine is guided by cumulative empiric experience. Recent in vitro and animal studies have confirmed the biological activity and therapeutic effects of several TCHMs in CKD. However, the level of evidence supporting TCHMs is limited to small, nonrandomized trials. Due to variations in the prescription pattern of TCHMs and the need for frequent dosage adjustment, which are inherent to the practice of traditional Chinese medicine, it has been challenging to design and implement large randomized clinical trials of TCHMs. Several TCHMs are associated with significant adverse effects, including nephrotoxicity. However, reporting of adverse effects associated with TCHMs has been inadequate. To fully realize the therapeutic use of TCHMs in CKD, we need molecular studies to identify active ingredients of TCHMs and their mechanism of action, rigorous pharmacologic studies to determine the safety and meet regulatory standards required for clinical therapeutic agents, and well-designed clinical trials to provide evidence-based support of their safety and efficacy.

Background: Evidence indicates that microRNAs (miRNA) play a role in the pathogenesis of chronic kidney diseases (CKD). We explored the possibility of using urinary miRNA as non-invasive biomarkers for CKD.Methods: We quantified miRNA expression in urinary sediment of 56 CKD patients who underwent kidney biopsy. Patients were followed for 16.2 ± 15.5 months.Results: Patients with diabetic glomerulosclerosis had lower urinary miR-15 expression, while those with IgA nephropathy had higher urinary miR-17 expression, than other diagnosis groups. Baseline proteinuria had significant inverse correlation with urinary expression of miR-15, miR-192, and miR-216a; baseline renal function correlated with urinary expression of miR-15, miR-17, miR-192, and miR-217. The rate of renal function decline correlated with urinary expression of miR-21 (r= 0.301,p= 0.026) and miR-216a (r= 0.515, p < 0.0001). Patients with a high urinary expression of miR-21 and miR-216a had better dialysis-free survival than those with low expression (log rank test,p= 0.005 andp= 0.003, respectively).Conclusions: Urinary miR-21 and miR-216a expression correlated with the rate of renal function decline and risk of progression to dialysis-dependent renal failure. Our results suggest that urinary miRNA profiling has the potential of further development as biomarkers of CKD.

Increasing evidence shows that transforming growth factor-beta TGF-beta1 (TGF-beta1) is upregulated and plays a diverse role in renal fibrosis by stimulating extracellular matrix (ECM) production, while inhibiting renal inflammation. Recent studies have identified that TGF-beta1, once activated, signals through its downstream signaling pathway to exert its biological effects. It is now well accepted that TGF-beta regulates fibrosis positively by receptor-associated Smads including Smad2 and Smad3, but negatively by an inhibitory Smad, called Smad7. We and other investigators have shown that gene transfer of Smad7 is able to inhibit renal fibrosis in a number of experimental models of chronic kidney diseases, including obstructive nephropathy, remnant kidney disease, and autoimmune crescentic glomerulonephritis. Blockade of Smad2/3 activation is a major mechanism by which overexpression of Smad7 inhibits renal scarring. Furthermore, our recent findings also demonstrate that Smad7 plays a critical role in anti-inflammation in chronic kidney diseases by blocking the NF.kappaB-dependent inflammatory pathway. Thus, Smad7 has a unique role in both anti-renal fibrosis and inflammation. These findings also indicate that targeting the TGF-beta/Smad signaling pathway by overexpressing Smad7 may provide a novel, specific, and effective therapy for chronic kidney diseases.

Observational studies have suggested that different chronic kidney diseases (CKDs) have differing relationships to smoking, but no randomized controlled trial has been conducted to examine this topic. In this article, we review available evidence concerning the relationship between smoking and each type of CKD in the general population as well as in patients with diabetes mellitus (DM), hypertension (HT), primary glomerulonephritis and kidney transplants. There is good evidence of a relationship between smoking and CKD in patients with IgA nephropathy and kidney transplant recipients, but not in patients with DM or HT. Interestingly, it has been reported that the effect of smoking on CKD progression varies depending on the CKD stage. This variation might indicate a cumulative effect of smoking, possibly through oxidative stress. A better understanding of the relationship between smoking and CKD would be useful for nephrologists.

Background. While dysmetabolism is common in patients with chronic kidney disease (CKD) and associated with mortality, the mechanisms mediating these changes are unclear. New data implicate fibroblast growth factor (FGF)-19 as a possible entero-hepatic modulator of lipid metabolism. Methods. Using samples previously gathered as part of a randomized placebo-controlled study of antioxidative therapy for postprandial dysmetabolism, we investigated short-term (4 h) postprandial changes in circulating FGF-19 (ELISA) and the relationship to metabolic markers in six haemodialysis (HD) patients and nine matched healthy subjects (HS), with each participant assessed on four separate occasions. Results. The postprandial FGF-19 response was blunted in patients [maximum change +34.63 (0.24–186) pg/mL] versus controls [maximum change +150.3 (31.2–378.7) pg/mL; P < 0.0001], and the area under the curve (AUC; pg × min × mL �1 )w as also significantly lower 18 019 (12 513–44 387) versus 38 517 (19 775–72 816; P < 0.01). In patients, we found univariate correlations between AUC FGF-19 with AUC C-peptide (rho = 0.71; P = 0.001), AUC insulin (rho = 0.63; P = 0.001), but not with AUCs for triglycerides (TG) or glucose. Finally, treatment with the antioxidative compounds N-acetyl cysteine or MP865, but not with placebo, was associated with higher plasma FGF-19 (NAC and MP865 coefficients �0.28 and �0.23, P < 0.05, respectively). Conclusion. In advanced CKD, the postprandial FGF-19 response appears to be blunted, with partial normalization following antioxidative treatments. A blunted FGF-19 response was associated with impaired insulin and C-peptide signalling.

Echosonography is a simple, noninvasive method of kidney visualization. The objective of this study was to compare the kidney echosonograpic characteristics with the kidney function and anthropometric characteristics in healthy subjects and patients with the chronic kidney disease (CKD).The study involved 49 patients (21 men; 46.02 ± 14.27 years) with CKD and the control group of 46 healthy persons (20 males; 45.45 ± 18.48 years). Physical examination, kidney echosonography and laboratory analyses including creatinine clearance (Ccr; 24 h and calculated by Cockroft--Gault (C--G) formula) were done in all persons.There was no significant difference in age and sex between two groups but serum creatinine concentration was significantly higher (218.8 vs. 84.5 μmol/L) and Ccr significantly lower (66.44 vs. 94.20 mL/min, C--G) in patient group. The left kidney was larger in both groups, but the only significant difference was in kidney depth (p 0.01). There was significant correlation between all measured kidney dimensions, volume, parenchymal thickness and serum creatinine concentration and Ccr (C--G) in patient group. In the controls, there was no significant correlation between the kidney size and function, but there was a significant correlation between the kidney width, depth, volume and patients' age and anthropometric parameters. On the contrary, all analyzed parameters of kidney size, except volume, did not correlate significantly with the anthropometric parameters of patients.Kidney size of patients with CKD correlated significantly with kidney function, while correlation with anthropometric parameters, which is otherwise present in healthy subjects, was lost in patients with CKD.

Chronic kidney disease (CKD) is now one of the major health problems all over the world and its early screening is vital to prevent the development of end-stage renal failure. This study was designed to evaluate the proportion of urban adults suffering from CKD as well as to have a preliminary idea about the determinants of this disorder. The screening program for CKD was arranged in a public place in Dhaka city, Bangladesh, and involved 634 adult partici-pants (>18 years of age) selected on first-come first-served basis. Socio-demographic, anthropometric, and clinical data were collected. Urinary protein was tested by the dipstick method, and serum glucose and creatinine were measured by an auto-analyzer. Estimated glomerular filtrate rate (eGFR) was calculated by using standard formula. CKD was diagnosed and classified accor-ding to the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. A total of 12.8% of the subjects were found to have CKD of whom 2.7% were in Stage 1, 4.1% in Stage 2, and 6% were in Stage 3. The proportion was strongly influenced by age, with the highest prevalence (38.5%) found at 60 years and above. The CKD group showed higher body mass index, waist-hip ratio, and systolic blood pressure, compared with their non-CKD counterparts (P = 0.02). On multiple regression analysis (after adjustment of some confounding variables), age, random blood sugar, and education showed significant association with the development of CKD. A substantial number of urban adults in Dhaka were found to be unaware about the existence of CKD and large-scale prevention programs should be undertaken to reduce the classical risk factors of these disorders.

Vegetarian diet is a very old practice that is liable to confer some health benefits. Recent studies have demonstrated that modification of the dietary pattern with a reduction of animal protein intake and increased consumption of plant-based foods could influence cardiovascular risk profile and mortality rate. Moreover, phosphate bioavailability from plant proteins is reduced. These statements could lead to some benefits for chronic kidney disease (CKD) patients. This review summarizes the characteristics and benefits of vegetarian diets in the general population and the potential beneficial effects of such a diet on phosphate balance, insulin sensitivity, and the control of metabolic acidosis in CKD patients. Potential drawbacks exist when a vegetarian diet is associated with protein intake that is too restrictive and/or insufficient energy intake, justifying an early and regular nutritional follow-up jointly assumed by a nephrologist and a renal dietitian.

Background: Studies in adults with chronic kidney diseases demonstrate that the orally available angiotensin II antagonist irbesartan reduces arterial pressure and pathological proteinuria, mostly with an excellent tolerability profile. Little information is available on irbesartan in childhood. Methods: A total of 44 pediatric outpatients with chronic kidney disease (27 male and 17, aged 3.7 to 18 years, median 10 years) were given irbesartan once a day during 18 weeks for arterial hypertension (N = 23), proteinuria (N = 8), or both (N = 13). Results: In patients with hypertension, the use of irbesartan 4.1 (3.1-5.3) mg/kg body weight daily (median and interquartile range) was associated with a decrease (P < .005) in arterial pressure by 17 (13-22)/10 (7-12) mm Hg. In patients with overt proteinuria the urinary protein excretion decreased (P < .01) during treatment with irbesartan (2.9 [2.0-4.8] mg/kg body weight) by 52 (0-75) mg/[m2 × h]), whereas plasma albumin increased (P < .05) by 4 (1-5) g/L. The frequency of abdominal pain, constipation, cough, diarrhea, dizziness, edema, fatigue, headache, insomnia, myalgia, orthostasis, and rash was similar before and with irbesartan. Plasma sodium slightly decreased, whereas plasma potassium increased, with irbesartan (P < .01). Conclusions: In pediatric patients with chronic kidney diseases, irbesartan given once a day for 18 weeks significantly reduces arterial pressure and proteinuria, with an excellent tolerability and side effect profile. Am J Hypertens 2002;15:1057-1063 © 2002 American Journal of Hypertension, Ltd

Chronic kidney disease (CKD) occurs commonly (prevalence of approximately 20% in a large series) after allogeneic hematopoietic stem cell transplantation (HSCT). There are three distinct clinical entities that occur after HSCT: thrombotic microangiopathy (TMA), nephrotic syndrome (NS), and idiopathic or graft-versus-host disease (GVHD)-related CKD. Acute renal function decline occurs in the majority of patients in the first months after transplantation. This acute kidney injury can persist and is a risk factor for the later development of CKD. However, the potentially independent role of GVHD, chronic inflammation, and chronic exposure to calcineurin inhibitors in the development and progression of CKD warrants further investigation. Careful monitoring of blood pressure, renal function, and proteinuria is mandatory in patients undergoing HSCT, especially older patients with pre-existent renal impairment. Renal function should be evaluated before HSCT and monitoring should occur at least every 6 to 12 months in these patients. Renal biopsies are indicated in patients with proteinuria and persistent or progressive rises in serum creatinine to determine etiology and prevent progression to end-stage renal disease (ESRD).

Background: Upper gastrointestinal (GI) symptoms are common in patients with severe chronic renal failure. The aim of this prospective study is to determine the prevalence of GI abnormalities and Helicobacter pylori (H. pylori) infection and assess the importance of GI evaluation among in pretransplantation with CKD patients Material and Methods: Between August 2008 and July 2010, 287 patients with CKD who were candidates for renal transplantation were included for the study. Endoscopic changes were described and multiple antral gastric biopsies were taken for detection of H. pylori infection. Gastric biopsy findings were compared to findings in 100 consecutive patients with normal renal function undergoing endoscopy for assessment of dyspepsia. Results: There were 197 males 90 females. The Mean age was 36.7 years. Duration of hemodialysis treatment prior to endoscopy was 17 ± 12.3 months. Symptoms of GI disturbance were found in 82(28.6%) of the 287 patients. In the 172 patients with endoscopic abnormalities, there were 49 asymptomatic and 123 symptomatic cases (P

Cardiovascular diseases constitute major cause of death in chronic kidney diseases (CKDs). We examined the effects of angiotensin inhibition either with angiotensin-converting enzyme inhibitor or with angiotensin receptor blocker on patient prognosis and heart-ankle pulse wave velocity (haPWV) in CKDs. Randomized controlled study was performed on 102 patients with non-diabetic CKDs. Patients were divided into two groups with or without angiotensin inhibition, and followed until death, creatinine clearance was halved or starting renal replacement therapy, whichever occurred first. For 4 years, haPWV was assessed repeatedly in the surviving patients. While both groups showed well blood pressure control throughout 4 years (129+/-1 to 131+/-2/71+/-1 to 73+/-2 mm Hg), renal prognosis was better in angiotensin inhibition group (P

BACKGROUND Previous research suggest that repeated lead-chelation therapy decelerates progression of renal insufficiency in non-diabetic (non-DM) patients with high-normal body lead burden (BLB). Study findings are limited by relatively short-term follow-up and small sample size. METHODS A total of 116 non-DM patients with chronic kidney diseases (serum creatinine level of 1.5-3.9 mg/dl), high-normal BLB (>60 microg and

Impact of water intake on the courses of chronic kidney and urinary tract diseases, such as urolithiasis, urinary tract infections, chronic kidney diseases (CKD), autosomal dominant polycystic kidney diseases and bladder cancer, has recently been studied. It still remains controversial whether increased water intake slows the progression of CKD or not. However, high water intake suppresses plasma levels of arginine vasopressin (AVP), which is expected to be beneficial for the preservation of the kidney function. Previous studies suggest that water intake suppresses plasma levels of AVP, and high levels of AVP have been suggested to play deleterious roles in animal models of kidney disease. Moreover, recent epidemic of CKD of unknown origin, which was supposed to be related to the insufficient water intake and chronic volume depletion, has been reported in Central America, further suggesting that the suppression of AVP by sustained water intake might be beneficial in this CKD population. Indeed, the data from recent studies were consistent with the view that high water intake is associated with slower progression of CKD. However, contradictory findings also exist. The intriguing effects of increased urine volume in preserving the glomerular filtration rate in human patients with CKD require more large and well-designed randomized prospective clinical trials.

Pentraxins are classical mediators of inflammation and markers of acute-phase reactions. Pentraxin-3 (PTX3) is believed to be a true independent indicator of disease activity. It has been associated with clinical outcomes in incident chronic kidney disease (CKD) and periodontal diseases. Periodontitis is lately being considered as a risk factor for CKD. However, no data are available on elevated PTX3 in patients with CKD associated with periodontitis.Sixty subjects were divided into three groups (n = 20) based on glomerular filtration rate (GFR) and periodontal parameters: healthy (group-1), CKD (group-2), and CKD with periodontitis (group-3). Plasma samples obtained from each patient were quantified for PTX3 using Enzyme-linked Immunosorbent Assay (ELISA).Both patient groups with CKD had higher plasma PTX3 concentrations than control subjects. However, there was no significant difference between the two groups (groups 2 and 3). In all groups, plasma PTX3 correlated positively with periodontal parameters. Group 3 patients had higher concentrations of PTX3 (6.338 ng/ml) than group 2 (5.41 ng/ml) and group 1 (1.835 ng/ml).Within the limits of the present study, the difference in plasma PTX3 levels between groups 2 and 3 was not found to be statistically significant (P0.05). However, as PTX3 values correlated positively with periodontal parameters, this model could contribute to identifying individuals with periodontitis at high risk of CKD. Thus, periodontal disease could serve as a risk factor for developing CKD. Further large-scale studies nullifying the confounders for CKD are warranted to confirm positive results.

Acute kidney injury (AKI) is considered to be a potential cause for developing chronic kidney disease (CKD); on the other hand, CKD predisposes to AKI. The lack of adequate epidemiological data makes it difficult to determine if AKI induces CKD in less developed countries. The etiology of AKI in rich populations, in whom sophisticated surgery, interventional radiology and oncology treatments are usually the cause of AKI, is very different from that of disadvantaged populations, where the origin of AKI is associated with endemic infections, obstetric problems, poisons, toxins and natural disasters. Any conclusions extrapolated from these two settings should be treated with caution. Moreover, people living in disadvantaged conditions are usually much younger than those in rich areas and this age factor could facilitate total recovery of renal function after AKI if treatment based on an adequate supply of water, rehydration and anti-infectious measures were provided. In the small segment of the population of less developed countries having an income per capita similar to that observed in the developed countries, the long-term outcome of AKI should also be expected to be similar. New data coming from two single centers analyzing only the long-term outcome of acute tubular necrosis (ATN) patients, with a normal or near normal renal function prior to the AKI episode, coincide in reporting a requirement for chronic dialysis among the surviving patients of 2%. If these data are confirmed, the importance of AKI as cause of CKD should be reconsidered, both in developed and less developed countries.

We previously reported that urinary excretion rates of angiotensinogen (AGT) provide a specific index of the activity of the intrarenal renin-angiotensin system in angiotensin II-dependent hypertensive rats. Meanwhile, we have recently developed direct enzyme-linked immunosorbent assays (ELISAs) to measure plasma and urinary AGT in humans. This study was performed to test a hypothesis that urinary AGT levels are enhanced in chronic kidney disease (CKD) patients and correlated with some clinical parameters. Eighty patients with CKD (37 women and 43 men, from 18 to 94 years old) and seven healthy volunteers (two women and five men, from 27 to 43 years old) were included. Plasma AGT levels showed a normal distribution; however, urinary AGT-creatinine ratios (UAGT/UCre) deviated from the normal distribution. When a logarithmic transformation was executed, Log(UAGT/UCre) levels showed a normal distribution. Therefore, Log(UAGT/UCre) levels were used for further analyses. Log(UAGT/UCre) levels were not correlated with age, gender, height, body weight, body mass index, systolic blood pressure, diastolic blood pressure, serum sodium levels, serum potassium levels, urinary sodium-creatinine ratios, plasma renin activity, or plasma AGT levels. However, Log(UAGT/UCre) levels were significantly correlated positively with urinary albumin-creatinine ratios, fractional excretion of sodium, urinary protein-creatinine ratios, and serum creatinine, and correlated negatively with estimated glomerular filtration rate. Log(UAGT/UCre) levels were significantly increased in CKD patients compared with control subjects (1.8801 +/- 0.0885 vs. 0.9417 +/- 0.1048; P = .0024). These data confirmed our earlier report and showed that a new ELISA assay is a valid approach for measuring urinary AGT.

Resistance to the anabolic action of growth hormone may contribute to the loss of strength and muscle mass in adult patients with chronic kidney disease. We tested this hypothesis by infusing growth hormone in patients to levels necessary to saturate hormone receptors. This led to a significant decrease of plasma potassium and amino acid levels in control and hyperkalemic patients with chronic kidney disease. These effects were completely or partially blunted in patients with elevated C-reactive protein levels. In forearm perfusion studies, growth hormone caused a further decrease in the negative potassium and protein balance of hemodialysis patients without inflammation but no effect was seen in patients with inflammation. Only IL-6 levels and age were found to be independent correlates in these growth hormone-induced variations in plasma potassium and blood amino acids. This shows that although a resistance to pharmacologic doses of growth hormone is not a general feature of patients with chronic kidney disease, there is a subgroup characterized by blunted growth hormone action. Our results support the hypothesis that uremia with inflammation, but not uremia per se, inhibits downstream growth hormone signaling contributing to muscle atrophy.

Summary. Hepatitis C virus (HCV) infection remains frequent in patients with chronic kidney disease and the detrimental role of HCV on survival is well-established in this population. Several authors have reported on efficacy and safety of antiviral therapy for hepatitis C in this polulation but there is no clear consensus on management. To evaluate efficacy and safety of antiviral therapy for hepatitis C in patients with chronic kidney disease, we performed a systematic review of the published medical literature and completed a meta-analysis of controlled clinical trials. The primary outcome was sustained virological response (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). We used the random effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses. We identified 13 studies including 539 unique patients; 10 (76.9%) concerned patients on maintenance dialysis. Only prospective, controlled clinical trials were included. Pooling of study results showed a significant increase of viral response in study (patients treated with antiviral therapy) than control patients (patients who did not receive therapy), the pooled odds ratio (OR) of failure to obtain a sustained viral response was 0.081 [95% confidence intervals (CI), 0.029–0.230], P = 0.0001. The pooled OR of drop-out rate was significantly increased in study vs control patients, OR = 0.389 (95% CI, 0.155–0.957), P = 0.04. The studies were heterogeneous with regard to viral response and drop-out rate. In the subset of clinical trials (n = 6) involving only dialysis patients receiving interferon (IFN) monotherapy for chronic HCV, there was a significant difference in the risk of failure to obtain a sustained viral response (study vs control patients), OR = 0.054 (95% CI, 0.019; 0.150), P = 0.0001 (random-effects model). No significant (NS) heterogeneity was found (Q = 14.604, P = 1.0). No difference in the drop-out rate between study and control patients was shown, OR = 0.920 (95% CI, 0.367; 2.311), NS. This result being homogeneous (Q = 3.639, P = 0.388). Our meta-analysis showed that the viral response was greater in patients with chronic kidney disease who received antiviral therapy than controls. No difference in the drop-out rate between study and control patients occurred in the subgroup of dialysis patients on IFN monotherapy. These results support IFN-based therapy for hepatitis C in patients on maintenance dialysis.

UNLABELLED: The severity and dynamics of renal tissue damage in chronic kidney disease (CKD) may be reflected by the urinary excretion of vasoactive and growth factors released by the damaged kidney. Urinary excretion of ET-1, TGF-beta1 and VEGF(165) was evaluated in 303 children with CKD stage II-IV (GFR 48 +/- 22 ml/min/1.73 m(2)) and 81 age-matched healthy controls. Major renal disease groups were hypo-/dysplastic kidney disease (N = 183), obstructive uropathies (N = 47), glomerulopathies (N = 34), nephronophthisis (N = 19) and polycystic kidney disease (N = 20). RESULTS: The mean urinary excretion rates of each of the three putative biomarkers were significantly elevated in CKD patients compared to controls: 965 +/- 2042 vs 216 +/- 335 fmol/g creatinine for ET-1; 252 +/- 338 vs 155 +/- 158 ng/g for VEGF; 31.6 +/- 37.0 vs 10.9 +/- 9.8 ng/g for TGF-beta1 (each P < 0.0001). The excretion of ET-1 and TGF-beta1 was highest in patients with obstructive uropathies. In the patients, ET-1, TGF-beta1 and VEGF excretion rates were inversely correlated with age (r = -0.22, -0.32 and -0.17, all P < 0.005) and renal function (r = -0.21, -0.13 and -0.15; P < 0.001; < 0.05; < 0.01; respectively) VEGF and TGF-beta1 excretion rates were positively correlated both in patients and controls. CONCLUSIONS: Children with CKD exhibit significantly elevated urinary excretion of ET-1, TGF-beta1 and VEGF(165) in comparison to healthy children. Urinary excretion of these biomarkers was most enhanced in patients with obstructive uropathies. A positive correlation between urinary TGF-beta1 and VEGF(165) excretion, shown both in patients and healthy controls, indicates an interdependent nature of their generation.

Anemia is a common complication of chronic kidney disease (CKD), particularly in dialysis patients. Correction of anemia in CKD patients includes the administration of both recombinant human erythropoietin and intravenous iron. An optimization of iron treatment requires obtaining a target hemoglobin level and avoiding an excessive body-iron overload. The reticulocyte hemoglobin content (CHr) has been shown to be an early indicator of iron-restricted erythropoiesis. The recent European guidelines for anemia treatment in CKD assessed the value for CHr >29 pg/cell as the reticulocyte parameter to evaluate a patient's iron needs. The reticulocyte hemoglobin equivalent (RET-He), recently introduced to determine the forward scatter of fluorescence-labeled reticulocytes, seems to be a sensitive indicator of iron-deficiency anemia. This study evaluates the concordance between the CHr parameter, used as a reference, and the new RET-He in a cohort of 57 dialysis patients referred to the Nephrology Unit of our hospital. All patients received erythropoietin, and iron was administered intravenously to maintain the hemoglobin level between 10 and 12 mg/dL. A total of 285 determinations were performed with both instruments. In the dialysis population, the 95% central range for CHr of 24.8 to 36.3 pg corresponds to a range for RET-He of 23.3 to 40.1 pg, with a mean bias of 1.12 pg between the 2 parameters. In comparison with CHr, the value of 30.5 pg for RET-He appeared to be the best cut-off point with a very good sensitivity and specificity to determine patients needing iron supplementation. Our study showed an excellent diagnostic efficiency of RET-He to evaluate patients needing iron support and demonstrated a strict correspondence between the classic CHr and the new Ret-He. This correspondence was independent of clinical changes, frequently occurring in dialysis patients. Both parameters could be used soon to guide and monitor iron treatment in dialysis patients.

Plasma homocysteine (Hcy) levels are increased significantly in patients with moderate renal failure and increase markedly in patients with end-stage renal disease. An increase in plasma Hcy level theoretically could be caused by an increased production rate (ie, transmethylation), a decreased rate of removal by transsulfuration or remethylation, or a decrease in the excretion of Hcy. Current evidence indicates that the major mechanism for hyperhomocysteinemia in renal failure is a decrease in Hcy removal from the body. However, it is debated whether this effect is the result of a decrease in the renal metabolic clearance or a result of extrarenal metabolic changes. The human kidney plays a major role in the removal of several aminothiols or Hcy-related compounds from the circulation (eg, cysteine-glycine, glutathione, AdoMet, and AdoHcy). However, the glomerular filtration of Hcy seems to be restricted because of protein binding. Besides glomerular filtration, the normal kidney can remove Hcy by plasma flow and peritubular uptake. Although in the low normal range in absolute terms, the flow through the transsulfuration pathway is reduced if related to Hcy levels in uremia; in addition, the remethylation pathway also is impaired. Besides the potential effect of the reduced renal mass on Hcy removal, available evidence suggests the occurrence of a generalized down-regulation of the methionine cycle and catabolism in uremia. AdoHcy, sulfate, and dimethylglycine currently are being investigated as retained solutes that can inhibit 1 or more pathways of Hcy metabolism. In addition, the high Hcy levels decrease in malnourished end-stage renal disease patients and change according to nutrient intake and several other nutritional parameters, indicating that circulating Hcy levels become an expression of nutritional status.

To examine if uremia influences muscle interleukin-6 (IL-6) metabolism we studied the exchange of IL-6 across the forearm in 16 patients with chronic kidney disease (CKD) (stages 3 and 4), in 15 hemodialysis (HD)-treated end-stage renal disease (ESRD) patients (n=15), and in six healthy controls. In addition, we performed an analysis of both IL-6 protein and IL-6 mRNA expression in muscle of CKD (stage 4) patients showing evidence of inflammation and in controls. A release of IL-6 from the forearm was observed in patients with elevated IL-6 plasma levels. Arterial IL-6 was directly related to released IL-6 (r=0.69; P

NO synthesis is inhibited by the dimethylarginine (DMA) ADMA, which accumulates, similar to SDMA, in the plasma of patients suffering from chronic renal failure (CRF). ADMA and possibly SDMA contribute to hypertension and atherosclerosis in patients with chronic renal disease: ADMA inhibits directly eNOS, whereas SDMA competes with the NO precursor arginine for uptake into the cells.In 26 control persons and 221 patients with kidney diseases of different stage as were CRF, end stage renal disease (ESRD), and patients after renal transplantation (RT), the plasma concentrations of ADMA (c(ADMA)), SDMA (c(SDMA)) and 20 endogenous amino acids (AA) were measured by HPLC and correlated to blood pressure, cardiac events, endothelial dysfunction, and diabetes mellitus.Both ADMA (1.04+/-0.04 vs. 0.66+/-0.04 microM) and SDMA (2.69+/-0.12 vs. 0.49+/-0.03 microM) were significantly (p0.001) elevated in all patients compared to healthy controls, whereas arginine concentration (51.4+/-2.3 vs. 76.0+/-5.2 microM) was decreased in dependence on the degree of kidney disease. In RT patients, SDMA levels were significantly decreased, but c(ADMA) remained enhanced. A strong correlation was found between SDMA and both serum urea and creatinine in CRF and RT patients. A linear correlation was found between ADMA and cholesterol concentrations in RT patients. Hypertension in CRF was accompanied by a further increase in the concentration of DMAs. There was no relation between DMAs and the occurrence of peripheral arterial occlusive disease or cerebrovascular diseases. In patients with cardiac diseases, c(SDMA) was additionally increased only in the CRF group.In patients with chronic kidney disease, c(ADMA) and c(SDMA) are significantly increased but cardiovascular diseases are evidently not correlated to changes in DMA concentrations in this group of patients.

Background : Chronic kidney disease is a progressive life threatening illness which may be complicated by psychological disorders and may invariably reduce the quality of life and survival of those affected. However, this negative effect on the quality of life of this patient population may be reduced if such psychological problems are recognized early and necessary interventions given. Aim: To determine the relationship between health related quality of life and the mental health of patients with chronic kidney disease. Methods: The health related quality of life of 113 consecutive adult chronic kidney disease patients attending renal clinic of University of Ilorin Teaching Hospital was determined using the 26 items WHOQOL-BREF, while the mental health of the patients were assessed with Schedule for Clinical Assessment in Neuropsychiatry, version 2.1. Psychiatric diagnoses were based on DSM-IV criteria. Results: The health related quality of life of chronic kidney disease patients with psychiatric disorders was significantly lower in all the domains of WHOQOL-BREF than those of chronic kidney disease patients without psychiatric diagnoses: Overall quality of life, p= 0.000; Health satisfaction, p=0.001; Physical health domain, p=0.000; Psychological health domain, p=0.000; Social relationship domain, p=0.000; Environment domain, p=0.000. Depression was found to be the most common type of psychiatric disorder (22.1%), followed by Generalized Anxiety Disorder (4.4%), Dysthymia (1.8%), Schizophrenia (1.8%) and Post-traumatic Stress Disorder (0.9%). Conclusion: Chronic kidney disease patients with psychiatric disorders have lower quality of life compared with their counterparts without psychiatric disorders. Early detection and management of psychiatric disorders in chronic kidney disease patients might bring about better quality of life of these patients. To achieve this, we call for better collaboration between mental health and renal physicians. Keywords : Quality of Life, Psychiatric Morbidity, Chronic Kidney Disease patients, Nigeria

To the Editor: Hsu et al. evaluated the association between chronic kidney disease (CKD) and risk of acute kidney injury (AKI). They demonstrated several important findings: (1) CKD is an important risk factor for the development of AKI; (2) even early CKD stage 3 kidney dysfunction is a risk factor for the development of AKI; and (3) AKI risk increased in a step-wise relationship with worsening kidney disease.1 The public health implication of their investigation is immense. In 2000, 20 million adults in the United States were affected by kidney disease,2 and as the prevalence of CKD increases, the incidence of AKI will also continue to increase.3

The burden of noncommunicable diseases is rising in India. A high prevalence of lifestyle-related diseases in perimenopausal women in the community makes them vulnerable to chronic kidney diseases (CKD). A cross-sectional community-based study was carried out among women >35 years of age in the village of Ballabgarh, Haryana (north India). Eligible women were selected by the probability proportionate to size sampling method. Estimation of glomerular filtration rate (GFR) was carried out by using the age- and body surface area (BSA)-adjusted Cockcroft-Gault (CG) and modification of diet in renal disease (MDRD) equations. Association of risk factors such as obesity, hyperlipidemia, hypertension, and diabetes mellitus with CKD was also assessed using multivariate logistic regression analysis. A total of 455 women were studied. The prevalence of low GFR (

Background Fibroblast growth factor 21 (FGF21) is a hepatic hormone involved in the regulation of lipid and carbohydrate metabolism. This study aims to test the hypothesis that elevated FGF21 concentrations are associated with the change of renal function and the presence of left ventricular hypertrophy (LVH) in the different stages of chronic kidney disease (CKD) progression. Methodology/Principal Findings 240 subjects including 200 CKD patients (146 outpatients and 54 long-term hemodialytic patients) and 40 healthy control subjects were recruited. All CKD subjects underwent echocardiograms to assess left ventricular mass index. Plasma FGF21 levels and other clinical and biochemical parameters in all subjects were obtained based on standard clinical examination methods. Plasma FGF21 levels were significantly increased with the development of CKD from early- and end-stage (P

randomly assigned to one of two treatment sequences: 8 weeks NAC (1,200 mg/day)/8 weeks washout/ 8 weeks placebo (sequence 1) or 8 weeks placebo/8 weeks washout/8 weeks NAC (1,200 mg/day) (sequence 2). The dosages of any drugs once established in the run-in period, were left unchanged throughout the study, as well as in the washout period. Circulating ACE concentration was determined in plasma with a commercial ELISA system (Human ACE Immunoassay Quantikine, RD p = 0.036). A similar conclusion was reached previously in experimental conditions showing that different antioxidants including NAC may decrease local endothelial ACE activity [2] . The molecular and cellular mechanisms by which oxidative stress may mediate ACE activity are not clear so far. Given that increased endothelial expression of ACE plays an important role in cardiovascular remodeling [3] , one may indicate that NAC not only improves endothelial In one of the previous issues of Blood Purification Sahin et al. [1] reported that N-acetylcysteine (NAC) could improve endothelial dysfunction in patients with chronic kidney disease (CKD). The authors suggested that this effect is related to the action of NAC as an antioxidant, i.e. free-radical scavenger, or as a reactive sulfhydryl compound that increases the reducing capacity of the cell. Here, we would like to extend these observations and present the results of our recent clinical study which indicate that NAC could also interfere with the renin-angiotensin system reducing the concentration of circulating angiotensin-converting enzyme (ACE). In a placebo-controlled, randomized, open two-period cross-over study, we evaluated the influence of NAC on plasma concentration of ACE in 20 nondiabetic patients with persistent proteinuria (0.4–6.36 g per 24 h) with normal or slightly lowered kidney function (eGFR 61–163 ml/min). Subjects entered the 8-week run-in period during which antihypertensive therapy was settled with a target blood pressure below 130/80 mm Hg. Next, patients were Published online: May 19, 2008

Non-invasive detection of diseases, based on urinary proteomics, is becoming an increasingly important area of research, especially in the area of chronic kidney disease (CKD). Different platforms have been used in independent studies, mostly capillary-electrophoresis coupled ESI-MS (CE-MS), liquid chromatography coupled mass spectrometry, and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). We have compared the performance of CE-MS with MALDI-MS in detecting CKD, based on a cohort of 137 urine samples (62 cases and 75 controls). Data cross-talk between the two platforms was established for the comparison of detected biomarkers. The results demonstrate superior performance of the CE-MS approach in terms of peptide resolution and obtained disease prediction accuracy rates. However, the data also demonstrate the ability of the MALDI-MS approach to separate CKD patients from controls, at slightly reduced accuracy, but expected reduced cost and time. As a consequence, a practical approach can be foreseen where MALDI-MS is employed as an inexpensive, fast, and robust screening tool to detect probable CKD. In a second step, high resolution CE-MS could be used in those patients only that scored negative for CKD in the MALDI-MS analysis, reducing costs and time of such a program.

Magnesium is involved in the regulation of blood pressure (BP). Abnormalities in serum magnesium are common in chronic kidney disease (CKD), yet its association with the development of hypertension and CKD progression in patients with CKD is unclear. We analyzed data from 3866 participants from the CRIC Study (Chronic Renal Insufficiency Cohort). Linear regression assessed the association of serum magnesium with baseline systolic BP (SBP) and diastolic BP (DBP). Logistic regression explored the association of serum magnesium with various definitions of hypertension. Cox proportional hazards models explored assessed the risk of incident hypertension and CKD progression. Mean serum magnesium was 2.0 mEq/L (±0.3 mEq/L). Higher magnesium was associated with lower SBP (−3.4 mm Hg [95% CI, −5.8 to −1.0 per 1 mEq/L]) and lower DBP (−2.9 mm Hg [95% CI, −4.3 to −1.5 per 1 mEq/L]). Higher magnesium was associated with a lower risk of American Heart Association–defined hypertension (SBP≥130 mm Hg or DBP≥80 mm Hg) at baseline (adjusted hazard ratio, 0.65 [95% CI, 0.49–0.86 per 1 mEq/L]), a lower risk of suboptimally controlled BP (SBP≥120 mm Hg or DBP≥80 mm Hg; adjusted odds ratio, 0.58 [95% CI, 0.43–0.78 per 1 mEq/L]). In time-to-event analyses, higher baseline serum magnesium was associated with a nominally lower risk of incident CRIC-defined hypertension (adjusted hazard ratio, 0.77 [95% CI, 0.46–1.31 per 1 mEq/L]). Higher magnesium was associated with a significantly lower risk of CKD progression (adjusted hazard ratio, 0.68 [95% CI, 0.54–0.86 per 1 mEq/L]). In patients with CKD, higher serum magnesium is associated with lower SBP and DBP, and with a lower risk of hypertension and CKD progression. In patients with CKD, whether magnesium supplementation could optimize BP control and prevent disease progression deserves further investigation.

Introduction: Orthostatic hypotension (OH) affects 5–20% of the population. Our study investigates the presence of OH in diabetic nephropathy (DNP) patients and the factors affecting OH in comparison with nondiabetic chronic kidney disease (NDCKD) patients. Method: Patients presented to the nephrology clinic, and those who consented were included in the study. DNP was defined by kidney biopsy and/or clinical criteria. NDCKD patients of the same sex, age, and eGFR were matched to DNP patients. Demographic parameters and medications were obtained from the records. OH was determined by Mayo clinic criteria. The same researcher used an electronic device to measure blood pressure (BP). All samples were taken and analyzed the same day for biochemical and hematologic parameters and albuminuria. Results: 112 (51 F, 61 M, mean age: 62.56 ± 9.35 years) DNP and 94 (40 F, 54 M, mean age: 62.23 ± 10.08 years) NDCKD patients were included. There was no significant difference between DNP and NDCKD groups in terms of OH prevalence (70.5 vs. 61.7%, p = 0.181). Male patients had significantly higher OH prevalence than female patients (74.7 vs. 60.0%, p = 0.026). There was no significant difference in change in systolic BP between the groups (24.00 [10.00–32.00] mm Hg vs. 24.00 [13.75–30.25] mm Hg, p = 0.797), but the change in diastolic BP was significantly higher in the DNP group (8.00 [2.00–13.00] mm Hg vs. 6.00 [2.00–9.00] mm Hg, p = 0.025). In the DNP group, patients with OH had significantly higher uric acid levels than those without OH (7.18 ± 1.55 vs. 6.36 ± 1.65 mg/dL, p = 0.017). And, 73.7% of patients on calcium channel blockers developed OH (p = 0.015), and OH developed in 80.6% of 36 patients on alpha-blockers (p = 0.049). Conclusion: OH prevalence is very high in CKD, and etiology of CKD does not have a statistically significant effect on the frequency of OH, despite a difference that could be meaningful clinically. Therefore, patients with CKD are checked for OH, with or without concurrent diabetes mellitus. Evaluation of postural BP changes should be a part of nephrology practice.

Background: Chronic kidney diseases become a public health concern as the rate of this diseases is increasing. Thus, the aim of the study was to evaluate the changes in key biomarkers in Bangladeshi CKD stages IV and V patients by using Renadyl capsule. Study Design: Open label randomized placebo controlled clinical trial. Methods: Data were collected from patients with CKD stage IV and V in 2017, in an out-patient setting in Kidney Foundation Hospital and Research Institute, Bangladesh. Patient’s information, medical history and clinical data were also collected. Health condition of the patients was collected by using SF-36 QOL questionnaire. Data were analyzed using SPSS software version 23.0. Results: Administration of Renadyl capsule improved the clinical and biochemical data of the patients. Renadyl administration improved the filtration rate, kidney size, creatinine level, heart rate and liver function. Patient’s physical and mental health was also improved. Conclusion: Renadyl administration appeared to be safe among chronic kidney patients with improved kidney function. However, more clinical trials are suggested to determine the efficacy and effects of Renadyl.