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Background/Aims: The aim of this study is to investigate the utility of clinical [age, gender, mean arterial pressure (MAP)] and laboratory parameters [eGFR, hemoglobin (Hgb), serum levels of creatinine, uric acid, albumin, proteinuria, hematuria] and also histopathological lesions (Oxford classification parameters, crescents, intensity and pattern of staining for C3, C1Q, IgA, IgG, IgM) as progression markers in patients with IgA Nephropathy (IgAN). Methods: A total of 111 IgAN patients with a follow-up period >1 year or who reached kidney failure [GFR category G5 chronic kidney disease (CKD)] <1 year were investigated. Primary endpoint was the development of kidney failure or eGFR decline ≥50% from the baseline. Kaplan-Meier and Cox proportional hazards analyses were performed. Results: Mean follow-up period was 33±29 months. Thirty-seven (33.3%) patients progressed to kidney failure and 4 (3.6%) patients developed eGFR decline ≥50% from the baseline after a median of 23 and 65 months, respectively. In multivariate Cox regression analysis, baseline levels of Hgb (HR:0.782, 95% CI 0.559-0.973, p=0.037), serum uric acid (HR:1.293, 95% CI 1.023-1.621, p=0.046), eGFR (HR:0.966, 95% CI 0.947-0.984, p=0.004) and intensity of C3 staining (HR:1.550, 95% CI 1.198-1.976, p=0.049) predicted primary endpoint. Serum uric acid level was associated independently with T score (β=0.303, p=0.005) in patients with eGFR>30 ml/min/m2. Conclusions: Hyperuricemia and the deposition of C3 are independent risk factors for IgAN progression. [ABSTRACT FROM AUTHOR]

[Display omitted] • Metabolomics reveals potential diagnostic markers for diabetic nephropathy (DN). • Lipid metabolism in podocytes emerges as pivotal in DN. • Cinaciguat activation of NO/sGC/PKG pathway shows promise in DN. • Tryptophan levels serve as prognostic indicators for DN progression. • Integration of metabolomics enhances understanding and management of DN. Diabetic nephropathy (DN), a severe complication of diabetes, involves a range of renal abnormalities driven by metabolic derangements. Metabolomics, revealing dynamic metabolic shifts in diseases like DN and offering insights into personalized treatment strategies, emerges as a promising tool for improved diagnostics and therapies. We conducted an extensive literature review to examine how metabolomics contributes to the study of DN and the challenges associated with its implementation in clinical practice. We identified and assessed relevant studies that utilized metabolomics methods, including nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) to assess their efficacy in diagnosing DN. Metabolomics unveils key pathways in DN progression, highlighting glucose metabolism, dyslipidemia, and mitochondrial dysfunction. Biomarkers like glycated albumin and free fatty acids offer insights into DN nuances, guiding potential treatments. Metabolomics detects small-molecule metabolites, revealing disease-specific patterns for personalized care. Metabolomics offers valuable insights into the molecular mechanisms underlying DN progression and holds promise for personalized medicine approaches. Further research in this field is warranted to elucidate additional metabolic pathways and identify novel biomarkers for early detection and targeted therapeutic interventions in DN. [ABSTRACT FROM AUTHOR]

Adult patients on hemodialysis experience a high prevalence of poor oral health and periodontitis. The chronic inflammation associated with poor periodontal health can increase the risk of cardiovascular disease and mortality among patients on hemodialysis. A systematic review of research articles published from 2012-2018 was conducted to synthesize current literature on the subject. Forty-three articles were identified. Findings were summarized into two categories: clinical measurements and lifestyle/quality of life. We suggest the development, implementation, and evaluation of oral health nursing interventions and periodontal treatments among patients on hemodialysis. [ABSTRACT FROM AUTHOR]

End stage renal disease (ESRD) affects African Americans more than any other ethnic group. Adherence is a challenge. Patients with ESRD must adhere to medication, diet, fluid restrictions, and dialysis treatment schedules if they do not receive a kidney transplant. The purpose of this exploratory, descriptive study was to assess adherence in 120 African Americans with ESRD undergoing hemodialysis (HD). Participants completed a demographic questionnaire and the ESRD Adherence Questionnaire (ESRD-AQ). Biomarkers were collected from medical records. Few participants (24%) adhered to dietary restrictions; however, fluid restriction was reported as the most difficult to manage, which was consistent with the interdialytic weight gain biomarker. Older participants were more adherent. Participants were adherent with HD attendance and medication. Participants reported frequent communication with the healthcare team, but a more formal process needs to be implemented with follow up to ensure understanding and reinforce adherence. [ABSTRACT FROM AUTHOR]

Glomerular filtration rate and/or creatinine are not accurate methods for renal failure prediction. This study tested homocysteine (Hcy) as a predictive and prognostic marker for end stage renal disease (ESRD). In total, 176 subjects were recruited and divided into:healthy normal group(108 subjects);mild-to-moderate impaired renal function group(21 patients);severe impaired renal function group(7 patients); andchronic renal failure group(40 patients) who were on regular hemodialysis. Blood samples were collected, and serum was separated for analysis of total Hcy, creatinine, high sensitive C-reactive protein (CRP), serum albumin, and calcium. Data showed that Hcy level was significantly increased from normal-to-mild impairment then significantly decreases from mild impairment until the patient reaches severe impairment while showing significant elevation in the last stage of chronic renal disease. Creatinine level was increased in all stages of kidney impairment in comparison with control. CRP level was showing significant elevation in the last stage. A significant decrease in both albumin and calcium was occurred in all stages of renal impairment. We conclude Hcy in combination with CRP, creatinine, albumin, and calcium can be used as a prognostic marker for ESRD and an early diagnostic marker for the risk of renal failure. [ABSTRACT FROM AUTHOR]

Aim Involvement of pro-inflammatory genes has been correlated with basic kidney diseases and end stage renal disease (ESRD). However, results at odds were often noted from such independent association studies. This study proposes a genome wide analysis approach to predict ESRD risk associated genes. Methods We included 42 single nucleotide polymorphisms (SNPs) showing association among north Indian ESRD cases and controls. ESRD cases comprised chronic glomerulonephritis (CGN), chronic interstitial nephritis (CIN), hypertension (HTN) and autosomal dominant polycystic kidney disease (ADPKD). Genotyping data obtained from our prior published reports were compared with Genome-Wide Association Studies (GWAS) SNPs retrieved from HapMap and GWASCentral databases using R-statistical package SNPAssoc. Linkage disequilibrium (LD), gene-gene interaction, classification and regression tree (CART) and pathway analysis were carried out in the present study supplemented with IL-6 and TNF-α levels estimation using enzyme linked immunosorbent assay (ELISA). Results Comparison of genotyping data with GWAS SNPs revealed significant associations for interleukin (IL)1-RN, IL-6, MTHFR, tumour necrosis factor-α (TNF-α) and CCR3 genes with ESRD. Nine SNPs were commonly associated with CGN, CIN, HTN, ADPKD and ESRD. LD (D = 0.9) and gene-gene interaction ( P = 0.0002) analyses revealed significant associations for IL-6 and TNF-α genes. In a consistent manner, CART analysis and functional analysis servers predict predisposing effects for TNF-α and IL-6 with ESRD. Finally, higher body circulating levels were observed for mutant TNF-α and IL-6 alleles among ESRD. Conclusion The study indicates significance for IL-6 and TNF-α gene with basic kidney diseases and ESRD. Extensive statistical tests, pathway analysis and functional assays also reflect attenuated level of significance for these SNPs. In future these may be brought from bench side to clinical practice as diagnostic biomarkers upon external and prospective replication and confirmation among other cohorts. [ABSTRACT FROM AUTHOR]

PurposeDisrupted bone metabolism in patients with chronic kidney disease (CKD) is associated with elevated concentrations of biochemical bone markers. Recently, animal studies show the role of osteocalcin in energy metabolism, which is partially confirmed in humans. The aim of our study was to evaluate the relationships between serum concentrations of bone markers and indices of energy metabolism in CKD patients on maintenance hemodialysis; in particular, the relationship between various forms of osteocalcin and adiponectin.Patients and methodsThe cross-sectional study included 155 hemodialyzed stage 5 CKD patients. Serum concentrations of glucose, insulin, adiponectin, bone alkaline phosphatase (bALP), tartrate resistant acid phosphatase (TRAP), carboxylated (cOC), undercarboxylated (ucOC), and intact osteocalcin (OC) were determined.ResultsIn total cohort, bALP, TRAP, cOC, and ucOC negatively correlated with BMI. All analyzed bone markers positively correlated with adiponectin in total cohort and in men. In multiple linear regression analysis including all patients, log(cOC) and log(intact OC) were the only bone markers that predicted log(adiponectin) (beta = 0.22;p = 0.016 and beta = 0.26;p = 0.010) independently of sex, dialysis vintage, CRP, insulin, iPTH concentrations, BMI, and age.ConclusionsOur data confirm the positive association between cOC, intact OC, and adiponectin concentrations in CKD patients on maintenance hemodialysis. [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of this study is to investigate the utility of clinical [age, gender, mean arterial pressure (MAP)] and laboratory parameters [eGFR, hemoglobin (Hgb), serum levels of creatinine, uric acid, albumin, proteinuria, hematuria] and also histopathological lesions (Oxford classification parameters, crescents, intensity and pattern of staining for C3, C1Q, IgA, IgG, IgM) as progression markers in patients with IgA Nephropathy (IgAN). Methods: A total of 111 IgAN patients with a follow-up period >1 year or who reached kidney failure [GFR category G5 chronic kidney disease (CKD)] <1 year were investigated. Primary endpoint was the development of kidney failure or eGFR decline ≥50% from the baseline. Kaplan-Meier and Cox proportional hazards analyses were performed. Results: Mean followup period was 33±29 months. Thirty-seven (33.3%) patients progressed to kidney failure and 4 (3.6%) patients developed eGFR decline ≥50% from the baseline after a median of 23 and 65 months, respectively. In multivariate Cox regression analysis, baseline levels of Hgb (HR:0.782, 95% CI 0.559-0.973, p=0.037), serum uric acid (HR:1.293, 95% CI 1.023- 1.621, p=0.046), eGFR (HR:0.966, 95% CI 0.947-0.984, p=0.004) and intensity of C3 staining (HR:1.550, 95% CI 1.198-1.976, p=0.049) predicted primary endpoint. Serum uric acid level was associated independently with T score (β=0.303, p=0.005) in patients with eGFR>30 ml/ min/m2. Conclusions: Hyperuricemia and the deposition of C3 are independent risk factors for IgAN progression. [ABSTRACT FROM AUTHOR]

The role of oxidative stress in patients with end stage renal disease (ESRD), which occurs at significantly higher levels than in the general population, is often underestimated in clinical practice. Emerging evidence highlights the strong correlation of oxidative stress with chronic inflammation and cardiovascular disease, which are highly prevalent in most patients on maintenance haemodialysis (HD) and are a major risk factor for mortality in this population. In this study, total plasma thiols and plasma S-thiolated proteins were measured in patients with ESRD, before and after a regular HD session, and compared to age-matched healthy subjects. We found a significant decrease in the level of total plasma thiols and, conversely, a significant increase in the level of S-thiolated proteins in these patients. In most patients, post-HD plasma level of total thiols did not differ from the one in healthy subjects, whereas plasma level of S-thiolated proteins was lower in HD patients than in age-matched healthy controls. This suggests that a single HD session restores plasma thiol redox status and re-establishes the antioxidant capacity of plasma thiols. Additionally, we determined protein thiolation index (PTI), i.e., the molar ratio between the sum of all low molecular mass thiols bound to S-thiolated plasma proteins and protein free cysteinyl residues. Patients with ESRD had a significantly higher PTI compared to age-matched healthy subjects and HD was associated with a decrease in PTI to normal, or lower than normal, levels. Although this study is limited in size, our results suggest that PTI is a useful indicator of thiol-specific oxidative stress in patients with ESRD on maintenance HD. This study also emphasizes that PTI determination is a cheap and simple tool suitable for large-scale clinical studies that could be used for routine screening of thiol-specific oxidative stress. [ABSTRACT FROM AUTHOR]

The incidence of end stage renal disease is more than three times higher in African Americans. Treatment regimens contribute to gastrointestinal (GI) complaints. This study's purpose was to examine the incidence of GI symptoms in African-American patients undergoing hemodialysis. Younger participants were more likely to report mild indigestion, while older participants reported severe indigestion or none at all. Females were more likely to report gastrointestinal symptoms. Commonly reported co-morbidities included hypertension, diabetes, and heart disease. Time on hemodialysis ranged from 1 to 279 months. Those who had been on hemodialysis the longest were more likely to report acid reflux, stomach rumbling, and mild diarrhea. This study provides a foundation for early identification of GI symptoms in African-Americans patients undergoing hemodialysis. [ABSTRACT FROM AUTHOR]

Aim: There is no data on osmol gap (OG) in chronic kidney disease (CKD) by stage and limited data on OG in adults on maintenance hemodialysis (HD). We aimed to examine the OG between different stages of CKD and to compare the OG pre- and post-HD in those on maintenance HD. Methods: We conducted a cross-sectional study of 67 patients. The participants were divided into six groups: Group 1-reference group (normal renal function), Group 2-CKD stage 2; Group 3-CKD stage 3; Group 4-CKD stage 4; Group 5-CKD stage 5 and not on dialysis. Group 6 were subjects on maintenance HD. Results: The means of OG ± standard deviation of Groups 1-6 were 15.25 ± 3.0, 20.73 ± 2.68, 22.85 ± 6.99, 24.11 ± 3.64, 25.15 ± 5.06, and 28.88 ± 3.45, respectively ( p < 0.001). In the HD group, the difference between the pre-HD and post-HD OG was statistically significant ( p < 0.001). Conclusion: There is a statistically significant upward trend for OG as CKD stage increases. The OG is elevated in patients on maintenance HD and is normalized by the HD. OG can be a valuable additional tool to suggest CKD stage and serve as a marker of dialysis adequacy. [ABSTRACT FROM AUTHOR]

End stage renal disease (ESRD) is the irreversible deterioration of renal function requiring renal replacement therapy by dialysis or transplant. Human leucocyte antigens (HLA) have been well examined however research still is required into the non-HLA antibodies. Antibody mediated rejection (AMR) can be seen in the absence of HLA antibodies on biopsies of patients who have received identical transplants; anti-endothelial cell antibodies may explain this. Investigation into endothelial cell antigens on donor and recipient endothelium may elucidate and stratify the degree of risk of any given transplant and may guide towards the best matched donor. Protein array analysis was carried out on 8 patient pairs using nitro-cellulose membranes and biotinylated detection antibodies. The fluorescence emitted was captured by X-Ray film and results were recorded with ImageJ software. A fold increase of more than 2 was considered to be positive. 11 proteins identified had a fold increase of increase ≥2 and were present in ≥2 patient pairs which may point to potential clinical utility. Nectin2/CD112 may be measured in order analyse graft survival time in transplant recipients. Prognosticating renal failure has clinical importance and potential markers that have been identified to aid which include MEPE, CRELD2, and TIMP-4. Novel pharmacological therapies for specific biomarkers identified in this study include JAM-A, E -Selectin, CD147, Galectin-3, JAM-C, PAR-1, and TNFR2. Protein analysis showed differences in expression of antigens between patients with and without Chronic Kidney Disease (CKD). This information could be used at the matching stage of renal transplantation and also in the treatment of rejection episodes. The results highlight biomarkers that potentially prognosticate and pharmacological therapies that may ameliorate kidney disease and rejection in ESRD and transplant recipients. [ABSTRACT FROM AUTHOR]

Abstract: Pregnancy-associated plasma protein-A (PAPP-A), a newly discovered member of insulin like growth factors (IGFs) axis, has been reported to be a biomarker in both cardiac and non-cardiac conditions. PAPP-A mainly acts as a protease cleaving IGF inhibitors — IGF binding proteins (IGFBPs), thereby setting free IGFs. In cardiac conditions, PAPP-A plays an important role in progressive atherosclerosis. As a biomarker, PAPP-A is not only sensitive, specific and early for diagnosis of acute coronary syndrome, but also an independent risk factor for all-cause mortality or combined cardiovascular events. In non-cardiac conditions, PAPP-A is a new anti-aging target. PAPP-A knock out (KO) mice have a prolonged lifespan than the wild type. In addition, PAPP-A is also a biomarker associated with malignant cancer and end stage renal disease. [Copyright &y& Elsevier]