Editorial

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8 pages, 188 KiB

Open AccessEditorial

Chronic Kidney Disease: The Silent Epidemy

by Antonio Bellasi, Luca Di Lullo and Biagio Di Iorio

J. Clin. Med. 2019, 8(11), 1795; https://doi.org/10.3390/jcm8111795 - 26 Oct 2019

Cited by 14 | Viewed by 3189

Abstract

Numerous observations suggest that chronic kidney disease (CKD) is an epidemic condition [...] Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

Research

Jump to: Editorial, Review, Other

17 pages, 3140 KiB

Open AccessArticle

Nutritional Therapy Modulates Intestinal Microbiota and Reduces Serum Levels of Total and Free Indoxyl Sulfate and P-Cresyl Sulfate in Chronic Kidney Disease (Medika Study)

by Biagio Raffaele Di Iorio, Maria Teresa Rocchetti, Maria De Angelis, Carmela Cosola, Stefania Marzocco, Lucia Di Micco, Ighli di Bari, Matteo Accetturo, Mirco Vacca, Marco Gobbetti, Mattia Di Iorio, Antonio Bellasi and Loreto Gesualdo

J. Clin. Med. 2019, 8(9), 1424; https://doi.org/10.3390/jcm8091424 - 10 Sep 2019

Cited by 84 | Viewed by 6807

Abstract

In chronic kidney disease (CKD), the gut-microbiota metabolites indoxyl sulfate (IS) and p-cresyl sulfate (PCS) progressively accumulate due to their high albumin-binding capacity, leading to clinical complications. In a prospective crossover controlled trial, 60 patients with CKD grades 3B–4 (GFR = 21.6 ± [...] Read more.

In chronic kidney disease (CKD), the gut-microbiota metabolites indoxyl sulfate (IS) and p-cresyl sulfate (PCS) progressively accumulate due to their high albumin-binding capacity, leading to clinical complications. In a prospective crossover controlled trial, 60 patients with CKD grades 3B–4 (GFR = 21.6 ± 13.2 mL/min) were randomly assigned to two dietary regimens: (i) 3 months of free diet (FD) (FD is the diet usually used by the patient before being enrolled in the Medika study), 6 months of very low protein diet (VLPD), 3 months of FD and 6 months of Mediterranean diet (MD); (ii) 3 months of FD, 6 months of MD, 3 months of FD, and 6 months of VLPD. VLPD reduced inflammatory Proteobacteria and increased Actinobacteria phyla. MD and VLPD increased some butyrate-forming species of Lachnospiraceae, Ruminococcaceae, Prevotellaceae, Bifidobacteriaceae, and decrease the pathobionts Enterobacteriaceae. The increased level of potential anti-inflammatory Blautia and Faecalibacterium, as well as butyrate-forming Coprococcus and Roseburia species in VLPD was positively associated with dietary intakes and it was negatively correlated with IS and PCS. Compared to FD and MD, VLPD showed a lower amount of some Lactobacillus, Akkermansia, Streptococcus, and Escherichia species. MD and VLPD reduced both the total and free serum IS (MD −36%, −40% and VLPD −69%, −73%, respectively) and PCS (MD −38%, −44% and VLPD −58%, −71%, respectively) compared to FD. VLPD reduced serum D-lactate compared to MD and FD. MD and, to a greater extent, VLPD are effective in the beneficial modulation of gut microbiota, reducing IS and PCS serum levels, and restoring intestinal permeability in CKD patients. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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15 pages, 1091 KiB

Open AccessArticle

Prevalence of Early Chronic Kidney Disease and Main Associated Factors in Spanish Population: Populational Study

by Carmen Expósito, Guillem Pera, Lluís Rodríguez, Ingrid Arteaga, Alba Martínez, Alba Alumà, María Doladé, Pere Torán and Llorenç Caballeria

J. Clin. Med. 2019, 8(9), 1384; https://doi.org/10.3390/jcm8091384 - 04 Sep 2019

Cited by 3 | Viewed by 3096

Abstract

The aim of this study was to determine the prevalence of early chronic kidney disease (EKD) (stages 1 and 2) and the factors associated. This was a populational study including individuals from 18–75 years randomly selected from 18 Primary Healthcare centers in the [...] Read more.

The aim of this study was to determine the prevalence of early chronic kidney disease (EKD) (stages 1 and 2) and the factors associated. This was a populational study including individuals from 18–75 years randomly selected from 18 Primary Healthcare centers in the area of Barcelonès Nord and Maresme (Catalunya, Spain). Variables: anamnesis, physical examination, blood pressure, and analysis. EKD was defined with by a glomerular filtration rate (GFR) ≥60 mL/min/1.73 m² and albumin/creatinine ratio (ACR) ≥17 mg/g in men and ≥25 mg/g in women confirmed with two determinations. 2871 individuals: 43% men, mean age 55 years (19–75), 32.2% obese, 50.5% abdominal obesity, 21.1% hypertensive, and 10.6% diabetic. Prevalence of EKD: With one determination 157 individuals (5.5%), 110 men (9%) and 47 women (2.8%); with two determinations 109 individuals (3.8%), 85 men (7%), and 24 women (1.5%). Factors independently associated with the multivariate logistic regression model: Man (OR 3.35), blood pressure ≥ 135/85 mmHg (OR 2.29), BMI ≥ 30 kg/m² (OR 2.48), glycemia ≥ 100 mg/dL (OR 1.73), smoker (OR 1.67) and age (OR 1.04). The prevalence varies if the diagnosis is established based on one or two analytical determinations, overestimated if only one determination is made and depends on the value chosen to define urine albumin excretion. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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11 pages, 1525 KiB

Open AccessArticle

The Effect of Health-Related Behaviors on Disease Progression and Mortality in Early Stages of Chronic Kidney Disease: A Korean Nationwide Population-Based Study

by Yookyung Lee, SuYeon Kwon, Jong Joo Moon, Kyungdo Han, Nam-Jong Paik and Won-Seok Kim

J. Clin. Med. 2019, 8(8), 1100; https://doi.org/10.3390/jcm8081100 - 25 Jul 2019

Cited by 9 | Viewed by 2943

Abstract

A healthy life style is associated with decreased risk of chronic kidney disease (CKD) and mortality in the general population. However, there is no definitive evidence of the benefits of physical activity and other health-related behaviors in the early-stage of CKD. This study [...] Read more.

A healthy life style is associated with decreased risk of chronic kidney disease (CKD) and mortality in the general population. However, there is no definitive evidence of the benefits of physical activity and other health-related behaviors in the early-stage of CKD. This study aimed to explore the association between health-related behaviors and end-stage renal disease (ESRD) and mortality in the early stages of CKD. The National Health Insurance Service (NHIS) database from 1 January 2009 to 31 December 2016 was used to screen 83,470 subjects with early stage CKD. Cox proportional hazard regression analysis was used to evaluate the association between health-related behaviors and ESRD and death. Kaplan–Meier curves for mortality and ESRD were plotted according to the physical activity, smoking status, and alcohol consumption pattern. Risk of death decreased significantly in subjects who engaged in sufficient physical activity (adjusted Hazard Ratio (HR) 0.73; 95% CI: 0.64–0.83; p < 0.001). Risk of ESRD and death increased significantly in the current smoker with adjusted HR of 1.44 (95% CI: 1.06–1.95; p < 0.02) and 1.61 (95% CI: 1.44–1.80; p < 0.001) respectively. Therefore, systematic interventions to encourage physical activity and smoking cessation need to be actively considered in the early stages of CKD. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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9 pages, 641 KiB

Open AccessArticle

Etelcalcetide in Patients on Hemodialysis with Severe Secondary Hyperparathyroidism. Multicenter Study in “Real Life”

by Domenico Russo, Rocco Tripepi, Fabio Malberti, Biagio Di Iorio, Bernadette Scognamiglio, Luca Di Lullo, Immacolata Gaia Paduano, Giovanni Luigi Tripepi and Vincenzo Antonio Panuccio

J. Clin. Med. 2019, 8(7), 1066; https://doi.org/10.3390/jcm8071066 - 20 Jul 2019

Cited by 14 | Viewed by 4795 | Correction

Abstract

Etelcalcetide is a new calcimimetic indicated for the treatment of secondary hyperparathyroidism (SHPT) in dialysis patients. Etelcalcetide efficacy in SHPT has been ascertained only in randomized controlled trials. This multicenter study was carried out in “real world” setting that is different from randomized [...] Read more.

Etelcalcetide is a new calcimimetic indicated for the treatment of secondary hyperparathyroidism (SHPT) in dialysis patients. Etelcalcetide efficacy in SHPT has been ascertained only in randomized controlled trials. This multicenter study was carried out in “real world” setting that is different from randomized controlled trials (RCTs) to (1) evaluate the effectiveness of etelcalcetide in SHPT, (2) to assess calcium, phosphorus, alkaline phosphatase changes, (3) to register gastrointestinal side effects. Data were collected from twenty-three dialysis units with n = 1190 patients on the charge. From this cohort, n = 168 (14%) patients were on treatment with etelcalcetide, and they were evaluated for statistics. A median weekly dose of etelcalcetide was 15 mg (7.5–45 mg). Patients were either naïve (33%) or switched from cinacalcet to obtain better control of SHPT with reduced side effects or pills burden. Serum parathyroid hormone (PTH) declined over time from a median value of 636 pg/mL to 357 pg/mL. The median time for responders (intact PTH (iPTH) range: two to nine times the upper normal limit) was 53 days; the percentage of responders increased (from baseline 27% to 63%) being similar in switched-patients and naïve-patients. Few patients had symptomatic hypocalcemia requiring etelcalcetide withdrawal (four cases (3%) at 30-day control, two cases (2%) at 60-day, one case (1%) at 90-day control). Side effects with etelcalcetide were lower (3–4%) than that registered during cinacalcet treatment (53%). Etelcalcetide is a new therapeutic option for SHPT with low side effects and pills burden. Etelcalcetide may improve adherence to therapy, avoiding unremitting SHP. It remains to be assessed whether etelcalcetide may reduce parathyroidectomy, vascular calcification, or mortality. Being etelcalcetide very potent in suppressing PTH levels, even in severe SHPT, future studies should evaluate the potential risk of more adynamic bone disease during long-term therapy. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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17 pages, 1625 KiB

Open AccessArticle

Circulating Lactonase Activity but Not Protein Level of PON-1 Predicts Adverse Outcomes in Subjects with Chronic Kidney Disease

by Chrysan J. Mohammed, Yanmei Xie, Pamela S. Brewster, Subhanwita Ghosh, Prabhatchandra Dube, Tiana Sarsour, Andrew L. Kleinhenz, Erin L. Crawford, Deepak Malhotra, Richard W. James, Philip A. Kalra, Steven T. Haller and David J. Kennedy

J. Clin. Med. 2019, 8(7), 1034; https://doi.org/10.3390/jcm8071034 - 15 Jul 2019

Cited by 16 | Viewed by 3405

Abstract

The burden of cardiovascular disease and death in chronic kidney disease (CKD) outpaces that of the other diseases and is not adequately described by traditional risk factors alone. Diminished activity of paraoxonase (PON)-1 is associated with increased oxidant stress, a common feature underlying [...] Read more.

The burden of cardiovascular disease and death in chronic kidney disease (CKD) outpaces that of the other diseases and is not adequately described by traditional risk factors alone. Diminished activity of paraoxonase (PON)-1 is associated with increased oxidant stress, a common feature underlying the pathogenesis of CKD. We aimed to assess the prognostic value of circulating PON-1 protein and PON lactonase activity on adverse clinical outcomes across various stages and etiologies of CKD. Circulating PON-1 protein levels and PON lactonase activity were measured simultaneously in patients with CKD as well as a cohort of apparently healthy non-CKD subjects. Both circulating PON-1 protein levels and PON lactonase activity were significantly lower in CKD patients compared to the non-CKD subjects. Similarly, across all stages of CKD, circulating PON-1 protein and PON lactonase activity were significantly lower in patients with CKD compared to the non-CKD controls. Circulating PON lactonase activity, but not protein levels, predicted future adverse clinical outcomes, even after adjustment for traditional risk factors. The combination of lower circulating protein levels and higher activity within the CKD subjects were associated with the best survival outcomes. These findings demonstrate that diminished circulating PON lactonase activity, but not protein levels, predicts higher risk of future adverse clinical outcomes in patients with CKD. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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15 pages, 994 KiB

Open AccessArticle

Fractional Excretion of Phosphate (FeP) Is Associated with End-Stage Renal Disease Patients with CKD 3b and 5

by Antonio Bellasi, Lucia Di Micco, Domenico Russo, Emanuele De Simone, Mattia Di Iorio, Raffaella Vigilante, Luca Di Lullo and Biagio Raffaele Di Iorio

J. Clin. Med. 2019, 8(7), 1026; https://doi.org/10.3390/jcm8071026 - 12 Jul 2019

Cited by 8 | Viewed by 4468

Abstract

Background: The perturbation of phosphate homeostasis portends unfavorable outcomes in chronic kidney disease (CKD). However, the absence of randomized clinical trials (RCT) fuels the discussion of whether phosphate or some other phosphorous-related factor(s) such as fibroblast growth factor 23 (FGF-23) mediates the [...] Read more.

Background: The perturbation of phosphate homeostasis portends unfavorable outcomes in chronic kidney disease (CKD). However, the absence of randomized clinical trials (RCT) fuels the discussion of whether phosphate or some other phosphorous-related factor(s) such as fibroblast growth factor 23 (FGF-23) mediates the cardiovascular and systemic toxicity. We herein test whether the fractional excretion of phosphate (FeP) as a marker of renal stress to excrete phosphorous predicts unfavorable outcomes in CKD patients. Methods: Retrospective, cross-sectional observational study. For current analysis, an historical cohort of 407 records of CKD stage 3b-5 patients attending between January 2010 and October 2015 at the Nephrology Unit of Solofra (AV), Italy were utilized. Demographic, clinical, laboratory, and outcome data were identified through the subjects’ medical records. We tested whether quartiles of FeP are associated with the risk of CKD progression or all causes of death. Parametric as well as non-parametric tests, linear and logistic regression, as well as survival analysis were utilized. Results: Overall, we investigated middle-age (mean 66.0, standard deviation 12.3 years) men and women (male 43%) with CKD stage 3b to 5 (creatinine clearance 32.0 (13.3) mL/min). Older age, lower diastolic blood pressure, poor renal function, as well as higher serum phosphate were associated with FeP. Patients with higher FeP were at an increased risk of starting dialysis or dying (hazard ratio 2.40; 95% confidence interval (1.44, 3.99)). Notably, when the two endpoints were analyzed separately, FeP was associated with renal but not all-cause survival. Conclusion: FeP is associated with ESRD, but not all-cause mortality risk in a large cohort of moderate to advanced CKD patients. Future efforts are required to validate FeP as a marker of nephron stress and risk factor for CKD progression in this high-risk population. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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18 pages, 1759 KiB

Open AccessArticle

Serologic and Histologic Predictors of Long-Term Renal Outcome in Biopsy-Confirmed IgA Nephropathy (Haas Classification): An Observational Study

by Shang-Feng Tsai, Ming-Ju Wu, Mei-Chin Wen and Cheng-Hsu Chen

J. Clin. Med. 2019, 8(6), 848; https://doi.org/10.3390/jcm8060848 - 14 Jun 2019

Cited by 10 | Viewed by 2817

Abstract

Background and objective: The Haas classification of IgA nephropathy should be validated for Asian populations. More detailed and newer predictions regarding renal outcome of IgA nephropathy remains mandatory. Materials: We conducted a retrospective cohort study between January 2003 and December 2013. [...] Read more.

Background and objective: The Haas classification of IgA nephropathy should be validated for Asian populations. More detailed and newer predictions regarding renal outcome of IgA nephropathy remains mandatory. Materials: We conducted a retrospective cohort study between January 2003 and December 2013. Clinical, Pathological, and laboratory data were all collected via available medical records. A Mann–Whitney U test was used for continuous variables and the Chi-square test was implemented for categorical variables. A Kaplan–Meier curve was put in place in order to determine patient survival and renal survival. The Youden index and Cox proportional hazard regression were used to investigate the possible factors for renal survival and predictive power. Results: All 272 renal biopsy-confirmed IgAN patients were enrolled for further studies. The univariate analysis showed that risk factors for poor renal outcome included stage 4–5 of Haas classification (HR = 3.67, p < 0.001), a poor baseline renal function (HR = 1.02 and p < 0.001 for higher BUN; HR = 1.14 and p < 0.001 for higher serum creatinine; HR = 0.95, p < 0.001 for higher eGFR), IgG ≤ 907 (HR = 2.29, p = 0.003), C3 ≤ 79.7 (HR = 2.76, p = 0.002), a higher C4 (HR = 1.02, p = 0.026), neutrophil-to-lymphocyte ratio > 2.75 (HR = 2.92, p < 0.001), and a platelet-to-lymphocyte ratio ≥ 16.06 (HR = 2.02, p = 0.012). A routine-checked markers, such as neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, in order to predict the renal outcome, is recommended. Conclusions: This is the first study to demonstrate that Haas classification is also useful for establishing predictive values in Asian groups. A lower serum IgG (≤907 mg/dL) and serum C3 (≤79.7 mg/dL) were both risk factors for poor renal outcome. Additionally, this is the first study to reveal that serum C4 levels, an NLR > 2.75 and a PLR > 16.06, S could suggest poor renal outcome. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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11 pages, 702 KiB

Open AccessArticle

The Effect of Aspirin on Preventing Vascular Access Dysfunction in Incident Hemodialysis Patients: A Prospective Cohort Study in Korean Clinical Research Centers for End-Stage Renal Disease (CRC for ESRD)

by Chan Ho Kim, Hyung Jung Oh, Yon Su Kim, Yong-Lim Kim, Jae Hyun Chang and Dong-Ryeol Ryu

J. Clin. Med. 2019, 8(5), 677; https://doi.org/10.3390/jcm8050677 - 14 May 2019

Cited by 5 | Viewed by 2631

Abstract

Background: Aspirin is often prescribed empirically to improve the patency of hemodialysis (HD) vascular access. Therefore, this study aimed to investigate the impact of aspirin on the survival of vascular access in incident HD patients with arteriovenous fistula (AVF) or arteriovenous graft (AVG). [...] Read more.

Background: Aspirin is often prescribed empirically to improve the patency of hemodialysis (HD) vascular access. Therefore, this study aimed to investigate the impact of aspirin on the survival of vascular access in incident HD patients with arteriovenous fistula (AVF) or arteriovenous graft (AVG). Methods: A prospective cohort of 881 incident HD patients was enrolled between 2009 and 2014. The primary outcome was defined as the first AVF/AVG intervention or salvage procedure, including percutaneous transluminal angioplasty or surgery for vascular access failure. Cox analyses were performed to determine the association between aspirin usage and the occurrence of the primary outcome. Results: The mean age of the patient group was 57.9 ± 13.4, and 63.8% of the patients were male. Aspirin was prescribed in 241 (27.4%) patients, and the median follow-up duration was 30 months. During follow-up, 180 (20.4%) patients experienced the primary outcome event. Univariate analysis showed that age, gender, presence of diabetes mellitus (DM), preexisting peripheral arterial disease, and the type of vascular access used (AVG versus AVF) were significantly associated with the development of the primary outcome. However, aspirin usage from the baseline was not significantly associated with primary outcome events (hazard ratio (HR): 1.16; 95% confidence interval (CI): 0.84–1.60; p = 0.378). Multivariate analysis showed that gender, the presence of DM, and the type of vascular access were still significantly associated with the occurrence of the primary outcome. Moreover, we did not observe the protective effect of taking aspirin on primary vascular access failure, even in subgroup analyses stratified according to gender, the presence of DM, and the type of vascular access. Conclusion: Physicians should carefully consider when they prescribe aspirin for the prevention of primary vascular access failure in Korean incident HD patients. In addition, larger prospective interventional studies are needed to elucidate the effect of aspirin on vascular access failure. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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17 pages, 1475 KiB

Open AccessArticle

A Novel Multi-Biomarker Assay for Non-Invasive Quantitative Monitoring of Kidney Injury

by Drew Watson, Joshua Y. C. Yang, Reuben D. Sarwal, Tara K. Sigdel, Juliane M. Liberto, Izabella Damm, Victoria Louie, Shristi Sigdel, Devon Livingstone, Katherine Soh, Arjun Chakraborty, Michael Liang, Pei-Chen Lin and Minnie M. Sarwal

J. Clin. Med. 2019, 8(4), 499; https://doi.org/10.3390/jcm8040499 - 12 Apr 2019

Cited by 29 | Viewed by 5119

Abstract

The current standard of care measures for kidney function, proteinuria, and serum creatinine (SCr) are poor predictors of early-stage kidney disease. Measures that can detect chronic kidney disease in its earlier stages are needed to enable therapeutic intervention and reduce adverse outcomes of [...] Read more.

The current standard of care measures for kidney function, proteinuria, and serum creatinine (SCr) are poor predictors of early-stage kidney disease. Measures that can detect chronic kidney disease in its earlier stages are needed to enable therapeutic intervention and reduce adverse outcomes of chronic kidney disease. We have developed the Kidney Injury Test (KIT) and a novel KIT Score based on the composite measurement and validation of multiple biomarkers across a unique set of 397 urine samples. The test is performed on urine samples that require no processing at the site of collection and without target sequencing or amplification. We sought to verify that the pre-defined KIT test, KIT Score, and clinical thresholds correlate with established chronic kidney disease (CKD) and may provide predictive information on early kidney injury status above and beyond proteinuria and renal function measurements alone. Statistical analyses across six DNA, protein, and metabolite markers were performed on a subset of residual spot urine samples with CKD that met assay performance quality controls from patients attending the clinical labs at the University of California, San Francisco (UCSF) as part of an ongoing IRB-approved prospective study. Inclusion criteria included selection of patients with confirmed CKD and normal healthy controls; exclusion criteria included incomplete or missing information for sample classification, logistical delays in transport/processing of urine samples or low sample volume, and acute kidney injury. Multivariate logistic regression of kidney injury status and likelihood ratio statistics were used to assess the contribution of the KIT Score for prediction of kidney injury status and stage of CKD as well as assess the potential contribution of the KIT Score for detection of early-stage CKD above and beyond traditional measures of renal function. Urine samples were processed by a proprietary immunoprobe for measuring cell-free DNA (cfDNA), methylated cfDNA, clusterin, CXCL10, total protein, and creatinine. The KIT Score and stratified KIT Score Risk Group (high versus low) had a sensitivity and specificity for detection of kidney injury status (healthy or CKD) of 97.3% (95% CI: 94.6–99.3%) and 94.1% (95% CI: 82.3–100%). In addition, in patients with normal renal function (estimated glomerular filtration rate (eGFR) ≥ 90), the KIT Score clearly identifies those with predisposing risk factors for CKD, which could not be detected by eGFR or proteinuria (p < 0.001). The KIT Score uncovers a burden of kidney injury that may yet be incompletely recognized, opening the door for earlier detection, intervention and preservation of renal function. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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12 pages, 896 KiB

Open AccessArticle

Temporal Trends of Severe Hypoglycemia and Subsequent Mortality in Patients with Advanced Diabetic Kidney Diseases Transitioning to Dialysis

by Ching-Chung Hsiao, Hui-Tzu Tu, Chi-Hung Lin, Kuan-Hsing Chen, Yung-Hsin Yeh and Lai-Chu See

J. Clin. Med. 2019, 8(4), 420; https://doi.org/10.3390/jcm8040420 - 27 Mar 2019

Cited by 13 | Viewed by 3204

Abstract

Background: Patients with diabetic kidney disease (DKD) are at higher risk of hypoglycemia than diabetic patients without DKD. We aimed to investigate the temporal trends of severe hypoglycemia in advanced DKD patients transitioning to dialysis and examine risk factors associated with severe hypoglycemia. [...] Read more.

Background: Patients with diabetic kidney disease (DKD) are at higher risk of hypoglycemia than diabetic patients without DKD. We aimed to investigate the temporal trends of severe hypoglycemia in advanced DKD patients transitioning to dialysis and examine risk factors associated with severe hypoglycemia. We also investigated the association of severe hypoglycemia episodes with one-year mortality after initiation of dialysis in patients with advanced DKD. Methods: Using the Taiwan National Health Insurance Research Database, 46,779 advanced DKD patients transitioning to dialysis (Peritoneal dialysis 4216, hemodialysis 42,563) between 1997 and 2011 were enrolled. We calculated the rates of severe hypoglycemia from 5 years before dialysis until 10 years after dialysis. Cox proportional hazard model was used to examine the risk factors of post end stage renal disease (ESRD) one-year hypoglycemia and post ESRD one-year mortality in advanced DKD patients transitioning to dialysis. Results: We found that 11.5% of advanced DKD patients had at least one episode of severe hypoglycemia the year leading up to dialysis initiation. Multivariate analysis revealed hemodialysis compared with peritoneal dialysis, stroke, use of sulfonylurea, glinide, and insulin were associated with higher risk of severe hypoglycemia one year after transitioning to dialysis. Increased frequency of severe hypoglycemia-related hospitalizations was associated with incrementally higher mortality risk one year after transitioning to dialysis (Pre-ESRD hypoglycemia: Hazard ratios: 1.28 (1.18–1.38, p < 0.001), 1.64 (1.49–1.81, p < 0.001) for one, two hypoglycemia-related hospitalizations, respectively; post-ESRD hypoglycemia: HRs of 1.56 (1.40–1.73, p < 0.001), 1.72 (1.39–2.12, p < 0.001) for one, two hypoglycemia-related hospitalizations, respectively (reference group: no hypoglycemia related hospitalization)). Conclusions: Among advanced DKD patients, we observed a progressive elevated risk of hypoglycemia during the critical dialysis transition period. Increased frequency of severe hypoglycemia-related hospitalizations was associated with higher mortality risk one year after transitioning to dialysis. Further study of glycemic management strategies which prevent hypoglycemia during the critical transition period are warranted. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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12 pages, 1034 KiB

Open AccessArticle

by Wubshet H. Tesfaye, Gregory M. Peterson, Ronald L. Castelino, Charlotte McKercher, Matthew Jose, Syed Tabish R. Zaidi and Barbara C. Wimmer

J. Clin. Med. 2019, 8(3), 395; https://doi.org/10.3390/jcm8030395 - 21 Mar 2019

Cited by 8 | Viewed by 4748

Abstract

This study aimed to examine the association between medication-related factors and risk of hospital readmission in older patients with chronic kidney disease (CKD). A retrospective analysis was conducted targeting older CKD (n = 204) patients admitted to an Australian hospital. Medication appropriateness [...] Read more.

This study aimed to examine the association between medication-related factors and risk of hospital readmission in older patients with chronic kidney disease (CKD). A retrospective analysis was conducted targeting older CKD (n = 204) patients admitted to an Australian hospital. Medication appropriateness (Medication Appropriateness Index; MAI), medication regimen complexity (number of medications and Medication Regimen Complexity Index; MRCI) and use of selected medication classes were exposure variables. Outcomes were occurrence of readmission within 30 and 90 days, and time to readmission within 90 days. Logistic and Cox hazards regression were used to identify factors associated with readmission. Overall, 50 patients (24%) were readmitted within 30 days, while 81 (40%) were readmitted within 90 days. Mean time to readmission within 90 days was 66 (SD 34) days. Medication appropriateness and regimen complexity were not independently associated with 30- or 90-day hospital readmissions in older adults with CKD, whereas use of renin-angiotensin blockers was associated with reduced occurrence of 30-day (adjusted OR 0.39; 95% CI 0.19–0.79) and 90-day readmissions (adjusted OR 0.45; 95% CI 0.24–0.84) and longer time to readmission within 90 days (adjusted HR 0.52; 95% CI 0.33–0.83). This finding highlights the importance of considering the potential benefits of individual medications during medication review in older CKD patients. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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14 pages, 642 KiB

Open AccessArticle

Anemia and Iron Deficiency in Children with Chronic Kidney Disease (CKD): Data from the Know-Ped CKD Study

by Keum Hwa Lee, Eujin Park, Hyun Jin Choi, Hee Gyung Kang, Il-Soo Ha, Hae Il Cheong, Young Seo Park, Heeyeon Cho, Kyoung Hee Han, Seong Heon Kim, Min Hyun Cho, Joo Hoon Lee and Jae Il Shin

J. Clin. Med. 2019, 8(2), 152; https://doi.org/10.3390/jcm8020152 - 29 Jan 2019

Cited by 14 | Viewed by 6088

Abstract

Children with chronic kidney disease (CKD) are at high risk of anemia, an important risk factor for cardiovascular disease and poor quality of life. The present study used baseline data from the Korean cohort study for Outcome in patients With Pediatric Chronic Kidney [...] Read more.

Children with chronic kidney disease (CKD) are at high risk of anemia, an important risk factor for cardiovascular disease and poor quality of life. The present study used baseline data from the Korean cohort study for Outcome in patients With Pediatric Chronic Kidney Disease (KNOW-PedCKD). A Total of 437 patients was included in the analyses excluding missing data. The characteristics of patients with and without anemia and those of patients with and without iron deficiency were compared. Logistic regression analysis and Pearson correlation were conducted to evaluate associated risk factors and correlations in children with CKD. Anemia in children with CKD was associated with older age, low body weight and body mass index (BMI) z-score, birth age, preceding glomerulonephritis, decreased estimated glomerular filtration rate (eGFR), low levels of serum albumin and calcium, high levels of serum intact parathyroid hormone (iPTH), and serum phosphorus. Anemia was correlated positively with changes in the BMI z-score, body weight, and serum albumin and cholesterol levels, but correlated negatively with serum calcium, iPTH, ferritin levels, and transferrin saturation. Iron deficiency in children with CKD was associated with young age, low hemoglobin and serum ferritin levels, high BMI z-scores, and low levels of serum iPTH. This is the first nationwide cohort study of anemia in Korean children with CKD and the first prospective pediatric CKD cohort study in Asia. The study results demonstrated that anemia and iron deficiency are affected by various factors, including age, BMI, and levels of serum iPTH. To improve the retrospective outcome of affected children, it is important to understand the effect of each of these factors and to attempt an early intervention to prevent anemia and iron deficiency by regular measurement of these parameters in children at risk. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

13 pages, 1676 KiB

Open AccessArticle

Effect of New-Onset Diabetes Mellitus on Renal Outcomes and Mortality in Patients with Chronic Kidney Disease

by Po-Ke Hsu, Chew-Teng Kor and Yao-Peng Hsieh

J. Clin. Med. 2018, 7(12), 550; https://doi.org/10.3390/jcm7120550 - 14 Dec 2018

Cited by 9 | Viewed by 3876

Abstract

Background: The incidence rates of diabetes mellitus (DM) and chronic kidney disease (CKD) are increasing worldwide and their coexistence can have a large negative impact on clinical outcomes. However, it is unclear how incident DM affects CKD patients. Methods: Incident CKD patients between [...] Read more.

Background: The incidence rates of diabetes mellitus (DM) and chronic kidney disease (CKD) are increasing worldwide and their coexistence can have a large negative impact on clinical outcomes. However, it is unclear how incident DM affects CKD patients. Methods: Incident CKD patients between 2000 and 2013 were identified from the National Health Insurance Research Database of Taiwan; they were classified as non-DM (n = 10,356), pre-existing DM (n = 6982), and incident DM (n = 1103). Non-DM cases were patients who did not develop DM before the end of the observation period. The outcomes of interest were end-stage renal disease (ESRD), mortality, and composite outcome (ESRD or death). The association between the DM groups and clinical outcomes was estimated using the inverse probability of group-weighted (IPW) multivariate-adjusted time-dependent Cox regression models. Results: During the study period of 14 years, 1735 (16.6%) patients in the non-DM group reached ESRD compared with 2168 (31.05%) in the pre-existing DM group and 111 (11.03%) in the incident DM group (p < 0.001). Moreover, 2219 (21.43%) patients in the non-DM group died compared with 1895 (27.14%) in the pre-existing DM group and 303 (27.47%) in the incident DM group (p < 0.001). Compared with the non-DM group, the pre-existing DM group was associated with a higher risk of ESRD [hazard ratio (HR) 2.54; 95% confidence interval (CI 2.43–2.65), death (HR 2.23; 95% CI 2.14–2.33), and a composite outcome (HR 2.29; 95% CI 2.21–2.36). Similarly, incident DM was also associated with a higher risk of ESRD (HR 1.12; 95% CI 1.06–1.19), death (HR 2.48; 95% CI 2.37–2.60), and a composite outcome (HR 1.77; 95% CI 1.70–1.84) compared with the non-DM group. Factors contributing to incident DM included old age, low monthly income, and having hypertension, hyperlipidemia, and ischemic heart disease, while pentoxifylline reduced the risk of incident DM. Conclusion: Similarly to pre-existing DM, CKD patients with incident DM carried a higher risk of ESRD, mortality, and a composite outcome compared with those with non-DM. For those at risk of incident DM, strict monitoring and intervention strategies must be adopted to help improve their clinical outcomes. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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9 pages, 1535 KiB

Open AccessArticle

Predictive Value of Cortical Thickness Measured by Ultrasonography for Renal Impairment: A Longitudinal Study in Chronic Kidney Disease

by Shotaro Hoi, Tomoaki Takata, Takaaki Sugihara, Ayami Ida, Masaya Ogawa, Yukari Mae, Satoko Fukuda, Chishio Munemura and Hajime Isomoto

J. Clin. Med. 2018, 7(12), 527; https://doi.org/10.3390/jcm7120527 - 07 Dec 2018

Cited by 16 | Viewed by 10674

Abstract

Background: Kidney size is associated with renal function, however it is not elucidated whether kidney size is a risk for the progression of chronic kidney disease. The aim of this study was to investigate the predictive value of morphological evaluation of kidney size [...] Read more.

Background: Kidney size is associated with renal function, however it is not elucidated whether kidney size is a risk for the progression of chronic kidney disease. The aim of this study was to investigate the predictive value of morphological evaluation of kidney size by ultrasonography for the progression of renal dysfunction. Methods: Morphological parameters including kidney length, volume, cortical thickness, and medullary thickness were measured by ultrasonography in 87 patients with chronic kidney disease, and adjusted by body size. Renal functions at baseline and after 2 years were measured and the associations of morphological parameters to decline in renal function over 2 years were analyzed. Results: Height-adjusted cortical thickness was correlated to decline in renal function (r = 0.426, p < 0.001). Height-adjusted cortical thickness could predict renal dysfunction with the area under the curve of 0.786, and height-adjusted cortical thickness of 4.0 mm/cm was a cut off value with a sensitivity of 72.5% and a specificity of 80.0% for the risk of a more than 30% decline in renal function or initiation of dialysis. Conclusions: We provide new insights into the utility of measuring cortical thickness by ultrasonography for predict future renal impairment. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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13 pages, 1561 KiB

Open AccessArticle

Competing-Risk Analysis of Death and End Stage Kidney Disease by Hyperkalaemia Status in Non-Dialysis Chronic Kidney Disease Patients Receiving Stable Nephrology Care

by Michele Provenzano, Roberto Minutolo, Paolo Chiodini, Vincenzo Bellizzi, Felice Nappi, Domenico Russo, Silvio Borrelli, Carlo Garofalo, Carmela Iodice, Toni De Stefano, Giuseppe Conte, Hiddo J. L. Heerspink and Luca De Nicola

J. Clin. Med. 2018, 7(12), 499; https://doi.org/10.3390/jcm7120499 - 01 Dec 2018

Cited by 29 | Viewed by 4115

Abstract

Hyperkalaemia burden in non-dialysis chronic kidney disease (CKD) under nephrology care is undefined. We prospectively followed 2443 patients with two visits (referral and control with 12-month interval) in 46 nephrology clinics. Patients were stratified in four categories of hyperkalaemia (serum potassium, sK ≥ [...] Read more.

Hyperkalaemia burden in non-dialysis chronic kidney disease (CKD) under nephrology care is undefined. We prospectively followed 2443 patients with two visits (referral and control with 12-month interval) in 46 nephrology clinics. Patients were stratified in four categories of hyperkalaemia (serum potassium, sK ≥ 5.0 mEq/L) by sK at visit 1 and 2: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). We assessed competing risks of end stage kidney disease (ESKD) and death after visit 2. Age was 65 ± 15 years, eGFR 35 ± 17 mL/min/1.73 m², proteinuria 0.40 (0.14–1.21) g/24 h. In the two visits sK was 4.8 ± 0.6 and levels ≥6 mEq/L were observed in 4%. Hyperkalaemia was absent in 46%, resolving 17%, new onset 15% and persistent 22%. Renin-angiotensin-system inhibitors (RASI) were prescribed in 79% patients. During 3.6-year follow-up, 567 patients reached ESKD and 349 died. Multivariable competing risk analysis (sub-hazard ratio-sHR, 95% Confidence Interval-CI) evidenced that new onset (sHR 1.34, 95% CI 1.05–1.72) and persistent (sHR 1.27, 95% CI 1.02–1.58) hyperkalaemia predicted higher ESKD risk versus absent, independently from main determinants of outcome including eGFR change. Conversely, no effect on mortality was observed. Results were confirmed by testing sK as continuous variable. Therefore, in CKD under nephrology care, mild-to-moderate hyperkalaemia status is common (37%) and predicts per se higher ESKD risk but not mortality. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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8 pages, 828 KiB

Open AccessArticle

The Number of Comorbidities Predicts Renal Outcomes in Patients with Stage 3–5 Chronic Kidney Disease

by Wen-Chin Lee, Yueh-Ting Lee, Lung-Chih Li, Hwee-Yeong Ng, Wei-Hung Kuo, Pei-Ting Lin, Ying-Chun Liao, Terry Ting-Yu Chiou and Chien-Te Lee

J. Clin. Med. 2018, 7(12), 493; https://doi.org/10.3390/jcm7120493 - 28 Nov 2018

Cited by 72 | Viewed by 6344

Abstract

Background: Chronic kidney disease (CKD) is a global health threat affecting approximately 10% of the adult population worldwide. Multimorbidity is common in CKD, but its impacts on disease outcomes are seldom investigated. Methods: This prospective cohort analysis followed patients, who were part of [...] Read more.

Background: Chronic kidney disease (CKD) is a global health threat affecting approximately 10% of the adult population worldwide. Multimorbidity is common in CKD, but its impacts on disease outcomes are seldom investigated. Methods: This prospective cohort analysis followed patients, who were part of a multidisciplinary CKD care program, for 10 years. We aimed to determine the impact of multimorbidity on renal outcomes. Results: Overall, 1463 patients with stage 3–5 CKD were enrolled and stratified by the number of comorbidities. Mean follow-up time was 6.39 ± 1.19 years. We found that stage 3–5 CKD patients with at least three comorbidities at enrollment initiated dialysis earlier (hazard ratio (HR): 2.971) than patients without comorbidities. Risk factors for multimorbidity included old age, smoking, and proteinuria. Conclusions: By analyzing the number of comorbidities, a simple and readily applicable method, we demonstrated an association between multimorbidity and poor renal outcomes in stage 3–5 CKD patients. In addition to current guideline-based approaches, our results suggest an urgent need for tailored CKD care strategies for high-risk groups. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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17 pages, 1329 KiB

Open AccessArticle

Upper Normal Serum Creatinine Concentrations as a Predictor for Chronic Kidney Disease: Analysis of 14 Years’ Korean Genome and Epidemiology Study (KoGES)

by Jong Hyun Jhee, Seun Deuk Hwang, Joon Ho Song and Seoung Woo Lee

J. Clin. Med. 2018, 7(11), 463; https://doi.org/10.3390/jcm7110463 - 21 Nov 2018

Cited by 9 | Viewed by 6663

Abstract

Both serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) have been used to assess kidney function in public health check-ups. However, when the sCr is within the normal levels but the eGFR is <60 mL/min/1.73 m², a dilemma arises, as [...] Read more.

Both serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) have been used to assess kidney function in public health check-ups. However, when the sCr is within the normal levels but the eGFR is <60 mL/min/1.73 m², a dilemma arises, as the patients might progress to chronic kidney disease (CKD) after several years. We aimed to evaluate the association between normal sCr and the risk of incident CKD in the general population. For this, 9445 subjects from the Korean Genome and Epidemiology Study, with normal sCr and eGFR of >60 mL/min/1.73 m² were analyzed. The subjects were classified into quartiles based on sCr levels. The primary outcome was the development of eGFR <60 mL/min/1.73 m² on two consecutive measures. During a mean follow-up of 8.4 ± 4.3 years, 779 (8.2%) subjects developed eGFR <60 mL/min/1.73 m². The incidence of the development of eGFR <60 mL/min/1.73 m² was higher in the higher quartiles than in the lowest quartile. In multivariable Cox analysis, the highest quartile was associated with an increased risk for the development of eGFR <60 mL/min/1.73 m² (hazard ratio (HR), 4.71; 95% confidence interval (CI), 3.29–6.74 in females; HR, 12.77; 95% CI, 7.69–21.23 in males). In the receiver operating characteristic curve analysis, adding sCr to the traditional risk factors for CKD improved the accuracy of predicting the development of eGFR <60 mL/min/1.73 m² (area under the curve, 0.83 vs. 0.80 in females and 0.85 vs. 0.78 in males), and the cutoff value of sCr was 0.75 mg/dL and 0.78 mg/dL in females and males. Cautious interpretation is necessary when sCr is within the normal range, considering that the upper normal range of sCr has a higher risk of CKD development. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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19 pages, 1721 KiB

Open AccessArticle

Long-Term Effects of Spironolactone on Kidney Function and Hyperkalemia-Associated Hospitalization in Patients with Chronic Kidney Disease

by Chen-Ta Yang, Chew-Teng Kor and Yao-Peng Hsieh

J. Clin. Med. 2018, 7(11), 459; https://doi.org/10.3390/jcm7110459 - 21 Nov 2018

Cited by 35 | Viewed by 6019

Abstract

Background: Spironolactone, a non-selective mineralocorticoid receptor antagonist, can protect against cardiac fibrosis and left ventricular dysfunction, and improve endothelial dysfunction and proteinuria. However, the safety and effects of spironolactone on patient-centered cardiovascular and renal endpoints remain unclear. Methods: We identified predialysis stage 3–4 [...] Read more.

Background: Spironolactone, a non-selective mineralocorticoid receptor antagonist, can protect against cardiac fibrosis and left ventricular dysfunction, and improve endothelial dysfunction and proteinuria. However, the safety and effects of spironolactone on patient-centered cardiovascular and renal endpoints remain unclear. Methods: We identified predialysis stage 3–4 chronic kidney disease (CKD) patients between 2000 and 2013 from the Longitudinal Health Insurance Database 2005 (LHID 2005). The outcomes of interest were end-stage renal disease (ESRD), major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), hyperkalemia-associated hospitalization (HKAH), all-cause mortality and cardiovascular mortality. The Fine and Gray sub-distribution hazards approach was adopted to adjust for the competing risk of death. Results: After the propensity score matching, 693 patients with stage 3–4 CKD were spironolactone users and 1386 were nonusers. During the follow-up period, spironolactone users had a lower incidence rate for ESRD than spironolactone non-users (39.2 vs. 53.69 per 1000 person-years) and a higher incidence rate for HKAH (54.79 vs. 18.57 per 1000 person-years). The adjusted hazard ratios for ESRD of spironolactone users versus non-users were 0.66 (95% CI, 0.51–0.84; p value < 0.001) and 3.17 (95% CI, 2.41–4.17; p value < 0.001) for HKAH. A dose-response relationship was found between spironolactone use and risk of ESRD and HKAH. There were no statistical differences in MACE, HHF, all-cause mortality and cardiovascular mortality between spironolactone users and non-users. Conclusion: Spironolactone represented a promising treatment option to retard CKD progression to ESRD amongst stage 3–4 CKD patients, but strategic treatments to prevent hyperkalemia should be enforced. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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8 pages, 499 KiB

Open AccessArticle

Angiopoietin-2: A Potential Mediator of the Glycocalyx Injury in Adult Nephrotic Patients

by Maria Moura Santana Chaves, Matheus de Souza Mendes, Maximilian Pinho Schwermann, Raquel Queiroz, Regina Freitas Coelho, Francisco Thiago Santos Salmito, Gdayllon Cavalcante Meneses, Alice Maria Costa Martins, Ana Cristina de Oliveira Monteiro Moreira and Alexandre Braga Libório

J. Clin. Med. 2018, 7(11), 401; https://doi.org/10.3390/jcm7110401 - 31 Oct 2018

Cited by 12 | Viewed by 2728

Abstract

Introduction: Glomerulopathy is a group of diseases that affect mainly young adults between the ages of 20 and 40 years. Recently, it has been demonstrated that syndecan-1, a biomarker of endothelial glycocalyx damage, is increased in nephrotic patients with near-normal renal function and [...] Read more.

Introduction: Glomerulopathy is a group of diseases that affect mainly young adults between the ages of 20 and 40 years. Recently, it has been demonstrated that syndecan-1, a biomarker of endothelial glycocalyx damage, is increased in nephrotic patients with near-normal renal function and it is important to endothelial dysfunction in these patients. Angiopoietin-2 (AGPT2) is an endothelial growth factor that promotes cell derangement. Here we evaluated AGPT2 levels in patients with nephrotic syndrome, near-normal renal function and the possible interaction of AGPT2 with endothelial glycocalyx derangement. Methods: This was a cross-sectional study performed from January through November 2017. Adult patients (age > 18 years) with nephrotic syndrome and without immunosuppression were included. Blood samples were drawn after a 12 h fast for later measurement of syndecan-1 and AGPT2. Mediation analyses were performed to assess the hypothesized associations of nephrotic syndrome features and AGPT2 with syndecan-1. Results: We included 65 patients, 37 (56.9%) of them female, with primary glomerular disease. Syndecan-1 in nephrotic patients was higher than in control individuals (102.8 ± 36.2 vs. 28.2 ± 9.8 ng/mL, p < 0.001). Correlation of syndecan-1 with the main features of nephrotic syndrome after adjustment for age and estmmated glomerular filtration rate (eGFR) demonstrated that syndecan-1 was significantly associated with 24-h urinary protein excretion, total cholesterol, LDL (low density lipoprotein)-cholesterol, HDL (high-density lipoprotein)-cholesterol, and triglycerides. Angiopoietin-2 was independently associated with serum albumin, 24 h urinary protein excretion, total cholesterol, and LDL-cholesterol, in addition to being strongly associated with syndecan-1 (0.461, p < 0.001). The results of the mediation analyses showed that the direct association between LDL-cholesterol and syndecan-1 was no longer significant after AGPT-2 was included in the mediation analysis. AGPT2 explained 56% of the total observed association between LDL-cholesterol and syndecan-1. Conclusion: The association between LDL-cholesterol and glycocalyx derangement in nephrotic patients is possibly mediated by AGPT2. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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23 pages, 4012 KiB

Open AccessArticle

AST-120 Reduces Neuroinflammation Induced by Indoxyl Sulfate in Glial Cells

by Simona Adesso, Irene Paterniti, Salvatore Cuzzocrea, Masaki Fujioka, Giuseppina Autore, Tim Magnus, Aldo Pinto and Stefania Marzocco

J. Clin. Med. 2018, 7(10), 365; https://doi.org/10.3390/jcm7100365 - 17 Oct 2018

Cited by 43 | Viewed by 4419

Abstract

Chronic kidney disease (CKD) involves multiple organ dysfunction, and the neurological complications that are often present in CKD patients support the idea of a crosstalk between the kidneys and the brain. Evidence suggests a possible role for products accumulating in these patients as [...] Read more.

Chronic kidney disease (CKD) involves multiple organ dysfunction, and the neurological complications that are often present in CKD patients support the idea of a crosstalk between the kidneys and the brain. Evidence suggests a possible role for products accumulating in these patients as uremic toxins in various CKD complications, including neurodegeneration. Indoxyl sulfate (IS), derived from tryptophan metabolism, is well-known as a uremic nephron-vascular toxin, and recent evidence suggests it also has a role in the immune response and in neurodegeneration. Inflammation has been associated with neurodegenerative diseases, as well as with CKD. In this study, we demonstrated that sera of CKD patients induced a significant inflammation in astrocyte cells which was proportional to IS sera concentrations, and that the IS adsorbent, AST-120, reduced this inflammatory response. These results indicated that, among the uremic toxins accumulating in serum of CKD patients, IS significantly contributed to astrocyte inflammation. Moreover, being also chronic inflammation associated with CKD, here we reported that IS further increased inflammation and oxidative stress in primary central nervous system (CNS) cells, via Nuclear Factor-κB (NF-κB) and Aryl hydrocarbon Receptor (AhR) activation, and induced neuron death. This study is a step towards elucidating IS as a potential pharmacological target in CKD patients. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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13 pages, 542 KiB

Open AccessArticle

Supplementation of Short-Chain Fatty Acid, Sodium Propionate, in Patients on Maintenance Hemodialysis: Beneficial Effects on Inflammatory Parameters and Gut-Derived Uremic Toxins, A Pilot Study (PLAN Study)

by Stefania Marzocco, Gholamreza Fazeli, Lucia Di Micco, Giuseppina Autore, Simona Adesso, Fabrizio Dal Piaz, August Heidland and Biagio Di Iorio

J. Clin. Med. 2018, 7(10), 315; https://doi.org/10.3390/jcm7100315 - 30 Sep 2018

Cited by 65 | Viewed by 6956

Abstract

Background: In end-stage renal disease (ESRD), gut-derived uremic toxins play a crucial role in the systemic inflammation and oxidative stress promoting the excess morbidity and mortality. The biochemical derangement is in part a consequence of an insufficient generation of short-chain fatty acids (SCFA) [...] Read more.

Background: In end-stage renal disease (ESRD), gut-derived uremic toxins play a crucial role in the systemic inflammation and oxidative stress promoting the excess morbidity and mortality. The biochemical derangement is in part a consequence of an insufficient generation of short-chain fatty acids (SCFA) due to the dysbiosis of the gut and an insufficient consumption of the fermentable complex carbohydrates. Aim of the study: The primary end-point was to evaluate the potential efficacy of SCFA (specifically, sodium propionate (SP)) for patients on maintenance hemodialysis (MHD) on systemic inflammation. Secondary end-points included potential attenuation of oxidative stress markers, insulin resistance and production of gut-derived uremic toxins indoxyl sulfate and p-cresol sulfate, as well as health status after SP supplementation. Study design: We performed a single-center non-randomized pilot study in 20 MHD patients. They received the food additive SP with a daily intake of 2 × 500 mg in the form of capsules for 12 weeks. Pre-dialysis blood samples were taken at the beginning, after six weeks and at the end of the administration period, as well as four weeks after withdrawal of the treatment. Results: The subjects revealed a significant decline of inflammatory parameters C-reactive protein (−46%), interleukin IL-2 (−27%) and IL-17 (−15%). The inflammatory parameters IL-6 and IFN-gamma showed a mild non-significant reduction and the anti-inflammatory cytokine IL-10 increased significantly (+71%). While the concentration of bacterial endotoxins and TNF-α remained unchanged, the gut-derived uremic toxins, indoxyl sulfate (−30%) and p-cresyl sulfate (−50%), revealed a significant decline. The SP supplementation reduced the parameters of oxidative stress malondialdehyde (−32%) and glutathione peroxidase activity (−28%). The serum insulin levels dropped by 30% and the HOMA-index by 32%. The reduction of inflammatory parameters was associated with a lowering of ferritin and a significant increase in transferrin saturation (TSAT). Four weeks after the end of the treatment phase, all improved parameters deteriorated again. Evaluation of the psycho-physical performance with the short form 36 (SF-36) questionnaire showed an enhancement in the self-reported physical functioning, general health, vitality and mental health. The SP supplementation was well tolerated and without important side effects. No patient had left the study due to intolerance to the medication. The SP supplementation in MHD patients reduced pro-inflammatory parameters and oxidative stress and improved insulin resistance and iron metabolism. Furthermore, SP effectively lowered the important gut-derived uremic toxins indoxyl and p-cresol sulfate. These improvements were associated with a better quality of life. Further controlled studies are required in a larger cohort to evaluate the clinical outcome. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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19 pages, 1981 KiB

Open AccessArticle

Salivary Biomarkers of Oxidative Stress in Children with Chronic Kidney Disease

by Mateusz Maciejczyk, Julita Szulimowska, Anna Skutnik, Katarzyna Taranta-Janusz, Anna Wasilewska, Natalia Wiśniewska and Anna Zalewska

J. Clin. Med. 2018, 7(8), 209; https://doi.org/10.3390/jcm7080209 - 10 Aug 2018

Cited by 63 | Viewed by 5037

Abstract

There are still missing non-invasive biomarkers of chronic kidney disease (CKD) in children. Therefore, the aim of the study was to evaluate oxidative stress indicators in the non-stimulated (NWS) and stimulated saliva (SWS) of CKD children (n = 25) and healthy controls [...] Read more.

There are still missing non-invasive biomarkers of chronic kidney disease (CKD) in children. Therefore, the aim of the study was to evaluate oxidative stress indicators in the non-stimulated (NWS) and stimulated saliva (SWS) of CKD children (n = 25) and healthy controls (n = 25). Salivary antioxidants (catalase (CAT), peroxidase (Px), superoxide dismutase (SOD), uric acid (UA), reduced glutathione (GSH), albumin), redox status (total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI)), and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), malondialdehyde (MDA)) were evaluated. We have demonstrated the significantly higher activity of SWS GPx and SOD, as well as elevated concentrations of UA and albumin in NWS and SWS of CKD children vs. the control group. TAC, TOS and OSI were significantly higher only in SWS, while oxidative damage products (AGE, AOPP and MDA) were significantly higher in both NWS and SWS of CKD children. ROC analysis showed a considerably high diagnostic value of AOPP in both NWS and SWS of CKD children compared to controls (AUC = 0.92; 0.98). CKD is responsible for disturbances in salivary antioxidant systems and oxidative damage to proteins and lipids. Salivary AOPP can be a potential biomarker of CKD in children. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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Review

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19 pages, 646 KiB

Open AccessReview

Kidney Disease in HIV Infection

by Gaetano Alfano, Gianni Cappelli, Francesco Fontana, Luca Di Lullo, Biagio Di Iorio, Antonio Bellasi and Giovanni Guaraldi

J. Clin. Med. 2019, 8(8), 1254; https://doi.org/10.3390/jcm8081254 - 19 Aug 2019

Cited by 35 | Viewed by 7255

Abstract

Antiretroviral therapy (ART) has significantly improved life expectancy of infected subjects, generating a new epidemiological setting of people aging withHuman Immunodeficiency Virus (HIV). People living with HIV (PLWH), having longer life expectancy, now face several age-related conditions as well as side effects of [...] Read more.

Antiretroviral therapy (ART) has significantly improved life expectancy of infected subjects, generating a new epidemiological setting of people aging withHuman Immunodeficiency Virus (HIV). People living with HIV (PLWH), having longer life expectancy, now face several age-related conditions as well as side effects of long-term exposure of ART. Chronic kidney disease (CKD) is a common comorbidity in this population. CKD is a relentlessly progressive disease that may evolve toward end-stage renal disease (ESRD) and significantly affect quality of life and risk of death. Herein, we review current understanding of renal involvement in PLWH, mechanisms and risk factors for CKD as well as strategies for early recognition of renal dysfunction and best care of CKD. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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16 pages, 496 KiB

Open AccessReview

Levamisole in Children with Idiopathic Nephrotic Syndrome: Clinical Efficacy and Pathophysiological Aspects

by Anne K. Mühlig, Jun Young Lee, Markus J. Kemper, Andreas Kronbichler, Jae Won Yang, Jiwon M. Lee, Jae Il Shin and Jun Oh

J. Clin. Med. 2019, 8(6), 860; https://doi.org/10.3390/jcm8060860 - 16 Jun 2019

Cited by 38 | Viewed by 7142

Abstract

Steroid sensitive nephrotic syndrome is one of the most common pediatric glomerular diseases. Unfortunately, it follows a relapsing and remitting course in the majority of cases, with 50% of all cases relapsing once or even more often. Most children with idiopathic nephrotic syndrome [...] Read more.

Steroid sensitive nephrotic syndrome is one of the most common pediatric glomerular diseases. Unfortunately, it follows a relapsing and remitting course in the majority of cases, with 50% of all cases relapsing once or even more often. Most children with idiopathic nephrotic syndrome respond initially to steroid therapy, nevertheless repeated courses for patients with relapses induce significant steroid toxicity. Patients with frequent relapses or steroid dependency thus require alternative treatment, such as cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil, levamisole, or rituximab. To reduce the relapse rate, several drugs have been used. Among these, levamisole has been considered the least toxic and least expensive therapy. Several randomized controlled trials (RCT) showed that levamisole is effective in reducing the relapse risk in steroid sensitive forms of nephrotic syndrome with a low frequency of side effects. Levamisole is a synthetic imidazothiazole derivative with immune-modulatory properties. In this article, we review recent data from randomized trials and observational studies to assess the efficacy of levamisole in frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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9 pages, 967 KiB

Open AccessReview

Very Low Protein Diet for Patients with Chronic Kidney Disease: Recent Insights

by Lucia Di Micco, Luca Di Lullo, Antonio Bellasi and Biagio R. Di Iorio

J. Clin. Med. 2019, 8(5), 718; https://doi.org/10.3390/jcm8050718 - 20 May 2019

Cited by 13 | Viewed by 5008

Abstract

Use of nutritional therapy (NT) in chronic kidney disease (CKD) patients is still debated among nephrologists, but it represents a fundamental point in the conservative treatment of CKD. It has been used for years and it has new goals today, such as (1) [...] Read more.

Use of nutritional therapy (NT) in chronic kidney disease (CKD) patients is still debated among nephrologists, but it represents a fundamental point in the conservative treatment of CKD. It has been used for years and it has new goals today, such as (1) the reduction of edema, diuretics, and blood pressure values with a low sodium-content diet; (2) the dose reduction of phosphate levels and phosphate binders; (3) the administration of bicarbonate with vegetables in order to correct metabolic acidosis and delay CKD progression; (4) the reduction of the number and the doses of drugs and chemical substances; and (5) the lowering of urea levels, the cure of intestinal microbioma, and the reduction of cyanates levels (such as indoxyl-sulphate and p-cresol sulphate), which are the most recent known advantages achievable with NT. In conclusion, NT and especially very low protein diet (VLPD) have several beneficial effects in CKD patients and slows the progression of CKD. Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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Open AccessCorrection

Correction: Etelcalcetide in Patients on Hemodialysis with Severe Secondary Hyperparathyroidism. Multicenter Study in “Real Life”. J. Clin. Med. 2019, 8, 1066

by Domenico Russo, Rocco Tripepi, Fabio Malberti, Biagio Di Iorio, Bernadette Scognamiglio, Luca Di Lullo, Immacolata Gaia Paduano, Giovanni Luigi Tripepi and Vincenzo Antonio Panuccio

J. Clin. Med. 2020, 9(4), 1224; https://doi.org/10.3390/jcm9041224 - 24 Apr 2020

Cited by 1 | Viewed by 1979

Abstract

The authors wish to make the following corrections to the previous publication [...] Full article

(This article belongs to the Special Issue Clinical Symptoms, Diagnostics and Treatments of Chronic Kidney Diseases (CKD))

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