Research

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15 pages, 2867 KiB

Open AccessArticle

Urinary Protein Profiling for Potential Biomarkers of Chronic Kidney Disease: A Pilot Study

by Abduzhappar Gaipov, Zhalaliddin Makhammajanov, Zhanna Dauyey, Zhannur Markhametova, Kamilla Mussina, Assem Nogaibayeva, Larissa Kozina, Dana Auganova, Pavel Tarlykov, Rostislav Bukasov, Zhandos Utegulov, Duman Turebekov, Maria Jose Soler, Alberto Ortiz and Mehmet Kanbay

Diagnostics 2022, 12(11), 2583; https://doi.org/10.3390/diagnostics12112583 - 25 Oct 2022

Cited by 2 | Viewed by 1935

Abstract

Proteinuria is a risk factor for chronic kidney disease (CKD) progression and associated complications. However, there is insufficient information on individual protein components in urine and the severity of CKD. We aimed to investigate urinary proteomics and its association with proteinuria and kidney [...] Read more.

Proteinuria is a risk factor for chronic kidney disease (CKD) progression and associated complications. However, there is insufficient information on individual protein components in urine and the severity of CKD. We aimed to investigate urinary proteomics and its association with proteinuria and kidney function in early-stage CKD and in healthy individuals. A 24 h urine sample of 42 individuals (21-CKD and 21-healthy individuals) was used for mass spectrometry-based proteomics analysis. An exponentially modified protein abundance index (emPAI) was calculated for each protein. Data were analyzed by Mascot software using the SwissProt database and bioinformatics tools. Overall, 298 unique proteins were identified in the cohort; of them, 250 proteins belong to the control group with median (IQR) emPAI 39.1 (19–53) and 142 proteins belong to the CKD group with median (IQR) emPAI 67.8 (49–117). The level of 24 h proteinuria positively correlated with emPAI (r = 0.390, p = 0.011). The emPAI of some urinary proteomics had close positive (ALBU, ZA2G, IGKC) and negative (OSTP, CD59, UROM, KNG1, RNAS1, CD44, AMBP) correlations (r < 0.419, p < 0.001) with 24 h proteinuria levels. Additionally, a few proteins (VTDB, AACT, A1AG2, VTNC, and CD44) significantly correlated with kidney function. In this proteomics study, several urinary proteins correlated with proteinuria and kidney function. Pathway analysis identified subpathways potentially related to early proteinuric CKD, allowing the design of prospective studies that explore their response to therapy and their relationship to long-term outcomes. Full article

(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis and Prognosis)

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10 pages, 494 KiB

Open AccessArticle

The Usefulness of Calcium/Magnesium Ratio in the Risk Stratification of Early Onset of Renal Replacement Therapy

by Rita Afonso, Roberto Calças Marques, Henrique Borges, Ana Cabrita and Ana Paula Silva

Diagnostics 2022, 12(10), 2470; https://doi.org/10.3390/diagnostics12102470 - 12 Oct 2022

Cited by 2 | Viewed by 1273

Abstract

Background: A growing number of studies have reported a close relationship between high serum calcium (Ca)/low serum magnesium (Mg) and vascular calcification. Endothelial dysfunction and vascular inflammation seem plausible risk factors for the enhanced progression of kidney disease. The aim of this study [...] Read more.

Background: A growing number of studies have reported a close relationship between high serum calcium (Ca)/low serum magnesium (Mg) and vascular calcification. Endothelial dysfunction and vascular inflammation seem plausible risk factors for the enhanced progression of kidney disease. The aim of this study was to evaluate the role of the Ca/Mg ratio as a predictor of the early onset of renal replacement therapy (RRT). Methods: This was a prospective study conducted in an outpatient low-clearance nephrology clinic, enrolling 693 patients with stages 4–5 of CKD. Patients were divided into two groups according to the start of renal replacement therapy (RRT). Results: The kidney’s survival at 120 months was 60% for a Ca–Mg ratio < 6 and 40% for a Ca–Mg ratio ≥ 6 (p = 0.000). Patients who started RRT had lower levels of Hb, Ca, Mg, albumin, and cholesterol and higher values of phosphorus, the Ca/Mg ratio, and PTH. High values of phosphorus and the Ca/Mg ratio and low levels of Mg and GFR were independent predictors of entry into RRT. A high Ca/Mg ratio, high phosphorus levels, and low levels of GFR were associated with a cumulative risk for initiation of RRT. Conclusions: In our population, the Ca/Mg ratio is an independent predictive factor for the initiation of a depurative technique. Full article

(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis and Prognosis)

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13 pages, 1915 KiB

Open AccessArticle

Machine Learning Models for the Prediction of Renal Failure in Chronic Kidney Disease: A Retrospective Cohort Study

by Chuan-Tsung Su, Yi-Ping Chang, Yuh-Ting Ku and Chih-Ming Lin

Diagnostics 2022, 12(10), 2454; https://doi.org/10.3390/diagnostics12102454 - 11 Oct 2022

Cited by 3 | Viewed by 1680

Abstract

This study assessed the feasibility of five separate machine learning (ML) classifiers for predicting disease progression in patients with pre-dialysis chronic kidney disease (CKD). The study enrolled 858 patients with CKD treated at a veteran’s hospital in Taiwan. After classification into early and [...] Read more.

This study assessed the feasibility of five separate machine learning (ML) classifiers for predicting disease progression in patients with pre-dialysis chronic kidney disease (CKD). The study enrolled 858 patients with CKD treated at a veteran’s hospital in Taiwan. After classification into early and advanced stages, patient demographics and laboratory data were processed and used to predict progression to renal failure and important features for optimal prediction were identified. The random forest (RF) classifier with synthetic minority over-sampling technique (SMOTE) had the best predictive performances among patients with early-stage CKD who progressed within 3 and 5 years and among patients with advanced-stage CKD who progressed within 1 and 3 years. Important features identified for predicting progression from early- and advanced-stage CKD were urine creatinine and serum creatinine levels, respectively. The RF classifier demonstrated the optimal performance, with an area under the receiver operating characteristic curve values of 0.96 for predicting progression within 5 years in patients with early-stage CKD and 0.97 for predicting progression within 1 year in patients with advanced-stage CKD. The proposed method resulted in the optimal prediction of CKD progression, especially within 1 year of advanced-stage CKD. These results will be useful for predicting prognosis among patients with CKD. Full article

(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis and Prognosis)

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11 pages, 6598 KiB

Open AccessArticle

Urinary Activin A: A Novel Biomarker for Human Acute Kidney Injury

by Izumi Nagayama, Akito Maeshima and Daisuke Nagata

Diagnostics 2022, 12(3), 661; https://doi.org/10.3390/diagnostics12030661 - 09 Mar 2022

Cited by 2 | Viewed by 1851

Abstract

Activin is a multifunctional cytokine belonging to the transforming growth factor (TGF)-β superfamily that regulates the growth and differentiation of cells in various organs. We previously reported that activin A, which is absent in normal kidneys, was significantly increased in the ischemic kidney, [...] Read more.

Activin is a multifunctional cytokine belonging to the transforming growth factor (TGF)-β superfamily that regulates the growth and differentiation of cells in various organs. We previously reported that activin A, which is absent in normal kidneys, was significantly increased in the ischemic kidney, and that the blockade of activin action by follistatin, an activin antagonist, significantly enhanced tubular regeneration after renal ischemia, suggesting that activin A acts as an endogenous inhibitor of tubular repair after kidney injury in rodents. However, the role of activin A in human acute kidney injury (AKI) remains unclear. In this analysis, we measured serum and urinary activin A in human AKI (n = 39) and tested if activin A might serve as a biomarker for AKI. Urinary activin A, which was undetectable in healthy controls, was significantly increased in AKI (0.0 ± 0.0 vs. 173.4 ± 58.8 pg/mL, p < 0.05). The urinary activin A level in patients with AKI stage 3, was significantly higher than that in patients with AKI stages 1 and 2. Patients who required renal replacement therapy (RRT) had a significantly higher urinary activin A level than patients who did not require RRT. Urinary activin A might be a useful non-invasive biomarker for the severity of AKI. Full article

(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis and Prognosis)

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12 pages, 1140 KiB

Open AccessArticle

Effect of Subclinical Hypothyroidism on the Association between Hemoglobin A1c and Reduced Renal Function: A Prospective Study

by Yuji Shimizu, Shin-Ya Kawashiri, Yuko Noguchi, Seiko Nakamichi, Yasuhiro Nagata, Takahiro Maeda and Naomi Hayashida

Diagnostics 2022, 12(2), 462; https://doi.org/10.3390/diagnostics12020462 - 11 Feb 2022

Cited by 2 | Viewed by 1909

Abstract

Subclinical hypothyroidism (SCH) was reported to be associated with accelerating endothelial dysfunction, which is recognized as one of the upstream mechanisms that leads to glomerular injury (lower glomerular filtration rate (GFR)). SCH was also reported to be associated with hyperglycemia, which is associated [...] Read more.

Subclinical hypothyroidism (SCH) was reported to be associated with accelerating endothelial dysfunction, which is recognized as one of the upstream mechanisms that leads to glomerular injury (lower glomerular filtration rate (GFR)). SCH was also reported to be associated with hyperglycemia, which is associated with higher hemoglobin A1c (HbA1c) levels and induces endothelial dysfunction. Therefore, SCH status could influence the association between HbA1c and reduced eGFR. To clarify those associations, we conducted a prospective study of 1580 Japanese individuals who participated in an annual health check-up in 2014 with 2.8 years of follow-up. All participants had free triiodothyronine (T3) and free thyroxine (T4) levels in the normal range. Among study participants, 88 were diagnosed as having SCH. Even though no significant correlation was observed between HbA1c and annual change in estimated GFR among participants without SCH (multi-adjusted standardized parameter estimate (β) = 0.03, p = 0.250), a significant inverse association was observed among participants with SCH (β = −0.26, p = 0.014). When those analyses were performed among participants who were not taking glucose lowering medication, the observed associations were essentially the same: β = 0.03, p = 0.266 for participants without SCH and β = −0.32, p = 0.006 for participants with SCH, respectively. Therefore, SCH status could influence the association between HbA1c and renal function. Full article

(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis and Prognosis)

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10 pages, 861 KiB

Open AccessArticle

Urinary Dipstick Is Not Reliable as a Screening Tool for Albuminuria in the Emergency Department—A Prospective Cohort Study

by Christian B. Nielsen, Henrik Birn, Frans Brandt and Jan D. Kampmann

Diagnostics 2022, 12(2), 457; https://doi.org/10.3390/diagnostics12020457 - 10 Feb 2022

Cited by 4 | Viewed by 3603

Abstract

Albuminuria is a sensitive marker for renal dysfunction. Urinary dipstick tests are frequently used to screen for urinary abnormalities in the emergency department (ED). The aim of this prospective cohort study is to evaluate the usefulness of urinary dipstick testing as a screening [...] Read more.

Albuminuria is a sensitive marker for renal dysfunction. Urinary dipstick tests are frequently used to screen for urinary abnormalities in the emergency department (ED). The aim of this prospective cohort study is to evaluate the usefulness of urinary dipstick testing as a screening tool for albuminuria in the ED setting and to determine the persistency of albuminuria identified in the acute setting. Urinary dipstick tests and spot urine samples were obtained simultaneously for analysis of the urinary albumin-creatinine ratio (ACR). Participants with positive dipsticks for protein were invited for a second urinalysis four to six weeks after admission. The study included 234 patients admitted to the ED. Urinalysis was performed on 178 patients of which 46% (n = 82) had positive urinary dipstick tests for proteinuria. The sensitivity and specificity of the dipstick test were low (72.7% and 55.7% respectively) when compared to the ACR. Of the 82 patients with positive dipsticks at admission, 35 were available for follow-up. We observed a significant reduction in ACR at follow-up when compared to ACR at admission (p = 0.004). This paper concludes that urinary dipstick tests are not a reliable means to screen for albuminuria in the ED setting. Full article

(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis and Prognosis)

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Review

Jump to: Research

15 pages, 2154 KiB

Open AccessReview

COUP-TFII in Kidneys, from Embryos to Sick Adults

by Sumiyasu Ishii and Noriyuki Koibuchi

Diagnostics 2022, 12(5), 1181; https://doi.org/10.3390/diagnostics12051181 - 09 May 2022

Cited by 1 | Viewed by 1822

Abstract

Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is an orphan nuclear hormone receptor of unknown ligands. This molecule has two interesting features: (1) it is a developmental gene, and (2) it is a potential hormone receptor. Here, we describe the possible roles of [...] Read more.

Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is an orphan nuclear hormone receptor of unknown ligands. This molecule has two interesting features: (1) it is a developmental gene, and (2) it is a potential hormone receptor. Here, we describe the possible roles of COUP-TFII in the organogenesis of the kidneys and protection from adult renal diseases, primarily in mouse models. COUP-TFII is highly expressed in embryos, including primordial kidneys, and is essential for the formation of metanephric mesenchyme and the survival of renal precursor cells. Although the expression levels of COUP-TFII are low and its functions are unknown in healthy adults, it serves as a reno-protectant molecule against acute kidney injury. These are good examples of how developmental genes exhibit novel functions in the etiology of adult diseases. We also discuss the ongoing research on the roles of COUP-TFII in podocyte development and diabetic kidney disease. In addition, the identification of potential ligands suggests that COUP-TFII might be a novel therapeutic target for renal diseases in the future. Full article

(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis and Prognosis)

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16 pages, 671 KiB

Open AccessReview

Beyond the Cardiorenal Syndrome: Pathophysiological Approaches and Biomarkers for Renal and Cardiac Crosstalk

by Oana Nicoleta Buliga-Finis, Anca Ouatu, Minerva Codruta Badescu, Nicoleta Dima, Daniela Maria Tanase, Patricia Richter and Ciprian Rezus

Diagnostics 2022, 12(4), 773; https://doi.org/10.3390/diagnostics12040773 - 22 Mar 2022

Cited by 13 | Viewed by 3598

Abstract

Cardiorenal syndrome encompasses complex multifactorial facets and carries significant morbidity and mortality worldwide. The bi-directional relationship between the heart and kidneys, where dysfunction in one organ worsens the function of the other, has been the leading motor for research in the last few [...] Read more.

Cardiorenal syndrome encompasses complex multifactorial facets and carries significant morbidity and mortality worldwide. The bi-directional relationship between the heart and kidneys, where dysfunction in one organ worsens the function of the other, has been the leading motor for research in the last few years. In the pathophysiological process, small noncoding RNAs, epigenetics, vascular growth factors, oxidative stress, hemodynamic factors, and biomarkers play a pivotal role in the development of cardiorenal syndrome. It is therefore important to elucidate all the mechanisms in order to provide diagnostic and treatments tools. This review summarizes the hemodynamic and non-hemodynamic pathways along with biomarkers that could be the next target for diagnosis, treatment, and prognosis in cardiorenal syndrome. Full article

(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis and Prognosis)

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16 pages, 972 KiB

Open AccessReview

Hyperuricemia and Progression of Chronic Kidney Disease: A Review from Physiology and Pathogenesis to the Role of Urate-Lowering Therapy

by Tao Han Lee, Jia-Jin Chen, Chao-Yi Wu, Chih-Wei Yang and Huang-Yu Yang

Diagnostics 2021, 11(9), 1674; https://doi.org/10.3390/diagnostics11091674 - 13 Sep 2021

Cited by 23 | Viewed by 7303

Abstract

The relationship between hyperuricemia, gout, and renal disease has been investigated for several years. From the beginning, kidney disease has been considered a complication of gout; however, the viewpoints changed, claiming that hypertension and elevated uric acid (UA) levels are caused by decreased [...] Read more.

The relationship between hyperuricemia, gout, and renal disease has been investigated for several years. From the beginning, kidney disease has been considered a complication of gout; however, the viewpoints changed, claiming that hypertension and elevated uric acid (UA) levels are caused by decreased urate excretion in patients with renal impairment. To date, several examples of evidence support the role of hyperuricemia in cardiovascular or renal diseases. Several mechanisms have been identified that explain the relationship between hyperuricemia and chronic kidney disease, including the crystal effect, renin–angiotensin–aldosterone system activation, nitric oxide synthesis inhibition, and intracellular oxidative stress stimulation, and urate-lowering therapy (ULT) has been proven to reduce renal disease progression in the past few years. In this comprehensive review, the source and physiology of UA are introduced, and the mechanisms that explain the reciprocal relationship between hyperuricemia and kidney disease are reviewed. Lastly, current evidence supporting the use of ULT to postpone renal disease progression in patients with hyperuricemia and gout are summarized. Full article

(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis and Prognosis)

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