Kidney Disease: Biomarkers, Diagnosis, and Prognosis: 2nd Edition

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 7084

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Guest Editor
Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, 1981 Tsujido, Kamoda, Kawagoe 350-8550, Saitama, Japan
Interests: nephrology; acute kidney injury; regenerative medicine; renal stem/progenitor cell; biomarker; activin-follistatin system
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Special Issue Information

Dear Colleagues,

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are a worldwide public health problem, with increasing incidence and prevalence, high costs, and poor outcomes. To overcome this problem, it is indispensable for us to explore or establish early detection methods/techniques and better treatment options for various kidney diseases, which include primary/secondary glomerulonephritis, rapidly progressive glomerulonephritis, nephrotic syndrome, acute kidney injury, diabetic nephropathy/diabetic kidney disease, chronic renal failure, renal fibrosis, and polycystic kidney disease.

Biochemical parameters such as serum creatinine and blood urea nitrogen levels and/or urinalysis are generally used for the early detection of kidney diseases. Kidney biopsy samples enable us to perform a histological diagnosis of kidney diseases. However, serum/urinary biomarkers, techniques, and approaches for the early diagnosis of kidney diseases, the evaluation of kidney disease activity, and renal prognosis are still lacking.

This Special Issue offers an open-access forum that aims to bring together a collection of original research and review articles addressing novel biomarkers, techniques, and approaches that will be valuable and helpful for the diagnosis or analysis of kidney diseases, assessment of kidney disease activity, and renal prognosis.

We hope that this Special Issue will help us in the diagnosis, evaluation, and treatment of kidney diseases in the clinical setting and will provide essential and insightful clues to further our understanding of the development and progression of kidney diseases.

Prof. Dr. Akito Maeshima
Guest Editor

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Keywords

  • primary/secondary glomerulonephritis
  • rapidly progressive glomerulonephritis
  • nephrotic syndrome
  • acute kidney injury
  • chronic kidney disease
  • diabetic nephropathy/diabetic kidney disease
  • chronic renal failure
  • kidney transplantation
  • renal fibrosis
  • polycystic kidney disease

Published Papers (6 papers)

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13 pages, 3030 KiB  
Communication
Identification of Messenger RNA Signatures in Age-Dependent Renal Impairment
by Katsunori Yanai, Shohei Kaneko, Akinori Aomatsu, Keiji Hirai, Susumu Ookawara and Yoshiyuki Morishita
Diagnostics 2023, 13(24), 3653; https://doi.org/10.3390/diagnostics13243653 - 13 Dec 2023
Viewed by 556
Abstract
In general populations, age-dependent renal impairment contributes to the progression of renal dysfunction. It has not been known which molecules are involved in age-dependent renal impairment. Messenger RNA (mRNA) has been reported to modulate various renal diseases, and we therefore investigated mRNA signatures [...] Read more.
In general populations, age-dependent renal impairment contributes to the progression of renal dysfunction. It has not been known which molecules are involved in age-dependent renal impairment. Messenger RNA (mRNA) has been reported to modulate various renal diseases, and we therefore investigated mRNA signatures in age-dependent renal impairment. We performed an initial microarray-profiling analysis to screen mRNAs, the expression levels of which changed in the kidneys of 50-week-old senescence-accelerated prone (SAMP1) mice (which have accelerated age-dependent renal impairments) compared with those of 50 wk old senescence-accelerated-resistant (SAMR1) mice (which have normal aged kidneys) and with younger (10 wk old) SAMP1 and SAMR1 mice. We next assessed the expressions of mRNAs that were differentially expressed in the kidneys of SAMP1-50wk mice by conducting a quantitative real-time polymerase chain reaction (qRT-PCR) and compared the expressions among the SAMP1-10wk, SAMR1-10wk, and SAMR1-50wk mice. The results of the microarray together with the qRT-PCR analysis revealed five mRNAs whose expression levels were significantly altered in SAMP1-50wk mouse kidneys versus the control mice. The expression levels of the five mRNAs were increased in the kidneys of the mice with age-dependent renal impairment. Our findings indicate that the five mRNAs might be related and could become therapeutic targets for age-dependent renal impairment. Full article
(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis, and Prognosis: 2nd Edition)
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13 pages, 1095 KiB  
Article
Evaluation of NAG, NGAL, and KIM-1 as Prognostic Markers of the Initial Evolution of Kidney Transplantation
by Guadalupe Tabernero, Moisés Pescador, Elena Ruiz Ferreras, Ana I. Morales and Marta Prieto
Diagnostics 2023, 13(11), 1843; https://doi.org/10.3390/diagnostics13111843 - 25 May 2023
Cited by 1 | Viewed by 1207
Abstract
Kidney transplantation is the best option for end-stage chronic kidney disease. Transplant viability is conditioned by drugs’ nephrotoxicity, ischemia–reperfusion damage, or acute rejection. An approach to improve graft survival is the identification of post-transplant renal function prognostic biomarkers. Our objective was to study [...] Read more.
Kidney transplantation is the best option for end-stage chronic kidney disease. Transplant viability is conditioned by drugs’ nephrotoxicity, ischemia–reperfusion damage, or acute rejection. An approach to improve graft survival is the identification of post-transplant renal function prognostic biomarkers. Our objective was to study three early kidney damage biomarkers (N-acetyl-d-glucosaminidase, NAG; neutrophil gelatinase-associated lipocalin, NGAL; and kidney injury molecule-1, KIM-1) in the initial period after transplantation and to identify possible correlations with main complications. We analysed those biomarkers in urine samples from 70 kidney transplant patients. Samples were taken on days 1, 3, 5, and 7 after intervention, as well as on the day that renal function stabilised (based on serum creatinine). During the first week after transplant, renal function improved based on serum creatinine evolution. However, increasing levels of biomarkers at different times during that first week could indicate tubular damage or other renal pathology. A relationship was found between NGAL values in the first week after transplantation and delayed graft function. In addition, higher NAG and NGAL, and lower KIM-1 values predicted a longer renal function stabilisation time. Therefore, urinary NAG, NGAL, and KIM-1 could constitute a predictive tool for kidney transplant complications, contributing to improve graft survival rates. Full article
(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis, and Prognosis: 2nd Edition)
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19 pages, 2215 KiB  
Article
NGAL as Biomarker of Clinical and Subclinical Damage of Kidney Function after Coronary Angiography
by Iliyana Petrova, Alexander Alexandrov, Georgi Vladimirov, Hristo Mateev, Ivaylo Bogov, Iva Paskaleva and Nina Gotcheva
Diagnostics 2023, 13(6), 1180; https://doi.org/10.3390/diagnostics13061180 - 20 Mar 2023
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Abstract
Contrast-induced acute kidney injury (CI-AKI) is a serious complication after angiographic examinations in cardiology. Diagnosis may be delayed based on standard serum creatinine, and subclinical forms of kidney damage may not be detected at all. In our study, we investigate the clinical use [...] Read more.
Contrast-induced acute kidney injury (CI-AKI) is a serious complication after angiographic examinations in cardiology. Diagnosis may be delayed based on standard serum creatinine, and subclinical forms of kidney damage may not be detected at all. In our study, we investigate the clinical use in these directions of a “damage”-type biomarker—neutrophil gelatinase-associated lipocalin (NGAL). Among patients with a high-risk profile undergoing scheduled coronary angiography and/or angioplasty, plasma NGAL was determined at baseline and at 4th and 24th h after contrast administration. In the CI-AKI group, NGAL increased significantly at the 4th hour (Me 109.3 (IQR 92.1–148.7) ng/mL versus 97.6 (IQR 69.4–127.0) ng/mL, p = 0.006) and at the 24th hour (Me 131.0 (IQR 81.1–240.8) ng/mL, p = 0.008). In patients with subclinical CI-AKI, NGAL also increased significantly at the 4th hour (Me 94.0 (IQR 75.5–148.2) ng/mL, p = 0.002) and reached levels close to those in patients with CI-AKI. Unlike the new biomarker, however, serum creatinine did not change significantly in this group. The diagnostic power of NGAL is extremely good—AUC 0.847 (95% CI: 0.677–1.000; p = 0.001) in CI-AKI and AUC 0.731 (95% CI: 0.539–0.924; p = 0.024) in subclinical CI-AKI. NGAL may be a reliable biomarker for the early diagnosis of clinical and subclinical forms of renal injury after contrast angiographic studies. Full article
(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis, and Prognosis: 2nd Edition)
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9 pages, 534 KiB  
Article
Development of an In-House EphA2 ELISA for Human Serum and Measurement of Circulating Levels of EphA2 in Hypertensive Patients with Renal Dysfunction
by Maki Murakoshi, Takumi Iwasawa, Takeo Koshida, Yusuke Suzuki, Tomohito Gohda and Kazunori Kato
Diagnostics 2022, 12(12), 3023; https://doi.org/10.3390/diagnostics12123023 - 02 Dec 2022
Cited by 3 | Viewed by 1132
Abstract
Identifying novel biomarkers of kidney function in patients with chronic kidney disease (CKD) has strong clinical value as current measures have limitations. This study aims to develop and validate a sensitive and specific ephrin type-A receptor 2 (EphA2) enzyme-linked immunosorbent assay (ELISA) for [...] Read more.
Identifying novel biomarkers of kidney function in patients with chronic kidney disease (CKD) has strong clinical value as current measures have limitations. This study aims to develop and validate a sensitive and specific ephrin type-A receptor 2 (EphA2) enzyme-linked immunosorbent assay (ELISA) for human serum, and determine whether its results correlate with traditional renal measures in patients with hypertension. The novel ELISA of the current study was validated and used to measure circulating EphA2 levels in 80 hypertensive patients with and without kidney function decline (eGFR less than 60 mL/min/1.73 m2). Validation of the EphA2 ELISA showed good recovery (87%) and linearity (103%) and no cross-reactivity with other Eph receptors. Patients with kidney function decline had lower diastolic blood pressure, and higher UPCR and EphA2 than those without kidney function decline. The association of age and eGFR with EphA2 was maintained in the stepwise multiple regression analysis. In a multivariate logistic model, EphA2 was associated with a lower eGFR (<60 mL/min/1.73 m2) after adjustment for age, sex, and UPCR. High circulating EphA2 levels have potential application as a clinical biomarker for the presence of CKD in patients with hypertension. Full article
(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis, and Prognosis: 2nd Edition)
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20 pages, 1100 KiB  
Systematic Review
Antenatal Determinants of Postnatal Renal Function in Fetal Megacystis: A Systematic Review
by Ugo Maria Pierucci, Irene Paraboschi, Guglielmo Mantica, Sara Costanzo, Angela Riccio, Giorgio Giuseppe Orlando Selvaggio and Gloria Pelizzo
Diagnostics 2024, 14(7), 756; https://doi.org/10.3390/diagnostics14070756 - 02 Apr 2024
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Abstract
Introduction: To evaluate the clinical usefulness of demographic data, fetal imaging findings and urinary analytes were used for predicting poor postnatal renal function in children with congenital megacystis. Materials and methods: A systematic review was conducted in MEDLINE’s electronic database from [...] Read more.
Introduction: To evaluate the clinical usefulness of demographic data, fetal imaging findings and urinary analytes were used for predicting poor postnatal renal function in children with congenital megacystis. Materials and methods: A systematic review was conducted in MEDLINE’s electronic database from inception to December 2023 using various combinations of keywords such as “luto” [All Fields] OR “lower urinary tract obstruction” [All Fields] OR “urethral valves” [All Fields] OR “megacystis” [All Fields] OR “urethral atresia” [All Fields] OR “megalourethra” [All Fields] AND “prenatal ultrasound” [All Fields] OR “maternal ultrasound” [All Fields] OR “ob-stetric ultrasound” [All Fields] OR “anhydramnios” [All Fields] OR “oligohydramnios” [All Fields] OR “renal echogenicity” [All Fields] OR “biomarkers” [All Fields] OR “fetal urine” [All Fields] OR “amniotic fluid” [All Fields] OR “beta2 microglobulin” [All Fields] OR “osmolarity” [All Fields] OR “proteome” [All Fields] AND “outcomes” [All Fields] OR “prognosis” [All Fields] OR “staging” [All Fields] OR “prognostic factors” [All Fields] OR “predictors” [All Fields] OR “renal function” [All Fields] OR “kidney function” [All Fields] OR “renal failure” [All Fields]. Two reviewers independently selected the articles in which the accuracy of prenatal imaging findings and fetal urinary analytes were evaluated to predict postnatal renal function. Results: Out of the 727 articles analyzed, 20 met the selection criteria, including 1049 fetuses. Regarding fetal imaging findings, the predictive value of the amniotic fluid was investigated by 15 articles, the renal appearance by 11, bladder findings by 4, and ureteral dilatation by 2. The postnatal renal function showed a statistically significant relationship with the occurrence of oligo- or anhydramnion in four studies, with an abnormal echogenic/cystic renal cortical appearance in three studies. Single articles proved the statistical prognostic value of the amniotic fluid index, the renal parenchymal area, the apparent diffusion coefficient (ADC) measured on fetal diffusion-weighted MRI, and the lower urinary tract obstruction (LUTO) stage (based on bladder volume at referral and gestational age at the appearance of oligo- or anhydramnios). Regarding the predictive value of fetal urinary analytes, sodium and β2-microglobulin were the two most common urinary analytes investigated (n = 10 articles), followed by calcium (n = 6), chloride (n = 5), urinary osmolarity (n = 4), and total protein (n = 3). Phosphorus, glucose, creatinine, and urea were analyzed by two articles, and ammonium, potassium, N-Acetyl-l3-D-glucosaminidase, and microalbumin were investigated by one article. The majority of the studies (n = 8) failed to prove the prognostic value of fetal urinary analytes. However, two studies showed that a favorable urinary biochemistry profile (made up of sodium < 100 mg/dL; calcium < 8 mg/dL; osmolality < 200 mOsm/L; β2-microglobulin < 4 mg/L; total protein < 20 mg/dL) could predict good postnatal renal outcomes with statistical significance and urinary levels of β2-microglobulin were significantly higher in fetuses that developed an impaired renal function in childhood (10.9 ± 5.0 mg/L vs. 1.3 ± 0.2 mg/L, p-value < 0.05). Conclusions: Several demographic data, fetal imaging parameters, and urinary analytes have been shown to play a role in reliably triaging fetuses with megacystis for the risk of adverse postnatal renal outcomes. We believe that this systematic review can help clinicians for counseling parents on the prognoses of their infants and identifying the selected cases eligible for antenatal intervention. Full article
(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis, and Prognosis: 2nd Edition)
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8 pages, 2066 KiB  
Case Report
Hyaline Vascular Type of Unicentric Castleman Disease in a Kidney with End-Stage Renal Disease: A Case Report of a Rare Entity at an Unusual Location and a Special Clinical Setting
by Chuan-Han Chen and Hsin-Ni Li
Diagnostics 2022, 12(11), 2878; https://doi.org/10.3390/diagnostics12112878 - 21 Nov 2022
Cited by 2 | Viewed by 1462
Abstract
Castleman disease (CD) is an unusual heterogeneous lymphoproliferative disorder that has been classified based on either clinical presentation and disease course or histologic features. Clinically, CD is divided into a unicentric CD (UCD) type and multicentric CD (MCD) type according to the extent [...] Read more.
Castleman disease (CD) is an unusual heterogeneous lymphoproliferative disorder that has been classified based on either clinical presentation and disease course or histologic features. Clinically, CD is divided into a unicentric CD (UCD) type and multicentric CD (MCD) type according to the extent of lymph node region involvement and the absence or presence of systemic symptoms. Histologically, it can be categorized into hyaline vascular (HV) type, plasma cell (PC) type and mixed type. The majority of HV-type CD involves a solitary lymph node, and excision surgery is often curative. On the contrary, MCD is a progressive and often fatal disease with lymphadenopathy in multiple nodes, and systemic therapy is needed. Herein we report a unique case of HV-type CD presenting as a single renal mass in a patient with end-stage renal disease (ESRD). Despite the rarity, CD should be included in the differential diagnosis of solitary renal mass lesions. An accurate diagnosis is important to avoid unnecessarily risky or extensive operations. Full article
(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis, and Prognosis: 2nd Edition)
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