Biomarkers Of Kidney Disease Research Articles

Kidney Biopsy in Autosomal Dominant Polycystic Kidney Disease

Proteinuria is an easily quantified biomarker of kidney disease and often a sign of glomerular pathology. Significant proteinuria is uncommon in cystic kidney diseases and should be further evaluated to exclude the presence of another simultaneous kidney disease. While renal biopsy is a valuable part of the diagnostic evaluation of proteinuria, careful consideration of risks and benefits is necessary before proceeding in a patient with bilateral renal cysts. We report the case of a man with Polycystic Kidney Disease (PKD) who was found to have nephrotic-range proteinuria. An ultrasound-guided kidney biopsy revealed evidence of Focal Segmental Glomerulosclerosis (FSGS), which was attributed to hyperfiltration-related injury in the context of extensive kidney cysts. Genetic testing did not reveal a cause of FSGS and showed a variant of uncertain significance in PKD1. We use this case to highlight three important issues that are applicable to patients with PKD: the role of diagnostic evaluation for proteinuria in cystic kidney disease, the feasibility of kidney biopsy despite the presence of bilateral renal cysts, and the roles and limitations of genetic testing in cystic kidney disease and FSGS.

Serum and Urinary Matrix Metalloproteinase-9 Concentrations in Dehydrated Horses.

Matrix metalloproteinase-9 is increased in renal tissue in human kidney disease, but its role as a biomarker for kidney disease has not been fully evaluated yet. The aim of this study was to evaluate serum MMP-9 (sMMP-9) and urinary MMP-9 (uMMP-9) concentrations in dehydrated horses. Dehydrated horses were prospectively included. Blood and urinary samples were taken at admission, and after 12, 24, and 48 h (t0, t12, t24, t48), an anti-equine MMP-9 sandwich ELISA was used. Four healthy horses served as the controls. Serum creatinine, urea, symmetric dimethylarginine (SDMA), urine-specific gravity, urinary protein concentration, fractional sodium excretion, and urinary gamma-glutamyl transferase/creatinine ratio (uGGT/Cr) were measured. Statistical analysis included a repeated measures ANOVA and mixed linear regression model. Overall, 40 dehydrated horses were included (mild dehydration 13/40, moderate 16/40, severe 11/40). Acute kidney injury was found in 1/40 horses; 7/40 horses showed elevated serum creatinine, 11/40 horses elevated serum SDMA, and 5/28 elevated uGGT/Cr at presentation. In dehydrated horses, sMMP-9 concentrations were significantly higher on t0 (median: 589 ng/mL, range: 172-3597 ng/mL) compared to t12 (340 ng/mL, 132-1213 ng/mL), t24 (308 ng/mL, 162-1048 ng/mL), and t48 (258 ng/mL, 130-744 ng/mL). In healthy horses, sMMP-9 (239 ng/mL, 142-508 ng/mL) showed no differences over time or compared to patients. uMMP-9 and uMMP-9/creatinine did not differ over time or to the controls. No differences were found between dehydration groups. Urinary casts (p = 0.001; estimate = 135) and uGGT/Cr (p = 0.03; estimate = 6.5) correlated with sMMP-9. Serum urea was associated with uMMP-9/Cr (p = 0.01, estimate 0.9). In conclusion, sMMP-9 was elevated at arrival in dehydrated patients compared to later measurements. Correlations to uGGT/Cr and urinary casts need further evaluation.

LC/MS-MS quantification of myo-inositol: a novel biomarker for kidney disease

Abstract Creatinine is the primary biomarker used for assessing kidney function in patients with suspected acute and chronic kidney injury. However, creatinine, a product of muscle creatine metabolism, is an imperfect proxy for renal function because it is subject to non-renal interferences including muscle mass, diet, and medications. Creatinine is particularly problematic as a biomarker of acute kidney injury (AKI) due to relatively high renal function reserve, requiring considerable kidney damage and time for a clinically significant change in creatinine to be detected. Given that AKI and chronic kidney injury (CKD) are associated with high mortality, morbidity, and contribute significantly to health care costs, there is an unmet need for highly sensitive and specific biomarkers for assessing renal function in patients. Myo-inositol oxygenase (MIOX) is a novel biomarker limitedly expressed in the proximal renal tubules. MIOX concentrations are elevated in mice with renal injury and in critically ill patients with AKI. Our previously published studies have demonstrated that elevation in MIOX concentrations precedes changes in creatinine concentrations by approximately 54 hours. Importantly, MIOX facilitates the conversion of myo-inositol to glucuronic acid. We developed a robust LC-MS/MS method to quantify myo-inositol in human plasma, hypothesizing that following renal injury (acute and chronic), plasma concentrations of myo-inositol will increase, and will correlate with increases in serum creatinine concentrations. A healthy outpatient cohort was identified from samples obtained from out-patients with normal plasma creatinine, eGFR>60, as well as normal urine protein: creatinine ratio, albumin: creatinine ratio, or urinalysis results that were pan-negative/pan-normal. Remnant samples from out-patients with clinically staged CKD who have not initiated dialyses were selected for the CKD group. In healthy adult out-patients with stable renal function, the central 95th% distribution of plasma myo-inositol concentrations was 16.61 - 44.2 uM (Median 27.7uM, 95% CI: 26.7-28-7). No sex-based differences in plasma myo-inositol were observed. We also observed excellent correlation between plasma myo-inositol and serum creatinine concentrations (r=0.84, 95% CI: 80-88), as well as excellent sensitivity (99%) and specificity (100%) at a myo-inositol concentration of 50.22uM for differentiating patients with stable kidney function from those with CKD. Patients with CKD exhibited higher plasma myo-inositol concentrations (p value <0.0001) with a central 95% percentile of 51.2-309.1 uM (Median 104.1 uM, 95% CI: 92.3- 113.6). These results imply that myo-inositol concentrations increase in accord with renal injury and MIOX buildup in patients with kidney dysfunction, making it a potential biomarker for renal impairment.

Association between continuous glucose monitoring-derived glycemic control indices and urinary biomarkers of diabetic kidney disease: Hyogo Diabetes Hypoglycemia Cognition Complications study

AimsGlomerular damage and proximal tubular damage play an important role in the pathogenesis of diabetic kidney disease. This study aimed to investigate the relationship between the urinary markers of proximal tubular injury, including urinary liver-type fatty acid-binding protein-to-creatinine ratio (uL-FABP/Cr) and urinary N-acetyl-β-d-glucosaminidase-to-creatinine ratio (uNAG/Cr), and glycemic control status.MethodsThis cross-sectional study included 245 and 39 patients with type 2 diabetes mellitus (T2DM) and non-T2DM (NDM), respectively. The participants of this study were fitted with retrospective CGM, and glycemic control indices, such as time in range (TIR) and glycemia risk index (GRI), were calculated.ResultsThe results were presented as medians (interquartile ranges). The uL-FABP/Cr was significantly higher in the microalbuminuria than in the normo-albuminuria group [4.2 (2.7–7.1) and 2.2 (1.4–3.4) μg/gCr, respectively, P < 0.001], while the uNAG/Cr in the normo-albuminuria group [6.3 (4.5–10.1) U/gCr] was significantly higher than that in the NDM group [5.3 (3.8–6.3) U/gCr, P = 0.048] but significantly lower than that in the microalbuminuria group [9.2 (6.4–11.1) U/gCr, P = 0.004]. The multivariate logistic regression analysis indicated that CGM-derived TIR was significantly associated with the urinary albumin-to-creatinine ratio [uAlb/Cr, odds ratio (OR) 0.985, 95% confidence interval (CI) 0.971–0.998, P = 0.029] and uNAG/Cr (OR 0.973, 95% CI 0.957–0.989, P = 0.001) independent of renal function. GRI was similarly associated with uAlb/Cr and uNAG/Cr.ConclusionThe findings of this study indicated that uNAG/Cr was elevated before albuminuria development and was associated with CGM-derived TIR and GRI.

Methylglyoxal Adducts Are Prognostic Biomarkers for Diabetic Kidney Disease in Patients With Type 1 Diabetes.

Over 30% of patients with type 1 diabetes develop diabetic kidney disease (DKD), significantly increasing mortality risk. The Diabetes Control and Complications Trial (DCCT) and follow-up study Epidemiology of Diabetes Interventions and Complications (EDIC) established that glycemic control measured by HbA1c predicts DKD risk. However, the continued high incidence of DKD reinforces the urgent need for additional biomarkers to supplement HbA1c. Here, we assessed biomarkers induced by methylglyoxal (MG), a metabolic by-product that forms covalent adducts on DNA, RNA, and protein called MG-adducts. Urinary MG-adducts were measured from patients with type 1 diabetes enrolled in DCCT/EDIC who did (cases, n=90) or did not (controls, n=117) develop DKD. Univariate and multivariable analysis revealed that measurements of MG-adducts independently predict DKD, even before established DKD biomarkers such as glomerular filtration rate and albumin excretion rate. Elevated levels of MG-adducts bestowed the greatest risk of developing DKD in a multivariable model that included HbA1c and other clinical covariates. Our work establishes a novel class of biomarkers to predict DKD risk and suggests that inclusion of MG-adducts may be a valuable tool to improve existing predictors of complications like DKD prior to overt disease to aid in identifying at-risk individuals and personalized risk management.

Quantitative profiling of carboxylic compounds by gas chromatography-mass spectrometry for revealing biomarkers of diabetic kidney disease

Diabetic kidney disease (DKD), a common microvascular complication of diabetes, currently lacks specific diagnostic indicators and therapeutic targets, resulting in miss of early intervention. To profile metabolic conditions in complex and precious biological samples and screen potential biomarkers for DKD diagnosis and prognosis, a rapid, convenient and reliable quantification method for carboxyl compounds by gas chromatography-mass spectrometry (GC–MS) was established with isobutyl chloroformate derivatization. The derivatives were extracted with hexane, injected into GC–MS and quantified with selected ion monitoring mode. This method showed excellent linearity(R2 > 0.99), good recoveries (81.1%-115.5%), good repeatability (RSD < 20%) and sensitivity (LODs: 0.20–499.90 pg, LOQs: 2.00–1007.00 pg). Among the 37 carboxyl compounds analyzed, 12 metabolites in short-chain fatty acids (SCFAs) metabolism pathway and amino acid metabolism pathway were linked with DKD development and among them, 6 metabolites were associated with both development and prognosis of DKD in mice. In conclusion, a reliable, convenient and sensitive method based on isobutyl chloroformate derivatization and GC–MS analysis is established and successfully applied to quantify 37 carboxyl compounds in biological samples of mice and 12 potential biomarkers for DKD development and prognosis are screened.

Elucidating NOX5 as a Potential Therapeutic Target and a Biomarker of Kidney Disease in Diabetes

Elucidating NOX5 as a Potential Therapeutic Target and a Biomarker of Kidney Disease in Diabetes

Distal Tubule Urinary Biomarkers in Diabetic Kidney Disease: Results from the VA NEPHRON-D Trial

Distal Tubule Urinary Biomarkers in Diabetic Kidney Disease: Results from the VA NEPHRON-D Trial

Podocyte-specific proteins in urinary extracellular vesicles of patients with IgA nephropathy: Vasorin and ceruloplasmin

Introduction: Urinary extracellular vesicles (uEVs) can be considered biomarkers of kidney diseases. EVs derived from podocytes may reflect podocyte damage in different glomerular diseases. IgA nephropathy (IgAN) is one of the most common forms of glomerulonephritis (GN) characterized by proteinuria and hematuria. This study aimed to analyze the uEVs of IgAN patients to understand the pathophysiological processes of the disease at the protein level. Methods: Patients with GN [biopsy-proven IgAN (n = 16) and membranous glomerulonephritis (MGN, n = 16)], and healthy controls (n = 16) were included in this study. The uEVs were extracted, characterized, and analyzed to evaluate the protein levels of candidate markers of IgAN, including vasorin precursor, aminopeptidase N, and ceruloplasmin by western-blot analysis. Results: Higher levels of both podocytes and EVs-related proteins were observed in the pooled urine samples of GN patients compared to the healthy controls. In IgAN patients, uEV-protein levels of vasorin were statistically lower while levels of ceruloplasmin were significantly higher compared to MGN (P = 0.002, P = 0.06) and healthy controls, respectively (P = 0.020, P= 0.001). Conclusion: Different levels of the studied proteins in uEVs may indicate podocyte injury and represent a direct association with the pathology of IgAN and MGN.

Prognostic Significance of Amino Acid and Biogenic Amines Profiling in Chronic Kidney Disease.

There is a pressing need for more precise biomarkers of chronic kidney disease (CKD). Plasma samples from 820 subjects [231 with CKD, 325 with end-stage kidney disease (ESKD) and 264 controls] were analyzed by liquid chromatography with tandem mass spectrometry (LC-MS/MS) to determine a metabolic profile of 28 amino acids (AAs) and biogenic amines to test their value as markers of CKD risk and progression. The kynurenine/tryptophan ratio showed the strongest correlation with estimated glomerular filtration rate values (coefficient = -0.731, p < 0.0001). Models created with orthogonal partial least squares-discriminant analysis (OPLS-DA) containing the metabolic signature showed a high goodness of fit and predictability for controls/CKD (R2X:0.73:R2Y:0.92:Q2:0.92, p < 0.0001) and lower values for CKD/ESKD (R2X:0.56:R2Y:0.59:Q2:0.55, p < 0.0001). Based on generated VIP scores, the most relevant markers for segregating samples into control/CKD and CKD/ESKD groups were citrulline (1.63) and tryptophan (1.47), respectively. ROC analysis showed that the addition of the metabolic profile to a model including CKD classic risk factors improved the AUC from 86.7% (83.6-89.9) to 100% (100-100) for CKD risk (p < 0.0001) and from 63.0% (58.2-67.8) to 96.5% (95.3-97.8) for the risk of progression from CKD to ESKD (p < 0.0001). Plasma concentrations of AAs and related amines may be useful as diagnostic biomarkers of kidney disease, both for CKD risk and for progression of CKD patients to ESKD.

Analysis of potential biomarkers for diabetic kidney disease based on single-cell RNA-sequencing integrated with a single-cell sequencing assay for transposase-accessible chromatin.

Diabetic kidney disease (DKD) is a renal microvascular disease caused by hyperglycemia that involves metabolic remodeling, oxidative stress, inflammation, and other factors. The mechanism is complex and not fully unraveled. We performed an integrated single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) and single-cell RNA-sequencing (scRNA-seq) analyses of kidneys from db/db and db/m mice to identify differential open chromatin regions and gene expression, particularly in genes related to proximal tubular reabsorption and secretion. We identified 9,776 differentially expressed genes (DEGs) and 884 cell type-specific transcription factors (TFs) across 15 cell types. Glucose and lipid transporters, and TFs related to the circadian rhythm in the proximal tubules had significantly higher expression in db/db mice than in db/m mice (P<0.01). Crosstalk between podocytes and tubular cells in the proximal tubules was enhanced, and renal inflammation, oxidative stress, and fibrosis pathways were activated in db/db mice. Western blotting and immunohistochemical staining results showed that Wfdc2 expression in the urine and kidneys of DKD patients was higher than that in non-diabetic kidney disease (NDKD) controls. The revealed landscape of chromatin accessibility and transcriptional profiles in db/db mice provide insights into the pathological mechanism of DKD.

Assessing the status of European laboratories in evaluating biomarkers for chronic kidney diseases (CKD) and recommendations for improvement: insights from the 2022 EFLM Task Group on CKD survey.

Chronic kidney disease (CKD) is a global health issue, ranking as the third leading cause of death worldwide. CKD diagnosis and management depend on clinical laboratory tests, necessitating consistency for precise patient care. Global harmonization of CKD testing through clinical practice guidelines (CPGs) is recommended. Prior to CPG development, assessing the current CKD testing landscape is crucial. In 2022, the European Federation of Laboratory Medicine (EFLM) conducted an online survey among European laboratories associated with EFLM, evaluating CKD testing practices, including new glomerular filtration rate (GFR) estimation methods. This report summarizes the 2022 survey findings and offers recommendations for improving CKD test standardization. An online survey was conducted in November 2022 using a questionnaire hosted on LimeSurvey sent to European laboratories affiliated with the EFLM. The survey results were recorded in Excel files and analysed. The results highlight significant discrepancies among countries in unit expression, methods, cystatin C use, and GFR calculation equations. Additionally, limited attention to pediatric renal biology specifics, varied proteinuria and albuminuria result expressions, and limited awareness of GFR measurement methods through iohexol clearance are noted. In an effort to enhance the standardization of crucial biomarkers utilized in nephrology for evaluating renal function and diagnosing kidney injuries, the EFLM Task Group on CKD suggests nine practical recommendations tailored for European laboratories. The group is confident that implementing these measures will minimize result expression discrepancies, ultimately leading to enhanced patient care.

B-196 LC/MS-MS Quantification of Myo-inositol: A Novel Biomarker for Kidney Disease

Abstract Currently accepted clinical standards for assessing kidney function include the measurement of creatinine for calculating estimated glomerular filtration rates (eGFR) and albumin to creatinine ratios. However, creatinine, a product of muscle creatine metabolism, is an imperfect proxy for renal function because it is subject to non-renal interferences. There is an unmet need for extremely sensitive and precise biomarkers for evaluating renal function in patients given that acute kidney injury (AKI) and chronic kidney disease (CKD) are linked to high mortality, morbidity, and contribute considerably to health care expenditures.Myo-inositol oxygenase (MIOX) is a novel biomarker limitedly expressed in the proximal renal tubules. MIOX concentrations are elevated in mice with renal injury and in critically ill patients with acute kidney injury (AKI), and increases are observed 54 h prior to changes in serum creatinine are observed. Importantly, MIOX facilitates the conversion of myo-inositol to glucuronic acid. We developed a robust LC-MS/MS method to quantify myo-inositol in human plasma and serum, hypothesizing that following renal injury (acute and chronic), plasma concentrations of myo-inositol will increase, and will correlate with increases in serum creatinine concentrations.In patients with stable renal function, the central 95% distribution of plasma myo-inositol concentrations was 16.61–44.2 µM (Median 27.7 µM, 95% CI: 26.7–28–7). No sex-based differences in plasma myo-inositol were observed. We also observed excellent correlation between plasma myo-inositol and serum creatinine concentrations (r = 0.84, 95% CI: 80–88), as well as excellent sensitivity (99%) and specificity (100%) at a myo-inositol concentration of 50.22 µM for differentiating patients with stable kidney function from those with CKD. Patients with CKD exhibited higher plasma myo-inositol concentrations (P value &amp;lt; 0.0001) with a central 95% percentile of 51.2–309.1 µM (Median 104.1 µM, 95% CI: 92.3–113.6).These results imply that myo-inositol concentrations increase in accord with renal tubular injury and MIOX buildup in patients with kidney dysfunction, making it a potential biomarker for renal impairment.

Analysis of a macrophage carbamylated proteome reveals a function in post-translational modification crosstalk

BackgroundLysine carbamylation is a biomarker of rheumatoid arthritis and kidney diseases. However, its cellular function is understudied due to the lack of tools for systematic analysis of this post-translational modification (PTM).MethodsWe adapted a method to analyze carbamylated peptides by co-affinity purification with acetylated peptides based on the cross-reactivity of anti-acetyllysine antibodies. We also performed immobilized-metal affinity chromatography to enrich for phosphopeptides, which allowed us to obtain multi-PTM information from the same samples.ResultsBy testing the pipeline with RAW 264.7 macrophages treated with bacterial lipopolysaccharide, 7,299, 8,923 and 47,637 acetylated, carbamylated, and phosphorylated peptides were identified, respectively. Our analysis showed that carbamylation occurs on proteins from a variety of functions on sites with similar as well as distinct motifs compared to acetylation. To investigate possible PTM crosstalk, we integrated the carbamylation data with acetylation and phosphorylation data, leading to the identification 1,183 proteins that were modified by all 3 PTMs. Among these proteins, 54 had all 3 PTMs regulated by lipopolysaccharide and were enriched in immune signaling pathways, and in particular, the ubiquitin-proteasome pathway. We found that carbamylation of linear diubiquitin blocks the activity of the anti-inflammatory deubiquitinase OTULIN.ConclusionsOverall, our data show that anti-acetyllysine antibodies can be used for effective enrichment of carbamylated peptides. Moreover, carbamylation may play a role in PTM crosstalk with acetylation and phosphorylation, and that it is involved in regulating ubiquitination in vitro.Graphical 9DSWmM7hoJm8b3LaxSLrsCVideo

Ppb-level detection of trimethylamine as biomarker in exhaled gas based on MoO3/V2O5 hierarchical heterostructure

The toxic gas trimethylamine (TMA) with fishy odor can not only be used as an indicator for evaluating seafood spoilage, but also as a biomarker for trimethylaminuria and kidney disease. This paper constructs a ppb-level trimethylamine gas sensor that operates at room temperature based on MoO3/V2O5 nanocomposites, which were fabricated by hydrothermal synthesis process. The adsorption energy of TMA on sensitive materials was calculated through the density functional theory, and the sensing mechanism was explored by simulating the adsorption process of TMA on the sensitive materials. The response (11.37%) of MoO3/V2O5 composites to ultra-low concentration (20 ppb) TMA was better than that of pure MoO3 nanorods (5.49%) and V2O5 nanospheres (6.36%) at room temperature. Compared with pure MoO3 sensors, an n-n heterojunction is formed between MoO3 and V2O5, which enhances the sensing performance of pure sensing material for TMA. In addition, the detection of exhaled gas in simulated kidney disease patients indicates that this sensor has great potential as an effective TMA detection tool in the field of non-invasive disease diagnosis.

Identification and detection of microRNA kidney disease biomarkers in liquid biopsies.

MicroRNAs (miRNAs) are emerging rapidly as a novel class of biomarkers of major organ disorders, including kidney diseases. However, current PCR-based detection methods are not amenable to development for high-throughput, cost-effective miRNA biomarker quantification. MiRNA biomarkers show significant promise for diagnosis and prognosis of kidney diseases, including diabetic kidney disease, acute kidney injury, IgA nephropathy and delayed graft function following kidney transplantation. A variety of novel methods to detect miRNAs in liquid biopsies including urine, plasma and serum are being developed. As miRNAs are functional transcripts that regulate the expression of many protein coding genes, differences in miRNA profiles in disease also offer clues to underlying disease mechanisms. Recent findings highlight the potential of miRNAs as biomarkers to detect and predict progression of kidney diseases. Developing in parallel, novel methods for miRNA detection will facilitate the integration of these biomarkers into rapid routine clinical testing and existing care pathways. Validated kidney disease biomarkers also hold promise to identify novel therapeutic tools and targets. http://links.lww.com/CONH/A43.

The Impact of COVID-19 Infection Control Measures on End-Stage Renal Disease Patients in a Community Hemodialysis Setting.

Several non-pharmaceutical infection control measures have been implemented at community-based hemodialysis centers to reduce the risk of Coronavirus Disease of 2019 (COVID-19) transmission,caused by the SARS-CoV-2 virus.However, there have been concerns that such measures may disrupt the routine and timely care required by patients, with adverse effects on their health outcomes.This cross-sectional study aims to determine the unintended consequences of COVID-19 infection control measures on hemodialysis patients. Electronic medical records were extracted from patients enrolled in community-based hemodialysis centers in Singapore.A baseline group prior of patients consisted of those enrolled in 2017, which was three years prior to the SARS-CoV-2-related pandemic (n = 548).This was compared with the study group of patients enrolled in 2019 (n = 426), just before the COVID-19 pandemic started.Medical records for these two groups were extracted from Januaryto July 2018 for the baseline group and from January to July 2020, respectively. Three regression models were built to study dialysis adherence, kidney disease biomarkers, and hospitalization episodes. There was no statistically significant difference in hospitalization and mortality outcomes, adherence to dialysis management, laboratory results for dialysis-related clearance, and anemia outcomes. There was a higher proportion of patients hospitalized for vascular access-related reasons in the study group as compared to the baseline group (OR 1.6, 95% CI: 1.10 to 2.29, P = 0.014).Patients in the study group had albumin levels 2.13% higher (95% CI: 0.88 to 3.39, P < 0.001) and alkaline phosphatase levels 7.3% lower (95% CI: 1.17 to 13.02, P = 0.020) than those in the baseline group. From this community-based hemodialysis study in Singapore, it was shown that the COVID-19 pandemic did not disrupt regular healthcare services for these patients.With strategies instituted fora coordinated health delivery workflow, ensuring sufficient capacity in the various healthcare delivery sites and overall pandemic preparedness, the patient clinical outcomes measures continued to be met with no adverse consequences noted.Some improvements in dialysis-related laboratory values and quality of care targets may be due to more stringent measures instituted to protect these vulnerable patients in the community.

D-Serine as a sensor and effector of the kidney.

D-Serine, a rare enantiomer of serine, is a biomarker of kidney disease and function. The level of D-serine in the human body is precisely regulated through the urinary clearance of the kidney, and its clearance serves as a new measure of glomerular filtration rate with a lower bias than creatinine clearance. D-Serine also has a direct effect on the kidneys and mediates the cellular proliferation of tubular cells via mTOR signaling and induces kidney remodeling as a compensatory reaction to the loss of kidney mass. In living kidney donors, the removal of the kidney results in an increase in blood D-serine level, which in turn accelerates kidney remodeling and augments kidney clearance, thus reducing blood levels of D-serine. This feedback system strictly controls D-serine levels in the body. The function of D-serine as a biomarker and modulator of kidney function will be the basis of precision medicine for kidney diseases.

Urine myo-inositol as a novel prognostic biomarker for diabetic kidney disease: a targeted metabolomics study using nuclear magnetic resonance.

As a leading cause of chronic kidney disease, clinical demand for noninvasive biomarkers of diabetic kidney disease (DKD) beyond proteinuria is increasing. Metabolomics is a popular method to identify mechanisms and biomarkers. We investigated urinary targeted metabolomics in DKD patients. We conducted a targeted metabolomics study of 26 urinary metabolites in consecutive patients with DKD stage 1 to 5 (n = 208) and healthy controls (n = 26). The relationships between estimated glomerular filtration rate (eGFR) or urine protein-creatinine ratio (UPCR) and metabolites were evaluated. Multivariate Cox analysis was used to estimate relationships between urinary metabolites and the target outcome, end-stage renal disease (ESRD). C statistics and time-dependent receiver operating characteristics (ROC) were used to assess diagnostic validity. During a median 4.5 years of follow-up, 103 patients (44.0%) progressed to ESRD and 65 (27.8%) died. The median fold changes of nine metabolites belonged to monosaccharide and tricarboxylic acid (TCA) cycle metabolites tended to increase with DKD stage. Myo-inositol, choline, and citrates were correlated with eGFR and choline, while mannose and myo-inositol were correlated with UPCR. Elevated urinary monosaccharide and TCA cycle metabolites showed associations with increased morality and ESRD progression. The predictive power of ESRD progression was high, in the order of choline, myo-inositol, and citrate. Although urinary metabolites alone were less predictive than serum creatinine or UPCR, myo-inositol had additive effect with serum creatinine and UPCR. In time-dependent ROC, myo-inositol was more predictive than UPCR of 1-year ESRD progression prediction. Myo-inositol can be used as an additive biomarker of ESRD progression in DKD.

Function follows form: the quest for the best prognostic imaging biomarker in ADPKD

Total kidney volume represents the most solid prognostic biomarker for autosomal dominant polycystic kidney disease, because it mirrors cyst growth that precedes kidney function decline. Considerable variability of glomerular filtration rate trajectories, however, remains unexplained by total kidney volume, and its calculation is time-consuming. Using deep learning algorithms, Gregory etal. determined total kidney volume and other, novel, imaging-based biomarkers. They achieved automation and improved prognostic accuracy for long-term kidney function loss, yet the study leaves some open questions and room for further improvement.