Marker Of Glomerular Filtration Rate Research Articles

Validating Low-Dose Iohexol as a Marker for Glomerular Filtration Rate by InVitro and InVivo Studies.

Clearance of an intravenous iohexol dose of 3235 mg is used to assess glomerular filtration rate (GFR), although systematic assessment of its pharmacokinetic (PK) properties is incomplete. The objectives of the present investigations were (i) to assess potential interactions of iohexol with important drug transporters, and (ii) whether a 259 mg dose could replace the current standard dose. Invitro, we evaluated whether iohexol inhibits or is transported by renal transporters (hOAT1/3, hOCT2, and hMATE1/2K) or other transporters (hOATP1B1/3, hOCT1, and hMDR1) using cell-based and vesicle-based systems. Invivo, we conducted a clinical trial with 12 volunteers with the administration of single intravenous doses of 3235 mg ("reference") and 259 mg ("test") using a changeover design. Plasma and urine samples were collected up to 24 h postdose. We assessed the dose linearity of iohexol pharmacokinetics using the standard bioequivalence approach and conducted a population PK analysis to characterize its profile. Our invitro findings indicate that iohexol is neither a substrate nor a significant inhibitor of the transporters, suggesting it is unlikely to participate in transporter-mediated drug-drug interactions invivo. In the clinical trial, the test/reference ratio for plasma clearance, calculated as dose divided by the area under the plasma concentration-time curve, was 1.01 (90% confidence interval 0.968-1.05), confirming dose linearity. Population PK analysis further supported these results, showing no significant effect of dose on renal clearance and negligible nonrenal clearance of iohexol. Low-dose iohexol is a suitable marker for precise GFR measurement, even when coadministered with other drugs.

CYSTATIN C AS A MARKER OF EARLY KIDNEY DAMAGE UNDER ARTERIAL HYPERTENSION (LITERATURE REVIEW)

The purpose of this study is to determine kidney functional activity in relation to cystatin C levels, as reported in recent literature. Materials and Methods. A bibliographic-semantic method was employed to assess the current state of research on this topic, analyzing findings from previous scientific studies using both literature sources and electronic resources. Results. Chronic kidney disease (CKD) is as prevalent as hypertension. It is well-known that arterial hypertension exacerbates kidney function, making the assessment of renal functional activity critical. Glomerular filtration rate (GFR) is commonly used to evaluate kidney function, relying on established indicators as well as newer, more objective markers. Among these, cystatin C has emerged as one of the most accurate and sensitive indicators for assessing kidney function. Its concentration in serum negatively correlates with GFR and is particularly valuable for detecting renal pathology even when creatinine levels remain unchanged. This insight has led to the development of an estimated GFR (eGFR) formula that incorporates cystatin C levels. Research suggests that cystatin C levels increase with hypertension, although studies on the specific relationship between cystatin C and hypertension remain limited. Some findings propose that serum cystatin C could serve as a predictor of disease severity, particularly in elderly hypertensive patients with coronary heart disease. The literature supports the utility of cystatin C as a reliable marker for assessing GFR, which facilitates early detection of CKD even when albumin excretion is normal, thus identifying kidney damage at an early stage. Ppotential mechanisms by which elevated cystatin C may contribute to cardiovascular damage are under investigation. As a highly informative endogenous marker of GFR, serum cystatin C not only aids in staging CKD but is especially valuable in identifying early renal dysfunction. Conclusion. The measurement of cystatin C enables a highly accurate assessment of kidney function and aids in evaluating cardiovascular risk, especially when hypertension coexists with chronic kidney disease. Further research is needed to improve predictions of chronic kidney progression at various stages and in the presence of comorbidities. Such insights will support more effective preventive strategies to slow the progression of this pathology.

Creatinine clearance is maintained in a range of wet-bulb globe temperatures and work-rest ratios during simulated occupational heat stress.

We tested the hypothesis that compliance with the National Institute for Occupational Safety and Health (NIOSH) heat stress recommendations will prevent reductions in glomerular filtration rate (GFR) across a range of wet-bulb globe temperatures (WBGTs) and work-rest ratios at a fixed work intensity. We also tested the hypothesis that noncompliance would result in a reduction in GFR compared with a work-rest matched compliant trial. Twelve healthy adults completed five trials (four NIOSH compliant and one noncompliant) that consisted of 4 h of exposure to a range of WBGTs. Subjects walked on a treadmill (heat production: approximately 430 W) and work-rest ratios (work/h: 60, 45, 30, and 15 min) were prescribed as a function of WBGT (24°C, 26.5°C, 28.5°C, 30°C, and 36°C), and subjects drank a sport drink ad libitum. Peak core temperature (TC) and percentage change in body weight (%ΔBW) were measured. Creatinine clearance measured pre- and postexposure provided a primary marker of GFR. Peak TC did not differ among NIOSH-compliant trials (P = 0.065) but differed between compliant versus noncompliant trials (P < 0.001). %ΔBW did not differ among NIOSH-compliant trials (P = 0.131) or between compliant versus noncompliant trials (P = 0.185). Creatinine clearance did not change or differ among compliant trials (P ≥ 0.079). Creatinine clearance did not change or differ between compliant versus noncompliant trials (P ≥ 0.661). Compliance with the NIOSH recommendations maintained GFR. Surprisingly, despite a greater heat strain in a noncompliant trial, GFR was maintained highlighting the potential relative importance of hydration.NEW & NOTEWORTHY We highlight that glomerular filtration rate (GFR) is maintained during simulated occupational heat stress across a range of total work, work-rest ratios, and wet-bulb globe temperatures with ad libitum consumption of an electrolyte and sugar-containing sports drink. Compared with a work-rest matched compliant trial, noncompliance resulted in augmented heat strain but did not induce a reduction in GFR likely due to an increased relative fluid intake and robust fluid conservatory responses.

Corticosteroids alter kidney development and increase glomerular filtration rate in larval zebrafish (Danio rerio).

Pharmaceutical drugs and other chemicals can impact organogenesis, either during pregnancy or by postnatal exposure of very preterm infants. Corticosteroids are administered to pregnant women at risk of preterm delivery in order to reduce neonatal morbidity and mortality. In addition, high-dose corticosteroid exposure of very preterm infants regularly serves to maintain blood pressure and to prevent and treat bronchopulmonary dysplasia, a form of chronic lung disease in prematurely born infants. Despite clinical benefits, there is increasing evidence of corticosteroid-mediated short- and long-term detrimental developmental effects, especially in the kidney. Here, we performed a detailed morphological and functional analysis of corticosteroid-mediated effects on pronephros development in larval zebrafish. About 24-h postfertilization (hpf) transgenic Tg(wt1b: EGFP) zebrafish larvae were exposed to a set of natural and synthetic corticosteroids (hydrocortisone, dexamethasone, 6α-methylprednisolone, betamethasone, prednisolone, fludrocortisone, 11-deoxycorticosterone) with varying glucocorticoid and mineralocorticoid potency for 24 h at different concentrations. A semiautomated, multiparametric in vivo workflow enabled simultaneous assessment of kidney morphology, renal FITC-inulin clearance, and heart rate within the same larva. All corticosteroids exerted significant morphological and functional effects on pronephros development, including a significant hypertrophy of the pronephric glomeruli as well as dose-dependent increases in FITC-inulin clearance as a marker of glomerular filtration rate. In conclusion, the present study demonstrates a significant impact of corticosteroid exposure on kidney development and function in larval zebrafish. Hence, these studies underline that corticosteroid exposure of the fetus and the preterm neonate should be carefully considered due to potential short- and long-term harm to the kidney.

#1645 The role of donor Cystatin-C in posttransplant outcomes in kidney transplantation

Abstract Background and Aims Cystatin-C is an established marker of glomerular filtration rate in kidney disease. High levels of cystatin-C have been associated with unfavorable outcomes (acute kidney injury, cardiovascular morbidity) in critically ill patients. The aim of this study was to evaluate the levels of Cystatin-C in donors after brain (DBD) and circulatory death (DCD) and investigate its association with posttransplant graft function. Method Plasma samples from 303 donors (283 deceased, 20 living donors; LD) were obtained from the Quality in Organ Donation (QUOD) and the Oxford Transplant (OTB) biobanks. QUOD is a national multi-center UK wide bioresource of deceased donor clinical samples collected during donor management and organ procurement. OTB is a living donor biobank established to obtain clinical samples as control cohorts. Only deceased donors with both grafts transplanted were included in the study. Plasma Cystatin-C from LD samples as assessed as an optimal control group. The samples were linked to donor and recipient metadata obtained from the National Transplant Registry (NHSBT). Using Luminex assays, plasma Cystatin-C was quantified in samples collected during donor management (prior to cross clamp in DBDs and LDs and at withdrawal of support in DCDs). We performed descriptive statistics and multivariate linear and logistic analysis to determine the association between Cystatin-C, primary non-function (PNF), delayed graft function (DGF), acute rejection (AR) and 12-month posttransplant graft function. Results Among 303 donors (median age: 50 years), 126 were DCDs, 157 DBDs (20.1% of them were expanded criteria donors, ECD) and 20 LDs. ECDs and DCDs had significantly higher levels of Cystatin-C, compared to DBDs. In a total of 606 recipients, 11 (1.9%) developed PNF, and 128 (21%) developed DGF (24 as pairs, 80 non-pairs). Forty-six recipients (7.6%) experienced at least one AR episode and 60 (10%) donors had lost the graft during follow-up. Donor levels of Cystatin-C were associated with DGF and were further elevated in donors of kidneys which developed PNF (P-value &amp;lt; .0001, Fig. 1). Grafts with acute rejections were retrieved from donors with higher levels of Cystatin-C, but the difference did not meet statistical significance. Cystatin-C levels were significantly lower (P-value &amp;lt; .0001) in donors who offered concordant grafts with optimal 12-month post-transplant function (eGFR &amp;gt;60 ml/min), compared with grafts with intermediate function (GFR 30-60 ml/min) or eGFR &amp;lt;30ml/min (Fig. 2). LDs had significantly lower levels of Cystatin-C compared to deceased donors in all studied outcomes (Figs 1 and 2). Cystatin-C during donor management was an independent risk factor for inferior 12-month paired graft function, after the implementation of three different multivariate models, including donor (β-coef = −11.3, P-value = .001), recipient (β-coef = −16, P-value &amp;lt; .001) and post-transplant characteristics (β-coef = −13.1, P-value = .002). Conclusion In a large cohort of deceased and living donors, we were able to evaluate the circulating levels of Cystatin-C during donor management with the use of high-end performance technology. The concentration of Cystatin-C was notably different among donor types and was significantly higher in donors with kidneys that developed PNF or had suboptimal graft function 12-month posttransplant. Our findings suggest that Cystatin-C may have a role in identifying higher-risk donors during donor management and offers the opportunity for granular assessment of donor kidney quality prior to transplantation.

Reno-protective effect of nicorandil and pentoxifylline against potassium dichromate-induced acute renal injury via modulation p38MAPK/Nrf2/HO-1 and Notch1/TLR4/NF-κB signaling pathways

BackgroundOccupational and environmental exposure to chromium compounds such as potassium dichromate (PDC) (K2Cr2O7) has emerged as a potential aetiologic cause for renal disease through apoptotic, and inflammatory reactions. The known potent antioxidants such as nicorandil (NIC) and/or pentoxifylline (PTX) were studied for their possible nephroprotective effect in PDC-treated rats. MethodsForty male Wistar rats were divided into five groups; control, PDC group, NIC+PDC, PTX+PDC group, and combination+PDC group. Nephrotoxicity was evaluated histopathologically and biochemically. Invasive blood pressure, renal function parameters urea, creatinine, uric acid and albumin, glomerular filtration rate markers Cys-C, Kim-1 and NGAL, inflammatory markers IL-1β, IL-6, TNF-α, TGF-β, COX-II, p38MAPK, NF-κB and TLR4, oxidative stress SOD, GSH, MDA, MPO, HO-1 and Nrf2 and apoptotic mediators Notch1 and PCNA were evaluated. Besides, renal cortical histopathology was assayed as well. ResultsPDC led to a considerable increase in indicators for kidney injury, renal function parameters, invasive blood pressure, oxidative stress, and inflammatory markers. They were markedly reduced by coadministration of PDC with either/or NIC and PTX. The NIC and PTX combination regimen showed a more significant improvement than either medication used alone. Our results demonstrated the nephroprotective effect of NIC, PTX, and their combined regimen on PDC-induced kidney injury through suppression of oxidative stress, apoptosis, and inflammatory response. ConclusionRenal recovery from PDC injury was achieved through enhanced MAPK/Nrf2/HO-1 and suppressed Notch1/TLR4/NF-κB signaling pathways. This study highlights the role of NIC and PTX as effective interventions to ameliorate nephrotoxicity in patients undergoing PDC toxicity.

Relationship between white matter lesion coalescence and plasma cystatin C in an ethnically diverse population

AbstractBackgroundBrain and kidney share anatomical similarities in terms of the small vessels serving their irrigation. Previous work have shown associations between markers of cerebral small vessel disease (CSVD) e.g. white matter hyperintensities (WMH) and markers of renal function e.g. cystatin C. Few studies have however investigated the relationship between renal function and more detailed descriptions of lesion shape and distributionMethod768 individuals from the tri‐ethnic SABRE cohort underwent brain MRI including T1w and FLAIR sequences. WMH were automatically segmented and an overall measure of coalescence was derived from the lesion map ranging from 0 (only punctuate lesions) to 4 (high level of coalescence). Regional coalescence measures according to distance from the ventricles were further derived in 4 equidistant layers. Clinic blood samples were available for 731 individuals (45% female, mean age 71.3 (SD 6.4) years) including from 311 European; 172 African Caribbean; and 248 South Asian ethnicity. Blood measures include plasma cystatin C, a marker of glomerular filtration rate, white blood cell count (WBC) and HbA1c. Associations between cystatin C and coalescence score or lesion volume expressed as percentage of total intracranial volume were investigated using robust linear regression adjusting for age, ethnicity, sex, HbA1c and WBC; all factors known to be associated with cystatin C levels and WMH.ResultCystatin C was positively associated with male sex, WBC and HbA1c, and differed across ethnicities being highest in South Asians and lowest in African Caribbeans. After adjusting for potential confounders, cystatin C was positively associated with overall coalescence score (b = 0.026 [0.004;0.047], p = 0.018) despite unconvincing evidence of an association with overall lesion volume (b = 0.003 [‐0.0003; 0.007], p = 0.066). Associations between cystatin C and coalescence score were stronger in the South Asian group (b = 0.066 [0.027;0.105], p interaction = 0.001). Associations between cystatin C and coalescence score were similar across different layers.ConclusionShape patterns of WMH, rather than overall WMH volume, may provide a more sensitive measure to assess the relationship with markers of small vessel disease in the kidneys.

Relationship between white matter lesion coalescence and plasma cystatin C in an ethnically diverse population.

AbstractBackground: Brain and kidney share anatomical similarities in terms of the small vessels serving their irrigation. Previous work have shown associations between markers of cerebral small vessel disease (CSVD) e.g. white matter hyperintensities (WMH) and markers of renal function e.g. cystatin C. Few studies have however investigated the relationship between renal function and more detailed descriptions of lesion shape and distributionMethod768 individuals from the tri‐ethnic SABRE cohort underwent brain MRI including T1w and FLAIR sequences. WMH were automatically segmented and an overall measure of coalescence was derived from the lesion map ranging from 0 (only punctuate lesions) to 4 (high level of coalescence). Regional coalescence measures according to distance from the ventricles were further derived in 4 equidistant layers. Clinic blood samples were available for 731 individuals (45% female, mean age 71.3 (SD 6.4) years) including from 311 European; 172 African Caribbean; and 248 South Asian ethnicity. Blood measures include plasma cystatin C, a marker of glomerular filtration rate, white blood cell count (WBC) and HbA1c. Associations between cystatin C and coalescence score or lesion volume expressed as percentage of total intracranial volume were investigated using robust linear regression adjusting for age, ethnicity, sex, HbA1c and WBC; all factors known to be associated with cystatin C levels and WMH.ResultCystatin C was positively associated with male sex, WBC and HbA1c, and differed across ethnicities being highest in South Asians and lowest in African Caribbeans. After adjusting for potential confounders, cystatin C was positively associated with overall coalescence score (b = 0.026 [0.004;0.047], p = 0.018) despite unconvincing evidence of an association with overall lesion volume (b = 0.003 [‐0.0003; 0.007], p = 0.066). Associations between cystatin C and coalescence score were stronger in the South Asian group (b = 0.066 [0.027;0.105], p interaction = 0.001). Associations between cystatin C and coalescence score were similar across different layers.ConclusionShape patterns of WMH, rather than overall WMH volume, may provide a more sensitive measure to assess the relationship with markers of small vessel disease in the kidneys.

Serum Cystatin C as a Marker for Acute Kidney Injury Evaluation in Neonates Treated with Colistin

Background Colistin is increasingly used worldwide due to the emergence of multi-drug resistant (MDR) gram negative bacilli with concerns about its side effects especially nephrotoxicity. Serum cystatin C (CysC) is an endogenous protease inhibitor produced at a constant rate by nucleated cells and used as a filtration marker of glomerular filtration rate (GFR). Aim to study the effect of colistin on serum cystatin C as a marker for acute kidney injury in neonates in relation to serum urea and serum creatinine. Patients and method 78 neonates with gestational age of at least 30 weeks after treatment with colistin or antibiotics were divided into two groups non – colistin group and colistin group 39 pateints on each group. Kidney function tests were assessed before treatment and also after treatment but together with Kidney Disease Improving Global Outcome (KDIGO) criteria &amp; serum cystatin C. Results Serum cystatin C was found to be significantly higher in colistin group than non – colistin group. No significant differences were found between both groups regarding serum creatinine, serum urea and even KDIGO criteria of acute kidney injury in neonates. Conclusion Serum cystatin C is an early marker of acute kidney injury in neonates which may not be detected by serum urea or serum creatinine

Medication-Related Adverse Events and Discordancies in Cystatin C–Based vs Serum Creatinine–Based Estimated Glomerular Filtration Rate in Patients With Cancer

Serum creatinine-based estimated glomerular filtration rate (eGFRcr) may overestimate the glomerular filtration rate (GFR) in patients with cancer. Cystatin C-based eGFR (eGFRcys) is an alternative marker of GFR. To determine whether the therapeutic drug levels and adverse events (AEs) associated with renally cleared medications were higher in patients with cancer whose eGFRcys was more than 30% lower than their eGFRcr. This cohort study analyzed adult patients with cancer at 2 major academic cancer centers in Boston, Massachusetts. These patients had their creatinine and cystatin C measured on the same day between May 2010 and January 2022. The date of the first simultaneous eGFRcr and eGFRcys measurement was considered to be the baseline date. The primary exposure was eGFR discordance, defined as an eGFRcys that was more than 30% lower than the eGFRcr. The primary outcome was risk of the following medication-related AEs within 90 days of the baseline date: (1) supratherapeutic vancomycin trough level greater than 30 μg/mL, (2) trimethoprim-sulfamethoxazole-related hyperkalemia (>5.5 mEq/L), (3) baclofen toxic effect, and (4) supratherapeutic digoxin level (>2.0 ng/mL). For the secondary outcome, a multivariable Cox proportional hazards regression model was used to compare 30-day survival of those with vs without eGFR discordance. A total of 1869 adult patients with cancer (mean [SD] age, 66 [14] years; 948 males [51%]) had simultaneous eGFRcys and eGFRcr measurement. There were 543 patients (29%) with an eGFRcys that was more than 30% lower than their eGFRcr. Patients with an eGFRcys that was more than 30% lower than their eGFRcr were more likely to experience medication-related AEs compared with patients with concordant eGFRs (defined as eGFRcys within 30% of eGFRcr), including vancomycin levels greater than 30 μg/mL (43 of 179 [24%] vs 7 of 77 [9%]; P = .01), trimethoprim-sulfamethoxazole-related hyperkalemia (29 of 129 [22%] vs 11 of 92 [12%]; P = .07), baclofen toxic effects (5 of 19 [26%] vs 0 of 11; P = .19), and supratherapeutic digoxin levels (7 of 24 [29%] vs 0 of 10; P = .08). The adjusted odds ratio for vancomycin levels more than 30 μg/mL was 2.59 (95% CI, 1.08-7.03; P = .04). Patients with an eGFRcys more than 30% lower than their eGFRcr had an increased 30-day mortality (adjusted hazard ratio, 1.98; 95% CI, 1.26-3.11; P = .003). Results of this study suggest that among patients with cancer with simultaneous assessment of eGFRcys and eGFRcr, supratherapeutic drug levels and medication-related AEs occurred more commonly in those with an eGFRcys more than 30% lower than their eGFRcr. Future prospective studies are needed to improve and personalize GFR estimation and medication dosing in patients with cancer.

Cystatin C as a Marker for Glomerular Filtration Rate in Critically Ill Neonates and Children: Validation Against Iohexol Plasma Clearance

Cystatin C as a Marker for Glomerular Filtration Rate in Critically Ill Neonates and Children: Validation Against Iohexol Plasma Clearance

D-Asparagine is an Ideal Endogenous Molecule for Measuring the Glomerular Filtration Rate

An ideal endogenous molecule for measuring glomerular filtration rate (GFR) is still unknown. However, a rare enantiomer of serine, d-serine, is useful in GFR measurement. This study explored the potential of other d-amino acids for kidney function assessment. This was a cross-sectional observational study of 207 living kidney transplant donors and recipients, for whom GFR was measured using clearance of inulin (C-in). Associations between levels of d-amino acids and GFR were analyzed using multivariate factor analysis. Fractional excretion (FE), a ratio of the clearance of a substance to C-in as a standard molecule, was calculated to monitor the excretion ratio after glomerular filtration. Dissociation from an ideal FE of 100% was assessed as a bias. Proportional bias against C-in was calculated using Deming regression. Multivariate analysis identified the blood level of d-asparagine to reflect GFR. Means of blood d-asparagine and clearance of d-asparagine (C-d-Asn) were 0.21 μM and 65.0 ml/min per 1.73 m2, respectively. Inulin-based FE (FEin) of d-asparagine was 98.67% (95% confidence interval [CI]: 96.43-100.90%) and less biased than those of known GFR markers, such as FEin of creatinine (147.93 [145.39-150.46]; P< 0.001) and d-serine (84.84 [83.22-86.46]; P< 0.001). A proportional bias of C-d-Asn to C-in was-7.8% (95% CI,-14.5 to-0.6%), which was minor compared to those of clearance of creatinine (-34.5% [-37.9 to-31.0%]) and d-serine (21.2% [13.9-28.9]). D-Asparagine acts similar to inulin in the kidney. Therefore, d-asparagine is an ideal endogenous molecule that can be used for GFR measurement.

Definitions, phenotypes, and subphenotypes in acute kidney injury-Moving towards precision medicine.

The current definition of acute kidney injury (AKI) is generic and, based only on markers of function, is unsuitable for guiding individualized treatment. AKI is a complex syndrome with multiple presentations and causes. Targeted AKI management will only be possible if different phenotypes and subphenotypes of AKI are recognised, based on causation and related pathophysiology. Molecular signatures to identify subphenotypes are being recognised, as specific biomarkers reveal activated pathways. Assessment of individual clinical risk needs wider dissemination to allow identification of patients at high risk of AKI. New and more timely markers for glomerular filtration rate (GFR) are available. However, AKI diagnosis and classification should not be limited to GFR, but include tubular function and damage. Combining damage and stress biomarkers with functional markers enhances risk prediction, and identifies a population enriched for clinical trials targeting AKI. We review novel developments and aim to encourage implementation of these new techniques into clinical practice as a strategy for individualizing AKI treatment akin to a precision medicine-based approach.

Proenkephalin A as a marker for glomerular filtration rate in critically ill children: validation against gold standard iohexol GFR measurements.

Accurate determination of glomerular filtration rate (GFR) is important. Several endogenous biomarkers exist for estimating GFR, yet, they have limited accuracy, especially in the paediatric population. Proenkephalin A 119-159 (PENK) is a novel and promising GFR marker, but its relation with age in children remains unknown. Also, the value of PENK has never been validated against measured GFR (mGFR) in children when compared to traditional GFR markers including serum creatinine (SCr), SCr-based estimated GFR (eGFR) and cystatin C (cysC). Critically ill children and term-born neonates were included in this single-centre, prospective study. Iohexol-based mGFR, SCr, and cysC were determined in each patient. eGFR was calculated using the bedside Schwartz equation, incorporating SCr and height. Spearman correlation coefficients were calculated to determine the correlation between mGFR and PENK, SCr, cysC and eGFR. For 97 patients (56 children and 41 neonates), mGFR, SCr, cysC and PENK levels were available. PENK levels were higher in young children and decreased to adultPENK reference values around two years of age. PENK levels were highly correlated with mGFR (ρ=-0.88, p<0.001), and similar to mGFR-eGFR correlation (ρ=-0.87, p<0.001). For cysC and SCr the correlation with mGFR was lower (ρ=-0.77 and ρ=-0.46, respectively. Both p<0.001). The correlation of PENK with mGFR was as good as SCr-based eGFR-mGFR correlation. To determine the added value of PENK in paediatric clinical care and prior to implementation, PENK reference values are needed and the development and validation of a paediatric PENK-based eGFR equation is necessary.

Biological Effects of Zinc Oxide Nanoparticles on Biochemical Parameters in Diabetic Nephropathy

Diabetic nephropathy is the end stage renal disease that occurs as a result of diabetes. Cardiovascular and renal complications share common risk factors such as blood pressure, blood lipids, and glycemic control. Chronic kidney disease may predict cardiovascular disease in the general population. The impact of diabetes on renal impairment changes with increasing age. Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population, indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic people. The American Diabetes Association and the National Institutes of Health recommend Estimated glomerular filtration rate (eGFR) calculated from serum creatinine at least once a year in all people with diabetes for detection of kidney dysfunction. eGFR remains an independent and significant predictor after adjustment for conventional risk factors including age, sex, duration of diabetes, smoking, obesity, blood pressure, and glycemic and lipid control, as well as presence of diabetic retinopathy.

Cystatin C as a marker of the rapid development of the atherosclerosis in patients with diabetes mellitus and chronic kidney disease

Introduction. The relationship between kidney dysfunction and cardiovascular system is multifaceted. Thus, the value of such a potential marker of glomerular filtration rate (GFR) as cystatin C cannot be underestimated as a predictor of the development of cardiovascular complications and atherogenesis factor in diabetes mellitus (DM) and chronic kidney disease (CKD). Objective was to evaluate the role of cystatin C as an atherogenesis factor in patients with DM and CKD. Materials and methods. The study involved 514 patients aged 25 to 80 years (the group of interest (n=449), the control group (n=65)). All patients underwent clinical and laboratory tests, sonography of the lower extremities vessels and brachiocephalic arteries (BCA). Results. The thickness of the intima-media complex increased with an increase of cystatin C level in the right carotid artery (CA) (from 0.80 [0.70; 0.90] mm to 0.97 [0.90; 1.02] mm) and in the left CA (from 0.90 [0.80; 0.94] mm to 0.92 [0.90; 1.10] mm). Logistic regression analysis demonstrated that an increase of cystatin C level &gt; 0.93 mg/l raises the risk of intima-media thickening by 2.5 times (OR 2.505, p=0.042) and by 5 times when increase of cystatin C&gt;1.38 mg/l (OR 4.718, p=0.001). At the same time, the association with homocysteine was unreliable (p=0.058). The level of cystatin C ≥0.82 mg/l with a sensitivity of 72 % and a specificity of 52 % allowed to predict the development of subclinical atherosclerosis in patients with DM and CKD (ROC AUC – 0.739). Conclusion. Cystatin C is not only a highly sensitive and accurate indicator of GFR, capable of detecting early stages of renal dysfunction, but also a highly effective predictive marker of atherosclerotic process in patients with DM and CKD.

MO955: Serum Cystatin C in Renal Transplantation: Beyond GFR Estimation, A Prognosis Marker?

Abstract BACKGROUND AND AIMS In renal transplantation, death with a functioning graft remains one of the main causes of graft loss. In the general population, renal function impairment is strongly associated with cardiovascular and all-cause mortality. Whether this association holds true for kidney transplant recipients (KTR) is unclear. This uncertainty is likely to be due, in part, to the fact that glomerular filtration rate (GFR) estimation based on serum creatinine (SCr) does not always provide an accurate evaluation of the graft function in KTR. As compared to SCr, we have previously shown in a large cohort of KTR that serum cystatin C (SCysC) is a much better marker of GFR. Herein, we sought to study the ability of the 1-year-post-transplant renal function to predict all-cause mortality according to the methods used to assess GFR. METHOD Four hundred and ten consecutive KTR for whom a measurement of GFR by inulin clearance was available at 1 year post-transplant were included. SCr and ScysC were measured with standardized methods. The association of the 1-year inulin clearance value the 1-year MDRD Study equation value and the 1-year CKD-EPI ScysC equation value with all-cause mortality was studied by ROC analysis and Cox model. RESULTS During a median follow-up of 17 years, 131 KTR died. Mean (±SD) inulin clearance at 1-year-post-transplant was 47 (±13) mL/min/1.73 m2. Areas under the ROC curves were similar for inulin and CKD-EPI ScysC equation values (0.62 for both), and were both significantly superior to that of the MDRD equation (0.54, P &amp;lt; 0.01). In Cox analysis, while all types of GFR evaluations were significantly associated to graft loss, only an inulin and a CKD-EPI ScysC equation values below 45 mL/min/1.73 m2 were associated with an excess risk of mortality (HR of 1.55, 1.45 and 1.01 for inulin, CKD-EPI ScysC and MDRD, respectively). CONCLUSION We conclude that ScysC-based GFR estimation might better predict KTR outcome as compared with a traditional SCr-based estimation. The one year-post transplant GFR value given by the CKD-EPI ScysC equation should be further evaluated as a potential surrogate marker for both graft and patient survival.

Reflections on the KDIGO Definition of Acute Kidney Injury and Its Integration in the Concept of Acute Diseases and Disorders and Chronic Kidney Diseases

Acute kidney injury (AKI) describes a heterogeneous group of conditions, without specification of their etiology and diagnosed only by indirect markers of glomerular filtration rate (GFR), such as serum creatinine and urine output. Bedside estimation of GFR and detection of structural alterations with novel biomarkers, and stress tests have more recently been developed. These novel findings should probably be included in future AKI definitions. Chronic kidney disease (CKD) is defined by abnormalities in kidney function and structure that persist over &gt;3 months and is classified according to cause, GFR, and albuminuria. Acute kidney disease (AKD) is the term representing patients with abnormalities of function and structure with a duration of ≤3 months that fall outside the definitions of AKI or CKD. Since AKI is by definition also AKD, 2 types of AKD have been proposed, one with and one without AKI. AKD without AKI is common, often undetected, occurs frequently in the outpatient population and shows increased risk of CKD, ESKD and mortality. Alternatively, AKD has also been defined as the period of incomplete recovery following an AKI episode, the latter limited for the duration of 7 days. This contribution discusses the pros and cons of the existence of these 2 definitions of AKD.

Association of Serum Beta-Trace Protein Levels in Patients with Chronic Kidney Disease: A Case-control Study

Introduction: Chronic Kidney Disease (CKD) is common disorder showing decreased Glomerular Filtration Rate (GFR) value (&lt;60 mL/min/1.73 m2 ). Because of limitations of creatinine as a biomarker of GFR, new alternative biomarkers are being investigated, such as Beta-Trace Protein (BTP) is low molecular weight proteins that are filtered by the glomeruli. Serum BTP have been shown to be more helpful for estimating GFR. Aim: To assess the role of Beta-Trace Protein (BTP) as a potential biomarker of Chronic Kidney Disease (CKD) in comparison to serum urea, serum creatinine, fasting blood sugar and Creatinine Clearance Rate (CCR). Materials and Methods: This case-control study was conducted at Government Medical College, Rajouri, Jammu and Kashmir, India, from February 2021 to December 2021. Total 50 known patients of kidney diseases and 50 healthy individuals above the age of 18 years were enrolled in the study. Blood samples were collected from all individuals and serum BTP, serum urea level, serum creatinine level, fasting blood sugar were measured. Correlation of BTP with serum urea level, serum creatinine level, Fasting Blood Glucose (FBG) level, and CCR was calculated by Pearson Correlation test. Results: In present study, 50 patients in case groups (33 male and 17 females) and 50 healthy controls (25 males and 25 females) were included. Among controls, the mean age of patients was 52.12±5.66 years and among cases 55.94±10.51 years. BTP level was increased two times (from 32.06±11.25 µg/ml to 66.36±27.80 µg/ml) in CKD patients than controls individuals. BTP level was positively correlated with serum urea level, serum creatinine level, and FBG level while negatively correlated with CCR. Conclusion: BTP may be a useful and reliable serum marker for identifying the magnitude of renal dysfunction in patients with CKD and may have its place beside serum creatinine as an alternative endogenous GFR marker.

Cystatin c – a marker of kidney function and predictor of cardiovascular disease and mortality

Over the past decade, serum cystatin C (SCC) has been often suggested as a marker of kidney function. Strong evidence has shown that SCC may improve classification of the glomerular filtration rate (GFR) to identify chronic kidney disease in certain clinical populations. SCC equations based on the SCC reference standard are considered state–of–the–art to estimate kidney function and the latest chronic kidney disease guidelines included several suggestions and recommendations that relate to SCC. The results of several previous studies have also suggested that SCC may be more useful than just a marker of GFR, as it may also be useful as a clinical marker to provide complementary information to established risk determinants, especially for high–risk populations. Additionally, other studies have reported that SCC may be a useful prognostic indicator of cardiovascular disease.