Serum Creatinine Measurements Research Articles

Effects of Helianthus annuus seeds on antioxidants, lipid profile and serum urea and creatinine in obesity induced rats using high fat diet

High-fat diets have been strongly associated with common metabolic diseases. Clinical practices often link these diseases, such as hyperlipidemia and oxidative stress resulting from the accumulation of reactive oxygen species, to severe conditions like cancer, diabetes, atherosclerosis, and cardiovascular diseases. Managing these conditions is often financially demanding. Helianthus annuus seeds, known to be non-toxic even at doses greater than 5000mg/kg in rats, with an LD50 greater than 5000mg/kg, has demonstrated efficacy in reducing elevated blood sugar levels and BMI in both animal and human studies. Therefore, further research is needed to explore the potential effects of sunflower seeds on antioxidants, lipid profiles, and serum urea and creatinine levels in rats induced with obesity using a high-fat diet. In this study, overnight fasting blood samples were collected to conduct lipid profile tests (HDL, LDL, VLDL, and triglycerides). These tests utilized a photometric system with procedures derived from the Diasys-G Emmany kit and the measurement and precipitation method. The modified Jaffe technique for in-vitro measurement of creatinine in serum was employed to measure urea and creatinine levels. The experiment involved 27 Wistar rats weighing between 350 and 400 grams, randomly divided into 9 groups, with 3 rats in each group. Group 1 served as the control, while groups 2 to 9 were subjected to various conditions: high-fat diets alone for 6 weeks (group 2), high-fat diets with high (5000mg/kg body weight), medium (3000 mg/kg body weight), or low (2000 mg / kg body weight) doses of Helianthus annuus seeds powder for 6 weeks (groups 3, 4, and 5, respectively). Additionally, there were variations in duration and doses in groups 6 to 9, where rats were fed high-fat diets 20 g/ kg / day /rats for 5 weeks and then supplemented with Helianthus annuus seeds powder (5000 mg / kg, 3000 mg / kg and 2000 mg / kg per rat for group 6,7,8 or Metformin 70 mg / kg per rat for group 9) for 1 week. The results revealed a significant (P < 0.05) increase in serum cholesterol, triglyceride, and low-density lipoprotein (LDL) levels in rats across all groups compared to the control. However, all groups supplemented with Helianthus annuus seeds alongside high-fat diets displayed a significantly increased HDL level (P < 0.05) compared to rats fed only high-fat diet alone. Creatinine levels were significantly increased in all Helianthus annuus seeds -supplemented groups compared to the high-fat diet alone, while urea levels showed no significant differences among the groups. Furthermore, rats in all Helianthus annuus seeds -supplemented groups alongside high-fat diets demonstrated a significantly increased glutathione reductase activity (P < 0.05) compared to the control and high-fat diet alone. The study indicated that sunflower seeds significantly bolster antioxidant protection, elevate HDL levels, and increase creatinine levels in rats fed high-fat diets, suggesting potential beneficial effects in mitigating the adverse impacts of high-fat diets on health parameters.

#2514 Clinical impact of the CKD-EPI 2021 versus the CKD-EPI 2012 formula on GFR estimation and CKD prevalence: results from a Dutch routine-care cohort

Abstract Background and Aims Quantifying the kidney function is crucial for diagnosing and monitoring kidney disorders in clinical practice. Recently, the CKD-EPI 2021 formula was developed for estimating glomerular filtration rate (eGFR), excluding the ethnicity variable. In this study, we aimed to analyze the impact in a Dutch routine-care cohort of introducing the new serum creatinine-based CKD-EPI 2021 formula on glomerular kidney function estimation and the prevalence of chronic kidney disease (CKD), compared to the now used CKD-EPI 2012 formula. Method All patients of 18 years and older of whom serum creatinine was measured between January 2013 and December 2023 at the University Medical Center Utrecht in the Netherlands, were included. Differences in the eGFR measured with the CKD-EPI 2012 formula and the new CKD-EPI 2021 formula were defined as median difference, stratified by gender, age categories, and CKD stages. Results 251.960 patients with 2.312.313 serum creatinine measurements were included in our analysis. Our findings indicate that the CKD-EPI 2021 formula results in a higher eGFR compared to the CKD-EPI 2012 formula (median +3.6 (Inter quartile range (IQR) 2.4 to 4.5) ml/min/1.73 m2 in men, and median +3.1 (IQR 2.0 to 4.0) ml/min/1.73 m2 in women). In total, 21.1% of the patients with CKD stage 2-5 according to the CKD-EPI 2012 formula were classified as having a better CKD stage using the new CKD-EPI 2021 formula; 26.1%, 20.5%, and 15.1% of the patients classified as having CKD stage 3A, 3B, and 4 were classified as having CKD stage 2, 3A, and 3B, respectively (Table 1). Conclusion The introduction of the CKD-EPI 2021 formula would have significant implications for kidney function estimation in the Dutch clinical setting. It is crucial to consider these differences when interpreting kidney function data and making clinical decisions, especially given the potential impact on diagnosing CKD and dosing medication.

#848 Influence of nutrition and other factors on preterm newborns’ kidney development

Abstract Background and Aims According to WHO, in 2020, preterm newborns represented around 10% of all newborns in the world. Premature birth is deeply connected with the risk of developing a chronic kidney disease later in life. This is caused by defects in kidney development (primarily the lower number of nephrons) that are often difficult to identify in the complicated clinical picture of premature babies. Our study aims at providing knowledge on the relationship between preterm infant kidney development and morbidities, nutrition, and blood biomarkers. Method Creatinine was measured in 130 extremely preterm newborns (less than 28 weeks of gestation) enrolled in a randomized controlled trial (Mega Donna Mega) in two Swedish neonatal intensive care units. Creatinine was measured in whole blood or serum with the enzymatic method. Individuals with 4 or more serum creatinine measurements (n = 92) were shortlisted for eGFR calculation. eGFR was calculated with the Wilhelm-Bals weight-based equation due to the lack of length measurements. The patients were divided in 3 groups based upon their kidney development status. This was indirectly assessed using the exponential regression curve describing the eGFR trends as model and the doubling time as discriminating parameter. Data about morbidity, treatment, nutrition, blood lipidomics and proteomics were also collected during the MegaDonnaMega trial and has been used to investigate the differences between the three groups. A linear model adjusted for sex and gestational age was used to analyse lipidomics and proteomics data in relation to eGFR. The omics analysis used average data from the first month of age. Data analysis was performed in R, SPSS, SAS and GraphPad statistical programs. Results Subjects were divided in 3 groups from best to worst kidney function development. The parameter used, doubling time, is inversely correlated to eGFR and kidney development. Subjects in group 1 reached the normal at-term birth eGFR (40 ml/min/1.73 m2) at around 50 days of age, whereas the other two groups were delayed (66 days for group 2, 78 for group 3). Subjects in group 2 and 3 were characterized by longer stay at the NICU, lower weight and length in respect to infants in group 1. Subjects in groups 2 and 3 also showed more co-morbidities in respect to group 1. Regarding nutrition, subjects administered with maternal milk had shorter doubling times when compared to those administered with donor or mixed milk. Six serum fatty acids correlated with the eGFR trends: heptadecanoic (FA 17:0) showed a negative correlation, while palmitoleic (16:1n-7), gamma-linolenic (18:3n-6), erucic (22:1n-9) docosapentaenoic (22:5n-6) and tricosanoic (23:0) acid showed positive correlations. 45 serum proteins correlated with the eGFR trends, in particular, inflammatory and proliferative pathways showed an inverse correlation with eGFR. Conclusion We have detected differences in the eGFR trends of preterm newborns that could be traced back to nutrition and other factors. Moreover, we identified several serum fatty acids and proteins that correlated with eGFR and therefore kidney development. The data indicates that postnatal kidney development may be important to consider in the clinical care of preterm newborns.

#1515 Myocardial remodeling is associated with redistribution of phosphate, PIT1/ERK1/2 up-regulation and signaling pathways alterations in mild CKD model

Abstract Background and Aims Patients with CKD have significantly increased cardiovascular risk, and heart failure is a leading cause of morbidity and mortality in these patients. Myocardial hypertrophy is a hallmark of cardiac remodeling and dysfunction in CKD and is known to be mediated by angiotensin II, catecholamines, hyperphosphatemia, hyperparathyroidism, increase in FGF23, decrease in Klotho and alterations in various signaling pathways including calcineurin, mitogen-activated protein kinase ERK1/2, calmodulin-dependent protein kinase II etc. Less well understood are the mechanisms of fibrosis and intramyocardial arterial remodeling in CKD, which may be related to hyperphosphatemia and decreased renal and systemic Klotho. The aim of this study was to evaluate the molecular and cellular features of myocardial remodeling in experimental mild CKD. Method We induced CKD by 3/4 nephrectomy (Nx) in adult male spontaneously hypertensive rats (SHR) with a follow-up period of 4 months. Animals were fed standard chow containing 0.6% phosphate. Sham-operated Wistar rats and SHR served as controls. We measured serum creatinine, renal interstitial fibrosis area, systolic blood pressure (BP), myocardial mass index (MMI), histological indices of myocardial hypertrophy, interstitial fibrosis and intramyocardial artery (IA) remodeling (H&E, Masson's trichrome, von Kossa stain), myocardial phosphorus content, serum levels of inorganic phosphate (Pi), PTH and FGF23. Myocardial expression of phosphate transporters PiT1, ERK1/2, WNT, BMP, Notch, Hedgehog signaling pathways and LRG4 molecules was evaluated by PCR-RT, IHC and IF (Zeiss LSM 710; study performed at the Centre for Collective Use “Confocal Microscopy” of the Pavlov Institute of Physiology, Russian Academy of Sciences). Results Chronic kidney injury and phosphate regulatory factors did not differ, whereas BP and MMI were higher in sham SHR vs. Wistar rats (Fig. 1). Nx rats showed features of mild chronic kidney injury before the elevation of serum PTH, FGF23 levels (Fig. 1). Myocardial P content and serum Pi were higher in Nx and in the combined SHR group and directly correlated with indices of IA remodeling. Cardiomyocyte diameter, myocardial interstitial and perivascular fibrosis were higher in Nx (Figs 1, 2a) and accompanied with upregulation in Ppp3ca mRNA (calcineurin A, Fig. 2b), Mapk1 mRNA (ERK2, Fig. 2b), phospho-ERK1/2 (Figs 1, 3), PiT1 (Figs 1, 2c), Lgr4 (Fig. 2c) and downregulation of Hes1 mRNA (Fig. 2b). PiT1 and pospho-ERK1/2 were co-expressed in IA media from SHR (Fig. 2c). In Nx, nestin and LGR4 were expressed by IA adventitia and media cells, myocardial interstitial cells, and occasionally co-localized (Fig. 2c). Hes1 expression was detected in IA and capillary endothelial cells and co-localised with Gli1 in IA media; Gli1 was also detected in cardiomyocyte nuclei (Fig. 2c). In SHR, beta-catenin expression in cardiomyocytes was more pronounced in Nx (Fig. 2c). Conclusion Mild CKD is associated with histological and molecular features of cardiomyocyte hypertrophy, myocardial fibrosis and intramyocardial arterial remodeling, which are probably modulated by phosphate redistribution and its tissue retention involving upregulation of PiT1 and ERK1/2, as well as alterations in signals related to progenitor regulation and myocyte hypertrophy.

#501 Evaluation of the accuracy of serum creatinine-based GFR calculations across the different levels of renal function among Filipinos

Abstract Background and Aims Chronic kidney disease (CKD) is a worldwide health concern which continues to increase in prevalence. Early studies have evaluated kidney function by measuring serum creatinine (sCr) and/or the estimated glomerular filtration rate (eGFR). To date, there are limited studies that correlate nuclear GFR scans and eGFR by equations that include the Cockroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) 2021 in Asians, specifically in a Filipino population. This study aims to compare the accuracy of GFR scan results and GFR estimated from the formulas across different levels of kidney functions, age groups, gender, and co-morbidities among a Filipino subset. Method A cross-sectional study was done among 2986 patients who underwent Nuclear GFR scan in a single kidney center. Results obtained were compared to estimated GFR results. Weighted Kappa and Bland-Altman Analyses were used to test for agreement between the measured and estimated GFR results. Results Absolute GFR values derived from the three equations demonstrated moderate reliability with results from nuclear scan when intraclass correlation coefficients were calculated with CKD-EPI 2021 being the highest. When further categorized into GFR levels, there was substantial level of agreement between each equation and GFR scan, with all weighted kappa coefficients being at least 0.700 with CG having the highest result (Table 1). Furthermore, when subgroup analysis was done according to age group, gender, and comorbidities, CG was found to be the most accurate per category (Table 2). Conclusion CKD-EPI 2021 was the most accurate in the actual GFR values however we cannot fully eliminate the utility of CG due to its categorical accuracy and in monitoring the deterioration of renal function.

#2333 Risk of NDI and CKD in individuals treated with lithium

Abstract Background and Aims Nephrogenic diabetes insipidus (NDI) is a known side effect of lithium treatment. Lithium has also been associated with the development of chronic kidney disease (CKD). The aims of this study were to examine the risk factors for NDI among persons on lithium treatment and the association of NDI and other risk factors with the development of chronic kidney disease (CKD). Method This was a retrospective cohort study of all persons in Iceland using lithium in the years 2003-2018. Lithium exposure was defined as at least one lithium prescription or at least one serum lithium measurement with a detectable lithium level. Patients with affective disorders (ICD-10 codes F30-F39) attending the outpatient clinics of Landspitali–The National University Hospital Mental Health Services in 2014-2016, without lithium exposure, served as controls. NDI was defined as concomitant serum sodium (SNa) >144 mmol/L and urine specific gravity (SG) <1.005; individuals with no SNa measurement after 2003 were excluded from the analysis. CKD stages 3-5 were defined according to the KDIGO guidelines for CKD as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. The eGFR was calculated from serum creatinine (SCr) using the CKD-EPI equation. The analysis of incident CKD was limited to the period when standardized SCr measurements had become available, in 2008-2018. Individuals with <2 SCr measurements after 2008 and those with CKD stages 3-5 before 2008 were excluded. In addition, this analysis specifically examined the relationship between the mean serum lithium concentration and the development of CKD, comparing those not exposed to lithium to 3 groups of lithium users with a mean serum lithium concentration of 0.3-0.59, 0.6-0.79 and 0.8-0.99 mmol/L. Acute kidney injury (AKI) was defined according to the SCr component of the KDIGO criteria for AKI, and other comorbid conditions were defined based on ICD-9 and ICD-10 diagnosis codes. Multivariable Cox regression with time-dependent covariables was used for risk assessment. Results In the analysis of the development of NDI, the group exposed to lithium consisted of 2252 individuals, of whom 58 (2.6%) met the criteria for NDI compared with 13 (1.0%) of the 1272 controls. When compared with those without lithium exposure. the risk of NDI was lithium concentration dependent, with a hazard ratio (HR) of 1.22 (95% CI, 0.50–2.98), 5.52 (95% CI, 2.81–10.85) and 10.03 (95% CI, 4.51–22.27) for groups with a mean lithium concentration of 0.3–0.59, 0.6–0.79 and 0.8–0.99 mmol/L, respectively. A previous diagnosis of CKD was also a significant risk factor (HR 3.00 [95% CI, 1.50–6.12]). In the CKD analysis, the group of lithium users comprised 1401 individuals. Of those, 192 (13.7%) developed CKD, compared with 39 (2.8%) of the 1406 controls. Analysis adjusted for initial eGFR showed that NDI was a significant risk factor for CKD (HR 1.90 [95% CI, 1.03-3.54]). Other significant risk factors were mean lithium concentration with HR of 1.25 (95% CI, 0.82–1.91), 2.84 (95% CI, 1.94–4.15) and 5.11 (95% CI, 3.22–8.07) for the groups with a mean lithium concentration of 0.6–0.79 and 0.8–0.99 mmol/L, respectively. Other significant risk factors were age per year (HR 1.03 [95% CI, 1.02–1.05]), diabetes (HR 1.62 (95% CI, 1.08–2.46]) and history of AKI (HR 1.92 [95% CI, 1.33–2.77]). Conclusion Lithium use is associated with NDI in a concentration-dependent manner. Long-term lithium treatment is associated with a risk of CKD, which also is concentration dependent, in patients with bipolar and unipolar mood disorders. NDI may be an important risk factor for CKD.

#1920 The impact of kidney function on cardiac diastolic dysfunction trajectories: insights from a longitudinal study

Abstract Background and Aims Although the association between kidney dysfunction and cardiac diastolic dysfunction has been investigated in cross-sectional studies, we currently lack a complete understanding of how the diastolic dysfunction changes over time in individuals with different kidney functions. Exploring the diastolic dysfunction trajectories is crucial as it can provide valuable insights into how kidney function influences cardiac health and which patients are at the highest cardiovascular risk. E/e’ is an echocardiography measure that estimates left ventricular filling pressure and diastolic dysfunction. This study evaluates how kidney function impacts changes in E/e′ over time. Method We identified patients from the Utrecht Patient Oriented Database (UPOD) who visited the outpatient clinic of Utrecht University Medical Center between January 2012 and April 2022. Patients who had received at least three echocardiography reports with a minimum of 12 months between them and had recorded serum creatinine measurements in their electronic health records were included. The estimated glomerular filtration rate (eGFR [mL/min/1.73 m2]) was calculated using the CKD-EPI 2021 creatinine formula without ethnicity and categorized as follows: eGFR ≥ 90, eGFR ≥ 60 - <90, eGFR < 60. Linear mixed-effect models were utilized to determine the impact of kidney function on changes in E/e′ over time. Results A total of 436 patients were included of whom 34.7% were women. The total number of echocardiography examination was 1308. Overall, the median eGFR for all patients was 78.2 mL/min/1.73 m2 [IQR: 61.9, 90.7]. Among them, 26.6%, 51.4%, and 22.0%, had an eGFR ≥ 90, eGFR ≥ 60 - < 90, and eGFR < 60, respectively. Patients with an eGFR < 60 had a higher prevalence of hypertension (64.6%) and cardiovascular disease (84.4%) compared to those with an eGFR ≥ 90, where the prevalence of hypertension and cardiovascular disease was 49.1% and 67.2%, respectively. Additionally, patients with an eGFR < 60 had the lowest mean ejection fraction of 44.9% ± 18.5% and the highest median E/e′ of 12.84 [10.10, 16.16]. The linear mixed model analysis showed that the estimated change in E/e′ per year depended on the level of kidney function. For patients with eGFR ≥ 60 - <90, E/e′ did not significantly change per year (p-value: 0.927). However, for patients with eGFR < 60, a statistically significant (p = 0.014) increase in the E/e′ of 0.45 (0.09, 0.81) was observed per year. Hypertension, diabetes mellitus, and cardiovascular disease were found to affect the change in E/e′, with estimates of 0.95 (0.41, 1.49), 1.82 (0.82, 2.89), and 1.25 (0.54, 1.97), respectively. Conclusion The trajectory of changes in E/e′ over time was significantly affected by varying levels of kidney function. Patients with impaired kidney function (eGFR < 60) have a higher E/e’ compared to those with normal kidney function (eGFR ≥ 90) and presented a significant increase of E/e’ per year.

Evaluation Of Biomarker-Based GFR Estimating Equations in Glomerular Disease

Introduction: Glomerular filtration rate (GFR) is typically estimated with equations that use biomarkers such as serum creatinine and/or cystatin-C. The impact of these different biomarkers on GFR estimates in glomerular disease patients is unclear. In this study, we compared the different GFR estimating equations in the Cure Glomerulonephropathy (CureGN) cohort of children and adults with glomerular disease. Methods: All available cystatin-C measurements from CureGN study participants were matched to same-day serum creatinine measurements to estimate GFR. To explore the strength of agreement between eGFR values obtained from the "Under 25” (U25) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations, we used intraclass correlation coefficients. Multivariable linear mixed effects models were used to determine which factors were independently associated with differences in eGFR values. Results: A total of 928 cystatin-C measurements were matched to same-day serum creatinine measurements from N=332 CureGN study participants (58% male, 69% White/Caucasian, 20% Black/African American). Among 628 measurements collected while study participants were under 25 years old, there was moderate agreement (0.731) in serum creatinine vs. cystatin-C U25 equations. Models showed that higher eGFR values were associated with larger differences between the two equations (p <0.001). Among 253 measurements collected while study participants were at least 18 years old, there was excellent agreement (0.891-0.978) among CKD-Epi equations using serum creatinine alone, cystatin-C alone, or the combination of both. Younger age was associated with larger differences between CKD-Epi equations (p=0.06 to p=0.016). Conclusion: Excellent agreement between CKD-Epi equations indicates continued use of serum creatinine only for GFR estimation could be appropriate for adults. In contrast, only moderate agreement between U25 equations indicates a need for more frequent measurement of cystatin-C among children and young adults, especially as eGFR increases.

Laboratory-based surveillance of chronic kidney disease in people with private health coverage in Brazil

BackgroundAlthough approximately 25% of Brazilians have private health coverage (PHC), studies on the surveillance of chronic kidney disease (CKD) in this population are scarce. The objective of this study was to estimate the prevalence of CKD in individuals under two PHC regimes in Brazil, who total 8,335,724 beneficiaries.MethodsOutpatient serum creatinine and proteinuria results of individuals from all five regions of Brazil, ≥ 18 years of age, and performed between 10/01/2021 and 10/31/2022, were analyzed through the own laboratory network database. People with serum creatinine measurements were evaluated for the prevalence and staging of CKD, and those with simultaneous measurements of serum creatinine and proteinuria were evaluated for the risk category of the disease. CKD was classified according to current guidelines and was defined as a glomerular filtration rate (GFR) < 60 ml/min/1.73 m² estimated by the 2021 CKD-EPI equation.ResultsThe number of adults with serum creatinine results was 1,508,766 (age 44.0 [IQR, 33.9–56.8] years, 62.3% female). The estimated prevalence of CKD was 3.8% (2.6%, 0.8%, 0.2% and 0.2% in CKD stages 3a, 3b, 4 and 5, respectively), and it was higher in males than females (4.0% vs. 3.7%, p < 0.001, respectively) and in older age groups (0.2% among 18-29-year-olds, 0.5% among 30-44-year-olds, 2.0% among 45-59-year-olds, 9.4% among 60-74-year-olds, and 32.4% among ≥ 75-year-olds, p < 0.001) Adults with simultaneous results of creatinine and proteinuria were 64,178 (age 57.0 [IQR, 44.8–67.3] years, 58.1% female). After adjusting for age and gender, 70.1% were in the low-risk category of CKD, 20.0% were in the moderate-risk category, 5.8% were in the high-risk category, and 4.1% were in the very high-risk category.ConclusionThe estimated prevalence of CKD was 3.8%, and approximately 10% of the participants were in the categories of high or very high-risk of the disease. While almost 20% of beneficiaries with PHC had serum creatinine data, fewer than 1% underwent tests for proteinuria. This study was one of the largest ever conducted in Brazil and the first one to use the 2021 CKD-EPI equation to estimate the prevalence of CKD.

Kidney Measurement and Glomerular Filtration Rate Evolution in Children with Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron, and over time the cystic dilatation leads to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts leads to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and hematuria. However, the presentation of ADPKD varies in children, from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by a mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end-stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra-normal kidney function, we explored the glomerular filtration rates dynamics and the renal ultrasound-adjusted percentiles. In total, 14 out of 16 patients had kidney percentiles over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 mL/min/1.73 m2 when compared to Schwartz eGFR 126.28 ± 33.07 mL/min/1.73 m2, p = 0.14). Also, when the quadratic equation was employed, not even a single patient reached the glomerular hyperfiltration threshold. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1 year of follow-up (quadratic ΔeGFR = -0.32 ± 5.78 mL/min/1.73 m2), as opposed to the Schwartz formula that can falsely classify children in a hyperfiltration state (ΔeGFR = 7.51 ± 19.46 mL/min/1.73 m2), p = 0.019.

N1F(Improved-Nephropathy 1 Formula) Ameliorates Renal Interstitial Fibrosis via Inhibiting Extracellular Matrix Deposition and Regulating the FGF23/P38MAPK/Wnt Pathway.

Renal fibrosis is the primary pathway in the progression of chronic kidney disease (CKD) towards end-stage renal failure. The currently used drugs currently are ineffective, and their mechanisms of action remain unclear. This study aims to investigate the nephroprotective effect of Improved-Nephropathy 1 Formula (N1F) in a rat model of unilateral ureteral obstruction (UUO) and explore the potential mechanisms of N1F-containing serum in treating TGF-ß1-induced human renal tubular epithelial cells (HK-2). SD rats received 2-week continuous N1F gavage starting on day 2 after UUO. HK-2 cells were pretreated with a P38MAPK inhibitor for 1 h in vitro, followed by induction of the cells with TGF-ß1 and treatment with N1F 48 h later. The chemical composition of N1F was analyzed using high-performance liquid chromatography-Q-Orbitrap high-resolution liquid mass spectrometry. Renal function was assessed by measuring serum creatinine (Scr), blood urea nitrogen (BUN) and urine protein (Upro) levels. Hematoxylin and eosin (HE) and Masson's trichrome (Masson) staining were used to evaluate the extent of renal tissue damage and fibrosis. Western blotting, immunohistochemistry, and immunofluorescence were used to detect the protein levels of relevant indices. The RNA levels of the relevant indices were detected using real-time fluorescence quantitative PCR (RT-qPCR). We identified 361 chemical components in the water extract of N1F. These chemical components of N1F significantly reduced the area associated with interstitial fibrosis in the kidneys of UUO rats and the levels of serum creatinine, urea nitrogen, and urinary protein. Additionally, N1F decreased the protein levels of FGF23, Wnt1, ß-catenin and p-P38MAPK/P38MAPK, along with the expression of renalfibrosis-associated proteins, α-SMA, FN, Collagen III, and Vimentin in the renal tissues of the UUO rats, while enhancing klotho and DKK1 protein levels. In vitro experiments revealed that inhibition of P38MAPK signaling significantly suppressed the expression of proteins related to the Wnt signaling pathway, with a concomitant decrease in the expression of FGF23 and an increase in the expression of Klotho. Notably, the P38MAPK inhibitor (SB203580) had similar effects to N1F in altering the above-mentioned indices in vitro. N1F may exhibit potential therapeutic efficacy against renal fibrosis by inhibiting the FGF23/P38MAPK/Wnt signaling pathway, consequently inhibiting extracellular matrix deposition due to renal injury.

Associations between long-term exposure to air pollution and kidney function utilizing electronic healthcare records: a cross-sectional study

BackgroundChronic kidney disease (CKD) affects more than 38 million people in the United States, predominantly those over 65 years of age. While CKD etiology is complex, recent research suggests associations with environmental exposures.MethodsOur primary objective is to examine creatinine-based estimated glomerular filtration rate (eGFRcr) and diagnosis of CKD and potential associations with fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) using a random sample of North Carolina electronic healthcare records (EHRs) from 2004 to 2016. We estimated eGFRcr using the serum creatinine-based 2021 CKD-EPI equation. PM2.5 and NO2 data come from a hybrid model using 1 km2 grids and O3 data from 12 km2 CMAQ grids. Exposure concentrations were 1-year averages. We used linear mixed models to estimate eGFRcr per IQR increase of pollutants. We used multiple logistic regression to estimate associations between pollutants and first appearance of CKD. We adjusted for patient sex, race, age, comorbidities, temporality, and 2010 census block group variables.ResultsWe found 44,872 serum creatinine measurements among 7,722 patients. An IQR increase in PM2.5 was associated with a 1.63 mL/min/1.73m2 (95% CI: -1.96, -1.31) reduction in eGFRcr, with O3 and NO2 showing positive associations. There were 1,015 patients identified with CKD through e-phenotyping and ICD codes. None of the environmental exposures were positively associated with a first-time measure of eGFRcr < 60 mL/min/1.73m2. NO2 was inversely associated with a first-time diagnosis of CKD with aOR of 0.77 (95% CI: 0.66, 0.90).ConclusionsOne-year average PM2.5 was associated with reduced eGFRcr, while O3 and NO2 were inversely associated. Neither PM2.5 or O3 were associated with a first-time identification of CKD, NO2 was inversely associated. We recommend future research examining the relationship between air pollution and impaired renal function.

Alzheimer's disease cerebrospinal fluid biomarkers and kidney function in normal and cognitively impaired older adults.

Recent Alzheimer's disease (AD) clinical trials have used cerebrospinal fluid (CSF) biomarker levels for screening and enrollment. Preliminary evidence suggests that AD risk is related to impaired renal function. The impact of kidney function on commonly used AD biomarkers remains unknown. Participants in studies conducted at the Goizueta Alzheimer's Disease Research Center (N=973) had measurements of serum creatinine and CSF AD biomarkers. General linear models and individual data were used to assess the relationships between biomarkers and eGFR. Lower estimated glomerular filtration rate (eGFR) was associated with lower amyloid beta (Aβ)42/tau ratio (p<0.0001) and Aβ42 (p=0.002) and higher tau (p<0.0001) and p-tau (p=0.0002). The impact of eGFR on AD biomarker levels was more robust in individuals with cognitive impairment (all p-values were<0.005). The association between eGFR and CSF AD biomarkers has a significant impact that varies by cognitive status. Future studies exploring this impact on the pathogenesis of AD and related biomarkers are needed. There is a significant association between Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers and both estimated glomerular filtration rate (eGFR) and mild cognitive impairment (MCI).Kidney function influences CSF biomarker levels in individuals with normal cognitive function and those with MCI.The impact of kidney function on AD biomarker levels is more pronounced in individuals with cognitive impairment.The variation in CSF tau levels is independent of cardiovascular factors and is likely directly related to kidney function.Tau may have a possible role in both kidney and cognitive function.

Global Validation of a Model to Predict Reduced Estimated GFR in People With Type 2 Diabetes Without Diagnosis of CKD

IntroductionA UK-developed minimal-resource pre-screening model for predicting reduced kidney function amongst people with type 2 diabetes and no diagnosis of chronic kidney disease (stage 3-5) was previously developed. This study aims to evaluate the performance of the model on a global population and assess its adequacy with and without regional adjustment. MethodsA retrospective observational study was performed using data collected in the iCaReMe global registry (NCT03549754) and the DISCOVER study (NCT02322762; NCT02226822). Patients were grouped by their World Health Organization classified region. An estimated glomerular filtration rate (eGFR) below 60 was the marker of reduced kidney function. A regional intercept re-calibration was applied to adjust for regional variation. Discrimination and calibration were evaluated for the UK-developed and re-calibrated models. ResultsA total of 14180 patients (46 countries, 6 regions) were identified with type 2 diabetes, no previous diagnosis of CKD and had a serum creatinine measurement or eGFR recorded. The UK-model underestimated risk when applied globally and was deemed inadequate. The model with regional-adjustment achieved the target sensitivity (80.5%; 95% CI: 78.8% - 82.3%) and demonstrated a relative improvement of 51.5% (95% CI: 48.1% - 55.1%) in the positive predictive value, compared to a screen-all approach. ConclusionsThe regional-adjusted model demonstrated adequate performance globally. Incorporating the model within practice could help clinicians to risk-stratify and prioritise patients at high risk. This could enable improved efficiency via risk-tailored screening, particularly in lower-to-middle income countries.

Features of structural and geometric cardiac remodeling in patients with diabetes mellitus depending on chronic kidney disease stages

Objective. To study the features of structural and geometric cardiac remodeling in patients with diabetes mellitus (DM) depending on the stage of chronic kidney disease (CKD). Materials and methods. We examined 499 patients (127 men and 322 women) with type 1 DM (133 people) and type 2 DM (316 people) aged 62 [52;69] years. The comparison group consisted of 65 randomly selected volunteering individuals (54 women and 11 men) without disorders of carbohydrate metabolism and kidney damage aged 59 [46;66] years. The laboratory examination of the patients included the measurement of serum creatinine, eGFR according to the CKD-EPI equation. An echocardiographic investigation was performed to study structural and geometric heart parameters. Left ventricular hypertrophy (LVH) was diagnosed when the left ventricular myocardial mass index (LVMI) exceeded 115 g/m2 in men and 95 g/m2 in women. Results. LVH was detected in 57.7 % of patients with DM, while in the comparison group – in 35.4 %. The frequency of LVH increased with a decrease in eGFR and was diagnosed in 100 % of cases with CKD 5. In patients with DM, the left ventricular concentric remodeling significantly predominated (29.2%). Multiple linear regression analysis demonstrated the influence of age (ß=0.30, p=0.01) and serum creatinine (ß = 0.15, p &lt; 0.0001) on the LVMI, independent of other factors, which confirms their independent pathogenetic significance. Conclusion. Thus, patients with DM regardless of the CKD stage have structural and functional changes in the LV myocardium. Regardless of the nitrogen-excretion function of the kidneys, the predominant pattern of LV remodeling is concentric. The study of the features of structural and functional restructuring of the left heart in patients with diabetes should be taken into account in determining the cardiovascular prognosis.

Development of a formula for estimated glomerular filtration rate in pregnant women from physiological hyperfiltration of serum creatinine

Increased body fluids during pregnancy complicates the application of estimated glomerular filtration rate (eGFR) formulas that are based on body surface area. Furthermore, gestational renal dysfunction cannot be identified if the serum creatinine (SCr) concentration is within the non-pregnant reference interval (RI) despite inadequate pregnancy-related renal hyperfiltration. 1484 SCr measurements from 957 healthy pregnant women were collected. The average SCr value of gestational week (GW) 0–3 was the representative SCr value of non-pregnant status. While the distribution of SCr measurements varied across GWs, it was transformed into a normal distribution using the bootstrap resampling method. A polynomial linear regression method was applied to achieve a continuous and smooth transformation of values. The normally distributed SCr values of each GW were compared to the non-pregnant status, leading to the calculation of SCr hyperfiltration. The final equation, (2 − SCr (μmol/L)/\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$/$$\\end{document}55.25)×\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ imes$$\\end{document} 103.1 ×\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ imes$$\\end{document} 55.25/(56.7 − 0.223 ×\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ imes$$\\end{document} GW − 0.113 ×\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ imes$$\\end{document} GW2+\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$+$$\\end{document} 0.00545 ×\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ imes$$\\end{document} GW3 − 0.0000653 ×\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ imes$$\\end{document} GW4), and reference intervals for both SCr and eGFR for each GW were obtained. These RIs and novel equations can be effectively used to monitor renal dysfunction in pregnant women.

Relationships between the Structural Characteristics of General Medical Practices and the Socioeconomic Status of Patients with Diabetes-Related Performance Indicators in Primary Care.

The implementation of monitoring for general medical practice (GMP) can contribute to improving the quality of diabetes mellitus (DM) care. Our study aimed to describe the associations of DM care performance indicators with the structural characteristics of GMPs and the socioeconomic status (SES) of patients. Using data from 2018 covering the whole country, GMP-specific indicators standardized by patient age, sex, and eligibility for exemption certificates were computed for adults. Linear regression models were applied to evaluate the relationships between GMP-specific parameters (list size, residence type, geographical location, general practitioner (GP) vacancy and their age) and patient SES (education, employment, proportion of Roma adults, housing density) and DM care indicators. Patients received 58.64% of the required medical interventions. A lower level of education (hemoglobin A1c test: β = -0.108; ophthalmic examination: β = -0.100; serum creatinine test: β = -0.103; and serum lipid status test: β = -0.108) and large GMP size (hemoglobin A1c test: β = -0.068; ophthalmological examination β = -0.031; serum creatinine measurement β = -0.053; influenza immunization β = -0.040; and serum lipid status test β = -0.068) were associated with poor indicators. A GP age older than 65 years was associated with lower indicators (hemoglobin A1c test: β = -0.082; serum creatinine measurement: β = -0.086; serum lipid status test: β = -0.082; and influenza immunization: β = -0.032). Overall, the GMP-level DM care indicators were significantly influenced by GMP characteristics and patient SES. Therefore, proper diabetes care monitoring for the personal achievements of GPs should involve the application of adjusted performance indicators.

Modulation of Stem Cell Factor by Forskolin Inhibits the Progression of Tubule Interstitial Fibrosis

Purpose Forskolin is primarily found in the roots of the Coleus forskohlii plant, historically employed in Southeast Asian and Indian Ayurvedic medicine. Mast cells play a crucial role in fibrosis progression, yet their activation and inhibition in animal models are understudied; thus, we explored forskolin’s impact on kidney fibrosis. Materials and Methods Forskolin was evaluated in a mouse model for stem cell factor-induced histamine release, and plasma histamine levels were measured using the enzyme-linked immunosorbent assay. Kidney fibrosis was developed by unilateral ureteral obstruction (UUO). Renal function was assessed by spectrophotometric measurements of serum blood urea nitrogen (BUN) and creatinine. The gene expression of collagen, transforming growth factor-beta (TGF-β), α-smooth muscle actin (α-SMA), interleukin-1 beta (IL-1β), and mast cell protease-5 (MCPT-5) in the kidney was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Histopathological changes in the renal tissues were examined by hematoxylin and eosin (H&amp;E) and Masson’s trichome stain. Results Our results showed that 3 mg/kg forskolin inhibited SCF-induced plasma histamine release in a mouse model. In the 7-day UUO model, forskolin significantly showed inhibition of serum creatinine and blood urea nitrogen compared with the disease group. Forskolin significantly inhibited elevated expression of collagen, TGF-β, α-SMA, IL-1β, and MCPT-5 in the kidneys. Histopathological observation of H&amp;E and Masson trichome-stained kidney forskolin demonstrated a reduction in inflammatory cells, pelvic and tubular dilation, and fibrosis. Conclusion Forskolin showed an anti-fibrotic effect in UUO-induced renal fibrotic mice. Most significantly, forskolin administration showed a decrease in the expression of the mast cell protease MCPT5 in the kidneys. These results imply that forskolin, through modifying SCF activity, may be a viable potential treatment for the attenuation of tubule-interstitial fibrosis.

Renal dysfunction caused by severe hypothyroidism diagnosed by renal biopsy: a case report.

There is a close relationship between thyroid dysfunction and renal dysfunction. However, thyroid dysfunction can unfortunately result in inaccurate measurements of serum creatinine and cystatin C levels. The chronic decrease in cardiac output due to hypothyroidism can reduce renal plasma flow (RPF) resulting in renal dysfunction. We report the case of a 36-year-old male in whom renal dysfunction detected during a company health check-up was found to be caused by severe hypothyroidism. His serum creatinine levels showed poor results, but serum cystatin C levels were within the normal range. The physician thus prioritized serum cystatin C for assessing the patient's renal function, and concluded that his renal function was normal. He subsequently visited our hospital, aged 36years, for a comprehensive examination. His serum creatinine level was 1.88mg/dL and his serum cystatin C level was 0.75mg/dL, indicating an unusual discrepancy between the two measurements. The patient also presented with fatigue, suggesting hypothyroidism, and we therefore evaluated his thyroid function. His free thyroxine level was below the sensitivity of the assay, while his thyroid-stimulating hormone level was > 100 μIU/mL. A renal biopsy was performed to further explore the underlying cause of his renal dysfunction, which suggested that reduced RPF could be the leading cause of his renal ischemia, with no indications of chronic glomerulonephritis or other abnormalities. His hypothyroidism and renal function improved after thyroid hormone replacement therapy. Given the limited reports of renal biopsy tissue examination during the acute phase of hypothyroidism, the current case provides important information regarding the diagnosis of renal dysfunction in patients with hypothyroidism.

The ICD-9 to ICD-10 transition has not improved identification of rapidly progressing stage 3 and stage 4 chronic kidney disease patients: a diagnostic test study

BackgroundThe International Classification of Diseases (ICD) coding system is the industry standard tool for billing, disease classification, and epidemiology purposes. Prior research has demonstrated ICD codes to have poor accuracy, particularly in relation to rapidly progressing chronic kidney disease (CKD) patients. In 2016, the ICD system moved to revision 10. This study examines subjects in a large insurer database to determine the accuracy of ICD-10 CKD-staging codes to diagnose patients rapidly progressing towards end-stage kidney disease (ESKD).Patients and methodsSerial observations of outpatient serum creatinine measurements from 2016 to 2021 of 315,903 patients were transformed to estimated glomerular filtration rate (eGFR) to identify CKD stage-3 and advanced patients diagnosed clinically (eGFR-CKD). CKD-staging codes from the same time period of 59,386 patients and used to identify stage-3 and advanced patients diagnosed by ICD-code (ICD-CKD). eGFR-CKD and ICD-CKD diagnostic accuracy was compared between a total of 334,610 patients.Results5,618 patients qualified for the progression analysis; 72 were identified as eGFR rapid progressors; 718 had multiple codes to qualify as ICD rapid progressors. Sensitivity was 5.56%, with positive predictive value (PPV) 5.6%. 34,858 patients were diagnosed as eGFR-CKD stage-3 patients; 17,549 were also diagnosed as ICD-CKD stage-3 patients, for a sensitivity of 50.34%, with PPV of 58.71%. 4,069 patients reached eGFR-CKD stage-4 with 2,750 ICD-CKD stage-4 patients, giving a sensitivity of 67.58%, PPV of 42.43%. 959 patients reached eGFR-CKD stage-5 with 566 ICD-CKD stage-5 patients, giving a sensitivity of 59.02%, PPV of 35.85%.ConclusionThis research shows that recent ICD revisions have not improved identification of rapid progressors in diagnostic accuracy, although marked increases in sensitivity for stage-3 (50.34% vs. 24.68%), and PPV in stage-3 (58.71% vs. 40.08%), stage-4 (42.43% vs. 18.52%), and stage-5 (35.85% vs. 4.51%) were observed. However, sensitivity in stage-5 compares poorly (59.02% vs. 91.05%).