Assessment Of Kidney Function Research Articles

Formulae for estimation of kidney function as an approach to calculating drug doses: A scoping review

Background: The kidneys are the main organ for drug excretion, and it is critical to assess kidney function when designing dosage regimens for drugs that undergo renal elimination. Various formulae have been used to estimate kidney function and safely adjust doses. Objective: This research reviewed studies that assessed patients' kidney function with various approaches to provide appropriate choices of kidney function estimation formulas based on patients' age and clinical conditions. Method: The search involved browsing scientific articles in PubMed and ScienceDirect with the keywords (("assessment") AND ("GFR") AND ("formula")) OR ("renal function") AND ("human")) AND (“Creatinine”). The articles included were those available in full text and English. Thirty articles addressing the formulae for kidney function assessment were reviewed. Result: The Schwartz formula is more appropriate for pediatric and adult patients, whereas the creatinine-based chronic kidney disease epidemiology (CKD-EPI) formula can be used in geriatrics, obese patients, and patients already known to have decreased kidney function. The cystatin C-based CKD-EPI formula is for patients with HIV and post-transplant patients. Conclusion: This study identified that physiological conditions, especially patients’ age and pathology, should be considered in devising formulae to estimate kidney function to accurately calculate safe drug doses.

#377 Assessment of kidney function by creatinine and cystatin C and cardiovascular outcomes in patients with atrial fibrillation

Abstract Background and Aims Atrial fibrillation (AF) in patients with chronic kidney disease are at an increased risk for ischemic and bleeding events and all-cause mortality. Accurate kidney function estimation is key for risk assessment. Creatinine is commonly used to calculate the Glomerular Filtration Rate (GFR). However, cystatin C has been described to be more sensitive than creatinine independent of muscle mass, autoimmune disease, inflammation or consuming diseases. Our aim was to evaluate the associations between kidney function, assessed by creatinine and cystatin C, and cardiovascular events (CVE), its individual components, and major bleedings. Method We enrolled 326 AF patients into two prospective, multicenter cohort studies. Creatinine and cystatin C were measured at baseline and clinical outcome events were assessed yearly. We calculated GFR using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula based on either creatinine (GFRcr), cystatin C (GFRcy) or both (GFRc2). Primary outcome was major CVE, defined as a composite of stroke or systemic embolism, myocardial infarction and cardiovascular death. Secondary outcomes were the individual components of major CVE and major bleeding. Multivariable adjusted Cox regression analyses were built to evaluate the associations between kidney function and outcome events. Results Mean age was 56 ± 9 years and 37% were female. Mean creatinine and cystatin С levels were 112 ± 21 μmol/l and 1.6 ± 0.3 mg/l, respectively, translating to a GFRc2 of 58.2 ± 16.8 ml/min/1.73 m2. Over a median follow-up of 2 years, the incidence rates for major CVE (per 100 person-years) across quartiles (Q1-Q4) of GFRc2 were 23.1, 20.3, 17.6 and 14.7, respectively. When using multivariable adjusted Cox regression analysis, major CVE was significantly associated with GFRcr (per 1 standard deviation: HR 0.89 (95% CI 0.79; 0.98) p = 0.01), GFRcy (HR 0.65 (CI 0.53; 0.72), p < 0.001) and GFRc2 (HR 0.74 (CI 0.63; 0.82), p < 0.001). This association was mainly driven by cardiovascular death. Major bleeding was associated with GFRcy (HR 0.78 (0.64-0.93) p = 0.001) and GFRc2 (HR 0.82 (0.69-0.97), p = 0.01), but not with GFRcr (HR 0.93 (95% CI 0.83-1.1) p = 0.33). Conclusion Among AF patients, GFR equations including cystatin C were associated both with major CVE and bleeding events, while creatinine based GFR equations were only associated with major CVE. Therefore, Cystatin C based GFR equations might offer more comprehensive risk stratification in patients with AF.

RFLSE: Joint radiomics feature‐enhanced level‐set segmentation for low‐contrast SPECT/CT tumour images

AbstractDoctors typically use non‐contrast‐enhanced computed tomography (NCECT) in the treatment of kidney cancer to map kidney and tumour structural information to functional imaging single‐photon emission computed tomography, which is then used to assess patient kidney function and predict postoperative recovery. However, the assessment of kidney function and formulation of surgical plans is constrained by the low contrast of tumours in NCECT, which hinders the acquisition of accurate tumour boundaries. Therefore, this study designed a radiomics feature‐enhanced level‐set evolution (RFLSE) to precisely segment small‐sample low‐contrast kidney tumours. Integration of high‐dimensional radiomics features into the level‐set energy function enhances the edge detection capability of low‐contrast kidney tumours. The use of sensitive radiomics features to control the regional term parameters achieves adaptive adjustment of the curve evolution amplitude, improving the level‐set segmentation process. The experimental data used low‐contrast, limited‐sample tumours provided by hospitals, as well as the public datasets BUSI18 and KiTS19. Comparative results with advanced energy functionals and deep learning models demonstrate the precision and robustness of RFLSE segmentation. Additionally, the application value of RFLSE in assisting doctors with accurately marking tumours and generating high‐quality pseudo‐labels for deep learning datasets is demonstrated.

Assessment of Kidney Function and Lipid Profile in Albino Rats Exposed to Azo-Dye Adulterated Palm Oil

Food is an important factor in human existence which makes exposure to adulterants in food an important environmental factor challenging the biological system. In West Africa, the manufacturing and processing of palm oil are done without proper hygienic monitoring; it is therefore almost impossible to detect fraud in the system. A major disadvantage associated with the use of adulterants in palm oil is that the adulterants have not undergone adequate research and the degree of health hazards they can pose to humans when consumed. This study was designed to evaluate the toxic effects of Azo dye adulterated palm oil on kidney function and Lipid profile in albino rats exposed to Azo-dye adulterated palm oil. Twenty-five albino rats were divided into five groups and treated as thus: Group I (control), Groups II and III were treated with only 1 ml/kg of unadulterated and adulterated palm oil respectively, while Groups IV and V were treated with only 50 mg/kg of Sudan III and IV dyes respectively for 28 days. Renal function tests, and lipid profiles were determined using analytical test kits. Data obtained were statistically analyzed with one-way analysis of variance (ANOVA) followed by tukey test using Graph Pad prism 9.0.0. The results were presented as mean ± standard error of mean (SEM). Differences between means of treated and control groups values at P ≤ 0.05 at 95% confidence interval were considered significant. The results showed a significant increase (p < 0.05) in creatinine, urea concentrations, Sodium ion (Na+) and Potassium ion (K+) in groups treated with adulterated palm oil, Sudan III, Sudan IV (groups III, IV and V respectively) when compared with control groups. A significant increase (p < 0.05) in low density lipoprotein (LDL), cholesterol, very low-density lipoprotein (VLDL) and Triacylglycerol (TAG) was observed in treated groups when compared with control groups while a significant decrease (p < 0.05) in high density lipoprotein level (HDL) observed in treated groups when compared with the control group. This suggests that adulterated palm oil can induce renal damage and alter lipid profile.

Linagliptin ameliorates tacrolimus-induced renal injury: role of Nrf2/HO-1 and HIF-1α/CTGF/PAI-1

BackgroundTacrolimus (TAC) is a frequently used immunosuppressive medication in organ transplantation. However, its nephrotoxic impact limits its long-term usage. This study aims to investigate the effect of linagliptin (Lina) on TAC-induced renal injury and its underlying mechanisms.Methods and resultsThirty-two Sprague Dawley rats were treated with TAC (1.5 mg/kg/day, subcutaneously) and/or Lina (5 mg/kg/day, orally) for 4 weeks. Histological examination was conducted, and serum and urinary biomarkers were measured to assess kidney function and integrity. Furthermore, ELISA, Western blot analysis and immunohistochemical assay were employed to determine signaling molecules of oxidative stress, profibrogenic, hypoxic, and apoptotic proteins. Tacrolimus caused renal dysfunction and histological deterioration evidenced by increased serum creatinine, blood urea nitrogen (BUN), urinary cystatin C, and decreased serum albumin as well as elevated tubular injury and interstitial fibrosis scores. Additionally, TAC significantly increased the expression of collagen type-1, alpha-smooth muscle actin (α-SMA), plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor-beta1 (TGF-β1) renal content. Moreover, TAC decreased the expression of nuclear factor erythroid-2-related factor2 (Nrf2), heme oxygenase 1 (HO-1), and mitochondrial superoxide dismutase (SOD2). In addition, TAC increased protein expression of hypoxia-inducible factor1-alpha (HIF-1α), connective tissue growth factor (CTGF), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG), as well as nitric oxide (NO), 4-hydroxynonenal, caspase-3 and Bax renal contents. Furthermore, TAC decreased Bcl-2 renal contents. The Lina administration markedly attenuated these alterations.ConclusionLina ameliorated TAC-induced kidney injury through modulation of oxidative stress, hypoxia, and apoptosis related proteins.

Automated Analysis of Split Kidney Function from CT Scans Using Deep Learning and Delta Radiomics.

Background: Differential kidney function assessment is an important part of preoperative evaluation of various urological interventions. It is obtained through dedicated nuclear medical imaging and is not yet implemented through conventional Imaging. Objective: We assess if differential kidney function can be obtained through evaluation of contrast-enhanced computed tomography(CT) using a combination of deep learning and (2D and 3D) radiomic features. Methods: All patients who underwent kidney nuclear scanning at Mayo Clinic sites between 2018-2022 were collected. CT scans of the kidneys were obtained within a 3-month interval before or after the nuclear scans were extracted. Patients who underwent a urological or radiological intervention within this time frame were excluded. A segmentation model was used to segment both kidneys. 2D and 3D radiomics features were extracted and compared between the two kidneys to compute delta radiomics and assess its ability to predict differential kidney function. Performance was reported using receiver operating characteristics, sensitivity, and specificity. Results: Studies from Arizona & Rochester formed our internal dataset (n = 1,159). Studies from Florida were separately processed as an external test set to validate generalizability. We obtained 323 studies from our internal sites and 39 studies from external sites. The best results were obtained by a random forest model trained on 3D delta radiomics features. This model achieved an area under curve (AUC) of 0.85 and 0.81 on internal and external test sets, while specificity and sensitivity were 0.84,0.68 on the internal set, 0.70, and 0.65 on the external set. Conclusion: This proposed automated pipeline can derive important differential kidney function information from contrast-enhanced CT and reduce the need for dedicated nuclear scans for early-stage differential kidney functional assessment. Clinical Impact: We establish a machine learning methodology for assessing differential kidney function from routine CT without the need for expensive and radioactive nuclear medicine scans.

Performance of modification of diet in renal disease and chronic kidney disease epidemiology collaboration equations versus 99TC-DTPA-renogram in assessing kidney function

Performance of modification of diet in renal disease and chronic kidney disease epidemiology collaboration equations versus 99TC-DTPA-renogram in assessing kidney function

Assessment of temporal changes in glomerular filtration rate following clamp ischemia in male and female rats using transcutaneous FITC-sinistrin clearance

Warm arterial clamping with reperfusion in rats is a commonly utilized model of ischemic kidney injury (IRI). Traditionally, changes in plasma creatinine or creatinine clearance have been utilized to assess kidney function in this model. A limitation of these approaches, however, is that changes in plasma creatinine are relatively slow to occur, resulting in low temporal fidelity. This limits our ability to relate changes in kidney function to histo-pathological changes observed during reperfusion of the kidneys. Transcutaneous assessment of FITC-sinistrin clearance enables accurate, repeated measurement of glomerular filtration rate in conscious animals over short segments of time (hours) without drawing blood. The goal of the current study was to characterize temporal changes in renal function in male and female rats after reperfusion from bi-lateral warm arterial clamp ischemia using transcutaneous FITC-sinistrin clearance. Our study was performed in age matched male (n=8) and female (n=5) Sprague Dawley rats (12-20wks of age). FITC sinistrin clearance was measured by affxing a miniaturized transcutaneous measurement device between the shoulder blades (MediBeacon) of rats. 50mg/kg of FITC-sinistrin was then injected i.v via the tail vein and the device allowed to record for ~3 hours. Measurements were taken either at pre-surgery (baseline), 1-3 hours, 24 hours or 7 days following reperfusion of the kidneys from warm bilateral arterial clamp ischemia. For the ischemic surgery, animals were anesthetized with isoflurane (2-5%, 95% O2) and the right and left kidneys were accessed by flank incisions. After being exposed, the renal arteries were separated from the renal veins via dissection. Both renal arteries were then clamped with microserrefines for 45 minutes. After the ischemic period, the clamps were removed, allowing blood flow to be restored to the kidneys. Body temperature was measured via a rectal probe and maintained at 37°C throughout the procedure by a servo-controlled heating table and UV heating lamp. The wounds were then closed, and the animals allowed to recover. Buprenorphine was administered as an analgesic. For each measurement, the ½ life of FITC sinistrin was determined using a 1-compartment model (MB Lab software) and glomerular filtration rate (GFR) per 100g of body weight rate calculated. Baseline GFR was 0.94±0.03ml/min/100g in males and 1.09±0.02/min/100g in females (PTTEST=0.04). Following 45 minutes of warm bilateral arterial ischemia and reperfusion, GFR fell to 0.24±0.08ml/min/100g in male and 0.36±0.15ml/min/100g in females within 1-3 hours of reperfusion. At 24 hours of reperfusion, GFR averaged 0.06±0.03ml/min/100g in males and 0.28±0.16ml/min/100g in females. GFR recovered in males and females by 7 days of reperfusion averaging 0.86±0.10ml/min/100g in males and 0.83±0.00ml/min/100g in females. There was no significant difference between FITC-sinistrin clearance between males and females at any time point after IRI. Our data indicate that most of the reduction in GFR is present immediately after releasing the clamp. This is consistent with continued vascular disturbances mediating the initial decline in glomerular filtration rate in this model (i.e. vasospasm). The absence of sex differences in GFR decline using this method suggests that sex-differences detected using plasma creatinine may be, at least in part, secondary to the more rapid production of creatinine in males than in females or greater baseline filtration/body weight ratio in females compared to males rather than differences in renal function decline to ischemia. American Heart Association Transformational Project Award 970585 to Paul O'Connor. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Biochemical changes associated with H. pylori infection in humans

Since its first isolation, H. pylori, a Gram-negative flagellated bacterium, has been the subject of intensive research because of its widespread dissemination and associations with several disorders. The bacterium is proven to be a causative factor for a number of gastric diseases, such as gastritis, gastric adenocarcinoma, and MALT-lymphoma. While H. pylori infection has been reported to be linked to several extra-gastric diseases, this study investigated extra-gastric manifestation of H. pylori using specific biomarkers in humans. The GERDs questionnaire was used to randomly chose 150 (one hundred and fifty) participants, of which 75 (seventy five) were found to be H. pylori positive and another 75 (seventy five) were chosen as negative controls. Samples were gathered, and biochemical characteristics were examined. The study revealed a significant (p<0.05) reduction in the levels of oxidative stress markers, glutathione peroxidase (GPX), vitamin C (vit C) and no significant difference was observed in malondialdehyde (MDA) and Total iron concentrations, although with a mean increase and reduction respectively. For the lipid profile biomarker results were statistically (p<0.05) significant for triglyceride (TG) and low density lipoprotein(LDLc) while no significant difference was observed in total cholesterol (TC) and high density lipoprotein (HDLc). Kidney function assessment revealed a statistical (p > 0.05) no significant different with sodium (Na+), potassium (K+), chloride (Cl-) and bicarbonate (HCO2-) concentrations while there was a significant difference in urea and creatinine concentrations when compared with the control subjects. In the liver function parameters, a statistical (p<0.05) significant difference was observed with the aminotransferases (ALT, AST, ALP) and conjugated bilirubin while total bilirubin had a no significant difference when compared with the control subjects. A correlation coefficient analysis of parameter in H. pylori positive subjects were significantly adjusted (p<0.05) for TG, total cholesterol, aminotransferases and bilirubin. The aim of the study was to investigate the biochemical changes of H. pylori infection in humans using specific biomarkers.

Chinese expert consensus on the guidance of anti-tumor drugs for patients with tumor combined chronic kidney disease (2024 edition)

The incidence of malignant tumors has steadily increased year by year in China in recent decades ascribed to the population aging and early cancer screening. The emergence of innovative anti-cancer drugs has bolstered the prognosis of cancer patients, making it a chronic disease. Kidney injuries are frequent complications of cancer treatment clinically manifested as acute kidney injury (AKI), chronic kidney disease (CKD), proteinuria, and electrolyte disorders, etc. Although kidney injuries affect up to 50% of the patients, there is a lack of professional management guidance for anti-cancer drug dosage adjustment. The clinical pharmacology branch of the Chinese Medical Association has initiated the "Chinese expert consensus on the guidance of anti-tumor drugs for patients with tumor combined chronic kidney disease (2024 edition)". We unified national multidisciplinary experts to analyze clinical evidence with the Delphi method, and conducted expert interviews and seminars focusing on kidney function assessment, anti-tumor drug dosage adjustment for kidney disease patients. We make recommendations on selection and dose adjustment of anti-tumor drugs (chemotherapy, small molecules and antibodies) according to chemotherapeutic drug classifications, providing practical and feasible scientific guidance for clinicians.

DKK3 promotes renal fibrosis by increasing MFF-mediated mitochondrial dysfunction in Wnt/β-catenin pathway-dependent manner

Background Chronic kidney disease (CKD) lacks effective treatments and renal fibrosis (RF) is one of CKD’s outcomes. Dickkopf 3 (DKK3) has been identified as an agonist in CKD. However, the underlying mechanisms of DKK3 in CKD are not fully understood. Methods H2O2-treated HK-2 cells and ureteric obstruction (UUO) mice were used as RF models. Biomarkers, Masson staining, PAS staining, and TUNEL were used to assess kidney function and apoptosis. Oxidative stress and mitochondria function were also evaluated. CCK-8 and flow cytometry were utilized to assess cell viability and apoptosis. Western blotting, IHC, and qRT-PCR were performed to detect molecular expression levels. Immunofluorescence was applied to determine the subcellular localization. Dual luciferase assay, MeRIP, RIP, and ChIP were used to validate the m6A level and the molecule interaction. Results DKK3 was upregulated in UUO mouse kidney tissue and H2O2-treated HK-2 cells. Knockdown of DKK3 inhibited oxidative stress, maintained mitochondrial homeostasis, and alleviated kidney damage and RF in UUO mice. Furthermore, DKK3 silencing suppressed HK-2 cell apoptosis, oxidative stress, and mitochondria fission. Mechanistically, DKK3 upregulation was related to the high m6A level regulated by METTL3. DKK3 activated TCF4/β-catenin and enhanced MFF transcriptional expression by binding to its promoter. Overexpression of MFF reversed in the inhibitory effect of DKK3 knockdown on cell damage. Conclusion Upregulation of DKK3 caused by m6A modification activated the Wnt/β-catenin pathway to increase MFF transcriptional expression, leading to mitochondrial dysfunction and oxidative stress, thereby promoting RF progression.

Utility of Cystatin C-based Equation for the Estimation of Glomerular Filtration Rate in a Pediatric Population.

The accurate assessment of kidney function is vital for the early detection of kidney damage. The estimated glomerular filtration rate GFR (eGFR) from serum cystatin C (CysC) and creatinine-based equations are commonly used in clinical practice as an alternative to the invasive measured glomerular filtration rate (mGFR), which is the usually accepted overall best index of kidney function in health and disease. Recently the CKiD under 25 (CkiD U25) equations have been shown to perform well in children and young adults with chronic kidney disease (CKD). In this focused report, we evaluated the performance of the CkiD U25 equations alongside 3 non-race-corrected (NRC) eGFR equations commonly used in pediatrics in our cohort. mGFR measured following the intravenous injection of tracer Tc-99mDTPA was retrospectively compared with eGFR from these equations in 57 patients (6 months to 22 years) from different races/ethnicities. Ordinary least squares regression analyses were used to assess correlation between the mGFRs and eGFRs. The average mGFR for this cohort was 84.1 mL/min/1.73 m2. The NRC creatinine equations overestimated eGFR across all groups, with the lowest bias for CKiD U25-creatinine (22.59 mL/min/1.73 m2). The best correlations to mGFR, P30, and lowest biases were the CKiD U25-CysC (0.6281, 80.7%, 3.72 mL/min/1.73 m2) and Schwartz CysC (0.6372, 77.2%, -4.68 mL/min/1.73 m2). Overall, both CKiD U25-CysC and Schwartz CysC provide a good estimation of mGFR with the CKiD U25-CysC having the overall best performance compared to mGFR in our study.

Loss of SAV1 in Kidney Proximal Tubule Induces Maladaptive Repair after Ischemia and Reperfusion Injury.

Kidney ischemia and reperfusion injury (IRI) is a significant contributor to acute kidney injury (AKI), characterized by tubular injury and kidney dysfunction. Salvador family WW domain containing protein 1 (SAV1) is a key component of the Hippo pathway and plays a crucial role in the regulation of organ size and tissue regeneration. However, whether SAV1 plays a role in kidney IRI is not investigated. In this study, we investigated the role of SAV1 in kidney injury and regeneration following IRI. A proximal tubule-specific knockout of SAV1 in kidneys (SAV1ptKO) was generated, and wild-type and SAV1ptKO mice underwent kidney IRI or sham operation. Plasma creatinine and blood urea nitrogen were measured to assess kidney function. Histological studies, including periodic acid-Schiff staining and immunohistochemistry, were conducted to assess tubular injury, SAV1 expression, and cell proliferation. Western blot analysis was employed to assess the Hippo pathway-related and proliferation-related proteins. SAV1 exhibited faint expression in the proximal tubules and was predominantly expressed in the connecting tubule to the collecting duct. At 48 h after IRI, SAV1ptKO mice continued to exhibit severe kidney dysfunction, compared to attenuated kidney dysfunction in wild-type mice. Consistent with the functional data, severe tubular damage induced by kidney IRI in the cortex was significantly decreased in wild-type mice at 48 h after IRI but not in SAV1ptKO mice. Furthermore, 48 h after IRI, the number of Ki67-positive cells in the cortex was significantly higher in wild-type mice than SAV1ptKO mice. After IRI, activation and expression of Hippo pathway-related proteins were enhanced, with no significant differences observed between wild-type and SAV1ptKO mice. Notably, at 48 h after IRI, protein kinase B activation (AKT) was significantly enhanced in SAV1ptKO mice compared to wild-type mice. This study demonstrates that SAV1 deficiency in the kidney proximal tubule worsens the injury and delays kidney regeneration after IRI, potentially through the overactivation of AKT.

Role of a Pharmacist in Postdischarge Care for Patients With Kidney Disease: A Scoping Review.

The objective was to explore and describe the role of pharmacists in providing postdischarge care to patients with kidney disease. PubMed, Embase (Elsevier), CINAHL (Ebscohost), Web of Science Core Collection, and Scopus were searched on January 30, 2023. Publication date limits were not included. Search terms were identified based on 3 concepts: kidney disease, pharmacy services, and patient discharge. Experimental, quasi-experimental, observational, and qualitative studies, or study protocols, describing the pharmacist's role in providing postdischarge care for patients with kidney disease, excluding kidney transplant recipients, were eligible. Six unique interventions were described in 10 studies meeting inclusion criteria. Four interventions targeted patients with acute kidney injury (AKI) during hospitalization and 2 evaluated patients with pre-existing chronic kidney disease. Pharmacists were a multidisciplinary care team (MDCT) member in 5 interventions and were the sole provider in 1. Roles commonly identified include medication review, medication reconciliation, medication action plan formation, kidney function assessment, drug dose adjustments, and disease education. Some studies showed improvements in diagnostic coding, laboratory monitoring, medication therapy problem (MTP) resolution, and patient education; prevention of hospital readmission was inconsistent. Limitations include lack of standardized reporting of kidney disease, transitions of care processes, and differences in outcomes evaluated. This review identifies potential roles of a pharmacist as part of a postdischarge MDCT for patients with varying degrees of kidney disease. The pharmacist's role in providing postdischarge care to patients with kidney disease is inconsistent. Multidisciplinary care teams including a pharmacist provided consistent identification and resolution of MTPs, improved patient education, and increased self-awareness of diagnosis.

Abstract P161: Association Between Kidney Function and Pre-Heart Failure: Insights From the Echocardiographic Study of Latinos (Echo-SOL)

Background: Impaired kidney function is an independent risk factor for heart failure (HF), but its association with pre-HF is not as well studied. We assessed kidney function in relation to pre-HF in a diverse Hispanic/Latino population in the US. Methods: Echocardiographic data from visit (V) 1 and 2 of Echo-SOL were analyzed (unweighted n=1643). Prevalent pre-HF was defined as any abnormal echocardiographic parameter at V1: left ventricular (LV) systolic dysfunction (LVSD) [ejection fraction <50%, global longitudinal strain >15%]; LV diastolic dysfunction (LVDD) >grade 1; and LV remodeling (LVR) [LV mass index >115 g/m2 in men, >95 g/m2 in women, relative wall thickness >0.42]. Incident pre-HF was defined at V2 among those without pre-HF at V1 (unweighted n=588). Kidney function was assessed by cystatin C (per 10 mg/L), eGFR (MDRD-traditional and CKD-EPI, per 5 mL/min/1.73 m2), and urine albumin creatinine ratio (UACR, per 10 units). Survey logistic regression analyses were used to examine the association of kidney function measures with prevalent and incident pre-HF and its domains (LVSD, LVDD, LVR), unadjusted and adjusted for age and sex and accounting for the complex survey design. Results: At V1 (mean age 56 years, 55% female), 66.7% had prevalent pre-HF; at V2, 66.3% had incident pre-HF. UACR was significantly associated with prevalent pre-HF and LVR in all models (Table 1-2). Higher cystatin C was significantly associated with incident pre-HF, LVDD, and LVR in all models; whereas eGFR (CKD-EPI) showed a marginal inverse relation with prevalent and incident pre-HF, LVDD and LVR, but only remained associated with LVR in adjusted models (Table 1-2). Conclusion: Declining kidney function (higher UACR and cystatin C) is associated with prevalent and incident pre-HF, diastolic dysfunction, and cardiac remodeling. Lower eGFR is also associated with cardiac remodeling in this population. Screening for kidney function could help us identify pre-HF and start protective therapies earlier to most effectively prevent overt HF.

Establishing age and gender-specific serum creatinine reference ranges for Thai pediatric population.

Accurate assessment of kidney function in children requires age and gender-specific reference ranges for serum creatinine. Traditional reference values, often derived from adult populations and different ethnic backgrounds, may not be suitable for children. This study aims to establish specific reference ranges for serum creatinine in the Thai pediatric population, addressing the gap in localized and age-appropriate diagnostic criteria. This retrospective study analyzed serum creatinine levels from Thai children aged newborn to 18 years, collected from the Laboratory Information System of the Queen Sirikit National Institute of Child Health from January 2017 to December 2021. The Bhattacharya method was employed to establish reference ranges, considering different age groups and genders. The study compared these newly established reference values with international studies, including those of Schlebusch H., Pottel H., and Chuang GT., to validate their relevance and accuracy. A total of 27,642 data entries (15,396 males and 12,246 females) were analyzed. The study established distinct reference ranges for serum creatinine, which varied significantly across different age groups and between genders. These ranges were found to gradually increase with age from 2 months to 18 years. The study also highlighted notable differences in reference values when compared with other ethnic populations. The study successfully establishes tailored reference ranges for serum creatinine in Thai children, providing a valuable tool for more accurate diagnosis and monitoring of kidney health in this demographic. This initiative marks a significant advancement in pediatric nephrology in Thailand and suggests a need for continuous refinement of these ranges and further research in this area.

Adalimumab as a cause of kidney injury in patients with Crohn's disease.

Adalimumab (ADM) is a recombinant human monoclonal antibody (anti-TNFα) used to treat inflammatory bowel diseases. It can cause kidney injury (KI). We describe two pediatric patients with Crohn's disease (CD) in whom ADM therapy was associated with kidney injury (KI). The drug was discontinued in both cases. For the first patient, changes were irreversible despite intensive glucocorticosteroid (GCS) therapy. For the second patient, discontinuation of ADM led to an improvement in kidney function. Due to the risk of KI in patients undergoing ADM therapy, careful assessment of kidney function and early specialist referral are required. Timely withdrawal of ADM can significantly reduce kidney damage, but in some cases, the kidney damage can be irreversible.

A Comparison of 68Ga-PSMA PET/CT-Based Split Renal Function with 99mTc-MAG3 Renography in Patients with Metastatic Castration-Resistant Prostate Carcinoma Treated with 177Lu-PSMA.

Physiological PSMA expression in the cells of the proximal renal tubules and consecutive radiopharmaceutical binding and retention could potentially lead to radioligand-therapy-induced nephrotoxicity. Thus, patients with metastatic castration-resistant prostate cancer undergo 99mTc-Mercaptoacetyltriglycine (MAG3) renal scintigraphy to assess kidney function and to exclude renal obstruction as part of their workup for PSMA-targeted radioligand therapy (RLT). 99mTc-MAG-3 renal scintigraphy often requires an additional visit to the nuclear medicine department and patients spend 30-90 min in the department, which is inconvenient and takes up camera time. In addition, the patients are subjected to a baseline 68Ga-PSMA PET/CT to assess for PSMA-positive disease prior to targeted radioligand therapy. The aim of this retrospective cross-sectional study was to compare 99mTc-MAG-3-based split renal function (SRF) with 68Ga-PSMA-derived SRF. This retrospective cross-sectional study included 28 patients with histologically proven metastatic castration-resistant prostate cancer (mCRPC) who received 177Lu-PSMA617. A comparison between the split renal function using 68Ga-PSMA PET/CT and the 99mTc-MAG-3-derived split renal function was carried out in 56 kidneys (n = 56). The SRF on 68Ga-PSMA was calculated using the volume and the average standard uptake value (SUVmean) within each VOI calculated as previously described by Roser et al.: SRF = (VOLUMEright) ∗ SUVmeanright/(VOLUMEright ∗ SUVmeanright + VOLUMEleft ∗ SUVmeanleft). Paired tests and correlation coefficients were used to compare 68Ga-PSMA and 99mTc-MAG-3. A visual comparison of kidney morphology on both studies was also performed. The median SRF of the right kidney was 49.9% (range: 3-91%) using 68Ga-PSMA PET/CT and 50.5% (range: 0-94%) with 99mTc-MAG3 scintigraphy. Notably, there was a strong correlation between SRF measurements obtained from PSMA and 99mTcMAG3, with a Pearson correlation coefficient of 0.957 (p < 0.001). Both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities; there were nine hydronephrotic kidneys, four shrunken kidneys and one obstructed kidney, and there was a strong positive correlation between 68Ga-PSMA kidney morphology and 99mTcMAG3 renal scintigraphy kidney morphology, with a correlation coefficient of 0.93. PSMA-derived split function demonstrated a high correlation with renal function assessed on diuretic 99mTc-MAG3 renograms. PET-derived split renal function may, therefore, be considered an alternative to diuretic renogram-based split function. Furthermore, both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities such as hydronephrosis, shrunken and obstructed kidneys. This correlation underscores the potential utility of 68Ga-PSMA imaging as a valuable tool for assessing kidney morphology as an alternative to renogram split function in clinical practice.

Withdrawal of renin-angiotensin system inhibitors’ effect on estimated glomerular filtration rate in adults with advanced kidney disease: the STOP-ACEi RCT

Background Renin–angiotensin system inhibitors, both angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, slow progression of mild and moderate chronic kidney disease. However, some evidence suggests that discontinuation of renin–angiotensin system inhibitors in patients with advanced chronic kidney disease might increase estimated glomerular filtration rate or slow its decline. Objective To test the hypothesis that stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or a combination of both, compared with continuing these treatments, improves or stabilises kidney function in patients with progressive stages 4 or 5 chronic kidney disease based on assessment of kidney function using the modification of diet in renal disease four-variable estimated glomerular filtration rate at 3 years, follow-up. Setting Thirty-seven UK hospitals with kidney services. Design An investigator-led multicentre open-label, randomised controlled trial of 411 participants with advanced (stage 4 or 5) progressive chronic kidney disease. Participants Adult patients with advanced (estimated glomerular filtration rate &lt; 30 ml/minute/1.73 m2) and progressive chronic kidney disease who were receiving either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or a combination of both. Interventions Participants were randomised in a 1 : 1 ratio using a centralised internet-based system to either discontinue renin–angiotensin system inhibitors (n = 206) or continue renin–angiotensin system inhibitors (n = 205). Main outcome measures The primary outcome was the estimated glomerular filtration rate at 3 years; measurements of estimated glomerular filtration rate made after commencing kidney replacement therapy were excluded. Secondary outcomes included development of end-stage kidney disease or starting kidney replacement therapy, a composite of either a &gt; 50% decline in estimated glomerular filtration rate or commencement of kidney replacement therapy (including end-stage kidney disease), cystatin C, hospitalisations, blood pressure, exercise capacity and quality of life. Cardiovascular events, death and safety were recorded. Results At 3 years, the least-squares mean (± standard error) estimated glomerular filtration rate was 12.6 ± 0.7 ml/minute/1.73 m2 in the discontinuation group and 13.3 ± 0.6 ml/minute/1.73 m2 in the continuation group [difference −0.7, 95% confidence interval (−2.5 to 1.0; p = 0.42)] with a negative value favouring the continuation group. The treatment effect did not differ (heterogeneity) when data were analysed by the pre-specified subgroups. End-stage kidney disease or kidney replacement therapy occurred in 128 (62%) and 115 (56%) participants randomised to the discontinue and continue renin–angiotensin system inhibitor groups, respectively (hazard ratio 1.28, 95% confidence interval 0.99 to 1.65). The numbers of cardiovascular events and deaths observed were similar for those randomised to discontinue (108 events and 20 deaths) or continue (88 events and 22 deaths) renin–angiotensin system inhibitors. Limitations Non-white ethnic backgrounds were poorly represented, limiting the generalisability of our findings. The open-label nature of the trial may have affected clinical care and subjective end points, such as quality of life and exercise capacity. We only included patients who were receiving renin–angiotensin system inhibitors at the time of randomisation, thus excluding those who had already discontinued these agents. Conclusions Discontinuing renin–angiotensin system inhibitors in advanced and progressive chronic kidney disease does not cause a clinically relevant change in estimated glomerular filtration rate or difference in its long-term decline. Future work Future work should focus on updating clinical guidelines. Further analyses, in addition to the prespecified analyses, may be undertaken if new estimated glomerular filtration rate equations are introduced into clinical practice. Subgroup analysis by kidney disease aetiology and gender may be undertaken to look for potential differences in outcome in specific groups. Trial registration This trial is registered as STOP ACEi EudraCT Number, 2013-003798-82; ISRCTN62869767. Funding This award was funded by the Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 11/30/07), a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership. This is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 5. See the NIHR Funding and Awards website for further award information.

Kidney volume normative values in Central European children aged 0-19years: a multicenter study.

The currently available kidney volume normative values in children are restricted to small populations from single-centre studies not assessing kidney function and including none or only a small number of adolescents. This study aimed to obtain ultrasound-based kidney volume normative values derived from a large European White/Caucasian paediatric population with normal kidney function. After recruitment of 1427 children aged 0-19years, 1396 individuals with no history of kidney disease and normal estimated glomerular filtration rate were selected for the sonographic evaluation of kidney volume. Kidney volume was correlated with age, height, weight, body surface area and body mass index. Kidney volume curves and tables related to anthropometric parameters were generated using the LMS method. Kidney volume predictors were evaluated using multivariate regression analysis with collinearity checks. No clinically significant differences in kidney volume in relation to height were found between males and females, between supine and prone position and between left and right kidneys. Males had, however, larger age-related kidney volumes than females in most age categories. For the prediction of kidney volume, the highest coefficient correlation was observed for body surface area (r = 0.94), followed by weight (r = 0.92), height (r = 0.91), age (r = 0.91), and body mass index (r = 0.67; p < 0.001 for all). This study presents LMS-percentile curves and tables for kidney volume which can be used as reference values for children aged 0-19years.