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Aim: Ankylosing spondylitis (AS) predominantly affects the spine and sacroiliac joints, with rare renal involvement. We investigated the incidence rate and risk factors for chronic kidney disease (CKD) in patients with AS and its relationship with long‐term nonsteroidal anti‐inflammatory drug (NSAID) use. Methods: We retrospectively analyzed data of patients diagnosed with AS from the Korean National Health Insurance service. The 3‐month, 6‐month, and 1‐year Assessment of SpondyloArthritis International Society (ASAS) NSAID Intake Scores were categorized into four groups, as follows: =0, >0 and ≤33.3, 33.3–66.6, and >66.6. Results: Of the 12 000 patients with AS, 150 were identified with CKD, and the incidence rate was 4.64 per 10 000 patient‐years. Factors significantly associated with CKD included age ≥60 years, Charlson Comorbidity Index, hypertension, and diabetes mellitus. In the nested case–control analysis, among the ASAS NSAIDs Intake Scores for 0–365 days from diagnosis, the ≥66.6 group had a significantly lower odds ratio than those of the =0 group. Conclusion: The present study established the incidence rate of CKD in Korean patients with AS. Though older age and comorbidities were found to be associated with a higher CKD risk, long‐term NSAID use was associated with a lower risk. Therefore, the optimal use of NSAIDs in inflammatory diseases requires extensive research. [ABSTRACT FROM AUTHOR]

As a sensitive and non‐invasive method for assessing changes in renal cortical blood perfusion in the elderly, contrast‐enhanced ultrasound (CEUS) can indirectly reflect changes in kidney filtration and reabsorption function, thus providing feasibility for early evaluation of renal function changes. However, significant differences exist among researchers in terms of operational methods, contrast agent selection, post‐data analysis, and many other aspects, leading to substantial heterogeneity in results. This hinders horizontal comparisons and greatly limits the clinical application of contrast‐enhanced ultrasound for evaluating renal cortical blood flow perfusion. Based on the latest domestic and overseas literature and discussions with clinical experts, this consensus provides recommended guidelines for the evaluation of renal cortical blood flow perfusion using contrast‐enhanced ultrasound. It is hoped that this consensus will promote a better understanding of CEUS among medical practitioners at all levels and standardize the examination of renal cortical blood flow perfusion with CEUS. [ABSTRACT FROM AUTHOR]

Cell senescence, glycolysis, and mitochondrial deficit jointly regulate the development of septic acute kidney injury (SAKI). This study aimed to explore the role of circular RNA HIPK3 (circHIPK3) in mitochondrial function in SAKI. The SAKI mouse model was established by Candida albicans infection, followed by Western blot assay, measurements of serum lactate, and adenosine triphosphate (ATP), 5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethylbenzimi‐dazolylcarbocyanine iodide (JC‐1) staining and flow cytometry. Human renal tubular epithelial cells were treated with lipopolysaccharide to establish the SAKI cell model, followed by cell counting kit‐8 assay, tests of hexokinase activity, lactate production, oxygen consumption rate, extracellular acidification rate, ATP, and JC‐1 staining, and Western blot assay. The roles of mitochondrial pyruvate carrier 1 (MPC1) were validated by kidney function tests, hematoxylin and eosin staining, periodic acid‐Schiff staining, and SA‐β‐gal staining. circHIPK3 downregulation reduced glycolysis and mitochondrial dysfunction both in vivo and in vitro through the microRNA (miR)‐148b‐3p/DNMT1/3a/Klotho axis. Inhibition of miR‐148b‐3p or Klotho increased glycolysis and mitochondrial dysfunction. Knockdown of MPC1 increased lactate content and decreased ATP levels and MMP both in vivo and in vitro. Collectively, circHIPK3, in concert with the miR‐148b‐3p/DNMT1/3a/Klotho axis, increased glycolysis, and inhibited the negative regulation of lactate production by MPC1, and aggravated mitochondrial dysfunction and cell senescence in SAKI. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to examine the effect of periodontitis on renal function and morphology in rats with or without nephrectomy (Nx)‐induced chronic kidney disease (CKD). Methods: Rats were divided into sham surgery (Sham), Sham with tooth ligation (ShamL), Nx, and NxL groups. Periodontitis was induced by tooth ligation at 16‐week olds. Creatinine, alveolar bone area, and renal histopathology were analyzed at 20‐week olds. Results: Creatinine did not differ between the Sham and ShamL groups or between the Nx and NxL groups. The ShamL and NxL groups (both p = 0.002) had less alveolar bone area than the Sham group. The NxL group had fewer glomeruli than the Nx group (p < 0.000). The periodontitis groups demonstrated more tubulointerstitial fibrosis (Sham vs. ShamL p = 0.002, Nx vs. NxL p < 0.000) and macrophage infiltration (Sham vs. ShamL p = 0.002, Nx vs. NxL p = 0.006) than the groups without periodontitis. Only the NxL group had greater renal TNFα expression than the Sham group (p < 0.003). Conclusions: These suggest that periodontitis increases renal fibrosis and inflammation in the presence or absence of CKD but does not affect renal function. Periodontitis also increases TNFα expression in the presence of CKD. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of valproate encephalopathy in a patient with bipolar affective disorder, without the presence of hyperammonemia. Valproic acid (VA) is commonly used to treat seizures, bipolar disorder, and migraines, but it can have side effects, including non-hyperammonaemic parkinsonism. The article describes the patient's clinical presentation, neuroimaging findings, and laboratory results, highlighting the diagnostic challenges and treatment options. The authors emphasize the importance of recognizing and managing idiosyncratic reactions to VA, such as non-hyperammonaemic encephalopathy, which may not have typical biochemical abnormalities. They believe that their findings will be valuable for clinicians managing similar cases in the future. [Extracted from the article]

Aim: We compared survival and perioperative outcomes of robot‐assisted laparoscopic partial nephrectomy (RAPN) and laparoscopic radical nephrectomy (LRN) for older patients (age 70 years or older) with stage 1 renal cell carcinoma (RCC). Methods: This retrospective, single‐center study included 260 patients who underwent RAPN and 44 patients who underwent LRN. The overall survival (OS) and perioperative outcomes were compared between these two groups using an inverse probability of treatment weighting (IPTW) analysis. Results: Compared with the LRN group, a trend of more complications was observed in the RAPN group, including a higher body mass index (24 vs. 22 kg/m2; P = 0.0002) and higher rates of hypertension (77% vs. 55%; P = 0.0029) and chronic kidney disease (62% vs. 36%; P = 0.0027). After adjustment by the IPTW analysis, the RAPN group had a shorter operative time (143 vs. 282 min; P = 0.033), shorter postoperative length of hospital stay (PLOS) (4.1 vs. 7.9 days; P = 0.004), and less change in the estimated glomerular filtration rate during surgery (−8.4% vs. −32%; P < 0.0001) than the LRN group; however, the perioperative complication rates were similar. Patients who underwent RAPN had better 5‐year OS than those who underwent LRN (95% vs. 90%; log‐rank, P = 0.017). Conclusion: RAPN resulted in better OS and surgical outcomes, with shorter operative time, shorter PLOS, and better renal function preservation, than LRN for older patients with stage 1 RCC. Therefore, RAPN may be the primary option for patients indicated for surgical intervention. Geriatr Gerontol Int 2024; 24: 269–274. [ABSTRACT FROM AUTHOR]

Obesity became a serious public health problem with enormous socioeconomic implications among the Egyptian population. The present investigation aimed to explore the efficacy of Zingiber officinale extract as a hypolipidemic agent combined with the commercially well‐known anti‐obesity drug simvastatin in obese rats. Thirty‐five male Wister rats were randomly divided into five groups as follows: group I received a standard balanced diet for ten weeks; high‐fat diet was orally administered to rats in groups II–V for ten weeks. From the fifth week to the tenth week, group III orally received simvastatin (40 mg/kg B.W.), group IV orally received Z. officinale root extract (400 mg/kg B.W.), and group V orally received simvastatin (20 mg/kg B.W.) plus Z. officinale extract (200 mg/kg B.W.) separately. Liver and kidney function tests, lipid profiles, serum glucose, insulin, and leptin were determined. Quantitative RT‐PCR analysis of PPAR‐γ, iNOS, HMG‐CoA reductase, and GLUT‐4 genes was carried out. Caspase 3 was estimated in liver and kidney tissues immunohistochemically. Liver and kidney tissues were examined histologically. The administration of Z. officinale extract plus simvastatin to high‐fat diet‐fed rats caused a significant reduction in the expression of HMG‐coA reductase and iNOS by 41.81% and 88.05%, respectively, compared to highfat diet (HFD)‐fed rats that received simvastatin only. Otherwise, a significant increase was noticed in the expression of PPAR‐γ and GLUT‐4 by 33.3% and 138.81%, respectively, compared to those that received simvastatin only. Immunohistochemistry emphasized that a combination of Z. officinale extract plus simvastatin significantly suppressed caspase 3 in the hepatic tissue of high‐fat diet‐fed rats. Moreover, the best results of lipid profile indices and hormonal indicators were obtained when rats received Z. officinale extract plus simvastatin. Z. officinale extract enhanced the efficiency of simvastatin as a hypolipidemic drug in obese rats due to the high contents of flavonoid and phenolic ingredients. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the association between trypsin‐like protease (TLP) activity in the oral cavity as an indicator of periodontal health status and kidney function in Japanese workers. Materials and Methods: This cross‐sectional study included 1117 Japanese workers (mean age = 43.8 years). Tongue‐swab TLP activity was quantified as a* value (the redness intensity of the matrix disc of the TLP activity assessment kit; a larger value indicates more intense enzymatic activity in the samples and poorer periodontal health status). Kidney function was assessed using the estimated glomerular filtration rate (eGFR; a lower value indicates poorer kidney function). We performed ordinal logistic regression analyses to assess the association of the a* value with three eGFR categories: ≥90, 60–89 and <60 mL/min/1.73 m2. Results: The prevalence for each eGFR category was as follows: ≥90 (31.6%), 60–89 (63.8%) and <60 mL/min/1.73 m2 (4.6%). After adjusting for potential confounders, the a* value was found to be significantly associated with reduced kidney function. The multivariable‐adjusted odds ratio (95% confidence interval) for reduced kidney function was 1.12 (1.02–1.22) per unit increase in the a* value. Conclusions: Higher TLP activity was associated with reduced kidney function in Japanese workers. [ABSTRACT FROM AUTHOR]

The meta‐analysis aimed to assess renal function (RF) as a risk factor for diabetic foot ulcers (DFUs). Using dichotomous or contentious random or fixed effect models, the outcomes of this meta‐analysis were examined, and the odds Ratio (OR) and the mean difference (MD) with 95% confidence intervals (CIs) were computed. 16 examinations from 2004 to 2023 were enrolled for the present meta‐analysis, including 808 914 individuals with diabetes mellitus (DM). DFU had significantly higher chronic renal failure (OR, 3.17; 95% CI, 1.97–5.09, p < 0.001), higher serum Creatinine (MD, 29.30; 95% CI, 9.68–48.92, p = 0.003), and a low estimated glomerular filtration rate (MD, −15.31; 95% CI, −19.36 to −11.26, p < 0.001) compared to non‐DFU patients with DM. The examined data revealed that DFU had significantly higher chronic renal failure, higher serum Creatinine, and a low estimated glomerular filtration rate compared to non‐DFU patients with DM. Yet, attention should be paid to its values since some comparisons had a low number of selected studies. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a major health concern with a growing disease burden and inequalities in access to treatments. Glomerular filtration rate (GFR) is accepted as the best overall measure of kidney function and is considered the most important measure for medications cleared by the kidneys. In clinical practice, equations that estimate GFR using validated prediction equations are routinely used. This practice update was developed by a Working Group comprising clinical pharmacists representing the Society of Hospital Pharmacists of Australia (SHPA) Specialty Practice streams of Nephrology, Oncology and haematology, Critical care and Infectious diseases. It is intended to provide practical recommendations for clinical pharmacists who use equations to estimate GFR for medication dosing decisions. The limitations of the various equations in use — such as the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI), the Cockcroft–Gault equation and Modification of Diet in Renal Disease — are summarised and compared to direct measures of kidney function using exogenous markers. The CKD‐EPI equation is recommended to be used routinely as a primary measure of kidney function. Dose adjustments should also consider medication‐specific, patient‐related, and disease‐related characteristics. Kidney function and the response to therapy should be continuously assessed by monitoring the signs, symptoms and disease outcomes, the emergence of adverse reactions or medication‐induced disorders and use therapeutic drug monitoring (if available) to adjust doses accordingly. [ABSTRACT FROM AUTHOR]

Background: Individuals with pre‐existing chronic kidney disease (CKD) are at an increased risk of experiencing severe symptoms if infected with COVID‐19. This report presents the case of a patient with CKD who contracted COVID‐19 and subsequently experienced rapid deterioration of kidney function, hair loss, and spontaneous remission of facial warts. Case presentation: A 60‐year‐old Chinese man with a decade‐long history of abnormal serum creatinine (Scr) levels and recently heightened fatigue sought treatment. The disease was previously managed and deemed resolved in 2020. However, when he contracted the novel coronavirus on December 20, 2022, he experienced persistent fatigue without other symptoms. In early January 2023, Scr levels was examined as more than 300 μmol/L. This was followed by hair loss, including eyebrows and lashes, and the spontaneous resolution of a longstanding facial wart. During this period, although the patient received kidney‐protecting drugs and a lifestyle optimization, Scr increased continuously and the disease eventually progressed to the uremic stage. As the patient still had relatively abundant urine volume, the patient chose peritoneal dialysis treatment. At a two‐month follow‐up, he had adhered to the CAPD protocol without complications and his hair had begun to regrow. After eight months, his hair had mostly regrown, and his Scr levels kept stable. Conclusion: This case may represent the inaugural instance of CKD patients experiencing rapid deterioration of renal function, hair loss, and spontaneous remission of common warts. The underlying mechanisms of this unique phenomenon warrant further researches and debate. [ABSTRACT FROM AUTHOR]

Objective: There is a growing prevalence of chronic kidney disease (CKD), a condition associated with a higher cardiovascular disease (CVD) risk. We assessed the association between self‐reported physical activity (PA) and CKD and also studied whether PA attenuates CKD‐associated CVD risk. Methods: A cohort of Spanish adults (18–64 years) participated in this nationwide study. Participants were categorized at baseline as being either inactive (performing no PA), regularly, or insufficiently active (meeting or not, respectively, international PA recommendations) and were followed for up to 5 years. The presence of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) and major CVD risk factors (diabetes, hypercholesterolemia, hypertension, obesity) was determined at baseline and at follow‐up. Results: 517 917 participants (44 ± 9 years, 67% male, CKD prevalence = 7%) were studied at baseline, with prospective analyses (median follow‐up = 2 years, range = 2–5) in a subcohort of 264 581 individuals. Compared to physical inactivity, cross‐sectional analyses at baseline showed that regular PA (odds ratio = 0.80; 95% confidence interval = 0.79–0.81), but not insufficient PA (1.02; 0.99–1.04) was associated with lower CKD prevalence. However, prospective analyses failed to confirm this association (p > 0.1). In turn, CKD was associated with a higher prevalence of hypertension (+3%) and diabetes (+5%) at baseline and with a greater incidence of hypertension at follow‐up (+37%). Among those participants with CKD, regular PA was associated with a lower prevalence (−45% to −7%) and incidence (−38% to −4%) of all CVD risk factors. Conclusion: Although PA might not reduce incident CKD in the middle term (~2 years), it can attenuate the CVD risk linked to this condition. [ABSTRACT FROM AUTHOR]

Background and Aim: The causal linkage between primary sclerosing cholangitis (PSC) and kidney function is unexplored despite their potential for long‐term detrimental effects on kidney function. Methods: Two‐sample summary‐level Mendelian randomization (MR) study was conducted to identify the association between PSC and kidney function. The genetic variants were extracted from the PSC‐specific multi‐trait analyzed genome‐wide association study (GWAS) of European ancestry. Summary‐level data for kidney function traits, including estimated glomerular filtration rate (eGFR), annual eGFR decline, and chronic kidney disease (CKD), were obtained from the CKDGen consortium. Multiplicative random‐effects inverse‐variance weighted (MR‐IVW), and a series of pleiotropy‐robust analyses were performed to investigate the causal effects and ascertain their robustness. Results: Significant causal associations between genetically predicted PSC and kidney function traits were identified. Genetically predicted PSC was associated with decreased log‐transformed eGFR (MR‐IVW; beta = −0.41%; standard error [SE] = 0.02%; P < 0.001), increased rate of annual eGFR decline (MR‐IVW; beta = 2.43%; SE = 0.18%; P < 0.001), and higher risk of CKD (MR‐IVW; odds ratio = 1.07; 95% confidence interval = 1.06–1.08; P < 0.001). The main findings were supported by pleiotropy‐robust analysis, including MR‐Egger with bootstrapped error and weighted median. Conclusions: Our study demonstrates that genetically predicted PSC is causally associated with kidney function impairment. Further studies are warranted to identify the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Objectives: To assess whether the extent of monosodium urate (MSU) crystal deposition estimated by ultrasound could predict renal and cardiometabolic events during urate‐lowering therapy (ULT). Methods: A prospective study on gout patients from two referral centers initiating ULT who underwent baseline ultrasound and were followed for 1 year. Ultrasound scans assessed six joints for double‐contour (DC) signs and tophi. A five‐point change (mL/min/1.73 m2) in the glomerular filtration rate at month 12 (M12) was considered significant. Outcomes of interest were renal function degraded versus improved and a composite cardiometabolic outcome (new hypertension, diabetes, atherosclerotic disease, and cardiovascular death). Homogeneity analyses and Cox regression models were performed. Results: One hundred sixty patients were recruited. At baseline, 81.1% of patients (n = 129) showed sonographic tophi with a mean number of 1.4 joints (±1.3) with a DC sign. At M12, 18 patients (11.3%) were lost to follow‐up. The serum urate (SU) target (<6.0 mg/dL) was reached in 86 patients (69.9%). Regarding renal function, 15.9% of patients showed improvement, while in 31.0% it degraded. Fourteen new cardiometabolic events occurred in 12 patients. Neither the DC sign nor tophi showed any significant impact on the outcomes of interest. Baseline SU level was higher in those with renal improvement but not with renal decline, while achieving the SU target protected against new cardiometabolic events (HR = 0.2; 95% CI: 0.05–0.81). Conclusions: Sonographic MSU crystal burden was unhelpful in predicting renal and cardiometabolic events during the first year of ULT. Reaching the SU target prevented cardiometabolic events, while its benefit in preserving/improving renal function is unclear. [ABSTRACT FROM AUTHOR]

Background: Hematopoietic cell transplant (HCT) patients undergo pre‐ transplant renal function evaluation to confirm transplant eligibility and tailor pharmacotherapy. There is limited evidence regarding the most accurate method of estimating creatinine clearance (CrCl) within this patient population and no studies exist that evaluate the weight utilized within the Cockcroft‐Gault (CG) equation in HCT patients. This study evaluates different weight and serum creatinine (SCr) adjustments utilized within the CG equation estimating for renal clearance in patients undergoing HCT. Objective: This is a retrospective, single center analysis of adult HCT patients who underwent pre‐transplant evaluation with a measured CrCl using a 24‐h urine creatinine collection. The primary outcome was to evaluate the correlation of various weights used in estimation of CrCl compared to measured CrCl. Key secondary outcomes include evaluation of the impact of various weights on estimated CrCl in subpopulations, evaluation of adjusting SCr to pre‐determined limits, and determination of an appropriate obesity threshold to utilize body weight adjustments. Results: Seven‐hundred and forty‐two patients were included in the study. In the primary analysis, CG utilizing adjusted body weight (ADjBW0.4) had a greater correlation (r =.812) to measured CrCl when compared to total or ideal body weight (r =.801 and r =.790 respectively). The threshold of 120% of ideal body weight (IBW) produced less bias and greater accuracy in comparison to the threshold of 140% IBW. In patients 60 years or older, rounding low SCr values up.8 or 1 mg/dL resulted in decreased correlation and a greater mean difference in comparison to not rounding SCr. Conclusion: In HCT patients who are overweight or obese, ADjBW.4 is the most accurate weight for the CG equation. In HCT patients who have a total body weight < 120% IBW, total body weight is the most accurate weight to utilize. Rounding up low SCr to.8 or 1 mg/dL does not improve the accuracy or led to less bias of the CG equation. [ABSTRACT FROM AUTHOR]

Objective: To assess 12‐month safety and efficacy of pegloticase + methotrexate (MTX) versus pegloticase + placebo (PBO) cotherapy in a PBO‐controlled, double‐blind trial (A randomized, double‐blind, placebo‐controlled, multicenter, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase [MIRROR RCT]). Methods: Patients with uncontrolled gout (serum urate level [SU] ≥7 mg/dl, oral urate‐lowering therapy failure or intolerance, and presence of one or more gout symptoms [one or more tophi, two or more flares in 12 months, gouty arthropathy]) were randomized 2:1 to receive pegloticase (8‐mg infusion every 2 weeks) with blinded MTX (oral 15 mg/week) or PBO for 52 weeks. Efficacy end points included proportion of responders (SU level <6 mg/dl for ≥80% of examined month) in the intent‐to‐treat population (ITT) (all randomized patients) during month 6 (primary end point), month 9, and month 12; proportion with resolution of one or more tophi (ITT); mean SU reduction (ITT); and time to SU‐monitoring pegloticase discontinuation. Safety was evaluated via adverse event reporting and laboratory values. Results: Month 12 response rate was significantly higher in patients cotreated with MTX (60.0% [60 of 100] vs. 30.8% [16 of 52]; difference: 29.1% [95% confidence interval (CI): 13.2%‐44.9%], P = 0.0003), with fewer SU discontinuations (22.9% [22 of 96] vs. 63.3% [31 of 49]). Complete resolution of one or more tophi occurred in 53.8% (28 of 52) versus 31.0% (9 of 29) of MTX versus PBO patients at week 52 (difference: 22.8% [95% CI: 1.2%‐44.4%], P = 0.048), more than at week 24 (34.6% [18 of 52] vs. 13.8% [4 of 29]). Consistent with observations through month 6, pharmacokinetic and immunogenicity findings showed increased exposure and lower immunogenicity of pegloticase when administered with MTX, with an otherwise similar safety profile. No infusion reactions occurred after 24 weeks. Conclusion: Twelve‐month MIRROR RCT data further support MTX cotherapy with pegloticase. Tophi resolution continued to increase through week 52, suggesting continued therapeutic benefit beyond month 6 for a favorable treatment effect. [ABSTRACT FROM AUTHOR]

Aim: To examine the association between body mass index (BMI)‐independent allometric body shape indices and kidney function. Materials and methods: We performed a two‐sample Mendelian randomization (MR) analysis, using summary statistics from UK Biobank, CKDGen and DIAGRAM. BMI‐independent allometric body shape indices were: A Body Shape Index (ABSI), Waist‐Hip Index (WHI) and Hip Index (HI). Kidney function outcomes were: urinary albumin‐to‐creatinine ratio (UACR), estimated glomerular filtration rate and blood urea nitrogen. Furthermore, we investigated type 2 diabetes (T2D) as a potential mediator on the pathway to albuminuria. The main analysis was inverse variance‐weighted random‐effects MR in participants of European ancestry. We also performed several sensitivity MR analyses. Results: A 1‐standard deviation (SD) increase in genetically predicted ABSI and WHI levels was associated with higher UACR (β = 0.039 [95% confidence interval: 0.016, 0.063] log [UACR], P = 0.001 for ABSI, and β = 0.028 [0.012, 0.044] log [UACR], P = 6 x 10−4 for WHI) in women, but not in men. Meanwhile, a 1‐SD increase in genetically predicted HI was associated with lower UACR in women (β = −0.021 [−0.041, 0.000] log [UACR], P = 0.05) and in men (β = −0.026 [−0.058, 0.005] log [UACR], P = 0.10). Corresponding estimates in individuals with diabetes were substantially augmented. Risk of T2D increased for genetically high ABSI and WHI in women (P < 6 x 10−19) only, but decreased for genetically high HI in both sexes (P < 9 x 10−3). No other associations were observed. Conclusions: Genetically high HI was associated with decreased risk of albuminuria, mediated through decreased T2D risk in both sexes. Opposite associations applied to genetically high ABSI and WHI in women only. [ABSTRACT FROM AUTHOR]

Background: High‐intensity training (HIT) programmes are popularly associated with improvements in exercise efficiency and body composition, although, at extremes, have been accompanied by concerns of secondary rhabdomyolysis and severe acute kidney injury (AKI). Beyond the anecdotal, robust literature on the physiological impact of HIT on renal function is currently limited. Aims: To investigate the acute impact of high‐intensity (CrossFit®) training on renal function, and to evaluate the incidence of AKI by Risk, Injury, Failure, Loss, End‐stage renal disease (RIFLE) criteria following CrossFit® training. Methods: Clinical and biochemical parameters were measured in 22 healthy adults before and after two CrossFit® workouts: 'Fran' (12 men, 10 women) and 'Macho Man' (9 men, 4 women). Results: Serum creatinine increased by 16 ± 10 μmol/L following Fran and 18 ± 12 μmol/L following Macho Man (P < 0.05). Cystatin C did not change significantly following Fran and increased by 0.06 ± 0.06 mg/L (P < 0.05) following Macho Man. AKI, as defined by RIFLE 'Risk' criteria, was observed in 5/22 (23%) participants following Fran and 5/13 (38%) participants following Macho Man. Urinary albumin/creatinine ratio rose by 18.7 ± 18.3 and 5.2 ± 6.0 mg/mmol following Fran and Macho Man respectively off non‐albuminuric baselines (P < 0.05). Conclusions: Intense (CrossFit®) exercise is associated with significant metabolic demands and alterations in parameters of renal physiology and function. The observed rise in both conventional and novel biomarkers of renal function following the workout Macho Man specifically might indicate a degree of transient subclinical functional impairment with CrossFit®‐type training. [ABSTRACT FROM AUTHOR]

The article explores the relationship between polypharmacy and renal function among elderly individuals. It discusses the number of medications influences renal health and emphasizes the implications for managing medication regimens in aging populations. It mentions the study originates from the Division of Geriatric and Community Medicine at Tohoku Medical and Pharmaceutical University in Sendai, Japan, authored by multiple researchers including Saki Nakayama, Yurika Hirota, and Yuiko Suzuki.

Background: Aboriginal and Torres Strait Islander people have higher rates of diabetes and its complications than non‐Aboriginal people. Rumbalara Aboriginal Co‐operative is the major primary healthcare provider for Aboriginal people in the Greater Shepparton region. Aims: To evaluate the baseline metabolic parameters and presence of diabetes complications in people with type 2 diabetes attending Rumbalara Aboriginal Co‐operative in 2017 and compare it with other Aboriginal and Torres Strait Islander studies and Australian specialist diabetes services. Methods: Clinical and biochemical characteristics, including diabetes type, age, weight, body mass index (BMI), blood pressure, micro‐ and macrovascular complications, glycosylated haemoglobin (HbA1c), haemoglobin, renal function, lipid profile, urine albumin:creatinine ratio, diabetes medications, renin angiotensin system inhibition therapies, HMG‐CoA reductase inhibitors and antiplatelet agents, were determined. Results: One hundred and twenty‐six individuals had diabetes, 121 had type 2 diabetes. One hundred and thirteen identified as Aboriginal and/or Torres Strait Islander. Median age was 57.5 (48–68) years, median HbA1c was 7.8% (6.8–9.6) and median BMI was 33.4 kg/m2 (29–42.3). Compared with other Australian Aboriginal and Torres Strait Islander populations, this population was older and had more obesity, but with better glycaemia management. Compared with specialist diabetes services, this population was of similar age, with greater BMI but comparable HbA1c. Conclusions: Aboriginal people living with type 2 diabetes attending this regional Aboriginal health service have comparable glycaemic management to specialist diabetes services in Australia, managed largely by primary care physicians with limited access to specialist care for the past 5 years. [ABSTRACT FROM AUTHOR]

Background: The study aimed to fully understand small bowel necrosis, a rare but fatal complication after esophagectomy. Methods: Patients who underwent esophagectomy for esophageal cancer at the Fudan University Shanghai Cancer Center from January 2013 to December 2021 were retrospectively reviewed. Clinical information on the demographics, presenting features, and outcomes of the cases were collected. Results: Of the 6607 patients during the study period, 11 (0.2%) underwent reoperation due to bowel necrosis, including nine males (81.8%) and two females (18.2%). Among them, eight cases (72.7%) had hypertension and seven (63.6%) suffered from lower thoracic esophageal cancer. Eight (72.7%) and three (27.3%) patients underwent the Ivor‐Lewis and McKewon procedures, respectively. Jejunostomy was performed in nine patients (81.8%). The first signs of bowel necrosis appeared within 5 days after esophagectomy. Abdominal distension and deteriorating renal function were observed in seven patients (63.6%). There was no evidence of mesenteric vascular occlusion in any of the 11 cases, except for the hepatic portal venous gas found in seven patients on the computed tomography (CT) scan. Eight (72.7%) of the 11 patients underwent reoperation within 24 h due to the onset of the first symptoms. Eight (72.7%) had ileal necrosis, and three (27.3%) died. Conclusion: Close attention should be paid to patients with abdominal distension, renal function damage, and portal hepatic venous gas after esophagectomy. These patients may suffer from small bowel necrosis, which may result in rapid disease progression. Exploratory laparotomy and bowel resection are effective treatments for such patients. [ABSTRACT FROM AUTHOR]

Objective: This research aimed to explore the effect of periodontitis on renal tissues injury in rats and the role of Sirtuin3 (Sirt3) and its regulation of autophagy in this progression. Material and Methods: Thirty Wistar rats were assigned into three groups: control, periodontitis (P), and periodontitis with gavage administration of Sirt3 activator resveratrol (P + RSV). To induce periodontitis, the wire ligature was placed around the cervical region of the rat maxillary first molar. After 8 weeks, micro-computed tomography (Micro-CT) and hematoxylin and eosin (HE) were used to evaluate the alveolar bone resorption and periodontal inflammation. Serum and urine biochemical indicators were measured to assess renal function. The pathological changes of the kidney were observed via HE and periodic acid Schiff (PAS) staining. Autophagosome was viewed by transmission electron microscopy (TEM). Real-time PCR and western blot were used to test expressions of Sirt3 and autophagy indicators in renal and periodontal tissues, including mammalian target of rapamycin (mTOR), phosphor-mTOR (p-mTOR), BECN1 (Beclin-1), and microtubule-associated protein 1 light chain 3 (LC3). Results: Alveolar bone destruction, resorption, and periodontal inflammation were observed in the P group (compared with the control group), and the above indexes were significantly improved after RSV intervention; the obvious changes in renal tissue structure in the P group were partially recovered after RSV intervention, while renal functional status was not affected (among the three groups); in addition, the levels of Sirt3 and autophagy in kidney and periodontal tissues of P group were inhibited, manifested as a decrease in the number of autophagosomes (renal tissue) and expressions of autophagy marker Beclin-1 and LC3 conversion rate and an increase in the expression of p-mTOR. After Sirt3 activation (RSV), the above indicators were significantly improved. Conclusion: Periodontitis causes renal structural damage in rats, which may be connected to the effect of Sirt3-induced autophagy. [ABSTRACT FROM AUTHOR]

Age and sex need to be considered in the establishment of reference intervals (RIs), especially in early life when there are dynamic physiological changes. Since data for important biomarkers in healthy neonates and infants are limited, particularly in Iranian populations, we have determined age‐specific RIs for 7 laboratory biochemical parameters. This cross‐sectional study comprised a total of 344 paediatric participants (males: 158, females: 186) between the ages of 3 days and 30 months (mean age: 12.91 ± 7.15 months). Serum levels of creatinine, urea, uric acid, calcium, phosphate, vitamin D and high‐sensitivity C‐reactive protein (hs‐CRP) were measured using an Alpha classic‐AT plus auto‐analyser. We determined age‐specific RIs using CLSI Ep28‐A3 and C28‐A3 guidelines. No sex partitioning was required for any of the biomarkers. Age partitioning was required for kidney function tests and phosphate. The serum concentration of urea and creatinine increased with age, while phosphate and uric acid decreased with age. Age partitioning was not required for serum calcium, vitamin D, and hs‐CRP, which remained relatively constant throughout the age range. Age‐specific RIs for 7 routine biochemical markers were determined to address critical gaps in RIs in early life to help improve clinical interpretation of blood test results in young children, including neonates. Established age partitions demonstrate the biochemical changes that take place during child growth and development. These novel data will ultimately better disease management in the Iranian paediatric population and can be of value to clinical and hospital laboratories with similar populations. [ABSTRACT FROM AUTHOR]

Objective: This healthcare improvement initiative was designed to increase inpatient osteoporosis treatment after hip fracture. Methods: A new protocol was developed by Geriatric Medicine and Endocrinology departments at a tertiary care hospital in Sydney. Its aim was to standardize assessment and treatment of osteoporosis in patients admitted with hip fracture. Eligible inpatients would receive intravenous zoledronic acid during their admission. A 6‐month sample of hip fracture patients admitted after the protocol's implementation was compared to a group admitted before. Data collected included demographics, biochemistry, treatment rates, adverse effects, and admission survival. Results: There was a considerable increase in osteoporosis treatment after introducing the protocol. Before the protocol's introduction, none of 36 eligible patients received treatment. After the intervention 79% (23 out of 29) of eligible patients were treated. All treated patients had renal function and serum calcium levels checked post‐infusion with no adverse outcomes. Eight patients developed flu‐like symptoms within 24 h of the infusion. There were no instances of arrhythmias, ocular inflammation, or death. The cost per patient treated was AUD $87. Conclusion: Adopting a standardized protocol for osteoporosis treatment in patients admitted for hip fracture was effective in improving treatment rates whilst being relatively safe and inexpensive. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common complication after liver transplantation (LT) that is independently associated with an increased risk of morbidity and mortality. This study aimed to evaluate the effects of administering gelatin‐low dose albumin versus albumin on renal function and other early outcomes in LT. Methods: This randomized controlled clinical trial was conducted on 140 patients undergoing LT from brain death donors. Patients were randomly assigned to two groups: albumin or modified gelatin with albumin. Blood samples were collected before (T0) and on the first (T1), second (T2), third (T3), fifth (T4), and last day of hospitalization (T5) after LT for the detection of laboratory parameters, including renal and liver function tests. Results: The incidence of AKT on the basis of RIFLE criteria was 31.42% in the gelatin group (R: 59.10%, I: 36.40%, and F: 4.50%) and 25.71% in the albumin group (R: 66.70%, I: 27.80%, and F: 5.50%) (p =.845). Two patients in the gelatin and one in the albumin groups required renal replacement therapy (RRT). There was no significant difference between groups when the trends of changes in renal and liver function parameters were assessed during the study period (T0–T5). Furthermore, the incidence of complications was similar across groups. Conclusion: This study showed that modified gelatin could be used without inappropriate outcomes on renal function in patients with normal preoperative kidney function tests undergoing LT. [ABSTRACT FROM AUTHOR]

Empiric antibiotic dosing frequently relies on an estimate of kidney function based on age, serum creatinine, sex, and race (on occasion). New non–race‐based estimated glomerular filtration rate (eGFR) equations have been published, but their role in supporting dosing is not known. Here, we report on a population pharmacokinetic model of vancomycin that serves as a useful probe substrate of eGFR in critically ill Thai patients. Data were obtained from medical records during a 10‐year period. A nonlinear mixed‐effects modeling approach was conducted to estimate vancomycin parameters. Data from 208 critically ill patients (58.2% men and 36.0% septic shock) with 398 vancomycin concentrations were collected. Twenty‐three covariates including 12 kidney function estimates were tested and ranked on the basis of the model performance. The median (min, max) age, weight, and serum creatinine was 69 (18, 97) years, 60.0 (27, 120) kg, and 1.53 (0.18, 7.15) mg/dL, respectively. The best base model was a 1‐compartment linear elimination with zero‐order input and proportional error model. A Thai‐specific eGFR equation not indexed to body surface area model best predicted vancomycin clearance (CL). The typical value for volume of distribution and CL was 67.5 L and 1.22 L/h, respectively. A loading dose of 2000 mg followed by maintenance dose regimens based on eGFR is suggested. The Thai GFR not indexed to BSA model best predicts vancomycin CL and dosing in the critically ill Thai population. A 5% to 10% absolute gain in the vancomycin probability of target attainment is expected with the use of this population‐specific eGFR equation. [ABSTRACT FROM AUTHOR]

Aim: To determine whether adolescents born before 28 gestational weeks have an increased risk for renal impairment. Methods: Swedish infants, born before 28 gestational weeks in 2001 and 2002, were identified from a local register. A total of 16 children, 12 females and 4 males, were examined at 16–17 years of age with 51Cr‐EDTA clearance. A comparison group (n = 26) was used. Results: Most study participants (n = 13) had normal blood pressure; one individual had hypertension stage 1. All study participants had results within the reference interval for ionised calcium, parathyroid hormone, intact fibroblast growth factor‐23 and for urinary albumin‐to‐creatinine ratio. Four out of 16 participants (25%) had a 51Cr‐EDTA clearance less than 90 ml/min/1.73 m2, indicating a reduced kidney function. Measured 51Cr‐EDTA clearance values were significantly lower in the study group than in the comparison group (p = 0.0012). Five study participants (31%) were referred for further investigations. Conclusion: Swedish children born before 28 gestational weeks have an increased risk of renal impairment later in life, suggesting that the kidney function in these individuals should be assessed, at least once, during adolescence. [ABSTRACT FROM AUTHOR]

Residual amounts of pyrethroids were detected in rice and vegetables of the Indian market. Thus, consumers are exposed to a mixture of pyrethroids on a daily basis through food. Though a large number of studies reported the toxic effects of pyrethroids, there are no reports that used doses equivalent to human consumption. In this study, male Wistar rats were exposed daily to a mixture of pyrethroids for 1–15 months which is equivalent to the amount present in rice and vegetables consumed by an average Indian each day. The oxidant‐antioxidant status (lipid peroxidation, nitric oxide; activities of catalase, glutathione peroxidase, glutathione S transferase, and superoxide dismutase) and anatomical changes in the general organs (liver, lung, and kidney) and male reproductive tract tissues (caput, cauda, testis, and prostate) were evaluated. Further, liver and kidney function tests, lipid profile, and complete blood picture were analyzed. Increased oxidative stress, perturbations in the antioxidant enzyme activities, and damage to the anatomical architecture were observed. Disturbances in the liver function and lipid profile were significant. Results of our study demonstrate that exposure to a mixture of pyrethroids at a dose that is equivalent to human consumption can cause systemic and reproductive toxicity, which may ultimately result in the development of lifestyle diseases. This first line of evidence will fuel further studies to determine the impact of food‐based pyrethroid exposure on the long‐term health of humans and to envisage policies to reduce pesticide content in food products. [ABSTRACT FROM AUTHOR]

Background: Comparative studies of kidney morphophysiology in nonhuman primates can help us investigate interspecies differences in growth and aging patterns. Methods: We tested the effect of age and sex in renal morphophysiology in 21 Alouatta caraya and 21 Sapajus apella (age range = 0.5–26 years) by ultrasound, red blood cell (RBC) count, and kidney function tests. Results: A. caraya had greater growth rate and absolute renal volume than S. apella, but the latter showed a greater relative renal volume and RBC count. There was a negative relationship between RBC and age, a positive relationship between creatinine and body mass, and an apparent negative relationship between creatinine and age only in S. apella. Conclusions: Our results indicate that A. caraya has a faster aging mechanism than S. apella, and the higher relative kidney volume in S. apella is suggestive of high metabolic demands in this species. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) during hospitalisation is frequent and associated with adverse outcomes. Aims: To evaluate the association between renal function recovery after AKI and short‐term post‐discharge mortality. Methods: This is a retrospective study of all AKI episodes codified in the electronic records of a single centre in 2013 and 2014. Epidemiological data and comorbidities at baseline and laboratory values at admission and discharge were collected. Persistent kidney dysfunction after AKI was defined as a last serum creatinine equal or above 1.2‐fold over baseline level. Patients were followed for 30 days after discharge. Results: Out of 1720 evaluated patients, 1541 (89%) were analysed. Of them, 869 (56%) recovered renal function. Independent predictors of renal function recovery after AKI were lower baseline estimated glomerular filtration rate (eGFR) (P < 0.001), higher admission eGFR (P < 0.001) and haemoglobin (P = 0.016), milder AKI (P = 0.037), absence of a history of heart failure (P < 0.001) and lower admission blood pressure (P < 0.001). After discharge, 46 (3%) patients died in the first 30 days. Persistent kidney dysfunction was associated (P = 0.01) with and independently predicted (odds ratio 2.6; 95% confidence interval 1.2–5.4; P = 0.01) short‐term post‐discharge mortality. Conclusions: Persistent kidney dysfunction after an AKI episode is an independent predictor of 30‐day post‐discharge mortality. This information might help select AKI patients who require closer follow up and monitoring after discharge. [ABSTRACT FROM AUTHOR]

Abrocitinib, an oral once‐daily Janus kinase 1 selective inhibitor, is under development for the treatment of atopic dermatitis. This phase 1, nonrandomized, open‐label, single‐dose study (NCT03660241) investigated the effect of renal impairment on the pharmacokinetics, safety, and tolerability of abrocitinib and its metabolites following a 200‐mg oral dose. Twenty‐three subjects with varying degrees of renal function (normal, moderate, and severe impairment) were enrolled. Active moiety exposures were calculated as the sum of unbound exposures for abrocitinib and its active metabolites. For abrocitinib, the adjusted geometric mean ratios (GMRs; %) for area under the concentration‐time curve from time 0 extrapolated to infinite time and maximum plasma concentration were 182.91 (90% confidence interval [CI], 117.09‐285.71) and 138.49 (90% CI, 93.74‐204.61), respectively, for subjects with moderate renal impairment vs normal renal function; corresponding GMRs were 121.32 (90% CI, 68.32‐215.41) and 99.11 (90% CI, 57.30‐171.43) for subjects with severe impairment vs normal renal function. Metabolite exposures generally increased in subjects with renal impairment. The GMRs of unbound area under the concentration‐time curve from time 0 extrapolated to infinite time and maximum plasma concentration of active moiety were 210.20 (90% CI, 154.60‐285.80) and 133.87 (90% CI, 102.45‐174.92), respectively, for subjects with moderate renal impairment vs normal renal function. Corresponding values were 290.68 (90% CI, 217.39‐388.69) and 129.49 (90% CI, 92.86‐180.57) for subjects with severe renal impairment vs normal renal function. Abrocitinib was generally safe and well tolerated. Both moderate and severe renal impairment led to higher exposure to abrocitinib active moiety, suggesting that abrocitinib dose should be reduced by half for patients with moderate or severe renal impairment. ClinicalTrials.gov identifier: NCT03660241 [ABSTRACT FROM AUTHOR]

Management of diabetic nephropathy (DN) is far from satisfactory. There is a rising role of the involvement of phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT) pathway in the pathogenesis of DN. This study aimed at investigating the renoprotective effects of PI3K/AKT pathway via sitagliptin in a rat model of DN. Thirty‐two male Wistar rats were divided into four groups (eight rats each): (I) control, (II) sitagliptin, (III) DN, and (IV) DN + sitagliptin. Fasting blood glucose (FBG), kidney index, and kidney function tests in both blood and urine were measured. The levels of superoxide dismutase (SOD), tumor necrosis factor‐alpha (TNF‐α), and transforming growth factor‐beta (TGF‐β) and gene expressions of PI3K, pPI3K, AKT, and pAKT in renal tissue were detected. Renal histopathological and immunohistochemical studies were evaluated. DN + sitagliptin group showed significant decrease in FBG and kidney index, improvement in kidney function tests, and a decrease in levels of TNF‐α and TGF‐β in renal tissues compared with DN group. This was associated with significant increase in SOD and gene expressions of PI3K and AKT and their phosphorylated active forms in renal tissue in DN + sitagliptin group compared with DN group. Moreover, DN + sitagliptin group showed apparent decrease in amount of collagen fibers and expression of alpha‐smooth muscle actin (α‐SMA) compared with DN group. This work shows that sitagliptin improved renal functions and histopathological changes, impeded inflammation, and oxidative stress and upregulated PI3K/AKT pathway which highlights its renoprotective effects in a rat model of DN. [ABSTRACT FROM AUTHOR]

Infants with acute kidney injury (AKI) who are critically ill often will have multiorgan dysfunctions. Objective of the present study was to find out mortality, recovery of kidney function at discharge and at 3 months, and to determine risk factors for mortality. Fifty‐two infants (24 newborns and 28 postneonatal) with AKI were included. Staging was done as per Kidney Disease Improving Global Outcomes classification. Patients were subjected to medical treatment and peritoneal dialysis (PD), wherever indicated. Kidney function tests were performed at admission, discharge, and at 3 months follow‐up. Median age of neonates was 8 days and postneonatal infants were 4.5 months. Stage 1, 2, and 3 AKI were present in 14 (26.9%), 16 (30.7%), and 22 (42.3%) cases, respectively. PD was required in 22 (42.3%) infants, and significantly higher in postneonatal than in neonates (57.1% vs. 25%, p < 0.05). Significant recovery of kidney function occurred at discharge and cases had normal parameters at 3 months. Mortality was 17.3%. Patients had significantly higher risk of mortality, if they had metabolic acidosis (OR 13.22, CI 2.33–74.94, p = 0.002) and needed ventilation (OR 14.93, 95% CI 1.7–130.97, p = 0.006) and PD (OR 6.53, 95% CI 1.20–35.48, p = 0.026). In logistic regression analysis, fluid overload (p < 001), hypotension (p < 0.01), and higher PRISM‐III score (p < 0.05) were found as significant risk factors for mortality. Medical management including PD led to good recovery of kidney function. Presence of fluid overload, hypotension, and higher PRISM‐III score adversely affected the outcome. [ABSTRACT FROM AUTHOR]

Background: Progressive renal impairment, given by an annual decline in estimated glomerular filtration rate (eGFR), has been described in patients with intestinal failure (IF) receiving home parenteral support (HPS). The objective of this study was to examine changes in eGFR over 5 years following initiation of HPS treatment and to identify potential risk factors for loss of renal function. Method: This retrospective database study investigates eGFR changes in nonmalignant IF patients discharged with HPS from Rigshospitalet, Copenhagen, in an 8‐year period. Results: One year after HPS initiation, mean eGFR decreased by 15.3 ml/min/1.73 m2. Paired t‐test showed a decline of 15.0 ml/min/1.73 m2 (95% CI, −18.3 to −11.6; P <.0001). Over the following years, eGFR continued to decrease but at insignificant lower rates. Decreased eGFR was associated with increasing age, female sex, increasing body weight, diabetes at HPS initiation, and a high requirement of HPS volume. Conclusion: In nonmalignant IF patients, the decrease of eGFR was mainly seen during the first year of HPS. This may be due to a higher risk of dehydration and possibly secondary hyperaldosteronism leading to renal damage following the onset of IF. However, the decrease in eGFR may also represent a higher production of creatinine due to a beneficial increase of muscle mass in the initial recovery phase. In general, once the patients were stabilized, the eGFR decline followed a physiological course resembling the background population. Patients with diabetes or high HPS volume needs seem to be more vulnerable and may require special attention. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated the risk of contrast‐associated acute kidney injury (CA‐AKI) is low post‐multimodal computed tomography (MMCT) in the evaluation of acute stroke. We provide a complementary study with long‐term renal follow up. A retrospective analysis was performed on all suspected strokes from January 2019 to June 2020 for those who had undergone computed tomography angiography, computed tomography perfusion or both. We identified 776 cases, of which 538 were excluded. The incidence of CA‐AKI was 7.6% (n/N = 18/238; 95% confidence interval = 4.2–11.0). All CA‐AKI cases had renal confounders. No AKI at >30 days was found in 60.5% (n = 144) of all cases studied. The long‐term renal outcome post‐MMCT in stroke evaluation is favourable at >30 days. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that requires long‐term management. Thus, dipeptidyl peptidase‐4 inhibitors (DPP‐4) need more investigations about their efficacy and safety profile as there is still no evidence of whether DPP‐4 inhibitors can be used as a first line option for T2DM drug‐naïve patients. In this randomized case‐controlled study, 60 drug‐naïve T2DM subjects were randomized into three groups, each group comprising 20 subjects. Group 1 was given sitagliptin 100 mg once daily, Group 2 was given vildagliptin 50 mg twice daily, and Group 3 served as the control group and was given metformin 1 g twice daily. Efficacy endpoints included changes in glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), and 2‐hr postprandial plasma glucose (PPG), and the secondary endpoints were related to safety profile were the assessment of liver and kidney function tests and complete blood count (CBC). All treatment regimens had comparable efficacy and safety profiles with the non‐significant relative superiority of vildagliptin in lowering HbA1c more than sitagliptin but significant (p = 0.011) regarding FPG reduction, vildagliptin significantly decreased HbA1c by −1.02% (p < 0.001), sitagliptin significantly decreased HbA1c by −0.96% (p < 0.001), and control significantly decreased HbA1c by −0.90% (p < 0.001) compared with baseline. The studied drugs showed moderate efficacy in lowering HbA1c levels with the non‐significant relative higher efficacy of DPP‐4 inhibitors. DPP‐4 inhibitors and metformin showed favourable effects on improving metabolic syndrome by decreasing blood pressure, serum triglycerides (TG), low‐density lipoprotein (LDL), total cholesterol, and increasing high‐density lipoprotein (HDL), plus their positive impacts on weight. As a final conclusion, the three medications are highly comparable. [ABSTRACT FROM AUTHOR]

Introduction: The association between the degree of isolated gestational proteinuria and preeclampsia with severe features and other placental‐mediated complications is controversial. The aim of this study was to evaluate whether a higher isolated proteinuria level is associated with an increased frequency of preeclampsia with severe features. Material and methods: This retrospective cohort study included pregnant women who were past 24 weeks of gestation and were diagnosed as having new‐onset proteinuria ≥300 mg in a 24‐h urine collection. Exclusion criteria included diagnosis of preeclampsia within 72 h from admission, chronic renal disease or chronic hypertension. The study population was divided into tertiles by proteinuria level and the association with preeclampsia with severe features was assessed in both bivariable and multivariable analysis. The main outcome measures was the development of preeclampsia with severe features. Results: Overall, 165 women were diagnosed with isolated gestational proteinuria, and 38 (23.0%) of them developed preeclampsia with severe features. Women in the increasing proteinuria tertile were more likely to develop preeclampsia with severe features (5.5%, 21.8%, 41.8%, respectively; p = 0.004). A multivariable logistic regression model controlling for background characteristics as well as gestational age at diagnosis, blood pressure, and kidney and liver function tests showed an increased risk of 14% to develop preeclampsia with severe features for every 500‐mg rise in proteinuria level (adjusted odds ratio = 1.14, 95% confidence interval 1.03–1.27). Conclusions: A higher isolated gestational proteinuria level was associated with an increased risk to develop preeclampsia with severe features among pregnant women past 24 weeks of gestation. [ABSTRACT FROM AUTHOR]

Aims: To investigate the clinical characteristics of health care‐seeking men presenting with lower urinary tract symptoms (LUTS) in China and to reveal risk factors for symptom severity. Methods: This multicenter, hospital‐based, cross‐sectional study recruited 1477 eligible male subjects, who were at least 45 years, seeking health care at 9 participating hospitals across the mainland China. The general medical information and subjective symptoms were recorded, followed by the measurement of prostate volume, urodynamic indices, and laboratory tests for kidney function, plus glucose/lipid metabolism. Univariate and multivariate linear regression were employed for the detection of risk factors for symptom severity. Results: The proportion of mild, moderate, and severe LUTS was 14.6%, 32.6%, and 52.8%, respectively, with 62.2% reporting the triple combination of storage, voiding, and postmicturition symptoms. Median prostate volume was 44.6 ml, and 71.1% were experiencing comorbidities. Thirteen independent risk factors for LUTS severity were identified, namely, nocturnal voiding episodes and the presence of straining and weak steam; the triple combination of symptom subtypes; general and nocturia quality of life; Qmax and bladder outlet obstruction index; and numbers of comorbidities, hypertension, estimated glomerular filtration rate, and cholesterol and glycosylated hemoglobin. Conclusions: The majority of health care‐seeking LUTS men present with moderate‐to‐severe and overlapping symptoms, with a high prevalence of both lower urinary tract dysfunction and systemic comorbidities. The evidence from both urological and nonurological independent risk factors demonstrate the multifactorial nature of LUTS, for which a multidisciplinary management is essential. [ABSTRACT FROM AUTHOR]

Background: Children with Down syndrome (DS) have different growth rates compared with normal children. The present study examined the reliability of a general formula, Uemura's formula, utilized in normal Japanese children to estimate renal function (estimated glomerular filtration rate – eGFR) in children with DS. Methods: This study included 758 children aged 2–18 years with DS who visited our medical center. Patients with congenital heart disease, or congenital anomalies of the kidney or urinary tract detected via abdominal ultrasonography, chronic glomerulonephritis, and vesicoureteral reflux, etc., were excluded. Height and serum creatinine data gathered from 2421 examinations of 379 children with DS (224 boys and 155 girls) were used to evaluate Uemura's formula. Results: The mean eGFR was lower in children with DS than in children without DS. Stage II chronic kidney disease was indicated in 44.6% of examinations and stage III in 0.8%. The association of eGFR with age differed between sexes. Boys with DS showed a significant but weak negative correlation between eGFR and age (r = −0.273, P < 0.001), whereas girls with DS showed a significant but very weak negative correlation (r = −0.111, P < 0.001). Conclusions: A new eGFR formula that takes into account specific growth rates and puberty is needed for children with DS because general renal function evaluation formulas are inappropriate for these patients. [ABSTRACT FROM AUTHOR]

Objectives: To identify predictors of renal function preservation, and to compare the global and split renal function outcomes of robot‐assisted partial nephrectomy and laparoscopic partial nephrectomy. Methods: Demographic, operative and pathological data, as well as renal function outcomes, of 251 patients who underwent laparoscopic (n = 104) and robot‐assisted (n = 147) partial nephrectomy between 2008 and 2018 were retrospectively analyzed. Propensity score matching (1:1) was carried out to adjust for potential baseline confounders. Functional outcomes were assessed based on the estimated glomerular filtration rate and dynamic renal scintigraphy (using 99mTc‐mercaptoacetyltriglycine), including renal volumetric analysis. Results: A total of 98 patients were allocated to each partial nephrectomy group. Ischemic (laparoscopic vs robot‐assisted partial nephrectomy: 29 vs 15 min, P < 0.001) and operative times (181 vs 100 min, P < 0.001) were shorter in robot‐assisted partial nephrectomy. The preservation ratio of global renal function at 3 months (88.3% vs 91.4%, P = 0.040) and 12 months (87.8% vs 91.5%, P = 0.010) postoperatively, and the renal function of the operated kidney (80.3% vs 88.2%, P < 0.001) were greater after robot‐assisted partial nephrectomy. In robot‐assisted partial nephrectomy, the volume of resected parenchyma was significantly smaller (27.2 vs 15.5 mL, P < 0.001), resulting in greater postoperative normal parenchymal volumes (120 vs 132 mL, P < 0.001) and a greater parenchymal preservation ratio (81.1% vs 90.1%, P < 0.001). The parenchymal preservation ratio was the strongest predictor of renal function preservation after surgery (P < 0.001, odds ratio 6.02). Conclusions: Robot‐assisted partial nephrectomy allows better preservation of split renal function than laparoscopic partial nephrectomy by increasing the parenchymal preservation ratio. This translates into better postoperative global renal function. [ABSTRACT FROM AUTHOR]

The article focuses on coronaviridae family is a broad emerging group of Ribonucleic Acid viruses that has affected humans repeatedly in the past few decades. Topics include the coagulation dysfunction is leading to life-threatening complications as disseminated intravascular coagulation and multiple organ failure in some patients, the diagnosis and treatment intervention are pivotal to management, and the limitations are of concern in resource-limited developing countries as Pakistan.

Background: The objective of this meta‐analysis of randomised controlled clinical trials (RCT) was to evaluate the effects of febuxostat on kidney function in patients with hyperuricaemia. Aims: Febuxostat is a xanthine oxidase inhibitor that decreases uric acid production. Recent studies suggested the renoprotective effect of febuxostat among hyperuricaemia patients. The aim of this study was to evaluate the effects of febuxostat on kidney function in patients with hyperuricaemia. Methods: We conducted electronic searches in PubMed, Embase and Cochrane Central Register of Controlled Trials from January 1960 to July 2019 to identify RCT that examined the effects of febuxostat in adult patients with hyperuricaemia on serum creatinine, estimated glomerular filtration rate (eGFR), albuminuria, blood pressure parameters, major cardiovascular events, diarrhoea, joint pain, stroke and arrhythmia. Results: Nine RCT with 2141 participants were included in this meta‐analysis. Compared to placebo, the febuxostat group showed a higher eGFR at 6 months with a weighted mean difference (WMD) of 2.86 mL/min/1.73 m2 (P < 0.001), as well as the end of studies (eGFR WMD 2.69 mL/min/1.73 m2, P < 0.001). There was also lower serum creatinine (SrCr WMD = −0.04 mg/dL, P < 0.001), reduction in systolic blood pressure (SBP WMD = −1.18 mmHg, P < 0.001) and diastolic blood pressure (DBP WMD = −1.14 mmHg, P = 0.04). There was no statistical difference between febuxostat and placebo in major cardiovascular events, diarrhoea, joint symptoms, stroke events and arrhythmia. Subgroup analysis among chronic kidney disease showed the febuxostat group had higher eGFR than the placebo group (eGFR WMD = 2.69 mL/min/1.73 m2, P < 0.001). Conclusion: Treating hyperuricaemia with febuxostat may slow the progression of chronic kidney disease irrespective of baseline renal function without significantly associated increased risks of major cardiovascular events, diarrhoea, joint symptoms, arrhythmia and stroke, compared to placebo. [ABSTRACT FROM AUTHOR]

Dedifferentiation of tubular epithelial cells is involved in both regeneration and fibrosis following acute kidney injury (AKI). Prostaglandin E2 receptor 4 (EP4) antagonist can inhibit the dedifferentiation of renal tubular cells. The present study investigated whether the time of blockage of EP4 receptors, using grapiprant, could affect the tubular regeneration or interstitial fibrosis in AKI. Cisplatin was used to induce AKI in 72 C57BL/6 adult female mice. Animals were assigned to four groups; control, cisplatin‐treated, cisplatin‐treated with early grapiprant intervention and cisplatin‐treated with late grapiprant intervention. AKI was assessed by kidney function tests and histopathology. Fibrosis was evaluated by Masson's trichrome and alpha smooth muscle actin (α‐SMA) expression. Markers of dedifferentiation, CD133, and epithelial to mesenchymal transition (EMT), vimentin were assessed. Early intervention with grapiprant significantly ameliorated AKI more efficiently than late intervention. However, even late intervention was useful in reducing the overall fibrosis as demonstrated by Masson's trichrome and α‐SMA expression. In both grapiprant‐treated groups, a parallel reduction of dedifferentiation (CD133) and EMT (vimentin) was evident. It seems that the progressive fibrotic changes that follow AKI could still be reduced possibly by targeting dedifferentiation and/or EMT. [ABSTRACT FROM AUTHOR]

Cisplatin is a highly cytotoxic anticarcinogenic drug used to treat several kinds of solid tumors such as liver tumors. With the increase in the incidences associated with hepatic tumors and a lack of selectivity of cisplatin to cancer cells, it is important to explore new therapeutic strategies against them. The present study was designed to verify the ability of gold nanoparticles (GNPs) to improve the hepatotherapeutic effect of cisplatin against DENA‐induced hepatic tumors and to declare its ability to reduce the renal toxicity induced by cisplatin. Forty male Wistar rats were divided into two groups (n = 20): Group (A)—negative control and group (B)—model of hepatocellular tumor induction. After 4 months, each group was subdivided into four subgroups as the following: Group (1) received normal saline, Group (2) was treated by cisplatin, Group (3) was treated by GNPs, Group (4) was treated by GNPs–cisplatin conjugates. Our results revealed a marked elevation in liver and kidney function tests and oxidant levels with a reduction in antioxidant levels in the DENA‐administrated group. Remarkable histopathological alterations in the liver and kidney tissue sections were observed and confirmed by the overexpression of the immunohistochemical staining of placental glutathione S‐transferase, Hep Par 1, and proliferating cell nuclear antigen. Noticeable improvements in all the measurable toxicological parameters were recorded in the group treated with either GNPs or GNPs–cisplatin conjugate not observed in the group treated with cisplatin. We can conclude that GNPs not only improve the distribution of cisplatin, targeting it to the site of tumors, but it also reduces the renal toxicity induced by cisplatin, which are the primary concerns in cancer therapy. [ABSTRACT FROM AUTHOR]

This work was designed to estimate the protective effect of Saraca indica L. leaves ethanolic exract against γ‐irradiation induced renal damage in rats. Phytochemical examinations of S. indica L. leaves extract resulted in the separation of three flavanone glycosides: Astilibin (1), Neoastilbin (2), and Eriodictyol‐7‐O‐α‐l‐rhamnopyranoside (3); two flavonols: Quercetin (4) and Quercetin‐3‐O‐α‐l‐arabinopyranosyl‐(1′′′‐6′′)‐O‐β‐D‐galactopyranoside (5) in addition of Gallic acid (6) and methyl gallate (7). Their structures elucidated by chemical evidences and spectroscopic analysis (1 and 2D‐NMR, ‐ESI‐MS, UV). Female rats were used and classified into: control, Ext (200 mg/kg body wt/day orally for 7 days), IRR (8Gy), Ext + IRR, and Sily+IRR groups (received silymarin 50 mg/kg b.wt orally as reference drug). Results showed that S. indica L. leaves extract ameliorated the kidney function tests, hs‐CRP, IL‐1β, ACE, TNF‐α, GSH, and MDA as well as, decreased the histopathological changes of kidney. In conclusion, S. indica L. leaves extract had a renoprotective activity against irradiation induced renal injury due to its flavononid contents. [ABSTRACT FROM AUTHOR]

d‐Galactosamine (d‐GalN) is a well‐known toxin that causes many metabolic and morphological abnormalities resulting in advanced renal failure and liver damage. Occupational exposure to low‐level ionizing radiation (<1 Gy) was shown to enhance cell protection via attenuating an established inflammatory process. The present study was therefore aimed to investigate the protective impact of Amphora coffaeiformis extract and low dose gamma radiation against d‐GalN induced renal damage in rats. Forty‐eight adult male Swiss albino rats were distributed equally into eight groups. The measurements included antioxidants activities (superoxide dismutase, catalase and glutathione peroxidase) as well as lipid peroxidation level in kidney tissue. Also, kidney function tests and inflammatory markers (tumor necrosis factor alpha and nuclear factor kappa‐light‐chain‐enhancer of activated B cells) were measured. Additionally, relative quantification of kidney nuclear factor erythroid 2‐related factor 2 (Nrf‐2) gene was estimated. Histopathological examination was also performed in kidney tissue. The results revealed decreases in antioxidant activities and downregulation of Nrf‐2 expression accompanied by increases in lipid peroxidation level, kidney function tests and inflammatory markers in d‐GaIN group. The treatment with Amphora algal extract and low dose gamma radiation ameliorated the previous measurements which were harmony with histopathological findings. In conclusion, A coffaeiformis extract and low dose gamma radiation provided marked functional and histological effects in the treating acute renal damage induced by d‐GalN in rats. [ABSTRACT FROM AUTHOR]

Within clinical small animal practice, diagnosis of both chronic kidney disease and acute kidney injury is common. To assess renal function, measurement of glomerular filtration rate is considered the gold standard. Currently, routine tests of kidney function include surrogate markers of glomerular filtration rate such as serum creatinine, and urea, each with their own limitations, whilst urine protein to creatinine ratio gives an indication of glomerular and tubular handling of protein, and urine specific gravity information about urine concentrating ability by the kidney. These parameters are used together with historical and physical examination data to give a diagnosis of kidney disease following which creatinine, proteinuria and blood pressure are used to stage chronic kidney disease and, together with urine output, grade acute kidney injury according to the International Renal Interest Society. However, there has been much concern that creatinine is insensitive when used to indicate early decline in renal function and this has highlighted the need for additional methods of diagnosing and monitoring these patients, with the potential to allow earlier therapeutic intervention. Symmetric dimethylarginine is a novel biomarker, which has been shown to perform as a surrogate marker of glomerular filtration rate in small animals. This article will review current research on symmetric dimethylarginine and the ways in which it may be utilised in small animal practice; current research supports the use of symmetric dimethylarginine as a screening test for detection of early chronic kidney disease according to International Renal Interest Society guidelines, but further research is required in to the usefulness of symmetric dimethylarginine as a tool for monitoring disease and the effect of non‐renal influences. [ABSTRACT FROM AUTHOR]

The estimated glomerular filtration rate (eGFR) equations based on serum creatinine (SCR) have been used for pediatric dose adjustment in drug labeling. This study evaluated the performance of those equations in estimating individual clearance of drugs that are predominantly eliminated by glomerular filtration, using clinical data from the renally eliminated drugs gadobutrol, gadoterate, amikacin, and vancomycin. The eGFR was compared with the observed drug clearance (CL) in 352 pediatric patients from birth to 12 years of age. Multiple eGFR equations overestimated the drug CL on average, including the original and bedside Schwartz equations, which showed an average eGFR/CL ratio between 1 and 3. Further analysis with bedside Schwartz equation showed a higher eGFR/CL ratio in the subjects with a lower SCR or CL. Supraphysiological eGFR as high as 380 mL/min/1.73 m2 was obtained using the bedside Schwartz equation for some of the subjects, most of whom are children < 2 years of age with SCR < 0.2 mg/dL. Excluding the subjects with supraphysiological eGFR from the analysis did not change the overall trend of overestimation. In conclusion, Schwartz equations led to an overestimation of drug clearance for the drugs evaluated. When greater precision is required in predicting eGFR for pediatric patients, such as in drug dosing, revised k constants for the Schwartz equation or new methods of glomerular filtration rate estimation may be necessary. [ABSTRACT FROM AUTHOR]

This study assessed the use of emulsion‐produced propolis nanoparticles for treating carbon tetrachloride (CCl4)‐induced liver fibrosis and nephropathy on albino rat model. The evaluation of hepatotoxicity, nephrotoxicity, and the treatment outcomes involved biochemical investigations of blood samples as well as molecular analysis, and histopathological assessment for liver and kidney tissue samples. CCl4 treatment caused elevated biochemical indicators of hepatotoxic and nephrotoxic effects as detected by liver and kidney functions tests, which improved gradually with propolis nanoparticles treatment. The molecular studies showed an increase in transforming growth factor β (TGF‐β), Nephrin, and Caspase‐9, while Bcl‐2 levels dropped in both liver and kidney tissue samples; such changes were normalized after treatment. The histological findings confirm both biochemical and molecular studies. Our results indicated that propolis nanoparticles had an anti‐inflammatory effect as proved by decreased expression of TGF‐β in liver tissue and Nephrin in kidney tissue. The propolis nanoparticles showed an anti‐apoptotic effect on liver and kidney tissue increasing the expression of Bcl‐2 and decreasing the expression of Caspase‐9. [ABSTRACT FROM AUTHOR]

Kidney disease affects pharmacokinetic (PK) profiles of not only renally cleared drugs but also nonrenally cleared drugs. The impact of kidney disease on drug disposition has not been fully elucidated, but describing the extent of such impact is essential for conducting dose optimization in kidney disease. Accurate evaluation of kidney function has been a clinical interest for dose optimization, and more scientists pay attention and conduct research for clarifying the role of drug transporters, metabolic enzymes, and their interplay in drug disposition as kidney disease progresses. Physiologically based pharmacokinetic (PBPK) modeling and simulation can provide valuable insights for dose optimization in kidney disease. It is a powerful tool to integrate discrete knowledge from preclinical and clinical research and mechanistically investigate system‐ and drug‐dependent factors that may contribute to the changes in PK profiles. PBPK‐based prediction of drug exposures may be used a priori to adjust dosing regimens and thereby minimize the likelihood of drug‐related toxicity. With real‐time clinical studies, parameter estimation may be performed with PBPK approaches that can facilitate identification of sources of interindividual variability. PBPK modeling may also facilitate biomarker research that aids dose optimization in kidney disease. U.S. Food and Drug Administration guidances related to conduction of PK studies in kidney impairment and PBPK documentation provide the foundation for facilitating model‐based dose‐finding research in kidney disease. [ABSTRACT FROM AUTHOR]