Endogenous Creatinine Clearance Research Articles

#2919 Renal functional reserve assessment in patients with coronary microvascular dysfunction and preserved renal function—experience of a center

Abstract Background and Aims Renal Functional Reserve (RFR) is a field of scientific debate and may be a valuable diagnostic tool for the early detection of subclinical renal disease. According to literature, chronic kidney disease is related to cardiovascular disease (CVD), however the available data on the association of early renal dysfunction and CVD are sparse. The aim of the present study is to evaluate RFR in patients with coronary microvascular dysfunction (CMD) and preserved renal function [eGFR≥ 60 ml/min/1.73 m2 (CKD-EPI) and proteinuria< 400 mg/24 h]. Method This is a single-center, prospective study enrolling patients with INOCA. We are presenting preliminary results. In the absence of significant coronary artery stenosis, functional coronary circulation assessment was performed for all patients and we estimated coronary flow reserve (CFR) and index of microvascular resistance (IMR). In all participants, RFR was estimated by endogenous creatinine clearance after oral protein load (cooked meal, 1.2 gr/kg). Normal RFR was defined as ≥30 ml/min/1.73 m2. Also, patients with INOCA were offered 24-hour Ambulatory Blood Pressure Monitoring (ABPM). Results A total of 22 participants have been enrolled so far in study: 10 without CMD—control group [7 female, mean age: 54.4 ± 8.1 years) and 12 with INOCA—CMD group (9 female, 75%, mean age: 53.5 ± 10.3 years). CMD patients were classified into 2 groups, structural and functional endotype (CFR<2.5 and an IMR≥25 were considered abnormal). The RFR value for CMD group is 7.4 ± 6.3 ml/min/1.73 m2, while for non-CMD group 36.3 ± 5.8 ml/min/1.73 m2 (p < 0.005), relationship that remained statistically significant after controlling for confounding factors. Regarding the two endotypes of MVD, it was found that RFR for the patients with the functional endotype is 3.5 ± 2.4 ml/min/1.73 m2, while for those with the structural endotype 9.3 ± 6.9 ml/min/1.73 m2 (p-value = 0.061). Furthermore, no statistically significant relationship emerged between RFR and IMR, CFR indices (p = 0.347, p = 0.263). According to data from 24 hr ABPM, there were no significant differences in ambulatory blood pressure (systolic and diastolic) between the two endotypes of CMD (p = 0.594, p = 0.243), as well as no relationship with RFR (p = 0.553, p = 0.594). However, the proportion of non-dippers (for both SBP and DBP) was significantly higher in functional CMD endotype (p < 0.05). It was not found correlation between RFR and non-dipping phenotype, both for SBP and DBP (p = 0.561, p = 0.238). Conclusion Abnormal RFR has been observed in all patients with microvascular dysfunction. In addition, patients with functional CMD show a lower RFR value compared to those with structural. RFR is not related to blood pressure or the non-dipping pattern. Given the hypothesis that the assessment of renal functional reserve is an early diagnostic tool for subclinical renal disease, the early identification of patients with specific phenotypes—such as INOCA and pathological RFR—could contribute to the individualization of therapeutic interventions.

Renal functional reserve assessment in patients with coronary microvascular dysfuntion and preserved renal function

Abstract Funding Acknowledgements None. Introduction Renal Functional Reserve (RFR) is a field of scientific debate and may be a valuable diagnostic tool for the early detection of subclinical renal disease. According to literature, chronic kidney disease is related to cardiovascular disease (CVD), however the available data on the association of early renal dysfunction and CVD are sparse. Aim The aim of the present study is to evaluate RFR in patients with coronary microvascular dysfunction (CMD) and preserved renal function [eGFR≥ 60 ml/min/1.73m2 (CKD-EPI) and proteinuria< 400mg/24h]. Methods This is a single-center, prospective study enrolling patients with CMD. We are presenting preliminary resuts. In the absence of significant coronary artery stenosis, functional coronary circulation assessment was performed for all patients. Coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured invasively. In all participants, RFR was estimated by endogenous creatinine clearance after oral protein load (cooked meal, 1.2gr/kg). Normal RFR was defined as ≥30 ml/min/1.73m2. Also, patients with CMD were offered 24-hour Ambulatory Blood Pressure Monitoring (ABPM). Results A total of 25 participants have been enrolled so far in study: 11 without CMD - non-CMD group [7 female, 64%, mean age: 52.9±8.8 years) and 14 with INOCA – CMD group (11 female, 79%, mean age : 53.5±10.3 years). CMD patients were classified into 2 groups, structural and functional endotype (CFR<2.5 and IMR≥25 were considered abnormal). The RFR value for CMD group is 7.4±6.3 ml/min/1.73m2, while for control group 36.3±5.8 ml/min/1.73m2 (p<0.005), This difference between groups was found to be statistically significant after controlling for confounding factors. It was found that RFR value for functional CMD endotype was 3.8±2.6 ml/min/1.73m2, while for patients with structural endotype 9.6±7,2 ml/min/1.73m2 (p=0.06). Furthermore, no statistical significance was found between RFR and IMR, CFR indices (p =0.35, p =0.23 respectively). According to data from 24hr ABPM , there were no significant differences in ambulatory blood pressure (systolic and diastolic) between the two endotypes of CMD (p=NS for all), as well as no relationship with RFR (p=0.6, p=0.6 respectively) was observed. However, the proportion of non-dippers (for both SBP and DBP) was significantly higher in functional CMD endotype (p<0.05). It was not found correlation between RFR and non-dipping phenotype, for both SBP and DBP (p=NS). Conclusion Abnormal RFR has been observed in all patients with microvascular dysfunction. In addition, patients with functional CMD show a lower RFR value compared to those with structural. RFR is not related to levels of BP or the non-dipping pattern. Given the hypothesis that the assessment of renal functional reserve is an early diagnostic tool for subclinical renal disease, the early identification of patients with specific phenotypes could contribute to the individualization of therapeutic interventions.

Effects of a Nursing Intervention Based on a Solution-Focused Approach on Renal Transplant Recipients’ Anxiety, Depression, and Quality of Life

Objective. To explore the effects of a nursing intervention based on a solution-focused approach on improving renal transplant recipients’ anxiety, depression, and quality of life. Methods. A total of 75 eligible recipients who underwent renal transplantation were recruited and randomly divided into intervention and control groups. The renal transplantation recipients in the intervention group received nursing intervention based on a solution-focused approach (SFA) developed by the research group. The SFA intervention included the following five stages: describing the problem, developing well-formed goals, exploring for exceptions, end of session feedback, and evaluating progress. Additional methods, such as empowerment, miracle questions, and scale mark questions, were included. The intervention began after informed consent, and baseline data were collected at admission, with each participant receiving five interventions lasting 30–60 minutes. The featured methods and five stages of the SFA could be interspersed and used repeatedly. The follow-up was performed at one, three, and six months postoperation. The control group received the usual care of comparable length and follow-up contact. The anxiety, depression, and quality of life of renal transplant recipients were measured and recorded using the Hospital Anxiety and Depression Scale (HADS) and the Quality of Life Scale for Patients of Renal Transplantation (QOL-RT). A trained research nurse collected all the baseline and follow-up data. Results. The baseline information of the patients, such as gender, age, BMI, endogenous creatinine clearance, anxiety, and depression, was similar between the two groups ( P > 0.05). The total scores of HADS (A), HADS (D), and total HADS in both groups showed a downward trend. The intervention group exhibited significantly lower HADS (A) (4.21 ± 1.85) and total HADS scores (7.81 ± 3.31) one month after surgery than the control group in the same period (5.50 ± 2.44 and 9.85 ± 4.19, respectively; P < 0.05). Fewer people in the intervention group had a HADS (A) score ≥8 than those in the control group at one month ( P < 0.05). Depression in the intervention group was significantly lower than that in the control group at three and six months ( P < 0.05). The total QOL-RT scores of the intervention group at one month (126.54 ± 9.62), three months (137.02 ± 7.69), and six months (144.89 ± 7.53) were higher than those of the control group (119.50 ± 11.58, 128.8 ± 10.80, and 138.61 ± 9.09, respectively; P < 0.05). Furthermore, the scores of the physiological function dimensions and treatment dimensions of the QOL-RT in the intervention group were higher than those in the control group at one, three, and six months after the intervention ( P < 0.05). The scores of the social function dimension in the intervention group were higher than those in the control group at three and six months after the intervention ( P < 0.05). Conclusion. Nursing intervention based on the SFA improved anxiety and depression among renal transplant recipients, thereby improving their quality of life.

Cadmium exposure exacerbates kidney damage by inhibiting autophagy in diabetic rats

The incidence of diabetes mellitus (DM) is gradually increasing, making it a widespread global health concern. Cadmium (Cd) is a common toxic heavy metal in the environment, and cadmium exposure may be associated with diabetic nephropathy (DN). However, the mechanism of Cd-induced DN remains unclear. In this study, we aimed to determine the effect of cadmium on diabetic kidney injury and the underlying mechanism in diabetic rats and a renal tubular epithelial cell line (NRK-52E cells). Our results could provide novel insights on the nephrotoxic mechanism of cadmium. HE, PAS, and Masson staining were used to observe pathological renal injury. COL-I, COL-IV, CTSB, and CTSD protein levels were detected by immunohistochemistry and western blotting. Immunofluorescence was used to detect the fluorescence intensity of p62 and LC3 proteins in kidney tissue. TEM was used to observe the ultrastructure of mitochondria and number of autophagosomes. After cadmium exposure, DM rats showed a dramatic decrease in body weight compared to the unexposed DM group. Relative kidney weight showed a contrasting trend after cadmium exposure. Urinary microalbumin/creatinine significantly increased in normal and DM rats after cadmium exposure. However, the trend was clearer in the DM groups than in the control groups. Endogenous creatinine clearance exhibited a contrasting trend. After cadmium exposure in DM rats, MDA content significantly increased and GSH, CAT, SOD, and GSH-PX activation reduced compared to normal controls. Pathological damage was more pronounced, and the expression of autophagy related proteins and apoptosis and fibrosis proteins was significantly higher in vivo and vitro in the cadmium-exposed groups than in unexposed controls. Further, lysosomal protein levels were lower, and ROS content and autophagosome count significantly higher in the cadmium exposed groups compared to the unexposed controls. Therefore, Cadmium exposure aggravates diabetic kidney injury via autophagy inhibition.

Relationship between the methylenetetrahydrofolate reductase (MTHFR) rs1801133 SNP and serum homocysteine levels of Zhuang hypertensive patients in the central region of Guangxi

BackgroundThe relationship between the methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphism (SNP) and serum homocysteine (Hcy) levels or H-type hypertension in different populations is inconsistent. This study aimed to explore the association between the MTHFR rs1801133 SNP and serum Hcy levels of Zhuang hypertensive patients in the central region of Guangxi.MethodsA total of 606 Zhuang inpatients with essential hypertension were recruited in our hospital from August 2016 to December 2018. The patients were divided into H-type hypertension (Hcy > 10 µmol/L, n = 528) and non–H-type hypertension (Hcy ≤ 10 µmol/L, n = 78) groups. At the same time, an age- and sex-matched group of 379 subjects with normal physical examination in our hospital were selected as the control group. Blood biochemical measurements and genotyping of the MTHFR rs1801133 SNP were performed.ResultsThe prevalence of H-type hypertension was 87.13%. The levels of serum Hcy in patients with hypertension were higher than those in control group (14.20 ± 5.78 μmol/L vs. 11.97 ± 5.39 μmol/L, P < 0.001), especially in patients with H-type hypertension (15.08 ± 5.65 μmol/L, P < 0.001). The frequencies of TT genotype (22.73%) and T allele (46.21%) in patients with H-type hypertension were significantly higher than those in control group (11.35% and 30.47%, respectively) and non–H-type hypertension group (10.26% and 28.85%, respectively; P < 0.001 for all). Multivariate linear regression analysis showed that serum Hcy levels were significantly correlated with creatinine, low-density lipoprotein cholesterol, endogenous creatinine clearance rate, and the MTHFR rs1801133 genotypes in control group, while serum Hcy levels were significantly correlated with creatinine, triglyceride, low-density lipoprotein cholesterol, endogenous creatinine clearance rate, glycosylated hemoglobin, and the MTHFR rs1801133 genotypes in H-type hypertension group (P < 0.05–0.001). Serum Hcy levels in the T allele carriers were higher than those in the T allele noncarriers in both H-type hypertension and control groups.ConclusionsThere was closely related between the MTHFR rs1801133 SNP and serum Hcy levels in Zhuang patients with H-type hypertension in the central region of Guangxi. The MTHFR SNP may be an important reason for the increase of serum Hcy levels in Zhuang patients with H-type hypertension in this region.

Comparative pharmacokinetics of six bioactive components of Shen-Wu-Yi-Shen tablets in normal and chronic renal failure rats based on UPLC-TSQ-MS/MS

Ethnopharmacological relevanceShen-Wu-Yi-Shen tablets (SWYST), a Chinese patent medicine consisting of 12 herbal medicines, was formulated by a famous TCM nephrologist, Zou Yunxiang. It is clinically used to improve the symptoms of nausea, vomiting, poor appetite, dry mouth and throat, and dry stool in patients with chronic renal failure (CRF) accompanied by qi and yin deficiency, dampness, and turbidity. SWYST can reduce urea nitrogen, blood creatinine, and urinary protein loss, and increase the endogenous creatinine clearance rate. However, little is known about its pharmacokinetics. Aim of studyTo compare the pharmacokinetics of six bioactive components after oral administration of SWYST in normal and adenine-induced CRF rats. Materials and methodsA method based on ultra-performance liquid chromatography coupled with a triple-stage quadrupole mass spectrometer (UPLC-TSQ-MS/MS) was developed and validated to determine the six bioactive compounds (albiflorin, paeoniflorin, plantagoguanidinic acid, rhein, aloe-emodin, and emodin) in rat plasma. Rat plasma samples were prepared using protein precipitation. Chromatography was performed on an Agilent Eclipse Plus C18 column (3.0 × 50 mm, 1.8 μm) using gradient elution with a mobile phase composed of acetonitrile and water containing 0.1% (v/v) formic acid, while detection was achieved by electrospray ionization MS under the multiple selective reaction monitoring modes. After SWYST administration, rat plasma was collected at different time points, and the pharmacokinetic parameters of six analytes were calculated and analyzed based on the measured plasma concentrations. ResultsThe UPLC-TSQ-MS/MS method was fully validated for its satisfactory linearity (r ≥ 0.9913), good precisions (RSD <11.5%), and accuracy (RE: -13.4∼13.1%), as well as acceptable limits in the extraction recoveries, matrix effects, and stability (RSD <15%). In normal rats, the six analytes were rapidly absorbed (Tmax ≤ 2 h), and approximately 80% of their total exposure was eliminated within 10 h. Moreover, in normal rats, the AUC0-t and Cmax of albiflorin, plantagoguanidinic acid, and rhein exhibited linear pharmacokinetics within the dose ranges, while that of paeoniflorin is non-linear. However, in CRF rats, the six analytes exhibited reduced elimination and significantly different AUC or Cmax values. These changes may reflect a decreased renal clearance rate or inhibition of drug-metabolizing enzymes and transporters in the liver and gastrointestinal tract caused by CRF. ConclusionsA sensitive UPLC-TSQ-MS/MS method was validated and used to investigate the pharmacokinetics of SWYST in normal and CRF rats. This is the first study to investigate the pharmacokinetics of SWYST, and our findings elucidate the causes of their different pharmacokinetic behaviors in CRF rats. Furthermore, the results provide useful information to guide further research on the pharmacokinetic-pharmacodynamic correlation and clinical application of SWYST.

Peculiarities of ionoregulatory renal function of rats in the dynamics of experimental diabetes mellitus development

Background. The purpose of the research was to study the peculiarities of ionoregulatory renal function in the dynamics of alloxan-induced experimental diabetes mellitus. Materials and methods. The experiments were carried out on 63 white non-linear mature male rats, 53 with experimental diabetes mellitus of varying duration induced by intraperitoneal administration of alloxan in a dose of 160 mg/kg of body weight, and 10 intact rats (control group). Ten, 20, 25, 30, 40 and 45 days after administration of the diabetogenic substance, the animals were withdrawn from the experiment. Ionoregulatory function of the kidneys was studied by means of the clearance method under condition of water induced 2-hour diuresis to determine the clearance of endogenous creatinine, glomerular filtration rate, sodium and potassium content in the urine and blood plasma. It was followed by calculation of the electrolyte excretion, intensity of their filtration, absolute and relative reabsorption, their proximal and distal tubular transport (including standardized by glomerular filtrate volume). Results. The ionoregulatory function of the kidneys in rats with alloxan-induced experimental diabetes is characterized by the intensification of natriuresis and kaliuresis at all stages of the experiment. An increase in the urinary sodium loss in the early stages of alloxan-induced experimental diabetes is primarily stipulated by glomerular hyperfiltration, followed by an enhancement of filtration sodium load to the nephron. The loss of proportionality between the filtered amount of sodium and its proximal reabsorption causes a decrease in the total reabsorption potential of the tubular segment of the nephron in the dynamics of alloxan-induced experimental diabetes. It is reflected primarily on the proximal tubules, and subsequently induces a functional weakening of the tubule-tubular connection and relative dysfunction of the distal segment of the nephron with subsequent inhibition of aldosterone-dependent regulatory mechanisms. Conclusions. The kaliuric reaction of the diabetic kidney may serve as one of the signs of decompensation of the renal blood flow autoregulation by tubuloglomerular feedback, which is an initiating factor for the dysfunction of the tubular apparatus of diabetic kidney.

Nierenersatztherapie

The clinical indications for initiating acute renal replacement therapy (ARRT) include life-threatening refractory disturbances of electrolyte, acid-base and fluid balances as well as severe clinical symptoms of the uremic syndrome. In most other cases a watch and wait strategy is justified; however, a consistent (at least daily) re-evaluation is mandatory. In intensive care patients with persistent oliguria or anuria for > 72 h despite stable hemodynamics and adequate volume status, initiation of RRT should be considered even in the absence of urgent clinical indications. For continuous RRT the guidelines recommend a total effluent volume (dialysate plus filtrate) of 20–25 ml/kg body weight/h which usually requires a higher prescription of effluent volume. The treatment duration and frequency of intermittent RRT should primarily be tailored to the patients’ individual needs regarding fluid, electrolyte, and acid-base balances. Treatment sessions every 2 days will usually be sufficient to achieve adequate solute clearance. Basic prerequisites for attempts at weaning from ARRT are stable hemodynamics, adequate fluid, electrolyte, and acid-base statuses and a urine output of at least 500 ml/24 h or a positive response to a furosemide stress test. The successful recovery of kidney solute clearance can be demonstrated by performing an endogenous creatinine clearance or quantification of the kinetic estimated glomerular filtration rate (KeGFR).

Osmotic concentration of urine in the dynamics of the development of alloxan-induced experimental diabetes

In order to clarify the peculiarities of the osmotic concentration of urine in the dynamics of the development of alloxan-induced experimental diabetes mellitus (DDM), studies were conducted on 54 sexually mature non-linear male white rats, in which DDM was simulated by a single intraperitoneal injection of alloxan solution (Alloxan monohydrate, "Acros Organics", Belgium) at a dose of 160 mg/kg of body weight after a previous 12-hour food deprivation with preserved access to water. 10, 25, and 45 days after the introduction of the diabetogenic substance, 24 alloxan-diabetic rats, as well as 30 control (intact) animals, were loading with tap water in a volume of 5% of body weight, urine was collected for 2 hours, euthanasia was performed by decapitation under light ether anesthesia. In blood samples, the level of glucose and creatinine was determined, in urine samples, after evaluating the water-induced 2-hour diuresis (in ml/100 g of body weight in 2 hours), the concentration of creatinine was determined, the clearance of endogenous creatinine, the clearance of osmotically free water, as well as relative (tubular) reabsorption of water, determined the content of glucose, urea, its excretion, including per 100 μl of glomerular filtrate, as well as urine osmolarity. The results of the study allow us to state that as the duration of experimental diabetes is prolonged, the pathogenetic significance of hyperfiltration, which determines the speed of fluid movement along the tubule and the intensity of its absorption, weakens in relation to the processes of osmotic concentration of urine, yielding to other factors, such as the osmolarity of the medulla of the kidneys, as well as the presence of substances in the liquid of the distal segment and collecting tubes, the reabsorption of which can change their concentration in the collecting tubes as the urine progresses. In diabetes, in addition to glucose, such substances include urea. Attempts to analyze the renal excretion of urea revealed that changes in its urinary concentration are definitely correlated with the dynamics of changes in urine osmolality. Moreover, it can be assumed that urea transport disorders in the diabetic kidney occur earlier than the ability to excrete osmotically active substances in general. A joint study of the processes of renal transport of urea and urine osmolarity can serve as an early verifier of tubulointerstitial damage. Nevertheless, to increase the reliability of the interpretation of the features of the osmotic concentration of urine in diabetes, we consider it necessary to study the nature of the renal transport of electrolytes (sodium, potassium, calcium, and ammonium).

Prevalence and risk factors of poor sleep quality in continuous ambulatory peritoneal dialysis patients in Nanchang, Southeast China

This study aimed to explore the prevalence and risk factors of poor sleep quality in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) at the peritoneal dialysis center of the First Affiliated Hospital of Nanchang University. This cross-sectional study was conducted from March 2019 to December 2019. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality of patients undergoing CAPD. A PSQI score of ≥5 was defined as poor sleep quality, whereas a PSQI of <5 was defined as good sleep quality. Logistic regression analysis was used to analyze risk factors for poor sleep quality. In total, 456 patients undergoing CAPD were investigated. The average PSQI score was 5.0 ± 2.9. Among the participants, 46.3% had poor sleep quality, and 45.6% were female patients. The average age was 49.4 ± 13.3 years. Compared with good sleepers, poor sleepers included a higher proportion of females and calcium–phosphorus (Ca × P) product, longer dialysis durations, lower total endogenous creatinine clearance rates, less residual renal function, and lower albumin levels. Multivariate logistic regression analysis showed that a long dialysis duration, low albumin level, and high Ca × P product were independent risk factors for poor sleep quality in patients undergoing CAPD. Odds ratios (95% confidence interval) for these risk factors were 1.01 (1.00–1.02), 0.95 (0.91–1.00), and 1.02 (1.00–1.03), respectively. Interventions aimed at improving albumin and Ca × P product levels may improve quality of life for CAPD patients.

Effect analysis of Shenkang injection on chronic renal insufficiency

To investigate the clinical effect of Shenkang injection on chronic renal insufficiency. Methods 88 patients with chronic renal insufficiency were selected as the research object and randomly divided into observation group and control group. The control group was given routine treatment, and the observation group was given Shenkang injection on this basis. The total effective rate, hemoglobin level (Hb), red blood cell count (RBC), urea nitrogen (BUN), serum creatinine (SCr) and endogenous creatinine clearance (Ccr) were compared between the two groups. Results The total effective rate of the observation group (93.18%) was significantly higher than that of the control group (77.27%), and all observation indexes were significantly better than the control group, the difference was statistically significant (P&lt;0.05). Conclusion Shenkang injection has a significant effect on chronic renal insufficiency patients, and can effectively improve the symptoms of weakness, anemia and so on.

Alprostadil for hypertensive nephropathy: A systematic review and meta-analysis of randomized controlled trials.

We performed a meta-analysis to evaluate the efficacy of alprostadil in the treatment of hypertensive nephropathy. Seven online databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure [CNKI] database, Wanfang Data Knowledge Service Platform, VIP Information Resource Integration Service Platform [cqVIP], and China Biology Medicine Disc [SinoMed]) were searched from inception to January 31, 2022, and a set of clinical indicators for hypertensive nephropathy was selected. The main indicators were 24-h urinary protein, serum creatinine, endogenous serum creatinine clearance rate, blood urea nitrogen, cystatin C, and mean arterial pressure. The methodological quality of the included trials was analyzed using a risk of bias assessment according to the Cochrane Manual guidelines, and a meta-analysis was performed. A random-effects model was implemented to pool the results. A total of 20 randomized controlled trials involving 1441 patients with hypertensive nephropathy were included in this review. Our findings showed that alprostadil had a positive effect on 24-h urinary protein (mean difference [MD] = −0.79, 95% confidence interval [CI] [−1.16, −0.42], P < 0.0001), serum creatinine (MD = −13.83, 95% CI [−19.34, −8.32], P < 0.00001), endogenous serum creatinine clearance rate (MD = 6.09, 95% CI [3.59, 8.59], P < 0.00001), blood urea nitrogen (MD = −6.42, 95% CI [−8.63, −4.21], P < 0.00001), cystatin C (MD = −0.26, 95% CI [−0.34, −0.18], P < 0.00001), and mean arterial pressure levels(MD = −13.65, 95% CI [−16.08, −11.21], P < 0.00001). Compared to conventional treatment alone, alprostadil combined with conventional treatment can improve renal function in patients with hypertensive nephropathy more effectively. However, additional large-scale, multicenter, rigorously designed randomized controlled trials are needed to verify these results. This is the first meta-analysis to evaluate the efficacy of alprostadil for hypertensive nephropathy, and the results may guide clinical practice.

C/MIC > 4: A Potential Instrument to Predict the Efficacy of Meropenem

This prospective study aimed to explore the determinants of meropenem trough concentration (Ctrough) in patients with bacterial pneumonia and to investigate the association between its concentration and efficacy. From January 2019 to December 2019, patients with pulmonary infections were prospectively enrolled from the intensive care unit. Factors affecting the meropenem trough concentration were analyzed, and a multiple linear regression model was constructed. Logistic regression analyses were used to investigate the relationship between Ctrough and clinical efficacy. A total of 64 patients were enrolled, in whom 210 meropenem concentrations were measured. Of the total, 60.9% (39/64) were considered clinically successful after treatment. Ctrough may increase with increased blood urea nitrogen, albumin, and concomitant antifungal use. By contrast, concentration may decrease with increased endogenous creatinine clearance rate. Six variables, including Ctrough/minimum inhibitory concentration (MIC) > 4, were associated with the efficacy of meropenem. There was an independent correlation between Ctrough/MIC > 4 and efficacy after fully adjusting for confounding factors. Based upon renal function indexes, it is possible to predict changes in meropenem concentration and adjust the dosage precisely and individually. Ctrough/MIC > 4 is a potential instrument to predict successful treatment with meropenem.

Creatinine as a Urinary Marker of the Purine Derivatives Excretion in Urine Spot Samples of Lambs Fed Peach Palm Meal.

Simple SummaryExperimental trials designed to predict the microbial protein synthesis in the rumen via urinary purine derivatives require access to 24-h urinary volumes. This technique is non-invasive but requires access to 24-h urinary volumes, which is impracticable in grazing animals or a large number of feedlot sheep. The challenge is to provide the possibility of using the purine derivatives and creatinine concentrations in a spot urine sample and the daily creatinine excretion in urine as accurate estimators of purine derivatives’ excretion per day.The objective was to evaluate the influence of diets on lambs using different levels of peach palm meal as a replacement for maize (0, 10, 40, 60, and 85% of diet dry matter) on the endogenous creatinine clearance (CC), urine concentration ratio of purine derivatives to creatinine (PDC index), and daily creatinine excretion (DCE) as a marker to estimate purine derivatives (PD) excretion from urinary spot samples collected at different time points (4, 8, 12, 16, 20, 24 h after morning feeding) compared to 24-h total urine collection. The measured parameters were voluntary intake, urinary volume, CC, DCE, the concentration of plasma creatinine, and PD and purine derivatives’ excretion (PDE). Five lambs were allocated to metabolic cages and distributed in a 5 × 5 Latin square. Urine collection was taken daily on days 16 to 19 of each experimental period. The inclusion of peach palm meal linearly reduced the intake of dry matter (g kg BW−0.75, p = 0.005), crude protein (g kg BW−0.75, p = 0.010), metabolizable energy (MJ kg BW−0.75, p = 0.010) and CC (p < 0.0001). It also quadratically affected the urinary volume (p = 0.008) and DCE (p = 0.004). There was a linear decrease for PDC index (p = 0.032) and PDE (p < 0.0001) measured in the 24-h total urine with peach palm meal levels. The different times of spot urine sampling did not affect (p > 0.05) the PDC index and PDE. Peach palm meal decreases the CC thereby compromising the use of a mean value of DCE as a PDE marker in spot urine samples. There is greater accuracy when using different values of DCE obtained for each diet as markers for the PDE in spot urine samples. Unconventional foodstuffs of low palatability affecting the voluntary intake of feed change the renal function.

MO1020: Alkaline Phosphatase to Prevent Ischemia Reperfusion Injury in Living Kidney Transplantation—A Safety Pilot Study

Abstract BACKGROUND AND AIMS Ischemia-reperfusion injury (IRI) during kidney transplant procedures can induce acute kidney injury (AKI) [1]. Extracellular ATP is a key player of pro-inflammatory processes during IRI in the kidney [2], whereas conversion of ATP into adenosine has protective effects to the kidney. Alkaline phosphatase (AP) is the only enzyme that converts ATP directly into adenosine by dephosphorylation[3]. In earlier clinical trials of AP in sepsis-associated AKI (SA-AKI), it was suggested that AP has a protective effect on endogenous creatinine clearance and mortality [4]. With the pathophysiologic similarity between SA-AKI and IRI, we aimed to evaluate the effect and feasibility of periprocedural AP to improve kidney function in living donor kidney transplantation. METHOD We conducted a pilot, phase II, double-blinded and randomized controlled trial comparing medicinal AP (tradename: `bRESCAP’, courtesy Alloksys Life Sciences) and placebo. All consecutive recipients of living donor kidneys were asked for informed consent. After randomization, intravenous AP (bolus 1000IU and 9000IU continuously) or placebo was administered at the start of the procedure and continued for the following 24 h. Graft function was measured with measured GFR (using an iohexol distribution curve) after 12 months. Plasma creatinine and a panel of novel injury biomarkers and systemic inflammation markers were measured in both urine and serum during the 7 days after the procedure. Drug reactions and adverse events (AEs) were monitored in the first 7 days. Secondary outcomes included all-cause mortality and dialysis dependency. RESULTS Between June 2019 and October 2019, 11 patients were enrolled. Patients did not differ between groups, bRESCAP (n = 5) and placebo (n = 6) at baseline: 36% were male; the median age was 58 [interquartile range (IQR) 40–65] years; and the median eGFR 12 (10–15) mL/min/1.73 m2. After 1 year, median measured GFR was similar in the bRESCAP group [52.2 (40.5–61.4)] and placebo group [52.4 (37.6–66.1)] (P = 1.000). Mixed model analysis showed no difference in the fall of plasma creatinine or cystatin-C over the first 7 days after the procedure. There were no adverse events observed in the bRESCAP group. CONCLUSION These pilot data indicate that bRESCAP can be administered safely but offers no benefits to recipients of kidneys from living donors. This study opens the way to study recipients of kidneys from deceased donors, where IRI plays a much more prominent role and frequently leads to delayed graft function.

MO366: Renal Functional Reserve as a Marker to Stratify the Risk of Kidney Injury in Hematopoietic Stem Cell Transplantation

Abstract BACKGROUND AND AIMS Haematopoietic stem cell transplantation (HSCT) is an effective treatment for myelo-lymphoproliferative disorders. Acute kidney injury (AKI) is a major complication of HSCT (incidence ≈15%–60%), usually occurs in the first 100 days post-transplant, and is associated with a significant increase in mortality and morbidity. In addition, it can lead to chronic renal failure (CKD). There are no scores to predict which patients will develop AKI or CKD post-HSCT. Routine pre-HSCT evaluation only considers the estimated glomerular filtrate value (eGFR) without examining the renal functional reserve (RFR). RFR is defined as the ability of the kidney to increase its glomerular filtration rate in response to higher functional demand (as in the case of HSCT). METHOD This prospective study aimed to evaluate the ability of RFR in HSCT candidate patients to stratify the risk of AKI incidence within 100 days of transplantation and predict eventual functional recovery. The secondary purpose was to identify the risk factors for the onset of AKI. A total of 41 HSCT candidate patients with normal baseline GFR (bGFR) were included in the study. A total of 15 days before the HSCT, a multiparametric nephrological evaluation and RFR test (RFR-T) were performed using an oral protein load (1–1.2 g/kg) with freeze-dried products (Prother®) and 10 mL/kg of oral hydration. GFR after protein loading (glomerular stress filtration rate, sGFR) and bGFR were measured with body surface corrected endogenous creatinine clearance (CrCl). Blood samples were taken at predefined time intervals concerning oral protein load (120–180–240 min). RFR was defined as the difference between the maximum value of sGFR and bGFR expressed as a percentage (normal RFR &amp;gt; 25%). RESULTS No correlation was found between bGFR and RFR values. Consistent with the literature, 25 of 41 patients (61%) developed AKI. Comparing the group that developed AKI with those that did not, no statistically significant differences emerged related to demographic, clinical, or multiparameter screening characteristics. RFR was lower in AKI + patients than in AKI- patients, with a value at the borderline of statistical significance (P = 0.06). Among the 25 patients who developed AKI, 7 patients (30%) recovered normal renal function in the follow-up, while 18 patients (70%) developed CKD. 71% of patients who recovered renal function demonstrated an RFR value&amp;gt;25%; no demographic and multiparameter screening variables correlated with the development of post-HSCT CKD. CONCLUSION RFR is a dynamic parameter with respect to the bGFR. It allows the identification of conditions of subclinical functional deterioration, capable of affecting both the onset of AKI and CKD post-HSCT. No other multiparameter screening variable has shown potential utility in this type of predictive assessment. The stratification of the risk of kidney injury through RFR represents the most promising marker in this sense. A reliable prediction of the risk of renal complication in these patients could lead to accurate multidisciplinary management able to improve the prognosis quoad vitam (severe in the case of AKI post-HSCT) and quoad valetudinem (severe in case of CKD post-HSCT).

Artificial Intelligence Algorithm-Based Computed Tomography Image in Assessment of Acute Renal Insufficiency of Patients Undergoing Percutaneous Coronary Intervention.

This study was aimed to analyze the changes in renal function of patients undergoing percutaneous coronary intervention (PCI) surgery and the characteristics of their computed tomography (CT) image based on artificial intelligence algorithms. In this study, 104 patients with coronary atherosclerotic heart disease (CAHD) were treated as the research objects. They were divided into an experimental group (patients who underwent CAG and PCI within 1 week after enhanced coronary CT (ECCT)) and the control group (patients who underwent CAG and PCI within 1–3 weeks after ECCT). Renal imaging scans of patients were performed by CT based on discrete inseparable shear transform (DNST) optimized algorithm, which was named as O-DNST. The results showed that the serum creatinine (Scr), blood urea nitrogen (BUN), and urine protein (UP) levels of patients in the experimental group were significantly higher than those of the control group 24–72 hours after surgery, while the levels of endogenous creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) were significantly lower than those of the control group (P < 0.05). The levels of β2 microglobulin (β2-MG), C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) in the experimental group were significantly higher than those in the control group 24–72 hours after surgery (P < 0.05). The incidence of contrast-induced nephropathy (CIN) in the experimental group (15.38%) was significantly higher than that in the control group (5.8%), and the difference was statistically significant (P < 0.05). The results showed that repeated application of contrast agent in a short period of time can promote the increase of serum inflammation levels in PCI patients, which may be a risk factor for CIN in PCI patients.

Performance of creatinine-based equations for estimating glomerular filtration rate compared to endogenous creatinine clearance.

Introduction:The guidelines recommend estimating the glomerular filtration rate using serum creatinine-based equations as a predictor of kidney disease, preferably adjusted for local population groups.Methods:Cross-sectional study that evaluated the performance of four equations used for estimating GFR compared to endogenous creatinine clearance (ClCr) in 1,281 participants. Modification of Diet equations in Renal Disease Study Group (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI with adjustment for local population (CKD-EPI local) and Full Age Spectrum (FAS) in comparison with endogenous creatinine clearance (ClCr). We used the Quantile Regression to calculate the median bias, interquartile range (IQR), Bland-Altman agreement analysis and 30% margin of error (P30).Results:The mean age of participants was 52.5 ± 16.5 years with 466 women (38%), median ClCr[IQR] of 92.0 [58.0; 122.0] mL/min/1.73 m2, with 320 (25%) participants presenting ClCr < 60 mL/min/1.73 m2. The performance of the local CKD-EPI and FAS equations were superior to MDRD and CKD-EPI in relation to variability (0.92 [0.89; 0.94]) and P30 (90.5% [88.7; 92, 0]). In the group with ClCr < 60 mL/min/1.73 m2, the local CKD-EPI and FAS equations showed less variability than the CKD-EPI and MDRD (0.90 [0.86; 0.98] and 1.05 [0.97; 1.09] vs. 0.63 [0.61; 0.68] and 0.65 [0.62; 0.70], P < 0.01) and best P30 (85.5) % [81.0; 90.0], 88.0% [84.0; 92.0] vs. 52.0% (46.0; 58.0) and 53.0% [47.0; 58 .5], P < 0.01).Conclusion:Local CKD-EPI and FAS equations performed better than CKD-EPI and MDRD when compared to ClCr.

Nephrotoxic Effects of Paraoxon in Three Rat Models of Acute Intoxication.

The delayed effects of acute intoxication by organophosphates (OPs) are poorly understood, and the various experimental animal models often do not take into account species characteristics. The principal biochemical feature of rodents is the presence of carboxylesterase in blood plasma, which is a target for OPs and can greatly distort their specific effects. The present study was designed to investigate the nephrotoxic effects of paraoxon (O,O-diethyl O-(4-nitrophenyl) phosphate, POX) using three models of acute poisoning in outbred Wistar rats. In the first model (M1, POX2x group), POX was administered twice at doses 110 µg/kg and 130 µg/kg subcutaneously, with an interval of 1 h. In the second model (M2, CBPOX group), 1 h prior to POX poisoning at a dose of 130 µg/kg subcutaneously, carboxylesterase activity was pre-inhibited by administration of specific inhibitor cresylbenzodioxaphosphorin oxide (CBDP, 3.3 mg/kg intraperitoneally). In the third model (M3), POX was administered subcutaneously just once at doses of LD16 (241 µg/kg), LD50 (250 µg/kg), and LD84 (259 µg/kg). Animal observation and sampling were performed 1, 3, and 7 days after the exposure. Endogenous creatinine clearance (ECC) decreased in 24 h in the POX2x group (p = 0.011). Glucosuria was observed in rats 24 h after exposure to POX in both M1 and M2 models. After 3 days, an increase in urinary excretion of chondroitin sulfate (CS, p = 0.024) and calbindin (p = 0.006) was observed in rats of the CBPOX group. Morphometric analysis revealed a number of differences most significant for rats in the CBPOX group. Furthermore, there was an increase in the area of the renal corpuscles (p = 0.0006), an increase in the diameter of the lumen of the proximal convoluted tubules (PCT, p = 0.0006), and narrowing of the diameter of the distal tubules (p = 0.001). After 7 days, the diameter of the PCT lumen was still increased in the nephrons of the CBPOX group (p = 0.0009). In the M3 model, histopathological and ultrastructural changes in the kidneys were revealed after the exposure to POX at doses of LD50 and LD84. Over a period from 24 h to 3 days, a significant (p = 0.018) expansion of Bowman’s capsule was observed in the kidneys of rats of both the LD50 and LD84 groups. In the epithelium of the proximal tubules, stretching of the basal labyrinth, pycnotic nuclei, and desquamation of microvilli on the apical surface were revealed. In the epithelium of the distal tubules, partial swelling and destruction of mitochondria and pycnotic nuclei was observed, and nuclei were displaced towards the apical surface of cells. After 7 days of the exposure to POX, an increase in the thickness of the glomerular basement membrane (GBM) was observed in the LD50 and LD84 groups (p = 0.019 and 0.026, respectively). Moreover, signs of damage to tubular epithelial cells persisted with blockage of the tubule lumen by cellular detritus and local destruction of the surface of apical cells. Comparison of results from the three models demonstrates that the nephrotoxic effects of POX, evaluated at 1 and 3 days, appear regardless of prior inhibition of carboxylesterase activity.

The Rehberg-Tareev test in assessing the glomerular filtration rate

The history of glomerular filtration rate assessment is presented, an important step of which was the glomerular filtration rate evaluation by the endogenous creatinine clearance (known as the RehbergTareev test). The article highlights the diagnostic value of the RehbergTareev test and its place among modern methods for assessing glomerular filtration rate.