We sought to assess agreement of cardiac output estimation between continuous pulmonary artery catheter (PAC) guided thermodilution (CO-CTD) and a novel pulse wave analysis (PWA) method that performs an analysis of multiple beats of the arterial blood pressure waveform (CO-MBA) in post-operative cardiac surgery patients. PAC obtained CO-CTD measurements were compared with CO-MBA measurements from the Argos monitor , in prospectively enrolled adult cardiac surgical intensive care unit patients. Agreement was assessed via Bland-Altman analysis. Subgroup analysis was performed on data segments identified as arrhythmia, or with low CO (less than 5 L/min). 927 hours of monitoring data from 79 patients was analyzed, of which 26 had arrhythmia. Mean CO-CTD was 5.29 ± 1.14 L/min (bias ± precision), whereas mean CO-MBA was 5.36 ± 1.33 L/min, (4.95 ± 0.80 L/min and 5.04 ± 1.07 L/min in the arrhythmia subgroup). Mean of differences was 0.04 ± 1.04 L/min with an error of 38.2%. In the arrhythmia subgroup, mean of differences was 0.14 ± 0.90 L/min with an error of 35.4%. In the low CO subgroup, mean of differences was 0.26 ± 0.89 L/min with an error of 40.4%. In adult patients after cardiac surgery, including those with low cardiac output and arrhythmia CO-MBA is not interchangeable with the continuous thermodilution method via a PAC, when using a 30% error threshold.The online version contains supplementary material available at 10.1007/s10877-022-00924-z. Cardiac surgery patients show dynamic and complicated changes in hemodynamics. Initially developed about five decades ago, pulmonary artery catheters (PACs) have long been used for invasive hemodynamic monitoring in these patients . EvidencPulse wave analysis devices are a class of minimally-invasive methods which analyze the arterial blood pressure wave form to determine stroke volume and cardiac output . These dHere we prospectively assess the agreement between a continuous PAC guided thermodilution method and cardiac output estimation using the novel MBA method in ICU patients after on-pump cardiac surgery. A previous study had compared the Argos to intermittent thermodilution in 31 patients in the ICU after off-pump cardiac surgery, but that study excluded patients with arrhythmias . Here weA cardiac output monitoring method can be considered interchangeable with the intermittent thermodilution method if the difference between the two is less than 30% per the Critchley and Critchley criterion . Peyton This study was reviewed and approved by the Wake Forest School of Medicine Institutional Review Board ; 6/18/2020). The IRB also determined that this research met the criteria for a waiver of consent entirely according to 45 CFR 46(d). The purpose of this work was to compare CO measurements between the multi-beat analysis method (MBA) and the continuous thermodilution (CTD) method via a pulmonary artery catheter. The study was conducted from July – December 2020 in the cardiovascular surgical intensive care unit of the Wake Forest Baptist Medical Center, a tertiary academic care center part of the Wake Forest School of Medicine.Adult patients scheduled for elective cardiac surgery  on cardiopulmonary bypass, and who received a radial arterial catheter and a pulmonary artery catheter per clinical indications were included in this study. Exclusion criteria included patients less than 18 years of age, those with mechanical circulatory support  or patients with moderate to severe aortic regurgitation, per the contraindications of the Argos monitor.After receiving patients in the ICU, standard blood pressure monitoring was continued via the previously established radial arterial catheter and a transducer connected to a bedside multi-parameter monitor . Standard ICU protocols were followed of leveling the pressure transducer to the right atrium and confirming zero of the system to atmospheric pressure. Square wave tests were performed if deemed clinically necessary, at the discretion of the bedside care team. The Argos monitor  received the radial blood pressure waveform from the bedside monitor via a reusable cable. Patient demographics were entered into the Argos monitor and cable connections were checked to ensure that the blood pressure waveform was being received correctly by the Argos monitor. Subsequently, the front screen of the Argos monitor was covered, so monitoring data was acquired in a user blinded fashion. Research personnel performed intermittent checks of the integrity of the recording system. No patient interventions were performed based on cardiac output numbers on the Argos monitor. Monitoring and data collection continued till patient discharge from the intensive care unit or discontinuation of the arterial line or failure of the arterial line, whichever came first.Cardiac output readings from the pulmonary artery catheter were calculated continuously by the HemoSphere monitor  and were recorded once every minute by a connected data capture system . The Argos monitor records CO-MBA measurements once every 5 s, while the Capsule system records CO-CTD once every minute. After each patient’s ICU stay, data from the Argos monitor and the Capsule system were exported to a computer for further analysis. Data synchronization was ensured by matching the timestamps from the two sources.100 patients were enrolled, of which 6 were excluded due to unavailability of cardiac output data from the pulmonary artery catheter (CO-CTD). Another 2 subjects were excluded due to removal of the pulmonary artery catheter before application of the Argos monitor. Another 2 subjects were excluded due to blood pressure waveforms unavailable to the Argos monitor (CO-MBA), potentially due to a loose cable connection. One subject was excluded because minute-by-minute CO-CTD could not be extracted from the Capsule system due to technical reasons.Blood pressure waveforms and continuous thermodilution measurements were visually inspected to determine any artifact or improperly damped waveforms. While the appearance of non-physiological signals is clear, inadequate damping is more difficult to assess. Overdamping, where the blood pressure waveform shows a progressive narrowing of pulse pressure, can be clinically easier to detect and correct, as the cause is often a kink or an air bubble in the transducer tubing . UnderdaContinuous thermodilution cardiac output has been shown to have a delayed response, especially under unstable hemodynamic conditions . For theAccordingly, we averaged the continuous thermodilution cardiac output with a one-hour sliding window, while keeping the sampling rate at one measurement every minute, to smooth over any instabilities and delays. CO-MBA was similarly averaged and then resampled to one measurement every minute to allow paired comparisons with CO-CTD. By using an averaging period at least twice as large as the longest delays in the CCO data, we aimed to reduce the influence of short-term changes that could potentially be due to delays in CO-CTD. In this data the time delays in continuous thermodilution were up to 24 min and therefore we used an averaging period of one hour.Patient demographic distributions were summarized as mean ± standard deviation for continuous quantities  and as integers for the Male/Female distribution. CO-CTD and CO-MBA distributions over all patients were summarized as mean ± standard deviation. CO-CTD and CO-MBA data pairs were analyzed according to correlation and Bland–Altman statistics, considering multiple observations within subjects , 17. SpePatient demographic distributions are summarized in Table Mean value of CO-CTD across all subjects was 5.29 ± 1.14 L/min. Mean CO-MBA was 5.36 ± 1.33 L/min. Correlation between CO-CTD and CO-MBA was 0.64  per Bland–Altman analysis was 0.14 ± 0.90 L/min. Correlation between CO-CTD and CO-MBA was 0.64 Fig. . Limits This prospective analysis of 927 h of data from 79 post-operative cardiac surgery patients recovering in the intensive care unit shows that CO-MBA did not meet the Critchley and Critchley interchangeability criterion with CO-CTD . HoweverIntermittent pulmonary artery thermodilution uses injection of several fluid boluses with a known volume and temperature into the right atrium. The temperature change detected by a distal thermistor is then used to calculate the cardiac output . In contA debate about the merits of PAC placement has been ongoing with multiple large-scale studies both showing and failing to show an overall clinical benefit to placement . AdverseWe identified 10 subjects (11%) as having consistently underdamped blood pressure signals on the arterial line and were excluded. For comparison, other investigators have previously excluded 9 out of 40 subjects (23%) and found 92 out of 300 subjects (31%) to have underdamping or resonant arterial lines in similar patient populations . The perUp to a third of patients have atrial and ventricular arrhythmias after cardiac surgery . Some ofGreiwe and colleagues previously compared CO-MBA to intermittent thermodilution in the post-cardiac surgery intensive care unit . They haThere are some limitations to this analysis. While we allowed for adjustments for CO response time differences between the two comparison methods by averaging both methods over a one-hour time scale, this may have the effect of reducing the variance in both methods. The choice of one hour as the averaging window is subjective, and may influence results. We are unsure of the clinical validity and relevance of an earlier detection of a change in cardiac output, however, our delay in response time reported (12–24 min) for the continuous thermodilution PAC is not different from published work reporting a response time of 10 min or more . FurtherCardiac output calculated using a multi-beat analysis is not interchangeable with continuous thermodilution CO in adult patients recovering in the intensive care unit after on-pump coronary artery bypass surgery. In arrhythmia and low CO subgroups, the multi-beat analysis method remained outside the interchangeability criterion of 30%.Supplementary file1 (DOCX 236 kb)Below is the link to the electronic supplementary material.


Urolithiasis is a known risk factor for chronic kidney disease (CKD). However, how CKD might affect the risk of incidence of urolithiasis is not widely studied.Urinary excretion of oxalate as well as other key factors related to urolithiasis was analyzed in a single center study of 572 patients with biopsy-proven kidney disease.2. Median urinary excretion of oxalate was 14.7 (10.4–19.1) mg/24-h and associated with current urolithiasis . Oxalate excretion was not associated with eGFR and urinary protein excretion. Oxalate excretion was higher in patients with ischemia nephropathy as compared with patients with glomerular nephropathy and tubulointerstitial nephropathy . And ischemia nephropathy (p = 0.027) was associated with urinary oxalate excretion on adjusted linear regression analysis. Urinary excretion of calcium and uric acid was correlated with eGFR and urinary protein excretion , with ischemia nephropathy and tubulointerstitial nephropathy associated with uric acid excretion (both p < 0.01) as well. Citrate excretion was correlated with eGFR (p < 0.001) on adjusted linear regression.The mean age of the cohort was 44.9 years and 60% were males. The mean eGFR was 65.9 ml/min/1.73 mExcretion of oxalate and other key factors related to urolithiasis was differentially associated with eGFR, urinary protein, and pathological changes in CKD patients. The influence of these intrinsic traits of the underlining kidney disease should be considered when evaluating urolithiasis risk in patients with CKD.The online version contains supplementary material available at 10.1007/s00240-023-01458-y. Chronic kidney disease (CKD) is a widely recognized public health concern, with an estimated prevalence of 10.8% in China . PreviouCalcium oxalate is the most common type of urolithiasis . CirculaOur study was approved by the ethics board of Peking University First Hospital (2021[0236]) and performed in accordance with the Declaration of Helsinki. Adult patients who were admitted from January 2021 to May 2022 were prospectively enrolled. Exclusion criteria included inability to provide consent, anuria/oliguria upon presentation, pregnancy, liver cirrhosis, New York Heart Association class III to IV congestive heart failure, recent chemotherapy for malignancy including hematologic tumors, hereditary kidney disease, kidney transplantation, or prior treatment with dialysis for at least 1 month. Those who did not receive renal biopsy were also excluded. Incomplete urine collection  was further excluded. Given that calcium supplementation might affect oxalate absorption from gut, those who were taking calcium at the time of urine collection were further excluded. The flowchart of patient selection was shown in Supplementary Fig. 1. All participants provided written informed consent and all data were de-identified.Demographic , medical history , and anthropometric measure  were collected from electronic medical charts. Laboratory data of serum and urinalysis and current medication at the time of renal biopsy were also collected.2, 60–89 ml/min/1.73 m2, 30–59 ml/min/1.73 m2, 15–29 ml/min/1.73 m2, and < 15 ml/min/1.73 m2, respectively. Serum calcium level (mmol/l) was corrected by the following equation: measured serum calcium level (mmol/l) + 0.02 ×  (g/l).Patients were categorized according to eGFR calculated by the CKD-EPI equation as: ≥ 90 ml/min/1.73 mCaOx index) and calcium phosphate (APCaP index) was calculated according to the formulas given below [Participants were provided a 24-h urine collection container the morning before renal biopsy and started to collect urine sample after voiding actively at 7 a.m. And then, participants urinated actively at 7 a.m. the second morning to end the collection with the last urine sample being collected in the container. The total urine volume was recorded and aliquots were taken after through mixing. Then, the urine samples were centrifuged with 4500r per minute for 15 min at 4 °C as soon as possible. Supernatant was sub-aliquoted and kept at − 20 °C for further measurement. Urine oxalate and citrate measurement was performed by Aquion RFIC . In brief, 1 ml of supernatant was acidified with 10 μl 12N hydrochloric acid and diluted 1:5–1:10 with purified water . Then, 5 ml diluted samples were de-proteinized by filtration through Dionex OnGuard II RP 1 cc Cartridge  and 700 μl processed samples were used for final measurement. Concentrations of potassium, sodium, chlorine, calcium, phosphate, magnesium, creatinine and uric acid were measured using the standard chemical colorimetric method. The 24-h excretion was calculated by multiplying the concentration by the urinary volume. Standardized estimates of the ion active products of calcium oxalate . Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. General linear regression model was performed to determine the variables that were associated with oxalate and other key urinary factors with the inclusion of variate with p < 0.05 by univariate analysis. A two-sided p-value of Continuous variables were expressed as means (SDs) or median  and compared with parametric ) or nonparametric tests , as appropriate. Categorical variables were expressed as percentages and analyzed with Chi-square test. Logistic regression analysis by forward likelihood ratio method was used to analyze the association of patient characteristics with urolithiasis  g/d. According to the major pathological finding on renal biopsy, the majority of patients  were with glomerular nephropathy (GN). There were another 33 (5.8%) and 34 (5.9%) patients found with tubulointerstitial nephropathy (TIN) and ischemia nephropathy as primary pathological diagnosis, respectively. Baseline characteristics of participants according to eGFR categories are given in Table Totally, 572 patients were enrolled with a mean age of 44.9 14.1) years and 343 (60.0%) were males. The mean eGFR was 65.9 (32.7) ml/min/1.73 m4.1 yearsp = 0.002). Logistic analysis showed that denary logarithm urinary oxalate excretion  was independently associated with current urolithiasis (Table p = 0.018), respectively , current urolithiasis (p = 0.046), higher BMI (p = 0.001), and urine pH (p = 0.001) in adjusted linear regression model  mg/d of the cohort. Patients with current urolithiasis had higher urinary oxalate excretion than those without  (Table p < 0.01)  Table . Differe1) Table .Chronic kidney disease is a worldwide public health concern. So does kidney stones –15. PatiApproximately 70–80% of the kidney stones contain oxalate. Even small increase in urinary oxalate could increase the risk of developing kidney stones . In the CaOx and APCaP with decreasing eGFR was observed. This result suggests that the stone risk might decrease as CKD progresses. However, the alterations induced by underlining kidney disease on other processes involved in stone formation should also be taken into account. For instance, the transit time for urine to flow across the kidney which may affect the nucleation and growth of crystals to become large enough to be trapped in the kidney [The formation of kidney stone is a complex and multistep process that includes urinary supersaturation, crystal nucleation, growth and aggregation . Urinarye kidney  might beThere are several limitations of our study. As a study carried out in a tertiary care center, our cohort was subject to certain selection bias and likely comprised higher risk patients with kidney disease. Therefore, it is not appropriate to extrapolate our results directly to the more generalized CKD populations. Only one sample of 24-h urine of each patient was collected and the impact of diet on patients’ 24-h urine parameters independent of renal function was not assessed.In conclusion, we evaluated the urinary mineral excretion related to urolithiasis in a large cohort of patients with biopsy-proven kidney diseases. Our findings showed different correlations of eGFR, urine protein, and pathological change with oxalate as well as other key urinary factors excretion. The influence of these intrinsic traits of underlining kidney disease should be taken into account when evaluating urolithiasis risk in patients with CKD.Flowchart of patient selection (JPG 179 KB)Below is the link to the electronic supplementary material.


There is controversy about the indication for nonalcoholic fatty liver disease (NAFLD) screening in patients with type 2 diabetes mellitus (T2D). The present study aims to contribute to NAFLD surveillance in patients with T2D, assessing the association of clinical and biological variables with hepatic stiffness and steatosis.A cross-sectional design was used, with data collection from electronic medical records, including adults with T2D who underwent transient elastography (TE) between June 2018 and December 2019. Liver stiffness and steatosis were evaluated using TE and controlled attenuation parameter (CAP), respectively, with cutoff points > 8 kpa for increased stiffness and > 275 dBm for steatosis. The relationship between clinical variables and elastography results were evaluated by bivariate correlation and multivariate analysis, using SPSS 27. Seventy-nine patients (n = 79) met the inclusion and exclusion criteria.Advanced fibrosis and hepatic steatosis were detected in 17,7% and in 21,5% of the patients, respectively. There was a direct and significant correlation between CAP and BMI, waist circumference, HbA1c, triglycerides levels, and insulin doses and an inverse correlation with HDL. The waist circumference, low levels of HDL cholesterol and the insulin dose maintained a significant association with CAP values in multivariate analysis. Elastography values showed an inverse correlation with HDL and a direct correlation with BMI and insulin dose. The association was only maintained for the insulin dose in multivariate analysis.Our results suggest that clinical factors such as insulin dose, waist circumference, and HDL cholesterol levels could identify T2D patients more likely to present NAFLD. Nonalcoholic fatty liver disease (NAFLD) is defined by the fat accumulation in hepatocytes without a secondary cause, such as alcohol consumption, use of steatogenic drugs or genetic syndromes . It is aThere is a bidirectional relationship between diabetes and NAFLD. People with T2D and NAFLD have a higher risk of progressing to steatohepatitis, cirrhosis and death. On the other hand, NAFLD seems to be associated with a higher risk of progressing to diabetes and its macro and microvascular complications . The preThe scientific society's guidelines are controversial about NAFLD screening in patients with T2D ,13 due tThere are different methods used to assess NAFLD. Liver biopsy is the “gold standard” for the assessment of steatosis and fibrosis and the only method capable of identifying the presence of steatohepatitis . HoweverThe present study aims to contribute to NAFLD surveillance in patients with T2D, assessing the association of clinical and biological variables with hepatic stiffness and steatosis.This is a cross-sectional study with electronic medical data of the Diabetes Unit outpatients from Policlínica Piquet Carneiro, Rio de Janeiro State University (UERJ). The study included patients with T2D who underwent TE between June 2018 and December 2019. The exclusion criteria included previous history of liver disease, history of alcohol abuse or use of steatosis-inducing drugs described in the medical record . The stu® . The median value of 10 successful acquisitions, with a success rate of at least 60% and an interquartile range of less than 30% expressed in kilopascals (kpa), was used to represent hepatic stiffness. Cutoff points for the definition of steatosis and advanced fibrosis were CAP > 275 dB/m and hepatic stiffness ≥ 8 kpa, respectively  and its classification as normal (18.5 to <25), overweight (25 to <30) or obesity (≥30) , degree of cardiovascular risk (CVR) , waist cty (≥30) . Accordity (≥30) .®, TRC NW 8 ImageNet Lite system, with a single ophthalmologist reading the image. DR was defined as present when at least one eye was affected by any degree of injury. Diabetes neuropathy and protective sensitivity of the feet were evaluated by the distal polyneuropathy assessment scale, as validated by Moreira and cols. (Glomerular filtration rate (GFR) was calculated by CKD-EPI formula . The urind cols. , and witnd cols. , respectStatistical analysis was performed using SPSS version 27 . Distribution of variables was tested for normality using the Kolmogorov-Smirnov test. An exploratory analysis was performed and continuous variables with normal distribution were expressed as mean and standard deviation, but those with asymmetric distribution were expressed as median (interquartile range). Categorical variables were expressed as frequencies. Student's t-test or Mann-Whitney test was used to compare means or medians between groups, when indicated. When comparing three groups, one-way analysis of variance (F) or Kruskal-Wallis (Z) was used according to the normality of the analyzed variable. In the same way, a bivariate Pearson or Spearman correlation was used to assess the correlations between the studied variables and the CAP and elastography values. Variables with p value < 0.1 were included in the linear regression multivariate analysis, in which variables without normal distribution were converted to logarithmic scale to fit the model. The multicollinearity test between variables included in the multivariate analysis was performed. A two-sided p value < 0.05 was considered statistically significant.Eight two patients underwent liver elastography between June 2018 and December 2019. Seventy-nine met the inclusion criteria. vs. 209.6 ± 50.0, p = 0.04, respectively) and in those with MS compared to those without . When comparing patients with normal BMI, overweight and obesity, significant differences were observed in CAP means between groups . Patients with GFR < 60 had lower CAP means compared to patients with GFR ≥60 . Individuals of normal weight or overweight had lower values of elastography than those with obesity [5 (vs. 5(vs. 6 (p = 0.012)]. No significant difference was observed when the elastography values were compared between the groups described above.There were no significant differences in CAP values according to sex; diabetes duration (< 10 or ≥10 years); HbA1c values (<7% or ≥7%); hypertension; neuropathy or altered protective sensitivity of the feet; and subgroups with ACR <30 or ≥30 mg/g or ACR <300 or ≥300 mg/g. Higher mean CAPs were observed in patients using insulin compared to those who did not  was higher in patients with advanced fibrosis (31 and Lombard and cols. found a higher risk of CVD and microvascular complications in patients with hepatic fibrosis (NAFLD has been associated with an increased risk of microvascular complications and CVD in T2D patients, but published data are heterogeneous. Ciardullo and cols.  found thfibrosis . In our The present study has several limitations. The associations obtained are at most moderate, the sample size is small and the exclusion of other causes of liver disease was based only on patient's medical records. The patients of the present study were from a specialized outpatient clinic at a tertiary care center, with prolonged disease duration, high prevalence of microvascular complications and high cardiovascular risk. Therefore our findings may not apply to populations with different characteristics. No causal relationship can be ascribed to the associations found, which requires prospective studies with larger samples. On the other hand, the associations found between clinical characteristics easily identifiable in medical practice and the presence of steatosis and/or fibrosis can help to determine which patients with T2D benefit the most from NAFLD diagnostic tests.Our study contributes to the study of NAFLD in people with T2D with the use of CAP and elastography, considering that those methods have been increasingly used in literature. As controversies still exist about the screening of NAFLD in T2D patients, our results suggest that clinical factors such as insulin dose, waist circumference, and HDL cholesterol levels could identify T2D patients more likely to present NAFLD. However, studies with a larger number of patients are needed to confirm these results and possibly identify the cutoff points for each of the variables that would indicate screening for NAFLD.


Aim/hypothesis: The relationship between peripheral blood leukocyte telomere length (LTL) and kidney dysfunction, especially in people with hypertension, remains unclear. No clinical study has explored the role of inflammation and oxidative stress in the relationship between LTL and kidney dysfunction. Therefore, we examined the relationship between baseline LTL and albuminuria progression and/or rapid renal function decline in Chinese patients with or without hypertension and investigated whether inflammation and oxidative stress played a mediating role in this relationship.Methods: We conducted a prospective study including 262 patients in a 7-year follow-up period from 2014 to 2021. Data on LTL, inflammation, oxidative markers, renal function, and urine protein levels were assessed. Kidney dysfunction was defined as either albuminuria progression, rapid decline in renal function, or the composite endpoint . Logistic regression and simple mediation models were used for the analysis.Results: In this cohort , 42(16.0%), 21(8.0%), and 59(22.5%) patients developed albuminuria progression, rapid eGFR decline, and the composite endpoint of kidney dysfunction, respectively. Logistic regression analysis showed that each standard deviation decrease of baseline LTL and the lower quartile (Q) of baseline LTL were significantly correlated with an increased risk of rapid decline in renal function ; and the composite endpoint of kidney dysfunction . The mediating analysis showed that tumor necrosis factor (TNF)-a partly mediated the relationship between LTL and rapid decline in renal function , and the mediating proportion was 22.4%.In subgroup analyses, LTL was inversely associated with rapid decline in renal function or the composite endpoint of kidney dysfunction only in patients with hypertension .Conclusion: Baseline LTL could independently predict kidney dysfunction at follow-up, especially in participants with hypertension. TNF-a partially mediated the negative association between LTL and kidney dysfunction. Telomeres are tandem repeats of the eukaryotic chromosomal terminal DNA sequence TTAGGG. Leukocyte telomere length (LTL) progressively shortens with each cell division, and telomeres attrition is a hallmark of cellular aging. Additionally, LTL has been associated with cardiovascular diseases, diabetes, cancer, and chronic kidney disease (CKD) LTL is associated with CKD and end-stage renal disease (ESKD) development, and albuminuria progression However, our previous study did not find the relationship between LTL and eGFR The most common causes of CKD are poorly controlled diabetes and hypertension Moreover, the mechanisms underlying the association between LTL and kidney dysfunction remain unclear. Some animal studies have shown that chronic inflammation and oxidative stress play important roles in LTL shortening as well as kidney dysfunction The purpose of our study was to examine the relationship between baseline LTL and albuminuria progression and/or rapid renal function decline during follow-up in patients with or without hypertension in rural Chinese communities and to investigate whether inflammation plays a mediating role in this relationship.2, 262 participants were included in this study.The current prospective study, which included a Chinese cohort from the suburb of Changping, Beijing, was conducted between March 2014 and July 2021, during a mean follow-up of 5.97±1.16 years. The research protocol and consent procedures were approved by the Ethics Committee of the Peking Union Medical College Hospital. All the participants provided written informed consent. After excluding participants who lacked baseline LTL results, albuminuria results, serum creatinine results, and had a baseline urine albumin-creatinine ratio [ACR] ≥300 mg/g Cr or eGFR <60 mL/min/1.73 m2 ≤BMI <28 kg/m2 and BMI ≥ 28 kg/m2, respectively.Demographic data collected at baseline included age; sex; history of use of anti-glycemic, antihypertensive, and anti-lipid drugs; and history of diabetes, hypertension, and hyperlipidemia. Anthropometric data, including height, weight, waist circumference (WC), hip circumference, systolic blood pressure (SBP), and diastolic blood pressure (DBP), were collected. The formula for calculating the body mass index (BMI) was height (in meter)/weight (in kilogram) squared. Overweight and obesity were defined as 24 kg/mUrine and blood samples were collected from participants during follow-up to assess albuminuria status and renal function progression. According to the World Health Organization criteria, normal glucose tolerance (NGT) was identified using the 75-g oral glucose tolerance test: fasting plasma glucose (FPG) <6.1 mmol/L and 2-hour post-load plasma glucose (2h-PG) <7.8 mmol/L. Pre-diabetes was indicated by impaired fasting glucose measured as 6.1 mmol/L ≤ FPG <7.0 mmol/L and 2h-PG <7.8 mmol/L, impaired glucose tolerance (IGT) measured as 7.8 ≤2h-PG <11.1 mmol/L and FPG <6.1 mmol/L, or both impaired fasting glucose and IGT. Diabetes was indicated by FPG ≥7.0 mmol/L or 2h-PG ≥11.1 mmol/L.eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation, based on the measurement of serum creatinine and anthropometric data, such as age and sex. ACR was calculated based on urine microalbumin and urine creatinine levels. The equations are as follows:where K=0.7  or 0.9 , α= -0.241  or -0.302 , and ACR=urinary albumin/urinary creatinine (mg/g Cr).LTL assays were performed using the blood samples collected at baseline. The details of the LTL measurements are described in our previous publication Oxidative stress and inflammatory marker levels were measured using the blood samples collected at baseline. TNF-α, interleukine-6(IL-6), 8-hydroxy-2 deoxyguanosine(8-OHDG); superoxide dismutase (SOD); glutathione reductase (GR) concentrations were determined using an ELISA kit  by the Beijing Institute of Biotechnology.Hypertension was defined either as having been diagnosed with hypertension, taking antihypertensive drugs, or SBP ≥140 mmHg and DBP ≥90 mmHg at rest.Kidney dysfunction was defined according to the following: (1) A rapid decline in eGFR: A rapid decline in eGFR was defined as decline in eGFR of ≥3.3% per year 2 test for categorical variables. Bonferroni correction was used for post-hoc comparisons.Participants were divided into quartiles (Q) based on their baseline LTL levels. Continuous variables with normal distribution are expressed as mean ± standard deviations (SDs), whereas non-normally distributed variables are presented as median and interquartile range. Categorical variables are expressed as numbers with corresponding percentages. Comparisons between groups were performed using a one-way analysis of variance for continuous variables and the χThe associations between LTL and the outcomes were analyzed using logistic regression analysis, with odds ratios (OR) and associated 95% confidence intervals (CIs) computed for quartiles of baseline LTL and one SD change in baseline LTL. For the computation of ORs for one SD decrease in baseline LTL, a minus z-score for log transformed LTL was calculated for each participant. Four models were generated: Model 1: not adjusted. Model 2: adjusted for age, sex. Model 3: adjusted for Model 2 +BMI, HbA1c, SBP, DBP, LDL-C, TG, UA. Model 4: adjusted for Model 3+ baseline ACR,baseline eGFR.To explore whether oxidative stress and inflammatory markers mediated the effect of LTL on kidney dysfunction, R package(mediation) was used for mediation analysis, and all mediation models were adjusted for age, sex, BMI, HbA1c, SBP, DBP, LDL-C, TG, UA, baseline ACR and baseline eGFR.A two-sided P<0.05 was considered statistically significant. Statistical analysis was performed using IBM SPSS Statistics for Windows, version 26.0  and R for Windows, version 4.2.3.P<0.05). However, age, sex, BMI, WHR, SBP, DBP, FPG, HbA1C TC, TG, HDL-C, LDL-C, IL-6, 8-OHdG, and GR did not differ between the four groups (P>0.05). Additionally, the percentages of participants with microalbuminuria, diabetes, hypertension, hyperlipidemia, hyperuricemia, and obesity were not significant different between groups .The baseline characteristics of participants are shown in Table During the follow-up period, 42 (16.0%) participants developed albuminuria progression,21 (8.0%) participants had a rapid decline in renal function,and 59 (22.5%) participants reached the composite endpoint of kidney dysfunction . Associations of baseline LTL with the risk of albuminuria progression and/or rapid decline in renal function are shown in Table P=0.03) (Table P for trend=0.031) , and the OR was 2.96 for Q1 versus Q4 of LTL  ]; indirect effect: β=0.013 95%CI ), whereas TNF-α partly mediated this negative effect of LTL on rapid decline in renal function and the proportion was 22.4% Table .P for interaction=0.045; OR=3.10 , P for interaction=0.036)  during follow-up. Additionally, we showed that TNF-α partly mediated the association between LTL and rapid renal function decline. Lastly, we found a negative association between baseline LTL and kidney dysfunction , which remained significant only in participants with hypertension in the subgroup analysis.This study posed three central questions: 1) whether there was an association between LTL and kidney dysfunction; 2) whether oxidative stress and inflammation played a mediating role in the association between LTL and kidney dysfunction; and 3) whether the association between baseline LTL and kidney dysfunction was affected by hypertension status.For the first question, we found a negative association between LTL and the composite endpoint of kidney dysfunction, which is consistent with previous studies. A prospective study including 132 individuals with type 1 diabetes and another study including 691 individuals with type 2 diabetes showed that telomere length is associated with albuminuria progression in vitro experiments, the cells with the shortest telomere exhibited the highest levels of TNF-a expression in vitro experiment revealed that short telomeres can mediate additional downstream activation of ZBP1(S), via TERRA, to form ZBP1 filaments on the mitochondria, thereby promoting the inflammatory cycle Akita (with diabetes) mice Regarding the second study question, our result suggests that LTL shortening increases the risk of rapid decline in renal function, in which TNF-a plays a mediating role. The relationship between telomeres and inflammation is complex. Inflammation can lead to telomeres dysfunction and cause telomeres shortening Regarding the last question, we found a more prominent association between shorter LTL and the risk of kidney dysfunction in participants with hypertension than that in participants without hypertension. Hypertension increases the risk of decreased eGFR, blood pressure is an important predictor of early renal function decline Our study has several strengths. First, our analysis focused on the relationship between LTL and kidney dysfunction in participants with hypertension, for which there are few related studies. Second, we analyzed the role of inflammatory stress in the LTL-CKD link and found that TNF-a mediates the effect between LTL and kidney dysfunction. However, our study has some drawbacks. This study included a small sample size and could not draw causal conclusions because of the study design. Future studies will expand the sample size and extend the follow-up period.LTL was negatively associated with the kidney dysfunction especially rapid decline in renal function during follow-up. TNF-a partially mediates the association between LTL and rapid decline in renal function. The association between LTL and kidney dysfunction is more pronounced in patients with hypertension. Therefore, LTL may be an important clinical predictor of kidney dysfunction in patients with hypertension. Future studies should be conducted using a larger population to better understand the role of LTL in changes in kidney function.Supplementary figures and table.Click here for additional data file.


Long-term exposure to air pollution and physical activity (PA) are linked to blood pressure and hypertension. However, the joint effect of air pollution and PA on blood pressure and hypertension are still unknown in Chinese middle-aged and older adults.2.5), or ≤10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbonic oxide (CO)] were estimated using satellite-based spatiotemporal models. PA was investigated using International Physical Activity Questionnaire. Generalized linear models were used to examine the associations of air pollution, PA score with blood pressure , and the prevalence of hypertension. Subgroup analysis was conducted to investigate the effects of air pollution on blood pressure and the prevalence of hypertension in different PA groups.A total of 14,622 middle-aged and older adults from the China Health and Retirement Longitudinal Study wave 3 were included in this study. Ambient air pollution [particulate matter with diameter ≤ 2.5 μm (PM2.5 (25.45 μg/m3), PM10 (40.56 μg/m3), SO2 (18.61 μg/m3), NO2 (11.16 μg/m3), CO (0.42 mg/m3) and PA score (161.3 MET/h-week), the adjusted odd ratio (OR) of hypertension was 1.207 : 1.137, 1.281), 1.189 , 1.186 , 1.186 , 1.288 , 0.948 , respectively. Long-term exposure to PM2.5, PM10, SO2, NO2, and CO was associated with increased SBP, DBP, and MAP levels. For example, each IQR increase in PM2.5 was associated with 1.20 mmHg  change in SBP, 0.66 mmHg  change in DBP, and 0.84 mmHg  change in MAP levels, respectively. Each IQR increase in PA score was associated with −0.56 mmHg  change in SBP, −0.32 mmHg  change in DBP, and −0.33 mmHg  change in MAP levels, respectively. Subgroup analysis found that the estimated effects in the sufficient PA group were lower than that in the insufficient PA group.The results showed that for each inter-quartile range (IQR) increase in PMLong-term exposure to air pollutants is associated with increased blood pressure and hypertension risk, while high-level PA is associated with decreased blood pressure and hypertension risk. Strengthening PA might attenuate the adverse effects of air pollution on blood pressure and hypertension risk. Hypertension has become the top leading risk factor for attributable death, accounting for ~10.8 million deaths each year . Previou2.5, PM10, and NO2 was associated with increased diastolic blood pressure (DBP) levels, and PM2.5 was associated with an increased prevalence of hypertension , mean arterial pressure (MAP) and the prevalence of hypertension  and NO2, further studies are needed to determine whether exposure to other air pollutants  can increase blood pressure and hypertension risk.Several studies have indicated that exposure to ambient air pollution was associated with increased blood pressure and the prevalence of hypertension . A systertension . A crossrtension . Howeverrtension . For exaobserved . TherefoPhysical activity (PA) has been demonstrated as an effective way against hypertension and other CVDs .Numerous studies have found that higher PA levels could reduce blood pressure levels and hypertension risk . A meta-2.5 in the associations between PA and hypertension incidence and indicated that PA was associated with decreased hypertension only among participants with low PM2.5 exposure  and PA with three blood pressure components  and the prevalence of hypertension, and investigate the effects of air pollution on blood pressure and prevalence of hypertension in different PA groups.In this study, we aimed to examine the associations of air pollution , which is established to collect a wide range of high microdata of middle-aged and older adults. Detailed description of the CHARLS study has been reported in previous studies . BrieflyAll participants signed informed consent and the CHARLS was approved by the Institutional Review Board of Peking University (Code: IRB00001052-11015).2.5, PM10, SO2, NO2, and CO were estimated at 0.1 degree (≈10 km) with space–time extremely randomized trees models using ground-based measurements, remote sensing products, and atmospheric re-analysis, and are collected from the ChinaHighAirPollutants (CHAP) dataset.R2  were 0.92 (10.76 μg/m3), 0.90 (21.12 μg/m3), 0.84 (10.07 μg/m3), 0.84 (7.99 μg/m3) and 0.80 (0.29 mg/m3) for daily PM2.5, PM10, SO2, NO2, and CO, respectively. Detailed information of the air pollution estimation is described in our previous study  via face-to-face interviews. Briefly, the frequency and duration of different intensities activity  during a week were investigated. PA duration score was calculated as the frequency (times/week) × duration (hour/time). And then PA score was assessed using metabolic equivalent (MET) a: PA score = 8.0 × vigorous PA duration +4.0 × moderate PA duration +3.3 × light PA duration , 33. AccThree-time SBP and DBP measurements were completed using electronic blood pressure monitors . Participants were asked not to eat, exercise, smoke or drink alcohol within 30 min before the blood pressure measurement. MAP was defined as DBP + 1/3 (SBP-DBP) . The thrNumerous potential confounders were included in our study according to previous studies of long-term exposure to air pollution with blood pressure and/or hypertension, including meteorological factors , sociodet-test, and the distribution discrepancy of categorical variables between the hypertension group and non-hypertension group was examined using Chi-square test (The characteristics of participants were described as mean ± standard deviation (SD) for continuous variables and counts  were described for categorical variables, respectively. The difference of continuous variables between the hypertension group and non-hypertension group was tested using Student’s are test , 44. TheGeneralized linear models (GLMs) were performed to examine the associations of air pollution with blood pressure and the prevalence of hypertension. The results were presented as change in mmHg for blood pressure and odd ratio (OR) for hypertension per inter-quartile range (IQR) increase in air pollutants. We first performed crude model without any adjustments. Then, temperature and relative humidity were adjusted in adjusted model 1. Finally, sociodemographic, socioeconomic variables, and health behaviors were additionally adjusted in adjusted model 2.v.s. Insufficient PA group)  , 32.Sensitivity analysis was also performed to evaluate the robustness of our results based on the full-adjusted model. Firstly, we examined the association of 2-year exposure with blood pressure and the prevalence of hypertension. Then, we excluded participants who were taking anti-hypertension medicine and evaluated whether the associations of air pollution with blood pressure were responsible for anti-hypertension medicine , 12, 45.p-value < 0.05 was set as statistical significance.All the statistical analyses were performed by R version 4.1.2 and the missing data for PA was imputed by using “mice” package , 33. A tA total of 14,622 participants from 430 communities in 120 county-level cities were included in this study. The distribution of participants in 27 Chinese provinces is shown in 2.5, PM10, SO2, NO2, CO were 61.87 ± 18.60 μg/m3, 103.13 ± 32.34 μg/m3, 33.74 ± 14.07 μg/m3, 31.94 ± 7.61 μg/m3, 1.28 ± 0.38 mg/m3, respectively. Person correlation analysis found high co-linearity among different air pollutants , 1.09 mmHg , 1.81 mmHg , 1.05 mmHg , 1.44 mmHg  increase in SBP, respectively. Each IQR increase in PM2.5, PM10, SO2, NO2, and CO was associated with 0.66 mmHg , 0.56 mmHg , 0.79 mmHg , 0.54 mmHg , 0.76 mmHg  increase in DBP, respectively. And each IQR increase in PM2.5, PM10, SO2, NO2 and CO was associated with 0.84 mmHg , 0.73 mmHg , 1.13 mmHg , 0.71 mmHg , 0.99 mmHg  increase in MAP, respectively.Higher PMd models . After a2.5, PM10, SO2, NO2, and CO was associated with 20.7% , 18.9% , 18.6% , 18.6% , 28.8%  increase in the prevalence of hypertension, respectively  was associated with an −0.56 mmHg , −0.32 mmHg , −0.33 mmHg  change in SBP, DBP and MAP, respectively. As for the prevalence of hypertension, each IQR increase in PA score was associated with a 5.2%  decrease in the prevalence of hypertension .P-interaction was not significant , except for PM10 with SBP . The patients/participants provided their written informed consent to participate in this study.ZN, SH, and JZ: conceptualization. JZ, FZ, JW, and ZD: data curation. JZ, FZ, ZN, and ZD: formal analysis. SH: funding acquisition. JZ, FZ, CX, XZ, and ZD: investigation. ZN and SH: methodology, supervision, and writing–review and editing. JZ, FZ, CX, and XZ: project administration. JZ and ZN: resources. JZ and FZ: software and roles and writing–original draft. ZN: validation. JZ, FZ, and ZN: visualization. All authors contributed to the article and approved the submitted version.This study was supported by the National Natural Science Foundation of China (no. 82102322).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


In this multicenter prospective study, we explored the relationship between pulmonary artery pressure (PAP) at rest and in response to a 6-min walk test (6MWT) in ambulatory patients with heart failure (HF) with an implantable PAP sensor .Between 5/2019 and 2/2021, HF patients with a CardioMEMS sensor were recruited from seven sites. PAP was recorded in the supine and seated position at rest and in the seated position immediately post-exercise.p < 0.0001), diastolic 15 ± 10 mmHg (p = 0.006), and mean 24 ± 13 mmHg (p < 0.0001). Patients with elevated PAP diastolic at rest (>15 mmHg) demonstrated a greater increase in post-exercise PAP.In our cohort of 66 patients, mean age was 70 ± 12 years, 67% male, left ventricular ejection fraction (LVEF) < 50% in 53%, mean 6MWT distance was 277 ± 95 meters. Resting seated PAPs were 31 ± 15 mmHg (systolic), 13 ± 8 mmHg (diastolic), and 20 ± 11 mmHg (mean). The pressures were lower in the seated rather than the supine position. After 6MWT, the pressures increased to PAP systolic 37 ± 19 mmHg (The measurement of PAP with CardioMEMS is feasible immediately post-exercise. Despite being well-managed, patients had severely limited functional capacity. We observed a significant increase in PAP with ambulation which was greater in patients with higher baseline pressures. Exercise intolerance is a cardinal manifestation of heart failure (HF). The standard 6-min walk test (6MWT) quantifies functional capacity and correlates strongly with the risk of heart failure (HF) hospitalization and mortality in patients with HF, regardless of ejection fraction (EF) . HemodynHeart failure management guided by an implantable pulmonary artery pressure sensor  reduces pulmonary artery pressure (PAP) and HF hospitalizations in HF patients compared to standard-of-care HF management as was demonstrated in the landmark CHAMPION trial . AmbulatWe hypothesized that PAP measured using an implantable sensor after a 6MWT in both supine and seated hemodynamic position could allow for more accurate correlation of hemodynamic variables with functional capacity. We therefore conducted a prospective multi-center pilot study to examine the effect of 6MWT on pulmonary pressures using the CardioMEMS (CM) sensor in patients with chronic HF.Patients who had a CM sensor implanted for clinical indications were recruited from seven sites across the United States from May 2019 to February 2021. PAP was recorded from the CM in the supine and seated position at rest and in the seated position post-exercise.Non-invasive blood pressure (BP) and heart rate (HR) were measured immediately pre- and post-exercise during PAP measurement from the CM with the patient in an upright seated position. Pulmonary artery systolic pressure (PASP), diastolic pressure (PADP) and mean pressure (PAMP) were recorded immediately before and after exercise. Upon completion of exercise the patient was seated with goal of measuring CM pressures within 30 s after termination of the 6MWT.Demographic data including New York Heart Association (NYHA) class, HF etiology , LVEF, comorbidities, cardiac medications, and implantable cardiac electronic device settings including rate-response information was collected. PAP data was measured at end expiration and PAP tracings from all sites were sent in de-identified form to Scripps Clinic for central adjudication by a heart failure cardiologist.t-test. Difference among the groups was compared with a one-way ANOVA test.Baseline characteristics were summarized as means and standard deviations for continuous variables and as frequencies and percentages for categorical variables. Pre-and post-exercise data were compared with a paired Sixty-six patients with a mean age of 70 ± 12 were enrolled. The majority were male (67%), NYHA class III (61%), with an LVEF <50% (53%). Five patients were NYHA I (7.6%), 17 NYHA II (25.8%), 40 NYHA III (60.6%), and 4 NYHA IV (6.0%) . There wp < 0.0001). Compared to pre-exercise seated pressure, pressures measured after 6MWT increased: PASP 37 ± 19 mmHg (p < 0.0001), PADP 15 ± 10 mmHg (p = 0.006), and PAMP 24 ± 13 mmHg (p < 0.0001). Mean increases after exercise were PASP 6 ± 11, PADP 2 ± 6, and PAMP 4 ± 8 mmHg. There was no difference in 6MWT distance or pre-and post-exercise pulmonary pressures in patients with normal versus reduced LVEF. Resting HR in the seated position was 76 ± 13 beats per minute, and it increased to 86 ± 15 beats per minute after the walk, p < 0.001.The mean 6MWT distance was 277 ± 95 m. Resting supine pressures were PASP 36 ± 17, PADP 16 ± 9, and PAMP 24 ± 12 mmHg . In the r = −0.28, –0.31, –0.27, –0.31, and −0.27, respectively, all p < 0.01). The distance walked in 6 min decreased significantly with increasing NYHA functional class . There were no sex-related differences in any pre-or post- exercise parameters.In 46 patients (70%), resting supine PADP was <20 mmHg. Only 28 patients (42%) were able to walk 300 m or more. There was a negative correlation of 6MWT distance with NYHA class, PASP, PADP, and PAMP supine, and PASP seated (p < 0.001) but not in individuals with PADP <15 mm Hg (p = 0.004) and from 74 ± 13 to 86 ± 16 beats per minute (p < 0.001), respectively. There was no correlation between PADP and 6MWT distance.As resting PADP is a therapeutic target in hemodynamic management with CM, we further stratified the cohort according to resting pressures. Because PADP is usually measured in a supine position in clinical practice, we used supine resting PADP to define cohorts with PADP≥15 mmHg and <15 mmHg. After 6MWT, there was a significant increase in all pulmonary pressures in patients with PADP ≥15 mm Hg (15 mm Hg . Heart rThe major findings of this study are: (1) measurement of pulmonary artery pressure after exercise was feasible in all patients; (2) pulmonary artery pressures fall significantly with change from supine to seated position, with the predominant effect on PASP; (3) with 6MWT, PAP increased significantly, regardless of EF; (4) the strongest hemodynamic correlate of 6MWT distance was supine PAP.Our study population represents a unique cohort of patients with chronic HF treated with the guidance of an implantable hemodynamic sensor (CardioMEMS). Despite being well managed, with 70% having PADP <20 mmHg at rest, which represents a typical hemodynamic goal .This study examined the ability to use a CardioMEMS sensor to monitor the effect of positional changes (supine vs. seated) and exercise on pulmonary pressures.We found that pulmonary pressures increase in the supine position and after exercise and that the greatest increase was seen in patients with baseline elevated pressures. Furthermore, supine pressures most reliably predicted walk distance.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Institutional Review Board. The patients/participants provided their written informed consent to participate in this study.RK, JA, and JH: writing and data collection. OJ, KB, MB, AB, AG, PM, MR, and AC: data collection. HO and SB: statistical analysis. EM, AS, and MF: writing. MG: writing, data collection, and statistical analysis. All authors contributed to the article and approved the submitted version.JA, OJ, MF, and KB are speakers for Abbott. KB also serves on the speakers bureau for Pfizer and Novartis and serves as a consultant for Abbott and Vectorius. MB and AB serve as consultants for Abbott. PM serves as a consultant for Abbott, AstraZeneca, Janssen, Daxor, and CVRx. AS reports receiving research funding from Abbott as part of the GUIDE-HF trial and reports serving on steering committees for Abbott, Boston Scientific, Biotronik, Story Health, and General Prognostics. AS also reports receiving consulting honoraria from Abbott, Boston Scientific, Edwards Lifesciences, Biotronik, Story Health, and General Prognostics. JH has received honoraria from Actelion Pharmaceuticals, Medtronic, Abbott, Boehringer, Ingelheim, Bayer, Lily as well as research grant support from Abbott and Impedimed.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


IPM revealed an absolute risk reduction in redGFR of 5.5% (11 of 199 CG patients) to 0% in the IPM visit IG, a relative risk reduction of 100%, NNT 18, indicating high efficacy of IPM and benefit in improving outcomes. There even remained an additive superimposed significant association that included patients in the IPM group before/beyond the 14 daily IPM interventions, with a relative redGFR risk reduction of 0.55 (55%) to 2.5% (5 of 204 patients), OR 0.48 [95% CI 0.438–0.538] (p < 0.001). Bacteriuria, loop diuretics, allopurinol, eGFR ≥ 60 mL/min/1.73 m2, eGFR < 60 mL/min/1.73 m2, and CKD 3b were significantly associated with redGFR; of the latter, 10.5% developed redGFR. Further multivariable regression analysis adjusting for these and established risk factors revealed an additive, superimposed IPM effect on redGFR with an OR 0.238 [95% CI 0.06–0.91], relative risk reduction of 76.2%, regression coefficient −1.437 including patients not yet visited in the IPM period. As consequences of the IPM procedure, the IG differed from the CG by a significant reduction of NSAIDs (p < 0.001), HCT (p = 0.028) and Würzburger pain drip (p < 0.001), and significantly increased prescription rate of antibiotics (p = 0.004). In conclusion, (1) more than 50% of CKD in geriatric patients was not pre-recognized and underdiagnosed, and (2) the electronic patient records-based IPM interdisciplinary networking strategy was associated with effective prevention of further periinterventional renal impairment and requires obligatory implementation in all elderly patients to urgently improve patient and drug safety.The aging global patient population with multimorbidity and concomitant polypharmacy is at increased risk for acute and chronic kidney disease, particularly with severe additional disease states or invasive surgical procedures. Because from the expertise of more than 58,600 self-reviewed medications, adverse drug reactions, drug interactions, inadequate dosing, and contraindications all proved to cause or exacerbate the worsening of renal function, we analyzed the association of an electronic patient record- and Summaries of Product Characteristics (SmPCs)-based comprehensive individual pharmacotherapy management (IPM) in the setting of 14 daily interdisciplinary patient visits with the outcome: further renal impairment with reduction of eGFR ≥ 20 mL/min (redGFR) in hospitalized trauma patients ≥ 70 years of age. The retrospective clinical study of 404 trauma patients comparing the historical control group (CG) before IPM with the IPM intervention group (IG) revealed a group-match in terms of potential confounders such as age, sex, BMI, arterial hypertension, diabetes mellitus, and injury patterns. Preexisting chronic kidney disease (CKD) > stage 2 diagnosed as eGFR < 60 mL/min/1.73 m Health care management in a global demographic context means treating the increasing numbers of geriatric patients worldwide with multimorbidity and polypharmacy. This interconnects with serious risks requiring the earliest possible preventive measures against e.g., renal failure, fall events, and cognitive impairment. The appropriateness of medication therapy for older people and the issues involved in drug and patient safety are a challenge that WHO continues to address ,2,3, andUnavoidable polypharmacy in multimorbidity, including age-related renal impairment and more prevalent chronic kidney disease (CKD), accordingly requires pharmacovigilance with a rigorous focus on the exclusion of any iatrogenic, drug-induced decline in renal function. In particular, the preexisting patient condition in combined organ deterioration and polypharmacy poses a high risk of drug-induced complications as caused by adverse drug reactions (ADRs), pharmacodynamic and pharmacokinetic drug-drug interactions (DDIs), overdose, and contraindications in these most vulnerable elderly and very old patients, notably in acute illnesses and in the perioperative course, which per se implies additional drug treatment, namely, narcotics, analgesics, antithrombotics, and antimicrobials. These risks turned out to be of high prevalence as learned from the own conceptualized and conducted, most comprehensive individual pharmacotherapy management (IPM) through >58,600 medication reviews. 2 or urinary albumin excretion ≥ 30 mg/l for persons over 70 years of age has been reported to be approximately 28%  = 186 × (creatinine[mg/dL]exp(−1.154)x age[years] exp(−0.203) correction factor * . And as a consequence of the study, now the UKH laboratory has been using the CKD-EPI equation for eGFR since 2016, which affects some of the later IG patients. The differentiated arguments for the use of the various estimated GFRs are of practical and clinical relevance  with high significance at  < 0.001 . 2 ; 13 patients with admission eGFR < 60 mL/min/1.73 m2, including 7.1% (6 of 79 patients) with CKD 3a, 10.5% (6 of 51 patients) with CKD 3b, and 3.3% (1 of 29 patients) with CKD 4.In total, 16 patients of the entire CG and IG developed redGFR: 1.4% (3 of 216 patients) with admission eGFR ≥ 60 mL/min/1.73 mWe also analyzed whether an application of the BIS-1 formula  introduc2 at UKH led to the introduction of the eGFR CKD-EPI instead of the MDRD formula in 2016. Thus, only in the later course of the IPM intervention phase, a small proportion of patients were assessed by this method. However, since the majority of the IG was estimated analogously to the entire CG via eGFR MDRD with the unification of all GFR values ≥60 mL/min/1.73 m2, we could not conduct a BIS-1 comparison for CKD stages 1 and 2 additionally. In the context of this study, our recommendation to adequately assess and further differentiate the renal function ≥ 60 mL/min/1.73 mThe application of BIS-1 indicates that the number of risk patients for redGFR from the CKD 3b stage would even be enhanced, shifting more patients from CKD 3a to CKD 3b. This would be of clinical relevance, as it was the patient group most prone to red GFR (10.5%), who therefore require particular vigilance and closer monitoring of eGFR. For patients with an IPM and an absolute risk reduction of eGFR of 5.5% (11 of 199 in CG versus 0 of 199 in IPM-IG)), a relative risk reduction of 100%, and a number needed to treat of NNT = 18, the latter cannot even be further reduced because it is impacted by the overall low incidence of the very strong outcome redGFR in the CG already.n = 16) with the clinically relevant variables selected from the results of the cross-tabulation calculations, adding established variables from literature data, was performed for age, gender, CKD, diabetes mellitus, arterial hypertension, NSAIDs, contrast media, allopurinol, Würzburger pain drip, antibiotic-requiring infections, bacteriuria, loop diuretics, thiazides, ACE-inhibitors, and polypharmacy (number of prescribed drugs). We applied a chi-square test and the resulting p-values including Fisher’s exact test for correction because of small samples and low numbers of expected frequencies revealed significant associations of redGFR with allopurinol (n = 6) p = 0.002, bacteriuria (n = 2) p = 0.007, loop diuretics (n = 11) p = 0.014, eGFR ≥60mL/min  (n = 3) p = 0.003, eGFR <60mL/min (n = 13) p = 0.004, and CKD 3b (n = 6) p = 0.016. The limited strength of the results due to low case numbers has to be considered. Additional potential confounders such as age, gender, diabetes mellitus, arterial hypertension, number of medications, and contrast media did not reveal a significant association with redGFR; again, a limited power has to be respected due to the very short periinterventional follow-up period as well as the small number of concerned patients.Contingency analysis for the entire patient study population on the association of redGFR , PPI, contrast media. The regression coefficient of the IPM (−1.437) was found to be significant  = 4.390, p = 0.036) even including all patients of the IG before/week after IPM, indicating IPM was associated with a superimposed reducing significant impact on redGFR with an effect outside the individual IPM visit, e.g., via optimized standard operating procedures on the part of the regular IPM in the intervention period as demonstrated for our completely IPM-altered analgesic treatment. In this model, the relative probability of redGFR was significantly reduced with OR = 0.238 [95% CI 0.06–0.91] for this entire IPM setting, confirming the assumption of a superimposed effect of IPM. The relative probability of a redGFR was reduced by 76.2% during the intervention period, even including patients before/beyond the 14 daily IPM visits. The regression coefficients of the examined independent variables of the multiple logistic regression were significant, indicating a relationship, between redGFR and the following independent variables: CKD <60 mL/min/1.73 m2 regression coefficient 2.893, p = 0.001; loop diuretics 1.397, p = 0.036; HCT −2.575, p = 0.023; IPM −1.437, p = 0.036. Again, there were no further associations with age within the already nearly homogeneous group of elderly to oldest patients, nor with gender, arterial hypertension, diabetes mellitus, heart failure, ACE inhibitors, ß-blockers, or contrast media.Multiple binary logistic regression analysis was performed to estimate the probability of an IPM-associated reduction in the dependent variable redGFR with respect to the simultaneous effects of multiple explanatory independent variables. Besides the model with our own verified variables we considered established risk factors for acute kidney injury: age, gender, arterial hypertension, diabetes mellitus, heart failure, CKD stages with eGFR <60 mL/min/1.73 mThe profound personal and socioeconomic implications of an increasing prevalence of renal dysfunction with all its accompanying cerebrocardiovascular comorbidities in an accelerating aging population urgently require strategies for the reliable prevention of CKD and acute kidney injury ,49. Our 2 is strong to intentionally capture the more severe degrees of renal decline since less pronounced variations of eGFR around 10 mL/min throughout the perioperative might be of minor relevance. Especially in the perioperative setting, a redGFR around 10 mL/min only may result from a variety of multifactorial and often transient causes, such as anesthetic and analgesic drugs and acute surgical effects, hydration status, blood pressure drop, bleeding issues, or an infectious course. In consequence, our focus on a more robust and powerful renal function parameter was to enable the analysis of a significant IPM effect more accurately. Acute kidney injury (AKI), besides urine volume, is determined by creatinine levels [2, although here the number of patients affected and thus its statistical power was considerably lower. The clinically relevant outcome redGFR ≥ 20 mL/min/1.73 me levels . Howevere levels ,64. This2 who do not have markers of kidney damage if confirmation of CKD is required.” [According to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the evaluation and management of CKD, the eGFR category is a risk predicting variable for the outcome of CKD to identify, apart from the cause of CKD, albuminuria category, other risk factors, and comorbid conditions . The estquired.” ,66. Prinquired.” ,68,69,70quired.” , furtherquired.” . To move forward in the management of CKD, we should not only provide recommendations for specific drugs and lists of typical nephrotoxic agents to be avoided. Moreover, we have to advocate an IPM for the entire drug list, accounting for the individual patient’s overall clinical condition while evaluating indications, contraindications, adverse events, DDIs, and dosages.It is an alarming result that possibly not only in surgical disciplines but also in outpatient care renal impairment is not always given the attention it urgently requires, especially in vulnerable geriatric patients often with preexisting renal impaired conditions. For the operative emergency setting, the main focus seems to be on avoiding surgical risks and complications and on secondary diagnoses that the patient has brought from the medical history. These diagnoses may already be outdated with gaps at the time of hospital admission. The unawareness of CKD even in advanced stages has been documented even more pronounced in various countries and medical disciplines ,74,75,76A broad spectrum of renally eliminated drugs already requires dose adjustment in advanced CKD, on the one hand. The other risk arises additionally from the nephrotoxic ADR potentials of further commonly prescribed drugs, which are typically amplified with dosage or by unrecognized pharmacodynamic or pharmacokinetic DDIs. Correspondingly, the study identified manifest redGFR from overdosed antibiotics, such as in patients before or outside the IPM visit. This classic clinical risk situation for redGFR indicates a need for IPM to be performed even more frequently than every 14 days. There is a high fluctuation of prescribing physicians, particularly in the staffing of night and weekend duty physicians, often involved in acute antibiotic intervention and obviously not always aware of the patient’s renal impairment. The findings challenge an obligatory up-to-date eGFR documentation with at least every inpatient and outpatient medication list to promote and ultimately ensure appropriate dosing, especially in renally pre-impaired elderly patients in the presence of polypharmacy. Antibiotics and even additional DDIs pose a significant risk of further renal injury ,79,80,81The higher rate of older women compared to men is not completely congruent with the population statistics for this age group. According to the German Federal Statistical Office, the gender distribution in 2021, e.g., among those aged 80–84 was: 41.9% men and 58.1% women, and among adults ≥ 85: 34.6% men and 65.4 women . As the Alongside the desirable efforts to deprescribe, some degree of polypharmacy often remains unavoidable in the case of multimorbidity, especially in old age. As underlined by our study results, this makes it all the more important to focus on optimizing this multimedication process, particularly for the age-related pre-impaired drug degrading or eliminating organs  and periOur focus comprised the entire medication list, not only drugs known for their nephrotoxicity such as NSAIDs, aminoglycosides, etc. The identified association of redGFR with loop diuretics and allopurinol has to be considered with caution due to the small numbers and the very short follow-up period. It does not reflect drug injury that may result from long-term treatment or prolonged inappropriate dosing. However, kidney injury by diuretics resulting in AKI is well established and documented, with pathological details revealing vacuolar degeneration of tubular epithelial cells as a common lesion induced by diuretics . In thisAlready in 1991, drug complications were found to be the most common type of adverse event in hospitalized patients, accounting for 19%, calling for better medical knowledge and prevention of treatment errors, as well as overcoming a high level of negligence . A signiWe identified an association of bacteriuria with redGFR. As known for CKD, there is an elevated risk of bacteriuria and urinary tract infections. This is partly due to CKD-associated metabolic and immunologic deterioration in terms of enhanced apoptosis of lymphocytes, increased levels of tumor necrosis factor α and interleukin-6 (IL-6), which depress neutrophil function, and enhanced levels of uremic toxins such as p-cresyl sulfate and indoxyl sulfate, which alter leukocyte adherence and migration at sites of injury. Furthermore, urinary tract infections precipitate worsening of renal function, especially in stages G3-G5 of CKD . Not onlThe IPM measure resulted in reduced HCT therapy. However, we intentionally combined it temporarily with loop diuretics to improve diuresis in critically impaired conditions. This probably may explain the obviously positive effect of HCT with redGFR although with low power numbers. HCT is known to enhance the effect of loop diuretics even in more advanced CKD by sequential nephron blockade .We have systematically reduced the almost classically overdosed and most frequently non-indicated PPI, the predominant pantoprazole from 40 mg to the prophylactic dose of 20 mg, in line with the gradual deprescription required in this context. Evidence has accumulated that PPI use is associated with an increased risk of CKD disease regarding the onset of CKD, progression of CKD, and renal failure . StudiesThe “triple whammy” in primary care, the concomitant use of a triple therapy combination of ACE inhibitors or ARBs plus diuretics plus NSAIDs was associated with an increased rate of AKI , the highest risk observed in the first 30 days  . ACE inhIPM addressed the high prevalence of anemia in our elderly patients and differentiated iatrogenic drug-induced anemias, either hematopoietic or hemorrhagic side effects, also cumulative by different drugs or enhanced by pharmacodynamic or pharmacokinetic DDIs, for reasonable targeted treatment.Apart from renal diseases, major risk factors and most frequent triggers for CKD onset and progression are arterial hypertension and diabetes mellitus . HoweverFor patients with severe acute medical conditions such as surgical or cerebrocardiovascular with metabolic diseases, optimizing prescribing would make much more sense than tightening up the demand for deprescribing because elderly patients often suffer from multiple serious comorbidities, each of which requires adequate drug therapy. As a result of IPM, it is most important and highly effective to address the entire ADRs, cumulative ADRs from pharmacodynamic DDIs, to exclude any undesired increase in drug bioavailability and risk of toxicity by pharmacokinetic DDIs, and to accurately adjust the dose according to the hepatic and renal organ function for drug metabolism and excretion.We documented the effect of IPM via different statistical models. The significant association with the decrease in redGFR was even maintained in the multivariable regression analysis for the overall IPM frame including patients before the 14 daily IPM-visit without an individual medication analysis. Yet, it is important to address, that these patients outside the IPM context remained particularly at risk of missed dose adjustment to renal function with the onset of antibiotics. Whether these cases result from lack of knowledge, disregard of renal function, or operational work stress remains questioned but indicates necessary efforts to consequently enhance attention in this particular respect. Independent of too high a dosage in antibiotics as a risk of nephrotoxicity in our study, an extensive spectrum of medications poses nephrotoxic ADRs. ADR from drug-induced nephrotoxicity remains one of the most common causes of acute kidney injury among hospitalized patients, such as from antimicrobials like antibiotics known to induce structural and functional renal impairment .The KDIGO AKI Guideline recommends that all people with CKD be considered at increased risk of AKI, which is further increased with intercurrent illness, investigations, and procedures. For most elderly patients admitted to a trauma center with fractures requiring investigation and surgical treatment, this is precisely the constellation that must be considered.p < 0.001) and simultaneous prescription of inadequate nephrotoxic agents at discharge demonstrates the cross-sector expansion of this high-risk problem, particularly for the elderly and, on this aspect profoundly susceptible patients [Accordingly, the IPM adhered to the KDIGO recommendations in the context of riskful contrast media , and indpatients . The Intpatients . As fromCKD is a well-recognized risk factor for AKI, which itself in turn accelerates CKD itself, and accordingly, AKI requires optimized care . The incp < 0.001), 4-fold hospital mortality and 2-fold discharge to post-hospitalization care, accounting for serious patient harm and increased health economic resource utilization [Because the incidence of AKI has increased in the last decades, and patient age is an important non-modifiable risk factor due to the physiologic decline of GFR and impaired renal reserve , we needlization . In the inpatient setting, inappropriate dosing accounts for up to 42% of medication errors, ranking it as one of the most important preventable risk factors. In addition to inappropriate medication dosing, advanced age, CKD, and the number of medications were evaluated as major risks for prescription errors. The substantial degree of incidental adverse events and negligence in hospitalized patients increased highly significantly with age. Rates of adverse events differed significantly across specialties, while negligence remained the same . The HarSeveral cardiovascular agents, besides antibiotics and NSADIs, have been identified as the most common causes of drug-induced kidney injury .In this context, the IPM also referred to statin doses in the individual elderly with regard to the entire medication list and patient condition. Patients with high potency statin treatment defined as ≥10 mg rosuvastatin, ≥20 mg atorvastatin, and ≥40 mg simvastatin, also often administered in the outpatient medication of our patient population, were hospitalized for AKI within the first 120 days from treatment start. This was 34% more than in the reduced doses in low potency statin treatment. The rate was even enhanced in patients without CKD , probablAs a drug, SGLT2 inhibitors, which have emerged as disease-modifying agents with benefits not only in CKD, number needed to treat (NNT) = 19, always pose ADR and DDI risks ,125. In The obviously high impact from IPM indicates a strong effect of drugs on the progression of renal impairment in the elderly population. Whether this applies only to hospitalized patients or also to elderly outpatients remains to be investigated accordingly but may be assumed. The fact, that the IPM results are impressive despite the inevitable increase in polypharmacy with age shows that the positive effect on redGFR can be achieved by comprehensive individual medication management alone, rather than by a necessary reduction in the number of medications.2. The concept of this study was the trigger for the introduction of eGFR CKD EPI in UKH for further assessments. We did not consider the prevalence or severity of certain conditions, such as the extent of possible blood pressure or glucose fluctuations or the severity of diabetes stage, tobacco or alcohol use, diet, or physical activity. Nevertheless, these remaining confounders are unlikely to explain the uniform strong IPM effect observed in reduced redGFR.This is a retrospective controlled clinical study with all its inherent limitations. It involves two sets of data collection conducted by the two same investigators for both. The patient records and datasets used were not explicitly designed for the study, and data on variables may be missing. Focusing on a wide range of possible associated variables risks more gaps in the findings. This is equally true for both, the CG and the IG. Randomly achieved highly matched groups between CG and IG minimized potentially relevant confounders and supported comparability. Although redGFR had already occurred at the time of recruitment, the study was not biased by knowledge of outcome status because both cohorts included samples blinded to the outcome. Since the progress of renal impairment was not reliably documented and coded in the patient discharge letter, we referred to a robust and most concise manifestation of further renal impairment with a further reduction of eGFR ≥ 20 mL/min throughout the in-hospital course as a strong criterion. The reference to eGFR values on admission to estimate CKD stages lacks long-term follow-up values and measurements of albuminuria. Both additional aspects for accurate calculation of possible progressive CKD stages were not applicable in the study in geriatric traumatology due to the unavailability of contemporaneous amounts of proteinuria/albuminuria and short perioperative hospital stay with a primarily surgical focus on fracture treatment. Another limitation was the laboratory calculation of eGFR values using the MDRD formula, which becomes less accurate, especially with increasing age, in the majority of our study population, without further subdivision of eGFR values above 60 mL/min/1.73 mThere was only one medication reviewer, with education and experience in internal medicine, nephrology, and clinical pharmacology. Her educational background may be an advantage in analyzing the drug list in a conceptual manner in more detail than clinical pharmacists or pharmacologists can do. Despite these being medication analyses of a single individual, the determinants of medication review are reproducible and clearly defined by all patient and medication scores depicted. The IPM internist has applied their decades of kidney transplant experience in treating similarly vulnerable kidneys of geriatric and intensive care patients analogously to the concept of this IPM.Although the data refer to a selected patient operative ward under hospital conditions, they may reflect the typically elderly patient conditions we need to treat nowadays, as they cover all out-hospital medications and reflect the real-world risk from uncontrolled polypharmacy complexities that lead to red eGFR and other organ injuries, fall events necessitating trauma surgery and risk for delirium and cognitive decline. IPM as an individual medication review that is conducted as intensively as possible from a synoptic internistic and clinical pharmacologic view does not consider genetic pharmacological aspects additionally. We did not measure blood values that attribute ADRs to iatrogenic medical agents due to elevated levels. We also did not include and adjust for intraoperative parameters such as type of operation for trauma, operation duration, severe prolonged blood pressure drops, and blood loss, which would have been of further interest. The head of geriatric traumatology assures that there have been no relevant changes in the intraoperative procedure for the treatment of all injury entities during the entire study period. Thus, from a surgical perspective, there are no structural reasons to expect a change in blood loss. The individual course was not assessed additionally.The more than 8 years of daily IPM experience with a critically ill or multimorbid elderly interdisciplinary patient population covers a particularly vulnerable group with polypharmacy and, partly, already reduced organ function. There is almost no possibility to clearly identify the entire frequency of ADR manifestation, but the more vulnerable the patient is as a result of preexisting illnesses, organ deterioration, and polypharmacy, the higher the ADR risk. The spectrum of ADRs and DDIs addressed is based primarily on the SmPCs. Their completeness and, in some cases, even the clearly defined metabolic pathways of active substances and risks from inactive metabolites are not always fulfilled, thus leaving out still unknown grey areas, which themselves may be additionally dangerous for the treated patients. It is a practice-based study with many years of continuity and experience. Because throughout the observation period, both, the senior traumatologist and the IPM physician remained the same, the recordings in the database can be considered fairly accurate and consistent. This is the first clinical study to document a strong association of medication review-based medical adjustments with the complete prevention of redGFR. The study topic addresses an urgent and demographically increasing public health problem, and IPM emerges as a compelling prevention tool that is still underrepresented. With the IPM, a continuity of interdisciplinary cooperation has been established in which the patient-oriented optimization of acute treatment in geriatric traumatology is always at the forefront. The continued focus on avoiding drug-induced risks and individually considering DDIs and overdosages is likely to have had an additional superimposed positive systemic class effect over the years. The compelling pilot data from our retrospective study on IPM efficacy support the feasibility of designing a future, more powerful study including a quantitatively larger experimental group to obtain more explicit statements and conclusions about IPM effect on redGFR. Ideally, a prospective, randomized controlled trial involving multiple medical disciplines would be beneficial to substantiate our findings and examine the extensively established IPM procedure in multiple settings to make further reliable conclusions about additional predisposing factors. But this raises ethical concerns in an effort to provide optimal care for all elderly patients entrusted to us.We have to accept that polypharmacy is almost unavoidable in elderly multimorbid adults, who often dispose various cerebrocardiovascular and organ diseases in the presence of metabolic and endocrinologic disorders. At the same time, especially these are the patients already suffering from age-related organ impairment that affects drug elimination capacities on the drug metabolism and excretion level. Given this background, despite high-level polypharmacy, the applied IPM consequently adapted to the patient’s very individual clinical condition, was associated with the potent prevention of iatrogenic redGFR through the appropriate prescription of each drug, taking into account all clinically relevant dose adjustments, ADRs, DDIs, missing prescriptions and contraindications from the individual drug list. With an optimized and overdue real-world drug and patient safety through pharmacovigilance, the same IPM does not only seem to prevent renal impairment and progression of CKD. It is also associated with the impressive reduction in complicating delirium  and fallThe documented severe discrepancy in manifest CKD versus diagnosed CKD contributes to a serious additional risk of overdosage in this high percentage of patients treated, re-transferring the unawareness to the ambulatory setting again. Awareness of renal impairment is the sine qua non for examining the appropriateness of a drug’s dose. Therefore, the doses are much more often too high than realized. The SmPC suggested normal dose may already be too high in elderly patients is unfortunately referenced in only a few drug SmPCs. Although the vast majority of drug consumers are elderly patients, drugs remain generally approved in healthier younger adults with regular organ function and without the broad spectrum of concomitant diseases, contraindications, and comedications that can exacerbate ADRs in the elderly per se through increased susceptibility at the level of pharmacodynamic action and, cumulatively, and through DDIs. 2 as well as with an eGFR < 60 mL/min/1.73 m2 was completely eliminated by IPM, the IPM effect may be preventive for both, iatrogenically induced onset of renal impairment and progression of manifest CKD. Therefore, it should be performed as early as possible and at regular intervals in all geriatric patients on a mandatory basis to prevent drug-induced and drug-enhanced renal injury. As a further patient and socioeconomic benefit, IPM also reduced the necessity of intensive care and hemodialysis. To compensate for and overcome these deficiencies and challenges, IPM seems an important preventive tool with its high impact on avoiding further renal impairment by drugs, even in very old patients over 80 years of age undergoing surgical intervention. Because redGFR associated with an eGFR ≥ 60 mL/min/1.73 mThe available electronic patient record supports IPM in optimizing safe and highly individualized prescribing, a task that digital tools currently are unlikely to cover as comprehensively. Yet, recording a CKD diagnosis in the medical record may at least help uncover potentially inadequate prescribing through clinical decision support. Given the pressing situation of CKD management, we should not only provide recommendations for specific drugs but advocate IPM for the entire drug list. For future direction, the extensive evidence resulting from more than 58,600 IPM self-conducted analyses from a daily broad-based polypharmacy real-world dataset corresponding to the current commonly prescribed drug combinations in older adults will be digitized to provide the specified drug risks directly with the use of the electronic patient record.A safe healthcare system inevitably demands eliminating any type of drug-related patient harm. To urgently prevent the drug-induced iatrogenic onset or progression of CKD in the increasing elderly patient population with polypharmacy worldwide, the study insights and effects require recommendations at both, the individual patient and the policy levels: It should become mandatory to document updated eGFR with each medication list and to ICD-code drug-induced renal injury as a separate diagnosis to increase physician awareness of this iatrogenic condition and to perform mandatory comprehensive IPM on a regular basis. Available guidelines are deficient in adequately addressing and compensating for the risk of polypharmacy for the onset or progression of CKD.