Insulin resistance (IR) is one of the risk factors for chronic kidney disease (CKD) and diabetes. The triglyceride–glucose (TyG) index is considered a reliable alternative marker of IR. We investigated the correlation between the TyG index and the severity of CKD in patients with latent autoimmune diabetes in adults (LADA).This cross-sectional study included 288 patients with LADA in the department of endocrinology at our hospital between January 2018 and January 2022. The TyG index was calculated as Ln [TG (mg/dl) × fasting blood glucose (FBG) (mg/dl) / 2]. All individuals were divided into either a LADA + CKD group or a LADA + non-CKD group according to the presence or absence of CKD. A correlation analysis, logistic regression analysis and receiver operating characteristics curve analysis were performed.P < 0.05). The positive relationship between the TyG index and the urinary albumin/creatinine ratio was significant . There was also a significant correlation between the TyG index and the eGFR  after adjusting for confounding factors. The area-under-the-curve value of the TyG index was 0.708 .A total of 130 (45.1%) participants were identified as having CKD. Compared with the non-CKD group, the CKD group had a longer disease duration and a higher proportion of smokers; patients were more likely to have hypertension and higher serum creatinine, triglyceride, cholesterol, low-density lipoprotein cholesterol, FBG, uric acid estimated glomerular filtration rates (eGFR) and TyG levels as well as lower high-density lipoprotein cholesterol levels (all The TyG index is significantly associated with the severity of CKD in patients with LADA. This conclusion supports the clinical application of the TyG index for the assessment of kidney disease in patients with LADA. Latent autoimmune diabetes in adults (LADA) is a type of adult-onset autoimmune diabetes that reflects the clinical characteristics of type 2 diabetes and the presence of type 1 diabetes-related autoantibodies. The clinical and genetic features of the disease are intermediate between those of typical type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), and it is labelled as ‘slowly evolving immune-mediated diabetes’ by the World Health Organization (WHO) [The triglyceride–glucose (TyG) index, comprising fasting plasma glucose and triglycerides (TGs), is significantly associated with the hyperinsulinemia-normal glucose clamp test and the homeostasis model assessment of IR (HOMA-IR) . A largeThis cross-sectional study included 288 patients with LADA at our hospital between January 2018 and January 2022. All individuals were divided into either a LADA + CKD group or a LADA + non-CKD group according to the presence or absence of CKD. The inclusion criteria for patients with LADA were as follows [The exclusion criteria were as follows: (1) participants with secondary diabetes, those who were pregnant and those with a malignancy; (2) participants in a state of ketoacidosis; (3) participants with a previous history of using statins or TG-lowering drugs; (4) participants who had used immunosuppressive drugs, antibiotics or steroid medication in the preceding 3 months; (5) patients with other severe diseases and (6) those with a lack of necessary laboratory or physical examination data.For the included patients, clinical data were extracted from electronic medical records, including age, sex, duration of LADA, height, weight, hypertension, systolic blood pressure (SBP), diastolic blood pressure (DBP), lipid profile and glucose metabolism indices. Blood samples were collected from the patients after fasting for 8 h. All blood and urine specimens were tested immediately after collection. Biomedical measurements were taken for serum or plasma separation upon blood collection. Overnight fasting blood samples were collected from each participant to test for fasting blood glucose (FBG), serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TGs, serum uric acid (UA), glycosylated haemoglobin A1c (HbA1c) and liver/renal functions. Serum C-peptide levels were detected by a chemiluminescent immunometric assay (Roche Diagnostics Ltd.). Urinary albumin and serum creatinine (Scr) were measured using laser immunonephelometry (Roche Diagnostics Ltd.). The serum levels of interleukin-10 (IL-10), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were quantified using the following enzyme-linked immunosorbent assay (ELISA) kits  in accordance with the manufacturer’s instructions: Human IL-10 ELISA Kit (ab46034), Human TNF-α ELISA Kit (ab181421), Human IL-6 ELISA Kit (ab178013), Human IL-1β ELISA Kit (ab100562). The optical density of the samples was determined at 450 nm using an ImmunoChem-2100 microplate reader .2 [Definition of variables: Hypertension was defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg following repeated examination or a prior diagnosis of hypertension by a physician. The estimated glomerular filtration rates (eGFRs) were calculated using the Chronic Kidney Disease Epidemiology Collaboration formula [2 . Body ma2 .t test or a one-way analysis of variance, with Bonferroni corrections for post hoc analysis. Non-normally distributed data were analysed using the Mann–Whitney test or the Kruskal–Wallis H test to identify statistical differences between groups. Categorical variables described the number and percentage of each type, and comparisons between groups were processed using Chi-squared or Fisher’s exact tests. Pearson’s correlation and partial correlation analyses were performed for the correlation analysis of the TyG index with other variables. Univariate and multivariate logistic regression analyses were performed to determine the effect of different TyG levels on the severity of CKD. Receiver operating characteristic curve (ROC) analyses were conducted to determine the severity of CKD in participants. A value of P < 0.05 was considered statistically significant.All analyses were performed using SPSS 26.0 software (IBM Statistics Group). The clinical characteristics of all the participants were described using means ± standard deviations for continuous variables and percentages for categorical variables. Normally distributed data were analysed using the Student’s P < 0.05). There was no difference in the expression levels of inflammation-related factors   .To understand the association between different TyG levels and UACRs in patients with LADA, we divided the participants into terciles according to the TyG index (P < 0.05) . After adjusting for age, sex, disease duration, body weight, serum UA and the presence of hypertension, the positive relationship between the TyG index and the UACR remained significant . There was also a significant correlation between the TyG index and the eGFR . After adjusting for confounding factors, a moderate relationship was identified between the TyG index and the eGFR    Fig. .The mechanisms for the association between the TyG index, LADA and kidney disease have not yet been clarified, but they are believed to include HOMA-IR, autoimmune, inflammation, lipid and glucose disorders . The TyGLatent autoimmune diabetes in adults is a well-recognised diabetes sub-type of immune-mediated type 1 diabetes. Previous studies revealed that patients with LADA displayed mixed innate immune cell features of T1DM and T2DM . AutoimmPodocytes are insulin-sensitive epithelial cells that create slit diaphragms within glomeruli to ensure proper filtration. Podocyte injury is a critical factor in the progression of kidney disease. Studies have shown that the inability of podocytes to respond to insulin may partially account for the decreased number of podocytes observed in early diabetic nephropathy in diabetic mice . RousseaLatent autoimmune diabetes in adults is an autoimmune-mediated type of diabetes, and T lymphocytes are a key factor in its pathogenesis . Data deDuring the initiation and progression of LADA, macrophages, NK cells, dendritic cells and neutrophils play a crucial role . StudiesInsulin resistance plays a crucial role in the occurrence of kidney disease in patients with LADA; at the same time, autoimmune damage, inflammation and glucose and lipid metabolism disorders promote the process. Pathological processes can result in increased TG and glucose levels, thus accelerating TyG levels, indicating that the TyG index is related to the occurrence of kidney disease in patients with LADA and is representative of disease severity. Glucose and lipid metabolism disorders in patients with LADA promote an increased IR; accordingly, IR-induced inflammation and immune response appear to be fundamentally linked to kidney disease in patients with LADA.Our study provides evidence for the association between the TyG index and kidney disease in patients with LADA despite the adjustments needed for traditional risk factors, such as age, smoking, disease duration, hypertension and UA. We showed that patients with LADA had an increased risk of kidney disease and a higher TyG index. In this study, TyG was used to emphasise the important role of IR in the occurrence of kidney disease in patients with LADA, providing a new way to indicate both LADA and the severity of kidney disease among at-risk patients.Our study has several limitations. First, the sample size of patients with LADA was relatively small, and its retrospective cross-sectional single-centre design may have caused bias. Future large-scale prospective studies are required to further clarify the predictive power of the TyG index on kidney disease risk among patients with LADA. Second, patients with severe kidney disease were not included in this study, which may have led to an underestimation of the efficacy of the TyG index in predicting kidney disease. Future studies should consider dividing subgroups according to the stages of CKD to further validate and generalise the conclusions of this study. Third, our study was based on a single TyG measurement, and the potential cardiovascular implications of changes in TyG  over time require further investigation.In conclusion, the TyG index is significantly associated with the severity of CKD in patients with LADA. The TyG index can be used as a supplement to the classic risk factors for CKD among patients with LADA, and the association may be higher and reflect lesion severity to some extent. This study supports the clinical application of the TyG index in evaluating kidney disease in the LADA population.


Hypertension is the most frequently occurring adverse event of lenvatinib, recognized relatively early in its course. However, the trend in blood pressure after the initiation of lenvatinib and the outcomes with antihypertensive treatment are unclear. This study aimed to clarify the association between baseline blood pressure and the incidence of lenvatinib‐induced hypertension in patients with thyroid cancer.This retrospective study included 65 patients without hypertension at the time of lenvatinib initiation. Patients were divided into two groups: those who developed hypertension grade ≥3 (HTN group) and those who did not develop hypertension grade ≥3 (non‐HTN group).Of the 65 patients, 46 (71%) developed hypertension grade ≥3. In both HTN and non‐HTN groups, blood pressure significantly increased the day after lenvatinib initiation. There was no significant difference in the elevated values of both the changes in systolic blood pressure (ΔSBP) and diastolic blood pressure (ΔDBP) between the two groups, with an average increase of 20 mmHg in SBP and 13 mmHg in DBP from baseline. The median (range) time to the onset of hypertension grade ≥3 was 2 days (1–12 days). In the multivariable analysis, patients with normal (SBP 120–129 mmHg and/or DBP 80–84 mmHg) or high‐normal baseline blood pressure (SBP 130–139 mmHg and/or DBP 85–89 mmHg) were at higher risk of developing hypertension grade ≥3 than those with optimal baseline blood pressure (SBP <120 mmHg and DBP <80 mmHg) .Lenvatinib‐induced hypertension appears the day after administration, and higher baseline blood pressure is a significant risk factor for developing hypertension grade ≥3. In cases of increased blood pressure with lenvatinib, early initiation of antihypertensives may prevent treatment interruption due to hypertension and maintain the therapeutic intensity of lenvatinib. To clarify the association between baseline blood pressure and the incidence of lenvatinib‐induced hypertension in patients with thyroid cancer, we analyzed the data of patients who were administered lenvatinib and hospitalized for the purpose of managing adverse events to examine the details of blood pressure changes during treatment and the risk factors for the development of hypertension grade ≥3.22.1We used an institutional database to identify all patients with thyroid cancer who were treated with lenvatinib and completed an initial inpatient treatment phase from May 1, 2015, to October 31, 2022. This study was approved by the review board of the National Cancer Center (research project no. 2022‐115). The requirement of informed consent was waived because this study was conducted according to a retrospective chart review protocol.Among the 73 patients with thyroid cancer treated with lenvatinib, a total of 8 patients who had uncontrolled hypertension (systolic blood pressure [SBP] ≥140 mmHg or diastolic blood pressure [DBP] ≥90 mmHg) at the start of lenvatinib administration were excluded from the study to examine the effect of lenvatinib on blood pressure under stable conditions. The remaining 65 patients who were administered 24 mg/day of lenvatinib in the hospital setting for thyroid cancer were included in the final analysis.2.2This was a single‐center retrospective study, and all data were extracted from medical records. Lenvatinib was started orally at 24 mg daily in all patients, with dose reduction or interruption at the physician's discretion in the event of unacceptable adverse events. Therefore, there was no unified protocol for dose reduction or interruption among attending physicians. Hypertension was graded with the Common Terminology Criteria for Adverse Events version 5.0. Trend in blood pressure changes with lenvatinib treatment, incidence of hypertension grade ≥3 (SBP ≥160 or DBP ≥100 mmHg), and antihypertensive treatment were evaluated early after lenvatinib initiation. Patients were classified into two groups: the hypertension group (HTN), consisting of patients who developed hypertension grade ≥3 while receiving lenvatinib, and the non‐hypertension group (non‐HTN), consisting of patients who did not develop grade ≥3 hypertension.The study period was 14 days, which was the length of hospitalization for the purpose of adverse event management, and detailed data on blood pressure changes from the start of lenvatinib administration after admission until withdrawal or dose reduction due to an adverse event or discharge from hospital were evaluated. Blood pressure was measured by nurses at least thrice a day as part of blood pressure assessments during hospitalization. During that blood pressure monitoring, if SBP was ≥160 and/or DBP was ≥100 mmHg, blood pressure was re‐measured after 30 min under rest instructions.Baseline blood pressure was defined as the average of values measured from the time of admission until lenvatinib was initiated. The median number of blood pressure measurements from admission to initiation of lenvatinib was 3 (interquartile range: 3–4). The mean daily blood pressure during lenvatinib treatment was the average blood pressure measured multiple times during the day. The change in blood pressure (ΔSBP and ΔDBP) was determined by subtracting the pre‐lenvatinib (baseline) blood pressure from the values measured at each time point after lenvatinib treatment. Baseline blood pressure was classified into three categories according to the 2018 ESC/ESH Clinical Practice Guidelines for the Management of Atrial Hypertension: optimal (SBP <120 mmHg and DBP <80 mmHg), normal (SBP 120–129 mmHg and/or DBP 80–84 mmHg), and high‐normal (SBP 130–139 mmHg and/or DBP 85–89 mmHg).2] = 194 × age‐0.287 × serum creatinine‐1.094 × [0.739 for women]).As for patient characteristics, history of hypertension was defined as a diagnosis of hypertension and receiving antihypertensive treatment prior to lenvatinib initiation. We also evaluated patients who had previously been diagnosed with diabetes, dyslipidemia, cardiovascular disease (CVD), or stroke prior to initiation of lenvatinib. History of CVD included arrhythmias, such as atrial fibrillation, coronary artery disease, myocardial infarction, chronic heart failure, and severe valvular disease diagnosed prior to lenvatinib initiation. Performance status was assessed using the Eastern Cooperative Oncology Group scale. The estimated glomerular filtration rate (eGFR) was calculated using the estimation equation for Japanese patients.2.3t‐test or Mann–Whitney U‐test. Categorical variables were compared using Pearson's chi‐squared test or Fisher's exact test. In addition, logistic regression analysis was used in the multivariate analysis. For factor selection, after all factors were introduced, two factors were extracted from those with small p‐values using the variable reduction method. A p < 0.05 was considered statistically significant. Statistical analysis was performed using SPSS statistics ver. 28.0 (IBM).Continuous variables are presented as the mean ± standard deviation or the median and interquartile range based on their distributions with or without normality. Categorical variables are presented as numbers and percentages. Normality was verified using the Shapiro–Wilk test. Continuous variables were compared using the unpaired Student's 33.1p = 0.004; DBP, p = 0.005). Baseline blood pressure was within the normal range (SBP <140 mmHg and DBP <90 mmHg) in all patients; however, the HTN group had the highest number of patients with high‐normal blood pressure, and the non‐HTN group had the highest number of patients with optimal blood pressure (p = 0.014).Of the 65 patients analyzed, 46 71%) developed hypertension grade ≥3 while receiving lenvatinib (HTN group), while 19 (29%) did not .The blood pressure trend of SBP and DBP in all 65 patients showed an increase in SBP and DBP from Day 1 after the start of lenvatinib and a leveling off trend after Day 3 Figure . However3.3p = 0.008). In the multivariable analysis, patients classified as having normal or high‐normal baseline blood pressure were at a higher risk of developing hypertension grade ≥3 than those with optimal baseline blood pressure .Table p = 0.014). Even patients with normal baseline blood pressure had a 28.9% increase in the incidence of hypertension Grade ≥3 when compared to those with optimal baseline blood pressure. Moreover, in the patients with high‐normal baseline blood pressure, there was a 37.6% increase in the incidence of hypertension Grade ≥3 compared with those with optimal baseline blood pressure.Figure 3.4As shown in Figure 4In this study, we investigated the actual blood pressure changes with lenvatinib and risk factors for the development of hypertension grade ≥3. The results showed that both SBP and DBP increased on Day 1 after lenvatinib initiation, with a median time to onset of hypertension grade ≥3 of 2 days. In addition, normal blood pressure and high‐normal blood pressure at baseline were found to be significantly associated with an increased risk for the development of hypertension grade ≥3. A previous study showed that hypertension occurred early in the course of lenvatinib treatment, and 47% of the patients treated with lenvatinib experienced their first occurrence of hypertension during cycle 1 of treatment.In the present study, lenvatinib caused hypertension grade ≥3 in 71% of patients, similar to the incidence in the Japanese population in the SELECT study.One case report described the treatment of a patient with thymic carcinoma using the same dose of lenvatinib as for thyroid cancer; the patient developed hypertension grade ≥3 the day after initiating lenvatinib and had difficulty managing his blood pressure.The 2018 ESC/ESH guidelines recommend treatment with antihypertensive drugs when SBP ≥140 mmHg and/or DBP ≥90 mmHg.In this study, no patient required lenvatinib treatment interruption due to hypertension during the study period. In patients who received antihypertensive treatment intervention, the median time to the initiation of antihypertensive intervention was 3 days after lenvatinib initiation. Thus, it is possible that early antihypertensive intervention prevented blood pressure elevation during the subsequent lenvatinib treatment period during the study period, leading to no requirements for dose reductions or interruptions due to hypertension. Currently, there is no clear evidence to support the use of a combination of ACEI/ARB and CCB as a method of blood pressure control during the use of antitumor drugs with VEGF inhibitory action. However, it has been reported that a combination of antihypertensive drugs with different mechanisms of action provides better antihypertensive effects than increasing the dose of one antihypertensive agent to control blood pressure.It is important to continue treatment for thyroid cancer without decreasing the dose of therapy as much as possible due to the limited treatment options available. A previous report showed that lenvatinib‐induced hypertension was significantly correlated with improved clinical outcomes in patients.Two important limitations of this study must be considered. First, the timing of blood pressure measurements differed because of the retrospective nature of this study, which could have affected blood pressure trends. Second, the timing of antihypertensive treatment initiation and dosage were at the discretion of the physician, and judgments based on the physician's experience and knowledge may have affected the antihypertensive effect. However, as per the results of this study, it is during the early period of treatment with high doses that hypertension is difficult to manage. Furthermore, early initiation of antihypertensive treatment for hypertension with lenvatinib allowed blood pressure management without treatment interruption, which is a significant result of this study.In conclusion, blood pressure increased from Day 1 after starting lenvatinib, and higher baseline blood pressure was a significant risk factor for developing hypertension grade ≥3. Early initiation of antihypertensive therapy, including combination drugs, may allow for better control of blood pressure, thus preventing treatment discontinuation and maintaining the therapeutic intensity of lenvatinib.Yuma Shibutani: Conceptualization ; data curation (lead); formal analysis (lead); investigation (lead); visualization (lead); writing – original draft (lead). Kazuko Tajiri: Conceptualization ; formal analysis (supporting); supervision (lead); writing – original draft (supporting); writing – review and editing (lead). Shinya Suzuki: Conceptualization (supporting); writing – review and editing (supporting). Tomohiro Enokida: Conceptualization (supporting); writing – review and editing (supporting). Atsunobu Sagara: Conceptualization (supporting); writing – review and editing (supporting). Susumu Okano: Writing – review and editing (supporting). Takao Fujisawa: Writing – review and editing (supporting). Fumiaki Sato: Writing – review and editing (supporting). Tetsuro Yumoto: Writing – review and editing (supporting). Motohiko Sano: Writing – review and editing (supporting). Toshikatsu Kawasaki: Writing – review and editing (supporting). Makoto Tahara: Conceptualization ; supervision ; writing – review and editing .This work was funded by the National Cancer Center Research and Development Fund (2023‐A‐12).This study was approved by the review board of the National Cancer Center (research project no. 2022–115).The requirement of informed consent was waived because this study was conducted according to a retrospective chart review protocol.Figure S1:Click here for additional data file.


No major differences were evident for lung, heart, liver, and kidney samples in regard to organ edema in comparison of EVT and MVT. Bowel tissue showed a higher percentage of edema in EVT compared to MVT . (4) Conclusions: The presented data suggest potential deterioration of renal function and intestinal mucosa function by an increase in tissue edema due to volume overload in ECMO therapy.(1) Background: Fluid resuscitation is a necessary part of therapeutic measures to maintain sufficient hemodynamics in extracorporeal membrane oxygenation (ECMO) circulation. In a post-hoc analysis, we aimed to investigate the impact of increased volume therapy in veno-arterial ECMO circulation on renal function and organ edema in a large animal model. (2) Methods: ECMO therapy was performed in 12 female pigs (Deutsche Landrasse × Pietrain) for 10 h with subsequent euthanasia. Applicable volume, in regard to the necessary maintenance of hemodynamics, was divided into moderate and extensive volume therapy (MVT/EVT) due to the double quantity of calculated physiologic urine output for the planned study period. Respiratory and hemodynamic data were measured continuously. Additionally, renal function and organ edema were assessed by blood and tissue samples. (3) Results: Four pigs received MVT, and eight pigs received EVT. After 10 h of ECMO circulation, no major differences were seen between the groups in regard to hemodynamic and respiratory data. The relative change in creatinine after 10 h of ECMO support was significantly higher in EVT (1.3 ± 0.3 MVT vs. 1.8 ± 0.5 EVT;  Extracorporeal membrane oxygenation (ECMO) is frequently used in clinical practice for various indications . The iniA particular focus of the underlying study was to investigate the impact of increased volume therapy in ECMO circulation on organ edema by analyzing retrospective data from a large animal experimental protocol performed by our study group. The study performed is a retrospective, not pre-planned, subanalysis of one particular study arm, which was part of a large animal experimental protocol investigating concomitant extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pumping (IABP) and was approved by the responsible ethical committee for animal care of the University of Cologne  . Data we2 100–150 mmHg, partCO2 35–45 mmHg, pH 7.35–7.45). Twelve female pigs (Deutsche Landrasse × Pietrain) were included in this study. Animals were premedicated with xylazin (2 mg/kg), tiletamin (10–12.5 mg/kg i.m.), and zolazepam (10–12.5 mg/kg i.m.). Deep sedation was induced with the intravenous application of propofol (1.5–2.5 mg/kg). Neuromuscular blockade was achieved with pancuronium (0.2 mg/kg i.v.). After endotracheal intubation, continuous anesthesia and analgesia were maintained with the intravenously administered propofol (4–6 mg/kg/h), midazolam (0.96–1.2 mg/kg/h), and fentanyl (0.012–0.025 mg/kg/h). Animals were ventilated with volume-controlled ventilation  using an air/oxygen mixture adjusted to keep arterial blood gas values in the physiologic range , the mean arterial pressure , and for blood sampling. A contralateral carotid artery was prepared, and carotidal blood flow was measured by a transit time flow probe . After sternotomy and pericardial incision, the pulmonary artery was cannulated for blood sampling and for pulmonary artery measurements . Pressure transducertip catheters  were placed into the right and left ventricles. Cardiac output (CO) was recorded by a transit time flow probe  placed around the ascending aorta. ECMO cannulas  were implanted through groin vessels . Heparin was applied intravenously as an anticoagulant drug. Extracorporeal circulation  was started after initial measurements and sampling of baseline parameters. An additional heater  was implemented into the ECMO circuit. The study protocol ended 10 h after the initiation of ECMO therapy . AnimalsHemodynamic measurements were performed during stable hemodynamic and respiratory conditions before extracorporeal circulation (t1) and 10 h after initiation of ECMO circulation (t2). All data were digitalized at a rate of 500 Hz using a 16-channel hemodynamic set-up and subsequently analyzed . Blood gas analysis was performed hourly. Additionally, creatinine values were sampled and analyzed for t1 and t2.Particular hemodynamic and respiratory parameters during ECMO circulation were targeted as follows:2 (indexed)ECMO-flow → 50 mL/kg/min/mMAP → 60–70 mmHgartO2 → 120–200 mmHgpTo maintain targeted mean arterial pressure, a fluid resuscitation protocol was tracked with a ratio of colloids and crystalloids of approximately 1:3. The study protocol strictly excluded blood transfusions. As the animals included in the previous investigation were retrospectively analyzed, the full population was divided into pigs who received moderate volume therapy and those receiving extensive volume therapy . The criThe primary outcome of this study was the relationship between organ edema. Tissue samples of the lung, heart, and liver were obtained at t1 and t2, and tissue samples of the kidneys and bowel were obtained only at t2. Probes were weighed (wet weight) and then freeze-dried after lyophilization. Dry weights were measured after the incubation of specimens at 110 °C for 2 days and corrected for residual water content. Organ edema was calculated by using the formula: % tissue water = (wet weight dry weight) wet weight and expressed as a percentage of the wet weight. All measurements were performed in duplicate, and the average was taken to balance the influence of hydrostatic distribution on the different organ tissue water contents.p-values < 0.05 were considered statistically significant.Statistical analysis was performed using Statistical Package for Social Sciences, version 23.0 . Data were evaluated for normality using one sample Kolmogorov-Smirnov test and expressed as the mean ± standard deviation. Univariate analysis was performed using either the Student t or Mann-Whitney U test for normally and non-normally distributed continuous variables, respectively. p < 0.01). After dichotomization of fluid administration within the study period, four pigs were included in the moderate volume therapy (MVT) group, and eight pigs were analyzed in the extensive volume therapy (EVT) group . Cumulatp = 0.666/MAP: 71 ± 9 mmHg MVT vs. 66 ± 11 mmHg EVT; p = 0.417/CVP: 12 ± 1 mmHg MVT vs. 13 ± 4 mmHg EVT; p = 0.683), except for a higher mean pulmonary arterial pressure in MVT . Additionally, respiratory data showed no statistical difference. FIO2 did not differ between the groups. The cardiac index was adjusted in regard to the targeted values and showed no difference between the groups during the study period (p = 0.484). Hemodynamic data showed no difference in accordance with the volume applied after 10 h of ECMO therapy (p = 0.128). Carotidal and coronary flow were comparable. Moreover, MVT did not impact respiratory data (p = 0.035) and haematocrit  in EVT. Lactic acid levels were higher in EVT.Baseline data are summarized in y period . After 1 therapy . Blood fory data . Blood gp = 0.033).Creatinine values were obtained at t1 and t2. Relative changes (creatinine ratio) of absolute values for both groups are presented in p = 0.857). Bowel tissue showed a higher percentage of edema in EVT compared to MVT .Tissue probes of the lung, heart, and liver were obtained at t1 and t2. The primary outcome showed that no major differences were evident for the mentioned organ samples in regard to the organ edema ratio . Due to From our analysis excessive fluid resuscitation might affect intestinal tissue structure and contribute to dysfunction of the intestinal barrier.Higher renal dysfunction in EVT was shown.The main findings of our analysis investigating the impact of volume overload during ECMO circulation were: The reasons for fluid overload in ECMO patients are heterogeneous and multifactorial. In clinical practice, fluid administration in ECMO patients frequently depends on intravascular hypovolemia, which causes the suction phenomenon of the ECMO circuit. Moreover, maintenance of targeted mean arterial pressure (>60 mmHg) is achieved by simultaneous vasopressor and volume therapy. In patients with compromised hemodynamics, initial excessive volume application might stabilize the hemodynamic situation and result in suction-free ECMO circulation. On the other side, this overload might negatively impact the following days’ ECMO support. Schmidt and colleagues from Paris and Melbourne were the first to report the impact of fluid balance on outcome after ECMO therapy . In theiAnother study group by Staudacher investigated 195 patients, showing that higher fluid balance was significantly associated with less survival in ECMO patients and might be useful for prognostication . In regaInterestingly, in our analysis, lactate levels differed between the groups. The fact that the hemoglobin differed might contribute to these circumstances. However, hemoglobin differences are expressed by fluid overload. It is speculative if low hemoglobin concentrations affected lactate levels or if the proven renal and intestinal dysfunction was followed by a lactic acid increase.Moreover, a fluid overload might lead to distension of the left ventricle, and physicians should be aware of such a complication. Actually, there are some strategies for ventricular unloading , and the right one depends on several parameters.p = 0.484). As our volume administration was based on targeted cardiac index and mean arterial pressure, fluid overload in EVT might affect end organ function. In translation to clinical settings, a targeted higher ECMO blood flow will result in more frequent ECMO suction events and thereby trigger volume therapy in non-hypovolemic patients. This iatrogenic-induced hypervolemia is known to affect renal function. Recently, Murphy and colleagues reported on a multicenter study analyzing the impact of AKI, fluid overload, and renal replacement therapy on mortality in neonatal ECMO patients [As fluid administration is essential for outcomes in ECMO patients, Bridges and colleagues recently published guidelines for fluid and electrolyte management in ECMO patients, with special attention to the development and therapeutic options of AKI . The autpatients . The autpatients . Moreover, ECMO circulation itself is known to induce a systemic inflammatory response, requiring fluid resuscitation. In addition, ECMO has been described as a risk factor for AKI . In clinp ≤ 0.005) were associated with higher survival to discharge rates. In general, indications to implement RRT are varying. A multicentric survey of ECMO centers showed that the most frequent indications for RRT in ECMO patients were fluid overload (43%), the prevention of EVT (16%), and the occurrence of AKI (35%) [To avoid the negative impact of fluid overload in ECMO patients, Thomas et al. suggest initiating in an early phase continuous renal replacement therapy (RRT) targeting in this way a negative fluid balance . The autKI (35%) . The tecKI (35%) . In accoKI (35%) . p = 0.049). Impact on several other tissue samples  was not shown. As already mentioned, fluid overload is known to impact organ function. In our analysis, organ edema was assessed and analyzed in comparison to MVT and EVT. Interestingly, organ edema in intestinal tissue samples showed significantly higher manifestation in EVT  reported on their large animal study investigating the impact of volume therapy on intestinal microcirculation . They shIn a clinical setting, intestinal dysfunction is of subordinate relevance next to cardiac, pulmonary, and cerebral failure and their importance in ECMO therapy. In regard to therapeutic measures, medication with ulinastatin is currently a topic of interest in ischemia-induced intestinal barrier dysfunction . UlinastIn general, patients receiving veno-arterial ECMO in a clinical scenario suffer some form of cardiogenic/hemodynamic severe compromise associated with capillary leak syndrome. This loss of intravascular volume to the interstitial space may significantly impact the findings of this study. Indeed, this situation may prompt further volume overload, interstitial edema, and, at least, more intestinal mucosa damage (and probably more edema in other organs). This assumption is somehow speculative and must be confirmed in further studies.As the study was not powered and designed with regard to the presented topic, results might be limited in this way. Moreover, the methodological classification of volume therapy in MVT and EVT was based on mathematical quantity and was not triggered by pathology-related thresholds. Furthermore, the division of the two cohorts is somehow arbitrary. In a clinical scenario, it may be difficult to objectively identify the point at which patients start to receive a liquid overload. By investigating healthy pigs in a purely experimental and artificial setting, the translation of our findings to clinical scenarios is somehow limited. Furthermore, 10 h of extracorporeal support does not correspond to clinical reality, in which systems are used for a significantly longer time. Therefore, our data cannot answer whether the observation time of 10 h is too short for changes in heart, lung, liver, or kidney tissue or whether fluid overload actually has no effect on these tissues. However, our data might encourage further investigation with a prospectively designed study protocol to address the impact of extensive volume therapy on ECMO circulation more explicitly.In our post-hoc investigation of volume therapy’s associated impact on renal function and tissue edema in ECMO circulation, the presented data suggest deterioration of renal function and potential deterioration of intestinal mucosa function by an increase in tissue edema.


Baseline, 12-month, and 24-month visits will be scheduled to collect demographic, clinical, biochemical, and urinary data. Additionally, an exercise capacity and psychosocial assessment will be performed. The study could provide new insights into using SGLT2 inhibitors for treating kidney manifestations in Fabry disease.Fabry disease (FD) is a rare genetic disorder caused by a deficiency in the α-galactosidase A enzyme, which results in the globotriaosylceramide accumulation in many organs, including the kidneys. Nephropathy is a major FD complication that can progress to end-stage renal disease if not treated early. Although enzyme replacement therapy and chaperone therapy are effective, other treatments such as ACE inhibitors and angiotensin receptor blockers can also provide nephroprotective effects when renal damage is also established. Recently, SGLT2 inhibitors have been approved as innovative drugs for treating chronic kidney disease. Thus, we plan a multicenter observational prospective cohort study to assess the effect of Dapagliflozin, a SGLT2 inhibitor, in FD patients with chronic kidney disease (CKD) stages 1–3. The objectives are to evaluate the effect of Dapagliflozin primarily on albuminuria and secondarily on kidney disease progression and clinical FD stability. Thirdly, any association between SGT2i and cardiac pathology, exercise capacity, kidney and inflammatory biomarkers, quality of life, and psychosocial factors will also be evaluated. The inclusion criteria are age ≥ 18; CKD stages 1–3; and albuminuria despite stable treatment with ERT/Migalastat and ACEi/ARB. The exclusion criteria are immunosuppressive therapy, type 1 diabetes, eGFR < 30 mL/min/1.73 m Fabry disease (FD) is a rare X-linked lysosomal storage disorder characterized by a deficiency in the activity of lysosomal α-galactosidase-A. This genetic mutation leads to the accumulation of globotriaosylceramide Gb3) in various cell types, including endothelial, cardiac, renal, and neuronal cells, resulting in progressive damage to the renal, cardiac, and nervous system . Kidney  in varioClinically, three presentations of FD can be identified . In hemiNephropathy is a major FD complication, characterized by a reduced glomerular filtration rate and proteinuria. In the absence of a specific therapy, impaired renal function progressively worsens over time, leading to end-stage renal disease being reached around the fourth or fifth decade of life. Proteinuria is the primary predictor for renal progression in both men and women with FD . AdditioThe FD treatment involves specific therapy, such as enzyme replacement therapy using Agalsidase alpha/Agalsidase beta and chaperone therapy using Migalastat , which aIn addition to the above therapies, other drugs such as ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) play a relevant nephroprotective role by reducing proteinuria and slowing the decline in the glomerular filtration rate (GFR). To achieve a nephroprotective effect, doses of ACEi/ARBs must be titrated to reduce proteinuria up to 0.5 g/24 h .However, the use of ACEi or ARBs is limited due to the risk of hyperkalemia and acute kidney injury. Although a double blockade of ACEi and ARB demonstrated a greater antiproteinuric effect in patients with or without diabetes and with microalbuminuria or proteinuria, it is not recommended due to increased adverse events . FurtherSGLT2 inhibitors (SGLT2i), initially introduced as hypoglycaemic drugs, have become increasingly popular in recent years for the treatment of CKD and heart failure, regardless of glycaemic control. These drugs act by inhibiting the sodium–glucose cotransporters channels present in the S1 tract of the proximal tubule, which are responsible for the majority of filtered glucose reabsorption. Several large randomized controlled trials showed the benefits of SGLT2i in both cardiac and renal function, not only in patients with diabetes but also in patients without diabetes . Indeed,SGLT2 inhibitors exert their nephroprotective effect through multiple mechanisms, including the re-establishment of glomerular tubular feedback, which protects against glomerular hyperfiltration damage. In depth, this involves the reduction in glucose and sodium reabsorption in the proximal tubule leading to increased sodium transport at the macula densa, increased adenosine release, afferent arteriole vasoconstriction, and a reduction in intraglomerular pressure . These eIn addition to these mechanisms, other factors can contribute to the nephroprotective effects of SGLT2 inhibitors, including the reduction in blood pressure values, an increase in hemoglobin and hematocrit values, a decrease in uric acid levels, and a reduction in oxidative stress and pro-inflammatory mediators ,28. These benefits suggest a potential role for SGLT2i in FD patients with CKD as these drugs could target the FD pathogenetic mechanisms, such as oxidative stress and inflammation, which are not completely addressed by ERT or chaperon therapy alone. However, further investigations and well-designed clinical trials are needed to thoroughly assess the effects of SGLT2i on Fabry nephropathy .2 per year and on clinical FD stability, defined by a FAbry STabilization indEX (FASTEX) score < 20 [With this background in mind, we have planned a multicenter observational prospective cohort study involving some Italian Nephrology and Internal Medicine Units. The study aims to evaluate the effect of an SGLT2 inhibitor, Dapaglifozin, in Fabry disease patients with CKD stages 1–3. Specifically, the primary objective will be to determine the effect of Dapaglifozin on albuminuria, with a target of achieving a 20% reduction in albuminuria. As secondary aim, we will assess the effect of Dapaglifozin on kidney disease progression, measured by a reduction in eGFR < 3 mL/min/1.73 more < 20 . Additio2 and evolution of T1 mapping pattern at magnetic resonance imaging (MRI), FASTEX score, 5 Times Sit to Stand Test (5STS) [The study was approved by the Hospital Ethics Committee for Clinical Trials CESC (Ref No. 5499/AO/22). The primary and secondary end-points will include albuminuria, estimated GFR calculated using the CKD-EPI formula, septum ventricular diameter and diastolic function detected at echocardiography, left ventricular mass index/mt (5STS) , 6 Minutt (5STS) , Cardiop2, and recurrent urinary tract infections will be excluded. The study will enroll male and female subjects aged 18 years or older with CKD stages 1–3, a genetic and biochemical diagnosis of FD and albuminuria for at least 6 months despite treatment with a stable dose of ERT or Migalastat for at least 12 months and ACEi or ARB titrated to the maximum tolerated dosage for at least 6 months. The subjects with immunosuppressive therapy, type 1 diabetes mellitus, eGFR < 30 mL/min/1.73 mOn the basis of previous evidence , we estiThe study will last two years and will include baseline, 12-month, and 24-month visits. At the baseline visit, the demographic data , anamnestic data , and clinical parameters  will be collected. Biochemical examinations  and a urinary sample  will also be tested.Additionally, the patient will undergo an exercise capacity assessment by means of the 6MWT, 5STS, and CPET tests and a psychosocial assessment using the following questionnaires: brief Illness Perception Questionnaire (BIPQ), Morisky Medication Adherence Scale 8 (MMAS-8), Chronic Illness Anticipated Stigma Scale (CIASS), Experience in Close Relationship Scale—Short Form (ECR-S), Health Care Relationship Trust Scale Revised (HCR-TS), Difficult Doctor–Patient Relationship Questionnaire 10 (DDPRQ-10), General Anxiety Disorder 7 (GAD 7), Patient Health Questionnaire 9 (PHQ-9), Edmonton Symptom Assessment System revised (ESAS-r), Severity of Dependence Scale (SDS), and Insomnia Severity Index (ISI). The qualities of life will be investigated using the 36-Item Short-form Survey (SF36). Finally, electrocardiogram (ECG), echocardiography, and cardiac MRI will be performed.During the 12-month visit, the medical history will be updated, clinical parameters will be recorded, blood and urine tests will be repeated, the exercise capacity will be assessed using 6MWT, 5STS, and CPET, and the FASTEX Index will be also compiled.At the 24-month visit, all the assessments and examinations from the baseline visit will be repeated. p-value of less than 0.05 will be considered statically significant for all tests. The statistical analysis will be performed using SPSS 21.0. The continuous variables will be presented as means and standard deviations, or medians and interquartile ranges depending on their distribution, which will be assessed using histograms and QQ plots. The nominal variables will be reported as frequencies and percentages. To determine any possible associations between SGLT2i and the variables of the primary and secondary outcomes, Pearson and Spearman tests will be used for continuous variables, the Fisher exact test for nominal variables, and the Student or Mann–Whitney tests for continuous and nominal variables. Finally, ANOVA tests will be performed for multicategory variables. A This study will be the first in the literature to evaluate the effect of Dapaglifozin in patients with albuminuria affected by CKD secondary to Fabry’s disease, primarily on renal outcomes  and, secondarily, on cardiovascular outcomes, exercise capacity, and quality of life. It will provide new compelling evidence on the use of SGLT2 inhibitors in the field of rare diseases.


Receiving a lung transplant conferred a higher risk than a liver or heart transplant for developing a creatinine increase ≥50% and ESKD. Peri-transplant mechanical ventilation, peri-transplant and post-transplant anticalcineurin overdose, nephrotoxicity, and the number of hospital admissions were significantly associated with a creatinine increase ≥50% and developing ESKD. Conclusions: Early and close follow-up by a nephrologist was associated with a decrease in the worsening of renal function.Background: Chronic kidney disease (CKD) is a common complication of a non-kidney solid organ transplant (NKSOT). Identifying predisposing factors is crucial for an early approach and correct referral to nephrology. Methods: This is a single-center retrospective observational study of a cohort of CKD patients under follow-up in the Nephrology Department between 2010 to 2020. Statistical analysis was performed between all the risk factors and four dependent variables: end-stage renal disease (ESKD); increased serum creatinine ≥50%; renal replacement therapy (RRT); and death in the pre-transplant, peri-transplant, and post-transplant periods. Results: 74 patients were studied . Patients who were not followed-up by a nephrologist in the pre-transplant ( Chronic kidney disease (CKD) is a common complication of a non-kidney solid organ transplant (NKSOT), causing increased morbidity and mortality in this group of patients. The increase in overall survival due to advancements in surgical techniques and immunosuppression management has promoted growth in the absolute number of patients who develop these complications ,2.A large study published in 2003 by Ojo AO et al. ,5,6. TogGenerally, there are pre-transplant, peri-transplant, and post-transplant predisposing factors in the middle- and long-term periods. However, specific characteristics in each type of transplant give different risks to developing CKD. In a series of renal biopsies from patients with NKSOT, variations in histological pattern were observed, demonstrating differences between the types of organ transplantation. For example, arteriolar hyalinosis was more common in heart and lung transplant recipients than in liver transplant recipients, while primary glomerular disease was more common in the latter .The knowledge of all the general and specific predisposing factors of each type of transplant may allow an early approach and minimize the progressive worsening of renal function and its short- and long-term complications. CKD is currently the eighth leading cause of death in developed countries, such as Spain. However, its incidence continues to grow, and it is estimated that it will be the second leading cause of death in Spain by 2100, after Alzheimer’s disease . This inThis is a single-center retrospective observational study on a cohort of CKD patients under follow-up in the Department of Nephrology at La Fe University and Politècnic Hospital in Valencia (Spain) from January 2010 to December 2020.This study was performed in accordance with the ethical principles of the Declaration of Helsinki as revised in 2013. The study belonged to the project “Enfermedad renal crónica en trasplante de órgano sólido no renal. Análisis de la incidencia, factores de riesgo y pronóstico global de los diferentes tipos de trasplante de órgano sólido no renal”, approved by the Hospital Universitari i Politècnic La Fe Clinical Research Ethics Committee, with the reference number 2021-302-1.2 at baseline were included.The cohort of patients was extracted from our hospital’s nephrology outpatient clinic and the End Stage Renal Disease Unit records, with a total of 212 patients: 44 heart transplant recipients, 93 liver transplant recipients, and 75 lung transplant recipients. Patients transplanted before 2010 (101 patients) or with combined renal transplantation (9 patients), and those with no follow-up in the outpatient clinic (28 patients) were excluded. A final population of 74 patients, 7 with a heart transplant, 34 with liver transplants, and 33 with a lung transplant, was obtained . SubjectPre-transplant period: Clinical and analytical variables present before the solid organ transplant until day 0 of the transplant.Peri-transplant period: From the transplant to hospital discharge.Post-transplant period: From hospital discharge to one year of follow-up in nephrology consultations.Patients who met the inclusion/exclusion criteria were evaluated retrospectively in three different periods :Pre-tranBaseline demographics, including age, gender, major comorbidities, and etiology of kidney disease, etiology of disease associated with the transplantation, and clinical and analytical data in the different study periods  were colt-test. Alternatively, if normality assumptions were violated, we employed the Mann–Whiney U test. To evaluate the increased risk of developing one of the categorical dependent variables, we conducted multinomial regression analyses.Statistical analysis was performed to assess the associations between all the risk factors and the four dependent variables: ESKD, increased serum creatinine ≥50%, renal replacement therapy, and death. For categorical risk factors, such as the type of transplant, we employed the Fisher’s exact test when the cell frequencies in the contingency table were less than 5, and the chi-square test for larger sample sizes. Continuous risk factors were assessed for normality using the Kolmogorov–Smirnov test. If the continuous variables followed a normal distribution, we utilized the Student’s Furthermore, we examined associations between normally distributed continuous variables and the dependent variables using the Pearson correlation coefficient. For continuous variables that did not follow a normal distribution, we used the Spearman correlation coefficient. Additionally, we utilized the Pearson correlation coefficient as a measure of association  for categorical data.The Kaplan–Meier statistic was used for survival analysis. In the Kaplan–Meier analysis, the outcome variables examined were the development of advanced ESKD and the need for renal replacement therapy, with the independent variable being the type of transplant. Censoring criteria were applied to individuals who did not develop ESKD or renal replacement therapy and completed the follow-up period. The mean follow-up duration was 59.61 months, with a maximum follow-up time of 142 months.p-value < 0.05 was considered statistically significant. Analyses were performed with IBM SPSS® Statistics version 26.A two-sided The datasets used and/or analyzed during the current study are available from the corresponding author upon request.The baseline characteristics are summarized in 2 (CKD) in 23% of the patients, and only 14.9% of the sample were followed-up by the nephrologist. The differences between transplants are summarized in In the pre-transplant period, 37.8% of patients were reported to have hypertension, 27.1% had diabetes mellitus, 25.7% had dyslipidemia, 14.9% had hyperuricemia, 23% were overweight, 18.9% were obese, 55.4% were ex-smokers, 8.1% were smokers, 6.8% had cardiorenal syndrome, and 18.9% suffered from hepatorenal syndrome. The pre-transplantation eGFR was <60 mL per minute per 1.73 mIn the peri-transplant period, 58.1% of the patients presented acute kidney injury (AKI), 5.4% required RRT, and only 18.9% were under nephrology follow-up. During their hospital admission, 51.4% of the patients showed surgical complications and 87.8% required blood transfusions. A total of 81.8% of the patients received tacrolimus ; 98.6% of the sample received mycophenolate, and 90.5% of the patients received corticosteroids. Changes into the initial immunosuppression were made in nearly 15% of the patients, fundamentally motivated by renal failure. A total of 20.3% of the patients presented graft rejection, 50% overdosed on calcineurin inhibitors for their reference levels, and 64.9% received nephrotoxic agents .In the post-transplant period, 23% of the patients developed hypertension, 23% had post-transplant diabetes mellitus (PTDM), and 17.5% had dyslipidemia. The mean number of hospital admissions was near 7, ranging from a minimum of 1 to a maximum of 23. A total of 78.4% developed infections; 66.2% of the patients presented an overdose of calcineurin inhibitors in more than three determinations; 68.9% required changes in immunosuppression due to adverse effects, including worsening of renal function; and 31.1% presented graft rejection. In addition, 77% of the sample received nephrotoxic drugs, mostly in combination. Finally, near 10% of the sample presented secondary thrombotic microangiopathy (TMA). The differences between transplants are summarized in 2. From the start of outpatient follow-up, renal function worsened in 45.9% of the sample, versus 54.1% who improved or maintained stability. Among the total sample, 45 patients (59.5%) experienced a 50% increase in their baseline creatinine levels, 24 patients (32.43%) reached ACKD (GFR < 30 mL/min/1.73 m2), 8 patients (10.8%) ended up in RRT, and 21 patients (28.4%) died. The mean time from the transplant to the start of follow-up in the nephrology outpatient clinic was 33 months. The mean eGFR was 39.24 mL/min/1.73 mp < 0.05). The highest risk was observed among lung transplant recipients, followed by heart transplant recipients, and finally, liver transplant recipients.Baseline creatinine levels increased by 50% in 45 patients. The mean age of these patients was 36.55 years, and most of them (75%) were males. The type of transplant was significantly associated with a 50% increase in baseline creatinine  were observed for lung transplant recipients with the absence of everolimus usage and the absence of changes in immunosuppression during the peri-transplant period, as well as hypertension in the post-transplant period.Regarding nephrotoxic factors during the peri-transplant period, after performing a multinomial regression analysis adjusted for other factors, the use of nephrotoxic antimicrobials did not retain its statistical significance, while the association with intravenous contrast administration remained significant, indicating a 3.16-fold increased risk of a 50% rise in serum creatinine levels. Detailed results of statistically significant associations are summarized in Not being followed-up by nephrology in the pre- and peri-transplant period were both significantly associated with the increased baseline serum creatinine by 50%. A delay in the follow-up by a nephrologist (each month), was associated with a 1.03-fold increased risk of increased serum creatinine.p < 0.05). Lung transplant recipients were at the highest risk. Compared with them, receiving a liver transplant presented a 6.94 times lower risk (HR 0.14 [95% CI] 0.045 to 0.463) and receiving a heart transplant, 7.19 times lower, although the latter was not significantly lower (HR 0.13 [95% CI] 0.015 to 1.28).Twenty-four patients reached ESKD. The mean age was 55.63 years, and most of them (66.7%) were men. The type of organ transplanted was significantly associated with reaching ESKD (p < 0.035), peri-transplant (p < 0.015) and post-transplant (p < 0.037) anticalcineurin overdose, peri-transplant (p < 0.028) and post-transplant nephrotoxic antimicrobials (p < 0.032), peri-transplant intravenous contrast (p < 0.004), and the number of hospital admissions (p < 0.02) were significantly associated with the worsening of renal function. In relation to nephrotoxic associated factors in the peri-transplant period, after doing a multinomial regression adjusted for the rest of the factors, the use of nephrotoxic antimicrobials lost its statistical significance; however, intravenous contrast showed an increased risk (3.62 times) to develop ESKD. Statistically significant results are summarized in Peri-transplant mechanical ventilation (p < 0.05).Regarding those lung transplant recipients, dyslipidemia in the post-transplant period was significantly associated with the development of ESKD , 121.5 months in heart transplantation recipients (95% CI of 86.70–155.297), 104 months in liver transplantation recipients (95% CI of 86.67–122.134), and 66.86 months in lung transplantation recipients (CI at 95% of 55.93–80.79) .p < 0.046), with an 8.4-fold increased risk (HR 8.4 [95% CI] 1.01 to 72.155). The median survival without reaching RRT was 124.93 months [95% CI] 112.42–137.43. This differs between transplants: 142 months in heart transplant, 118 months in liver transplant [95% CI] 107.94–129.67, and 104 months in lung transplant [95% CI] 92.85–115.88  were men. It was significantly associated with the overdose of calcineurin inhibitors in the peri-transplant period (5–115.88 . Howeverp < 0.028) period and the number of hospital admissions in the post-transplant (p < 0.006) period, with a 1.18-fold increased risk of death for each hospital admission (HR 1.118 [95% CI] 1.026 to 1.217).Twenty-one of the patients died during the follow-up period. The mean age at transplant was 54.25 years, most of them (76.2%) were men. The type of organ transplanted was not statistically associated with any of the exitus variables. It was significantly associated with active smoking in the pre-transplant , followed by heart transplant recipients (33.71 months), and ending with lung transplant recipients (38.64 months). The delay in follow-up was significantly associated with a 50% increase in baseline creatinine, with an increased risk of developing a renal event of 1.03 times for each month without a follow-up.In the literature, several studies have shown that pre-transplant kidney damage increased the risk of CKD ,15,16. IIn our study, we observed no significant cardiovascular risk factor associated with the development of ESKD. Nevertheless, active smoking was associated with mortality.Similarly, investigations have reported that peri-transplant kidney damage is significantly related to developing CKD ,17,18. Tp < 0.035) and a 50% increase in serum creatinine (p < 0.001), with an increased risk of 2.95 and 6.36 times, respectively.Analyzing our results from this period, the requirement for mechanical ventilation was associated with the development of ESKD  was significantly associated with progression to ESKD. Nonetheless, this variable lost significance when adjusted for other variables of risk, although it maintains a 2.6-fold increased risk of developing it. Similarly, it occurs with the use of intravenous contrast for a 50% increase in baseline creatinine. When adjusting for other nephrotoxic drugs, despite having a 2.59-fold increased risk, it loses significance.Two main limitations should be considered when interpreting our findings. Firstly, the small sample size of 74 patients in this study may restrict the generalizability of the results. Larger sample sizes are crucial to enhance statistical power and improve the representativeness of the findings. Secondly, the single-center design of the study introduces potential biases and may limit the external validity of the results. Replicating the study in multiple centers will strengthen the overall findings and increase their generalizability to a broader population.Currently, there is a growing increase in the number and comorbidity of patients who receive a NKSOT; the multidisciplinary management of these patients is of vital importance, especially with the collaboration of different hospital departments and units. Thus, an early follow-up by a nephrologist is associated with a decrease in the decline of renal function, mainly, by acting on the renal-specific risk factors, such as the nephrotoxicity related to calcineurin inhibitor overdose, preventing AKI, and allowing the identification of patients at higher risk during the pre-surgical period. Of interest, those patients requiring mechanical ventilation during peri-transplantation or those with the highest number of hospital admissions need special attention and monitoring by the nephrology department. Further studies are required to evaluate these findings.


P < .05), and there was no correlation between blood concentration and clinical characteristics such as age, gender, and dosage (P > .05). The blood concentration of roxadustat was correlated with clinical efficacy. The higher the blood concentration, the better the clinical efficacy, meaning it might be a predictor of efficacy.Roxadustat has been associated with the efficacy and safety in patients with chronic kidney disease-related anemia. However, the relationship between roxadustat blood concentration and clinical efficacy is lacking. To explore of the correlation between clinical efficacy and blood concentration of roxadustat in patients with renal anemia of chronic kidney diseases, so as to provide reference for rational clinical drug use. A total of 46 patients were selected with a diagnosis of renal anemia who were prescribed roxadustat at the department of nephrology of the First Hospital of Hebei Medical University from December 2019 to March 2020. The roxadustat blood concentration was determined at 12 weeks of treatment, according to the cumulative response rate, patients were divided into the response group and the nonresponse group, and the relationship between roxadustat blood concentration and treatment effect was analyzed. We also explored the correlation between various factors and the blood concentration. The patients in the response group had higher roxadustat blood concentrations than the nonresponse group ( The overall prevalence of CKD in China is 10.8% and is expected to increase in the coming decades, particularly in rural areas. Anemia is one of the most severe and inevitable complications associated with CKD. Currently, the standard of care includes oral or intravenous iron supplementation, erythropoiesis-stimulating agents, and red blood cell transfusion. Multiple trials have demonstrated that these anti-anemia therapies increased the potential risks .,6 Therefore, new strategies are required to address these problems.As a serious public health challenge with increasing global mortality and morbidity, chronic kidney disease (CKD) is characterized by progressive loss of kidney function, leading to dialysis or kidney transplantation. The apparent clearance of roxadustat is 1.2 to 2.65 L/hours, and the apparent volume of distribution is 22 to 57 L, the elimination half-life is 9.6 to 16 hours, the plasma binding is 99% and The pharmacokinetic profile of roxadustat was unaffected by hemodialysis/hemodiafiltration.,9The effects of roxadustat on hemoglobin (Hb) are linear, long-lasting, and likely irreversible, and the concentration at the half-maximum effect was 10 to 36 µg/mL. Numerous studies have shown that roxadustat is safe and effective in patients with CKD,but little literature has been reported on the blood concentration of roxadustat. The main aim of this study was to analyze the relationship between blood concentrations and curative effect. The secondary aim was to explore the factors of affecting drug concentration.Roxadustat is an orally administered, small molecule hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor for the treatment of anemia in patients with CKD. The drug inhibits HIF prolyl hydroxylase enzymes and promotes erythropoiesis by increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin.This is a retrospective observational study. From December 2019 to March 2020，outpatients in First Hospital of Hebei Medical University diagnosed with CKD were treated with roxadustat. The study was approved by the Ethics Committee of the First Hospital of Hebei Medical University (20220753).; Exclusion criteria were as follows: Patients who cannot complete the follow-up study; Patients with poor control of blood pressure; Patients with history of malignancy; Patients with severe liver impairment or active hepatitis; Patients with hereditary hematologic diseases such as thalassemia, sickle cell anemia, or other known causes of anemia other than CKD.Inclusion criteria were as follows: Age 18 to 90 years; End-stage kidney disease patients who are receiving maintenance hemodialysis; Renal anemia, defined as Hb < 120 g/L or Hb is maintained normal by ESA; Willing to participate in the study with treatment of roxadustat and all selected patients who had been treated with recombinant human EPO were administered with roxadustat to correct anemia 1 week after discontinuation of EPO 10,000 IU per week and 3 days after discontinuation of EPO 3000 IU per weekThe dosage of roxadustat was 100 mg for patients weighing 45 to 60 kg and 120 mg for patients weighing > 60 kg. The drug was taken orally 3 times a week. The dosage of roxadustat was adjusted according to the degree of Hb change over the past 4 weeks, as described in the drug’s instructions.18 column  at a flow rate of 0.50 mL/minutes with mobile phase methanol (0.1% formic acid)–water  solution. The injection volume was 5 μL. Electron spray ionization ion source was used for mass spectrometry and positive ion multiple reaction monitoring scanning detection. The method was proved to be liner in the range of 1 to 1000 ng/mL for roxadustat. The limit of quantification for roxadustat was 1 ng/mL. The intra–day and inter–day RSD of roxadustat were <10%. Extraction recovery rate was 87.96% to 102.82%.The venous blood samples about 2 to 3 mL were collected before the oral administration of roxadustat in heparin tube, and plasma samples were obtained by centrifuging the blood samples at 4000 r/minutes for 10 minutes, and the supernatants were stored at − 80°C until required for analysis. Plasma concentrations of roxadustat were measured using liquid chromatography–tandem mass spectrometry method. Physcion was used as the internal standard. The gradient elution was performed on a Phenomenex Kinetex C Response group: the Hb level ≥ 100 g/L or change in Hb from baseline ≥ 10g/L, Nonresponse group: the Hb level < 100 g/L and change in Hb from baseline ≥ 10g/L.According to the cumulative response at the time of blood concentration determination, patients were divided into the response group and the nonresponse group.P < .05 was considered statistically significant. Continuous variables are expressed as the mean ± standard deviation, and classified variables are described as numbers and percentages. When the data fit the normal distribution, an independent 2-sample t test was used in the comparison of means between groups. When the data did not conform to a normal distribution, the Mann–Whitney U test was used for unpaired continuous variables between groups. General linear bivariate spearman linear correlation was used to test the relationship between roxadustat concentration and related characteristics.Data were analyzed using SPSS version 26.0. A total of 46 CKD patients were tested for blood drug concentration after roxadustat treatment, the average blood concentration of roxadustat was 3327.96 ± 4454.04 ng/mL .P < .05). The effects of roxadustat on others clinical characteristics are shown in Table Hb was 102.22 ± 15.33 g/L in the pretreatment phase and 109.93 ± 16.37 g/L in the posttreatment phase, and the serum iron was 12.59 ± 4.39 μmol/L in the pretreatment phase and 17.52 ± 6.82 μmol/L in the posttreatment phase, which suggested that roxadustat increased Hb and iron, and the changes were statistically significant (P < .05) ; 9 patients, accounting for 19.57% (9/46), were included in the nonresponse group. The blood concentrations of roxadustat in the nonresponse group were lower than those in the response group, and the differences were statistically significant (5) Table .P > .05).Potential clinical characteristics that may have influenced the concentration of roxadustat were summarized and calculated in Table  As a HIF prolyl hydroxylase inhibitor, the novel agent roxadustat may increase endogenous erythropoietin concentrations by regulating the HIF, which is activated via the inhibition of certain activated domains. In our study, roxadustat demonstrated prospective efficacy for the treatment of CKD patients with anemia, the Hb level after roxadustat treatment was significantly higher than the baseline value, and the iron metabolism-related indicators were significantly improved, which is consistent with previous studies.,17Anemia is a common complication of CKD caused by impaired oxygen sensing during renal failure.,19 the optimal duration of treatment and dosage have not been well defined so far. As far as we know, no data are available for determining the concentration-effect relationship of roxadustat. All patients who were enrolled had been exposed to roxadustat for at least 12 weeks and were stable at the current dosage for 1 weeks to ensure a steady blood concentration. Our data showed a significant correlation between clinical efficacy and plasma concentration. The plasma concentration of roxadustat in the response group was higher than that in the nonresponse group. Statistical analysis showed that the difference of roxadustat concentration between the 2 groups was statistically significant (P < .05). Some factors, such as Hb, iron metabolism, residual renal function and dialysis adequacy have been demonstrated as predictors of the response to roxadustat. As shown in our data, the plasma concentration of roxadustat also might be a potential reference for determining the response.Although many studies have verified the effectiveness of roxadustat for renal anemia, Consistent with the findings, the results of the bivariate Spearman linear correlation test showed that gender, age and other factors had no clinically relevant effect on the blood concentration of roxadustat. It is according to the pharmacology of reasoning, and the real reason further analysis is needed.The researchers developed a population pharmacokinetic model of roxadustat in the target population, The results showed that none of the investigated intrinsic or extrinsic factors  resulted in a significant change in roxadustat exposure outside of the defined no-effect boundaries.Our study has the following limitations. First, this was a single-center study with a relatively small sample size, which might lead to the uneven distribution of the ratio in our cohort. Second, this was an observational study and selection bias could not be completely eliminated. Therefore, the correlations of clinical efficacy and plasma concentrations of roxadustat in CKD patients presented here should be regarded as preliminary. Further prospective, larger-scale clinical trials are needed to verify the finding.In conclusion, there is a correlation between roxadustat concentration and the efficacy. The blood concentration of roxadustat in the response group was higher than the nonresponse group for CKD patients treated with roxadustat, which might be helpful for the prediction of efficacy.The authors are thankful for clinicians and nurses in the department of nephrology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.Conceptualization: Chunhua Zhou.Data curation: Chunhua Zhou.Formal analysis: Chunhua Zhou.Funding acquisition: Chunhua Zhou.Investigation: Chunhua Zhou.Methodology: Yanjing Zhang, Chunhua Zhou.Project administration: Yanjing Zhang, Chunhua Zhou.Resources: Yanjing Zhang.Software: Yanjing Zhang.Supervision: Yanjing Zhang.Validation: Yanjing Zhang, Yu Jing.Visualization: Yanjing Zhang, Yu Jing.Writing – original draft: Yanjing Zhang, Yu Jing.Writing – review & editing: Yu Jing.


P/A ratio has been well studied in patients prior to undergoing refractive surgery, but its postoperative value remains less so. We aimed to examine the value of preoperative characteristics of refractive surgery patients in predicting the 1-year postoperative P/A ratio in LASIK, PRK, and SMILE using both linear and multivariate regression analyses. This was a retrospective study that included patients with manifest refraction spherical equivalents (MRSE) from −7.71D to −0.25D. In total, 164 eyes underwent LASIK, 183 underwent PRK, and 46 underwent SMILE. All patients had preoperative and 1-year postoperative front sagittal and back sagittal keratometry measurements at 4, 5, and 6 mm around the corneal vertex. Postoperative P/A after LASIK, PRK, and SMILE was found to be significantly correlated with MRSE and preoperative P/A. Stepwise variable selection in multivariate regression revealed that spherical equivalent was the most significant predictor of postoperative P/A. When coupled with other preoperative characteristics, including P/A, age, asphericity, and keratometry, the multivariate regressions were able to produce models with high predictive value in LASIK (adjusted R Corneal refractive power is vital to assess outcomes in refractive and cataract surgery. It depends on several factors, including corneal thickness, tissue index refraction, and the curvature of the anterior and posterior corneal surface. In the past, optical devices such as keratometers could only measure anterior corneal curvature and thickness. Calculation of corneal refractive power was therefore based on fixed parameters such as an estimated posterior-to-anterior corneal curvature radii ratio (P/A ratio) of 0.82. However, the arrival of optical coherence tomography and Scheimpflug imaging allow for simultaneous measurement of the anterior and posterior corneal curvature, resulting in an accurate measurement of the P/A ratio. Inaccuracies in not only corneal refractive power but also P/A ratio have been shown to contribute significantly to the error in intraocular lens calculations . An accuAdditionally, the P/A ratio could be a useful indicator of the risk of keratectasia. P/A, by nature of its quotient, can quantify the changes in posterior corneal curvature relative to the anterior surface when measured before and after a corneal intervention. In the same vein, posterior corneal elevation commonly occurs after refractive surgery and represents the earliest signs of iatrogenic keratectasia . ExpandiMany studies have characterized P/A ratio in patients who have not yet undergone refractive surgery, but few have evaluated it postoperatively. We aimed to describe P/A ratio in patients after undergoing refractive surgery and hypothesized that certain preoperative characteristics could correlate with its value. The purpose of this study was to first examine demographic factors and preoperative measurements that could influence P/A ratio. Additionally, we conducted multivariate analyses not only to assess which of these preoperative variables contributed the most predictive value but also to construct a model by which to accurately predict the postoperative P/A ratio in LASIK, PRK, and SMILE.The present study was conducted at a corneal refractive surgery center with approval by the Biomedical Research Alliance of the New York Institutional Review Board (#A20-12-547-823). All participating patients provided informed consent. A group of patients diagnosed with myopia or compound myopic astigmatism received either PRK, LASIK, or SMILE between June 2020 to March 2022. Criteria for inclusion were the following: adults ≥ 18 years old and best corrected visual acuity (BCVA) 20/25 or better. Exclusion criteria included the following: ocular disease , infectious or autoimmune disease , hyperopic astigmatism, hyperopia, eyes with monovision, and patients requiring subsequent enhancement refractive surgery. The group of patients was divided into 3 separate groups per type of surgery received including PRK, LASIK, and SMILE.F = (1.3376 − 1)/r × 1000 and KB = (1.336 − 1.376)/r × 1000, respectively, where r is the corneal radius, KF is anterior keratometry, and KB is posterior keratometry. Corneal asphericity  was measured at an 8-mm zone around the vertex.All patients included in the study were evaluated preoperatively with manifest refraction, visual acuity exam, tonometry, slit-lamp examination, and dilated fundus exam. These were repeated at the 1-year postoperative visit. All patients also received tomographic imaging via Pentacam (Oculus) both pre- and postoperatively. Tomography data were exported into Microsoft Excel. Keratometry was measured at a 3-mm zone in 15-degree intervals centered around the corneal vertex of the anterior cornea as the average of the flat (K1) and steep (K2) simulated keratometry readings. Keratometry was also measured at 4-, 5-, and 6-mm zones around corneal vertex for the anterior and posterior cornea. Anterior and posterior corneal radii were calculated using the equations KA single surgeon (MM) performed all surgeries at one site. PRK and LASIK surgical equipment included the WaveLight Allegretto Wave Excimer Laser System . In LASIK, a 100 µm flap was performed by an FS200  femtosecond laser. The planned optical zone and blended zones were created at 6.5 mm and 9 mm, respectively, for LASIK and PRK patients. SMILE was conducted with Visumax 500 kHz femtosecond laser  with the creation of a 6.5 mm optical zone and a 0.5 mm transition zone for all SMILE patients. Specific details of the surgical procedures can be found in the following references ,4,5.Statistical analyses were conducted using Microsoft Excel and IBM SPSS Statistical software . The Shapiro–Wilk test was used to assess normalcy of data distribution. After populations were determined to be non-normal in distribution, Spearman’s rank correlation was run for analysis of the effect on independent preoperative characteristics on the postoperative P/A ratio. Preoperative characteristics that were found to be significant were used for multivariate regression. Collinearity was further assessed with the variance inflation factor and collinearity tolerance statistics. Variables were excluded if the variance inflation factor exceeded 4 or if tolerance was below 0.25. Residual plots were produced between the standardized residual error and the predicted value for postoperative P/A for LASIK, PRK, and SMILE at 6 mm. The independence of residuals was assessed using Durbin–Watson tests, with values of 1.5 to 2.5 indicating independence. For an alpha value of 0.05 and a power of 0.80, a minimum sample size of 35 eyes was calculated for a medium effect size using G*Power . Significance was adjusted using Bonferroni corrections.This study included a total of 393 eyes from 215 patients that underwent LASIK, SMILE, or PRK surgery, consisting of 99 females (46.0%) and 116 males (54.0%). Of these eyes, 164 (91 patients) underwent LASIK, 183 (100 patients) underwent PRK, and 46 (25 patients) underwent SMILE. Demographic data of the eyes are shown in Preoperative characteristics and their correlation with P/A both preoperatively and postoperatively are shown in When looking at postoperative PA, age was found to positively correlate with P/A at the 6-mm zone in LASIK patients  and PRK  . AnterioAnterior keratometry positively correlated with P/A ratio in LASIK at 4 mm (r = 0.226), 5 mm (r = 0.224), and 6 mm (r = 0.240), but negatively correlated with P/A ratio in PRK . Posterior keratometry was found to positively correlate with postop P/A at all zones in PRK  and SMILE  patients. Posterior keratometry was not found to be correlated with P/A in LASIK patients .2: 0.946, p < 0.001). At 5 mm, MRSE, preoperative P/A ratio, age, and posterior corneal radius were selected as predictors of postoperative P/A ratio . At 6 mm, MRSE, preoperative P/A ratio, age, anterior corneal radius, and anterior corneal asphericity were selected as predictors of postoperative P/A ratio .All of the independent variables listed above were also run in multivariate analyses to examine their effect on postoperative P/A ratio in LASIK patients at 4-mm, 5-mm, and 6-mm central zones in 2: 0.900, p < 0.001). In addition to the previous independent variables, age was selected as a preoperative predictor of postoperative P/A in step-down multivariate analysis at both 5 mm  and 6 mm .Multivariate regression was also performed for PRK patients in 2: 0.882, p < 0.001). In addition to the previous preoperative independent variables, age was also selected as a preoperative predictor of postoperative P/A in step-down multivariate analysis at both 5 mm  and 6 mm .Finally, multivariate regression was also repeated for SMILE patients in Residual plots are shown for postoperative P/A at 4 mm, 5 mm, and 6 mm for LASIK, PRK, and SMILE . All resOur study looked at three populations that had similar mean ages and an even distribution of males and females. However, the populations have different average cylinder value, spherical equivalent, and pachymetry. This is largely due to certain characteristics being optimal for specific surgeries. For instance, SMILE is optimal for severely myopic patients but can only correct up to 3 diopters of cylinder. PRK is more suited to those patients with thinner corneas. Some may say that these differences could hinder the strength of our study, but it is critical to note that we never directly compare the surgery groups against one another and are simply studying the correlations within each group itself.In our preoperative combined population, age was found to positively correlate with P/A ratio, suggesting a relative steepening of the anterior cornea in older patients. This finding is reflected in a study by Hasegawa et al. that also found a positive correlation, but it contradicts a study by Dubbelman that instead found a negative one ,7. This Spherical equivalent had a negative correlation with preoperative P/A in the combined population in our study. Although Tang et al. found no significant correlation between the two, they demonstrated a slight negative trend, which is consistent with our study . This suPreoperative P/A positively correlated with postoperative P/A globally across all zones and surgery groups. This indicates that patients with higher preoperative P/A ratios can expect to have a higher postoperative P/A ratio.When we looked at all patients preoperatively, we found no correlation with anterior Q value . This isPosterior Q value was positively correlated with preoperative P/A at all zones, which is consistent with the findings of the Tang study. We found that posterior Q continued to positively correlate with postoperative P/A in LASIK and SMILE at 4 mm, 5 mm, and 6 mm as well as in PRK at 4 mm and 5 mm. This suggests that corneas that are more oblate will have a greater P/A ratio compared to less oblate corneas after LASIK, PRK, or SMILE.Pachymetry was negatively correlated with preoperative P/A, which is consistent with previous studies ,9. This Anterior keratometry was found to negatively correlate with preoperative P/A in the 4-mm zone. This suggests that a smaller preoperative P/A is associated with greater anterior keratometric power, which is consistent with what is found in the literature . AnterioPosterior keratometry was found to positively correlate with preoperative P/A in all patients, which reflects what has been reported in the literature . Posteri2: 0.957, PRK adjusted R2: 0.934, SMILE adjusted R2: 0.894).Multivariate analyses were then run using the above preoperative characteristics to generate predictive models of postoperative PA. Across all multivariate analyses, preoperative spherical equivalent had the greatest standard coefficient in LASIK, SMILE, and PRK, indicating that it is the greatest predictor of postoperative P/A ratio across all surgeries. Preoperative P/A ratio was also consistently the second greatest predictor in all groups. When looking at the model for each zone within each surgery, we found that the 6-mm paracentral zone consistently had the highest coefficient of determination in all surgeries (LASIK adjusted RUsing the 6-mm model in There are several limitations in our study. First, our study is retrospective and thus could be subject to selection bias and information bias. Prospective studies are needed to further characterize the validity of preoperative characteristics in predicting postoperative P/A ratio. Given the lack of post-refractive P/A ratios in the literature, it was difficult to validate our study by comparison. Secondly, our sample sizes are not the same across all groups, namely with SMILE having a much smaller relative population. Additionally, Scheimpflug imaging has certain limitations, and its accuracy in measuring keratometry can be affected by factors such as tear film quality, corneal deposits, and corneal scarring. Furthermore, our study did not account for the natural correlation that occurs between the left and right eyes of a single patient. However, the intercorrelation between eyes would produce greater variance in the data, and thus significance would be more difficult to achieve. Our study primarily made inferences on correlations that were significant, and the overall conclusions would likely remain the same. The demographics were also not completely normalized between surgical groups with PRK having thinner corneas on average, and SMILE having more myopic patients with less average cylinder diopters. However, our study did not directly compare the correlations between groups as this was not the goal of this study. Furthermore, each refractive surgery attracts patients with particular preoperative characteristics because they may be ideal candidates for a particular procedure. Despite the strong predictive value of our model, further research is needed to explore the clinical repercussions of P/A ratio, with recent studies looking at its ability to add precision in IOL calculations.P/A ratios have been well-studied in patients prior to undergoing refractive surgery, but not postoperatively. Our study showed that age, spherical equivalent, asphericity, pachymetry, and keratometry not only correlated preoperatively with P/A ratios, but also continued to correlate with P/A postoperatively. Additionally, spherical equivalent and preoperative P/A had the strongest correlations with postoperative PA, which was represented by their contribution to the predictive models. The confluence of independent contributions of preoperative characteristics allows for an extremely accurate, predictive model of postoperative P/A ratio.


To compare the clinical effects of hemodialysis (HD) and peritoneal dialysis (PD) in the treatment of end-stage renal disease (ESRD) patients.Clinical data of ESRD patients who received HD (n=74) and PD (n=77) for more than 12 months in the First People’s Hospital of Tonglu County from October 2020 to November 2021 were retrospectively selected. Renal function indexes, blood pressure, and complication rates in the two groups before the first dialysis and at the end of the observation period were compared.P<0.05). After the dialysis, albumin (ALB) and cardiac ejection fraction (EF) levels significantly increased, and ALB levels were significantly higher in the HD group while EF levels were significantly higher in the PD group (P<0.05). Levels of whole parathyroid hormone (iPTH), systolic blood pressure, and diastolic blood pressure indicators in both groups decreased compared to before the dialysis, and were significantly lower in the PD group compared to the HD group of patients (P<0.05). PD was associated with significantly lower total incidence of complications compared to HD (P<0.05).After the dialysis, the urea nitrogen (BUN) levels decreased in both groups, and were significantly lower in the PD group compared to the HD group. Urea clearance index (Kt/V) increased, and were significantly higher in the PD group compared to the HD group (Peritoneal dialysis is more effective in maintaining the hemodynamic stability for ESRD patients, reducing blood pressure level, improving the clearance rate of molecular substances, and protecting the renal function of patients compared to hemodialysis. End Stage Renal Disease (ESRD) is the most advanced stage of chronic kidney disease (CKD).3The main causes of ESRD include renal damage caused by glomerulonephritis, diabetes nephropathy, hypertensive arteriole sclerosis and polycystic kidney.6Patients with ESRD need to undergo dialysis treatment to continue and maintain their lives.A total of 151 ESRD patients  who received dialysis treatment for more than 12 months in the First People’s Hospital of Tonglu County from October 2020 to November 2021 were selected retrospectively. The average age of the patients was 57.28 ± 8.47 years. Patients were divided into the HD group (n=74) and the PD group (n=77) according to the dialysis mode.Patients aged > 18 yearsConforming to ESRD clinical diagnostic criteria.13The condition is relatively stable.Patients without active inflammation.Complete clinical data.Patients with malignant tumors.Severely infection.Patients with cerebral hemorrhage and myocardial infarction.Serious dysfunction of important organs .Cognitive disorders and mental diseases.Recent history of surgery.This study conforms to the relevant rules and regulations of the Ethics Committee of our hospital .Before the HD and PD treatment, patients in both groups were given routine treatment, including prevention of infection, treatment of diabetes, heart failure, metabolic acidosis, water-electrolyte disorders, and hypovolemia. Close monitoring of patients’ basic physiological indices such as blood glucose, blood lipids, blood pressure, and heart rate, was done.2, the blood flow rate was set at 200~400 ml/minute, bicarbonate was used as the dialysate. The dialysis frequency was 2~3 times per week, and the duration of each dialysis was about 4 hours. If the patient’s blood sugar rose, subcutaneous or intravenous insulin was given to control blood sugar, and the dosage was adjusted appropriately according to the patient’s blood sugar level.Jinbao AK100 dialyzer and Jinbao P-14L dialyzer (Sweden) were used for the treatment. HD patients underwent percutaneous central venous intubation with bicarbonate dialysate. The surface area was 1.4 mThe Baite peritoneal dialysis tube and surgical incision method were used to enter the abdominal cavity, and the glucose dialysate with the concentration of 1.5%~4.5% was selected for the treatment. The flow rate was set at 200 ml/time, the frequency was four times per day, about 2000 mL per time, 4~6 hours in the daytime, 8~10 hours in the evening, and then adjusted appropriately according to the peritoneal balance test results. If the patient’s blood sugar rose, insulin was added to the peritoneal dialysis fluid, and the dosage was adjusted appropriately according to the patient’s blood sugar level. According to the patient’s condition, they can fall asleep or keep a small amount (≤ 500ml) overnight after the last dialysis fluid drainage to ensure the effectiveness of daytime dialysis.Both groups of patients were treated with diuretics, calcium antagonists and β receptor blockers based on their blood pressure to control the blood pressure levels. The BUN, Kt/V, ALB, and iPTH, blood pressure, and complications of two groups of patients before the first dialysis and 12 months after full dialysis were recorded. The detection of serum BUN and ALB was performed using a fully automated biochemical analyzer . The detection of serum iPTH was carried out using chemiluminescence method . Kt/V formula: Kt/V=-ln (R-0.008t) + (4-3.5R) × UF/Wt, where ln is the natural logarithm; R is blood urea nitrogen after dialysis/blood urea nitrogen before dialysis; T is the time of one dialysis, unit: h; UF is the ultrafiltration amount, in liters; Wt is the patient’s weight after dialysis, in kilograms.t test, and the intra group comparison was conducted by paired t test. Data of non-normal distribution were expressed by median and interquartile interval. Mann-Whitney U test was used for intergroup comparison, and Wilcoxon signed rank test was used for intra group comparison. Counting data were represented by the number of cases. P<0 .05 was the significance threshold. SPSS v26.0  was used for statistical analysis.Sample size was calculated by referring to the Kt/V values of previous literature,P>0.05)  .P>0.05). After the dialysis, BUN levels in both groups decreased significantly, and were significantly lower in the PD group compared to the HD group. The Kt/V increased after the treatment, and were significantly higher in the PD group compared to the HD group (P<0.05)  .P>0.05). After the dialysis, ALB and EF levels significantly increased, and ALB levels were significantly higher in the HD group while EF levels were significantly higher in the PD group (P<0.05). Levels of iPTH, systolic blood pressure, and diastolic blood pressure indicators in both groups decreased compared to before the dialysis, and were significantly lower in the PD group compared to the HD group of patients (P<0.05) (P<0.05)  . There w(P<0.05) .This study showed that PD is associated with significant improvement in the indicators, such as BUN, KT/V, blood pressure levels, and incidence of complications compared to HD. Our results indicate that PD can control blood pressure, protect renal function, and achieve more significant clinical effects in ESRD patients more effectively than HD. Xu XD et alStudies shows that HD can easily lead to the increase of blood pressure in patients, while PD has better control effect on blood pressure.25During maintenance dialysis, dietary restrictions and simultaneous filtration of small molecular nutrients  may worsen the nutritional status of the patients, leading to hypoproteinemia and anemia.30It is a single-center retrospective study with small sample size and short observation time, which may lead to some bias in the judgment of efficacy. Further follow-up studies with larger sample size that will observe the survival rate of patients, and further explore the dialysis scheme of ESRD patients, are needed.Compared with HD, PD treatment can effectively maintain the hemodynamic stability of ESRD patients, reduce blood pressure level, improve the clearance rate of molecular substances, effectively protect the renal function of patients.YZ: Conceived and designed the study.YZ: Collected the data and performed the analysis.YZ: Was involved in the writing of the manuscript and is responsible for the integrity of the study.All authors have read and approved the final manuscript.