Renal Kidney Research Articles

Obstacles and Opportunities for Albuminuria Testing Based on the Perspective of Primary Care: A Qualitative Study.

Albuminuria testing is an easy way to identify, early on, a higher risk of cardiovascular and renal kidney morbidity and mortality in patients at-risk. In France, the urine albumin-to-creatinine ratio is an indicator for Remuneration for Public Health Objectives (pay-for-performance P4P) for patients with diabetes or hypertension. These tests must be performed annually by general practitioners (GPs), but are not sufficiently performed, although drug therapies depend on them. We wanted to understand the practice of urinary protein screening assays by means of a qualitative study on the experience of GPs in a French region, with a view to developing facilitating strategies. This qualitative, semiopragmatic, phenomenological study analyzed in-depth interviews held with a purposive sample (age, gender, training, type of practice, rural/urban context) of 27 general practitioners, with triangulation of researchers until data saturation. GPs recognized the assay as a systematic screening tool in accordance with the guidelines, but limited it to patients with diabetes or hypertension encouraged by P4P. Noting that their intervention was limited to kidney-protective measures already in place and, unaware of the new drugs, they saw no benefits and considered it a non-priority test. The existence of several urinary assays with varying intervention thresholds, changes in guidelines and the fact that specialists in laboratory medicine can decide which test to use depending on reimbursement by the health insurance scheme, all contributed to GPs' confusion in prescribing and interpreting tests. One consequence of this was inappropriate referral to the nephrologist. These tests required them to adopt a patient-centered educational approach, making it difficult for certain patients to perform them. GPs were aware of guideline recommendations to screen for albuminuria in patients with diabetes and hypertension but had difficulty interpreting the results. Their lack of perceived clinical consequences and new drugs should be targeted to improve the situation.

Nuclear receptor 4A1 ameliorates renal fibrosis by inhibiting vascular endothelial growth factor A induced angiogenesis in UUO rats

IntroductionAngiogenesis is closely related to renal fibrosis; however, its basic mechanism remains unclear. In our study, we found that nuclear receptor 4A1 (NR4A1) inhibits vascular endothelial growth factor A (VEGFA)-induced angiogenesis, ameliorating renal fibrosis. MethodsWe prepared a renal fibrosis animal model with unilateral ureteral obstruction (UUO) and NR4A1 knockdown UUO mice model, Using Human umbilical vein endothelial cells (HUVECs) to conduct all in vitro experiments. We then detected and analyzed the expression levels of NR4A1 and other genes related to angiogenesis and fibrosis. ResultsThe angiogenesis related genes, such as VEGFA, vascular endothelial growth factor receptor-2 (VEGFR-2), endoglin (CD105), as well as the expression of fibrosis related genes that included, α-smooth muscle actin (α-SMA), Vimentin, and Collagen I are all significantly increased in the UUO rat model. In addition, the expression of NR4A1 of the kidney tissue of UUO rats was significantly reduced. Therefore, according to the above results, we speculated that angiogenesis may exacerbate renal fibrosis and NR4A1 may repress renal fibrosis by inhibiting angiogenesis. To further verify the above results, we used VEGFA to stimulate HUVECs with (or without) overexpression or knockdown of NR4A1. The results showed that with prolonged stimulation using VEGFA, the expression of NR4A1 decreases. Overexpression of NR4A1 significantly inhibits the expression of related indicators of angiogenesis and renal fibrosis. Furthermore, knockdown of NR4A1 induces endothelial cell proliferation and migration; therefore, exacerbating angiogenesis and fibrosis. Finally, the results of NR4A1 knockdown UUO mice showed that knockdown of NR4A1 can aggravating kidney damage and induce the expression of angiogenesis and renal fibrosis related indicators, while UUO can significantly induce kidney damage, angiogenesis and renal fibrosis. When knockdown of NR4A1, renal kidney damage, angiogenesis and fibrosis becomes more severe than UUO. Thus, all of these results indicate that NR4A1 can ameliorate renal fibrosis by inhibiting angiogenesis. ConclusionsNR4A1 can inhibit angiogenesis to ameliorate renal fibrosis.

#1928 Stepwise incremental hemodialysis and low-protein diet supplemented with keto-analogues to preserve residual kidney function: a pilot study

Abstract Background and Aims Studies have demonstrated that chronic dialysis with residual kidney function (RKF) had better survival rates in comparison to those with diminished or absent RKF and are also further associated with improved cardiovascular outcomes. Thus, the strategic preservation of RKF following the initiation of hemodialysis or during transitional periods emerges as a crucial consideration. Compelling evidence suggests that more frequent hemodialysis may contribute to an accelerated decline in RKF, contrasting with the beneficial effects of a low-protein diet (LPD) supplemented with keto-analogues, which has been shown to delay the progression of kidney function decline in the chronic kidney disease (CKD) non-dialysis population. Our pilot study aims to investigate the impact of a stepwise incremental hemodialysis with LPD supplemented with keto-analogues approach on the preservation of RKF after the need to initiate dialysis. Method This open-label, randomized controlled trial (RCT) pilot study employed a 1:1 allocation ratio (Groups 1 and 2) and included 30 patients in CKD stage V non-dialysis, aged ≥18 years, with an eGFR of 5-10 ml/min/1.73 m² as per the CKD-EPI equation, and a urine output of ≥800 ml/day. Exclusion criteria comprised patients with active infection or inflammation, indicated by C-reactive protein (CRP) levels exceeding 10 mg/L, individuals with cancer, or those with a body mass index (BMI) ≥35 kg/m². Group 1 underwent once-weekly hemodialysis (HD) initiation lasting 4 hours, coupled with a low-protein diet (LPD) of 0.6 g/kg/day supplemented with keto-analogues (0.12 g/kg/day) on non-dialysis days and a regular protein diet (1.0 g/kg/day) on dialysis days. In contrast, Group 2 underwent twice-weekly HD initiation (4 hours each) and maintained a regular protein diet (1.0 g/kg/day) every day. A stepwise incremental approach to HD frequency (once to twice per week in Group 1 and twice to thrice per week in Group 2) was implemented if renal kidney function (RKF) fell below 3 ml/min/1.73 m², eqKt/V was ≤1.2/session, Kru was <3 mL/min, ultrafiltration rate exceeded 15 ml/kg/hour, serum potassium was >5.5 mEq/L, and serum phosphate or serum albumin were outside the ranges of >5.5 mg/dL and <3.5 g/dL, respectively. The study spanned a duration of 12 months. Results A total of 30 patients were enrolled in the study and randomized into Group 1 (N = 15) and Group 2 (N = 15). There were no significant differences in baseline characteristics, including age (58.0 ± 19.3 vs 61.9 ± 16.8 years; p = 0.638), BMI (24.0 ± 3.8 vs 23.5 ± 3.6 kg/m²; p = 0.751), eGFR (6.9 ± 1.4 vs 6.2 ± 1.9 mL/min/1.73 m²; p = 0.241), urine volume (2226 ± 729 vs 1690 ± 986 mL/day; p = 0.128), and serum albumin (3.8 ± 0.3 vs 3.6 ± 0.3 g/dL; p = 0.123). In both groups, urine volume decreased over 12 months but Group 1 exhibited significantly higher urine volumes compared to Group 2 at M6 (1697 ± 442 vs 1063 ± 480; p = 0.01), M9 (1453 ± 522 vs 918 ± 404; p = 0.02), and M12 (1119 ± 429 vs 768 ± 367; p = 0.03). Consistent with urine volume, there were significant differences in creatinine clearance (CCr) at M6 (3.9 ± 0.5 in Group 1 vs 2.7 ± 1.8 in Group 2; p = 0.05) and M9 (3.5 ± 0.3 in Group 1 vs 1.9 ± 0.9 in Group 2; p = 0.01). In Group 1, there was a need to increase the rate of dialysis to twice/week in 5 patients at average of 3.6 months after start of study. No significant differences in hospitalization, adverse effects, and patient survival were observed between the two groups. The body weight of all participant were well maintained and no sign of malnutrition. Conclusion Stepwise incremental HD initiated as once-weekly hemodialysis coupled with LPD with keto-analogue supplementation better preserved urine output and CCr compared with twice weekly HD on a regular protein diet. In a period of 12 months after initiation of dialysis, we demonstrated that this stepwise strategy was feasible.

Effect of vinpocetine against acrylamide-induced nephrotoxicity in rats.

Vinpocetine (VIN) is a synthetic drug derived from the natural alkaloid vincamine. The antioxidation and anti-inflammation effects of VIN allow it to be used for multiple therapeutic purposes. So, the research aims to discover the possibility of using VIN to improve the nephrotoxicity of acrylamide (ACR). Twenty-four male albino rats were used in the trial: rats in the control group received 0.5 mL of oral saline, rats in the VIN group received an oral dose of VIN (5 mg/kg), rats in the ACR group received an oral dose of ACR (38.27 mg/kg), and rats in the VIN + ACR group received VIN and then ACR 1 h later. Rat blood and kidneys were collected 10 days after the experiment began to assess biochemical parameters and to examine both renal histopathological and immunohistochemistry. The ACR-treated rats showed high levels of serum kidney function biomarkers (creatinine, urea, and uric acid), serum protein biomarkers (total protein, albumin, and globulin), renal kidney injury molecule (KIM)-1, renal malondialdehyde (MDA), and renal caspase-3 immunoexpression. Moreover, ACR lowed both renal superoxide dismutase (SOD) activity and renal glutathione (GSH) level and caused renal histological alterations. While administration of VIN improved serum kidney function biomarkers, serum protein biomarkers, renal KIM-1, renal oxidative stress biomarkers (MDA, SOD, and GSH), renal caspase-3 immunoexpression, and renal histological alterations induced by ACR. The study confirmed the ability of VIN to reduce the nephrotoxic effects of ACR, which was evident through the results of biochemical parameters and histological and immunohistochemical examinations of the kidney tissues.

Stigma and related factors among renal dialysis patients in China.

Stigma is an important psychological concept that is being studied in many diseases. However, there have been few studies on stigma in renal dialysis patients in China. This study aimed to investigate the level of stigma and its potential influencing factors among Chinese renal dialysis patients. A cross-sectional study was conducted among renal dialysis patients in two Chinese dialysis centers between April 2022 and July 2022. Two hundred four renal kidney patients were interviewed with a questionnaire on demographic variables using the Social Impact Scale (SIS), Resilience Scale-14 (RS-14), Herth Hope Index(HHI), Multidimensional Scale of Perceived Social Support (MSPSS), Revised Life Orientation Test(LOT-R), Perceived Stress Scale (PSS-4) and Fear of Progression (FoP). T-test/univariate one-way ANOVA, Pearson's R, and hierarchical linear regression analysis were used to investigate the factors that influence stigma. Renal dialysis patients in China experienced a moderate level of stigma (52.36 ± 8.16). Stigma was negatively correlated with resilience, hope, and perceived social support, whereas it was positively associated with perceived stress and fear of progression. However, it showed no significant relationship between optimism and stigma. Hierarchical linear regression analysis showed that hope (β = -0.318, P < 0.001), social support (β = -0.193, P < 0.01), perceived stress (β = 0.197, P < 0.01), and fear of progression (β = 199, P < 0.01) were found to be associated with stigma among the renal dialysis patients. All four variables in the model could explain 34.6% of the variance in stigma among renal dialysis patients in China. According to this study, renal dialysis patients in China face a moderate level of stigma. Stigma was found to be negatively related to hope and social support but positively associated with perceived stress and fear of progression. Future research on the stigma of renal dialysis patients should include hope-based interventions, proper and specific social support strategies, stress management interventions, and more disease-related information.

Minimally invasive strategies of surgical coronary artery revascularization for the aging population.

The increasing prevalence of elderly or frail patients with severe coronary disease, who are not suitable for interventional coronary revascularization, necessitates the exploration of alternative treatment options. A less invasive approach, such as minimally-invasive off-pump coronary-artery-bypass (MICS-CABG) grafting through mini-thoracotomy, which avoids both extracorporeal circulation and sternotomy, may be more appropriate for this patient population. This study, a retrospective, monocentric analysis, aimed to evaluate the long-term outcomes of these patients. The study included 172 patients aged 80 years or older, who underwent MICS-CABG between 2007 and 2018. The patients underwent single, double, or triple-vessel revascularization using the left internal thoracic artery, and in some cases, the radial artery or saphenous vein. Follow-up, mean duration of 50.4±30.8 months, was available for 163 patients (94.7%). The mean age of the patients was 83.2±3.0 years, 77.3% of them were male. The EuroSCORE I additive was 11.0±12.1. There were no conversions to sternotomy or cardiopulmonary-bypass. The postoperative 30-day mortality rate was 2.9%, with 5 deaths. The in-hospital rate of major adverse cardiac and cerebrovascular events was 4.7% (perioperative myocardial infarction 1.2%, perioperative stroke 2.3%, repeat revascularization 1.2%). Acute renal kidney injury, (stage 3 KDOQI or more), occurred in 5 patients (2.9%) and new-onset atrial fibrillation in 6 patients (3.5%). The 1-, 3-, 5- and 8-year actuarial survival rate of the 30-day survivors was 97%, 82%, 73%, and 42%, respectively. MICS-CABG grafting is associated with excellent early and long-term outcomes in eligible octogenarians.

Kidney Biopsy in Pregnant Women with Glomerular Diseases: Focus on Lupus Nephritis

Despite significant improvements of renal and obstetrical management, pregnancies in women with glomerular diseases and with lupus nephritis continue to be associated with increased complications both for the mother and the fetus as compared to those of pregnancies in healthy women. To reduce the risk of these complications, planning pregnancy in a phase of stable remission of the underlining disease is necessary. A kidney biopsy is an important event in any phase of pregnancy. A kidney biopsy can be of help during counselling before pregnancy in cases of incomplete remission of the renal manifestations. In these situations, histological data may differentiate active lesions that require the reinforcement of therapy from chronic irreversible lesions that may increase the risk of complications. In pregnant women, a kidney biopsy can identify new-onset systemic lupus erythematous (SLE) and necrotizing or primitive glomerular diseases and distinguish them from other, more common complications. Increasing proteinuria, hypertension, and the deterioration of kidney function during pregnancy may be either due to a reactivation of the underlying disease or to pre-eclampsia. The results of the kidney biopsy suggest the need to initiate an appropriate treatment, allowing the progression of the pregnancy and the fetal viability or the anticipation of delivery. Data from the literature suggest avoiding a kidney biopsy beyond 28 weeks of gestation to minimize the risks associated with the procedure vs. the risk of preterm delivery. In case of the persistence of renal manifestations after delivery in women with a diagnosis of pre-eclampsia, a renal kidney assessment allows the final diagnosis and guides the therapy.

Neonatal administration of zingerone prevents the subsequent development of high dietary fructose-induced early features of nephropathy in rats.

Excessive consumption of fructose-rich diets in early life stages increases the risk for developing nephropathy in adulthood. We investigated the potential preventive effects of neonatally administered zingerone on the development of dietary fructose-induced nephropathy. Four-day-old suckling male and female rat pups were orally gavaged (10 ml/kg) with: distilled water (Con group), 20% fructose solution (Fru group), 20% fructose solution + 40 mg/kg zingerone in distilled water (ZFru group), or 40 mg/kg of zingerone (Zgr group) for 14 days. Thereafter, Con and Zgr groups continued on plain drinking water while Fru and ZFru groups drank 20% fructose solution ad libitum for 10 weeks. The Fru group had significantly increased plasma concentration of the renal injury marker kidney injury molecule one (KIM-1) and decreased glomerular urinary space area compared to the controls in both sexes (p < 0.05). These alterations were prevented by neonatally administered zingerone. Zingerone administration neonatally is a potential prophylaxis for longterm high-fructose diet-induced nephropathy.

Poricoic acid A suppresses renal fibroblast activation and interstitial fibrosis in UUO rats via upregulating Sirt3 and promoting β-catenin K49 deacetylation

Renal interstitial fibrosis is the common pathological process of various chronic kidney diseases to end-stage renal disease. Inhibition of fibroblast activation attenuates renal interstitial fibrosis. Our previous studies show that poricoic acid A (PAA) isolated from Poria cocos is a potent anti-fibrotic agent. In the present study we investigated the effects of PAA on renal fibroblast activation and interstitial fibrosis and the underlying mechanisms. Renal interstitial fibrosis was induced in rats or mice by unilateral ureteral obstruction (UUO). UUO rats were administered PAA (10 mg·kg−1·d−1, i.g.) for 1 or 2 weeks. An in vitro model of renal fibrosis was established in normal renal kidney fibroblasts (NRK-49F cells) treated with TGF-β1. We showed that PAA treatment rescued Sirt3 expression, and significantly attenuated renal fibroblast activation and interstitial fibrosis in both the in vivo and in vitro models. In TGF-β1-treated NRK-49F cells, we demonstrated that Sirt3 deacetylated β-catenin (a key transcription factor of fibroblast activation) and then accelerated its ubiquitin-dependent degradation, thus suppressing the protein expression and promoter activity of pro-fibrotic downstream target genes (twist, snail1, MMP-7 and PAI-1) to alleviate fibroblast activation; the lysine-49 (K49) of β-catenin was responsible for Sirt3-mediated β-catenin deacetylation. In molecular docking analysis, we found the potential interaction of Sirt3 and PAA. In both in vivo and in vitro models, pharmacological activation of Sirt3 by PAA significantly suppressed renal fibroblast activation via facilitating β-catenin K49 deacetylation. In UUO mice and NRK-49F cells, Sirt3 overexpression enhanced the anti-fibrotic effect of PAA, whereas Sirt3 knockdown weakened the effect. Taken together, PAA attenuates renal fibroblast activation and interstitial fibrosis by upregulating Sirt3 and inducing β-catenin K49 deacetylation, highlighting Sirt3 functions as a promising therapeutic target of renal fibroblast activation and interstitial fibrosis.

ACUTE KIDNEY INJURY IN PATIENTS WITH ACUTE LEUKEMIA AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION: A SERIES OF CLINICAL CASES

Relevance: Acute renal kidney injury is a severe complication in patients with acute leukemia who underwent hematopoietic stem cell&#x0D; transplantation (HSCT). According to statistics, acute renal dysfunction often occurs in the first 100 days after HSCT.&#x0D; This study aimed to evaluate kidney function in patients with acute leukemia after hematopoietic stem cell transplantation.&#x0D; Methods: The article presents clinical cases of patients with acute lymphoblastic leukemia who developed acute renal failure after&#x0D; HSCT. The dynamics of the functional state of kidneys in patients with acute lymphoblastic leukemia after HSCT are described.&#x0D; Results: The acute kidney disorder in the studied patients was mainly caused by HSCT complications. We have identified renal kidney&#x0D; damage in the form of acute tumor lysis and thrombotic microangiopathy.&#x0D; Conclusion: Patients with acute lymphoblastic leukemia risk developing acute kidney disorder during HSCT, which requires careful&#x0D; monitoring of kidney function, especially in the early post-transplant period

ACUTE RENAL DISORDER IN PATIENTS WITH ACUTE LEUKEMIA&#x0D; AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION:&#x0D; A SERIES OF CLINICAL CASES

Relevance: Acute renal kidney disorder is a serious complication in patients with acute leukemia who underwent hematopoietic stem cell&#x0D; transplantation (HSCT). According to statistics, acute renal dysfunction often occurs in the first 100 days after HSCT.&#x0D; This study aimed to evaluate kidney function in patients with acute leukemia after hematopoietic stem cell transplantation.&#x0D; Methods: The article presents clinical cases of patients with acute lymphoblastic leukemia who developed acute renal failure after HSCT. The&#x0D; dynamics of the functional state of kidneys in patients with acute lymphoblastic leukemia after HSCT are described.&#x0D; Results: The acute kidney disorder in the studied patients was mainly caused by HSCT complications. We have identified renal kidney damage&#x0D; in the form of acute tumor lysis and thrombotic microangiopathy.&#x0D; Conclusion: Patients with acute lymphoblastic leukemia risk developing acute kidney disorder during HSCT, which requires careful monitoring of kidney function, especially in the early post-transplant period.

Protective effects of endothelial progenitor cell microvesicles carrying miR‑98‑5p on angiotensin II‑induced rat kidney cell injury

With the increasing number of patients with hypertensive nephropathy worldwide, it has posed a major threat to health and studies on its treatment and pathogenesis are imminent. The present study investigated the mechanism through which microRNA (miR)-98-5p in microvesicles (MVs) secreted by endothelial progenitor cells (EPCs) is involved in the repair of angiotensin II (Ang II)-induced injury of rat primary renal kidney cells (PRKs). After isolation of rat renal cortical sections, PRKs were isolated by density gradient centrifugation and identified by immunofluorescence staining. Transmission electron microscopy identifies successful separation of Mvs. An in vitro cell injury model was constructed using Ang II. The Gene Expression Omnibus was used to analyze the differentially expressed genes between diabetic rats and normal rats, and the Kyoto Encyclopedia of Genes and Genomes was used to analyze the signaling pathways involved in these differentially expressed genes. Reverse transcription-quantitative PCR was used to analyze the effect of EPC-MVs on the expression of miRNA induced by Ang II, and the levels of target genes and signaling pathway-related proteins involved were analyzed by western blot. luciferase was used to detect the targeted binding of miR-98-5p to insulin-like growth factor 1 receptor (IGF1R). Enzyme-linked immunosorbent assay was used to analyze the effect of EPC-MVs on Ang II-induced oxidative stress and inflammation levels on PRKs. Cell Counting Kit-8 was used to analyze the effect of EPC-MVs on the cell viability of PRKs induced by Ang II. The results showed that treatment of PRKs with Ang II decreased cell viability, whereas oxidative stress and inflammation were increased. However, EPC-MVs alleviated Ang II-induced damage of the PRKs. During this process, the Ang-II-induced downregulation of miR-98-5p was reversed by EPC-MVs, so miR-98-5p may be a key factor regulating the action of EPC-MVs. Dual-luciferase assay confirmed that miR-98-5p targets IGF1R. It was subsequently demonstrated that EPC-MVs overexpressing miR-98-5p promoted phosphorylation of PI3K/Akt/endothelial nitric oxide synthase (eNOS), and inhibited the oxidative stress and inflammation in PRKs, which were reversed by the overexpression of IGF1R. In conclusion, the results of the present study demonstrated that EPC-MVs with high expression of miR-98-5p can activate the PI3K/Akt/eNOS pathway by regulating IGF1R, as well as protect PRKs from Ang II-induced oxidative stress, inflammation and inhibition of cell viability.

Incidence and risk factors of urinary tract infection in neonatal sepsis

BackgroundNeonates with sepsis may have concurrent urinary tract infection (UTI), which may be asymptomatic or have nonspecific symptoms. Failure to diagnose UTI, resulting in a delay of appropriate therapy, has been reported to cause renal scarring, hypertension, and kidney failure among infants. This study aimed to determine the contribution of UTI to neonatal sepsis and to assess different risk factors that could be associated with UTI. This cross-sectional study was conducted at the Neonatal Intensive Care Unit (NICU) of Fayoum University Hospital, Fayoum, Egypt, between March 2018 and January 2019. Neonates of both genders from birth to the 28th day of life with clinical features of either early- or late-onset sepsis (during or after the first 3 days of life, respectively) were enrolled in this study. All neonates were subjected to complete history taking from the parents, full clinical examination, and laboratory investigations including complete blood count, C-reactive protein, blood culture, and urine culture.ResultsThe current study included 100 neonates admitted to the NICU with clinical and laboratory features of sepsis. Positive blood culture (proven sepsis) was detected in 60%, and the proportion of positive urine culture (UTI) in the entire study group was 11%. The incidence of UTI was 11.7% in proven sepsis compared to 10% in suspected sepsis, and it was 16.36% in late-onset sepsis (LOS) versus 4.44% in early-onset sepsis (EOS). There was a statistically significant association between poor feeding and feeding intolerance and positive urine culture (UTI). Leukopenia and expert panel criteria score showed high sensitivity (81.80% and 90.90%, respectively) but low specificity for the diagnosis of UTI.ConclusionsGram-negative bacteria have been highly suspected in cases of neonatal sepsis. Poor feeding and feeding intolerance have association with positive urine culture. Finally, urine culture for sepsis was recommended especially in the late type.

Arterial stiffness in patients with type 1 diabetes and its comparison to cardiovascular risk evaluation tools

BackgroundArterial stiffness is a potential biomarker for cardiovascular disease (CVD) risk in patients with type 1 diabetes (T1D). However, its relation with other CV risk evaluation tools in T1D has not been elucidated yet. This study aimed to evaluate arterial stiffness in T1D patients free from known CVD, and compare it to other CV risk evaluation tools used in T1D.MethodsCross-sectional study in adults with a T1D duration of at least 10 years and without established CVD. Patients were categorized in CVD risk groups based on 2019 European Society of Cardiology (ESC) guidelines, and the STENO T1D risk engine was used to estimate 10-year risk for CV events. Arterial stiffness was evaluated with carotid-femoral pulse wave velocity (cf-PWV). Coronary artery calcium (CAC) score was assessed and carotid ultrasound was performed. Ambulatory 24-h blood pressure and central hemodynamic parameters were evaluated. Data on renal function and diabetic kidney disease was retrieved.Results54 patients (age: 46 ± 9.5 years; T1D duration: 27 ± 8.8 years) were included. One-fourth of patients showed prematurely increased aortic stiffness based on cf-PWV (24%). Cf-PWV was significantly associated with CAC score, carotid intima-media thickness, central hemodynamic parameters and diabetic kidney disease. Based on STENO, 20 patients (37%) were at low, 20 patients (37%) at moderate, and 14 patients (26%) at high 10-year risk for CV event. Cf-PWV was strongly associated with the STENO score (rs = + 0.81; R2 = 0.566, p < 0.001), increasing with each higher STENO group (p < 0.01). However, cf-PWV was not significantly different between the two CV risk groups (high versus very high) based on ESC criteria, and ESC criteria compared to STENO classified 10 patients more as having > 10% 10-year risk for CV events (n = 44/54; 81.5% versus n = 34/54; 63%).ConclusionsThis study demonstrated that a substantial proportion of long-standing T1D patients free from known CVD show premature arterial stiffening. Cf-PWV strongly associates with the STENO risk score for future CV events and with cardiovascular imaging and function outcomes, thereby illustrating the clinical importance of arterial stiffness. The data, however, also show considerable heterogeneity in CV risk and differences in risk categorisation between the STENO tool and ESC criteria.There is a need for refinement of CV risk classification in T1D, and future studies should investigate if evaluation of arterial stiffness should be implemented in T1D clinical practice and which patients benefit the most from its assessment.

Antibiotic therapy for infectious hemodialysed patients in Bamako: Pharmacokinetic analyses and first improvement suggestions

Infection which occurs in renal kidney failure patient have to be therapeutically managed immediately and the treatment must be aggressive to be quickly efficient. In Bamako (Mali). Posology adaptation cause a problem in nephrology, especially for the most common used antibiotics to care these infections. Drug dosage is not routinely performed in Bamako. The main objective of this work is to compare anthropometric, clinical and pharmacokinetic profiles and the clinical future between infected hemodialysis patients following an antibiotic therapy in Bamako and Lyon (hospital used as a reference). To reach these objectives, a preliminary punctual study of clinical pharmacokinetic of vancomycin were set up at Bamako, following the personalization therapeutics model from Lyon. Bamako patients' samples were imported to France and dosage analysis were performed at Lyon. BestDose software was used to view and compare complete pharmacokinetic profile. It includes for the first time, in routine, the 50 ml/mn of the renal function during dialyses for 58 patients: 31 for Bamako and 21 for Lyon. The residual concentration at the beginning of the dialysis session was compared. In Bamako, patients are younger, the renal failure is more severe and arteriovenous fistula are never set up, treatments are limited in dose and in duration; the residual concentration before the dialyses are too low; as a consequence, infections are rarely quickly reduced and more especially the death linked to these infections are more important (9 in Bamako versus 1 in Lyon). Urgent corrective measures have to be proposed: propose a conciliation between therapeutic requirements formulated within Lyon protocols and the financial ability of the patient, to promote arteriovenous fistula creation as soon as possible, and develop first dose strategy (unfortunately there is often only one dose): a more aggressive dose estimated from simulation profile performed in this study.

MO239: Clinical Evaluation of Immunological and Clinical Recurrence of Immune-Mediated Nephropathies after SARS-COV-2 Vaccine

Abstract BACKGROUND AND AIMS The mass vaccination for COVID-19 has raised new concerns for patients with immune-mediated nephropathies: there is a small but growing literature of case-reports linking SARS-CoV-2 vaccines with heightened off-target immune responses leading to de novo or relapsing glomerular diseases [1, 2]. Aim of this study was to evaluate how many and how severe were the relapses of immune-mediated nephropathies after the SARS-CoV-2 vaccine in a single center. METHOD This is a retrospective study held in Italy from the start of the vaccination campaign (late December 2020) to December 31st 2021. We included all patients with an immune-mediated nephropathy (either on or off immunosuppressive therapy—IS), excluding patients with an end-stage renal disease or kidney transplant. In Italy we used mRNA (Comirnaty by Pfizer-BioNTech or Spikevax by Moderna) or adenoviral vector vaccines (Vaxzevria by AstraZeneca or Janssen), without any preference for patients with kidney disease, but those on active IS were given preferentially an mRNA vaccine. There was no active surveillance of lab tests after vaccination and post-vaccine tests were either concomitant to programmed visits or suggested on a patient by patient basis. Recurrence was defined as relapse of nephrotic or nephritic syndrome, doubling of urinary proteins with a max value &amp;gt; 1 g/24h, acute kidney injury with an active urinary sediment, or positivization or 5-fold increase of serological markers of disease activity (i.e.: ANCA in AAV). RESULTS A total of 38 patients (M: F 28:10, age at vaccine 45.9 ± 19.1 years) completed the vaccination protocol: among them, the most common nephropathy was membranous nephropathy (n = 12, 31.6%), followed by IgA nephropathy (n = 7, 18.4%), minimal change disease (n = 6, 15.8%) and ANCA-associated vasculitis (n = 6, 15.8%); 26 patients (68.4%) had at least one other comorbidity. We observed six relapses (4 MN, 1 IgA, 1 AAV), of which only one (MN) developed a mild oedema. The mean time from the first vaccine dose to the relapse was 101 ± 71 days (5–199 days) and only two episodes occurred within 4 weeks from a vaccine dose. We could not find an association between recurrences and maintenance IS at the time of vaccine or any other variable. The overall post-vaccine incidence rate of relapses was 35.8/100 patient-years, as compared with 14.0/100 patient-years historically observed in the same cohort [IRR 2.55, 95% confidence interval (CI) 0.89–5.97]. CONCLUSION Relapses of immune-mediated nephropathies are not common after SARS-CoV-2 vaccine and we did not observe any clinically relevant relapse. However the overall rate of relapse seems to be a little higher than prior vaccination [3], but only 2/6 patients recurred soon after a vaccine dose. As these relapses seem to be self-limiting, a post-vaccine monitoring could be useful in patients at high risk of severe disease.

MO624: The Relationship Between Renal Tubular Epithelial Cell Necroptosis and The Severity of Diabetic Nephropathy

Abstract BACKGROUND AND AIMS Diabetic nephropathy (DN), a common complication of diabetic patients, usually contributes to end-stage renal failure. Accidental cell death (ACD) and regulated cell death (RCD) cause renal cell loss and deteriorate renal function during the progression of DN. MLKL is the executor of necroptosis, a major form of RCD. The multimer of phosphorylated MLKL (p-MLKL) gather at the cell membrane and form the leaking pores, performing the last step of necroptosis. This study aims to study the relationship of p-MLKL expression and the disease severity in DN patients, providing promising treatment target. METHOD A total of 30 patients who diagnosed with DN clinical-pathologically in the Peking University First Hospital from January 1998 to August 2018 were enrolled (excluding DN with primary or secondary glomerular diseases, DN combined with thrombotic microangiopathies and small vasculitis). p-MLKL were stained on renal biopsy kidney sections by immunohistochemistry. Image-Pro Plus 6.0 software (IPP) was used to analyze the expression of p-MLKL on 10 randomly taken images for each patient. The relationship between p-MLKL expression and clinical-pathological parameters was explored. Clinical parameters of plasma creatinine, peak plasma creatinine during renal biopsy period, estimated glomerular filtration rate (eGFR) were used. DN pathological changes contained: (i) glomerular lesions, (ii) arteriole lesions (iii) tubular lesions and (iv) tubules chronic interstitial lesions. RESULTS Compared with normal control, the positive expression of p-MLKL could be detected in the renal tubular interstitium of patients with DN. However, no p-MLKL positive signal was seen in the glomeruli. Patients with p-MLKL positive signals accounted for 73.33% (22/30) of the enrolled patients. Among the 30 patients, the value of p-MLKL kidney tissue IOD (integrated optical density) was positively correlated with peak serum creatinine (r = 0.373, P = 0.042), the pathological score of spherical sclerosis (r = 0.364, P = 0.048) and tubular brush border (TBB) loss (r = 0.363, P = 0.049). CONCLUSION The expression of necroptosis marker p-MLKL was significantly correlated with the clinical-pathological changes of DN patients. Its role in the progression of DN deserves further exploration.

EFFECTIVENESS OF USE DIALIZER REUSE ON UREA REDUCTION RATIO IN HEMODIALYSIS PATIENTS AT KARSA HUSADA BATU HOSPITAL

Chronic Kidney Disease (CKD) is an end-stage disease of the kidneys, the causes are multiple, can cause to uremia and cannot be renewed.Hemodialysis is a therapy for renal kidney disease. One of the appraisal adequacy of hemodialysis therapy is to use the URR (Urea Reduction Ratio) that assessment by measuring urea before and after hemodialysis therapy. Hemodialysis therapy uses a dialyser that can be used repeatedly in the same patient. The use of dialysers at Karsa Husada Batu Hospital can be used up to 7 times reuse. The research objective was to determine the effectiveness of using a reuse dialyzer to URR. This research design uses comparative descriptive appraisal is a difference between reuse to 1,3,5,7 and using a cross-sectional approach. Sampling using purposive sampling with a sample size of 26 respondents. The different test was used Kruskal Wallis by assessing the URR at the dializer in 1,3,5,7 reuse. Significance of 0.802 (p&amp;gt; 0.05) was obtained, which means that there is no significant difference in the URR value of chronic renal disease patients with hemodialysis therapy using dialyzer reuse to 1,3,5,7. For the URR assessment, it has decreased and increased but is still in normal limits. The dializer reuse up to seven can still be said to be effective in accordance with the guidelines for the management of End-Stage Renal Disease. It is hoped that there will be studies investigating the factors that affect the total volume dilation of dialyser reuse.keywords : Hemodialysis, Dialyzer Reuse , Urea Reduction Ratio

Impact of Renal Replacement Therapy on Mortality and Renal Outcomes in Critically Ill Patients with Acute Kidney Injury: A Population-Based Cohort Study in Korea between 2008 and 2015.

The outcomes depending on the type of renal replacement therapy (RRT) or pre-existing kidney disease in critically ill patients with acute kidney injury (AKI) have not been fully elucidated. All adult intensive care unit patients with AKI in Korea from 2008 to 2015 were screened. A total of 124,182 patients, including 21,165 patients with pre-existing kidney disease, were divided into three groups: control (no RRT), dialysis, and continuous RRT (CRRT). In-hospital mortality and progression to end-stage kidney disease (ESKD) were analyzed according to the presence of pre-existing kidney disease. The CRRT group had a higher risk of in-hospital mortality. Among the patients with pre-existing kidney disease, the dialysis group had a lower risk of in-hospital mortality compared to other groups. The risk of ESKD was higher in the dialysis and CRRT groups compared to the control group. In the CRRT group, the risk of ESKD was even higher in patients without pre-existing kidney disease. Although both dialysis and CRRT groups showed a higher incidence of ESKD, in-hospital mortality was lower in the dialysis group, especially in patients with pre-existing kidney disease. Our study supports that RRT and pre-existing kidney disease may be important prognostic factors for overall and renal outcomes in patients with AKI.

Urine-Derived Kidney Progenitor Cells in Cystinosis.

Nephropathic cystinosis is an inherited lysosomal storage disorder caused by pathogenic variants in the cystinosin (CTNS) gene and is characterized by the excessive shedding of proximal tubular epithelial cells (PTECs) and podocytes into urine, development of the renal Fanconi syndrome and end-stage kidney disease (ESKD). We hypothesized that in compensation for epithelial cell losses, cystinosis kidneys undertake a regenerative effort, and searched for the presence of kidney progenitor cells (KPCs) in the urine of cystinosis patients. Urine was cultured in a specific progenitor medium to isolate undifferentiated cells. Of these, clones were characterized by qPCR, subjected to a differentiation protocol to PTECs and podocytes and assessed by qPCR, Western blot, immunostainings and functional assays. Cystinosis patients voided high numbers of undifferentiated cells in urine, of which various clonal cell lines showed a high capacity for self-renewal and expressed kidney progenitor markers, which therefore were assigned as cystinosis urine-derived KPCs (Cys-uKPCs). Cys-uKPC clones showed the capacity to differentiate between functional PTECs and/or podocytes. Gene addition with wild-type CTNS using lentiviral vector technology resulted in significant reductions in cystine levels. We conclude that KPCs present in the urine of cystinosis patients can be isolated, differentiated and complemented with CTNS in vitro, serving as a novel tool for disease modeling.