Changes In Renal Function Research Articles

MO630: Association Between Inflammatory Markers and Progression of Diabetic Kidney Disease

Abstract BACKGROUND AND AIMS Diabetes mellitus is the major cause of end-stage renal disease. Patients with diabetic kidney disease (DKD) have a higher risk of mortality, mostly from cardiovascular complications. Previous studies have shown that inflammatory cytokines are involved in the pathogenesis of microvascular diabetic complications, including DKD. Standard biomarkers including serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria are relatively insensitive to small changes in renal function. Thus, availability of novel biomarkers is necessary to detect kidney injury and predict clinically significant outcomes in diabetic patients. The aim of our study was to find relation between serum inflammatory and growths markers and CKD in patients with DT2. METHOD A total of 155 patients with DT2, aged 34–84 years [60 (60; 72)], were examined. All patients underwent standard clinical and laboratory examination, with an assessment of the levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, high-sensitivity C-reactive protein (hs-CRP), vascular endothelial growth factor A (VEGF-A) and fibroblast growth factor-23 (FGF-23) in baseline plasma samples. Renal function was assessed based on the levels of serum creatinine, cystatin C, eGFR, which was calculated according to the CKD-EPI formula, and albuminuria, which was assessed as albumin/creatinine ratio (A/C). RESULTS The levels of VEGF-A, FGF-23, TNF-α, hs-CRP and Il-6 were significantly higher in diabetic patients with CKD 5 in comparison with stages 1–4. There were positive significant association between VEGF-A, FGF-23, TNF-α, hs-CRP, IL-6 and markers of renal function (creatinine, A/K). Thus VEGF-A, TNF-α and hs-CRP showed a weak and moderate correlation with creatinine, while IL-6 and FGF-23 showed a strong correlation (r = 0.70, P < 0.001, r = 0.71, P < 0.001, respectively). In addition, IL-6 significantly correlated with cystatin C (r = 0.71, P < 0.001). A strong negative correlation was also observed between IL-6 and eGFR (r=−0.73, P < 0.001). In both unadjusted and adjusted analyses, probability of decreased eGFR was associated strongly with FGF-23 (COR (95% CI 1.890); 1.362–2.622, P < 0.001), IL-6 (1.527; 1.251–1.863, P <.001), hs-CRP (1.405; 1.231–1.602, P <.001). When evaluating the dependence of the probability of decreased eGFR on the FGF-23 using the ROC analysis, the cut-off value of FGF-23 which corresponds to the highest Youden's J statistic was 0.9 pmol/L. The sensitivity and specificity of the method were 75.3% and 74.5%, respectively [AUC 0.832 ± 0.035 (95% CI 0.764–0.901), P < 0.001]. The cut-off value of IL-6 was 3.1 mg/mL. The sensitivity and specificity of the method were 64.3% and 73.7%, respectively [AUC 0.750 ± 0.029 (95% CI 0.694–.807), P<0.001]. The cut-off value of hs-CRP was 5.8 mg/L. The sensitivity and specificity of the method were 72.2% and 75.7%, respectively (AUC 0.749 ± 0.029 (95% CI 0.693–.806) P < 0.001). CONCLUSION Involvement of mediators of inflammation and fibrogenesis in the processes of tubulointerstitial damage in patients with diabetes and CKD, confirmed by their negative correlation with GFR and positive with creatinine and albuminuria, indicates a high risk of a decrease in GFR in patients with diabetes with an increase in IL-6 ≥3.1 mg/mL, FGF-23 ≥0.9 pmol/L and hs-CRP ≥5.8 mg/mL along with traditional risk factors.

MO380: Bio-Conductivity Measurement for Electrical Impedance Tomography (EIT) in Chronic Kidney Disease—A Non-Invasive and Portable Monitoring Approach

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) is an escalating global health concern, and non-invasive means for early CKD detection is eagerly awaited. Kidneys are water- and electrolytes-rich organs with good bio-conductivity. Kidney fibrosis and tubular atrophy are characteristic pathological changes in CKD [1], and is associated with restricted blood perfusion, fluid diffusion [2,3] and hence reduced bio-conductivity. Electrical impedance tomography (EIT) emerges as a non-invasive, ionizing radiation-free imaging technique measuring dielectric properties of the body parts [4]. This study investigated the relationship of EIT indices and renal function in patients with various stages of CKD. METHOD We prospectively recruited 98 patients with different stages of CKD (Stage 1, n = 16; Stage 2, n = 15; Stage 3, n = 20, Stage 4, n = 36 and Stage 5, n = 11). EIT measurements were performed at two frequencies (33.6 and 100 kHz) using a portable EIT device with an electrode belt consisting of 16 gel electrodes. EIT data was pre-processed and reconstructed as mean conductivity maps. Frequency differencing was then performed between conductivity maps at two frequencies. Kidney-related dielectric parameters were extracted around the kidney region located at lower one-third of the frequency differencing conductivity map. Conductivity changes between frequencies were then computed and further regressed with individual biometrics. Predicted eGFR values was then computed and compared with the standard eGFR scores to evaluate its effectiveness on classifying CDK stages. RESULTS The detected mean bio-conductivity changes were −3.9, −67.5, −133.5, −212.6 and −294.7 (a.u.) in patients with CKD Stage 1, 2, 3, 4 and 5, respectively (Fig. 1A). Patients with more advanced stages of CKD tend to show more reduction in bio-conductivity, and eGFR correlated positively with reduction in bio-conductivity (R2 = 0.37, P < 0.001) (Fig. 1B). EIT-predicted eGFR (eGFREIT) was further computed by the captured conductivity changes and individual biometrics (Fig. 2). eGFREIT showed significant correlation with eGFR measured by blood tests (R2 = 0.54, P < 0.001). CONCLUSION EIT showed good correlation with renal function changes in CKD patients, and thus holds promise to be developed into a non-invasive and portable device for early CKD detection in both clinical and community settings.

MP56-01 RENAL FUNCTIONAL CHANGES AFTER CYSTECTOMY: WHO IMPROVES AND WHO DOES NOT?

You have accessJournal of UrologyCME1 May 2022MP56-01 RENAL FUNCTIONAL CHANGES AFTER CYSTECTOMY: WHO IMPROVES AND WHO DOES NOT? Benjamin Croll, Dattatraya Patil, Khushali Vashi, Mehrdad Alemozaffar, Viraj Master, Christopher Filson, Kenneth Ogan, Vikram Narayan, and Shreyas Joshi Benjamin CrollBenjamin Croll More articles by this author , Dattatraya PatilDattatraya Patil More articles by this author , Khushali VashiKhushali Vashi More articles by this author , Mehrdad AlemozaffarMehrdad Alemozaffar More articles by this author , Viraj MasterViraj Master More articles by this author , Christopher FilsonChristopher Filson More articles by this author , Kenneth OganKenneth Ogan More articles by this author , Vikram NarayanVikram Narayan More articles by this author , and Shreyas JoshiShreyas Joshi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002639.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A significant decline in renal function following radical cystectomy has been documented in numerous settings and with a variety of urinary diversions. Implications of poor post-operative renal function include the need for renal replacement therapy and exclusion from adjuvant therapies. In the present study, we seek to better characterize two groups of particular interest: those with pre-operative renal impairment (PORI) who improve post-operatively and those with normal renal function who subsequently develop chronic renal insufficiency after surgery. METHODS: A prospectively maintained, single-institutional database retrospectively identified 367 patients who underwent radical cystectomy between 2013 and 2021. Patients were stratified by the presence of PORI, defined as having Stage III CKD (CKD3) or worse (n=142, 38.7%). Variables included the presence of ureteral obstruction before surgery and within one year post-operatively, diabetes, neoadjuvant chemotherapy, age, and rates of major complications. RESULTS: Compared to those with PORI, those with better renal function had a lower incidence of diabetes (33.1% vs. 20.4%, p=0.007). Rates of major complications after cystectomy were not significantly different between those with PORI vs. normal renal function (15.5% vs. 13.8%, p=0.649). Of those with PORI, 21 (23.3%) experienced renal function improvement to GFR >59 mL/min/1.73 m2 at 12 months post-operatively. Of these improved patients, 12 (57.1%) initially presented with ureteral obstruction. Within the remaining 225 patients without PORI, 49 patients (36.3%) developed CKD3 at 12 months post-operatively. Among these patients with renal function decline, 16 (32.7%) had ureteral obstruction within one year after surgery. Presence of diabetes, age >70, history of neoadjuvant chemotherapy, and type of diversion were not significantly different between the above groups. CONCLUSIONS: While 36.3% of patients with normal pre-operative renal function experienced a decline to CKD3 at one year, 23.3% of patients with PORI had resolution of CKD3 at one year. Ureteral obstruction appears to play a significant role in changes in long-term renal function. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e971 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Benjamin Croll More articles by this author Dattatraya Patil More articles by this author Khushali Vashi More articles by this author Mehrdad Alemozaffar More articles by this author Viraj Master More articles by this author Christopher Filson More articles by this author Kenneth Ogan More articles by this author Vikram Narayan More articles by this author Shreyas Joshi More articles by this author Expand All Advertisement PDF DownloadLoading ...

Plasma proteomics reveals an improved cardio-metabolic profile in patients with type 2 diabetes post-liraglutide treatment.

BackgroundDiabetes mellitus is a chronic multisystem disease with a high global prevalence, including in Saudi Arabia. The Glucagon-like Peptide (GLP-1) receptor agonist liraglutide is known to lower glucose levels, reduce weight and improve cardiovascular outcome. However, mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes mellitus (T2DM) remain unclear.MethodsIn the present study, a 2D-DIGE MALDI-TOF mass spectrometric approach combined with bioinformatics and network pathway analysis explore the plasma proteomic profile. The study involved 20 patients with T2DM with mean age of 54.4 ± 9.5 years and Hemoglobin A1c (HbA1c) between 8% and 11% (inclusive).ResultsA statistically significant change (p < .006) was observed in HbA1c with no significant changes in body weight, renal function, or markers of dyslipidemia post-treatment with liraglutide. 2 D-DIGE gel analysis identified significant changes (⩾1.5-fold change, Analysis of variance (ANOVA), p ⩽ 0.05) in 72 proteins, (62 down and 10 up) in liraglutide pre-treatment compared to the post-treatment state. Proteins identified in our study were found to regulate metabolic processes including acute phase response proteins, enzymes, apolipoproteins with involvement of the inflammatory signaling pathways, NF-κB, AKT, and p38 MAPKConclusionLiraglutide treatment decreased levels of acute phase response that to reduce the systemic chronic inflammatory state and oxidative stress, and eventually improve the cardio-metabolic profile in these patients.

Optimizing antithrombotic therapy for atrial fibrillation in cancer

Atrial fibrillation (AF) may be a pre-existing disease before cancer diagnosis, may be a direct effect of the neoplasm or, more often, appears as a post-surgical complication, especially after thoracic surgery. AF may also develop as a consequence of chemotherapy or radiotherapy. The management of the anticoagulation in cancer patients with AF is challenging, and data on these patients are lacking. The use of vitamin K antagonists (VKAs) may be problematic because of the unpredictable therapeutic response and high bleeding risk in patients with active cancer who are undergoing chemotherapy and who may experience thrombocytopenia and/or changes in renal or hepatic function. Low molecular weight heparins and direct oral anticoagulants (DOACs) could be preferred. However, the possible pharmacological interactions of DOACs with anti-cancer and anti-arrhythmic drugs and the bleeding risks in thrombocytopenic patients should be considered. Based on these considerations, a careful evaluation of the antithrombotic strategy with the best efficacy/safety ratio is always needed in cancer patients and anticoagulation for AF should be tailored individually. An ongoing consultation of oncologists/hematologists with cardiologists and coagulation experts in a multidisciplinary approach, with a periodic re-assessment of the benefits of anticoagulation with changes in cancer status/advancement and treatment plans is needed.

Aging Female Offspring Exposed to Maternal Hyperandrogenemia have Increased Renal Mitochondrial Content and Decreased Mitochondrial Reactive Oxygen Species

BackgroundPolycystic ovary syndrome (PCOS), the most common endocrine disorder in women, is characterized by hyperandrogenemia and elevated blood pressure. PCOS women who get pregnant have offspring with intrauterine growth restriction (IUGR). We use a clinically‐relevant rat model of PCOS, the hyperandrogenemic females (HAF), which develop most of the features of PCOS. Offspring of HAF dams are born with IUGR. We have previously shown that aging female HAF offspring are normotensive and are protected against angiotensin (Ang) II‐induced hypertension (HT). HT and Ang II‐induced HT have been shown to be associated with mitochondrial dysfunction. This study was performed to explore the renal mitochondrial function in aging female HAF offspring as a potential protective mechanism against Ang II HT.MethodsFemale Sprague Dawley rats were implanted with either 5α‐dihydrotestosterone (DHT; 7.5 mg/90 d, s.c.; HAF) or placebo pellets starting at 4 wks of age. HAF and controls were mated and allowed to deliver and lactate. Litters were culled to 4 males and 4 females on postnatal day 2. Female offspring were allowed to age to 16‐18 mos with no treatments, then euthanized and kidneys were collected for mitochondrial isolations (n = 3‐4, 1 rat/litter). Mitochondrial respiration and reactive oxygen species (mtROS) production were measured simultaneously by an Oroboros Fluorespirometer using glutamate/malate, succinate, oleate (long‐chain fatty acid; LCFA), or octanoate (medium chain fatty acid; MCFA). Complex IV activity, a marker of oxidative phosphorylation capacity, was measured by respirometry. Data were normalized to mitochondrial content using citrate synthase (CS) activity.ResultsDespite similar renal complex I and II‐driven respiration, renal LCFA (517 ± 24 vs 353 ± 34 nmol e‐/min/mg protein, p &lt; 0.05) and MCFA (783 ± 58 vs 593 ± 58 nmol e‐/min/mg protein, p &lt; 0.05) oxidation were significantly higher in HAF vs control offspring, respectively. Renal CS activity was significantly higher in HAF vs control offspring (884 ± 93 vs 616 ± 62 nmol/min/mg protein, respectively, p &lt; 0.05). After normalization to CS activity, renal complex I and II‐driven respiration, LCFA and MCFA oxidation were similar between HAF and control offspring. Importantly, renal LCFA‐mediated ROS (4x10‐4 ± 7x10‐5 vs 8x10‐4 ± 2x10‐4 nmol e‐/CS activity, p &lt; 0.05) and MCFA‐mediated ROS (6x10‐4 ± 10‐4 vs 10‐3± 2x10‐4 nmol e‐/CS activity, p &lt; 0.05) production were lower in HAF vs control offspring, respectively. Renal complex I and II‐mediated ROS production and complex IV activity were similar between HAF and control offspring.ConclusionAging female HAF offspring have increased renal mitochondrial LCFA and MCFA oxidation that is due to increased mitochondrial content. They also have decreased mtROS production indicating a protection against renal mitochondria‐mediated oxidative stress compared to controls. Further studies are needed to determine if these differences have a mechanistic link to the protection against Ang II HT and whether there are changes in renal mitochondrial function following Ang II infusion in female HAF offspring.

Mitochondrial‐derived ROS Contribute to the Development of Hypertensive‐Diabetic Kidney Injury

Hypertension (HTN) is common in diabetes mellitus (DM) and substantially increases the risk for diabetic nephropathy. Current therapies only slow the progression to end‐stage renal disease (ESRD) in hypertensive‐diabetic patients rather than halt it. Thus, new insights into the mechanisms of this disease are needed.To investigate the mechanisms by which HTN and DM interact to promote renal injury, we developed a model combining streptozotocin (STZ)‐induced type 1 DM and inter‐renal aorta constriction (AC)‐induced HTN in male Wistar rats. In this model (Wistar‐DM+AC), both kidneys are exposed to the same levels of hyperglycemia, circulating hormones, and neural influences, but the left kidney below the AC has normal to slightly reduced blood pressure (BP), while the right kidney above the AC is exposed to elevated BP. To assess the roles of mitochondrial‐derived reactive oxygen species (ROS) and mitochondrial dysfunction in causing kidney injury, Wistar‐DM+AC rats were also treated with saline vehicle or mito‐TEMPO, a mitochondrial‐targeted antioxidant, for 6 weeks starting 2 weeks after AC surgery (0.4mg/kg/day, osmotic mini‐pump). Eight weeks after AC or sham surgery, glomerular filtration rate (GFR) and urinary albumin excretion (UAE) in left and right kidneys were measured separately by collecting urine from each kidney to evaluate the change of renal function. Mitochondrial oxygen consumption rate and superoxide generation from the cortex of left and right kidneys were measured simultaneously by Oroboros high‐resolution respirometry.Kidneys exposed to DM or HTN alone had only mild glomerular injury and slightly increased UAE. In contrast, right kidneys from Wistar‐DM+AC rats which had been exposed to DM plus HTN for 8 weeks had much greater increases in UAE (3.4±0.7 vs1.9±1.3 μg/min), significantly reduced GFR (0.5±0.1 vs 0.7±0.1 ml/min/g of kidney weight) as well as reduced mitochondrial oxygen consumption rate and increased mitochondrial ROS generation compared to left kidneys of Wistar‐DM+AC rats. In Wistar‐DM+AC rats that received mitoTEMPO treatment, the right kidneys exposed to the same levels of elevated BP and blood glucose had lower albumin excretion (1.7±0.3 μg/min), higher GFR (1.3±0.2 ml/min/g of kidney weight), and preserved mitochondrial oxygen consumption with reduced mitochondrial‐derived ROS compared to the right kidneys of vehicle‐treated Wistar‐DM+AC rats.These results suggest that mitochondrial‐derived ROS may contribute to kidney injury when HTN is superimposed on DM. Pharmacological inhibition of mitochondrial ROS generation attenuates kidney injury and may be a potential therapeutic strategy for diabetic nephropathy.

Factors associated with renal function change after unilateral adrenalectomy in patients with primary aldosteronism.

Decreased glomerular filtration rate has been reported in patients with primary aldosteronism after unilateral adrenalectomy. Glomerular hyperfiltration has been assumed to mask the preoperative subtle renal impairment. In this study, we investigated predictors for decreased estimated glomerular filtration rate after adrenalectomy in patients with primary aldosteronism. From January 2006 through September 2018, 328 patients with confirmatory diagnoses of primary aldosteronism received unilateral laparoscopic adrenalectomy and subsequent follow-up for 12 months. We prospectively collected related parameters of the clinical outcomes and renal function to identify predictors of renal function impairment at 12 months after surgery. Patients were stratified into three groups by preoperative estimated glomerular filtration rate level: 144 (43.9%) with estimated glomerular filtration rate ≥90, 130 (39.6%) with estimated glomerular filtration rate within 60-89.9, and 54 (16.5%) with estimated glomerular filtration rate <60 mL/min/1.73 m2 . The estimated glomerular filtration rate decreased significantly at the 6th month and remained stable at the 12th month, postoperatively. Patients with estimated glomerular filtration rate ≥90 had better clinical outcome with 59.6% success rate (P = 0.006) among three groups. Multivariate logistic regression analysis indicated that preoperative estimated glomerular filtration rate (odds ratio 1.012, P = 0.02) and hypokalemia (odds ratio 2.018, P = 0.024) were associated with renal impairment at 12th month after adrenalectomy. Multivariate linear regression analysis revealed high preoperative estimated glomerular filtration rate (β = 0.261, P < 0.001), high preoperative systolic blood pressure (β = 0.168, P = 0.003), high level of microalbuminuria (β = 0.024, P = 0.001), and low level of serum potassium (β = -4.883, P = 0.007) were associated with estimated glomerular filtration rate percentage decline at 12th month after adrenalectomy. Estimated glomerular filtration rate declined significantly after adrenalectomy in patients with estimated glomerular filtration rate ≥90. The study provided important information to identify primary aldosteronism patients with higher risk of estimated glomerular filtration rate decline after adrenalectomy and might help to adopt early interventions to improve the outcomes.

Effects of prolonged cold ischemia on the DCD kidney function and Inflammasome expression in rat kidney transplants

BackgroundAcute kidney injury (AKI) is the main reason for the bad outcome of the donation of circulatory death (DCD) kidney after transplantation. Prolonged cold storage (CS) is a risk factor for the occurrence of the delayed graft function in DCD kidney. The protein NLR-domain containing receptor 3 (NLRP3) plays a crucial role in renal ischemia reperfusion injury by triggering inflammasome formation. Herein, we investigated whether the NLRP3 signal participate in the CS-induced damage of DCD kidney in rat kidney transplantation models. Materials and methodsDCD kidney and living donor (LD) kidney of SD rats were preserved in UW solution at 4 °C for 2 h or 18 h, and then transplanted into syngeneic recipient. Thus, the animals were randomly divided into 4 groups: 2-h LD group, 2-h DCD group, 18-h LD group and 18-h DCD group. The renal function and pathological changes were determined. The expressions of NLRP3 and inflammatory factor IL-1β were assessed. The concentration of ferrous iron (Fe2+) was analyzed both in kidneys and in the preservation solution. The renal morphological changes were examined by hematoxylin eosin staining. ResultsOur results showed that the levels of Cr and BUN were higher in 18-h LD group as compared to the 2-h LD group, which were remarkably increased in 18-h DCD group. The expression levels of NLRP3 and IL-1β were increased by 18-h CS compared to 2-h CS in both LD kidney and DCD kidney. In addition, the Fe2+ concentration has significantly increased in 18-h LD group than that in 2-h LD group, and the elevation of Fe2+ was more remarkable in DCD kidneys. ConclusionIn conclusion, our study demonstrated that prolonged hypothermic storage of DCD kidney deteriorated the graft function via the increased Fe2+ concentration, which was associated with the upregulation of NLRP3 expression.

Dynamics of kidney disorders in children with juvenile idiopathic arthritis taking into account therapy resume

Introduction. In the study of the course and consequences of rheumatic diseases much attention is paid to comorbid conditions that significantly affect the function of internal organs, including kidneys. According to the concept of cardiorenal ratios, even minor renal impairment can be an independent risk factor for cardiovascular events and death. Objective. To determine the features of functional disorders of the kidneys in children and adolescents with juvenile idiopathic arthritis (JIA), taking into account the nature of the disease and therapy. Materials and methods. 85 children (8–18 years) with JIA, oligo- (61.5 %) and polyarthritis (38.5 %), 63 girls and 22 boys were examined. The average duration of the disease was 84.13 ± 6.28 months. The study was conducted twice with an interval of one year. Determination of renal status included studies of urinary sediment, concentration and nitrogen excretion capacity of the kidneys (fluctuations in specific weight during the day, daily proteinuria, creatinine and urea in the blood, glomerular filtration rate (GFR)). Statistical processing of the material was performed using parametric (Student's t-test (p), Fisher's angular transformation) and non-parametric parameters (Wilcoxon-Mann-Whitney), correlation and regression analysis. Results. Changes in renal function did not depend on the sex of patients and included proteinuria (9.09 %), namely microalbuminuria, which occurred in all variants of arthritis; reduction of GFR (8.26 %) – only in polyarthritis and uveitis-associated variants. Comparison of the frequency of renal changes in patients with varying degrees of disease activity showed their absence in the inactive stage of JIA. With active inflammatory process functional disorders of the kidneys occurred from 16.67 % to 26.32 % of cases, regardless of the degree of activity One year later there are positive changes: increased glomerular filtration rate (p ≤ 0.05), a tendency to decrease serum creatinine (p ≤ 0.1) on the background of basic methotrexate therapy up to 15 mg/m2/week. The combination of methotrexate therapy with the anti-TNF immunobiological drug (adalimumab) showed greater efficacy in improving renal function, a significant increase in GFR (p ≤ 0.05), a decrease in serum creatinine (p ≤ 0.05) and proteinuria (р ≤ 0,05). Conclusions. Children with JIA have changes in renal function, more often with uveitis-associated arthritis and methotrexate over 15 mg/m2/week. The inclusion of immunobiological drugs in the treatment not only reduces the activity of the disease, but also reduces the risk of concomitant comorbid lesions of internal organs, including kidneys.

Study to Assess for Improvement in Renal Function following Anderson Hynes Pyeloplasty for Congenital Pelvi Ureteric Obstruction in Children

Background: Pelvi Ureteric Junction Obstruction (PUJO) is defined as an obstruction to the free flow of urine from the renal pelvis to the proximal ureter1. It is the most common cause of obstructive uropathy in the paediatric age group. Aims: To check for improvement in renal function following Anderson Hynes pyeloplasty for congenital PUJ obstruction and to find out at what age should a child be operated for best improvement in renal functions. Material and Methods: A total of 20 patients undergoing Anderson Hynes Pyeloplasty were included after they satisfied the inclusion and exclusion criteria. Results: In this study it was observed that post Anderson Hynes pyeloplasty, a total of 60% children showed improvement in renal functions, in 30% there was no change in renal function while 10% showed deterioration in renal functions, requiring re-operation. The improvement was statistically significant Mean eGFR in cases improved from 32.25 to 38.5 mL/min/1.73 m2 after Anderson Hynes pyeloplasty. The improvement was statistically significant Mean renal functions in cases improved from 29.05% to 33.7% after Anderson Hynes pyeloplasty. No complications were reported in 85% of the cases after Anderson Hynes pyeloplasty. UTI developed in 2 cases (10%) while pyonephrosis was seen in 1 case (5%). Conclusion: Anderson Hynes Pyeloplasty is an effective treatment for congenital Pelvi Ureteric Junction obstruction in pediatric population. In this study it was observed that the earlier we operate the better is the improvement in function.

Predictors of renal impairment and proteinuria after commencement of antiretroviral therapy in a Zimbabwean HIV cohort.

Renal disease prevalence varies widely amongst reported cohorts of people living with HIV (PLWHIV) in sub-Saharan Africa. Renal function testing is not routine in those commencing antiretroviral therapy (ART) in the region, however. Further data on renal disease prevalence and the change associated with ART use are therefore needed. To explore changes in renal function and associated predictors after 1year of ART in an adult cohort of PLWHIV from Zimbabwe. A retrospective analysis of patients who attended the Newlands Clinic between January 2007 and September 2019. Eligible patients were aged ≥18years and had measures of serum creatinine at baseline and after 1year of ART. Predictors of renal function change were assessed by multiple linear regression. 1729 patients were eligible for inclusion. Median age was 36years (IQR 30-43) and 62.8% were female. After 1year of ART, the proportion of patients with an estimated glomerular filtration rate (eGFR) <60ml/min/1.732 did not significantly change (2.0% vs. 1.2%; p=0.094), but there was a decrease in the proportion of patients with proteinuria (11.0% vs. 5.6%; p<0.001). Hypertension (B=-6.43; 95% CI -8.97 to -3.89; p<0.001) and baseline proteinuria (B=-7.33; 95% CI -10.25 to -4.42; p<0.001) were negative predictors of change in eGFR from baseline, whereas diabetes status was not associated (p=0.476). Proteinuria was common, but its prevalence halved after 1year of ART. Screening for hypertension could be a simple way to identify patients at risk of renal function decline.

Renal cortex thickness and changes in renal function after transcatheter aortic valve implantation.

The association between renal morphological findings and changes in renal function in patients undergoing transcatheter aortic valve implantation (TAVI) is unexplored. We aimed to investigate the association between renal morphological findings and changes in renal function in patients undergoing TAVI. Among 283 consecutive patients undergoing TAVI between 2018 and 2021, the study sample included 224 patients. Renal morphological measurements were performed by preoperative multidetector computed tomography. Estimated glomerular filtration rate (eGFR) improvement and deterioration were defined as positive or negative changes in an eGFR of ≥10% one month after TAVI. The renal cortex thickness index was defined as the ratio of total renal cortex thickness to body surface area. The incidences of eGFR improvement and deterioration were 33.9% and 24.1%, respectively. The renal cortex thickness index had a significant correlation with changes in eGFR (r=0.34, p<0.01). The index of the area under the curve of renal cortex thickness for eGFR improvement and deterioration were 0.73 and 0.68, respectively. The cut-off values were 5.82 mm/m2 for eGFR improvement (odds ratio [OR]: 0.10; 95% confidence interval: 0.05-0.20; p<0.01) and 4.89 mm/m2 for eGFR deterioration (OR: 9.07; 95% confidence interval: 4.55-18.6; p<0.01). The renal cortex thickness index was associated with changes in renal function in patients who underwent TAVI. Its measurements might be useful for predicting the renal function change in patients undergoing TAVI.

Impact of mTOR Inhibitor Conversion Protocol on Renal Function in Cardiac Transplant Recipients

<h3>Purpose</h3> Renal insufficiency is common in heart transplant recipients and is associated with increased all-cause cardiovascular mortality. The use of mammalian target of rapamycin inhibitor (mTORi)-based immunosuppression may help mitigate the renal insufficiency associated with calcineurin inhibitors (CI), however complete CI withdrawal is associated with an increased risk of rejection. This study aims to evaluate the effect of mTORi-based immunosuppression with low dose tacrolimus on renal function in patients post-cardiac transplant. <h3>Methods</h3> This was a single-center retrospective study of adult heart transplant recipients who were initiated on an mTORi at least six months post-transplant. The primary outcome of this study was change in renal function from pre-conversion to 3-, 6-, and 12-months post-mTORi initiation. Patients served as their own controls from pre-to-post conversion. <h3>Results</h3> A total of 61 heart transplant patients met inclusion criteria. At baseline, all patients remained on concomitant tacrolimus which was continued in 84% of patients at one year. Renal function for all patients was significantly improved at 3 months (p = 0.001) and 6 months (p = 0.004) post conversion, although the largest impact was seen in those with a baseline eGFR < 35mL/min/1.73m2. Change in renal function over time also differed by goal tacrolimus level. For patients with FK level less than 4 ng/mL, there was a significant main effect of time on eGFR (p=0.0004). There were no significant differences in renal function for the goal tacrolimus ranges of 4-6 ng/mL or 6-8 ng/mL at any time point. There were no identified safety concerns and no difference in rejection. <h3>Conclusion</h3> Overall, conversion to mTORi-based immunosuppression with low dose CI was shown to be associated with improved renal function at 3- and 6-months post conversion. Renal recovery appeared to be greatest for patients with baseline eGFR <35 mL/min/1.73m2 and in those with an FK goal < 4 ng/mL. To our knowledge, this is one of the first studies to describe the impact of FK goal levels on renal function post-conversion to mTORi-based immunosuppression. These results suggest renal improvement may be feasible while maintaining low target levels of CI therapy.

Impact of Treatment Strategies and Hemodynamics on Kidney Function After Heart Transplantation

<h3>Purpose</h3> Renal failure is a common finding in patients with end stage heart failure. While some patients show stable or even improved kidney function after orthotopic heart transplantation (OHT), progressive kidney dysfunction is a common, severe comorbidity after OHT. We quantified changes in kidney function after OHT and determined predictors of persistent kidney dysfunction in a uniformly phenotyped, contemporary cohort treated in our center. <h3>Methods</h3> We analysed data of consecutive OHT recipients being transplanted between 2020 and 2021. Clinical characteristics including hemodynamic data and diuretic regimen were assessed. We performed regression analyses to identify predictors of short-term renal outcome defined as a change of renal function after seven days and one month. <h3>Results</h3> The cohort consisted of 42 OHT recipients (33 men, 78%), median age 54 (IQR 8), ejection fraction of 21% (IQR 8), TAPSE 13 mm (IQR 4), cardiac index of 1.8 L/min/m² (IQR 0.3). Right heart failure was present 16 patients (38 %). 13 patients (33 %) were on mechanical circulatory support prior to OHT and 22 (52%) patients required inotropes. Median pre-operative Creatinine was 1.72 mg/dL (IQR 0.80). Creatinine increased to a maximum of 2.90 mg/dL (IQR 1.51) 10 days after OHT but stabilized on day 30 with 2.25 mg/dL (IQR 1.23). Higher baseline creatinine (p = 0.002) and higher central venous pressure on the first day after OHT (p = 0.025) were associated with more severe kidney disease one month after OHT. Furthermore, right heart failure was associated with stage II/III kidney disease one month after OHT (p = 0.037, OR 5.7, 95% CI 1.3-25.9). Other pre-operative hemodynamic parameters and diuretic drug management had no impact on renal outcome. <h3>Conclusion</h3> In our study, high baseline creatinine and high CVP on the first day after OHT were associated with a more severe decrease of renal function after OHT pointing out the importance of an optimized fluid management in OHT candidates to clear high CVP in favour of good renal outcome. Further studies are needed to determine the optimal treatment regime for this topic with high impact on severity of chronic renal failure and survival after OHT.

Risk factors of acute kidney injury during BCMA CAR-T cell therapy in patients with relapsed/refractory multiple myeloma.

To explore the risk factors of acute kidney injury (AKI) during B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy in patients with relapsed/refractory multiple myeloma (MM). The clinical data of 99 patients with relapsed/refractory MM who received BCMA CAR-T cell therapy in the First Affiliated Hospital of Zhejiang University School of Medicine from July 2018 to December 2021 was retrospectively analyzed. Dynamic changes of renal function before and after chemotherapy preconditioning and after CAR-T cell infusion were observed. Logistic regression was used to analyze the independent risk factors associated with the occurrence of AKI. Among 99 patients, the AKI occurred in 25 cases with an incidence rate of 25.3%, and the median time was 8.0 (5.5,11.0) d. The AKI grade 1, 2 and 3 accounted for 8.0%, 12.0% and 36.0%, respectively. Logistic regression analysis showed that serum creatinine (SCr) after chemotherapy preconditioning ( OR=1.020, P<0.001), and the grade of cytokine release syndrome (CRS) ( OR=6.501, P<0.01) were independent risk factors for AKI during treatment. The area under the ROC curve (AUC) of SCr after chemotherapy preconditioning in predicting AKI was 0.800 (95% CI: 0.694-0.904, P<0.001); using 83.0 μmol/L as cut-off value, the sensitivity, specificity and Youden index of SCr were 72.0%, 80.8% and 0.528, respectively. The incidence of AKI in patients with grade 3-4 CRS was 39.1%, while that was 13.2% in patients with CRS<grade 3 ( χ 2=8.767, P<0.01). AKI mostly occurred within 15.0 d after CAR-T cell infusion, causing transient severe renal damage. Patients with abnormal renal function after chemotherapy preconditioning should be alert to the occurrence of AKI, and attention should be paid to the management of the CRS.

Outcomes Associated with Early Post-Heart Transplant Restrictive Hemodynamics

<h3>Purpose</h3> The implications of the development of restrictive hemodynamics (RH) in the absence of overt graft dysfunction post heart transplantation (OHT) are unclear. We sought to determine the incidence of patients with post-OHT RH profiles and the respective clinical outcomes associated with this pathophysiologic state. <h3>Methods</h3> We retrospectively analyzed 164 (2008-2020) patients who underwent OHT at our institution. Hemodynamics were obtained during scheduled endomyocardial biopsies. Right atrial pressure ≥ 12, pulmonary capillary wedge pressure > 15, and cardiac index > 2.2 L/min/m2 in the absence of graft dysfunction by echocardiography and without evidence of rejection met criteria for a RH profile. We sought to identify if RH profiles persisted at 12 months in addition to rate of heart failure admissions, change in renal function (glomerular filtration rate, GFR), and calcineurin inhibitor protocol deviation (decreases in dosing) compared to controls who did not have primary graft dysfunction or abnormal hemodynamics. <h3>Results</h3> Of 164 patients, 39 had RH profiles at week 4. There was an increased risk of heart failure admissions in those with RH profiles (incident rate ratio 1.81, 95% CI 1.78-1.85, P<0.001) (Panel A). The weekly diuretic dose at 9 months in the RH group was 308 mg/week compared to 127 mg/week in controls (P=0.005) (Panel B). Lower GFR was observed in those with RH at 4 weeks compared to controls, though no significant decline in GFR was observed longitudinally (Panel C). Calcineurin inhibitor protocol deviation occurred in 15 of 39 patients with RH and in 23 of 125 patients without RH (P=0.02). RH persisted at one year in 25.6% of patients (10/39). <h3>Conclusion</h3> Post-OHT patients who develop a RH profile are more likely to experience heart failure hospitalizations, decreases in calcineurin-inhibitor dosing, and have higher loop diuretic doses. The majority tend to normalize their hemodynamic profile at 1 year. Further studies are required to elucidate what factors contribute to the development of this phenotype.

Neobladder creation in patients with chronic kidney disease: A viable diversion strategy.

Renal function impairment is often cited as a contraindication to continent diversion strategies. There is little evidence exploring renal function changes between continent and incontinent surgery in patients with preoperative chronic kidney disease (CKD), in particular CKD3B. This was a retrospective review of two high-volume centers performing robotic assisted radical cystectomy (RARC) with orthotopic neobladder (ONB) or ileal conduit (IC) between 2014 to 2020. Patients were stratified based on CKD estimated glomerular filtration (eGFR) stage, which was estimated via the CKD-EPI equation. Postoperative renal function was compared for up to 60 months postoperative. Surgical, post-surgical, complications, and readmission data were gathered and compared between all patients RESULTS: 522 cystectomy patients, 430 with IC and 125 with ONB, were included. eGFR decline was statistically significant in a matched cohort of IC and ONB patients only at 3 months. There were no statistically significant differences between readmission rates, time to readmission, or complications. 34.6% of stage 3B patients had hydronephrosis on imaging prior to surgery, compared to 11.4%, 22.1% and 21.8% of CKD stage 1, 2, and 3A patients. CKD stage 3B had statistically and clinically improved eGFR through 24 months. ONB surgery may be a viable diversion strategy in patients previously thought to be contraindicated due to low renal function.

Nephro Defensive Efficiency of Cichorium Intybus Against Toxicity Caused by Copper Oxide Nanoparticles

The penetration of nanotechnology into the medical world is constantly growing, and this raises concerns about its toxicity. This study aimed to illustrate the defense ability of Cichorium intybus (CI) against the nephrotoxicity induced by copper oxide nanoparticles (CuONPs) in a rat model. 32 laboratory rats were evenly distributed into 4 groups, each containing 8 animals. CON rats did not receive any dosage, whereas, CuONPs animals were dosed with copper oxide nanoparticles. As for the CuONPs + CI group, intoxicated rats were dosed with Cichorium intybus extract. Lastly, CI rats were given C.intybus extract only. The parameters of renal function, oxidative stress, and renal histological changes were measured. Animals treated with CuONPs showed negative changes in all examined parameters of kidneys compared to the CON group. However, co-administration of plant extract with NPs showed a clear improvement effect of these toxic changes. We concluded that the high dose of CuONPs causes significant kidney damage, and CI extract has a defensive effect against this toxicity. Keywords: Nephrotoxicity, nanoparticles, oxidative stress, histological changes.

Evaluation of the effects of two different anesthesia methods on postoperative renal functions in geriatric patients undergoing hip fracture surgery: a prospective randomized trial

Aim: The choice of anesthesia management for hip fracture surgery is among the modifiable risk factors that can affect the outcome. This study aims to investigate the effects of two different anesthesia techniques on kidney functions with the RIFLE (Risk, Injury, Failure, Loss, and End-stage renal failure) risk score in patients who were operated on for hip fracture.&#x0D; Material and Method: Serum creatinine values lower than 1.5 times (Normal value: 1.2 mg/dL) and glomerular filtration rate (GFR) below 60 mg/dl, over 65 years old, without serious comorbidity, hemoglobin (Hb) value over 9 g/dl 60 patients were included. The demographic data and biochemical parameters of the patients were recorded. The patients were randomized into two groups as spinal anesthesia (Group S) and general anesthesia (Group G). During the surgery, a urinary catheter was applied to the patients and urine output was monitored. Balance liquid electrolyte regimen was applied and after Hb control, an appropriate blood regimen was planned with Hb above 9 g/dl. Postoperatively, patients were followed at 6th, 12th, and 24th hours on the first day, and then at 24-hour intervals in the first postoperative week, and were evaluated with the RIFLE risk scores.&#x0D; Results: There was no statistically significant difference between the groups in terms of demographic data, fracture type, laboratory values, and urine volumes (p &gt; 0.05). In the comparison of intragroup urea values, the decrease in the 5th time interval compared to the baseline value was statistically significant in Group G. There was no statistically significant difference between the measurement times in Group S (p &gt; 0.05). Preoperative creatinine values were found to be statistically significantly higher than other measurement times in the patient group in Group S (p &lt; 0.05). In both groups, it was found that all measurement time urine amounts were statistically different from each other (p &lt; 0.05). In comparisons between groups, There was no statistically significant difference in terms of RIFLE risk score and postoperative outcome at all measurement times (p&gt;0.05).&#x0D; Conclusion: There is no difference between the anesthesia method applied in hip fracture surgery and the change in renal function of patients, based on RIFLE criteria and laboratory parameters. In addition, a significant improvement in renal functions was observed in both groups, especially during the discharge period, according to preoperative values, which may indicate that the stress response to surgery can be effectively limited in both anesthesia methods.