Impaired Renal Function Research Articles

O54 THE EFFECT OF SACUBITRIL/VALSARTAN TREATMENT ON HYPERTENSIVE PATIENTS

Background and Objective: Sacubitril/Valsartan was approved in Japan in 2020 for the treatment of heart failure and subsequently for the treatment of hypertension. It is a drug with a novel mechanism of action that inhibits both angiotensin receptors and neprilysin. Besides its cardioprotective and antihypertensive effects, a subanalysis of previous clinical trials in heart failure patients has shown that it tends to slow the rate of decline in renal function, and is expected to have therapeutic effects against CKD. However, its effect on renal function in hypertensive patients is unknown. In this study, we examined renal prognosis in patients with essential hypertension. Methods: 166 consecutive patients who received an initial dose of ARNI(Sacubitril/Valsartan) (N=104) or ARB (Azilsartan) (N=42) and had blood tests performed before and within 3 months after the first dose at Osaka University Hospital from June 2020 to April 2023 were analyzed retrospectively. Results: ARNI tended to be administered to elderly patients and patients with impaired renal function in both male and female patients. eGFR did not decrease in the ARNI group at either 3 or 12 months post-dose. eGFR decreased over time in the ARB group at 3 and 12 months post-dose. 5 patients on ARNI had drug discontinuations that were thought to be due to adverse drug events (hypotension in 2, numbness in 1, dizziness in 1, syncope in 1 patient). Conclusions: In this study, ARNI tended to be administered in more elderly hypertensive patients. Although there were a few treatment interruptions due to adverse drug events, the adverse effects on renal function were rather minor compared to ARBs, and under careful management, ARNI may be a useful antihypertensive treatment modality even in elderly patients and patients with impaired renal function.

Inflammatory Markers Influencing Mortality Rates in Diabetic Foot Ulcer – A Prospective Study

This study aimed to explore the relationship between inflammatory markers, apolipoprotein E (ApoE) levels, renal function, and mortality in patients with diabetic foot ulcers (DFUs). Conducted as a single-center prospective study at the Clinical County Emergency Hospital of Arad, Romania, the study included 90 patients diagnosed with infected DFUs. The main objective was to determine the risk factors for mortality over a three-year follow-up period, focusing on early versus late deaths. The results indicated a significant correlation between elevated levels of ApoE, pentraxin 3 (PTX3), procalcitonin (PCT), and impaired renal function with increased mortality. Patients with higher levels of these biomarkers, particularly those with impaired renal function, were more likely to experience early death, especially within the first 90 days after surgery. The findings underscore the critical role of these factors in predicting mortality and highlight the need for early intervention and aggressive management of these risk factors to improve outcomes in this vulnerable population. Despite advancements in medical and surgical care, the prognosis for patients with DFUs remains poor, particularly due to the recurrent nature of the ulcers and the presence of comorbidities like chronic kidney disease.

P045 HEALTH AND CARE STATUS OF HYPERTENSIVE PATIENTS IN PRIMARY CARE UNITS IN THE CONOCOTO-QUITO-ECUADOR DISTRICT: BASELINE OF THE HEARTS INITIATIVE - 2019

Background: Hypertension is a significant global public health problem due to the burden of disease and premature death it causes. Its control depends on the quality and timeliness of diagnosis, treatment, and patient follow-up. Studies show an increase in prevalence, poor control, and low coverage in the diagnosis, treatment, and follow-up of hypertensive patients. In response to this problem, since 2019 the Ministry of Health of Ecuador has implemented the HEARTS Initiative proposed by PAHO in primary health care units. This study is part of the baseline prior to its implementation. Objective: To identify the health and care status of hypertensive patients attending primary care units in the Conocoto district. Methodology: A descriptive retrospective study was conducted, reviewing the medical records of 681 patients who attended follow-up consultations in the 9 health units of the district. Results: The average age of the patients was 67.12 years (SD 14.2), with 72.1% being women and 96.7% of mixed ethnicity. The average annual number of consultations was 4.24; 40.4% of the patients were overweight and 41% obese. Of the patients who underwent laboratory tests, 45.1% had hypercholesterolemia, 48% had low HDL, and 10.9% had impaired renal function. An electrocardiogram was performed in 3.4% and a funduscopy in 1.7%. Most patients received counselling on lifestyle changes; 31.9% of the patients had uncontrolled hypertension; depending on the health unit this ranged from 11.3% to 52.3%. Conclusions: The lack of hypertension control is lower than reported in other studies, although many patients do not have the minimum necessary tests. Follow-up should be improved, not only of blood pressure control but also of the patient's clinical condition.

A Comprehensive Review on Understanding Magnesium Disorders: Pathophysiology, Clinical Manifestations, and Management Strategies.

Magnesium is vital in a broad spectrum of physiological processes, including enzyme activity, energy production, and neuromuscular function. Despite its crucial role, magnesium disorders - comprising both deficiency (hypomagnesemia) and excess (hypermagnesemia) - are frequently underrecognized and inadequately managed in clinical practice. Magnesium deficiency is widespread, particularly among populations with chronic illnesses, the elderly, and those experiencing malnutrition, often leading to significant neuromuscular, cardiovascular, and metabolic complications. Conversely, hypermagnesemia, though less common, poses serious risks, especially in individuals with impaired renal function or those receiving high doses of magnesium supplements or medications. This review comprehensively examines magnesium disorders, detailing their pathophysiology, clinical manifestations, and management strategies. It highlights the essential functions of magnesium in maintaining cellular integrity, cardiovascular health, and bone structure and discusses the global prevalence and risk factors associated with magnesium imbalances. By offering insights into the current understanding of magnesium homeostasis and its disruptions, this review aims to enhance the awareness and treatment of magnesium-related conditions, ultimately improving patient outcomes across diverse clinical settings.

Impact of diabetes mellitus and hypertension on renal function during first-line targeted therapy for metastatic renal cell carcinoma: a retrospective multicenter study.

Renal function deterioration during systemic therapy in patients with metastatic renal cell carcinoma (mRCC) is a long-term concern in treatment planning. Although hypertension (HTN) and diabetes mellitus (DM) are the most common factors that affect chronic kidney disease (CKD) development and progression, their impact on renal function during targeted therapy is unclear. This study investigated whether DM and HTN were associated with a decline in renal function during first-line targeted therapy for mRCC. This retrospective multicenter study analyzed patients receiving first-line targeted therapy for mRCC. They were classified as follows: group 1: HTN-, DM-; group 2: HTN+, DM-; group 3: HTN-, DM+; and group 4: HTN+, DM+. Changes in renal function and factors affecting progression to stage 4 CKD after targeted therapy were analyzed. Among the 424 enrolled patients, 303 (71.5%) and 121 (28.5%) were treated with sunitinib and pazopanib, respectively [median duration: 10.3 months, interquartile range (IQR), 3.1-37.0 months]. Although all groups showed a decreased mean estimated glomerular filtration rate (eGFR) after treatment (P<0.001 for group 1, group 2, and group 4, P=0.02 for group 3, respectively), there were no significant differences in changes in eGFR (∆eGFR) between groups (P=0.10). However, actual renal function change calculated using percent ∆eGFR (%∆eGFR) showed differences between groups (P=0.02); the %∆eGFR of group 4 was significantly lower compared with group 1 (P=0.008). The mean progression time to stage 4 CKD in group 4 (38.6 months) was significantly shorter compared to the other groups (P<0.001). Multivariate analysis identified increased age (P=0.008), increased number of metastatic sites (P=0.047), and DM and HTN coexistence (P<0.001) as predictors of progression to stage 4 CKD. Patients with DM and HTN experienced further decline in renal function and had a higher risk of progression to stage 4 CKD after targeted therapy compared to patients without these risk factors. Recognition and proactive management of DM and HTN are necessary to facilitate the proper administration of life-prolonging oncological treatments.

Acute kidney injury: the experience of a tertiary center of Pediatric Nephrology.

Acute kidney injury (AKI) is an abrupt deterioration of kidney function. The incidence of pediatric AKI is increasing worldwide, both in critically and non-critically ill settings. We aimed to characterize the presentation, etiology, evolution, and outcome of AKI in pediatric patients admitted to a tertiary care center. We performed a retrospective observational single-center study of patients aged 29 days to 17 years and 365 days admitted to our Pediatric Nephrology Unit from January 2012 to December 2021, with the diagnosis of AKI. AKI severity was categorized according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The outcomes considered were death or sequelae (proteinuria, hypertension, or changes in renal function at 3 to 6 months follow-up assessments). Forty-six patients with a median age of 13.0 (3.5-15.5) years were included. About half of the patients (n = 24, 52.2%) had an identifiable risk factor for the development of AKI. Thirteen patients (28.3%) were anuric, and all of those were categorized as AKI KDIGO stage 3 (p < 0.001). Almost one quarter (n = 10, 21.7%) of patients required renal replacement therapy. Approximately 60% of patients (n = 26) had at least one sequelae, with proteinuria being the most common (n = 15, 38.5%; median (P25-75) urinary protein-to-creatinine ratio 0.30 (0.27-0.44) mg/mg), followed by reduced glomerular filtration rate (GFR) (n = 11, 27.5%; median (P25-75) GFR 75 (62-83) mL/min/1.73 m2). Pediatric AKI is associated with substantial morbidity, with potential for proteinuria development and renal function impairment and a relevant impact on long-term prognosis.

Chinese herbal medicine alleviates renal impairment induced by immunosuppressants in patients post living donor liver transplantation

Background and aimPatients post liver transplantation (LT) with long-term immunosuppression agents will suffer from renal function impairment. Chinese herbal medicine (CHM) has been reported to relieve chronic kidney disease progression. Nevertheless, there are a lack of high-quality reports related to CHM reducing renal dysfunction in post-LT patients. We aim to investigate whether CHM alleviates renal impairment induced by immunosuppressants in patients having undergone LT. Materials and methodsWe conducted a hospital-based retrospective cohort study including patients with LT from January 1, 2003 to March 31, 2020. We matched the CHM users to non-users at a 1:1 ratio according to baseline variables, comorbidities and drug use status by propensity score (PS) matching. ResultsThe study enrolled a total of 1052 LT patients. After PS matching, 554 patients were included with a 1:1 ratio. CHM and non-CHM users exhibited a significant difference of improved urine protein to creatinine ratio (UPCR) over several 3-month follow-up periods. CHM users exhibited an alleviated decrease in GFR compared to non-CHM users after 12 months of follow-up (CHM: 58.1 to 56.3 ml/min/1.73 m2; non-CHM: 59.8 to 54.7 ml/min/1.73 m2). Among HCC patients, CHM users had alleviated GFR, UPCR and blood urea nitrogen impairments compared to non-CHM users. The most commonly prescribed herbs and formulas are noted. ConclusionWe herein report that CHM could protect renal function after 12 months of follow-up compared to non-CHM users, without liver function impairment. However, the long-term effects and exact renal protection mechanisms require further investigations to confirm.

Abstract P423: Blood Pressure and Renal Function Outcomes After Revascularization of Renal Artery Stenosis in Patients from 3 Different Clinical Settings

The effects of renal percutaneous transluminal angioplasty (rPTA) of renal artery stenosis (RAS) on BP and renal function are controversial. We aim to search for possible differences in these outcomes in different clinical settings. We conducted an observational analysis of effects of rPTA in patients with RAS diagnosed as a result of: screening patients with peripheral artery disease (Vascular Dpt.; G1, n = 20), patients with resistant hypertension or with clinical suspicion of RAS (Hypertension Unit; G2, n = 28) or kidney transplant patients with renal function impairment and/or elevation of BP (Transplantation Unit; G.3, n = 21). RAS is defined as a reduction of ≥70% of the renal artery lumen. Sixty-nine patients were examined (mean age 67±12yr, 64% male). Overall, mean±S.D. baseline SBP/DBP (mmHg) was 147.4±20.6 and 75.7±1.8, and the estimated glomerular filtration rate (eGFR) was 48.7±27.0 mL/min/1.73m 2 . G.1 exhibited a higher prevalence of smoking patients (90%) and patients with past major vascular events (100%), lower DBP (70.0±9.8 mmHg) and better renal function (eGFR: 62.5±23.2 mL/min/1.73m 2 ), compared to G.2 and G.3. Twelve months after rPTA, BP decreased only in patients in G.2 and G.3: variation of (Δ) SBP(mmHg): mean (95%CI)= -18.9 (-26.7 to -11.0) and -20.0 (-29.8 to -10.1), respectively; p&lt;0.001 for both; ΔDBP (mmHg): mean (95%CI)= -6.6 (-10.7 to -2.4), p=0.003 and -6.3 (-11.7 to -0.8), p=0.027, respectively. Regarding renal function, it only improved in G.3: ΔeGFR (mL/min/1.73m 2 ): mean (95%CI)= 8.9 (1.5 to 16.4), p=0.022. ΔSBP was associated with baseline SBP (r= -0.709, p&lt;0.001) and the origin group (Rho = -0.362, p = 0.003); ΔeGFR was associated with baseline eGFR (r= -0.508, p&lt;0.001) and the origin group (Rho = 0.356, p = 0.004). Overall, median ΔSBP was -11 mmHg, and median ΔeGFR was +1.0 mL/min/1.73m 2 . An ANOVA analyzed factors associated with these changes. After adjusting for confounders, ΔSBP was dependent on baseline SBP and group of origin (both p&lt;0.05; adjusted R 2 0.340). ΔeGFR was dependent on baseline eGFR and diabetes (both p&lt;0.05; adjusted R 2 0.123). Blood pressure decreased in patients with suspected RAS because of resistant hypertension 12 months after rPTA. Both BP and renal function improved after rPTA in kidney transplant patients with diagnosis of RAS. Higher BP levels and lower eGFR correlated with better results. Patients with peripheral artery disease screened for RAS showed no change in BP or renal function after rPTA.

Renal Cortical Imaging with Tc-99m DMSA in Children: An Institutional Review.

Background Urinary tract infection (UTI) is one of the commonly encountered conditions in children. Dimercaptosuccinic acid (DMSA) scintigraphy is widely advocated for functional and morphological evaluation of the renal cortex including parenchymal defect. Moreover, only a small percentage of renal defects are detected by ultrasound. We aimed to examine DMSA scintigraphy of children and identify factors associated with cortical defect. Methods Patients aged ≤ 18 years old who underwent DMSA scintigraphy (November 18, 2019-February 2, 2023, 30 children) were included. All children received intravenous injections of 99m Tc-DMSA followed by static planar and single-photon-emission computed tomography imaging at 3 hours. Cortical findings and differential functions of the worst affected kidney were graded accordingly. Grade I has no more than two cortical defects, grade II has more than two cortical defects with normal parenchyma between the defects, while grade III is when generalized damage is noted, and grade IV is when a shrunken kidney is seen with no DMSA uptake. Normal functioning kidney is when the relative function at 45 to 55%, mildly reduced function at 40 to 44%, and substantially impaired function at 10 to 39%, while nonfunctioning is when the differential split renal function < 10%. All data were then statistically analyzed. Results Majority was female (53%). The mean age was 5.85 years. UTI episodes were 73%. Twenty-two children had congenital urinary tract anomalies. All patients with vesicoureteric refluxes (VURs) had positive defects. Scintigraphy showed abnormalities in 17 children affecting unilateral (64%) or both kidneys (36%). There were 17 children (57%) respectively in the abnormal DMSA scan findings category with normal until significant impairment of the functioning kidney category. VURs were significantly associated with abnormal scintigraphy ( p < 0.05). A significant association was found between abnormal DMSA scan findings and differential renal function ( p < 0.05). Conclusion Significant association was noted between VURs and abnormal DMSA scintigraphy, abnormal DMSA scan findings, and impaired differential renal function. Special consideration should be given to these cases.

The Impact of Empagliflozin on Renal Function and Kidney Injury Markers in Patients with Diabetic Nephropathy

Background: Diabetic nephropathy affects approximately 50% of type 2 diabetes patients. Early detection of kidney disease is crucial to reducing the deterioration of renal function. Reversing microalbuminuria towards normal showed beneficial effects in delaying the onset of renal impairment or even reversing the progression of the disease. Recently, empagliflozin, a sodium/glucose cotransporter-2 inhibitor, has received attention for its anti-inflammatory and reno-cardioprotective effects. Objective: This interventional open-label randomized clinical trial aimed to evaluate the clinical outcome of empagliflozin as an add-on therapy for renal function parameters and other injury markers in type 2 diabetic nephropathy patients. Methods: The study enrolled twenty-one type 2 diabetic patients with nephropathy and nineteen without nephropathy. Each group received empagliflozin 10 mg/day for 16 weeks as an add-on to the traditional treatment. Blood and urine samples were collected at baseline and at week 16 to evaluate the glycemic status, renal function, tubular injury markers, and inflammatory and oxidative stress markers. Results: After 16 weeks, empagliflozin significantly reduced glycated hemoglobin A1c and urinary albumin/creatinine ratios in the nephropathy group. Compared with the non-nephropathy group, empagliflozin showed a significant increase in serum creatinine and a significant decrease in eGFRcr. Empagliflozin significantly reduced serum kidney injury molecule-1, cystatin C, interleukin-18, c-reactive protein, and malondialdehyde in both groups. Conclusions: Adding empagliflozin to the traditional oral antidiabetic drugs in diabetic nephropathy improved albuminuria with a mild increment in serum creatinine. Empagliflozin also effectively reduced renal injury markers, as well as inflammatory and oxidative stress markers.

Subcutaneous amikacin administration in red-eared sliders (Trachemys scripta elegans) produces prolonged detectable plasma concentrations without biochemistry evidence of impaired renal function.

To establish pilot data on the plasma concentrations of SC amikacin at 2 doses in red-eared sliders and evaluate concurrent plasma biochemistry parameters. 8 adult red-eared sliders (Trachemys scripta elegans). Amikacin was administered SC at target doses of 5 and 10 mg/kg with a 3-week washout period. Blood samples were collected at 0, 24, 48, 72, and 96 hours postadministration. Plasma amikacin concentrations were quantified using liquid chromatography tandem mass spectrometry. Plasma biochemistry analyses were performed before amikacin administration, 1 week post 5-mg/kg administration, and 1 week post 10-mg/kg administration. Mean maximum amikacin plasma concentrations were recorded 24 hours after 5-mg/kg and 10-mg/kg dosing and were 17.5 ± 2.32 µg/mL and 23.6 ± 2.92 µg/mL, respectively. Mean plasma concentrations after 5-mg/kg dosing steadily decreased to 9.1 ± 0.92 µg/mL by 96 hours postadministration. Amikacin remained detectable in all plasma samples 3 weeks post 5-mg/kg dosing with a mean plasma concentration of 1.04 ± 0.22 µg/mL. Mean plasma concentrations after 10-mg/kg dosing did not decrease over the 96-hour study period. There were no clinically relevant changes in biochemistry parameters. Amikacin persists at detectable plasma levels for at least 3 weeks after SC administration of a 5-mg/kg dose in red-eared sliders, which has not previously been reported in any species. No biochemistry changes consistent with renal toxicity occurred after either dose. Use caution with repeated amikacin dosing in this species until further studies can better characterize cumulative amikacin pharmacokinetics and toxic threshold.

P07-12 Impaired renal function is a confounding factor in the use of plasma citrulline as a marker of intestinal toxicity in rodents

P07-12 Impaired renal function is a confounding factor in the use of plasma citrulline as a marker of intestinal toxicity in rodents

The Mayo Adhesive Probability Score as a Predictor of Postoperative Renal Function in Robot-assisted Partial Nephrectomy.

The aim of this study was to evaluate the Mayo Adhesive Probability (MAP) score as a predictor of split renal function deterioration after robot-assisted partial nephrectomy (RAPN). A total of 30 patients who underwent RAPN were identified retrospectively. The parameters evaluated included patient characteristics, tumor diameter, MAP score, warm ischemic time (WIT), and renal function. Split renal function was evaluated using Tc-99m DTPA renal scintigraphy before and six months after surgery. Univariate and multivariate logistic regression analyses were performed. Nine patients (30.0%) showed more than 90% preservation of split renal function on the operated side. The MAP score (p=0.015), cT1b tumor (p=0.0002), and WIT (p=0.044) were associated with preservation of split renal function six months after surgery on univariate analysis. The MAP score was the strongest predictor of preservation of split renal function six months after surgery on multivariable analysis (p=0.007). On receiver-operating characteristic (ROC) curve analysis, the MAP score (cutoff value 3.0; p=0.01) was a significant predictor of split renal function six months after surgery. The MAP score was significantly associated with postoperative split renal function six months after RAPN on the operated kidney side. The MAP score is useful for predicting split renal function after RAPN.

The impact of bronchiectasis and its severity on long-term renal outcomes.

<sec><title>INTRODUCTION</title>While bronchiectasis is associated with adverse cardiovascular outcomes, data regarding its impact on long-term renal outcomes is lacking.</sec><sec><title>METHODS</title>We reviewed bronchiectasis patients followed up at Queen Mary Hospital in 2017 and examined their clinical/renal outcomes in the subsequent five years. The relationships between the severity of bronchiectasis as defined by FACED (FEV1, Age, Chronic colonisation, Extension, Dyspnoea) scores and adverse renal outcomes were evaluated.</sec><sec><title>RESULTS</title>A total of 315 bronchiectasis patients were included. Seventy-five patients (23.8%) showed renal progression. Baseline FACED score showed a positive correlation with renal progression over 5 years of follow-up (adjusted odds ratio [aOR] 1.30 (95% CI 1.083-1.559, P = 0.005). Patients with moderate-to-severe bronchiectasis (FACED score ≥3) showed an increased risk of renal progression (aOR 1.833, 95% CI 1.082-3.106; P = 0.024) and more rapid decline in estimated glomerular filtration rate than those with mild disease (-4.77 ± 4.19 mL/min/1.73 m²/year vs. -3.49 ± 3.94 mL/min/1.73 m²/year; P = 0.006). Patients who developed renal progression had a higher risk of death (adjusted hazard ratio [aHR] 3.056, 95% CI 1.505-6.206; P = 0.002) and subsequent rates of hospitalisation (1.56 ± 2.81 episodes/year vs. 0.60 ± 1.18 episodes/year; P < 0.001) compared to those without renal progression.</sec><sec><title>CONCLUSIONS</title>Progressive renal function deterioration is prevalent among bronchiectasis patients, and the severity of bronchiectasis is a robust predictor of renal progression.</sec>.

Prognostic value of novel cardiovascular magnetic resonance transit times beyond the pulmonary circulation in patients with ventricular dysfunction.

To evaluate the prognostic value of transit time (TT) assessment in the systemic circulation and organ perfusion in patients with ventricular dysfunction (VD). The primary endpoint was defined as death, heart failure admission, or ventricular arrhythmias, and the secondary endpoint was worsening renal function. A retrospective study on 139 patients who underwent cardiac magnetic resonance for VD evaluation and 50 controls. TT was measured as peak-to-peak time in signal intensity over time curves obtained at different stages of circulation (right cavities, left cavities, aorta, and peripheral organs) from first-pass perfusion images. Outcomes were monitored over a median follow-up of 15 months. A total of 139 patients were included (84% male, age 63 [57-70] years). Patients exhibited significantly prolonged TT compared to controls, with in-patients showing longer times than outpatients. Among the 29 patients reaching the primary endpoint, both PTT and STT were significantly prolonged (PTT: 9.75 s vs 13.4 s, p < 0.01; STT: 4.77 s vs 7.00 s, p < 0.01). Concurrent prolongation of PTT (> 10 s) and STT (> 5 s) was associated with a higher event probability (42.3%), compared to isolated abnormalities (6.3% for PTT, 6.7% for STT). Multivariate analysis revealed that combined PTT and STT alteration independently predicted the combined endpoint (HR IC 95%: 8.685 (2.415-31.236), p = 0.001). Prolonged RPT was independently associated with renal function deterioration (OR IC 95%: 1.129 (1.015-1.256), p = 0.024). Evaluation of TT beyond pulmonary circulation provides prognostic insights into VD. Simultaneous assessment of PTT and STT enhances specificity compared to isolated PTT evaluation, predicting combined adverse events. RPT is independently associated with renal impairment. For the first time, it is described that transit time can be evaluated in systemic circulation and in peripheral organs and that this assessment can be easily made from conventional CMR perfusion images and holds significant prognostic value. Pulmonary transit time is a valuable hemodynamic parameter; systemic transit time may also be valuable. Transit time can be measured in the systemic circulation, and is longer in patients with ventricular dysfunction. Systemic transit time assessed by magnetic resonance imaging identifies patients with ventricular dysfunction who will experience events during follow-up.

AAV-mouse DNase I sustains long-term DNase I expression invivo and suppresses breast cancer metastasis.

Neutrophil extracellular traps (NETs) have been implicated in the pathology of various inflammatory conditions. In cancer, NETs have been demonstrated to induce systemic inflammation, impair peripheral vessel and organ function and promote metastasis. Here we show that the plasma level of NETs is significantly higher in patients with metastatic breast cancer compared to those with local disease, or those that were considered cured at a 5-year follow-up, confirming NETs as interesting therapeutic targets in metastatic breast cancer. Administration of DNase I is one strategy to eliminate NETs but long-term treatment requires repeated injections and species-specific versions of the enzyme. To enhance administration and therapeutic efficacy, we have developed an adeno-associated virus (AAV) vector system for delivery of murine DNase I and addressed its potential to counteract cancer-associated pathology in the murine MMTV-PyMT model for metastatic mammary carcinoma. The AAV vector is comprised of capsid KP1 and an expression cassette encoding hyperactive murine DNase I (AAV-mDNase I) under the control of a liver-specific promotor. This AAV-mDNase I vector could support elevated expression and serum activity of murine DNase I over at least 8 months. Neutrophil Gelatinase-Associated Lipocalin (NGAL), a biomarker for kidney hypoperfusion that is upregulated in urine from MMTV-PyMT mice, was suppressed in mice receiving AAV-mDNase I compared to an AAV-null control group. Furthermore, the proportion of mice that developed lung metastasis was reduced in the AAV-mDNase I group. Altogether, our data indicate that AAV-mDNase I has the potential to reduce cancer-associated impairment of renal function and development of metastasis. We conclude that AAV-mDNase I could represent a promising therapeutic strategy in metastatic breast cancer.

T1 Mapping of the Abdomen, From the AJR "How We Do It" Special Series.

By exploiting different tissues' characteristic T1 relaxation times, T1-weighted images help distinguish normal and abnormal tissues, aiding assessment of diffuse and local pathologies. However, such images do not provide quantitative T1 values. Advances in abdominal MRI techniques have enabled measurement of abdominal organs' T1 relaxation times, which can be used to create color-coded quantitative maps. T1 mapping is sensitive to tissue microenvironments including inflammation and fibrosis and has received substantial interest for noninvasive imaging of abdominal organ pathology. In particular, quantitative mapping provides a powerful tool for evaluation of diffuse disease by making apparent changes in T1 occurring across organs that may otherwise be difficult to identify. Quantitative measurement also facilitates sensitive monitoring of longitudinal T1 changes. Increased T1 in liver helps to predict parenchymal fibro-inflammation, in pancreas is associated with reduced exocrine function from chronic or autoimmune pancreatitis, and in kidney is associated with impaired renal function and aids diagnosis of chronic kidney disease. In this review, we describe the acquisition, postprocessing, and analysis of T1 maps in the abdomen and explore applications in liver, spleen, pancreas, and kidney. We highlight practical aspects of implementation and standardization, technical pitfalls and confounding factors, and areas of likely greatest clinical impact.

Predictive value of perioperative NT-proBNP levels for acute kidney injury in patients with compromised renal function undergoing cardiac surgery: a case control study

BackgroundAcute kidney injury (AKI) significantly increases morbidity and mortality following cardiac surgery, especially in patients with pre-existing renal impairments. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and dysfunction, conditions often exacerbated during cardiac surgery and prevalent in chronic kidney disease (CKD) patients. Elevated NT-proBNP levels can indicate underlying cardiac strain, hemodynamic instability and volume overload. This study evaluated the association between perioperative changes in NT-proBNP levels and the incidence of AKI in this particular patient group.MethodsThis retrospective study involved patients with impaired renal function (eGFR 15–60 ml/min/1.73 m²) who underwent cardiac surgery from July to December 2022. It analyzed the association between the ratio of preoperative and ICU admittance post-surgery NT-proBNP levels and the development of AKI and AKI stage 2–3, based on KDIGO criteria, using multivariate logistic regression models. Restricted cubic spline analysis assessed non-linear associations between NT-proBNP and endpoints. Subgroup analysis was performed to assess the heterogeneity of the association between NT-proBNP and endpoints in subgroups.ResultsAmong the 199 participants, 116 developed postoperative AKI and 16 required renal replacement therapy. Patients with AKI showed significantly higher postoperative NT-proBNP levels compared to those without AKI. Decreased baseline eGFR and increased post/preoperative NT-proBNP ratios were associated with higher AKI risk. Specifically, the highest quantile post/preoperative NT-proBNP ratio indicated an approximately seven-fold increase in AKI risk and a ninefold increase in AKI stage 2–3 risk compared to the lowest quantile. The area under the receiver operating characteristic curve for predicting AKI and AKI stage 2–3 using NT-proBNP were 0.63 and 0.71, respectively, demonstrating moderate accuracy. Subgroup analysis demonstrated that the positive association between endpoints and logarithmic transformed post/preoperative NT-proBNP levels was consistently robust in subgroup analyses stratified by age, sex, surgery, CPB application, hypertension, diabetes status and fluid balance.ConclusionPerioperative NT-proBNP level changes are predictive of postoperative AKI in patients with pre-existing renal deficiencies undergoing cardiac surgery, aiding in risk assessment and patient management.

The role of kidney biopsy in deciphering diabetic versus non-diabetic origin of kidney disease among patients with type 2 diabetes mellitus and nephrotic range proteinuria: A retrospective study

BackgroundDiabetes mellitus (DM) is tightly associated with the increased prevalence of diabetic kidney disease (DKD). Nonetheless, severe renal function impairment and/or nephrotic range-proteinuria could also result from non-diabetic renal disease (non-DRD) among patients with DM. The ‘Gold standard’ for the differential diagnosis between DKD and non-DRD is kidney biopsy, although no real consensus exists. Thus, this study intends to associate the clinical and biochemical profile of patients with DM and renal disease with the histopathological data of kidney biopsy.In addition, we aimed to evaluate the role of kidney biopsy, especially when other causes, other than DM, are highly suspected among patients with DM and kidney disease. MethodsThirty two patients with T2DM and nephrotic range levels of proteinuria or with co-existing factors pointing towards a non-diabetic origin of kidney disease were studied, retrospectively. All 32 patients underwent kidney biopsy and were classified according to histopathological findings into 3 groups: a) isolated diabetic kidney disease (DKD), b) non-diabetic kidney disease (NDKD) and c) mixed kidney disease (MKD). ResultsFifteen out of the 32 patients had findings of an isolated DKD, while 17 out of 32 patients suffered from NDKD (13 patients) or MKD (4 patients). DKD patients were younger (p = 0.016) and had a higher HbA1c value (p = 0.069, borderline statistical significance), while the NDKD patients had significantly shorter disease duration (p = 0.04). Furthermore, the incidence of diabetic retinopathy (DR) was lower among the NDKD patients (p < 0.001), who had also significantly less interstitial fibrosis (p = 0.02). Finally, the presence of DR, higher levels of interstitial fibrosis and longer T2DM duration were recognized as factors, which were positively associated with DKD. ConclusionThis study advocates the usefulness of kidney biopsy in patients with T2DM and nephrotic range levels of proteinuria, especially when DR is absent and shorter disease duration is observed.

Ischemia time in partial nephrectomy: to rush really matters?

Aim: The growth in the incidence of small renal masses has led the implementation of laparoscopic partial nephrectomy to become the technique of choice. However, arterial clamping and secondary renal ischemia still mean a controversial issue due to the risk of renal failure. Our objective is to evaluate the existing literature and its relationship to our experience. Methods: We performed a retrospective study of our series over six years. We analyzed different clinical, perioperative and postoperative functional outcome variables and compared the relationship between tumor complexity and the need for ischemia as well as the relation between ischemia time and renal function over a follow-up time of 6 months. For the discussion, we led a review of the literature on the subject and the paradigm shift that has taken place over the years. Results: A total of 148 patients, most of them male (68.2%) with an average age of 62.4 [standard deviation (SD) 1.7] years, had a Charlson index of 3 [interquartile range (IQR) 1-4]. The average R.E.N.A.L. score was 6 (IQR 5-8). Intraoperative complications were observed in 8.1% of the cases, most of which involved bleeding from a major artery or vein (7.4%). Postoperative complications occurred in 23.6% of the patients, the majority being classified as Clavien 2. Arterial clamping was carried out in 52.7% of the interventions, with a median ischemia time of 8 min (IQR 0-18). The average hospital stay was three days (IQR 2-5). Previous median glomerular filtration rate (GFR) was 83 mL/min/1.73 m2 (IQR 66.2-93.6). On the first postoperative day, the median GFR was 78.4 (SD 21.8), and at 6 months, it was 75.2 (SD 22). We found no statistically significant differences between having hypertension or diabetes mellitus and GFR after surgery, but we found differences in the correlation of a Charlson index ≥ 3 and deterioration of renal function, being the P values 0.01, 0.08 and 0.00 for the first postoperative day, after three and 6 months, respectively. No statistically significant differences were found in whether having a previous chronic kidney disease influenced the decision to perform arterial clamping or not, with a P value of 0.104. Statistically significant differences were found in the relationship between R.E.N.A.L. score and ischemia time. Conclusion: Renal tumors with a higher R.E.N.A.L. score involve the need to accomplish a longer arterial clamping, but its relationship with the deterioration of renal function is unclear, since there are other risk factors, such as patient’s comorbidities.