The effect of endoscopic renal and ureteral stone surgeries on renal blood flow in children: a prospective trial.

AIM: To assess the impact of endoscopic stone surgeries on renal perfusion and blood flow in children. MATERIALS AND METHODS: Children who underwent percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), ureterorenoscopy (URS), endoscopic combined intrarenal surgery (ECIRS) were included to the study. Renal Doppler ultrasonography (RDUS) was performed one day before the operation, and on the postoperative 1st day and 1st month. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were measured, and resistive index (RI) was calculated with the (PSV-EDV)/PSV formula. RDUS parameters were compared before and after surgery and between ipsilateral and contralateral kidneys. RESULTS: A total of 45 children with a median age was 8 (2-17) years were included (15 (33.3%) girls, 30 (66.7%) boys). PCNL was performed in 13 children (28.9%), RIRS 11 (24.4%), URS 12 (26.7%), and ECIRS 9 (20%). There was no significant difference in renal and segmental PSV, EDV and RI values of operated kidney in the preoperative, postoperative periods. There was no significant difference between RDUS parameters of the ipsilateral and contralateral kidneys in preoperative or postoperative periods. PSV and EDV values were significantly higher in the 1st postoperative month in the group without preoperative DJ stent than in the group with DJ stent (p = 0,031, p = 0,041, respectively). However, RI values were similar. The mean RI were below the threshold value of 0.7 in each period. CONCLUSION: RDUS parameters didn't show a significant difference in children. Endoscopic surgeries can be safely performed in pediatric stone disease.

Study on the Effects of Angiotensin Receptor/Neprilysin Inhibitors on Renal Haemodynamics in Healthy Dogs.

An angiotensin receptor/neprilysin inhibitor (ARNI), a heart failure treatment, is a combination drug made up of sacubitril, a neprilysin inhibitor, and valsartan, a vascular receptor blocker. No human or veterinary studies regarding the effect of ARNI on renal haemodynamics in the absence of cardiac or renal issues exist. Therefore, we investigated the effect of ARNI on renal haemodynamics in five healthy dogs. ARNI was administered to all five dogs at an oral dose of 20 mg/kg twice daily for 4 weeks. Renal haemodynamics were assessed on the day before ARNI administration (BL), on Day 7, and on Day 28. The glomerular filtration rate (GFR) significantly increased on Day 28 compared to BL and Day 7, whereas renal plasma flow increased on Day 7 and Day 28 compared to BL. Systolic blood pressure significantly decreased between BL and Day 28. Plasma atrial natriuretic peptide (ANP) concentrations increased on Day 7 compared to BL. Additionally, ANP concentrations increased on Day 28 in three of the five dogs. Different ANP concentrations were observed in the remaining two dogs. Both urine output volume and heart rate remained relatively stable and did not exhibit significant change. In conclusion, ARNI may enhance renal haemodynamics in healthy dogs. ARNI could be a valuable drug for treating both heart and kidney disease in dogs.

Dynamic rubidium-82 PET/CT as a novel tool for quantifying hemodynamic differences in renal blood flow using a one-tissue compartment model.

PURPOSE: Assessing renal perfusion in-vivo is challenging and quantitative information regarding renal hemodynamics is hardly incorporated in medical decision-making while abnormal renal hemodynamics might play a crucial role in the onset and progression of renal disease. Combining physiological stimuli with rubidium-82 positron emission tomography/computed tomography (82Rb PET/CT) offers opportunities to test the kidney perfusion under various conditions. The aim of this study is: (1) to investigate the application of a one-tissue compartment model for measuring renal hemodynamics with dynamic 82Rb PET/CT imaging, and (2) to evaluate whether dynamic PET/CT is sensitive to detect differences in renal hemodynamics in stress conditions compared to resting state. METHODS: A one-tissue compartment model for the kidney was applied to cardiac 82Rb PET/CT scans that were obtained for ischemia detection as part of clinical care. Retrospective data, collected from 17 patients undergoing dynamic myocardial 82Rb PET/CT imaging in rest, were used to evaluate various CT-based volumes of interest (VOIs) of the kidney. Subsequently, retrospective data, collected from 10 patients (five impaired kidney functions and five controls) undergoing dynamic myocardial 82Rb PET/CT imaging, were used to evaluate image-derived input functions (IDIFs), PET-based VOIs of the kidney, extraction fractions, and whether dynamic 82Rb PET/CT can measure renal hemodynamics differences using the renal blood flow (RBF) values in rest and after exposure to adenosine pharmacological stress. RESULTS: The delivery rate (K1) values showed no significant (p = 0.14) difference between the mean standard deviation (SD) K1 values using one CT-based VOI and the use of two, three, and four CT-based VOIs, respectively 2.01(0.32), 1.90(0.40), 1.93(0.39), and 1.94(0.40) mL/min/mL. The ratio between RBF in rest and RBF in pharmacological stress for the controls were overall significantly lower compared to the impaired kidney function group for both PET-based delineation methods (region growing and iso-contouring), with the smallest median interquartile range (IQR) of 0.40(0.28-0.66) and 0.96(0.62-1.15), respectively (p < 0.05). The K1 of the impaired kidney function group were close to 1.0 mL/min/mL. CONCLUSIONS: This study demonstrated that obtaining renal K1 and RBF values using 82Rb PET/CT was feasible using a one-tissue compartment model. Applying iso-contouring as the PET-based VOI of the kidney and using AA as an IDIF is suggested for consideration in further studies. Dynamic 82Rb PET/CT imaging showed significant differences in renal hemodynamics in rest compared to when exposed to adenosine. This indicates that dynamic 82Rb PET/CT has potential to detect differences in renal hemodynamics in stress conditions compared to the resting state, and might be useful as a novel diagnostic tool for assessing renal perfusion.

Interaction of Angiotensin-(1-7) with kinins in the kidney circulation: Role of B1 receptors.

Changes in renal hemodynamics impact renal function during physiological and pathological conditions. In this context, renal vascular resistance (RVR) is regulated by components of the Renin-Angiotensin System (RAS) and the Kallikrein-Kinin System (KKS). However, the interaction between these vasoactive peptides on RVR is still poorly understood. Here, we studied the crosstalk between angiotensin-(1-7) and kinins on RVR. The right kidneys of Wistar rats were isolated and perfused in a closed-circuit system. The perfusion pressure and renal perfusate flow were continuously monitored. Ang-(1-7) (1.0-25.0 nM) caused a sustained, dose-dependent reduction of relative RVR (rRVR). This phenomenon was sensitive to 10 nM A-779, a specific Mas receptor (MasR) antagonist. Bradykinin (BK) promoted a sustained and transient reduction in rRVR at 1.25 nM and 125 nM, respectively. The transient effect was abolished by 4 µM des-Arg9-Leu8-bradykinin (DALBK), a specific kinin B1 receptor (B1R) antagonist. Accordingly, des-Arg9-bradykinin (DABK) 1 µM (a B1R agonist) increased rRVR. Interestingly, pre-perfusion of Ang-(1-7) changed the sustained reduction of rRVR triggered by 1.25 nM BK into a transient effect. On the other hand, pre-perfusion of Ang-(1-7) primed and potentiated the DABK response, this mechanism being sensitive to A-779 and DALBK. Binding studies performed with CHO cells stably transfected with MasR, B1R, and kinin B2 receptor (B2R) showed no direct interaction between Ang-(1-7) with B1R or B2R. In conclusion, our findings suggest that Ang-(1-7) differentially modulates kinin's effect on RVR in isolated rat kidneys. These results help to expand the current knowledge regarding the crosstalk between the RAS and KKS complex network in RVR.

Anterograde Aortic Bypass Technique for Renal Preservation in Aneurysmal Repair With Horseshoe Kidney: A Novel Approach With Reduced Renal Ischemic Time.

The purpose of this article is to highlight an innovative technique in the surgical management of aortic aneurysms in the presence of a horseshoe kidney. The technique involves an anterograde aortic bypass from the distal thoracic aorta to the major renal artery with the primary advantage to a significant reduction in renal ischemia time.

Changes in renal blood flow after surgically induced weight loss: can bariatric surgery halt the progression of chronic kidney disease?

BACKGROUND: We previously demonstrated how kidney injury in patients with morbid obesity can be reversed by bariatric surgery (BaS). OBJECTIVE(S): Based on previous experience, we hypothesize patients' potentially reversible kidney injury might be secondary to reduction in renal blood flow (RBF), which improves following BaS. SETTING: Academic Hospital. METHODS: We conducted a retrospective analysis of patients who underwent BaS at our institution from 2002 to 2019. We identified patients with chronic kidney disease (CKD) using the estimated glomerular filtration rate (eGFR) from the CKD Epidemiology Collaboration Study (CKD-EPI) classification system. We used the BUN/Creatinine (Cr) ratio pre- and postoperatively to determine a prerenal (decreased RBF) versus intrinsic component as the responsible cause of CKD in this patient population. Decreased RBF was defined as BUN/Cr > 20 preoperatively. RESULTS: Our analysis included n = 2924 patients, of which 11% (n = 325) presented decreased RBF. From our original sample, only n = 228 patients had the complete data necessary to assess both eGFR and RBF (BUN/Cr). Patients with baseline CKD stage 2 demonstrated preoperative BUN/Cr 20.85 ± 10.23 decreasing to 14.99 ± 9.10 at 12-month follow-up (P < .01). Patients with baseline CKD stage 3 presented with preoperative BUN/Cr 23.88 ± 8.75; after 12-month follow-up, BUN/Cr ratio decreased to 16.38 ± 9.27 (P < .01). Patients with CKD stage 4 and ESRD (eGFR < 30) did not demonstrate a difference for pre- and postoperative BUN/Cr 21.71 ± 9.28 and 19.21 ± 14.58, respectively. CONCLUSION(S): According to our findings, patients with CKD stages 1-3 present improvement of their kidney function after BaS. This amelioration could be secondary to improvement of the RBF, an unstudied reversible mechanism of kidney injury in the bariatric population.

Change in renal blood flow in response to intrarenal pressure alterations induced by ureteroscopy in an in-vivo porcine model.

INTRODUCTION: High irrigation rates are commonly used during ureteroscopy and can increase intrarenal pressure (IRP) substantially. Concerns have been raised that elevated IRP may diminish renal blood flow (RBF) and perfusion of the kidney. Our objective was to investigate the real-time changes in RBF while increasing IRP during Ureteroscopy (URS) in an in-vivo porcine model. METHODS: Four renal units in two porcine subjects were used in this study, three experimental units and one control. For the experimental units, RBF was measured by placing an ultrasonic flow cuff around the renal artery, while performing ureteroscopy in the same kidney using a prototype ureteroscope with a pressure sensor at its tip. Irrigation was cycled between two rates to achieve targeted IRPs of 30 mmHg and 100 mmHg. A control data set was obtained by placing the ultrasonic flow cuff on the contralateral renal artery while performing ipsilateral URS. RESULTS: At high IRP, RBF was reduced in all three experimental trials by 10-20% but not in the control trial. The percentage change in RBF due to alteration in IRP was internally consistent in each porcine renal unit and independent of slower systemic variation in RBF encountered in both the experimental and control units. CONCLUSION: RBF decreased 10-20% when IRP was increased from 30 to 100 mmHg during ureteroscopy in an in-vivo porcine model. While this reduction in RBF is unlikely to have an appreciable effect on tissue oxygenation, it may impact heat-sink capacity in vulnerable regions of the kidney.

Renal arterial infusion of tempol prevents medullary hypoperfusion, hypoxia, and acute kidney injury in ovine Gram-negative sepsis.

AIM: Renal medullary hypoperfusion and hypoxia precede acute kidney injury (AKI) in ovine sepsis. Oxidative/nitrosative stress, inflammation, and impaired nitric oxide generation may contribute to such pathophysiology. We tested whether the antioxidant and anti-inflammatory drug, tempol, may modify these responses. METHODS: Following unilateral nephrectomy, we inserted renal arterial catheters and laser-Doppler/oxygen-sensing probes in the renal cortex and medulla. Noanesthetized sheep were administered intravenous (IV) Escherichia coli and, at sepsis onset, IV tempol (IVT; 30 mg kg-1 h-1 ), renal arterial tempol (RAT; 3 mg kg-1 h-1 ), or vehicle. RESULTS: Septic sheep receiving vehicle developed renal medullary hypoperfusion (76 ± 16% decrease in perfusion), hypoxia (70 ± 13% decrease in oxygenation), and AKI (87 ± 8% decrease in creatinine clearance) with similar changes during IVT. However, RAT preserved medullary perfusion (1072 ± 307 to 1005 ± 271 units), oxygenation (46 ± 8 to 43 ± 6 mmHg), and creatinine clearance (61 ± 10 to 66 ± 20 mL min-1 ). Plasma, renal medullary, and cortical tissue malonaldehyde and medullary 3-nitrotyrosine decreased significantly with sepsis but were unaffected by IVT or RAT. Consistent with decreased oxidative/nitrosative stress markers, cortical and medullary nuclear factor-erythroid-related factor-2 increased significantly and were unaffected by IVT or RAT. However, RAT prevented sepsis-induced overexpression of cortical tissue tumor necrosis factor alpha (TNF-α; 51 ± 16% decrease; p = 0.003) and medullary Thr-495 phosphorylation of endothelial nitric oxide synthase (eNOS; 63 ± 18% decrease; p = 0.015). CONCLUSIONS: In ovine Gram-negative sepsis, renal arterial infusion of tempol prevented renal medullary hypoperfusion and hypoxia and AKI and decreased TNF-α expression and uncoupling of eNOS. However, it did not affect markers of oxidative/nitrosative stress, which were significantly decreased by Gram-negative sepsis.

The differences in renal hemodynamic response following high-intensity exercise between younger and older males.

BACKGROUND: Renal blood flow (RBF) decreases with exercise, but this change is only temporary, and habitual exercise may be an effective method to improve renal function. The kidney shows structural and functional changes with aging, but it is unclear how aging affects the hemodynamic response of the kidneys to exercise. Therefore, we evaluated the differences in the hemodynamic response of the kidneys to high-intensity exercise between younger and older men. METHODS: Sixteen men (8 young and 8 older) underwent an incremental exercise test using a cycle ergometer with a 1-min warm up followed by exercise at 10-20 W/min until the discontinuation criteria were met. Renal hemodynamics were assessed before exercise, immediately after exercise, and at 60-min after exercise using ultrasound echo. RESULTS: High-intensity exercise significantly reduced RBF in both groups (younger: ∆ - 53 ± 16%, p = 0.0005; older: ∆ - 53 ± 19%, p = 0.0004). In the younger group, RBF returned to the pre-exercise level 60-min after exercise (∆ - 0.4 ± 5.7%, p > 0.9999). In contrast, RBF 60-min after exercise was significantly lower than that before exercise in the older group (∆ - 24 ± 19%, p = 0.0006). The older group had significantly lower RBF than younger adults 60-min after exercise (423 ± 32 vs. 301 ± 98 mL/min, p = 0.0283). CONCLUSIONS: Our findings demonstrate that RBF following high-intensity exercise recovered 60-min after exercise in younger group, whereas RBF recovery was delayed in the older group.

Impaired microvascular circulation in distant organs following renal ischemia.

Mortality in acute kidney injury (AKI) patients remains very high, although very important advances in understanding the pathophysiology and in diagnosis and supportive care have been made. Most commonly, adverse outcomes are related to extra-renal organ dysfunction and failure. We and others have documented inflammation in remote organs as well as microvascular dysfunction in the kidney after renal ischemia. We hypothesized that abnormal microvascular flow in AKI extends to distant organs. To test this hypothesis, we employed intravital multiphoton fluorescence imaging in a well-characterized rat model of renal ischemia/reperfusion. Marked abnormalities in microvascular flow were seen in every organ evaluated, with decreases up to 46% observed 48 hours postischemia (as compared to sham surgery, p = 0.002). Decreased microvascular plasma flow was found in areas of erythrocyte aggregation and leukocyte adherence to endothelia. Intravital microscopy allowed the characterization of the erythrocyte formations as rouleaux that flowed as one-dimensional aggregates. Observed microvascular abnormalities were associated with significantly elevated fibrinogen levels. Plasma flow within capillaries as well as microthrombi, but not adherent leukocytes, were significantly improved by treatment with the platelet aggregation inhibitor dipyridamole. These microvascular defects may, in part, explain known distant organ dysfunction associated with renal ischemia. The results of these studies are relevant to human acute kidney injury.

Arterial spin labeling and diffusion-weighted MR imaging: quantitative assessment of renal pathological injury in chronic kidney disease.

PURPOSE: The aim of the study was to investigate the performance of arterial spin labeling (ASL), diffusion-weighted imaging (DWI), and clinical biomarkers in assessing renal pathological injury in CKD. MATERIALS AND METHODS: Forty-five biopsy-proven CKD patients and 17 healthy volunteers underwent DWI and ASL examinations. Renal cortical blood flow (RBF) and apparent diffusion coefficient (ADC) values were acquired. Correlations between RBF, ADC, serum creatinine (SCr), estimated glomerular filtration rate (eGFR), and pathological scores were assessed. The diagnostic efficacy of SCr, eGFR, RBF, and ADC in assessing renal pathological injury was assessed by ROC curve analysis. RESULTS: The cortical RBF, ADC, SCr, and eGFR were significantly correlated with the renal histology score (all p < 0.01). The AUC values of SCr, eGFR, RBF, and ADC were 0.705 (95% confidence interval (CI): 0.536-0.827), 0.718 (0.552-0.839), 0.823 (0.658-0.916), and 0.624 (0.451-0.786), respectively, in discriminating the minimal-mild renal pathological injury group (N = 30) from the control group (N = 17). The diagnostic ability of ASL was significantly higher than that of DWI (p = 0.049) and slightly but not significantly higher than that of eGFR and SCr (p = 0.151 and p = 0.129, respectively). When compared with that of eGFR, the sensitivity of ASL in detecting early renal injury increased from 50 to 70% (p = 0.014). However, in differentiating between the minimal-mild and moderate-severe renal injury groups (N = 15), there was no significant difference in diagnostic ability among the four parameters (all p > 0.05). CONCLUSION: ASL is practicable for noninvasive evaluation of renal pathology, especially for predicting early renal pathological injury in CKD patients.

Effects of mesenchymal stem cells in renovascular disease of preclinical and clinical studies: a systematic review and meta-analysis.

Renal artery stenosis (RAS) causes severe renovascular hypertension, worsening kidney function, and increased cardiovascular morbidity. According to recent studies, mesenchymal stem cells (MSCs) administration is a promising therapy for the improvement of RAS outcomes. The meta-analysis aims to evaluate the therapeutic effects of MSC therapy on RAS. We performed a search in MEDLINE, Web of Science, Embase, and Cochrane Library from inception to 5, October 2022. We included 16 preclinical and 3 clinical studies in this meta-analysis. In preclinical studies, the pooled results indicated that animals treated with MSCs had lower levels of systolic blood pressure (SBP) (SMD = - 1.019, 95% CI - 1.434 to - 0.604, I2 = 37.2%, P = 0.000), serum creatinine (Scr) (SMD = - 1.112, 95% CI - 1.932 to - 0.293, I2 = 72.0%, P = 0.008), and plasma renin activity (PRA) (SMD = - 0.477, 95% CI - 0.913 to 0.042, I2 = 43.4%, P = 0.032). The studies also revealed increased levels of renal blood flow (RBF) in stenotic kidney (STK) (SMD = 0.774, 95% CI - 0.351 to 1.197, I2 = 0%, P = 0.000) and the glomerular filtration rate (GFR) of STK (SMD = 1.825, 95% CI 0.963 to 2.688, I2 = 72.6%, P = 0.000). In clinical studies, the cortical perfusion and fractional hypoxia of the contralateral kidney (CLK) were alleviated by MSC therapy. Taken together, this meta-analysis revealed that MSCs therapy might be a promising treatment for RAS. However, due to the discrepancy between preclinical studies and early clinical trials outcomes, MSC therapy couldn't be recommended in clinical care for the moment, more high-quality randomized controlled clinical trials are needed to validate our conclusions and standardize MSCs protocols.

Effects of Elamipretide on Autophagy in Renal Cells of Pigs with Metabolic Syndrome.

Autophagy eliminates excessive nutrients and maintains homeostasis. Obesity and metabolic syndrome (MetS) dysregulate autophagy, possibly partly due to mitochondria injury and inflammation. Elamipretide (ELAM) improves mitochondrial function. We hypothesized that MetS blunts kidney autophagy, which ELAM would restore. Domestic pigs were fed a control or MetS-inducing diet for 16 weeks. During the 4 last weeks, MetS pigs received subcutaneous injections of ELAM (0.1 mg/kg/day, MetS + ELAM) or vehicle (MetS), and kidneys were then harvested to measure protein expression of autophagy mediators and apoptosis. Systemic and renal venous levels of inflammatory cytokines were measured to calculate renal release. The function of isolated mitochondria was assessed by oxidative stress, energy production, and pro-apoptotic activity. MetS slightly downregulated renal expression of autophagy mediators including p62, ATG5-12, mTOR, and AMPK vs. control. Increased mitochondrial H2O2 production accompanied decreased ATP production, elevated apoptosis, and renal fibrosis. In MetS + ELAM, mito-protection restored autophagic protein expression, improved mitochondrial energetics, and blunted renal cytokine release and fibrosis. In vitro, mitoprotection restored mitochondrial membrane potential and reduced oxidative stress in injured proximal tubular epithelial cells. Our study suggests that swine MetS mildly affects renal autophagy, possibly secondary to mitochondrial damage, and may contribute to kidney structural damage in MetS.

The moderate-intensity continuous exercise maintains renal blood flow and does not impair the renal function.

Exercise is restricted for individuals with reduced renal function because exercising reduces blood flow to the kidneys. Safe and effective exercise programs for individuals with reduced renal function have not yet been developed. We previously examined the relationship between exercise intensity and renal blood flow (RBF), revealing that moderate-intensity exercise did not reduce RBF. Determining the effects of exercise duration on RBF may have valuable clinical applications. The current study examined the effects of a single bout of continuous exercise at lactate threshold (LT) intensity on renal hemodynamics. Eight adult males participated in this study. Participants underwent 30 min of aerobic exercise at LT intensity using a cycle ergometer. Evaluation of renal hemodynamics was performed before and after exercise, in the recovery phase using ultrasound echo. Furthermore, blood and urine samplings were conducted before and after exercise, in the recovery phase. Compared with resting, RBF was not significantly changed immediately after continuous exercise (319 ± 102 vs. 308 ± 79 ml/min; p = 0.976) and exhibited no significant changes in the recovery phase. Moreover, urinary kidney injury molecule-1 (uKIM-1) level exhibited no significant change immediately after continuous exercise (0.52 ± 0.20 vs. 0.46 ± 0.27 µg/g creatinine; p = 0.447). In addition, the results revealed no significant change in urinary uKIM-1 in 60-min after exercise. Other renal injury biomarkers exhibited a similar pattern. These findings indicate that a single bout of moderate-intensity continuous exercise maintains RBF and does not induce renal injury.

Estradiol Supplement or Induced Hypertension May Attenuate the Angiotensin II Type 1 Receptor Antagonist-Promoted Renal Blood Flow Response to Graded Angiotensin II Administration in Ovariectomized Rats.

Backgrounds: Estrogen replacement therapy (ERT) and hypertension may influence females' renin-angiotensin system (RAS) and its components. The angiotensin II (Ang II) type 1 receptor (AT1R) antagonist (losartan) may promote renal blood flow (RBF), and it is widely used in the clinic to control hypertension. The main objective of this study was the effects of estradiol or induced hypertension on RBF response to Ang II in losartan-treated ovariectomized (OVX) rats. Methods: Two groups of OVX rats were treated with placebo (group 1) and estradiol (group 2) for period of four weeks, and another group of OVX rats was subjected to induce hypertension by two-kidney one clip (2K1C) model (group 3). All the groups were subjected to the surgical procedure under anesthesia, and AT1R was blocked by losartan. RBF and renal vascular resistance (RVR) responses to Ang II administration were determined and compared. Results: Mean arterial (MAP) and renal perfusion (RPP) pressures in group 3 and uterus weight (UT) in group 2 were significantly more than other groups (P < 0.05). Ang II infusion resulted in dose-related percentage change increase in RBF and decrease in RVR. However, these responses in the OVX-estradiol and OVX-hypertensive rats were significantly lower than in the OVX-control group (P < 0.05). For instance, at the dose of 1000 ng/kg/min of Ang II administration, the percentage change of RBF was 45.1 ± 10.4%, 17.9 ± 2.3%, and 16.7 ± 4.7% in the groups of 1 to 3, respectively. Conclusion: Losartan prescription in some conditions such as hypertension or ERT could worsen RBF and RVR responses to Ang II.

Microvascular remodeling and altered angiogenic signaling in human kidneys distal to occlusive atherosclerotic renal artery stenosis.

BACKGROUND: Renal artery stenosis (RAS) is an important cause of chronic kidney disease and secondary hypertension. In animal models, renal ischemia leads to downregulation of growth factor expression and loss of intrarenal microcirculation. However, little is known about the sequelae of large-vessel occlusive disease on the microcirculation within human kidneys. METHOD: This study included five patients who underwent nephrectomy due to renovascular occlusion and seven nonstenotic discarded donor kidneys (four deceased donors). Micro-computed tomography was performed to assess microvascular spatial densities and tortuosity, an index of microvascular immaturity. Renal protein expression, gene expression and histology were studied in vitro using immunoblotting, polymerase chain reaction and staining. RESULTS: RAS demonstrated a loss of medium-sized vessels (0.2-0.3 mm) compared with donor kidneys (P = 0.037) and increased microvascular tortuosity. RAS kidneys had greater protein expression of angiopoietin-1, hypoxia-inducible factor-1α and thrombospondin-1 but lower protein expression of vascular endothelial growth factor (VEGF) than donor kidneys. Renal fibrosis, loss of peritubular capillaries (PTCs) and pericyte detachment were greater in RAS, yet they had more newly formed PTCs than donor kidneys. Therefore, our study quantified significant microvascular remodeling in the poststenotic human kidney. RAS induced renal microvascular loss, vascular remodeling and fibrosis. Despite downregulated VEGF, stenotic kidneys upregulated compensatory angiogenic pathways related to angiopoietin-1. CONCLUSIONS: These observations underscore the nature of human RAS as a microvascular disease distal to main vessel stenosis and support therapeutic strategies directly targeting the poststenotic kidney microcirculation in patients with RAS.

Effect of Papaverine on Renal Artery Blood Flow during Robot-Assisted Partial Nephrectomy: A Randomized Controlled Study.

BACKGROUND: During robot-assisted partial nephrectomy (RAPN), renal artery clamping is necessary to optimize the surgical field. However, renal artery clamping can induce renal blood flow reduction and postoperative renal dysfunction. Papaverine is used as a potent vasodilator agent. We determined if periarterial administration of papaverine after renal artery clamping improved intraoperative renal artery blood flow and early postoperative glomerular filtration rate (GFR) compared with placebo in RAPN. PATIENTS AND METHODS: In this randomized controlled trial, 96 patients who underwent RAPN were enrolled between November 2019 and December 2020. Patients were administered periarterial normal saline as a placebo (placebo group) or papaverine (papaverine group) just after renal artery declamping. The primary outcome was renal artery blood flow by Doppler ultrasound 2 min after periarterial administration of papaverine or placebo after renal artery declamping. The secondary outcome was GFR estimated by renal scan 3 months after RAPN. RESULTS: Renal artery blood flow and GFR were significantly higher in the papaverine group than in the placebo group (538.0 [376.6-760.0] mL/min versus 338.8 [205.8-603.4] mL/min, P = 0.002 and 93.5 ± 17.1 mL/min/1.73 m2 versus 85.9 ± 15.8 mL/min/1.73 m2, P = 0.033, respectively). CONCLUSIONS: Periarterial papaverine administration increased intraoperative renal artery blood flow and early postoperative GFR in RAPN, suggesting that papaverine administration has beneficial effects on renal perfusion after renal artery clamping and could be a valuable option for improving renal function after RAPN.

Detection of impaired renal allograft function in paediatric and young adult patients using arterial spin labelling MRI (ASL-MRI).

The study aimed to discriminate renal allografts with impaired function by measuring cortical renal blood flow (cRBF) using magnetic resonance imaging arterial spin labelling (ASL-MRI) in paediatric and young adult patients. We included 18 subjects and performed ASL-MRI on 1.5 T MRI to calculate cRBF on parameter maps. cRBF was correlated to calculated glomerular filtration rate (GFR) and compared between patient groups with good (GFR ≥ 60 mL/min/1.73 m2) and impaired allograft function (GFR < 60 mL/min/1.73 m2). Mean cRBF in patients with good allograft function was significantly higher than in patients with impaired allograft function (219.89 ± 57.24 mL/min/100 g vs. 146.22 ± 41.84 mL/min/100 g, p < 0.008), showing a highly significant correlation with GFR in all subjects (r = 0.75, p < 0.0001). Also, the diffusion-weighted imaging (DWI-MRI) apparent diffusion coefficient (ADC) and Doppler measurements of peak-systolic and end-diastolic velocities and the resistive index (PS, ED, RI) were performed and both methods showed no significant difference between groups. ADC implied no correlation with GFR (r = 0.198, p = 0.464), while PS indicated moderate correlation to GFR (r = 0.48, p < 0.05), and PS and ED moderate correlation to cRBF (r = 0.58, p < 0.05, r = 0.56, p < 0.05, respectively). Cortical perfusion as non-invasively measured by ASL-MRI differs between patients with good and impaired allograft function and correlates significantly with its function.

Feasibility of renal perfusion quantification by Fourier decomposition MRI.

PURPOSE: To evaluate the feasibility of perfusion measurements in the human kidney by Fourier decomposition MRI (FD-MRI). METHODS: Renal perfusion measurements by FD-MRI and arterial spin labeling (ASL) were performed using a 1.5 T whole-body MR-scanner (Magnetom Avanto, Siemens Healthineers AG, Germany) in 15 healthy volunteers (mean age 33.0 ± 13.6 years). Five healthy volunteers were measured twice to evaluate the reproducibility. Besides, five patients with renal artery stenosis (RAS) (mean age 58.4 ± 16.2 years) were included in the study to evaluate potential clinical use of the FD-MRI for evaluating renal perfusion. For renal FD-MRI, coronal 2D-TrueFisp sequence (1 section; section thickness: 10 mm; FOV: 400 × 400 mm 2; TR/TE: 2.06/0.89 ms; 250 images; 0,36 s/image), for renal ASL, coronal FAIR-TrueFisp sequence (1 section; section thickness: 10 mm; FOV: 400 × 400 mm2; TR/TE 4.0/2.0 ms, TI 1200 ms, 30 averages; 8,32 s/average) were acquired without any triggering. Perfusion parameter maps of the kidneys were calculated for both methods. After manual segmentation, ROI-based analysis (whole kidney, cortex and medulla, respectively) was performed and the results were subsequently compared using the Student t-test. RESULTS: The acquisition times were 1.30 min and 4.16 min, for renal FD-MRI and ASL, respectively. No significant difference in global renal perfusion (RBF) between both methods was detected (mean RBF in the right kidney: 308.4 ± 31.5 mL/100 mL/min for FD-MRI; 315.2 ± 41.1 for ASL; in the left kidney: 315.6 ± 32.8 mL/100 mL/min for FD-MRI; 310.2 ± 39.1 mL/100 mL/min for ASL, respectively). The results indicated good reproducibility of both considered methods. However, cortico-medullar differentiation was not possible by FD-MRI, probably due to lower SNR compared to ASL. Significant difference in the side-separated RBF were measured by FD-MRI as well as by ASL (p < 0.05) in patients with RAS. CONCLUSIONS: FD-MRI is a novel, rapid approach for contrast-free perfusion quantification in the human kidney. Main advantage of this new method compared to ASL perfusion is the significant shorter acquisition time and lower dependency on patient's compliance. However, lower SNR of FD-MRI needs further improvement to make FD-MRI a competitive alternative to ASL.