Features of renal blood flow in acute kidney injury in premature infants with hemodynamically significant patent ductus arteriosus

Hemodynamically significant patent ductus arteriosus (HSPDA) in premature infants leads to renal hypoperfusion due to the phenomenon of «stealing» of the systemic circulation, which can contribute to the development of acute kidney injury (AKI). The use of ultrasound Doppler sonography of the renal vessels can be effective in assessing renal blood flow and in the early diagnosis of acute renal failure. Purpose — to assess the prognostic significance of the state of renal blood flow in the first day of life in premature infants with HSPDA in the early diagnosis of AKI. Materials and methods. We examined 40 preterm infants (gestational age 29–36 weeks) with HSPDA. Distribution of the examined patients: the group with AKI — 23 children, the group without AKI — 17 children. The observation period was 10 days. The patients underwent echocardiography with Doppler analysis using a broadband microconvex probe with a frequency of 5–8 MHz (TOSHIBA Nemso XG) at 5–11 hours of life. Color Doppler ultrasound scanning of renal vessels was performed on the first, third and tenth days of life. The parameters of blood flow in the main renal and interlobar renal arteries were studied: peak systolic velocity (PSV) and end diastolic velocity (EDV) of blood flow, resistance index (RI). Diagnosis and stratification of AKI severity met the KDIGO neonatal modification criteria. Results. On the third to fifth day of life, AKI was diagnosed in 23 (57.5%) children, but already in the first day of life, compared with patients without AKI, a significant decrease in PSV parameters of blood flow in the main renal artery was noted (20.6±5.87 cm/sec versus 25.4±6.17 cm/sec in children without AKI, p<0.02). In addition, the main changes in the first day of life in patients with AKI were revealed at the level of the interlobar renal artery, namely: a decrease in PSV blood flow (11.10±3.329 cm/sec versus 18.48±3.014 cm/sec in children without AKI, p<0.001) and EDV of blood flow (2.83±2.063 cm/sec versus 6.16±2.447 cm/sec in children without AKI, p<0.001), increased RI (0.758±0.137 versus 0.666±0.1216 in children without AKI, p<0.02). On the third day of life at AKI, there was a disorder in the parameters of blood flow in the interlobaric renal artery, the value of which on the tenth day of life did not differ from the parameters of children without AKI. Conclusions. In premature infants with HSPDA, who were diagnosed with AKI on the third to fifth day of life, in the first day of life, there is a decrease in PSV blood flow parameters in the main renal artery, changes in blood flow in the interlobar renal artery, namely: a decrease in PSV and EDV blood flow, an increase in RI. Thus, the assessment of the state of blood flow in the interlobar renal artery on the first day of life in premature infants with HSPDA is of diagnostic value for the timely determination of the risk group for AKI. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local ethics committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: premature infants, patent ductus arteriosus, renal blood flow, acute kidney injury.

Efficiency of empagliflosin in combined nephroprotective therapy in patients with type 2 diabetes mellitus

INTRODUCTION. The data obtained in clinical studies of recent years of the possible inhibitors of sodium-glucose cotransporter type 2 (SGLT2) nephroprotective effect in type 2 diabetes mellitus necessitate the further study of these drug's effect on kidney injury risk factors.THE AIM: to study the effect of SGLT2 inhibitor empagliflozin as part of combination therapy on the main mechanisms of kidney damage in patients with type 2 diabetes.PATIENTS AND METHODS. We have completed a clinical randomized study in parallel groups in patients with type 2 diabetes of nephroprotective effects of SGLT2 inhibitor empagliflozin during 2 years. The study included 244 patients with type 2 diabetes with a preserved glomerular filtration rate (GFR) and moderate arterial hypertension (AH), who had previously taken perindopril and indapamide, but did not reach target blood pressure (BP) values. Patients were randomized into 2 groups: Group I (n = 120) took Perindopril 10 mg per day, Indapamide retard 1.5 mg per day, β-blocker Carvedilol 12.5-25 mg 2 times a day; Group II (n = 124) was additionally prescribed empagliflozin 25 mg per day. The study endpoints were GFR changes, albuminuria, and renal blood flow as measured by Doppler imaging. Also studied the dynamics of blood pressure and glycemic control.RESULTS. It was found that empagliflozin as part of complex therapy for type 2 diabetes is able to reduce albuminuria and prevent a decrease in GFR within a 2-year follow-up period. The use of empagliflozin promoted an increase in the rate of renal blood flow and a decrease in intrarenal vascular resistance and had a corrective effect on the daily dynamics of blood pressure and glycemic control.CONCLUSION. Empagliflozin improves intrarenal and systemic hemodynamics, prevents a decrease in GFR, reduces albuminuria, and improves glycemic control in type 2 diabetes.

Renal Denervation in Combination With Angiotensin Receptor Blockade Prolongs Blood Pressure Trough During Hemorrhage

Majority of patients with hypertension and chronic kidney disease (CKD) undergoing renal denervation (RDN) are maintained on antihypertensive medication. However, RDN may impair compensatory responses to hypotension induced by blood loss. Therefore, continuation of antihypertensive medications in denervated patients may exacerbate hypotensive episodes. This study examined whether antihypertensive medication compromised hemodynamic responses to blood loss in normotensive (control) sheep and in sheep with hypertensive CKD at 30 months after RDN (control-RDN, CKD-RDN) or sham (control-intact, CKD-intact) procedure. CKD-RDN sheep had lower basal blood pressure (BP; ≈9 mm Hg) and higher basal renal blood flow (≈38%) than CKD-intact. Candesartan lowered BP and increased renal blood flow in all groups. 10% loss of blood volume alone caused a modest fall in BP (≈6–8 mm Hg) in all groups but did not affect the recovery of BP. 10% loss of blood volume in the presence of candesartan prolonged the time at trough BP by 9 minutes and attenuated the fall in renal blood flow in the CKD-RDN group compared with CKD-intact. Candesartan in combination with RDN prolonged trough BP and attenuated renal hemodynamic responses to blood loss. To minimize the risk of hypotension-mediated organ damage, patients with RDN maintained on antihypertensive medications may require closer monitoring when undergoing surgery or experiencing traumatic blood loss.

Comparison of Intra Abdominal Pressure Monitoring Techniques and the Effects of the Abdominal Compartment Syndrome

Background: Abdominal compartment syndrome (ACS) is a life-threatening condition that develops in the setting of increasing and uncontrolled intra-abdominal hypertension (IAH), leading to cardiovascular, respiratory, neurologic and/or renal dysfunction. Aims: To establish a porcine model for the evaluation of the effects of IAH on renal blood flow (RBF) and to determine if IVC pressure and/or Camino fiberoptic direct intraabdominal pressure measurements can accurately predict IAPs that have been derived using bladder pressure measurements. Methods: Abdominal laparotomy, placement of IAP and RBF measuring devices, and fascial closure were performed on six adult feeder pigs with a mean body weight of 25 +/- 5 kg. A Transonic Doppler flow probe, a suprapubic bladder catheter, a Camino fiberoptic probe, and a triple lumen central venous catheter were placed and then baseline measurements were taken of renal blood flow, bladder pressure, direct intra-peritoneal Camino pressure and IVC pressure, respectively. Normal saline was then infused into the abdomen to simulate increasing IAP. Following a 5–10-minute stabilization period, all measurements were again taken. Results: The correlation between IVC pressure and bladder pressure was 0.98, with a mean bias of -0.5 (SD 2.0; 95% CI: -0.9, -0.2). The correlation between direct IAP readings by Camino probe and bladder pressure was 0.91, with a mean bias of -3.9 (SD 4.3; 95% CI: -4.6, -3.2). There was a strong negative correlation (-0.95) between RBF and bladder pressure. At an IAP of 20 mmHg, RBF reduced by an average of 45.4% (95% CI: 40%, 50.8%). Upon abdominal decompression, RBF returned to 66.6% (95% CI: 54.3%, 78.9%) of its baseline value. Conclusions: A porcine model is effective in accurately measuring changes in real time RBF. RBF progressively declines as IAP increases, however upon decompression, it fails to achieve complete recovery. IVC pressure measurements correlate well with, and therefore may substitute, the gold standard bladder pressure measurements as representatives of IAP. Keywords: Abdominal Compartment syndrome, renal blood flow, intrabdominal hypertension, bladder pressure

Pericyte-mediated constriction of renal capillaries evokes no-reflow and kidney injury following ischemia

Acute kidney injury is common, with ~13 million cases and 1.7 million deaths/year worldwide. A major cause is renal ischemia, typically following cardiac surgery, renal transplant or severe hemorrhage. We examined the cause of the sustained reduction in renal blood flow (no-reflow), which exacerbates kidney injury even after an initial cause of compromised blood supply is removed. After 60 min kidney ischemia and 30-60 min reperfusion, renal blood flow remained reduced, especially in the medulla, and kidney tubule damage was detected as Kim-1 expression. Constriction of the medullary descending vasa recta and cortical peritubular capillaries occurred near pericyte somata, and led to capillary blockages, yet glomerular arterioles and perfusion were unaffected, implying that the long-lasting decrease of renal blood flow contributing to kidney damage was generated by pericytes. Blocking Rho kinase to decrease pericyte contractility from the start of reperfusion increased the post-ischemic diameter of the descending vasa recta capillaries at pericytes, reduced the percentage of capillaries that remained blocked, increased medullary blood flow and reduced kidney injury. Thus, post-ischemic renal no-reflow, contributing to acute kidney injury, reflects pericytes constricting the descending vasa recta and peritubular capillaries. Pericytes are therefore an important therapeutic target for treating acute kidney injury.

Renal artery aneurysms

Renal artery aneurysms are a rare condition and are usually found when other abdominal organ diseases are being searched. Among the causes of renal artery aneurysms, atherosclerosis and fibromuscular dysplasia predominate. However, they can also be observed in congenital Ehlers-Danlos syndrome, neurofibromatosis, arteritis, and due to traumatic effects. Most patients have an asymptomatic course of the disease. Literature data suggest slow growth of aneurysms, and their progression is associated with arterial hypertension, absence of wall calcification and pregnancy in young women. The aim of surgical treatment is to prevent aneurysm rupture, eliminate the risk of renal parenchyma embolism and correct arterial hypertension. Most authors believe that surgical treatment is indicated for asymptomatic course of the disease when the aneurysm is over 20 mm in diameter, aneurysm growth is over 5 mm within a year, arterial hypertension resistant to drug therapy, renal artery dissection and aneurysm presence in women of childbearing age. There are a number of surgical and endovascular techniques to restore renal blood flow. Both open and endovascular interventions are used for renal artery trunk surgery. For aneurysms of the renal artery branches, aortorenal shunting by autovenous or internal iliac artery as well as extracorporeal surgeries are more often used. The use of endografts is most appropriate for localization of aneurysms in the renal artery trunk, while embolization with microspirals and glue is most effective for saccular aneurysms. The embolization technique can cause embolization of the renal parenchyma itself as a potential complication, which aggravates arterial hypertension. The authors present the literature and their own data on various techniques to restore the renal blood flow. Up to 80-90% of the operated kidneys can be saved in the long term. Reconstructive surgery reduces the level of arterial pressure and reduces the number of antihypertensive drugs used and the need for renal replacement therapy.

Effects of levosimendan on renal blood flow and glomerular filtration in patients with acute kidney injury after cardiac surgery: a double blind, randomized placebo-controlled study

Background Acute kidney injury (AKI) is a common and serious complication after cardiac surgery, and current strategies aimed at treating AKI have proven ineffective. Levosimendan, an inodilatating agent, has been shown to increase renal blood flow and glomerular filtration rate in uncomplicated postoperative patients and in patients with the cardiorenal syndrome. We hypothesized that levosimendan through its specific effects on renal vasculature, a preferential vasodilating effect on preglomerular resistance vessels, could improve renal function in AKI-patients with who did not have clinical indication for inotropic support. Methods In this single-center, double-blind, randomized controlled study, adult patients with postoperative AKI within 2 days after cardiac surgery, who were hemodynamically stable with a central venous oxygen saturation (ScvO2) ≥ 60% without inotropic support were eligible for inclusion. After randomization, study drug infusions, levosimendan (n = 16) or placebo (n = 13) were given for 5 h. A bolus infusion of levosimendan (12 µg/kg), were given for 30 min followed by 0.1 µg/kg/min for 5 h. Renal blood flow and glomerular filtration rate were measured using infusion clearance of para-aminohippuric acid and a filtration marker, respectively. As a safety issue, norepinephrine was administered to maintain mean arterial pressure between 70–80 mmHg. Intra-group differences were tested by Mann–Whitney U-tests, and a linear mixed model was used to test time and group interaction. Results Twenty-nine patients completed the study. At inclusion, the mean serum creatinine was higher in the patients randomized to levosimendan (148 ± 29 vs 127 ± 22 µmol/L, p = 0.030), and the estimated GFR was lower (46 ± 12 vs 57 ± 11 ml/min/1.73 m2, p = 0.025). Levosimendan induced a significantly (p = 0.011) more pronounced increase in renal blood flow (15%) compared placebo (3%) and a more pronounced decrease in renal vascular resistance (− 18% vs. − 4%, respectively, p = 0.043). There was a trend for a minor increase in glomerular filtration rate with levosimendan (4.5%, p = 0.079), which did differ significantly from the placebo group (p = 0.440). The mean norepinephrine dose was increased by 82% in the levosimedan group and decreased by 29% in the placebo group (p = 0.012). Conclusions In hemodynamically stable patients with AKI after cardiac surgery, levosimendan increases renal blood flow through renal vasodilatation. Trial registration NCT02531724, prospectly registered on 08/20/2015. https://clinicaltrials.gov/ct2/show/NCT02531724?cond=AKI&cntry=SE&age=1&draw=2&rank=1