Background:Systolic anterior motion (SAM) of the mitral valve is a hallmark feature of hypertrophic obstructive cardiomyopathy (HOCM) and a primary cause of dynamic left ventricular outflow tract obstruction. This case report highlights an unusual presentation of SAM associated with acute haemodynamic collapse. Case summary:A 36-year-old male with HOCM presented with recurrent episodes of syncope. After a multidisciplinary evaluation, he underwent percutaneous intramyocardial septal radiofrequency ablation (PIMSRA). Approximately 1-h post-procedure, the patient developed severe haemodynamic collapse. Transthoracic echocardiography revealed abnormal proximal displacement of the anterior mitral valve leaflet, bringing it into close proximity with the septum. The patient was treated emergently with high-dose intravenous norepinephrine, stabilizing his condition. At the 18-month follow-up, the patient reported no recurrence of syncope. Discussion:Proximal displacement of the anterior mitral leaflet, a rare and severe form of SAM, is an uncommon yet critical complication associated with haemodynamic collapse and syncope. This phenomenon warrants heightened attention during PIMSRA for the treatment of HOCM.

The pathogenesis of ischemic acute kidney injury remains unclear. Red blood cell (RBC) trapping presents as the accumulation of many, tightly packed, RBC in the outer-medullary plexus and is a hallmark of ischemic AKI. We have recently reported that extravasation of toxic heme from the RBC congested medullary capillaries is a cause of tissue injury. This suggests that preventing RBC trapping from occurring may limit tissue injury. The pathogenesis of RBC trapping, however, is poorly understood. While it is clear that RBC trapping occurs in response to occlusion of vessels that drain the renal medulla, the location, as well as the nature of the occlusion, remain unknown. The current study was designed to identify the location of the obstruction responsible for RBC trapping in the rat kidney following ischemia/reperfusion. Our study was performed in 10–12-week-old male and female Sprague Dawley rats. Rats were anesthetized with isoflurane (2-5%) and body temperature maintained at 37°C using a heated table and UV lamp. Flank incisions were performed, and renal ischemia caused by placing a clamp on one of the renal arteries for 45 minutes followed by a 1-hour reperfusion period. The contralateral kidney was used as a non-ischemic control. At the end of the reperfusion period, kidneys were harvested for histological analysis. To identify the location of the vascular obstruction in the kidney, prior to the end of the ischemic period, either 50mg/kg of the plasma protein marker Evans blue or the lipid dye Vybrant DIL (0.12mg) was injected into the tail vein. In non-ischemic control kidneys, both the cortical and medullary vasculature was stained. In contrast, following 1-hour of reperfusion from ischemia, the majority of the cortical glomeruli were unstained, suggesting poor re-flow in this region. In contrast the juxtamedullary glomeruli that supply the medulla with blood were stained, indicating reperfusion of these vessels. In kidneys in which significant RBC trapping occurred, tightly packed RBCs were observed in both the vasa recta bundles and surrounding outer-medullary plexus capillaries. RBC in the vasa recta bundles stained positive, indicating these RBC had entered the kidney on reperfusion. In contrast, most of the RBCs in the capillary plexus were unstained. The interlobular and arcuate veins that drain the outer medulla often contained what appeared to be sludged blood, which was unstained, indicating these vessels had not reperfused. In many cases, however, an internal core of tightly packed stained RBC could be observed within the center of these vessels, indicating that the obstruction had occurred further downstream. In some animals tightly packed, stained RBC could be observed as far downstream as the large interlobar and segmental veins. In these examples, trapped RBC were surrounded by a homogeneous material, devoid of significant structure or cells. Our data indicate that venous obstruction leading to RBC trapping is localized to the large veins of the kidney which drain both the cortex and medulla. The absence of RBC trapping in the cortex is likely due to failure of this region to reperfuse while the obstruction is present. The nature of the obstruction remains unclear. In some cases, unstained sludged blood appeared to line the vascular wall, perhaps preventing smaller veins from draining. In many cases, however, a homogeneous material, largely devoid of cells, appeared to prevent the flow of blood through the large renal veins. Further studies are required to identify the nature of the material obstructing the large veins following ischemia. NIDDK 1R01DK138150-01A1 to Paul O'Connor AHA Transformational Project Award to Paul O'Connor APS SURF fellowship to Angela Ajith This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

The pathogenesis of ischemic acute kidney injury remains unclear. While tissue injury in ischemic AKI is currently thought to result primarily from hypoxia, we have argued that most injury may be secondary to transient venous obstruction at the onset of reperfusion, which results in the extravasation of plasma and toxic heme proteins into the surrounding tissue. Consistent with this, the weight of ischemic kidneys is known to be increased, however, it is unknown if this increase in kidney weight occurs at the onset of reperfusion or later as part of an inflammatory response. In the current study, we tested the hypothesis that extravasation of plasma occurs at the onset of reperfusion, resulting in rapid increases in kidney volume and interstitial pressure, prior to initiation of an inflammatory response. Our study was performed in 10–12-week-old male and female Sprague Dawley rats. Rats were anesthetized with isoflurane (2-5%). In experiment 1 (n=18), a midline incision was performed and a loose tie placed around the abdominal aorta superior to the left renal artery. The wound was then closed, and the left kidney imaged by ultrasound (Vevo3100). Rats were maintained at 37°C using a heated table and UV lamp. After a baseline period, the left kidney was made ischemic for 45 minutes by retracting the tie around the aorta before releasing the tie for a further 1-hour reperfusion period. 3D scans of the kidney were performed to determine kidney volume and percent vascularity (Doppler positive) at baseline, at the initiation of ischemia, at the end of ischemia, at the initiation of reperfusion and at 1 hour of reperfusion before the animals were humanely sacrificed and kidneys taken for histology. In experiment 2, flank incisions were performed and renal ischemia caused by placing clamps on both renal arteries. Prior to the end of the ischemic period, 50mg/kg of the plasma protein marker Evans blue was injected into the tail vein. Following reperfusion, urine was collected from the bladder and the kidneys harvested for histology. Experiment 3, mirrored experiment 2, except the left kidney was placed in a cup to prevent kidney movement and a pressure probe inserted into the kidney (Mikro-tip, Millar) to measure interstitial pressure. At baseline kidney volume averaged 616mm 3 and vascularity was 11.45% of kidney volume. Kidney volume decreased to 413mm 3 and vascularity to 3.6% at the onset of ischemia. Kidney volume increased across the ischemic period to 568mm 3 while vascularity remained at 3.7%. At the onset of reperfusion there was an initial decline in kidney volume to 542mm3 before increasing to 643mm 3 by 1-hour post-reperfusion. Vascularity at the onset of reperfusion was 7.8% before increasing to baseline levels at 1-hour post reperfusion. Kidneys with the greatest % increase in volume on reperfusion has significantly greater tubular injury than those that remained near baseline levels. Consistent with the increase in kidney volume resulting from extravasation of plasma, kidneys with large increase in volume demonstrated significant extravasation of Evan’s blue labelled blood proteins, with the surface of the kidney turning dark blue. Changes in interstitial pressure were consistent with the volume changes observed. Our data indicate that there is significant extravasation of blood proteins into the renal parenchyma at the onset of reperfusion and that this results in marked increases in kidney volume and pressure. As this occurs prior to the infiltration of significant numbers of immune cells, and kidneys with the largest increases in volume had the most severe tubular injury, these results are consistent with venous obstruction at the onset of reperfusion as a primary cause of cortical edema and tubular injury. NIDDK 1R01DK138150-01A1 to Paul O'Connor AHA Transformational Project Award to Paul O'Connor APS SURF fellowship to Angela Ajith This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Warm arterial clamping with reperfusion in rats is a commonly utilized model of ischemic kidney injury (IRI). Traditionally, changes in plasma creatinine or creatinine clearance have been utilized to assess kidney function in this model. A limitation of these approaches, however, is that changes in plasma creatinine are relatively slow to occur, resulting in low temporal fidelity. This limits our ability to relate changes in kidney function to histo-pathological changes observed during reperfusion of the kidneys. Transcutaneous assessment of FITC-sinistrin clearance enables accurate, repeated measurement of glomerular filtration rate in conscious animals over short segments of time (hours) without drawing blood. The goal of the current study was to characterize temporal changes in renal function in male and female rats after reperfusion from bi-lateral warm arterial clamp ischemia using transcutaneous FITC-sinistrin clearance. Our study was performed in age matched male (n=8) and female (n=5) Sprague Dawley rats (12-20wks of age). FITC sinistrin clearance was measured by affxing a miniaturized transcutaneous measurement device between the shoulder blades (MediBeacon) of rats. 50mg/kg of FITC-sinistrin was then injected i.v via the tail vein and the device allowed to record for ~3 hours. Measurements were taken either at pre-surgery (baseline), 1-3 hours, 24 hours or 7 days following reperfusion of the kidneys from warm bilateral arterial clamp ischemia. For the ischemic surgery, animals were anesthetized with isoflurane (2-5%, 95% O2) and the right and left kidneys were accessed by flank incisions. After being exposed, the renal arteries were separated from the renal veins via dissection. Both renal arteries were then clamped with microserrefines for 45 minutes. After the ischemic period, the clamps were removed, allowing blood flow to be restored to the kidneys. Body temperature was measured via a rectal probe and maintained at 37°C throughout the procedure by a servo-controlled heating table and UV heating lamp. The wounds were then closed, and the animals allowed to recover. Buprenorphine was administered as an analgesic. For each measurement, the ½ life of FITC sinistrin was determined using a 1-compartment model (MB Lab software) and glomerular filtration rate (GFR) per 100g of body weight rate calculated. Baseline GFR was 0.94±0.03ml/min/100g in males and 1.09±0.02/min/100g in females (PTTEST=0.04). Following 45 minutes of warm bilateral arterial ischemia and reperfusion, GFR fell to 0.24±0.08ml/min/100g in male and 0.36±0.15ml/min/100g in females within 1-3 hours of reperfusion. At 24 hours of reperfusion, GFR averaged 0.06±0.03ml/min/100g in males and 0.28±0.16ml/min/100g in females. GFR recovered in males and females by 7 days of reperfusion averaging 0.86±0.10ml/min/100g in males and 0.83±0.00ml/min/100g in females. There was no significant difference between FITC-sinistrin clearance between males and females at any time point after IRI. Our data indicate that most of the reduction in GFR is present immediately after releasing the clamp. This is consistent with continued vascular disturbances mediating the initial decline in glomerular filtration rate in this model (i.e. vasospasm). The absence of sex differences in GFR decline using this method suggests that sex-differences detected using plasma creatinine may be, at least in part, secondary to the more rapid production of creatinine in males than in females or greater baseline filtration/body weight ratio in females compared to males rather than differences in renal function decline to ischemia. American Heart Association Transformational Project Award 970585 to Paul O'Connor. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sodium bicarbonate (NaHCO3) is commonly utilized as a therapeutic to treat metabolic acidosis in people with chronic kidney disease (CKD). While increased dietary sodium chloride (NaCl) is known to promote volume retention and increase blood pressure, the effects of NaHCO3 loading on blood pressure and volume retention in CKD remain unclear. In the present study, we compared the effects of NaCl and NaHCO3 loading on volume retention, blood pressure, and kidney injury in both 2/3 and 5/6 nephrectomy remnant kidney rats, a well-established rodent model of CKD. We tested the hypothesis that NaCl loading promotes greater volume retention and increases in blood pressure than equimolar NaHCO3. Blood pressure was measured 24 h daily using radio telemetry. NaCl and NaHCO3 were administered in drinking water ad libitum or infused via indwelling catheters. Rats were housed in metabolic cages to determine volume retention. Our data indicate that both NaHCO3 and NaCl promote hypertension and volume retention in remnant kidney rats, with salt-sensitivity increasing with greater renal mass reduction. Importantly, while NaHCO3 intake was less pro-hypertensive than equimolar NaCl intake, NaHCO3 was not benign. NaHCO3 loading significantly elevated blood pressure and promoted volume retention in rats with CKD when compared with control rats receiving tap water. Our findings provide important insight into the effects of sodium loading with NaHCO3 in CKD and indicate that NaHCO3 loading in patients with CKD is unlikely to be benign.

Abstract Red blood cell (RBC) trapping is common in ischemic acute kidney injury (AKI) and presents as densely packed RBCs that accumulate within and engorge the kidney medullary circulation. In this study, we tested the hypothesis that “RBC trapping directly promotes tubular injury independent of extending ischemia time.” Studies were performed on rats. Red blood cell congestion and tubular injury were compared between renal arterial clamping, venous clamping, and venous clamping of blood-free kidneys. Vessels were occluded for either 15 or 45 min with and without reperfusion. We found that RBC trapping in the medullary capillaries occurred rapidly following reperfusion from renal arterial clamping and that this was associated with extravasation of blood from congested vessels, uptake of blood proteins by the tubules, and marked tubular injury. To determine if this injury was due to blood toxicity or an extension of ischemia time, we compared renal venous and arterial clamping without reperfusion. Venous clamping resulted in RBC trapping and marked tubular injury within 45 min of ischemia. Conversely, despite the same ischemia time, RBC trapping and tubular injury were minimal following arterial clamping without reperfusion. Confirming the role of blood toward tubular injury, injury was markedly reduced in blood-free kidneys with venous clamping. Our data demonstrate that RBC trapping results in the rapid extravasation and uptake of blood components by tubular cells, causing toxic tubular injury. Tubular toxicity from extravasation of blood following RBC trapping appears to be a major component of tubular injury in ischemic AKI, which has not previously been recognized.

Despite receiving approximately 20% of cardiac output, the kidneys are highly susceptible to ischemic injury, which is most prominent in the renal outer medulla. Previous studies have suggested that vascular congestion may explain the susceptibility of this region to injury. Further, increased injury has been reported in models where the renal vein is occluded compared to the renal artery. The goal of the current study was to determine whether renal arterial versus venous clamping would alter the severity of red blood cell congestion in the outer medulla. We hypothesized that venous clamping would result in greater vascular congestion than arterial clamping due to continued inflow of arterial blood. Ischemia reperfusion (IR) surgeries were performed on male and female WKY rats (10-14 weeks). For each animal, the renal artery for one kidney and renal vein for the other kidney were clamped for a period 15 (n=7 male, 6 female) or 45 (n= 6 male, 5 female) minutes. The kidneys (right or left) which received arterial or venous clamping were rotated for each animal. Following ischemia, the kidneys were excised while the clamps remained on the vessels, without reperfusion. Vascular congestion of the outer medulla was scored blinded on a scale of 0 (0% congestion) to 5 (100% congestion) in trichrome stained kidneys sections. We found that there was significantly greater congestion of red blood cells in both the vasa recta and outer-medullary plexus with venous clamping when compared to arterial clamping for both 15 minutes (p=0.0008, p<0.0001, respectively) (Fig. A) and 45 minutes (p=0.0001, p<0.0001, respectively) (Fig. B). There was no significant effect of sex observed on degree of vascular congestion regardless of the location or duration of the clamp. Our data indicates that red blood cell congestion is exacerbated by renal venous occlusion, which may explain the increased tubular injury that has been observed in this model. Therefore, future studies will investigate injury following recovery from renal artery versus vein clamping. Understanding the cause(s) of vascular congestion is essential for the development of clinically effective treatment options for acute kidney injury. Novel therapeutic approaches that prevent or reverse red blood cell congestion of the renal medulla may be effective in limiting ischemic acute kidney injury.

ABSTRACT Vascular congestion is common in ischemic acute kidney injury (AKI) and represents densely packed red blood cells (RBC) in the kidney circulation. In this study we tested the hypothesis that ‘vascular congestion directly promotes tubular injury’. Studies were performed in male and female Wistar-Kyoto rats. Vascular congestion and tubular injury were examined between renal venous clamping, arterial clamping and venous clamping of blood perfused and blood free kidneys. Vessels were occluded for either 15 or 45 minutes without reperfusion. We found that venous clamping resulted in greater vascular congestion than arterial clamping, particularly in the outer-medullary region (P<0.001). Venous clamping resulted in significant tubular injury, including cell swelling, tubular degeneration and luminal cast formation following as little as 15 minutes of occlusion. Tubular injury was significantly less following arterial clamping (P<0.001). Numerous red droplets were observed within tubular cells which were most prominent following venous clamping. Electron microscopy and immunohistochemistry identified these as derived from RBCs and indicated that RBCs from congested renal capillaries were extravasated and phagocytosed by tubular cells. CD235a staining confirmed tubular uptake and secretion of RBCs. Cast formation and tubular swelling were absent from blood free kidneys following venous clamping (P<0.001). Our data demonstrate that congestion of the kidney results in the rapid, mass extravasation and uptake of RBCs by tubular cells causing toxic injury to the tubules. Tubular toxicity from extravasation of RBCs appears to be a major component of tubular injury in ischemic AKI which has not previously been recognized.

Background Vascular congestion of the renal medulla & mdash;trapped red blood cells in the medullary microvasculature & mdash;is a hallmark finding at autopsy in patients with ischemic acute tubular necrosis. Despite this, the pathogenesis of vascular congestion is not well defined.& nbsp;Methods In this study, to investigate the pathogenesis of vascular congestion and its role in promoting renal injury, we assessed renal vascular congestion and tubular injury after ischemia reperfusion in rats pretreated with low-dose LPS or saline (control). We used laser Doppler flowmetry to determine whether pretreatment with low-dose LPS prevented vascular congestion by altering renal hemodynamics during reperfusion.& nbsp;Results We found that vascular congestion originated during the ischemic period in the renal venous circulation. In control animals, the return of blood flow was followed by the development of congestion in the capillary plexus of the outer medulla and severe tubular injury early in reperfusion. Laser Doppler flowme-try indicated that blood flow returned rapidly to the medulla, several minutes before recovery of full cortical perfusion. In contrast, LPS pretreatment prevented both the formation of medullary congestion and its associated tubular injury. Laser Doppler flowmetry in LPS-pretreated rats suggested that limiting early reperfusion of the medulla facilitated this protective effect, because it allowed cortical perfusion to recover and clear congestion from the large cortical veins, which also drain the medulla.& nbsp;Conclusions Blockage of the renal venous vessels and a mismatch in the timing of cortical and medullary reperfusion results in congestion of the outer medulla's capillary plexus and promotes early tubular injury after renal ischemia. These findings indicate that hemodynamics during reperfusion contribute to the renal medulla's to ischemic injury.

Vascular congestion, or red blood cell (RBC) trapping, of the renal outer medulla (OM) is a common finding in acute tubular necrosis caused by ischemia reperfusion (IR). Work from our laboratory suggests that vascular congestion originates in the renal venous vasculature of the cortex and OM during the ischemic phase. Following reperfusion, RBCs then fill the OM plexus capillaries as the venous drainage vessels of this region remain blocked. We have also previously reported that pretreatment with low dose lipopolysaccharide (LPS) attenuates IR‐induced vascular congestion, however the mechanisms remain unknown. In the current study, we hypothesized that pretreatment with LPS prevents vascular congestion by delayed reperfusion of blood to the OM following ischemia.

BACKGROUND:World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) is a progressive, debilitating disease. Previous observational studies have demonstrated that pulmonary artery denervation (PADN) reduces pulmonary artery pressures in PAH. However, the safety and effectiveness of PADN have not been established in a randomized trial. OBJECTIVES:The aim of this study was to determine the treatment effects of PADN in patients with group 1 PAH. METHODS:Patients with WHO group 1 PAH not taking PAH-specific drugs for at least 30 days were enrolled in a multicenter, sham-controlled, single-blind, randomized trial. Patients were assigned to receive PADN plus a phosphodiesterase-5 inhibitor or a sham procedure plus a phosphodiesterase-5 inhibitor. The primary endpoint was the between-group difference in the change in 6-minute walk distance from baseline to 6 months. RESULTS:Among 128 randomized patients, those treated with PADN compared with sham had a greater improvement in 6-minute walk distance from baseline to 6 months (mean adjusted between-group difference 33.8 m; 95% CI: 16.7-50.9 m; P < 0.001). From baseline to 6 months, pulmonary vascular resistance was reduced by -3.0 ± 0.3 WU after PADN and -1.9 ± 0.3 WU after sham (adjusted difference -1.4; 95% CI: -2.6 to -0.2). PADN also improved right ventricular function, reduced tricuspid regurgitation, and decreased N-terminal pro-brain natriuretic peptide. Clinical worsening was less (1.6% vs 13.8%; OR: 0.11; 95% CI: 0.01-0.87), and a satisfactory clinical response was greater (57.1% vs 32.3%; OR: 2.79; 95% CI: 1.37-5.82) with PADN treatment during 6-month follow-up. CONCLUSIONS:In patients with WHO group 1 PAH, PADN improved exercise capacity, hemodynamic status, and clinical outcomes during 6-month follow-up. (Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension [PADN-CFDA]; NCT03282266).

Introduction:Patients with late-onset transthyretin Val30Met-associated hereditary transthyretin amyloidosis (hATTR) in non-endemic areas still remain undiagnosed because of diverse clinical presentations and various non-specific symptoms. Case Presentation:A 76-year-old male patient presented with progressive numbness, pain and weakness in his limbs, sweating, constipation and unexplained weight loss over the past seven years. He has shortness of breath, edema and hypotension for one month. The low QRS voltage on limb leads was not consistent with left ventricular hypertrophy, which is an important clue of cardiac amyloidosis (CA). The results of echocardiography speckle tracking imaging were consistent with CA. Serum immunofixation electrophoresis was negative, and serum-free light chain Fκ/Fλ ratio is normal or close to normal (0.26-1.65) for the patient, so AL amyloidosis can be excluded. A missense mutation c. 148 G-A Val30Met (p.Val50Met) was detected in TTR gene sequencing. The genetic finding confirmed hATTR Val30Met, familial amyloid polyneuropathy (FAP) and CA for the patient. The treatment effect was poor, and he died of cardiac involvement. Conclusion:It is challenge to make early diagnosis in patients with hATTR, due to the diversity of symptoms. Echocardiography is a vital tool in initial diagnosis. Genetic testing played vital roles in the definitive diagnosis of this disease. Raising awareness is critical for early diagnosis and provides opportunities for early treatment.

The aggregation of red blood cells in the microvascular of the renal medulla is a hallmark of ischemic acute kidney injury (AKI). Our lab has recently shown that pretreatment with low dose lipopolysaccharide (LPS) prior to ischemia‐reperfusion (IR) prevents this vascular congestion. It remains unknown, however, whether prevention of medullary vascular congestion improves recovery from IR. The goal of the current study was to test the hypothesis that ‘prevention of vascular congestion with low dose LPS improves functional recovery of the kidney and attenuates rarefaction of the renal medulla following IR’.

Over the past decade there has been increasing support for a role of the immune system in the development of hypertension. Our lab has previously reported that female spontaneously hypertensive rats (SHR) have a blood pressure (BP)-dependent increase in anti-inflammatory renal regulatory T cells (Tregs), corresponding to lower BP compared to males. However, little is known regarding the mechanism for greater renal Tregs in females. The current study was designed to test the hypothesis that the greater relative abundance of renal Tregs in female SHR is due to greater Treg production. To test this hypothesis, T cell profiles were measured in the spleen by flow cytometry in male and female SHR at 5 weeks and 14 weeks of age.  Splenic Tregs did not differ between males and females, suggesting sex differences in renal Tregs is not due to differences in production. To assess the role of the spleen in sex differences in renal Tregs and BP control, rats were randomized to receive sham surgery (CON) or splenectomy (SPLNX, n=6) at 12 wks of age and implanted with telemeters to measure BP. After 2 weeks, kidneys were harvested for flow cytometric analysis of T cells. Splenectomy increased BP in both sexes after 2 weeks. Renal Tregs decreased in both sexes after splenectomy, abolishing the sex differences in renal Tregs. In conclusion, splenic Tregs were comparable in male and female SHR, suggesting that sex differences in renal Tregs is due to differences in renal Treg recruitment, not Treg production.

Over the past decade there has been increasing support for a role of the immune system in the development of hypertension. Our lab has previously reported that female spontaneously hypertensive rats (SHRs) have a blood pressure (BP)-dependent increase in anti-inflammatory renal regulatory T cells (Tregs), corresponding to lower BP compared with males. However, little is known regarding the mechanism for greater renal Tregs in females. The current study was designed to test the hypothesis that the greater relative abundance of renal Tregs in female SHR is due to greater Treg production. To test this hypothesis, T cell profiles were measured in the spleen by flow cytometry in male and female SHR at 5 and 14 weeks of age. Splenic Tregs did not differ between males and females, suggesting sex differences in renal Tregs is not due to differences in production. To assess the role of the spleen in sex differences in renal Tregs and BP control, rats were randomized to receive sham surgery (CON) or splenectomy (SPLNX) at 12 weeks of age and implanted with telemeters to measure BP. After 2 weeks, kidneys were harvested for flow cytometric analysis of T cells. Splenectomy increased BP in both sexes after 2 weeks. Renal Tregs decreased in both sexes after splenectomy, abolishing the sex differences in renal Tregs. In conclusion, splenic Tregs were comparable in male and female SHRs, suggesting that sex differences in renal Tregs is due to differences in renal Treg recruitment, not Treg production.

Impairments in insulin sensitivity can occur in patients with chronic kidney disease, and previous work has suggested that metabolic acidosis may be the underlying cause. Our study investigated the effect of acid or alkali loading on insulin sensitivity in a rodent model of chronic kidney disease. We found that renal mass reduction increases the blood glucose response to insulin and that this is not acutely reversed by the development of acidosis.

Acute kidney injury (AKI) is common and has a mortality rate as high as 60%. Vascular congestion is a hallmark of AKI and is the aggregation of red blood cells (RBC) in the capillaries of the renal medulla following ischemia. Studies have shown that the severity of vascular congestion directly correlates with the recovery of renal function following ischemia. We recently reported that pretreatment with low dose lipopolysaccharide (LPS) attenuates vascular congestion following ischemia‐reperfusion injury (IRI) in rats. It remains unknown, however, if LPS prevents the formation of congestion or aids in the clearance of congestion following reperfusion. We hypothesized that ‘low dose LPS stimulates the clearance of RBC aggregates during early reperfusion’. To test this hypothesis, male WKY rats (10wks) were pretreated (i.p) with 1000μg/kg LPS (serotype O111:B4) or saline daily for 3 days. Following pretreatment, a 45‐minute warm, bilateral ischemia was performed. Rats were randomized to either 0, 1, 2, 6, 10, or 24 hour(s) of reperfusion (n=4/group). Following reperfusion, blood was collected for measurement of erythrocyte sedimentation rate (ESR). Congestion of the medullary vasa recta (VR) and peritubular (PT) capillaries was assessed in histological sections (blinded, scale: 0–5, 0=0% congestion, 5=100% congestion). Medullary VR congestion was not different between saline and LPS treated rats at time 0 (no reperfusion) with a score of 4 (80%) for both. Following reperfusion for 1, 2, 6, and 10 hours, VR congestion in saline treated rats remained elevated (average score: 4.09). In contrast, in LPS treated rats, VR congestion rapidly declined (within 1 hour), such that between 1–10 hours of reperfusion VR congestion averaged 1.89 (pTREATMENT<0.0001). PT congestion was minimal for both saline and LPS treated rats at time 0 (no reperfusion) but rapidly increased in saline treated rats to >60% at 6 hours. Conversely, in LPS treated rats PT congestion remained low (average 13.4%, pINTERACTION=0.0144) across the 24 hour reperfusion period. In saline treated rats, ESR, which is a marker of inflammation, was less than 2mm at 1–10 hours of reperfusion but increased to 7mm at 24 hours post‐ischemia. In LPS treated rats, ESR increased in a time dependent manner from 0mm at time 0 to 10mm at 24 hours (pTREATMENT<0.0001). We recently reported that pretreatment with LPS reduced vascular congestion 24 hours following ischemia‐reperfusion, however it was unclear whether LPS prevents the development of congestions or contributes to a quicker reperfusion. In this study, we tracked congestion following different hour(s) of reperfusion and found that LPS aids in flushing the VR following reperfusion which prevents the development of PT congestion. We speculate the early immune response evoked by LPS pretreatment, evident by ESR, is responsible for the rapid clearance of congestion in these animals. Understanding the mechanism by which LPS promotes this protective response to attenuate renal medullary congestion following ischemia may provide new methods to improve recovery and mortality rate from ischemic AKI.