Renal Congestion Research Articles

Pathophysiology of Cardiorenal Syndrome and Use of Diuretics and Ultrafiltration as Volume Control.

Acute or chronic dysfunction of the heart or kidneys can cause dysfunction of other organs. This interaction between the heart and kidneys is characterized as cardiorenal syndrome (CRS). Recently, a preponderance of data indicated that venous congestion plays an important role in the combination of renal and cardiac diseases. This review aims to focus on the pathophysiology of venous congestion that leads to renal impairment in heart failure and the use of diuretics or ultrafiltration as decongestive therapy in CRS. We found that although clinical studies have confirmed that decongestive therapy has a definite role in decreasing volume overload and the consequent symptom improvement in patients with CRS, the impact of diuretics or ultrafiltration on the improvement of kidney function or mortality remains uncertain. A precise assessment of volume status is required to determine the adequacy of decongestion. Objective measures of renal venous congestion may be a future metric to assess the adequacy of the diuretic response in patients and guide therapeutic decision making.

Chemodectoma in a Dog

Background: The chemodectoma is a rare neoplasm that originates from chemoreceptors located mainly in the aortic body, and carotid body and sinus, and responsible for detecting variations in blood pH, oxygen pressure and carbon dioxide. Dogs of brachiocephalic breeds and aged between 7 and 15 years have greater propensity. A neoplasm involves infiltrative growth in the vessels at the heart base, which leads to Congestive Heart Failure (CHF). The definitive diagnosis is performed by histopathological and/or immunohistochemical examination. The aim was to report a case of chemiodectoma in a dog, showed the disease clinical characteristics.Case: A 13-year-old male undefined breed dog was examinated in the medical clinic of small animal of Veterinary Hospital, Federal Rural University of Pernambuco (UFRPE) with respiratory effort, hyporexia, and edema in face, cervical, ventral thorax and thoracic limbs, with thirty days evoluted. About physical examination, we observed cachexia, orthopneic position, cyanosis and edema with a positive Godet sign, as well as 8% dehydration degree. Thoracic auscultation presented mixed dyspnea and muffled heart sounds. Chest radiography detected an radiopacity increase in pulmonary section and metastatic neoplastic process associated with pleural and pericardial effusion. Fluid therapy with lactated ringer and posterior thoracentesis in the right hemithorax region was performed for greater respiratory comfort for the patient. Hematological count and biochemical profiles stated normochromic normocytic anemia, relative and absolute lymphopenia, thrombocytopenia, as well as increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The patient died after 12 hours when was submitted to necroscopic examination and histopathological evaluation. An infiltrative tumor of cardiac base was observed invading the light of the right atrium, obstructing the venous return, as well as a large thrombus located in the left ventricle and diffuse nodules in the lungs. Hydrothorax and hydroperitoneum were observed with serous fluid, with hepatic, renal and brain congestion, and duodenum hemorrhage. Histologically, the tumor was characterized as a chemodectoma with pulmonary metastasis.Discussion: Cardiac tumors are uncommon for canine population. A study sampled 729,265 dogs with observed incidence reaching 0.19%. The most common type is hemangiosarcoma with 69%, followed by chemiodectoma and lymphoma. Authors describe predisposed brachycephalic breeds such as Boxer, Boston Terrier and French Bulldog. In our case, the patient had elongated snout and undefined breed. Deregulation of chemoreceptors, which detect changes in pH and partial oxygen and carbon dioxide pressures, can result in hyperpnea and dyspnoea. Edema represents a deficit in venous return from the cranial and cervical regions, with consequent increase in hydrostatic pressure and liquid leakage into the thoracic cavity and subcutaneous tissue, thus inferring the Caudal Vena Cava Syndrome (CVCS). Tumors from the cardiac base, integrated with the large arteries insertion and adjacent to the atria, can cause pericardial effusion observed in this case. Chemodectomas are described as essentially benign tumors with low metastatic potential. In this case, pulmonary metastasis was detected. Surgical treatment is recommended when feasible. In this case, the patient had late veterinary care, in addition to the contraindication for surgery by the lung metastasis presence.

INQUISITION OF CARDIOPULMONARY AND KIDNEY LESIONS PRODUCED BY NATURAL PERACUTE AND ACUTE CLOSTRIDIUM TYPE D ENTEROTOXEMIA IN CHINKARA DEER

This study describes the clinical signs, postmortem lesions and histopathological findings in chinkara deer died during an outbreak of enterotoxaemia. The study included 7 chinkara deer. During the outbreak, 5 chinkara deer died without clinical signs while 2 chinkara deer showed clinical signs before death. Clinical signs including greenish watery diarrhea, chocolate colored urine, herding in a corner with head down, fever, anorexia and opisthotonos. After death of these 7 deer, necropsy performed and observed soft and swollen kidneys, straw color fluid in abdominal cavity, edematous and congested lungs, hydrothorax, hydropericardium, hemorrhages and ballooning of small and large intestine and watery contents in the small intestine. In per-acute cases multifocal petechial hemorrhages on jejunal mucosa and myocardium were frequently observed. The histologic changes were perivascular cuffing in lungs and proteinaceous fluid in alveoli, pulmonary edema and hemorrhagic enteritis. Disruption of renal tubular epithelial cells, necrosis and congestion observed in histopathological section of kidneys. Affected deer was treated with different drugs and supplements but unfortunately prognosis was death. Enterotoxaemia is more fatal in young deer than adult. On the basis of this study we found that enterotoxaemia clinical signs, postmortem lesions and histopathological changes in deer are same as other animals such as sheep and goats.

Abstract 14468: Right Heart: Renal Venous Stasis Determinant in Acute Heart Failure

Introduction: The heart-kidney interaction in heart failure (HF) is a matter of special interest, especially due to its strong prognostic significance. The search for a reliable, non-invasive parameter with high pathophysiological and prognostic impact to evaluate HF-related renal congestion remains attractive. Doppler evaluation of intra-renal venous flow (IRVF) has been recently employed in HF patients, with a spectrum of findings ranging from a normal continuous flow to a monophasic discontinuous one, indicative of low and high degrees of renal congestion, respectively. Hypothesis: We postulated a role for right atrial dynamics in the renal congestion pathophysiology. The impairment in atrial deformation and pump function may play a primary role increasing the pulsatile backward load in the venous system, especially in acute heart failure (AHF) patients. Methods: 119 consecutive AHF patients were prospectively investigated within 48 hours from admission. Doppler-derived descriptors of renal hemodynamics included the renal arterial resistive index, IRVF pattern, venous impedance index and renal venous stasis index (RVSI). Results: Right atrial peak longitudinal strain (RAPLS) showed a strong correlation with IRVF pattern (Fig A) and various indices of RV function (TAPSE, S’, FAC) and RV coupling as represented by the TAPSE/PASP ratio (Fig B). At multivariate regression analysis, TAPSE/PASP ratio emerged as the main determinant of RVSI. On the other hand, considering only patients with a clearly impaired RV coupling (TAPSE/PASP <0.30), RAPLS emerged as the best determinant of RVSI (Fig C-D). Conclusions: Our data confirms the main role of the right heart in determining renal stasis in HF patients. When RV to pulmonary circulation uncoupling is severe, the right atrium becomes the key balancing factor in the venous renal flow response. Studies on the mechanistic contribution of the RA dysfunction and the recovery potential of interventions are warranted.

Abstract 13330: Intrarenal Doppler Ultrasonography Reflects Hemodynamics and Predicts Prognosis in Patients With Heart Failure

Introduction: We aimed to clarify clinical implications of intrarenal hemodynamics (congestion and hypoperfusion) assessed by intrarenal Doppler ultrasonography (IRD) and their prognostic impacts in patients with heart failure (HF). Methods and Results: We performed IRD and measured interlobar renal artery velocity time integral (VTI) and intrarenal venous flow (IRVF) patterns (monophasic or non-monophasic pattern) to assess intrarenal hypoperfusion and congestion in HF patients (n=341). These patients were categorized based on 1) VTI: high VTI (VTI ≥ 14.0 cm, n=231) or low VTI (VTI < 14.0 cm, n=103); and 2) IRVF: monophasic (n=36) or non-monophasic (n=305) pattern. We performed right-heart catheterization, and examined post-discharge cardiac event rate such as cardiac death and rehospitalization due to worsening HF. Regarding renal perfusion, cardiac index was positively correlated with VTI (R=0.270, P=0.040). Concerning renal congestion, levels of right atrial pressure were higher in monophasic pattern than in non-monophasic pattern (9.0 vs. 7.2 mmHg, P=0.029). Importantly, HF patients with low VTI and a monophasic IRVF pattern (subset 4) had the highest cardiac event rate ( Figure ). In the Cox proportional hazard analysis, the combination of low VTI and a monophasic IRVF pattern was found to be a strong predictor of cardiac events (HR 8.357, 95% CI 3.365-20.752). Conclusion: Intrarenal hypoperfusion and congestion assessed by IRD imaging reflected cardiac output and right atrial pressure, and was useful to risk-stratify HF patients.

Renal Vein Thrombosis due to Posterior Nutcracker Syndrome

Thrombosis of the left renal vein (LRV) is a rare occurrence usually associated with hypercoagulable disorders. It may also be caused by extrinsic compression due to anatomical variations. Such variations, known as nutcracker phenomenon (NP), are usually completely asymptomatic, and they have been described in three variants: a narrowed aortomesenteric angle (AMA) with entrapment of the LRV; a second, rarer variant with an anomalous retro aortic LRV compressed between the abdominal aorta (AA) and the spine (posterior nutcracker syndrome, PNCS); and a third variant with a duplicated LRV with a pre- and retroaortic course, compressed both anteriorly and posteriorly. The development of symptoms secondary to NP is mainly due to renal congestion, often difficult to identify, and includes flank pain, ipsilateral varicocele, hematuria, and orthostatic proteinuria, among others. The most severe complication of NCS is LRV thrombosis with or without associated predisposing prothrombotic factors. The present case associates a PNCS to LRV thrombosis with a floating thrombus in the inferior vena cava and pulmonary embolism.

Renal Negative Pressure Treatment as a Novel Therapy for Cardio-Renal Syndrome

Introduction Decongestion is the primary therapeutic objective in most acute decompensated heart failure (ADHF) hospitalizations. However, congestion itself commonly represents a barrier to successful diuresis. Renal congestion results in increased renal tubular pressures, reducing glomerular filtration and urine output. This is further aggravated by loop diuretics, which also increase tubular pressures. Because each nephron is a fluid filled column, renal negative pressure treatment (rNPT) applied to the urinary collecting system should reduce tubular pressure, potentially improving kidney function and diuresis. Hypothesis rNPT will improve diuresis, natriuresis, and renal function in a congestion predominate heart failure (CHF) model. Methods Ten ∼80 kg pigs underwent thoracotomy with implantation of a pericardial, Swan Ganz, & bilateral ureteral JuxtaFlow® catheters. High dose furosemide (400mg bolus, then 80mg/hr) was administered since HF clinical use of rNPT will be in conjunction with loop diuretics. Each animal served as its own control with randomization of L vs. R kidney to -30 mmHg rNPT or no rNPT. HF was induced via cardiac tamponade (∼200 ml of pericardial 6% hydroxyethyl starch) and IV normal saline. Pericardial pressure was maintained at 20-22.5 mmHg. Results Prior to HF induction, rNPT increased urine output (UOP) & creatinine clearance (CrCl) compared to the control kidney during furosemide diuresis (p lt 0.001 for all, Figure). HF induction achieved the target hemodynamic profile with stable cardiac output & elevated filling pressures (Figure). UOP, sodium excretion, and CrCl decreased during HF (p lt 0.001 for all, Figure), but were higher consistently in rNPT kidney vs. control (p lt 0.05 for all, Figure). UOP (p=0.38) was the same in rNPT during HF as control prior to HF (Figure). Conclusions rNPT with the JuxtaFlow® system resulted in significantly increased diuresis, natriuresis, and creatinine clearance, both in the presence and absence of experimental HF. Notably, rNPT rescued the congested cardio-renal phenotype with equivalent diuresis and natriuresis during HF with rNPT as was observed in the non-HF period without rNPT. Additional research into the efficacy of the JuxtaFlow® system in human ADHF is warranted.

Doppler Interrogation of the Femoral Vein in the Critically Ill Patient: The Fastest Potential Acoustic Window to Diagnose Right Ventricular Dysfunction?

To report the use of common femoral vein Doppler interrogation as a simple technique to diagnose right ventricular dysfunction. Case report. Cardiac surgical ICU. Postoperative cardiac surgical patients. Common femoral pulsed-wave and color Doppler examination associated with hepatic, portal, and renal venous Doppler measurement were obtained in both patients and before and after treatment in patient number 1. In addition, right ventricular pressure waveform examination was obtained in patient number 2. The technique to obtain common femoral venous Doppler is described. Two cases of patients presenting with right ventricular dysfunction and fluid overload with portal and renal venous congestion in the perioperative period undergoing complex multivalvular cardiac surgery are presented. Hemodynamic waveform monitoring was performed alongside echocardiographic, hepatic, and renal venous flow Doppler assessment, and spectral Doppler profiles of the common femoral veins were examined. Those findings were useful in confirming our diagnosis and guiding our response to treatment. An algorithm was developed and tested on two additional hemodynamically unstable patients. Doppler examination of the common femoral vein is a simple, fast, and noninvasive technique that could be useful to rule in the presence of right ventricular dysfunction with venous congestion and help guide the management of such patients.

EFFECT OF NICOTINE SMOKE ON LIVER AND KIDNEYS OF ADULT MALE ALBINO RATS: AN EXPERIMENTAL STUDY

Apart from heart and lungs, being cited as the main affected organs by nicotine smoke and hence, contributing for the morbidity and mortality, other organs like kidneys, gastrointestinal tract, liver, reproductive organs, endocrine glands, skin etc. are also affected. In the current study we planned to evaluate the effects of nicotine smoke on liver and kidneys. The study was conducted on 12 inbred adult Wistar albino rats; 6 animals acting as control and remaining 6 acting as test group. The animals of control group were given only sterile water where as animals of test group were exposed to smoke produced from the nicotine wrapped in a cotton wool in the dose of 6mg/day three times a day for each session of 5 minutes each for 5 days. Each rat was exposed to the smoke produced due to nicotine separately in a closed inhalational chamber and not in groups. The rats were sacrificed after the period of experimentation and testis were dissected out and subjected further to tissue processing for histological examination. The histological examination of tissue sections of liver of test group animals revealed distorted or normal lobular architecture of hepatic lobules with dilated and congested central vein, portal venule and hepatic sinusoids. Also, there was presence of focal inflammatory aggregates especially around bile canaliculi at portal triads. On the other hand, the tissue sections of liver of control group showed normal hepatic architecture with normal hepatocytes. The renal specimens of the control group also demonstrated normal renal architectural pattern; with glomeruli surrounded by urinary space and renal tubules present in cortex and medulla composed of collecting tubules, loop of henle and convoluted tubules. On the contrary, the renal sections of test group showed dilation of urinary space, shrunken and distorted glomeruli with some renal tubules showing solid cord like pattern and some showing eosinophilic material in lumen, focal inflammatory infiltrates and renal congestion.
 Keywords: Nicotine smoke, liver, kidney

Abstract P038: Renoprotective Effect Of SGLT1/2 Inhibitor In Rat Renal Congestion Model

Renal venous congestion by increased central venous pressure in congestive heart failure is responsible for renal dysfunction. We have created a novel rat renal congestion model presenting increased renal interstitial hydrostatic pressure and vasa recta expansion, which leads to renal congestion-mediated fibrosis. Current clinical trials suggest the renoprotective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in heart failure patients; however, the underlying mechanisms are still discussing. Thus, we investigated the effect of phlorizin, a commercially available SGLT1/2 inhibitor, in our renal congestion model. All animal procedures were performed in accordance with the policies and guidelines of the “Position of the American Heart Association on Research Animal Use” and were approved by the Tohoku Medical and Pharmaceutical University Animal Experiment Committee (registration number: A18019-a, A19039-cn and A20005-cn). The inferior vena cava between the renal veins was ligated, which induced congestion only in the left kidney. Phlorizin (400 mg/kg body weight) or saline were injected subcutaneously daily from 1 day before the operation. Both the right control kidney and left congested kidney were collected 3 days after the surgery. Increased kidney weight and renal fibrosis were observed in the congested kidneys. Phlorizin attenuated the increased kidney weight and suppressed renal fibrosis staining. Molecules related to kidney injury (Kim1) and fibrosis (Fn1 and αSma) were also suppressed by Phlorizin in the congested kidney. Low-vacuum electron microscopy revealed the vasa recta dilatation in the congested kidney. This morphological change was alleviated by Phlorizin. These results suggest that SGLT1/2 inhibitor could suppress renal congestion-mediated fibrosis. This mechanism could be a potential therapeutic target for renoprotection against heart failure.

Pyrethroid-Induced Organ Toxicity and Anti-Oxidant-Supplemented Amelioration of Toxicity and Organ Damage: The Protective Roles of Ascorbic Acid and α-Tocopherol.

The pyrethroid toxicants, fatal at high doses, are found as remnants of crop pesticides and ingredients of commercially available insecticides. The toxic effects of high-content insecticidal pyrethroid formulations are available in 0.05 g, 1.17 g, and 0.04 g pyrethroid-instilled products, namely burning coils, pyrethroid-soaked mats, and liquid formulations of pyrethroids that release pyrethroid vapor/smoke upon heating. They provided 5.46 g/kg, 21.15 g/kg, and 4.24 g/kg of toxicants to the experimental animals over a total of 3 weeks/5 h per os (p.o.) administration, producing necrosis, hyperemia, and fatty changes in the liver; fiber separation in cardiac muscles; atrophy, lymphatic infiltration, blood vessel congestion, and hyperemia in the heart tissues of the experimental animals. The glomerular tuft necrosis, cytoplasmic degeneration of renal tubular cells, necrotic tubules, congestion, and dilatation of blood vessels were observed in the kidney tissue of intoxicated animals. Air-space enlargement, interstitial inflammation, lymphocyte infiltration aggregates, connective tissue infiltration by inflammatory cells, and hyperemia were found in the lung tissues. The pyrethroid toxicants also produced nervous tissue degeneration and decreased neurons in the brain, which were observed through histopathological examinations of the brain, lungs, heart, kidneys, and liver. The protective effects of ascorbic acid (AA/vitamin C) and α-tocopherol (E307/vitamin E) at 100 mg/kg oral doses administered daily for the entire period of the toxicant exposure of three weeks to the experimental mice, aged between 3–4 months and weighing ≈30 g, ameliorated the tissue damage, as observed through the histopathological examinations. The ascorbic acid caused recovery of the liver, kidney, brain, and heart tissue damage, while α-tocopherol was effective at ameliorating the damage in the kidneys and lung tissue compared with the control groups. The high levels of tissue damage recovery suggested a prophylactic effect of the concurrent use of ascorbic acid and α-tocopherol for the subjects under the exposure of pyrethroids.

Doppler-Derived Intrarenal Venous Flow Mirrors Right-Sided Heart Hemodynamics in Patients With Cardiovascular Disease.

Interruption in Doppler intrarenal venous flow (IRVF) has been used in assessing renal congestion and in the prediction of prognosis of cardiovascular diseases. However, there is a paucity of pathophysiological knowledge, so we aimed to clarify the determinants of IRVF interruption. Intrarenal Doppler studies were performed within 24 h before right-side catheterization studies. The interruption in IRVF in 73 patients was divided into a continuous pattern, and 4 discontinuous types based on the timing of interruption. Type 1, with an interruption in early systole, was associated with a-wave elevation of right atrial pressure (RAP). Type 2, with an interruption in early diastole, was associated with v-wave elevation, tricuspid regurgitation (TR), and right ventricular dysfunction. Both Type 1 and 2 were observed even in the normal range of mean RAP. Type 3, with an interruption throughout systole, was observed in advanced right heart failure patients with markedly elevated RAP, particularly elevated x-descend and atrial fibrillation. Finally, Type 4, with limited flow at systole, was observed in 2 of the patients with pulmonary arterial hypertension. IRVF interruption was closely related to RAP elevation at each specific point of the cardiac cycle rather than to mean RAP levels, suggesting that the characteristics of IRVF mirror right-sided heart hemodynamics, not mean RAP.

Prognostic Impact of Changes in Intrarenal Venous Flow Pattern in Patients With Heart Failure

BackgroundIt remains unclear whether intrarenal venous flow (IRVF) patterns in patients with heart failure (HF) could change over the clinical course, and whether the changes could have a clinical impact. Thus, this study aimed to clarify these characteristics as well as to identify the relation between changes in the IRVF pattern and renal impairment progression. Methods and ResultsPatients with HF with repetitive IRVF evaluations were enrolled. Doppler waveforms of IRVF were classified into the following 3 flow patterns: continuous, biphasic discontinuous, and monophasic discontinuous. Primary end points included death from cardiovascular diseases and unplanned hospitalization for HF. Finally, 108 patients with adequate images were enrolled. The IRVF in 35 patients (32.4%) shifted to another pattern at the follow-up examinations. The median brain natriuretic peptide level in the continuous flow pattern at follow-up was significantly decreased (183 to 60 pg/mL, P < .001), whereas that of the discontinuous flow pattern at follow-up was increased (from 339 to 366 pg/mL, P = .042) and the estimated glomerular filtration rate was decreased (from 55 to 50 mL/min/1.73 m2, P = .013). A multivariable Cox proportional hazard model analysis revealed that the discontinuous pattern at follow-up (P < .001) and brain natriuretic peptide (P = .021) were significantly associated with the end points, independent of age, estimated glomerular filtration rate, and serum sodium level. ConclusionsThe IRVF pattern could be changed depending on the status of congestion. Persistent or worsened renal congestion, represented by discontinuous flow patterns, during the clinical courses indicated a poor prognosis accompanied by renal impairment in patients with HF.

Nephrology and Coronavirus Disease 2019

AbstractNovel coronavirus disease 2019 (COVID-19) has emerged as a threat to the human population worldwide. Old age and presence of comorbidities are risk factors for severe complications of the disease, as many of these patients are not able to mount effective or have an aberrant antiviral response. Patients with chronic kidney disease are at high risk of COVID-19 and its complications, especially those with end-stage renal disease (ESRD). Patients have repeated exposure to crowding in dialysis units, and face the uncertainties of health care system sustainability during periods of increasing demand and scarce supply. Acute kidney injury (AKI) is a notable complication in patients with COVID-19 with an incidence of up to 25% in specific populations. Patients with AKI have a higher mortality rate. The etiology and pathogenesis of AKI in COVID-19 are multifactorial. Direct viral invasion and cytopathic effects on renal tubular cells and indirect factors like hypovolemia, rhabdomyolysis, renal vein congestion, and hypercoagulable state play a role in causing AKI in these patients. Renal replacement therapy in the form of continuous renal replacement therapy is most widely used worldwide mostly due to hemodynamic instability of critically sick patients with COVID-19. Anticoagulation therapy is critical as most COVID-19 patients have increased clotting tendency and extracorporeal circuit thrombosis is common. ESRD patients in China had mild-to-moderate symptoms commonly. However, the data from Spain and Italy report a higher mortality rate in ESRD patients than the general population. Strict screening and uniform adherence to infection control practices have led to a decreased risk of cross-infection among other patients and dialysis personnel in dialysis units. The association between nephrology and COVID-19 is unique and focus on further research on kidney pathology along with the strengthening of existing dialysis facilities are needed.

P0201ASSOCIATION OF INTRARENAL VEIN FLOW PATTERNS WITH CARDIAC FUNCTION IN OUTPATIENTS WITH CHRONIC KIDNEY DISEASE AND HEART FAILURE

Abstract Background and Aims In patients with chronic kidney disease (CKD) and heart failure (HF), renal venous congestion plays a key role in determining renal dysfunction and a worse prognosis. Αim of this ongoing study is to identify Doppler intrarenal venous flow patterns reflecting renal congestion in patients with CKD and HF and to detect possible associations with cardiac function parameters. Prognostic implications will be evaluated at a next stge. Method We prospectively enroll outpatients affected by CKD stages 3-4 and HF, in stable clinical conditions and in conventional therapy. All patients undergo clinical evaluation, routine biochemistry, transthoracic echocardiogram and renal echo-Doppler. Pulsed Doppler flow recording is performed at the level of the right interlobular renal veins at the end-expiratory phase. The intrarenal venous flow patterns are divided into five types according to the waveforms of the flow. Type A and B are characterized by a continuous flow and considered normal waveforms. Type C is characterized by a short interruption and/or reversal flow during the end-diastolic or protosystolic phase. Type D and E are characterized by a wide interruption and/or reversal flow, respectively. Types C, D and E are considered abnormal and reflect increasing venous pressure within the kidneys. Results Until now, 36 patients (27males / 9 females), 13 (36%) diabetics, aged 69.4±10.6 years old, have been included, and baseline characteristics are presented. Twenty patients (55%) have CKD stage 3, and 16 patients CKD stage 4 (45%). Fifteen (40%) of these patients have HF New York Heart Association (ΝΥΗA) class II, 18 (50%) ΝΥΗΑ class ΙΙΙ and 3 (10%) ΝΥΗΑ class IV. Mean ejection fraction (EF) is 34.5±7.8%, moderately reduced in 9 (25%) and severely reduced in 27 (75%) of these patients. By analyzing the waveforms, we noticed that 27 patients (75%) had venous patterns of continuous flow (type A 18% and type B 57%) and 9 (25%) had venous patterns with not continuous flows (21% type C and 4% type D). The patients with renal venous patterns A and B had higher EF than those with renal venous patterns C and D (36±8% vs. 30±5%, p=0.045). We have also observed that worsening HF according to NYHA classification was significantly associated to more pathological renal venous patterns (rho=0.402, p=0.034) Conclusion In patients with CKD and HF we may observe abnormal intrarenal vein flow patterns, in the context of renal congestion, related to the functional state of the heart. Further studies will indicate the clinical and prognostic significance of these measurements to better characterize patients with cardio-renal syndrome.

Pretreatment with low dose lipopolysaccharide promotes rapid decongestion of medullary capillaries

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&lt;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 &gt;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&lt;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.Support or Funding InformationNIH PO1HL134604 and DK099548

SUN-054 A CASE WITH ASCITES, PROTEINURIA AND OLIGURIA FOLLOWING POST-PARTUM HELLP SYNDROME TREATED BY EXTRACORPOREAL ULTRAFILTRATION: RENAL CONGESTION AS THE 4TH CATEGORY OF ACUTE KIDNEY INJURY

Heart failure often causes acute kidney injury (AKI) and the relationship is called cardiorenal syndrome. Not only low cardiac output, but also renal congestion is increasingly considered as the major cause of AKI among heart failure patients. Renal congestion may be also caused by other pathologic conditions such as liver cirrhosis and hypoalbuminemia. Decongestion by diuretics can improve cardiorenal syndrome, but it is difficult to prove that the kidney rather than the heart was the main site of action. In the present report, a patient developed severe HELLP syndrome immediately after delivery of a baby. Thrombocytopenia and elevated liver enzymes were largely improved within a week, but anuria and severe ascites continued, which were resistant to oral or iv diuretics. We believe this was a unique case with purely mechanical renal congestion, not associated with heart failure or liver dysfunction. N/A. The case was a 27-year-old woman. Ascites appeared during pregnancy and a baby was delivered by emergency caesarean section at 38 weeks. At that time, there was no hypertension and proteinuria. At 3 days after delivery (D3), hypertension (160/90 mmHg), thrombocytopenia (18,000/uL), liver dysfunction (AST 1,928 U/L, ALT 622 U/L, LDH 2,352 U/L), and indirect bilirubin-dominated jaundice developed (TBIL 3.6 mg/dL, DBIL 0.9 mg/dL). HELLP syndrome was diagnosed. Abdominal fullness, edema, punctate hemorrhage, gross hematuria, proteinuria (2.4 g/gCr) were observed, but renal function was normal (serum Cr 0.68 mg/dL). Carperitide (atrial natriuretic peptide), antihypertensive, loop diuretic and tolvaptan were started for hypertension, fluid retention, edema and oliguria. Thrombocytopenia and liver dysfunction gradually improved, but weight gain (62 → 69 kg) and renal function worsening (D11, Cr 6.6 mg/dL) were observed. It seemed difficult to correct fluid excess by drug treatment, and hemodialysis and ultrafiltration were performed for 3 consecutive days on D11-13, resulting in an increase in urine output and improvement of proteinuria (to 0.4 g/gCr). The patient was discharged on D24 at 59 kg, and Cr was improved to 1.0 mg/dL on D28. HELLP syndrome may cause intra organ bleeding and renal failure, potentially resulting in a severe clinical outcome. In this case, although the primary disease seemed to be improving, ascites resulted in oliguria likely due to an increase in the abdominal pressure, and the level of ascites appeared to exceed the limit of natural recovery. Only 3 days of acute renal replacement therapy with ultrafiltration was sufficient to trigger resolution of all the clinical abnormalities such as ascites, oliguria and proteinuria. There were no signs of prerenal, renal parenchymal or post-renal AKI. This was a unique AKI case caused purely by reversible renal congestion, suggesting that renal congestion is the fourth, independent category of AKI.

Effect of electroacupuncture on renal fibrosis in spontaneously hypertension rats and its related mechanisms

To observe the effect of electroacupuncture (EA) on blood pressure, renal fibrosis and expression of tissue inhibitors of metalloproteinase-1 (TIMP-1), plasminogen activator inhibitor 1 (PAI-1), and alpha smooth muscle actin (α-SMA) in spontaneous hypertension rats (SHR), so as to explore its mechanisms underlying improving hypertensive renal damage. Forty male SHR (15 weeks in age) were randomly divided into 5 groups: model, medication (Losartan), Shenshu, Geshu, and Shenshu＋Geshu groups(n=8 rats in each group), and the same age-old male 8 Wistar-Kyoto (WKY) rats were used as the normal control group. Rats of the medication group were treated by gavage of Losartan potassium solution (3 mg/mL, 30 mg·kg-1·d-1, once a day for 12 weeks), and those of the 3 EA groups treated by EA stimulation of bilateral "Shenshu" (BL23), "Geshu"(BL17) or both BL23 and BL17 (2 Hz/100 Hz, 1 mA, 15 min each time, once every other day for 12 weeks). The systolic blood pressure of the tail artery was measured before, and 4, 8 and 12 weeks after the intervention. The expression of TIMP-1, PAI-1 and α-SMA proteins of the right kidney tissue was measured by immunohistochemistry. Histopathological changes of the right renal tissue were observed under light microscope after H.E. stain. The blood pressure was significantly higher in the mo-del group than those in the normal control group (P<0.01), and considerably decreased at the 4th , 8th, and 12th week of the interventions in the medication and 3 EA groups (P<0.01). The expression levels of renal TIMP-1, PAI-1 and α-SMA proteins were notably higher in the model group than those in the normal control group and considerably decreased at the 12th week of the interventions in the medication and 3 EA groups than in the model group (P<0.01). H.E. staining of the renal tissue showed disordered arrangement of the renal cells, congestion and dilation of capillaries with thickened vascular wall, renal tubule atrophy and lumen stenosis with some necrosis of renal tubules, protein tubule and cell tubules, increase of some glomerular mesangial matrix and hyperplasia of fibrous tissue in the model group, which was re-latively milder in the medication and 3 EA groups. EA of BL23 and BL17 can reduce the blood pressure in SHR, which may be related to its function in down-regulating expression of TIMP-1, PAI-1 and α-SMA proteins.

Positive association between intra-operative fluid balance and post-operative acute kidney injury in non-cardiac surgery: the NARA-AKI cohort study.

Little is known about the association between intra-operative fluid balance (IFB) and post-operative acute kidney injury (AKI) in non-cardiac surgery. This is a retrospective cohort study. Adults who underwent non-cardiac surgery under general anesthesia from 2007 to 2011 at Nara Medical University Hospital were included. Those with obstetric or urological surgery, missing data, or pre-operative dialysis were excluded. Exposure of interest was IFB, defined as (amount of fluid administration - urine output - amount of bleeding)/body weight. Outcome variable was post-operative AKI within 1week after surgery. Data were analyzed using logistic regression models and restricted cubic spline (RCS) analysis. Among 5168 subjects, AKI was observed in 309 (6.0%). Higher IFB (per 1 standard deviation) was independently associated with post-operative AKI after adjustment for potential confounders (odds ratio [95% confidence interval] of 1.18 [1.06-1.31]). The RCS curve showed an increase in expected probability of AKI associated with increase in IFB above 40mL/kg. Subgroup analyses indicated higher IFB was especially associated with AKI among those with lower serum albumin, higher C-reactive protein, or positive proteinuria. The association was similar across intra-operative urine output or amount of bleeding (p for interaction 0.34 and 0.47, respectively), suggesting the association was not due to intra-operative oliguria or large amount of bleeding necessitating volume resuscitation. Higher IFB was independently associated with increase in post-operative AKI. Excessive fluid administration might have caused renal congestion and subsequent AKI. Avoiding fluid overload might be important in prevention of AKI.

Renal function, electrolytes, and congestion monitoring in heart failure.

Congestion, renal function, and electrolyte imbalance (particularly potassium) are common problems in the management of the complex multi-morbid patient with heart failure (HF). Poor control of these fundamental clinical features is associated with adverse outcomes. Close monitoring of serum potassium and renal function is recommended by most current guidelines during the management of an episode of acute decompensated HF, yet the recommendations remain poorly implemented. Physicians are advised to treat a state of euvolaemia after an admission with decompensated HF and residual congestion is a marker of worse outcome, yet control of congestion is poorly assessed and managed in real-world practice. This document reflects the key points discussed by a panel of experts during a Heart Failure Association meeting on physiological monitoring of the complex multi-morbid HF patient, and here, we present to aspects related to renal function, electrolyte, and congestion monitoring.