Decrease In Renal Perfusion Research Articles

#2500 Renal perfusion and SGLT2i

Abstract Background and Aims Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) have revolutionized treatment of type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD), improving cardiovascular and renal endpoints. This improvement could be due to a decrease in renal perfusion (RP), attenuating glomerular hyperfiltration thus leading to kidney protection. This has been demonstrated in patients with type 1 diabetes and in animal studies, but not in patients with DM2 and it has never before been investigated in patients with CKD. Our aim was to examine the effects of the SGLT2i empagliflozin on RP in patients with DM2, DM2 and CKD and non-diabetic CKD, respectively. Methods We conducted three randomized, double-blind placebo controlled cross-over studies, including patients with: Participants were randomized to four weeks' treatment with empagliflozin 10 mg or matching placebo and were, after a washout period of at least two weeks, crossed over to four weeks of the opposite treatment. At the end of each treatment period we measured RP using 82Rb-PET/CT and standardized GFR using 99mTc-DTPA-clearence. We also measured 24-hour ambulatory blood pressure (BP), urinary albumin/creatinine ratio (UACR) and Hb1Ac. Results A total of 49 patients completed the studies, 16 in the DM2-group, 17 in the DM2-CKD-group and 16 in the CKD-group. In the combined study-population empagliflozin reduced RP compared to placebo by 4% (geometric mean ratio: 0.96, 95% CI: 0.94; 0.99, p = 0.0171). This change was most pronounced in the DM2-CKD-group, with a reduction of 6% (geometric mean ratio: 0.94, 95% CI: 0.91; 0.97), p < 0.001). There was a decrease of 4% in the DM2-group and 1% in the CKD-group, though these changes were not statistically significant (p = 0.29 and 0.72, respectively, see Fig. 1). In the 29 patients with a UACR > 30 mg/g, empagliflozin treatment led to a significant decrease in UACR in the combined study-population (geometric mean ratio: 0.61, 95% CI: 0.46; 0.80, p = 0.001), again primarily driven by a decrease in the DM2-CKD-group (geometric mean ratio: 0.51, 95% CI: 0.31; 0.85, p = 0.014), with non-significant decreases in the remaining groups. Empagliflozin decreased standardized GFR and BP in the combined population as well as in all sub-groups, while we found no change in Hb1Ac. For further details, see Table 1. Conclusion Short-term empagliflozin treatment reduces RP, GFR, BP and albumin excretion. Relative changes in RP and UACR were most pronounced in patients with concomitant DM2 and CKD, whereas changes in BP and GFR were seen in all groups.

Evaluating Short-Term and Long-Term Risks Associated with Renal Artery Stenosis Position and Severity: A Hemodynamic Study.

Background: Moderate renal artery stenosis (50-70%) may lead to uncontrolled hypertension and eventually cause irreversible damage to renal function. However, the clinical criteria for interventional treatment are still ambiguous in this condition. This study investigated the impact of the position and degree of renal artery stenosis on hemodynamics near the renal artery to assess the short-term and long-term risks associated with this disease. Methods: Calculation models with different degrees of stenosis (50%, 60%, and 70%) located at different positions in the right renal artery were established based on the computed tomography angiography (CTA) of a personalized case. And computational fluid dynamics (CFD) was used to analyze hemodynamic surroundings near the renal artery. Results: As the degree of stenosis increases and the stenosis position is far away from the aorta, there is a decrease in renal perfusion. An analysis of the wall shear stress (WSS)-related parameters indicated areas near the renal artery (downstream of the stenosis and the entrance of the right renal artery) with potential long-term risks of thrombosis and inflammation. Conclusion: The position and degree of stenosis play a significant role in judging short-term risks associated with renal perfusion. Moreover, clinicians should consider not only short-term risks but also independent long-term risk factors, such as certain regions of 50% stenosis with adequate renal perfusion may necessitate prompt intervention.

Abstract #1406144: Safety and Efficacy of SGLT2 Inhibitors Use in Patient with Diabetes After Renal Transplant

The sodium glucose cotransporter2 inhibitors (SGLT2i) are preferred anti-glycemic agents for patients with diabetes mellitus (DM) and chronic kidney disease (CKD). These agents have been shown to slow the progression of kidney disease. There is limited experience of SGLT2i in renal transplantation (RT). Concerns have been that the glycosuria induced osmotic diuresis might cause a decrease in renal perfusion and there might be a possible increased risk of urinary tract infections (UTI). We therefore performed a retrospective review of data of patients with DM and RT treated with SGLT2i compared to those without SGLT2i. The primary outcome was the change in eGFR or serum creatinine at 1-year. Secondary outcomes were documentations of serious adverse events (SAE). Data were retrieved from the electronic medical record of a Midwestern academic medical center using the program Epic and the sub-program Slicer/ Dicer. The search algorithm inclusion criteria were: “Diabetes Mellitus” “kidney transplant”, and “medicine: sodium glucose transport inhibitor”, which resulted in an inclusion of 44 patients in the “SGLT2i group”. A comparator group of patients with DM and RT who matched the above screening criteria (except for SGLT2i use), was then retrieved. We then devised a propensity score by performing a multivariate regression analysis with the covariates of age, type of transplant, duration of transplantation, and baseline eGFR. Data from 44 patients on SGLT2i were closely matched (by standardized effects size) for age, estimated GFR, duration and source of transplant with 70 control patients with DM and RT who were not on SGLT2i. Weight changed in SGLT2i group from baseline at 3, 6 and 12months (by -4.1 ± 3.3 kg, -5.1 ± 5.0 kg and -5.2 ± 6.5 kg) and did not change in controls (p [ANOVA, drug] = 0.009). There was no significant difference at 3, 6 or 12 months in changes in: A1c, systolic or diastolic blood pressure, hematocrit, hemoglobin, total cholesterol, LDL cholesterol, HDL cholesterol, or serum triglycerides. There were no documented significant increases in SAE in those on SGLT2i compared with controls in hospitalizations for acute kidney injury, episodes of acute transplant rejections, amputations, cellulitis, diabetic ketoacidosis, or outpatient treatment for urinary tract infections, or genital mycotic infections. Use of SGLT2i in patients with diabetes and renal transplant showed beneficial effect in reducing weight without a higher risk of SAE. Longer follow up may be necessary to define the impact on eGFR.

Kidney`s functional state assessment when using different regimens of intraoperative fluid therapy

The aim of the research. To study the kidneys functional state when using different regimens of intraoperative fluid therapy in high cardiac risk patients during abdominal surgery.
 Materials and methods. 142 patients who underwent abdominal surgical interventions mainly for oncoproctological diseases of the gastrointestinal tract, aged over 50 years old and with a history of stable coronary heart disease were divided into four groups depending on the way of intraoperative fluid therapy, which was performed according to two regimens: restrictive (R) and liberal (L). R1 (n=36) with rate of intraoperative fluid therapy 3–5 ml/ kg/ h, R2 (n=35) patients received 5–8 ml/kg/h during surgery, L1 (n=35) with intraoperative fluid rate of 8–11 ml/kg/h and L2 (n=36) – more than 11 ml/kg/h intraoperatively. The study of the functional state of the kidneys included the determination of such indicators as urea, creatinine, diuresis, the degree of AKI according to KDIGO in two stages of the study – before surgery and 18–24 hours after.
 Results. The greatest tendency to develop acute kidney injury was observed in R1 subgroup with a restrictive intraoperative fluid therapy regimen, and the smallest in L1 subgroup with a relatively liberal regimen. The R2 and L2 subgroups took an intermediate place in the number of renal complications. A high tendency to develop renal dysfunction in patients of R1 subgroup was associated with circulatory hypokinesia and a moderate decrease of renal perfusion.
 Conclusions. The study found that restriction of infusion in R1 subgroup contributed to the development of renal dysfunction in almost half of the patients. First of all it was associated with a decrease of GFR in conditions of circulatory hypokinesia, which is larger in R1 subgroup and amounted to about 35 %. The safest regimens of intraoperative fluid therapy in relation to renal function in the perioperative period were relatively liberal (subgroup L1) and relatively restrictive (subgroup R2), which provided the least number of complications in patients

C16. BRASH (Bradycardia, Renal Failure, AV Nodal Blocker, Shock, and Hyperkalemia) Syndrome: Lost in Plain Sight

Abstract Background Bradycardia, Renal failure, AV-Nodal blockers, Shock, Hyperkalemia (BRASH) Syndrome new clinical entities due to a vicious cycle in which hyperkalemia from renal failure synergizes with AV-nodal blockers, consequently between the clinical condition of patients with the degree of hyperkalemia and bradycardia are inappropriate, Furthermore, the symptoms may be refractory to typical positive chronotropic interventions or overdose antidotes. Case Illustration A hypertensive 70-years old female with history of heart failure with routinely consume spironolactone, diltiazem, and beta blocker admitted with bradycardia and shock after watery diarrhea and vomit 3 days before. The electrocardiogram showed junctional rhythm 40 beats per minutes. Laboratory findings Hyperkalemia (6.8 mEq/L) and acute kidney injury (urea 58.6 mg/dL, creatinine 3.13 mg/dL, eGFR 16.23) was presented. Refractory hyperkalemia occured, but by using pacemaker, providing adequate fluids, and the return of renal perfusion, hyperkalemia can be overcome. Discussion BRASH syndrome usually triggered by hypotension in the elderly due to hypovolemia or an overdose of antihypertensive drugs. The natural compensation response for hypotension is to increase heart rate, but AV-nodal blockers blunt this response, which causes a decrease in renal perfusion. This ultimately results in hyperkalemia and accumulation of AV-nodal blockers which produce a synergistic effect causes bradycardia and decreased renal perfusion. Treatment involves supportive care including hemodynamic support with fluids and management of bradycardia, and also avoid trigger factor.

C16. BRASH (Bradycardia, Renal Failure, AV Nodal Blocker, Shock, and Hyperkalemia) Syndrome: Lost in Plain Sight

Abstract Background Bradycardia, Renal failure, AV-Nodal blockers, Shock, Hyperkalemia (BRASH) Syndrome new clinical entities due to a vicious cycle in which hyperkalemia from renal failure synergizes with AV-nodal blockers, consequently between the clinical condition of patients with the degree of hyperkalemia and bradycardia are inappropriate, Furthermore, the symptoms may be refractory to typical positive chronotropic interventions or overdose antidotes. Case Illustration A hypertensive 70-years old female with history of heart failure with routinely consume spironolactone, diltiazem, and beta blocker admitted with bradycardia and shock after watery diarrhea and vomit 3 days before. The electrocardiogram showed junctional rhythm 40 beats per minutes. Laboratory findings Hyperkalemia (6.8 mEq/L) and acute kidney injury (urea 58.6 mg/dL, creatinine 3.13 mg/dL, eGFR 16.23) was presented. Refractory hyperkalemia occured, but by using pacemaker, providing adequate fluids, and the return of renal perfusion, hyperkalemia can be overcome. Discussion BRASH syndrome usually triggered by hypotension in the elderly due to hypovolemia or an overdose of antihypertensive drugs. The natural compensation response for hypotension is to increase heart rate, but AV-nodal blockers blunt this response, which causes a decrease in renal perfusion. This ultimately results in hyperkalemia and accumulation of AV-nodal blockers which produce a synergistic effect causes bradycardia and decreased renal perfusion. Treatment involves supportive care including hemodynamic support with fluids and management of bradycardia, and also avoid trigger factor.

Abstract MP08: New Function Of Sox6 In Renovascular Hypertension Induced Oxidative Stress And Kidney Damage Through Renin, Prorenin And The (pro)renin Receptor Expression Control.

Introduction: During renovascular hypertension induced by renal artery stenosis (RAStenosis), smooth muscle cells are recruited to produce and release renin compensating for the decrease in renal perfusion. In renovascular hypertension, renin expression increases causing a surge in angiotensin II, oxidative stress and kidney damage. Here we present a new function of the transcription factor Sox6 in kidney injury and oxidative damage during RAStenosis. Methods: We used a mouse model in which Sox6 is knockout specifically in renin expressing cells (Ren1d Cre /Sox6 fl/fl -Sox6-KO). We developed a modified 2-kidney 1-clip (2K1C) Goldblatt model to induce RAStenosis. We measured superoxide production (pmol/mg pr) in kidney using high-performance liquid chromatography in Sox6-KO and Ren1d Cre /Sox6 wt/wt (Sox6-WT) littermates. Renin, prorenin, (pro)renin receptor (PRR) and N-GAL expressions were measured using Western blot using β-actin as housekeeping gene. Western blot band density analysis was performed using ImageJ. Kidney injury was determined by measuring creatinine clearance. Results: We found that Sox6-KO mice exhibit lower expression of renin (0.36 vs. 0.45, SEM= 0.11 n= 11-15, p<0.01), and prorenin (1.25 vs. 2.07, SEM=0.30, n=11-15, p<0.05) and mice are protected against renovascular hypertension (SBP, 114.5 vs. 131.1, SEM=5.31 n=13-15, p<0.01), and kidney injury measuring N-GAL expression (1.3 vs. 2.7, SEM=0.38, n=6-8, p<0.01) and creatinine clearance (2372 vs. 1341, SEM=342.3, n=4-5, p<0.05). Furthermore, we found that the levels of superoxide were significantly lower in Sox6-KO mice compared to Sox6-WT littermates (218 vs 47, SEM=50.6, N=7, P<0.01). The expression of PRR was significantly lower in Sox6-KO compared to Sox6-WT during RAStenosis (1.23 vs. 0.72, SEM=0.33, n=2-5, p<0.01). Conclusions: Our results show that Sox6 depletion in renin expressing cells inhibits the increase in renovascular hypertension and prevents the increase in renin, prorenin, PRR, and N-GAL expression as well as superoxide production, preserving creatinine clearance during RAStenosis. These results suggest that Sox6 has a new function in hypertension and kidney injury induced by RAS.

Validation of multiparametric MRI by histopathology after nephrectomy: a case study

ObjectivesRenal multiparametric MRI (mpMRI) is a promising tool to monitor renal allograft health to enable timely treatment of chronic allograft nephropathy. This study aims to validate mpMRI by whole-kidney histology following transplantectomy.Materials and methodsA patient with kidney transplant failure underwent mpMRI prior to transplantectomy. The mpMRI included blood oxygenation level-dependent (BOLD) MRI, T1 and T2 mapping, diffusion-weighted imaging (DWI), 2D phase contrast (2DPC) and arterial spin labeling (ASL). Parenchymal mpMRI measures were compared to normative values obtained in 19 healthy controls. Differences were expressed in standard deviations (SD) of normative values. The mpMRI measures were compared qualitatively to histology.ResultsThe mpMRI showed a heterogeneous parenchyma consistent with extensive interstitial hemorrhage on histology. A global increase in T1 (+ 3.0 SD) and restricted diffusivity (− 3.6 SD) were consistent with inflammation and fibrosis. Decreased T2 (− 1.8 SD) indicated fibrosis or hemorrhage. ASL showed diminished cortical perfusion (− 2.9 SD) with patent proximal arteries. 2DPC revealed a 69% decrease in renal perfusion. Histological evaluation showed a dense inflammatory infiltrate and fibrotic changes, consistent with mpMRI results. Most interlobular arteries were obliterated while proximal arteries were patent, consistent with ASL findings.DiscussionmpMRI findings correlated well with histology both globally as well as locally.

Dual assessment of kidney perfusion and pH by exploiting a dynamic CEST-MRI approach in an acute kidney ischemia-reperfusion injury murine model.

Several factors can lead to acute kidney injury, but damage following ischemia and reperfusion injuries is the main risk factor and usually develops into chronic disease. MRI has often been proposed as a method with which to assess renal function. It does so by measuring the renal perfusion of an injected Gd-based contrast agent. The use of pH-responsive agents as part of the CEST (chemical exchange saturation transfer)-MRI technique has recently shown that pH homeostasis is also an important indicator of kidney functionality. However, there is still a need for methods that can provide more than one type of information following the injection of a single contrast agent for the characterization of renal function. Herein we propose, for the first time, dynamic CEST acquisition following iopamidol injection to quantify renal function by assessing both perfusion and pH homeostasis. The aim of this study is to assess renal functionality in a murine unilateral ischemia-reperfusion injury model at two time points (3 and 7 days) after acute kidney injury. The renal-perfusion estimates measured with iopamidol were compared with those obtained with a gadolinium-based agent, via a dynamic contrast enhanced (DCE)-MRI approach, to validate the proposed method. Compared with the contralateral kidneys, the clamped ones showed a significant decrease in renal perfusion, as measured using the DCE-MRI approach, which is consistent with reduced filtration capability. Dynamic CEST-MRI findings provided similar results, indicating that the clamped kidneys displayed significantly reduced renal filtration that persisted up to 7 days after the damage. In addition, CEST-MRI pH imaging showed that the clamped kidneys displayed significantly increased pH values, reflecting the disturbance to pH homeostasis. Our results demonstrate that a single CEST-MRI contrast agent can provide multiple types of information related to renal function and can discern healthy kidneys from pathological ones by combining perfusion measurements with renal pH mapping.

Single-dose diclofenac in healthy volunteers can cause decrease in renal perfusion measured by functional magnetic resonance imaging.

We investigated changes of renal perfusion after topical and oral diclofenac administration in healthy volunteers using functional magnetic resonance imaging (MRI) with arterial spin labelling (ASL). Twenty-four healthy human participants (21-51years) underwent 1.5T MRI before and 1h after a single oral dose of diclofenac (50mg). Twelve of 24 participants underwent an additional MRI examination following 3-day topical diclofenac administration. For renal perfusion imaging, a flow-sensitive alternating inversion-recovery TrueFISP ASL sequence was applied. Plasma concentrations of diclofenac and serum concentrations of thromboxane were determined. After oral diclofenac application, large interindividual differences in plasma concentrations were observed (range <3-4604nm). Topical diclofenac application did not result in relevant systemic diclofenac levels (range 5-75nm). MRI showed a significant reduction of renal perfusion in individuals with diclofenac levels ≥225nm (baseline: 347±7 vs diclofenac: 323±8ml/min/100g, P<0.01); no significant differences were observed in participants with diclofenac levels <225nm. Diclofenac levels correlated negatively with thromboxane B2 levels pointing towards target engagement. Single-dose diclofenac caused a decrease in renal perfusion in participants with diclofenac levels ≥225nm. We demonstrated that even a single dose of diclofenac can impair renal perfusion, which could be detrimental in patients with underlying chronic kidney disease or acute kidney injury.

NSAID associated bilateral renal infarctions: a case report.

Renal infarctions (RIs) are caused by interruptions in the renal arterial blood flow. RIs are generally considered to be rare, however we present the case of a 37 year old woman whose renal infarction was likely due to the vasoconstrictive effects of non-steroidal anti-inflammatory drugs. Although high-dose non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause a decrease in renal perfusion, they have not been accepted as causative agents in renal infarction. Theoretically, patients in prostaglandin dependent states should be more vulnerable to renovascular vasoconstriction and resulting hypoperfusion in the presence of NSAIDs. Given the high prevalence of NSAID use, we suspect that this mechanism of renal injury may be more prevalent than previously thought.

The Absence of Endothelial Sodium Channel α (αENaC) Reduces Renal Ischemia/Reperfusion Injury.

The epithelial sodium channel (ENaC) has a key role in modulating endothelial cell stiffness and this in turn regulates nitric oxide (NO) synthesis. The physiological relevance of endothelial ENaC in pathological conditions where reduced NO bioavailability plays an essential role remains largely unexplored. Renal ischemia/reperfusion (IR) injury is characterized by vasoconstriction and sustained decrease in renal perfusion that is partially explained by a reduction in NO bioavailability. Therefore, we aimed to explore if an endothelial ENaC deficiency has an impact on the severity of renal injury induced by IR. Male mice with a specific endothelial sodium channel α (αENaC) subunit gene inactivation in the endothelium (endo-αENaCKO) and control littermates were subjected to bilateral renal ischemia of 22 min and were studied after 24 h of reperfusion. In control littermates, renal ischemia induced an increase in plasma creatinine and urea, augmented the kidney injury molecule-1 (Kim-1) and neutrophil gelatinase associated lipocalin-2 (NGAL) mRNA levels, and produced severe tubular injury. The absence of endothelial αENaC expression prevented renal tubular injury and renal dysfunction. Moreover, endo-αENaCKO mice recovered faster from renal hypoxia after the ischemia episode as compared to littermates. In human endothelial cells, pharmacological ENaC inhibition promoted endothelial nitric oxide synthase (eNOS) coupling and activation. Altogether, these data suggest an important role for endothelial αENaC in kidney IR injury through improving eNOS activation and kidney perfusion, thus, preventing ischemic injury.

Renal Perfusion during Hemodialysis: Intradialytic Blood Flow Decline and Effects of Dialysate Cooling.

Residual renal function (RRF) confers survival in patients with ESRD but declines after initiating hemodialysis. Previous research shows that dialysate cooling reduces hemodialysis-induced circulatory stress and protects the brain and heart from ischemic injury. Whether hemodialysis-induced circulatory stress affects renal perfusion, and if it can be ameliorated with dialysate cooling to potentially reduce RRF loss, is unknown. We used renal computed tomography perfusion imaging to scan 29 patients undergoing continuous dialysis under standard (36.5°C dialysate temperature) conditions; we also scanned another 15 patients under both standard and cooled (35.0°C) conditions. Imaging was performed immediately before, 3 hours into, and 15 minutes after hemodialysis sessions. We used perfusion maps to quantify renal perfusion. To provide a reference to another organ vulnerable to hemodialysis-induced ischemic injury, we also used echocardiography to assess intradialytic myocardial stunning. During standard hemodialysis, renal perfusion decreased 18.4% (P<0.005) and correlated with myocardial injury (r=-0.33; P<0.05). During sessions with dialysis cooling, patients experienced a 10.6% decrease in perfusion (not significantly different from the decline with standard hemodialysis), and ten of the 15 patients showed improved or no effect on myocardial stunning. This study shows an acute decrease in renal perfusion during hemodialysis, a first step toward pathophysiologic characterization of hemodialysis-mediated RRF decline. Dialysate cooling ameliorated this decline but this effect did not reach statistical significance. Further study is needed to explore the potential of dialysate cooling as a therapeutic approach to slow RRF decline.

Bacteria, Bones, and Stones: Managing Complications of Short Bowel Syndrome.

Short bowel syndrome (SBS) occurs in patients who have had extensive resection. The primary physiologic consequence is malabsorption, resulting in fluid and electrolyte abnormalities and malnutrition. Nutrient digestion, absorption, and assimilation may also be diminished by disturbances in the production of bile acids and digestive enzymes. Small bowel dilation, dysmotility, loss of ileocecal valve, and anatomical changes combined with acid suppression and antimotility drugs increase the risk of small intestinal bacterial overgrowth, further contributing to malabsorption. Metabolic changes that occur in SBS due to loss of colonic regulation of gastric and small bowel function can also lead to depletion of calcium, magnesium, and vitamin D, resulting in demineralization of bone and the eventual development of bone disease. Persistent inflammation, steroid use, parenteral nutrition, chronic metabolic acidosis, and renal insufficiency may exacerbate the problem and contribute to the development of osteoporosis. Multiple factors increase the risk of nephrolithiasis in SBS. In the setting of fat malabsorption, increased free fatty acids are available to bind to calcium, resulting in an increased concentration of unbound oxalate, which is readily absorbed across the colonic mucosa where it travels to the kidney. In addition, there is an increase in colonic permeability to oxalate stemming from the effects of unabsorbed bile salts. The risk of nephrolithiasis is compounded by volume depletion, metabolic acidosis, and hypomagnesemia, resulting in a decrease in renal perfusion, urine output, pH, and citrate excretion. This review examines the causes and treatments of small intestinal bacterial overgrowth, bone demineralization, and nephrolithiasis in SBS.

Diagnostic criteria of hepatorenal syndrome and modern methods of therapy (literature review)

Hepatorenal syndrome (HRS) is a variant of functional renal failure in acute or chronic liver pathology. Type 1 HRS entails a rapidly progressive decline in kidney function within few days and without liver transplantation, 95,0 % of patients die within the next few weeks. With type 2 HRS, kidney function remains stable or gradually declining over several months. HRS diagnosis is based on the exclusion of other causes of renal failure. Pathophysiological changes in renal failure in the case of HRS are quite complex – they include an increase in the synthesis of vasoactive substances, which lead to a decrease in renal perfusion, a decrease in resistance in peripheral arteriovenous anastomosis, the development of portal hypertension, ascites, a decrease in colloidal osmotic pressure and a consistently increasing delay of sodium and water in the kidneys. HRS therapy is based on acid-base balance and anemia correction, intravenous administration of albumin, paracentesis, the removal of nephrotoxic agents and the renal replacement therapy is only symptomatic. areast-font-family:Times New Roman;mso-bidi-font-family:Times New Roman; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA'>, 420012

Recombinant erythropoietin acutely decreases renal perfusion and decouples the renin-angiotensin-aldosterone system.

The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double‐blinded, cross‐over study. Sixteen healthy subjects were tested with placebo, or low‐dose rhEPO for 2 weeks, or high‐dose rhEPO for 3 days. Subjects refrained from excessive salt intake, according to instructions from a dietitian. Renal clearance studies were done for measurements of renal plasma flow, glomerular filtration rate (GFR) and the segmentel tubular handling of sodium and water (lithium clearance). rhEPO increased arterial blood pressure, total peripheral resistance, and renal vascular resistance, and decreased renal plasma flow in the high‐dose rhEPO intervention and tended to decrease GFR. In spite of the decrease in renal perfusion, rhEPO tended to decrease reabsorption of sodium and water in the proximal tubule and induced a prompt decrease in circulating levels of renin and aldosterone, independent of changes in red blood cell mass, blood volumes, and blood pressure. We also found changes in biomarkers showing evidence that rhEPO induced a prothrombotic state. Our results suggest that rhEPO causes a direct downregulation in proximal tubular reabsorption that seems to decouple the activity of the renin‐angiotensin‐aldosterone system from changes in renal hemodynamics. This may serve as a negative feed‐back mechanism on endogenous synthesis of EPO when circulating levels of EPO are high. These results demonstrates for the first time in humans a direct effect of rhEPO on renal hemodynamics and a decoupling of the renin‐angiotensin‐aldosterone system.

Plasma potassium concentrations in neonatal diarrhoeic calves are correlated with serum aldosterone concentrations but not with insulin concentrations

Hyperkalaemia is a clinically relevant electrolyte imbalance in neonatal diarrhoeic calves which was previously associated with severe dehydration and acidaemia. The present study assessed the association of plasma potassium (cK) with serum aldosterone and insulin concentrations, since these hormones are involved in the regulation of potassium homeostasis. Serum aldosterone (rs=0.62), but not insulin concentrations (rs=0.22) were closely correlated to cK in 123 hospitalised neonatal diarrhoeic calves. Median values for serum aldosterone concentrations in 38 hyperkalaemic calves (cK>5.8mmol/L) were 3.2 and 15.3 times higher (P<0.001) than in 85 non-hyperkalaemic diarrhoeic calves and nine healthy control calves, respectively. Aldosterone, but not insulin secretion, appears to be highly stimulated in dehydrated diarrhoeic calves with hyperkalaemia, but hypovolaemia and a concomitant decrease in renal perfusion and urinary flow rate are likely to limit the efficacy of aldosterone-induced control mechanisms in these animals.

The prevalence and clinical significance of anemia in patients hospitalized with acute heart failure.

In a cohort of patients hospitalized with acute heart failure (AHF) the prevalence of anemia and the existence of a correlation between anemia and the severity of the clinical picture were assessed. Methods:50 consecutive patients (34 men, 16 women, mean age 67.5 years) hospitalized with AHF were enrolled. Statistical analysis was performed for studying correlations between anemia and the presence/levels of diverse parameters (clinical, laboratory, echocardiographic, treatment related) reflecting the severity and prognosis of AHF (α=0.05). Results:21 patients (14 men, 7 women, mean age 69.6 years), representing 42%, had anemia at admission. Comparing patients with and without anemia there were no significant differences regarding age, gender, presence of atrial fibrillation (p=0.75), diabetes (p=1), ischemic heart disease (p=0.9), left ventricular ejection fraction (EF) (p=1), hypotension (p=0.34) and tachycardia>100 b/min at admission (p=0.75), level of eGFR (p=0.72), and need of high dose (>80 mg/day) loop diuretic (p=0.23). However, EF showed a significant positive correlation with eGFR only in AHF patients with anemia (r=0,65, p=0.001). In a multiple regression model, EF had a significant effect on the eGFR quartiles (p=0,004). Conclusions:Anemia is a frequent finding in patients hospitalized with AHF. The presence of anemia was not correlated with other factors related to AHF severity and prognosis. However, a low EF associated with low eGFR was characteristic for patients with anemia, suggesting that the decrease of renal perfusion by low cardiac output further aggravates anemia on the background of chronic kidney disease.

Correlation between serum albumin and creatinine levels in children with nephrotic syndrome

Background Nephrotic syndrome is a glomerular disordercharacterized by massive proteinuria, hypoalbuminemia, edema,and hyperlipidemia. Hypoalbuminemia in nephrotic syndromeleads to hypovolemia, a decrease in renal perfusion and glomerularfiltration rate. Serum creatinine level reflects the glomerularfiltration rate.Objective The aim of this study was to determine the correlationbetween serum albumin and creatinine levels in children withnephrotic syndrome.Methods A cross-sectional study was carried out on children withidiopathic nephrotic syndrome, aged between 1 to 14 years old,admitted to Pediatric Department in Hasan Sadikin Hospitalfrom January 2001 to September 2007. We used data frompatients' medical records to obtain serum albumin and creatininelevels during nephrotic stage. Statistical analysis using Pearsoncorrelation test was performed to establish the correlation betweenserum albumin and creatinine levels. The type of correlation wasdetermined by regression analysis.Results Subjects were 113 children, consisted of 81 boys (72%)with mean of age 6.8 (SD 3.3) years. Mean of serum albumin andcreatinine levels were 1.4 (SD 0.4) g/dL and 0.7 (SD 0.4) mg/dL, respectively. Analysis using Pearson correlation test showeda moderate (r=-0.478) significant correlation (P&lt;O.Ol) betweenserum albumin and creatinine levels in children with nephroticsyndrome. Regression analysis suggested a negative linearrelationship between serum albumin level as the independentvariable (X) and serum creatinine level as the dependent variable(Y) by using equation Y = 1.328-0.460X.Conclusion In patients with nephrotic syndrome there is amoderate negative correlation between serum albumin andcreatinine levels.

The prevalence and clinical significance of anemia in patients hospitalized with acute heart failure

: In a cohort of patients hospitalized with acute heart failure (AHF) the prevalence of anemia and the existence of a correlation between anemia and the severity of the clinical picture were assessed. Methods: 50 consecutive patients (34 men, 16 women, mean age 67.5 years) hospitalized with AHF were enrolled. Statistical analysis was performed for studying correlations between anemia and the presence/levels of diverse parameters (clinical, laboratory, echocardiographic, treatment related) reflecting the severity and prognosis of AHF (α=0.05). Results: 21 patients (14 men, 7 women, mean age 69.6 years), representing 42%, had anemia at admission. Comparing patients with and without anemia there were no significant differences regarding age, gender, presence of atrial fibrillation (p=0.75), diabetes (p=1), ischemic heart disease (p=0.9), left ventricular ejection fraction (EF) (p=1), hypotension (p=0.34) and tachycardia>100 b/min at admission (p=0.75), level of eGFR (p=0.72), and need of high dose (>80 mg/day) loop diuretic (p=0.23). However, EF showed a significant positive correlation with eGFR only in AHF patients with anemia (r=0,65, p=0.001). In a multiple regression model, EF had a significant effect on the eGFR quartiles (p=0,004). Conclusions: Anemia is a frequent finding in patients hospitalized with AHF. The presence of anemia was not correlated with other factors related to AHF severity and prognosis. However, a low EF associated with low eGFR was characteristic for patients with anemia, suggesting that the decrease of renal perfusion by low cardiac output further aggravates anemia on the background of chronic kidney disease.