The Effect of Ischemia and Hypoxia on Renal Blood Flow, Energy Metabolism and Function in Vivo

In obesity, renal damage is caused by increase in renal blood flow (RBF), glomerular capillary pressure (P GC ), and single nephron glomerular filtration rate but the mechanism behind this alteration in renal hemodynamics is unclear. P GC is controlled mainly by the afferent arteriole (Af-Art) resistance. Af-Art resistance is regulated by mechanism similar to that in other arterioles and in addition, it is regulated by two intrinsic feedback mechanisms: 1) tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to an increase in sodium chloride (NaCl) in the macula densa, via sodium–potassium-2-chloride cotransporter-2 (NKCC2) and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation and is mediated by connecting tubule via epithelial sodium channel (ENaC). CTGF is blocked by the ENaC inhibitor benzamil. Attenuation of TGF reduces Af-Art resistance and allows systemic pressure to get transmitted to the glomerulus that causes glomerular barotrauma/damage. In the current study, we tested the hypothesis that TGF is attenuated in obesity and that CTGF contributes to this effect. We used Zucker obese rats (ZOR) while Zucker lean rats (ZLR) served as controls. We performed in-vivo renal micropuncture of individual rat nephrons while measuring stop-flow pressure (P SF ), an index of P GC. TGF response was measured as a decrease in P SF induced by changing the rate of late proximal perfusion from 0 to 40nl/min in stepwise manner.CTGF was calculated as the difference of P SF value between vehicle and benzamil treatment, at each perfusion rate. Maximal TGF response was significantly less in ZOR (6.16 ± 0.52 mmHg) when compared to the ZLR (8.35 ± 1.00mmHg), p<0.05 , indicating TGF resetting in the ZOR. CTGF was significantly higher in ZOR (6.33±1.95 mmHg) when compared to ZLR (1.38±0.89 mmHg), p<0.05 . When CTGF was inhibited with the ENaC blocker Benzamil (1μM), maximum P SF decrease was 12.30±1.72 mmHg in ZOR and 10.60 ± 1.73 mmHg in ZLR, indicating that blockade of CTGF restored TGF response in ZOR. These observations led us to conclude that TGF is reset in ZOR and that enhanced CTGF contributes to this effect. Increase in CTGF may explain higher renal blood flow, increased P GC and higher glomerular damage in obesity.

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Anaesthesia and the Kidney

Anaesthesia and Intensive Care ◽

10.1177/0310057x8301100402 ◽

1983 ◽

Vol 11 (4) ◽

pp. 292-320 ◽

Cited By ~ 23

Author(s):

Michael J. Cousins ◽

George Skowronski ◽

John L. Plummer

Keyword(s):

Blood Flow ◽

Renal Blood Flow ◽

Flow Distribution ◽

Distal Tubule ◽

Juxtaglomerular Apparatus ◽

Anaesthetic Management ◽

Anatomy And Physiology ◽

Sympathetic Nervous Systems

Applied anatomy and physiology of the kidney are briefly reviewed. This includes an account of renal blood flow, glomerular filtration rate, juxtaglomerular apparatus, renal autoregulation and intra-renal blood flow distribution, tubular transport mechanisms, solute handling in proximal tubule, function of loop of Henle and distal tubule system. This section concludes with a summary of changes in tubule fluid along the length of the nephron. Acute effects of anaesthesia are reviewed in detail. Indirect effects include those on circulatory and sympathetic nervous systems, autoregulation, endocrine systems such as those involving antidiuretic hormone, adrenaline and noradrenaline, renin-angiotensin and aldosterone. Direct effects of anaesthesia on renal function have now been confirmed both in vitro and in vivo. Delayed direct nephrotoxicity of anaesthetics relates predominantly to methoxyflurane (MOF) and its metabolism to inorganic fluoride. Other factors are MOF dose, genetics, age, enzyme induction, obesity, other nephrotoxic drugs. Clinical implications are presented. Enflurane nephrotoxicity is rare but aetiologic factors are similar to the foregoing. Isoflurane and halothane are not nephrotoxic. A consideration of the influence of anaesthetic management on the incidence and severity of postoperative acute renal failure concludes the review.

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INCREASING TIME OF INTESTINAL ISCHEMIA/REPRFUSION (II/R) DECREASES RENAL BLOOD FLOW AND FUNCTION

Shock ◽

10.1097/00024382-200606001-00069 ◽

2006 ◽

Vol 25 (Supplement 1) ◽

pp. 23

Author(s):

L. Wang ◽

F. Liu ◽

L. Bartula ◽

S. Myers

Keyword(s):

Blood Flow ◽

Renal Blood Flow ◽

Intestinal Ischemia ◽

And Function

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Drug-Drug Interactions Between Lithium and Cardiovascular as Well as Anti-Inflammatory Drugs

Pharmacopsychiatry ◽

10.1055/a-1157-9433 ◽

2020 ◽

Vol 53 (05) ◽

pp. 229-234

Author(s):

Maike Scherf-Clavel ◽

Susanne Treiber ◽

Jürgen Deckert ◽

Stefan Unterecker ◽

Leif Hommers

Keyword(s):

Blood Flow ◽

Renal Function ◽

Serum Concentration ◽

Drug Interactions ◽

Renal Blood Flow ◽

Serum Levels ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

And Function ◽

Bipolar Affective Disorders

Abstract Introduction Lithium is the gold standard in treating bipolar affective disorders. As patients become increasingly older, drug-drug interactions leading to decreased excretion of lithium represent a key issue in lithium safety. As no study considered the effect of comedications on lithium serum concentration in combination, we aimed to quantify the impact of drugs affecting renal blood flow and function and thus potentially interacting drugs (diuretics, ACE inhibitors, AT1 antagonists, and non-steroidal anti-inflammatory drugs) on lithium serum levels in addition to age, sex, and sodium and potassium serum levels as well as renal function. Methods Retrospective data of lithium serum levels were analyzed in 501 psychiatric inpatients (2008–2015) by means of linear regression modelling. Results The number of potentially interacting drugs was significantly associated with increasing serum levels of lithium in addition to the established factors of age, renal function, and sodium concentration. Additionally, absolute lithium levels were dependent on sex, with higher values in females. However, only NSAIDs were identified to increase lithium levels independently. Discussion Routine clinical practice needs to focus on drugs affecting renal blood flow and function, especially on NSAIDs as over-the-counter medication that may lead to an increase in lithium serum concentration. To prevent intoxications, clinicians should carefully monitor the comedications, and they should inform patients about possible intoxications due to NSAIDs.

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