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Palm, Fredrik
Publications (10 of 83) Show all publications
Melville, J. M., Palm, F. & Hultstrom, M. (2016). Editorial Material: Renal oxygenation during haemorrhage is not aggravated by angiotensin II AT1-receptor blockade in ACTA PHYSIOLOGICA, vol 216, issue 2, pp 153-155. Acta Physiologica, 216(2), 153-155
Open this publication in new window or tab >>Editorial Material: Renal oxygenation during haemorrhage is not aggravated by angiotensin II AT1-receptor blockade in ACTA PHYSIOLOGICA, vol 216, issue 2, pp 153-155
2016 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 216, no 2, p. 153-155Article in journal, Editorial material (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-124624 (URN)10.1111/apha.12580 (DOI)000367950300002 ()26300043 (PubMedID)
Available from: 2016-02-09 Created: 2016-02-08 Last updated: 2017-11-30
Liss, P., Hansell, P., Fasching, A. & Palm, F. (2016). Iodinated contrast media inhibit oxygen consumption in freshly isolated proximal tubular cells from elderly humans and diabetic rats: Influence of nitric oxide. Upsala Journal of Medical Sciences, 121(1), 12-16
Open this publication in new window or tab >>Iodinated contrast media inhibit oxygen consumption in freshly isolated proximal tubular cells from elderly humans and diabetic rats: Influence of nitric oxide
2016 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 1, p. 12-16Article in journal (Refereed) Published
Abstract [en]

Objectives Mechanisms underlying contrast medium (CM)-induced nephropathy remain elusive, but recent attention has been directed to oxygen availability. The purpose of this study was to evaluate the effect of the low-osmolar CM iopromide and the iso-osmolar CM iodixanol on oxygen consumption (QO(2)) in freshly isolated proximal tubular cells (PTC) from kidneys ablated from elderly humans undergoing nephrectomy for renal carcinomas and from normoglycemic or streptozotocin-diabetic rats. Materials PTC were isolated from human kidneys, or kidneys of normoglycemic or streptozotocin-diabetic rats. QO(2) was measured with Clark-type microelectrodes in a gas-tight chamber with and without each CM (10 mg I/mL medium). L-NAME was used to inhibit nitric oxide (NO) production caused by nitric oxide synthase. Results Both CM reduced QO(2) in human PTC (about -35%) which was prevented by L-NAME. PTC from normoglycemic rats were unaffected by iopromide, whereas iodixanol decreased QO(2) (-34%). Both CM decreased QO(2) in PTC from diabetic rats (-38% and -36%, respectively). L-NAME only prevented the effect of iopromide in the diabetic rat PTC. Conclusions These observations demonstrate that CM can induce NO release from isolated PTC in vitro, which affects QO(2). Our results suggest that the induction of NO release and subsequent effect on the cellular oxygen metabolism are dependent on several factors, including CM type and pre-existing risk factors for the development of CM-induced nephropathy.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2016
Keywords
human; Contrast media; nitric oxide; oxygen consumption; proximal tubule; rat
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-127063 (URN)10.3109/03009734.2016.1144664 (DOI)000372123700002 ()26933994 (PubMedID)
Note

Funding Agencies|Swedish Research Council Medicine and Health; Swedish Diabetes Foundation; Swedish Medical Association

Available from: 2016-04-13 Created: 2016-04-13 Last updated: 2017-11-30
Franzén, S., Pihl, L., Khan, N., Gustafsson, H. & Palm, F. (2016). Pronounced kidney hypoxia precedes albuminuria in type 1 diabetic mice. American Journal of Physiology, 310(9), F807-F809
Open this publication in new window or tab >>Pronounced kidney hypoxia precedes albuminuria in type 1 diabetic mice
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2016 (English)In: American Journal of Physiology, ISSN 0002-9513, E-ISSN 2163-5773, Vol. 310, no 9, p. F807-F809Article in journal (Refereed) Published
Abstract [en]

Intrarenal tissue hypoxia has been proposed as a unifying mechanism for the development of chronic kidney disease, including diabetic nephropathy. However, hypoxia has to be present before the onset of kidney disease in order to be the causal mechanism. In order to establish if hypoxia precedes the onset of diabetic nephropathy, we implemented a minimally invasive electron paramagnetic resonance oximetry technique using implanted oxygen sensing probes for repetitive measurements of in vivo kidney tissue oxygen tensions in mice. Kidney cortex oxygen tensions were measured before and up to 15 days after the induction of insulinopenic diabetes in male mice and compared to normoglycemic controls. On day 16, urinary albumin excretions and conscious glomerular filtration rates were determined in order to define the temporal relationship between intrarenal hypoxia and disease development. Diabetic mice developed pronounced intrarenal hypoxia three days after the induction of diabetes, which persisted throughout the study period. On day 16, diabetic mice had glomerular hyperfiltration, but normal urinary albumin excretion. In conclusion, intrarenal tissue hypoxia in diabetes precedes albuminuria thereby being a plausible cause for the onset and progression of diabetic nephropathy.

Place, publisher, year, edition, pages
American Physiological Society Journals, 2016
Keywords
nephropathy, diabetes, hypoxia, EPR
National Category
Physiology
Identifiers
urn:nbn:se:liu:diva-125526 (URN)10.1152/ajprenal.00049.2016 (DOI)000375115700001 ()
Note

The status of this article was previous Manuscript.

Funding agencies: Swedish Research Council; Swedish Heart Lung Foundation; Swedish Diabetes Foundation

Available from: 2016-02-26 Created: 2016-02-25 Last updated: 2018-01-10Bibliographically approved
Hansell, P. & Palm, F. (2015). A role for the extracellular matrix component hyaluronan in kidney dysfunction during ACE-inhibitor fetopathy. Acta Physiologica, 213(4), 795-804
Open this publication in new window or tab >>A role for the extracellular matrix component hyaluronan in kidney dysfunction during ACE-inhibitor fetopathy
2015 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 213, no 4, p. 795-804Article, review/survey (Refereed) Published
Abstract [en]

Despite data showing that inhibitors of the renin-angiotensin system increase the risks of fetal morbidity and dysfunctionality later in life, their use during pregnancy has increased. The fetopathy induced by angiotensin converting enzyme (ACE) inhibitors is characterized by anuria, hypotension and growth restriction, but can also be associated with pulmonary hypoplasia. In the kidney, this fetopathy includes atrophy of the medulla, reduced number of glomeruli, developmental lesions of tubules and vessels, tubulointerstitial inflammation and extracellular matrix accumulation. Although angiotensin II (Ang II) inhibition during nephrogenesis interferes with normal growth and development, this review will focus on effects of the heavily accumulated matrix component hyaluronan (HA). An important mechanism of HA accumulation during nephrogenesis is disruption of its normal reduction as a consequence of lack of Ang II activation of hyaluronidase. Hyaluronan has very large water-attracting properties and is pro-inflammatory when fragmented. The ensuing inflammation and interstitial oedema affect kidney function. Hyaluronan is colocalized with CD44 overexpression and infiltrating immune cells. These properties make HA a plausible contributor to the observed structural and functional kidney defects associated with the fetopathy. Available data support an involvement of HA in kidney dysfunction of the foetus and during adulthood due to the physico-chemical characteristics of HA. No clinical treatment for HA accumulation exists. Treatment with the HA-degrading enzyme hyaluronidase and an HA synthesis inhibitor has been tested successfully in experimental models in the kidney, heart and pancreas. Reduced HA accumulation to reduce interstitial oedema and inflammation may improve organ function, but this concept needs to be tested in a controlled study before causal relationships can be established.

Place, publisher, year, edition, pages
Wiley: 12 months, 2015
Keywords
ACE inhibitor; dysfunction; fetopathy; hyaluronan; kidney
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-116941 (URN)10.1111/apha.12456 (DOI)000351208100008 ()25600777 (PubMedID)
Available from: 2015-04-10 Created: 2015-04-10 Last updated: 2017-12-04
Nordquist, L., Friederich-Persson, M., Fasching, A., Liss, P., Shoji, K., Nangaku, M., . . . Palm, F. (2015). Activation of Hypoxia-Inducible Factors Prevents Diabetic Nephropathy. Journal of the American Society of Nephrology, 26(2), 328-338
Open this publication in new window or tab >>Activation of Hypoxia-Inducible Factors Prevents Diabetic Nephropathy
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2015 (English)In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 26, no 2, p. 328-338Article in journal (Refereed) Published
Abstract [en]

Hyperglycemia results in increased oxygen consumption and decreased oxygen tension in the kidney. We tested the hypothesis that activation of hypoxia-inducible factors (HIFs) protects against diabetes-induced alterations in oxygen metabolism and kidney function. Experimental groups consisted of control and streptozotocin-induced diabetic rats treated with or without chronic cobalt chloride to activate HIFs. We elucidated the involvement of oxidative stress by studying the effects of acute administration of the superoxide dismutase mimetic tempol. Compared with controls, diabetic rats displayed tissue hypoxia throughout the kidney, glonnerular hyperfiltration, increased oxygen consumption, increased total mitochondrial leak respiration, and decreased tubular sodium transport efficiency. Diabetic kidneys showed proteinuria and tubulointerstitial damage. Cobalt chloride activated HIFs, prevented the diabetes-induced alterations in oxygen metabolism, mitochondrial leak respiration, and kidney function, and reduced proteinuria and tubulointerstitial damage. The beneficial effects of tempol were less pronounced after activation of HIFs, indicating improved oxidative stress status. In conclusion, activation of HIFs prevents diabetes-induced alteration in kidney oxygen metabolism by normalizing glomerular filtration, which reduces tubular electrolyte load, preventing mitochondrial leak respiration and improving tubular transport efficiency. These improvements could be related to reduced oxidative stress and account for the reduced proteinuria and tubulointerstitial damage. Thus, pharnnacologic activation of the HIF system may prevent development of diabetic nephropathy.

Place, publisher, year, edition, pages
American Society of Nephrology, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-114575 (URN)10.1681/ASN.2013090990 (DOI)000348623700012 ()25183809 (PubMedID)
Note

Funding Agencies|Swedish Medical Research Council; Swedish Society for Medical Research; Swedish Heart-Lung Foundation; Swedish Diabetes Foundation; Japanese Society for Promotion of Science [24390213]

Available from: 2015-02-27 Created: 2015-02-26 Last updated: 2017-12-04
ONeill, J., Fasching, A., Pihl, L., Patinha, D., Franzén, S. & Palm, F. (2015). Acute SGLT inhibition normalizes O-2 tension in the renal cortex but causes hypoxia in the renal medulla in anaesthetized control and diabetic rats. American Journal of Physiology - Renal Physiology, 309(3), F227-F234
Open this publication in new window or tab >>Acute SGLT inhibition normalizes O-2 tension in the renal cortex but causes hypoxia in the renal medulla in anaesthetized control and diabetic rats
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2015 (English)In: American Journal of Physiology - Renal Physiology, ISSN 0363-6127, E-ISSN 1522-1466, Vol. 309, no 3, p. F227-F234Article in journal (Refereed) Published
Abstract [en]

Early stage diabetic nephropathy is characterized by glomerular hyperfiltration and reduced renal tissue PO2. Recent observations have indicated that increased tubular Na+-glucose linked transport (SGLT) plays a role in the development of diabetes-induced hyperfiltration. The aim of the present study was to determine how inhibition of SLGT impacts upon PO2 in the diabetic rat kidney. Diabetes was induced by streptozotocin in Sprague-Dawley rats 2 wk before experimentation. Renal hemodynamics, excretory function, and renal O-2 homeostasis were measured in anesthetized control and diabetic rats during baseline and after acute SGLT inhibition using phlorizin (200 mg/kg ip). Baseline arterial pressure was similar in both groups and unaffected by SGLT inhibition. Diabetic animals displayed reduced baseline PO2 in both the cortex and medulla. SGLT inhibition improved cortical PO2 in the diabetic kidney, whereas it reduced medullary PO2 in both groups. SGLT inhibition reduced Na+ transport efficiency [tubular Na+ transport (TNa)/renal O-2 consumption (QO(2))] in the control kidney, whereas the already reduced TNa/QO(2) in the diabetic kidney was unaffected by SGLT inhibition. In conclusion, these data demonstrate that when SGLT is inhibited, renal cortex PO2 in the diabetic rat kidney is normalized, which implies that increased proximal tubule transport contributes to the development of hypoxia in the diabetic kidney. The reduction in medullary PO2 in both control and diabetic kidneys during the inhibition of proximal Na+ reabsorption suggests the redistribution of active Na+ transport to less efficient nephron segments, such as the medullary thick ascending limb, which results in medullary hypoxia.

Place, publisher, year, edition, pages
American Physiological Society, 2015
Keywords
diabetes; oxgen consumption; renal hypoxia; sodium-glucose linked transport; sodium transport
National Category
Physiology
Identifiers
urn:nbn:se:liu:diva-121112 (URN)10.1152/ajprenal.00689.2014 (DOI)000359731400005 ()26041448 (PubMedID)
Note

Funding Agencies|Swedish Heart and Lung Foundation; Swedish Diabetes Foundation; Swedish Research Council Medicine and Health

Available from: 2015-09-07 Created: 2015-09-07 Last updated: 2018-01-11
Persson, P., Friederich-Persson, M., Fasching, A., Hansell, P., Inagi, R. & Palm, F. (2015). Adenosine A(2)a receptor stimulation prevents proteinuria in diabetic rats by promoting an anti-inflammatory phenotype without affecting oxidative stress. Acta Physiologica, 214(3), 311-318
Open this publication in new window or tab >>Adenosine A(2)a receptor stimulation prevents proteinuria in diabetic rats by promoting an anti-inflammatory phenotype without affecting oxidative stress
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2015 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 214, no 3, p. 311-318Article in journal (Refereed) Published
Abstract [en]

AimDiabetic patients are at increased risk for kidney disease. There is presently no clinical treatment available that effectively protects kidney function in diabetics. This study investigates whether chronic stimulation of the adenosine A(2a) receptor (A(2a)AR) protects kidney function in insulinopenic diabetic rats. MethodsStreptozotocin-induced diabetic rats and corresponding controls were chronically treated with the adenosine A(2a)AR agonist CGS21680 throughout the four-week diabetes duration. Kidney function was thereafter investigated, and urine and plasma samples were collected for analysis of protein, oxidative stress and inflammatory markers. ResultsGlomerular filtration rate, renal blood flow, filtration fraction and diabetes-induced kidney hypoxia were all unaffected by chronic A(2a)AR stimulation. Furthermore, diabetic rats had increased oxidative stress, which was further increased by chronic A(2a)AR stimulation. However, the 10-fold increased urinary protein excretion observed in the diabetic rats was completely prevented by chronic A(2a)AR stimulation. These beneficial effects were accompanied by reduced levels of the pro-inflammatory TNF- and increased levels of the anti-inflammatory IL-10 as well as decreased infiltration of macrophages, glomerular damage and basement membrane thickness. ConclusionChronic A(2a)AR stimulation prevents proteinuria and glomerular damage in experimental diabetes via an anti-inflammatory mechanism independent of oxidative stress and kidney hypoxia.

Place, publisher, year, edition, pages
Wiley: 12 months, 2015
Keywords
CGS21680; diabetes mellitus; diabetic nephropathy; kidney; macrophages; tumour necrosis factor-alpha
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-120031 (URN)10.1111/apha.12511 (DOI)000356306300007 ()25891445 (PubMedID)
Available from: 2015-07-06 Created: 2015-07-06 Last updated: 2017-12-04
Palm, F. (2015). Editorial Material: ET-1 increases reactive oxygen species in hypoxic glomeruli during high salt intake in ACTA PHYSIOLOGICA, vol 213, issue 3, pp 559-560. Acta Physiologica, 213(3), 559-560
Open this publication in new window or tab >>Editorial Material: ET-1 increases reactive oxygen species in hypoxic glomeruli during high salt intake in ACTA PHYSIOLOGICA, vol 213, issue 3, pp 559-560
2015 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 213, no 3, p. 559-560Article in journal, Editorial material (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-114971 (URN)10.1111/apha.12443 (DOI)000348531600005 ()25535871 (PubMedID)
Available from: 2015-03-10 Created: 2015-03-06 Last updated: 2017-12-04
Franzén, S. & Palm, F. (2015). Endothelin type A receptor inhibition normalises intrarenal hypoxia in rats used as a model of type 1 diabetes by improving oxygen delivery. Diabetologia, 58(10), 2435-2442
Open this publication in new window or tab >>Endothelin type A receptor inhibition normalises intrarenal hypoxia in rats used as a model of type 1 diabetes by improving oxygen delivery
2015 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no 10, p. 2435-2442Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis Intrarenal tissue hypoxia, secondary to increased oxygen consumption, has been suggested as a unifying mechanism for the development of diabetic nephropathy. Increased endothelin-1 signalling via the endothelin type A receptor (ETA-R) has been shown to contribute to the development of chronic kidney disease, but its role in kidney oxygen homeostasis is presently unknown. Methods The effects of acute ETA-R inhibition (8 nmol/l BQ-123 for 30-40 min directly into the left renal artery) on kidney function and oxygen metabolism were investigated in normoglycaemic control and insulinopenic male Sprague Dawley rats (55 mg/kg streptozotocin intravenously 2 weeks before the main experiment) used as a model of type 1 diabetes. Results Local inhibition of ETA-R in the left kidney did not affect BP in either the control or the diabetic rats. As previously reported, diabetic rats displayed increased kidney oxygen consumption resulting in tissue hypoxia in both the kidney cortex and medulla. The inhibition of ETA-Rs restored normal kidney tissue oxygen availability in the diabetic kidney by increasing renal blood flow, but did not affect oxygen consumption. Furthermore, ETA-R inhibition reduced the diabetes-induced glomerular hyperfiltration and increased the urinary sodium excretion. Kidney function in normoglycaemic control rats was largely unaffected by BQ-123 treatment, although it also increased renal blood flow and urinary sodium excretion in these animals. Conclusions/interpretation Acutely reduced intrarenal ETA-R signalling results in significantly improved oxygen availability in the diabetic kidney secondary to elevated renal perfusion. Thus, the beneficial effects of ETA-R inhibition on kidney function in diabetes may be due to improved intrarenal oxygen homeostasis.

Place, publisher, year, edition, pages
SPRINGER, 2015
Keywords
BQ-123; Diabetic nephropathy; Endothelin type; A receptor; Hypoxia; Kidney function; Rats
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-122101 (URN)10.1007/s00125-015-3690-9 (DOI)000361538600027 ()26173672 (PubMedID)
Note

Funding Agencies|Swedish Research Council; Swedish Diabetes Foundation; Family Ernfors Fund

Available from: 2015-10-19 Created: 2015-10-19 Last updated: 2017-12-01
Stridh, S., Palm, F., Takahashi, T., Ikegami-Kawai, M. & Hansell, P. (2015). Inhibition of mTOR activity in diabetes mellitus reduces proteinuria but not renal accumulation of hyaluronan. Upsala Journal of Medical Sciences, 120(4), 233-240
Open this publication in new window or tab >>Inhibition of mTOR activity in diabetes mellitus reduces proteinuria but not renal accumulation of hyaluronan
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2015 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 4, p. 233-240Article in journal (Refereed) Published
Abstract [en]

Objectives. Accumulation of extracellular matrix (ECM) components is an early sign of diabetic nephropathy. Also the glycosaminoglycan hyaluronan (HA) is elevated in the renal interstitium during experimental diabetes. The mammalian target of rapamycin (mTOR) pathway participates in the signaling of hyperglycemia-induced ECM accumulation in the kidney, but this has not yet been investigated for HA. We hypothesized that interstitial HA accumulation during diabetes may involve mTOR activation.Methods. Diabetic rats (6 weeks post-streptozotocin (STZ)) were treated with rapamycin to inhibit mTOR or vehicle for 2 additional weeks. Kidney function (glomerular filtration rate, renal blood flow, urine output) and regional renal HA content were thereafter analyzed. The ability of the animals to respond to desmopressin was also tested.Results. Diabetic animals displayed hyperglycemia, proteinuria, hyperfiltration, renal hypertrophy, increased diuresis with reduced urine osmolality, and reduced weight gain. Cortical and outer medullary HA was elevated in diabetic rats. Urine hyaluronidase activity was almost doubled in diabetic rats compared with controls. The ability to respond to desmopressin was absent in diabetic rats. Renal blood flow and arterial blood pressure were unaffected by the diabetic state. In diabetic rats treated with rapamycin the proteinuria was reduced by 32%, while all other parameters were unaffected.Conclusion. Regional renal accumulation of the ECM component HA is not sensitive to mTOR inhibition by rapamycin, while proteinuria is reduced in established STZ-induced diabetes. Whether the diabetes-induced renal accumulation of HA occurs through different pathways than other ECM components, or is irreversible after being established, remains to be shown.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2015
Keywords
Diabetes mellitus; hyaluronan; hyaluronidase; mTOR; nephropathy; rapamycin
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-123835 (URN)10.3109/03009734.2015.1062442 (DOI)000365684900002 ()26175092 (PubMedID)
Note

Funding Agencies|Swedish Science Council (Medicine) grant [10840]

Available from: 2016-01-11 Created: 2016-01-11 Last updated: 2017-12-01
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