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0000-0001-7637-3661
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Institute for Breathing and Sleep
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Publisher: Wiley
Date: 2021
DOI: 10.1111/IMJ.14775
Publisher: Public Library of Science (PLoS)
Date: 09-01-2012
Publisher: S. Karger AG
Date: 2012
DOI: 10.1159/000341732
Abstract: b i Background/Aims: /i /b The effects of haemodialysis on the microcirculation are poorly understood. This study examined the changes in small vessel calibre. b i Methods: /i /b 24 patients (including 12 males, median age 62.5 years, range 30–87) underwent digital retinal photography immediately before and after routine haemodialysis. Arteriolar and venular calibres were measured from the images by a trained grader using a highly reproducible, computer-assisted method. b i Results: /i /b Patients had an average 2.0 ± 0.3 litres of fluid removed with dialysis, and their mean arterial blood pressure fell by 6.8 mm Hg (CI 13.8–0.2, p = 0.06). Retinal arteriole calibre did not change (mean difference 2.3 µm, CI –1.1 to 5.7, p = 0.17) but the venules dilated (mean difference 12.7 µm, CI 7.3–18.3, p 0.001). Calibre returned to baseline by 2 h. Venules dilated less in diabetics than non-diabetics (mean difference –6.2 µm, CI –9.6 to –2.9, p 0.01). Retinal venular dilatation correlated positively with the volume of fluid removed per kilogramme body weight (5.9, CI 0.2–11.5, p = 0.04), and negatively with the fall in mean arterial pressure (–0.36, CI –0.72 to –0.01, p 0.05) after adjusting for age, gender, diabetes and dyslipidaemia. b i Conclusion: /i /b Haemodialysis is associated with systemic venular dilatation.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.BONE.2021.116260
Abstract: Measurement of bone mineral density (BMD) is recommended in patients with chronic kidney disease (CKD). However, most persons in the community and most patients with CKD have osteopenia, suggesting fracture risk is low. Bone loss compromises bone microarchitecture which increases fragility disproportionate to modest deficits in BMD. We therefore hypothesized that patients with CKD have reduced estimated failure load due to deterioration in microarchitecture irrespective of whether they have normal femoral neck (FN) BMD, osteopenia or osteoporosis. We measured distal tibial and distal radial microarchitecture in 128 patients with CKD and 275 age- and sex-matched controls using high resolution peripheral quantitative computed tomography, FN-BMD using bone densitometry and estimated failure load at the distal appendicular sites using finite element analysis. Patients versus controls respectively had: lower tibial cortical area 219 (40.7) vs. 237 (35.3) mm Bone fragility is likely to be present in patients with CKD despite them having osteopenia or normal BMD. Measuring microarchitecture may assist in targeting therapy to those at risk of fracture.
Publisher: Wiley
Date: 04-2010
Publisher: American Physiological Society
Date: 09-2013
DOI: 10.1152/AJPRENAL.00407.2012
Abstract: Salt reabsorption is the major energy-requiring process in the kidney, and AMP-activated protein kinase (AMPK) is an important regulator of cellular metabolism. Mice with targeted deletion of the β1-subunit of AMPK (AMPK-β1 −/− mice) had significantly increased urinary Na + excretion on a normal salt diet. This was associated with reduced expression of the β-subunit of the epithelial Na + channel (ENaC) and increased subapical tubular expression of kidney-specific Na + -K + -2Cl − cotransporter 2 (NKCC2) in the medullary thick ascending limb of Henle. AMPK-β1 −/− mice fed a salt-deficient diet were able to conserve Na + , but renin secretion increased 180% compared with control mice. Cyclooxygenase-2 mRNA also increased in the kidney cortex, indicating greater signaling through the macula densa tubular salt-sensing pathway. To determine whether the increase in renin secretion was due to a change in regulation of fatty acid metabolism by AMPK, mice with a mutation of the inhibitory AMPK phosphosite in acetyl-CoA carboxylase 1 [ACC1-knockin (KI) S79A mice] were examined. ACC1-KI S79A mice on a normal salt diet had no increase in salt loss or renin secretion, and expression of NKCC2, Na + -Cl − cotransporter, and ENaC-β were similar to those in control mice. When mice were placed on a salt-deficient diet, however, renin secretion and cortical expression of cyclooxygenase-2 mRNA increased significantly in ACC1-KI S79A mice compared with control mice. In summary, our data suggest that renin synthesis and secretion are regulated by AMPK and coupled to metabolism by phosphorylation of ACC1.
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.ATHEROSCLEROSIS.2007.12.003
Abstract: Endothelial cell lipotoxicity mediated by accumulation of free fatty acids is an early event in the pathogenesis of atherosclerosis. The energy-sensor AMP-activated protein kinase (AMPK) is a key regulator of endothelial cell lipid metabolism. To test the hypothesis that bradykinin (BK) regulates AMPK and fatty acid oxidation in endothelium, stimulations of bovine aortic endothelial cells (BAECs) with bradykinin were performed. BK stimulation caused a 2.3-fold increase in AMPK activity (p<0.05). Activation of AMPK by BK in BAECs was inhibited by STO-609, an inhibitor of calmodulin-dependent kinase kinase (CaMKK), which is a known kinase upstream of AMPK. BK stimulation of BAECs also increased phosphorylation of acetyl-CoA carboxylase and this was inhibited by both STO-609 and over expression of an adenovirus encoded AMPK dominant negative (Ad-AMPK-DN). Furthermore, BK caused a 1.7-fold increase in palmitate oxidation in BAECs (p<0.05) and this increase was completely inhibited by the Ad-AMPK-DN (p<0.005). Inhibition of AMPK activation in response to BK by STO-609 had no effect on activating phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser(1177), consistent with CaMKK and AMPK not being required for phosphorylation of eNOS in response to BK. In conclusion, BK stimulates endothelial cell fatty acid oxidation by CaMKK-dependent activation of AMPK. The effect of BK on endothelial lipid metabolism represents a novel pathway for targeting fatty acid mediated endothelial cell dysfunction.
Publisher: Wiley
Date: 04-2010
Publisher: The Royal Society
Date: 10-2021
Abstract: Anticipatory behaviour is the expectation of a near-future event based on information processed in the past and influences an animal's tactical decisions, particularly when there are significant fitness consequences. The grass lizard ( Takydromus viridipunctatus ) perches on blades of grass at night which likely reduces the probability of predation by terrestrial predators such as snakes, rodents and shrews. During twilight (starting 30 min before sunrise), they move from above the grass to within grass clumps and this is thought to afford the lizard protection while reducing detection by avian predators. Here, we examined how lizards shift their behaviour as a function of visual detectability to their primary predator, the cattle egret ( Bubulcus ibis ). We show that the lizards shift from their perch site during twilight at the earliest time at which egrets depart communal roosts. At the same time, visual modelling shows a dramatic increase in the detectability of the lizards to the visual system of egrets. Therefore, anticipatory behaviour in response to environmental cues acts to reduce predation risk as lizards become more conspicuous and predators become more active. Grass lizard anticipatory behaviour appears to be finely tuned by natural selection to adjust to temporal changes in predation risk.
Publisher: Elsevier BV
Date: 02-2007
Publisher: Massachusetts Medical Society
Date: 02-04-2009
Publisher: Wiley
Date: 31-05-2020
DOI: 10.1111/NEP.13722
Publisher: American Physiological Society
Date: 11-2005
DOI: 10.1152/AJPRENAL.00458.2004
Abstract: A fundamental aspect of acute renal ischemia is energy depletion, manifest as a falling level of ATP that is associated with a simultaneous rise in AMP. The energy sensor AMP-activated protein kinase (AMPK) is activated by a rising AMP-to-ATP ratio, but its role in acute renal ischemia is unknown. AMPK is activated in the ischemic heart and is reported to phosphorylate both endothelial nitric oxide synthase (eNOS) and acetyl-CoA carboxylase. To study activation of AMPK in acute renal ischemia, the renal pedicle of anesthetized Sprague-Dawley rats was cross-cl ed for increasing time intervals. AMPK was strongly activated within 1 min and remained so after 30 min. However, despite the robust activation of AMPK, acute renal ischemia did not increase phosphorylation of the AMPK phosphorylation sites eNOS-Ser 1177 or acetyl-CoA carboxylase-Ser 79 . Activation of AMPK in bovine aortic endothelial cells by the ATP-depleting agent antimycin A and the antidiabetic drug phenformin also did not increase phosphorylation of eNOS-Ser 1177 , confirming that AMPK activation and phosphorylation of eNOS are dissociated in some situations. Immunoprecipitation studies demonstrated that the dissociation between AMPK activation and phosphorylation of eNOS-Ser 1177 was not due to changes in the physical associations between AMPK, eNOS, or heat shock protein 90. In conclusion, acute renal ischemia rapidly activates the energy sensor AMPK, which is known to maintain ATP reserves during energy stress. The substrates it phosphorylates, however, are different from those in other organs such as the heart.
Publisher: Wiley
Date: 28-03-2021
DOI: 10.1111/HDI.12924
Abstract: Hemodialysis (HD) with medium cut‐off (MCO) dialyzers may expand molecular clearance, predominantly larger middle molecules (molecular weight 25–60 kDa). However, the impact of MCO dialyzers on long‐term clearance of various other components of the uremic milieu is unknown. The tRial Evaluating Mid cut‐Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL‐HD) provided an opportunity to assess the effect of MCO dialyzers on protein‐bound uremic toxins and novel markers of mineral metabolism. This exploratory sub‐study of REMOVAL‐HD evaluated changes in protein‐bound solutes (total and free indoxyl sulfate [IS] and p ‐cresyl sulfate [PCS]) and mineral metabolism markers (intact fibroblast growth factor‐23 [iFGF23], fetuin‐A and endogenous calciprotein particles [CPP‐1 and CPP‐2]). Mid‐week, pre‐HD serum s les were collected at baseline and after 12 and 24 weeks of MCO use in stable adult patients. Change from baseline to Week 12 and 24 was estimated using linear mixed effects models. Eighty‐nine participants were studied (mean age 67 ± 15 years, 38% female, 51% diabetic, median urine output 200 ml/24 h). Serum iFGF23 was reduced at Week 12 compared to baseline (−26.8% [95%CI −39.7, −11.1], p = 0.001), which was sustained at Week 24 (−21.7% [95%CI ‐35.7, −4.5], p = 0.012). There was no significant change in serum IS, PCS, fetuin‐A, CPP‐1, or CPP‐2. The use of a MCO dialyzer over 24 weeks was associated with a sustained reduction in FGF23, while other measured components of the uremic milieu were not significantly altered. Further studies are required to determine whether FGF23 reduction is associated with improved patient outcomes.
Publisher: Wiley
Date: 08-2022
DOI: 10.1111/DGD.12800
Abstract: Sex chromosomes in poikilothermal vertebrates are characterized by rapid and erse evolution at the species or population level. Our previous study revealed that the Taiwanese frog Odorrana swinhoana (2n = 26) has a unique system of multiple sex chromosomes created by three sequential translocations among chromosomes 1, 3, and 7. To reveal the evolutionary history of sex chromosomes in the Odorrana species complex, we first identified the original, homomorphic sex chromosomes, prior to the occurrence of translocations, in the ancestral‐type population of O. swinhoana . Then, we extended the investigation to a closely related Japanese species, Odorrana utsunomiyaorum , which is distributed on two small islands. We used a high‐throughput nuclear genomic approach to analyze single‐nucleotide polymorphisms and identify the sex‐linked markers. Those isolated from the O. swinhoana ancestral‐type population were found to be aligned to chromosome 1 and showed male heterogamety. In contrast, almost all the sex‐linked markers isolated from O. utsunomiyaorum were heterozygous in females and homozygous in males and were aligned to chromosome 9. Morphologically, we confirmed chromosome 9 to be heteromorphic in females, showing a ZZ‐ZW sex determination system, in which the W chromosomes were heterochromatinized in a stripe pattern along the chromosome axis. These results indicated that after ergence of the two species, the ancestral homomorphic sex chromosome 1 underwent highly rapid and erse evolution, i.e., sequential translocations with two autosomes in O. swinhoana, and turnover to chromosome 9 in O. utsunomiyaorum , with a transition from XY to ZW heterogamety and change to heteromorphy.
Publisher: American Physiological Society
Date: 04-2013
DOI: 10.1152/AJPRENAL.00601.2012
Abstract: Albuminuria is associated with the additional loss in the urine of small molecular weight proteins normally degraded by the proximal convoluted tubule (PCT), and competition for binding to the megalin/cubilin reuptake system has been considered the likely cause. We have previously reported that deficiency of the intrinsic lysosomal protein Limp-2 causes tubular proteinuria due to reduced fusion of endosomes with lysosomes in the PCT leading to inadequate proteolysis. To determine whether this mechanism also contributes to the tubular proteinuria induced by albumin overload in normal mice, wild-type (WT) mice received daily BSA injections intraperitoneally for 10 days, using untreated Limp-2 −/− mice as positive controls for inadequate proteolysis. BSA overload induced significant urinary loss of megalin and cubilin ligands in WT mice. Tubular uptake of Alexa-conjugated BSA, administered by intravenous injection, was not reduced in the PCT of mice receiving intraperitoneal BSA. Expression of the tubular protein receptor megalin was also unchanged. There was a delay in proteolysis of reabsorbed proteins in WT mice receiving BSA, evidenced by an increased quantity of retinol-binding protein (RBP) in the kidney cortex, increased basal distribution of endocytosed RBP in cells of the PCT, and persistence of exogenous Alexa-conjugated BSA and RBP after injection. Upregulation of cathepsin L and normal fusion of lysosomes with endosomes were apparently not sufficient to maintain normal clearance of endocytosed proteins. The data suggest that in the presence of competition from albumin overload, reabsorption of filtered proteins is limited by the capacity of lysosomal degradation rather than receptor-mediated endocytosis.
Publisher: Wiley
Date: 04-2002
DOI: 10.1046/J.1444-0903.2001.00199.X
Abstract: We describe three cases of acute renal failure in young men who ingested wild mushrooms with the intent of producing hallucinations. Two cases remained dialysis dependent and, in these cases, renal biopsy revealed tubulointerstitial nephritis and fibrosis. Similar cases have been reported in other countries, but not in Australia. The most recognized mushroom nephrotoxin is orellanine, however the causative mushroom species and the actual toxin involved in these cases are unknown.
Publisher: Informa UK Limited
Date: 03-2014
DOI: 10.3109/09687688.2014.902128
Abstract: The co-transporter activity of Na(+)-K(+)-2Cl(-) 1 (NKCC1) is dependent on phosphorylation. In this study we show the energy-sensing kinase AMPK inhibits NKCC1 activity. Three separate AMPK activators (AICAR, Phenformin and A-769662) inhibited NKCC1 flux in a variety of nucleated cells. Treatment with A-769662 resulted in a reduction of NKCC1(T212/T217) phosphorylation, and this was reversed by treatment with the non-selective AMPK inhibitor Compound C. AMPK dependence was confirmed by treatment of AMPK null mouse embryonic fibroblasts, where A-769662 had no effect on NKCC1 mediated transport. AMPK was found to directly phosphorylate a recombinant human-NKCC1 N-terminal fragment (1-293) with the phosphorylated site identified as S77. Mutation of Serine 77 to Alanine partially prevented the inhibitory effect of A-769662 on NKCC1 activity. In conclusion, AMPK can act to reduce NKCC1-mediated transport. While the exact mechanism is still unclear there is evidence for both a direct effect on phosphorylation of S77 and reduced phosphorylation of T212/217.
Publisher: S. Karger AG
Date: 2020
DOI: 10.1159/000505567
Abstract: b i Background: /i /b A new class of dialysis membrane, the mid cut-off (MCO) dialyzer, has been developed to improve the clearance of uremic toxins in hemodialysis (HD). The a tRial Evaluating Mid cut-Off Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) study aimed to determine if regular use of MCO dialyzer was safe and specifically did not result in a significant loss of albumin. b i Methods: /i /b This investigator initiated, crossover, longitudinal, device study was conducted across 9 centers in Australia and New Zealand ( i n /i = 89). Participants had a 4-week wash-in with high-flux HD, followed by 24-week intervention with MCO HD and a subsequent 4-week wash-out with high-flux HD. The primary outcome was change in serum albumin between weeks 4 and 28. Secondary outcomes included trends in serum albumin, changes in kappa- and lambda-free light chains (FLC), 6-min walk test (6MWT), malnutrition inflammation score (MIS), restless legs score and quality of life. b i Results: /i /b Participants had a mean age of 66 ± 14 years, 62% were men, 45% were anuric, and 51% had diabetes. There was no reduction in serum albumin following treatment with MCO HD (mean reduction –0.7 g/L, 95% CI –1.5 to 0.1). A sustained, unexplained reduction in serum albumin (& #x3e %) was not observed in any participant. A reduction in FLC was observed 2 weeks into MCO HD (lambda-FLC: Δ –9.1 mg/L, 95% CI –14.4 to –3.7 kappa-FLC: Δ –5.7 mg/L, 95% CI –9.8 to –1.6) and was sustained for the rest of the study intervention. Both FLC increased after the cessation of MCO use. There was no improvement in restless legs symptoms, quality of life, 6MWT or MIS scores. b i Conclusions: /i /b Regular HD using the MCO dialyzer did not result in a significant fall in serum albumin. There were no effects on quality of life, functional status or nutrition. b i Trial Registration: /i /b Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482.
Publisher: Springer Science and Business Media LLC
Date: 03-09-2020
DOI: 10.1038/S41598-020-71475-Z
Abstract: Fatty acid oxidation is the major energy pathway used by the kidney, although glycolysis becomes more important in the low oxygen environment of the medulla. Fatty acid oxidation appears to be reduced in renal fibrosis, and drugs that reverse this improve fibrosis. Expression of glycolytic genes is more variable, but some studies have shown that inhibiting glycolysis reduces renal fibrosis. To address the role of glycolysis in renal fibrosis, we have used a genetic approach. The crucial control point in the rate of glycolysis is 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase. Phosphorylation of the kidney isoform, PFKFB2, on residues Ser 468 and Ser 485 stimulates glycolysis and is the most important mechanism regulating glycolysis. We generated transgenic mice with inactivating mutations of Ser 468 and Ser 485 in PFKFB2 (PFKFB2 KI mice). These mutations were associated with a reduced ability to increase glycolysis in primary cultures of renal tubular cells from PFKFB2 KI mice compared to WT cells. This was associated in PFKFB2 KI mice with increased renal fibrosis, which was more severe in the unilaternal ureteric obstruction (UUO) model compared with the folic acid nephropathy (FAN) model. These studies show that phosphorylation of PFKFB2 is important in limiting renal fibrosis after injury, indicating that the ability to regulate and maintain adequate glycolysis in the kidney is crucial for renal homeostasis. The changes were most marked in the UUO model, probably reflecting a greater effect on distal renal tubules and the greater importance of glycolysis in the distal nephron.
Publisher: Elsevier BV
Date: 09-2022
Publisher: American Physiological Society
Date: 07-2014
DOI: 10.1152/AJPRENAL.00524.2013
Abstract: Enhanced tubular reabsorption of salt is important in the pathogenesis of obesity-related hypertension, but the mechanisms remain poorly defined. To identify changes in the regulation of salt transporters in the kidney, C57BL/6 mice were fed a 40% fat diet [high-fat diet (HFD)] or a 12% fat diet (control diet) for 14 wk. Compared with control diet-fed mice, HFD-fed mice had significantly greater elevations in weight, blood pressure, and serum insulin and leptin levels. When we examined Na + transporter expression, Na + -K + -2Cl − cotransporter (NKCC2) was unchanged in whole kidney and reduced in the cortex, Na + -Cl − cotransporter (NCC) and α-epithelial Na + channel (ENaC) and γ-ENaC were unchanged, and β-ENaC was reduced. Phosphorylation of NCC was unaltered. Activating phosphorylation of NKCC2 at S126 was increased 2.5-fold. Activation of STE-20/SPS1-related proline-alanine-rich protein kinase (SPAK)/oxidative stress responsive 1 kinase (OSR1) was increased in kidneys from HFD-fed mice, and enhanced phosphorylation of NKCC2 at T96/T101 was evident in the cortex. Increased activity of NKCC2 in vivo was confirmed with diuretic experiments. HFD-fed mice had reduced activating phosphorylation of AMP-activated protein kinase (AMPK) in the renal cortex. In vitro, activation of AMPK led to a reduction in phospho-SPAK hospho-OSR1 in AMPK +/+ murine embryonic fibroblasts (MEFs), but no effect was seen in AMPK −/− MEFs, indicating an AMPK-mediated effect. Activation of the with no lysine kinase/SPAK/OSR1 pathway with low-NaCl solution invoked a greater elevation in phospho-SPAK hospho-OSR1 in AMPK −/− MEFs than in AMPK +/+ MEFs, consistent with a negative regulatory effect of AMPK on SPAK/OSR1 phosphorylation. In conclusion, this study identifies increased phosphorylation of NKCC2 on S126 as a hitherto-unrecognized mediator of enhanced Na + reabsorption in obesity and identifies a new role for AMPK in regulating the activity of SPAK/OSR1.
Publisher: SAGE Publications
Date: 27-06-2021
DOI: 10.1177/13674935211028410
Abstract: The management of chronic kidney disease is complex. With disease management being the responsibility of parents in the paediatric renal clinic, the responsibility is gradually shifted to adolescents and young adults during the transition to adult care. This multi-perspective qualitative study aimed to explore the experiences of adolescents and young adults, their parents and health professionals to gain an insight into transitional care. Focussing on the transition process and transfer to adult care, 18 adolescents and young adults and eight mothers participated in in idual semi-structured interviews. Additionally, three focus groups were conducted with 20 multidisciplinary health professionals. Data were transcribed verbatim and analysed thematically. Similar responses from adolescents and young adults and mothers included the reluctance to leave the paediatric health service. Mothers found the transition to adult care more challenging than the adolescents and young adults. While health professionals acknowledged that engaging adolescents and young adults in their own care was challenging, they believed parents had an important role in facilitating their child’s independence. This study highlights that health professionals in both paediatric and adult health services need to work collaboratively. However, importantly, health professionals need to be mindful that parents require an equal amount of engagement as adolescents and young adults, if not more, to mitigate parental barriers in achieving a successful transfer.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1038/KI.2013.289
Abstract: AMG 416 (velcalcetide), a novel peptide agonist of the calcium-sensing receptor, lowers plasma parathyroid hormone in preclinical uremic animal models and in normal healthy in iduals. Here, we studied its efficacy in hemodialysis patients suffering from secondary hyperparathyroidism. Major inclusion criteria were hemodialysis for at least 3 months, serum parathyroid hormone over 300 pg/ml, a corrected serum calcium of 9.0 mg/dl or more, and stable doses of vitamin D analogs for at least 3 weeks prior to screening. Twenty-eight patients were enrolled in one of five cohorts (5, 10, 20, 40, 60 mg). Cohorts 1-3 (four patients each) were treated in a two-period crossover design, while cohorts 4 and 5 (eight patients each) were randomized 1:1 to AMG 416 or placebo. Patients were admitted to a clinical research unit following hemodialysis and studied for 3 days prior to discharge for hemodialysis. Single intravenous doses of AMG 416 from 5 to 60 mg were well tolerated, and plasma levels increased in a dose-related manner. AMG 416 treatment was associated with significant, dose-dependent reductions in serum parathyroid hormone and fibroblast growth factor 23. Compared with placebo, all dose groups of 10 mg or more were associated with attenuation in the rise in serum phosphate during the interdialytic period. Dose-dependent reductions in serum calcium were observed and were well tolerated. Thus, AMG 416 represents a novel therapeutic approach for the treatment of secondary hyperparathyroidism in hemodialysis patients.
Publisher: Wiley
Date: 23-02-2022
DOI: 10.1111/CTR.14606
Abstract: Achieving therapeutic tacrolimus levels is an essential component of balancing immunosuppression in kidney transplantation. At our institution, the starting tacrolimus dose was reduced from .075 mg/kg BD (higher dose [HD]) to .050 mg/kg BD (lower dose [LD]), to better achieve our target level of 6–10 μg/L in the early posttransplant period. Kidney transplant recipients (KTRs) transplanted 1‐year before (HD: n = 64) and after (LD: n = 63) the starting dose reduction were retrospectively compared. Achieved tacrolimus levels were significantly lower in the LD group during the first 14 days posttransplant, but not at day 21 or day 28. A higher proportion of LD KTRs achieved therapeutic levels (day 1–3: 36.1% vs. 18.8% day 4–7: 50.8% vs. 40.6%, day 8–14: 83.6% vs. 71.7%), while the HD KTRs were more likely to have supratherapeutic levels. Tacrolimus dose was significantly lower on day 5 compared to day 0 in the HD group but similar in the LD group. Rates of delayed graft function, posttransplant diabetes, and treated rejection at 6 months and graft outcomes at 3 years were all similar. Lowering the starting tacrolimus dose increased the proportion of KTRs achieving therapeutic range and minimized dose changes early posttransplant without an impact on clinical outcomes.
Publisher: S. Karger AG
Date: 2015
DOI: 10.1159/000380960
Abstract: b i Background: /i /b Denosumab, a RANK-ligand inhibitor, is an effective treatment for osteoporosis in postmenopausal women and men. Unlike the bisphosphonates, it is not excreted by the kidney. Little is known, however, about its efficacy and safety in patients with severe chronic kidney disease (CKD). b i Methods: /i /b A retrospective study was performed in CKD 4-5D patients from a tertiary referral hospital who were treated with denosumab between 1st January 2011 and 31st March 2014. Data collected included information about the following: CKD stage, fracture history, bone mineral density, serum calcium levels pre and post denosumab treatment, episodes of hypocalcemia, relevant medications and adverse events. b i Results: /i /b Eight patients with CKD-5 and 6 patients with CKD-4 were identified (all female, mean age 77.1 ± 9.9). The mean pre-denosumab calcium value was 2.42 ± 0.12 mmol/l, PTH 20.2 ± 14.7 pmol/l and 25-OH vitamin D 69.1 ± 30.1 nmol/l. After denosumab treatment, 6/8 patients with CKD-5/5D, and 2/5 patients with CKD-4 developed severe hypocalcemia. Two patients developed direct adverse complications of hypocalcemia (seizure, laryngospasm, prolonged QT sub c /sub ). Among the patients who developed hypocalcemia, the median time to serum calcium nadir was 21 days and the median time to correction of hypocalcemia was 71 days. Treatment of hypocalcemia required large doses of oral calcium and calcitriol, and increases in dialysate calcium concentration. b i Conclusions: /i /b A high rate of severe hypocalcemia was observed in patients with advanced CKD treated with denosumab. If denosumab is used in patients with severe CKD, close monitoring and aggressive replacement of calcium and calcitriol is required to avoid the development of hypocalcemia.
Publisher: Wiley
Date: 04-2010
Publisher: Wiley
Date: 04-2010
Publisher: Wiley
Date: 04-2010
Publisher: Wiley
Date: 28-11-2018
DOI: 10.1111/NEP.13427
Abstract: In contrast to peritoneal dialysis, residual kidney function (RKF) is commonly disregarded for haemodialysis (HD) patients and not regularly monitored or taken into account in routine clinical care. This is despite evidence that higher levels of RKF in HD patients are associated with better outcomes, including survival, total solute clearance, nutrition, inflammation and fluid balance. This review aims to summarise the clinical effects of RKF specifically in HD patients. Some level of RKF is present in over 80% of patients at the time of dialysis initiation, and while this declines over time, up to 30% of patients on HD for 5 years still have a measurable level of native kidney function. There is little evidence on how best to preserve RKF in HD patients, although it has been observed that intensive HD regimens in incident HD patients appear to accelerate RKF decline. RKF is not commonly factored into HD prescription and measures of adequacy, despite the fact that some guidelines such as Kidney Disease Outcomes Quality Initiative (KDOQI) and European Best Practice Guidelines suggest that it is reasonable to do so. This likely relates, at least in part, to perceived concerns regarding the inconvenience of timed urine collections and to the complexity and lack of consensus regarding the methods for integrating the intermittent clearance of HD with the continuous clearance of native renal function. Further research is required into how best to maintain and maximise the benefits of RKF in HD patients.
Publisher: American Physiological Society
Date: 03-2005
DOI: 10.1152/AJPRENAL.00190.2004
Abstract: The AMP-activated protein kinase (AMPK) is a key controller of cellular energy metabolism. We studied its expression and regulation by salt handling in the kidney. Immunoprecipitation and Western blots of protein lysates from whole rat kidney using subunit-specific antibodies showed that the α 1 -catalytic subunit is expressed in the kidney, associated with the β 2 - and either γ 1 - or γ 2 -subunits. Activated AMPK, detected by immunohistochemical staining for phospho-Thr 172 AMPK (pThr 172 ), was expressed on the apical surface of the cortical thick ascending limb of the loop of Henle, including the macula densa, and some parts of the distal convoluted tubule. Activated AMPK was also expressed on the basolateral surface of the cortical and medullary collecting ducts as well as some portions of the distal convoluted tubules. AMPK activity was increased by 25% in animals receiving a high-salt diet, and this was confirmed by Western blotting for pThr 172 . Low-salt diets were associated with reduced levels of the α-subunit of AMPK, which was highly phosphorylated on Thr 172 . Surprisingly, both low- and high-salt media transiently activated AMPK in the macula densa cell line MMDD1, an effect due to changes in osmolality, rather than Na + or Cl − concentration. This study, therefore, demonstrates regulation of AMPK by both a high- and a low-salt intake in vivo and suggests a role for the kinase in the response to changes in osmolality within the kidney.
Publisher: S. Karger AG
Date: 2014
DOI: 10.1159/000360273
Abstract: b i Background: /i /b Optimal timing of arteriovenous fistula (AVF) surgery in chronic kidney disease (CKD) is uncertain. b i Methods: /i /b A single-centre retrospective study of pre-dialysis CKD patients having first AVF surgery. b i Results: /i /b The median estimated glomerular filtration rate (eGFR) at the time of AVF surgery in 100 patients was 15 ml/min/1.73 m sup /sup , with patients classified as having an early AVF if eGFR was ml/min/1.73 m sup /sup (n = 46) or a late AVF if eGFR was ≤15 ml/min/1.73 m sup /sup (n = 54). In the eGFR ≤15 group, 81% of patients started haemodialysis (HD), compared with 63% of the eGFR patients (p = 0.04). The median time to starting HD was 30.3 months in the eGFR group compared to 10.7 months for the eGFR ≤15 group (log rank p = 0.018). There were no differences in the requirements for a dialysis catheter (eGFR 24% vs. eGFR ≤15 11%, p = 0.20) or additional access procedures between the two groups. b i Conclusions: /i /b AVF surgery with an eGFR ml/min/1.73 m sup /sup was associated with a higher risk of AVF non-use and a more prolonged time to the need for HD.
Publisher: Springer Science and Business Media LLC
Date: 27-08-2020
Publisher: MDPI AG
Date: 11-12-2015
Publisher: Springer Science and Business Media LLC
Date: 25-05-2020
DOI: 10.1186/S13063-020-04359-2
Abstract: Delayed graft function, the requirement for dialysis due to poor kidney function post-transplant, is a frequent complication of deceased donor kidney transplantation and is associated with inferior outcomes and higher costs. Intravenous fluids given during and after transplantation may affect the risk of poor kidney function after transplant. The most commonly used fluid, isotonic sodium chloride (0.9% saline), contains a high chloride concentration, which may be associated with acute kidney injury, and could increase the risk of delayed graft function. Whether using a balanced, low-chloride fluid instead of 0.9% saline is safe and improves kidney function after deceased donor kidney transplantation is unknown. BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-center, double-blind, randomized controlled trial. The primary objective is to compare the effect of intravenous Plasma-Lyte 148 (Plasmalyte), a balanced, low-chloride solution, with the effect of 0.9% saline on the incidence of delayed graft function in deceased donor kidney transplant recipients. From January 2018 onwards, 800 participants admitted for deceased donor kidney transplantation will be recruited over 3 years in Australia and New Zealand. Participants are randomized 1:1 to either intravenous Plasmalyte or 0.9% saline peri-operatively and until 48 h post-transplant, or until fluid is no longer required whichever comes first. Follow up is for 1 year. The primary outcome is the incidence of delayed graft function, defined as dialysis in the first 7 days post-transplant. Secondary outcomes include early kidney transplant function (composite of dialysis duration and rate of improvement in graft function when dialysis is not required), hyperkalemia, mortality, graft survival, graft function, quality of life, healthcare resource use, and cost-effectiveness. Participants are enrolled, randomized, and followed up using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. If using Plasmalyte instead of 0.9% saline is effective at reducing delayed graft function and improves other clinical outcomes in deceased donor kidney transplantation, this simple, inexpensive change to using a balanced low-chloride intravenous fluid at the time of transplantation could be easily implemented in the vast majority of transplant settings worldwide. Australian New Zealand Clinical Trials Registry: ACTRN12617000358347 . Registered on 8 March 2017. ClinicalTrials.gov: NCT03829488 . Registered on 4 February 2019.
Publisher: Massachusetts Medical Society
Date: 18-02-2021
Publisher: Springer Science and Business Media LLC
Date: 25-09-2021
DOI: 10.1186/S12983-021-00431-Y
Abstract: Quantity discrimination, the ability to discriminate a magnitude of difference or discrete numerical information, plays a key role in animal behavior. While quantitative ability has been well documented in fishes, birds, mammals, and even in previously unstudied invertebrates and hibians, it is still poorly understood in reptiles and has never been tested in an aquatic turtle despite the fact that evidence is accumulating that reptiles possess cognitive skills and learning ability. To help address this deficiency in reptiles, we investigated the quantitative ability of an Asian freshwater turtle, Mauremys sinensis , using red cubes on a white background in a trained quantity discrimination task. While spontaneous quantity discrimination methods are thought to be more ecologically relevant, training animals on a quantity discrimination task allows more comparability across taxa. We assessed the turtles’ quantitative performance in a series of tests with increasing quantity ratios and numerosities. Surprisingly, the turtles were able to discriminate quantities of up to 9 versus 10 (ratio = 0.9), which shows a good quantitative ability that is comparable to some endotherms. Our results showed that the turtles’ quantitative performance followed Weber’s law, in which success rate decreased with increasing quantity ratio across a wide range of numerosities. Furthermore, the gradual improvement of their success rate across different experiments and phases suggested that the turtles possess learning ability. Reptile quantitative ability has long been ignored and therefore is likely under-estimated. More comparative research on numerical cognition across a ersity of species will greatly contribute to a clearer understanding of quantitative ability in animals and whether it has evolved convergently in erse taxa.
Publisher: Springer Science and Business Media LLC
Date: 28-02-2019
Publisher: Elsevier BV
Date: 06-2006
Publisher: Wiley
Date: 13-08-2022
DOI: 10.1111/IMJ.15636
Abstract: There is a lack of data on how to best optimise uptake of COVID‐19 vaccination in dialysis patients. To understand attitudes and beliefs about COVID‐19 and vaccination uptake in dialysis patients. A single‐centre, cross‐sectional study involving a clinical audit and an anonymous survey of adult maintenance dialysis patients was conducted. The vaccination uptake during the study period was 77.5% at least single dose, compared with 70% in Victoria during the same period. Participants were more likely to be vaccinated if they believed COVID‐19 was a serious problem that is worse for people on dialysis. Those unvaccinated were more likely to overestimate the risk of vaccine complications and less likely to have the annual influenza vaccine. Despite over 80% of participants agreeing that they would have the vaccine if recommended by their nephrologist, less than 40% reported receiving information from this source. A predominant reason for vaccine hesitancy was concern regarding vaccine safety. Over 60% of those who were unvaccinated were still open to the vaccine, indicating a significant opportunity to improve vaccination rates through medical consultation and direction. Vaccine hesitancy for COVID‐19 in dialysis patients associates with less informed health beliefs, both about the disease and the risks of vaccination. Patients are more likely to get vaccinated if it is recommended by their nephrologist. Clinicians caring for dialysis patients have a key role in providing high‐quality education and advice, representing an urgent opportunity for improvement in vaccination uptake against COVID‐19.
Publisher: S. Karger AG
Date: 2015
DOI: 10.1159/000368527
Abstract: b i Background/Aims: /i /b Intravascular volume expansion due to sodium retention is involved in the pathogenesis of obesity-related hypertension. Institution of high fat diet (HFD) feeding leads to an initial state of positive sodium balance due to enhanced tubular reabsorption of sodium, but which tubular sodium transporters are responsible for this remains undefined. b i Methods: /i /b C57/Bl6 mice were fed control or HFD for 3 weeks. Blood pressures were recorded by tail cuff method. Sodium transporter expression and phosphorylation were determined by Western blotting. In vivo activity of NCC was determined using natriuretic responses to hydrochlorothiazide. Expression of NCC mRNA was determined using qPCR. b i Results: /i /b At 3 weeks HFD mice had significant weight gains compared to control mice, but blood pressures were not yet elevated. There were no changes in expression or phosphorylation of the bumetanide-sensitive cotransporter, NKCC2, or in expression of subunits of the amiloride-sensitive ion channel, ENaC. However, there were significant increases in mRNA and protein expression of the thiazide-sensitive co-transporter, NCC, in kidneys from HFD mice. Consistent with this, HFD mice had increased in vivo activity of NCC. b i Conclusions: /i /b Increased expression of NCC promotes the sodium loading response to institution of HFD feeding before onset of hypertension.
Publisher: American Physiological Society
Date: 04-2009
DOI: 10.1152/AJPRENAL.90372.2008
Abstract: The energy-sensing kinase AMP-activated protein kinase (AMPK) is associated with the sodium-potassium-chloride cotransporter NKCC2 in the kidney and phosphorylates it on a regulatory site in vitro. To identify a potential role for AMPK in salt sensing at the macula densa, we have used the murine macula densa cell line MMDD1. In this cell line, AMPK was rapidly activated by isosmolar low-salt conditions. In contrast to the known salt-sensing pathway in the macula densa, AMPK activation occurred in the presence of either low sodium or low chloride and was unaffected by inhibition of NKCC2 with bumetanide. Assays using recombinant AMPK demonstrated activation of an upstream kinase by isosmolar low salt. The specific calcium/calmodulin-dependent kinase kinase inhibitor STO-609 failed to suppress AMPK activation, suggesting that it was not part of the signal pathway. AMPK activation was associated with increased phosphorylation of the specific substrate acetyl-CoA carboxylase (ACC) at Ser 79 , as well as increased NKCC2 phosphorylation at Ser 126 . AMPK activation due to low salt concentrations was inhibited by an adenovirus construct encoding a kinase dead mutant of AMPK, leading to reduced ACC Ser 79 and NKCC2 Ser 126 phosphorylation. This work demonstrates that AMPK activation in macula densa-like cells occurs via isosmolar changes in sodium or chloride concentration, leading to phosphorylation of ACC and NKCC2. Phosphorylation of these substrates in vivo is predicted to increase intracellular chloride and so reduce the effect of salt restriction on tubuloglomerular feedback and renin secretion.
Publisher: Wiley
Date: 10-2020
DOI: 10.1111/IMJ.15030
Publisher: Wiley
Date: 10-2021
DOI: 10.1111/IMJ.15198
Abstract: Driving is a complex task requiring multiple cognitive domains and the musculoskeletal system. Cognitive dysfunction is associated with driving impairment. Dialysis patients are known to have a high prevalence of cognitive impairment and other comorbidities, and may be at risk of driving impairment. No Australian guidelines address driving safety in dialysis patients. To estimate the proportion of dialysis patients who were driving and those at risk of driving impairment, and to investigate the agreement between objective and subjective markers of risk. This single‐centre study involved dialysis patients voluntarily completing two questionnaires relating to risk of driving impairment the first questionnaire focussed on objective markers, and the second questionnaire focussed on subjective markers. Risk of driving impairment was established using pre‐determined criteria, and the agreement between objective and subjective markers was estimated using Cohen kappa. A total of 44.8% (99/221) of patients participated 76.8% (76/99) of participants were driving, and 76.3% (58/76) of drivers were at risk of driving impairment. Factors associated with at‐risk driving included post dialysis dizziness, leg weakness or numbness, falling asleep while driving and hypoglycaemia. Sixteen patients reported collisions since commencing dialysis. The questionnaires displayed slight agreement (Cohen kappa = 0.20) between objective and subjective markers. Dialysis patients are at risk of driving impairment based on self‐reported questionnaire responses. Discrepancies between patients' perceptions and objective markers were apparent. Further research into appropriate risk assessments, as well as development of guidelines to aid in determining driving safety in dialysis patients, is needed.
Publisher: Wiley
Date: 10-09-2015
DOI: 10.1002/PATH.4600
Abstract: The high-energy requirement of the kidney and the importance of energy metabolism in renal physiology has been appreciated for decades, but only recently has there emerged a strong link between impaired renal energy metabolism and chronic kidney disease (CKD). The mechanisms underlying the association between changes in energy metabolism and progression of CKD, however, remain poorly understood. A new study from Qiu and colleagues reported in the Journal of Pathology has advanced this understanding by showing that, after renal injury, the energy sensor AMPK inhibits epithelial-mesenchymal transition and inflammation, processes important in the pathogenesis of CKD. Furthermore, this study identifies an interaction between AMPK and CK2β as an important mechanism in the anti-fibrotic effect. CK2β has previously been shown to interact with STK11 (also known as LKB1) to regulate cellular polarity. These findings are consistent with the known roles of the LKB1-AMPK pathway in sustaining cellular energy homeostasis and epithelial cell polarity, and add to growing evidence linking the suppression of energy metabolism to CKD. They emphasize the importance of energy metabolism in general and the LKB1-AMPK axis in particular as key investigational and therapeutic targets in the battle against CKD.
Publisher: Wiley
Date: 22-05-2006
DOI: 10.1111/J.1748-1716.2006.01582.X
Abstract: In the kidney nitric oxide (NO) has numerous important functions including the regulation of renal haemodynamics, maintenance of medullary perfusion, mediation of pressure-natriuresis, blunting of tubuloglomerular feedback, inhibition of tubular sodium reabsorption and modulation of renal sympathetic neural activity. The net effect of NO in the kidney is to promote natriuresis and diuresis. Significantly, deficient renal NO synthesis has been implicated in the pathogenesis of hypertension. All three isoforms of nitric oxide synthase (NOS), namely neuronal NOS (nNOS or NOS1), inducible NOS (iNOS or NOS2) and endothelial NOS (eNOS or NOS3) are reported to contribute to NO synthesis in the kidney. The regulation of NO synthesis in the kidney by NOSs is complex and incompletely understood. Historically, many studies of NOS regulation in the kidney have emphasized the role of variations in gene transcription and translation. It is increasingly appreciated, however, that the constitutive NOS isoforms (nNOS and eNOS) are also subject to rapid regulation by post-translational mechanisms such as Ca(2+) flux, serine/threonine phosphorylation and protein-protein interactions. Recent studies have emphasized the role of post-translational regulation of nNOS and eNOS in the regulation of NO synthesis in the kidney. In particular, a role for phosphorylation of nNOS and eNOS at both activating and inhibitory sites is emerging in the regulation of NO synthesis in the kidney. This review summarizes the roles of NO in renal physiology and discusses recent advances in the regulation of eNOS and nNOS in the kidney by post-translational mechanisms such as serine/threonine phosphorylation.
Publisher: Wiley
Date: 24-04-2023
DOI: 10.1111/IMJ.16051
Abstract: Tunnelled central venous catheters (T‐CVCs) are used globally as vascular access for patients on haemodialysis (HD) but are associated with increased sepsis, mortality, cost and length of hospitalisation compared with more permanent HD vascular access. The reasons for using T‐CVC are varied and poorly understood. A significant and increasing proportion of incident HD patients in Victoria, Australia, have required T‐CVC over the last decade. To explore reasons for a significant and increasing proportion of incident HD patients in Victoria, Australia, having required T‐CVC over the last decade. With rates of starting HD with definitive vascular access consistently below a Victorian quality indicator target of 70%, an online survey was developed to explore reasons why the rate remained lower than desired and to help inform future decisions about this quality indicator. The survey was completed by dialysis access coordinators over an 8‐month period and involved all public nephrology services in Victoria. Of the 125 surveys completed, 101 incident HD patients had no attempt at permanent vascular access prior to T‐CVC insertion. For almost half of these (48 patients), there was no active medical decision not to create permanent vascular access prior to commencing dialysis. Reasons for insertion of the T‐CVC included deterioration of kidney function faster than anticipated, surgical referral being overlooked, complications related to peritoneal dialysis requiring a change in dialysis modality and changes to initial decisions regarding dialysis modality for kidney failure. These survey results provide an opportunity for quality improvement initiatives with respect to dialysis access planning and care.
Publisher: Oxford University Press (OUP)
Date: 29-12-2009
DOI: 10.1093/NDT/GFP715
Abstract: Crescentic glomerulonephritis is a rare complication of AA amyloidosis. There are no clinical case reports of this complicating AL amyloidosis. A 67-year-old man developed rapidly progressive glomerulonephritis (RPGN) on a background of primary AL amyloidosis and IgGkappa multiple myeloma. Investigations for causes of glomerulonephritis were negative, and a renal biopsy confirmed crescentic glomerulonephritis and amyloid deposition. He progressed to end stage kidney disease (ESKD) requiring dialysis after 2 months and died 7 months after diagnosis after further treatment of multiple myeloma failed to arrest progression. We believe this to be the first clinical case report of RPGN complicating primary (AL) renal amyloidosis and multiple myeloma.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-11-2022
Publisher: Wiley
Date: 19-12-2006
DOI: 10.1111/J.1440-1711.2005.01388.X
Abstract: AMP-activated protein kinase (AMPK) is a key energy sensor, known to regulate energy metabolism in erse cell types. Hypoxia is encountered frequently in the microenvironments of inflammatory lesions and is a critical regulator of function in inflammatory cells. Energy deficiency is one of the consequences of hypoxia, but its potential role in modulating leucocyte function has received little attention. Using micropore chemotaxis assays to assess migratory responses of the monocyte-like cell line U937, it was found that the AMPK activators AICAR and phenformin rapidly reduced random migration (chemokinesis) as well as chemotaxis due to stromal cell-derived factor (SDF)1alpha. There was an approximate 50% reduction in both chemokinesis and chemotaxis following 30 min preincubation with both AICAR and phenformin (P < 0.01), and this continued with up to 24 h preincubation. The binding of SDF1alpha to its receptor CXCR4 was unaltered, suggesting AMPK was acting on downstream intracellular signalling pathways important in cell migration. As AMPK and statins are known to inhibit HMG CoA reductase, and both reduce cell migration, the effect of mevastatin on U937 cells was compared with AMPK activators. Mevastatin inhibited cell migration but required 24 h preincubation. As expected, the inhibitory effect of mevastatin was associated with altered subcellular localization of the Rho GTPases, RhoA and cdc42, indicating decreased prenylation of these molecules. Although the effect of AMPK activation was partially reversed by mevalonate, this was not associated with altered subcellular localization of Rho GTPases. The data suggest that activation of AMPK has a general effect on cell movement in U937 cells, and this is not due to inhibition of HMG CoA reductase. These are the first data to show an effect of AMPK on cell movement, and suggest a fundamental role for energy deficiency in regulating cellular behaviour.
Publisher: American Physiological Society
Date: 05-2010
DOI: 10.1152/AJPRENAL.00005.2010
Abstract: The ultrasensitive energy sensor AMP-activated protein kinase (AMPK) orchestrates the regulation of energy-generating and energy-consuming pathways. AMPK is highly expressed in the kidney where it is reported to be involved in a variety of physiological and pathological processes including ion transport, podocyte function, and diabetic renal hypertrophy. Sodium transport is the major energy-consuming process in the kidney, and AMPK has been proposed to contribute to the coupling of ion transport with cellular energy metabolism. Specifically, AMPK has been identified as a regulator of several ion transporters of significance in renal physiology, including the cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial sodium channel (ENaC), the Na + -K + -2Cl − cotransporter (NKCC), and the vacuolar H + -ATPase (V-ATPase). Identified regulators of AMPK in the kidney include dietary salt, diabetes, adiponectin, and ischemia. Activation of AMPK in response to adiponectin is described in podocytes, where it reduces albuminuria, and in tubular cells, where it reduces glycogen accumulation. Reduced AMPK activity in the diabetic kidney is associated with renal accumulation of triglyceride and glycogen and the pathogenesis of diabetic renal hypertrophy. Acute renal ischemia causes a rapid and powerful activation of AMPK, but the functional significance of this observation remains unclear. Despite the recent advances, there remain significant gaps in the present understanding of both the upstream regulating pathways and the downstream substrates for AMPK in the kidney. A more complete understanding of the AMPK pathway in the kidney offers potential for improved therapies for several renal diseases including diabetic nephropathy, polycystic kidney disease, and ischemia-reperfusion injury.
No related grants have been discovered for Peter Mount.