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advances in renal pharmacology Flashcards

1
Q

new advances in renal pharma - 4

A

targeting renal inflammasomes to treat hypertension

kidney organoids for developing viral drugs

novel drugs for renal cell carcinoma

regen med approaches

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2
Q

hypertension is associated with inc expression of ____ and ___ and accumulation of ___ and ___ in kidneys

A

adhesion mols

pro inflammatory cytokines

inflammatory T cells

macrophages

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3
Q

hypertension’s resulting inflammatory events in kidneys are thought to contriubte to ___ ___ and ___

A

renal fibrosis
kidney damage

can cause reset of blood pressure at chronically elevated levels

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4
Q

hypoxia, inflammation, oxidative stress contribute to chronic kidney disease pathogenisis via

A

tubular cell injury

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5
Q

hypoxia, inflammation, oxidative stress contribute to chronic kidney disease pathogenisis via tubular cell injury. this can cause

A

transdifferentiation of kidney fibroblasts to myofibroblasts

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6
Q

hypoxia can result from damage to the

A

glomerulus

reduces blood flow to nephron

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7
Q

hypoxia triggers

A

cytokine and chemokine production

thus inflammation

also leads to fibrosis, which further inhibits flow of oxygen

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8
Q

what are inflammasomes

A

cytosolic signalling complexes

sense danger signals from pathogens or damaged host cells

respond by initiating inflammatory cascade

mediate inflammation in chronic inflammatory disease

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9
Q

examples of chronic inflammatory disease - 4

A

rheumatoid arthritis

gout

alzheimer’s disease

atherosclerosis

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10
Q

inflammasomes relevance in novel treatment

A

new evidence - hypertension development and inflammation partially depends on presence of functional NLRP inflammasome complex

which could be targeted for treating renal dysfunction, and high BP in hypertension

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11
Q

inflammasome as novel drug target study

A

MCC950 (selective small molecule inhibitor of NLRP3 inflammasome) reduces renal inflammation and fibrosis

improves renal function in mice

modest reduction in blood pressure

more research needed

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12
Q

what are organoids

A

in vitro cellular aggregates that usually contain more than one type of cell from the tissue of origin, and functional structures of organ of origin

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13
Q

how are organoids found

A

can be grown using pleuripotent stem cells

some already established for various organs e.g. intestine, retina, liver

under research

removes needs for animal testing, more accurate to human cell responses to drugs

closer to personalised medicine - patient derived renal organoids, help predict response

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14
Q

kidney organoid study

A

mini kidneys that are similarly structured to human kidneys

cultured from patients pleuripotent urine stem cells

allows modelling of various disorders including kidney infection, viruses following kidney transplants

also found in 2019 that kidney organoids express the expected proteins e.g. kidney epithelium cells were podocin positive and proximal tubules were aquaporin positive

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15
Q

causes of renal cell carcinoma/ kidney cancer - 5

A

smoking

hypertenstion

dialysis

genetic predisposition (PKC)

obesity

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16
Q

kidney cancer is ___ to detect

A

difficult

as rarely cause pain or bleeding

17
Q

kidney cancer is ___ to chemotherapy

A

often resistant

18
Q

it is easier to treat renal cell carcinoma before ____

A

metastasis

19
Q

new drugs for kidney cancer - 3

A

nivolumab

cabozantinib

levatinib

treatments are pathway specific to patient’s tumour, patients stratified to identify needs and best match - genomic sequencing - personalised meds

20
Q

most drugs for targeting kidney cancer inhibit the __ pathway

A

VEGFR

as inhibition dec blood supply to tumour, halting tumour growth

21
Q

drugs targeting angiogenesis examples - 9

A

1st - bevacizumab

sorafenib

sunitinib

pazopanib

axitinib

cabozantinib

lenvatinib

temsirolimus

everolimus

22
Q

drugs targeting angiogenesis - bevacizumab

A

metastatic colon cancer

2004 approved

now used for multiple cancers

23
Q

drugs targeting angiogenesis - sorafenib and sunitinib

A

first antianiogenesis drugs targeting RCC, targets VEGFR

24
Q

drugs targeting angiogenesis - pazopanib and axitinib

A

inhibit tyrosine kinase receptors - VEGFRs

25
Q

drugs targeting angiogenesis - cabozantinib and lenvatinib

A

more effective VEGFR inhibitors

26
Q

drugs targeting angiogenesis - temsirolimus and everolimus

A

inhibit different enzyme linked to angiogenesis called mTOR

27
Q

targeted therapy in kidney cancer - VHL study

A

VHL = gene called Von Hippel-Lindau tumour suppressor

inactivated in most with renal carcinoma

accounts for 70% of kidney cancers, links to hypoxia

VHL suppresses tumours by regulating angiogenesis

lead to new therapies such as humanised monoclonal antibodies against VEGF, small mol TK inhibitors, mTOR inhibitors

28
Q

new drugs have inc survival post diagnosis to

A

2.5 years

29
Q

drawbacks of recent drugs

A

lots of side effects

dont often completely reverse cancer

some do not work on early stage tumours

thus, regen med

30
Q

current role of regen in kidney

A

kidney has limited potential to regen

31
Q

renel regen CD133 glycoprotein study

A

renal repair after injury depends on clonal expansion of cells

kidney cells that express CD133 are resistant to damage and can proliferate

CD133 expressing cells were treated with chemotherapy cisplatin

this led to cell damage by cisplatin and lost CD133 signature

recovery phase did, however, lead to re acquirement of CD133

lack of CD133 = lack of cell proliferation

so, may be linked to Wnt signalling, whihc is involved in development of various kidney disorders

future - infuse CD133 to help pt repair damaged kidneys

32
Q

regen med - decellularisation study

A

rat kidneys have been decellularized via detergent perfusion

which yielded acellular scaffolds

seeded them with epithelial and endothelial cells

perfused cell seeded constructs in whole organ bioreactor

33
Q

regen med - 3d bioprinting

A

cells used as ink to print new organs

34
Q

regen med - regenerating human kidneys in other species study

A

rat derived nephrons generated in mice by combining transplantation of rat derived nephron progenitors with native nephron progenitor’s conditional elimination

35
Q

nanoparticles and liposome useand example

A

Utilizing nanoparticles and liposomes to deliver drugs directly to kidney tissues can improve therapeutic outcomes and reduce systemic side effects

inc penetration of renal tissue, controlled release

e.g. gold nanoparticles for ACE inhibitors directly to kidneys to prevent chronic kidney disease in a study model

36
Q

wearable artificial kidneys WAK

A

5 types currently under development

one human trial, no sig side effects

aims to provide continuous dialysis

inc quality of life, mimic natural kidney function better than traditional dialysis machinery

342 (21 decks)

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