advances in renal pharmacology

Question 1

new advances in renal pharma - 4

Answer 1

targeting renal inflammasomes to treat hypertension

kidney organoids for developing viral drugs

novel drugs for renal cell carcinoma

regen med approaches

Question 2

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

Answer 2

adhesion mols

pro inflammatory cytokines

inflammatory T cells

macrophages

Question 3

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

Answer 3

renal fibrosis
kidney damage

can cause reset of blood pressure at chronically elevated levels

Question 4

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

Answer 4

tubular cell injury

Question 5

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

Answer 5

transdifferentiation of kidney fibroblasts to myofibroblasts

Question 6

hypoxia can result from damage to the

Answer 6

glomerulus

reduces blood flow to nephron

Question 7

hypoxia triggers

Answer 7

cytokine and chemokine production

thus inflammation

also leads to fibrosis, which further inhibits flow of oxygen

Question 8

what are inflammasomes

Answer 8

cytosolic signalling complexes

sense danger signals from pathogens or damaged host cells

respond by initiating inflammatory cascade

mediate inflammation in chronic inflammatory disease

Question 9

examples of chronic inflammatory disease - 4

Answer 9

rheumatoid arthritis

gout

alzheimer’s disease

atherosclerosis

Question 10

inflammasomes relevance in novel treatment

Answer 10

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

Question 11

inflammasome as novel drug target study

Answer 11

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

Question 12

what are organoids

Answer 12

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

Question 13

how are organoids found

Answer 13

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

Question 14

kidney organoid study

Answer 14

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

Question 15

causes of renal cell carcinoma/ kidney cancer - 5

Answer 15

smoking

hypertenstion

dialysis

genetic predisposition (PKC)

obesity

Question 16

kidney cancer is ___ to detect

Answer 16

difficult

as rarely cause pain or bleeding

Question 17

kidney cancer is ___ to chemotherapy

Answer 17

often resistant

Question 18

it is easier to treat renal cell carcinoma before ____

Answer 18

metastasis

Question 19

new drugs for kidney cancer - 3

Answer 19

nivolumab

cabozantinib

levatinib

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

Question 20

most drugs for targeting kidney cancer inhibit the __ pathway

Answer 20

VEGFR

as inhibition dec blood supply to tumour, halting tumour growth

Question 21

drugs targeting angiogenesis examples - 9

Answer 21

1st - bevacizumab

sorafenib

sunitinib

pazopanib

axitinib

cabozantinib

lenvatinib

temsirolimus

everolimus

Question 22

drugs targeting angiogenesis - bevacizumab

Answer 22

metastatic colon cancer

2004 approved

now used for multiple cancers

Question 23

drugs targeting angiogenesis - sorafenib and sunitinib

Answer 23

first antianiogenesis drugs targeting RCC, targets VEGFR

Question 24

drugs targeting angiogenesis - pazopanib and axitinib

Answer 24

inhibit tyrosine kinase receptors - VEGFRs

Question 25

drugs targeting angiogenesis - cabozantinib and lenvatinib

Answer 25

more effective VEGFR inhibitors

Question 26

drugs targeting angiogenesis - temsirolimus and everolimus

Answer 26

inhibit different enzyme linked to angiogenesis called mTOR

Question 27

targeted therapy in kidney cancer - VHL study

Answer 27

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

Question 28

new drugs have inc survival post diagnosis to

Answer 28

2.5 years

Question 29

drawbacks of recent drugs

Answer 29

lots of side effects dont often completely reverse cancer some do not work on early stage tumours thus, regen med

Question 30

current role of regen in kidney

Answer 30

kidney has limited potential to regen

Question 31

renel regen CD133 glycoprotein study

Answer 31

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

Question 32

regen med - decellularisation study

Answer 32

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

Question 33

regen med - 3d bioprinting

Answer 33

cells used as ink to print new organs

Question 34

regen med - regenerating human kidneys in other species study

Answer 34

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

Question 35

nanoparticles and liposome useand example

Answer 35

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

Question 36

wearable artificial kidneys WAK

Answer 36

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