CS19 Flashcards
What is diabetic nephropathy?
kidney damage/disease cause by diabetes
-high blood sugar(and high blood pressure) can cause damage to the small blood vessels and tiny filters in you kidneys. This can cause leakage/ dysfunction = high protein in urine(searly sign of kidnay disease)
How many people with daibetes need treatment for diabetic nephropathy?
almost 1 in 5
What are the symptoms of diabetic nephropathy?
no visible symptoms in early stages which is why it is important to have tests for kidney disease.
If kidney disease progresses you could see symptoms like swollen ankles feet and hands, blood in urine, feeling really tired , being short of breath, feeling sick.
How can you reduce the risk of developing kidney disease?
keep blood sugar levels within target range, keep blood pressure down, get support to stop smoking, eat healthily, keep active, go to all medical appointments
What blood test can you use to test for kidney disease?
eGFR-tests for a waste product called creatinine
If you develop late stage idney disease or kidney failure nhow is it treated?
dialysis or kidney transplant
What are the 3 layer of the glomerulus filtration barrier?
- Endothelial cells of glometular capillaries
- Glomerular basement membrane
- epithelial cells of bowmans capsule called podocytes
Describe the glomerular capillary endothelium?
has perforations called fenestrations which are pores about 70nm. These limit the filtration of cellular components e.g. RBCs.
-surounding the luminal surface of the endothelial cells is glycocalyx consisting of negatively charged glycosaminoglycans which hinder the diffusion of negatively charged molecules.
Describe the make-up and structure of the glomerular basement membrane?
made up of mostly:
- collagen type IV
- heparan sulfate proteoglycans -restrict the movement of negaively charged molecules across the basement membrane
- lamina.
Has 3 layers:
- inner thin layer(lamina rara interna)
- thick layer(lamina densa)
- outer dense layer(lamina rara externa)
These layers help limit the filtration of larger molecules
Describe the structure and function of podocytes?
Specialised epithelial cells
- Foot like process projet from these and interdigitate to form filtration slits which are bridges by a thin diaphragm which has very small pores prevent ing large molecules from crossing
- negatively charged gycoproteins cover the podocytes restricting filtration of large negatively charged ions(anions)
What effects the filtration rate of a molecule?
size and charge
- filtration rate of molecules of the same chrge is inversly related to their molecular weight (easier if smaller)
- Negatively charged large molecules are less easily filtered thn positively charged molecules of the same size
What is the responsible for 10-25% of cases of nephrotic syndrome?
Describe?
Minimal change Glomerulonephritis- disease that damges glomeruli but damage cant be seen under a light microscope only under an electron microscope. There is diffuse effacement of podocytes foot processes causing the widening of filtration slits and microvillous change.
-pathology thought to be due to a T-cell derived factor
What are the symptoms of nephrotic syndrome?
- Proteinuria
- hypoalbuminemia
- oedema
What is alport syndrome and symptoms?
genetic disease characterised by progressive chronic kidney disease with symptoms of haematuria, sensorineural deafness and ocular abnormalities.
-the inheritance is mostly x-linked with mutations for α5 chain of type IV collagen. This results in thinning of the lamina densa of the glomerular basement membrane with areas of multi-layering producing a basket weave appearance.
In later stages of the disease, glomerulosclerosis, interstitial fibrosis and tubular atrophy occur
What is the treatment for Alport syndrome?
No definitive treatment but ACE inhibitors are given to reduce proteinuria and progression of renal kidney disease as well as to control hyprtension.
Where is renin released from and waht 3 things stuimulate this release?
- Renin released from granular cells of the renal juxtaglomerular apparatus (JGA) in response to one of three factors:
- Reduced sodium delivery to the distal convoluted tubule detected by macula densa cells
- Reduced perfusion pressure in the kidney detected by baroreceptors in the afferent arteriole
- Sympathetic stimulation of the JGA via β1 adrenoreceptors
What inhibits the release of renin?
ANP -Atrial natriuretic peptide
-this is released in response to increases in blood pressure
How is angiotensin II formed?
Where is angiotensin II formed?
Angiotenisin precursor protein produced in the liver and cleaved by renin to form angiotensin I.
Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme (ACE).
This conversion occurs mainly in the lungs where ACE is produced by vascular endothelial cells, although ACE is also generated in smaller quantities within the renal endothelium.
What are the effect of angiotenisin II?
Cardiovasuclar effects:
-acts on AT1 receptors found on the enothelium of arterioles to achieve vasoconstriction. This signalling occurs via a Gq protein, to activate phospholipase C = increase intracellular calcium = increase in total peripheral resistance and consequently, blood pressure
Neural effects:
-acts at the hypothalamus to increase thirst, = increased fluid consumption= increased blood volume =increased blood pressure.
ADH-secretion increased from the posterior pituitary gland= mess fluid lost in urine=more conventrated urine
NA- stimulates the sympathetic nervous system = increased release of noradrenaline (NA) which is assosiated with “fight or flight” response in stressful situations = Increase in cardiac output, Vasoconstriction of arterioles, Release of renin.
Renal effects:
-increases Na+ reabsorption in PCT and those in the attatched image
How is aldosterine released?
Describe its effects?
Angiotensin II acts on the adrenal cortex to stimulate the release of aldesterone( mineralocorticoid) released from the zona glomerulosa
Acts on the principal cells of the collecting ducts i the nephron to increase the expression of apical epithelial Na+ channels (ENaC) to reabsorb urinary sodium. also increases the activity of the basolateral Na+/K+/ATPase. This leads to more sodium reabsorption and more potassium excretion therefore increased aldesterone causes reduced levels of potassium in blood,
What do ACE inhibtiors do?
treat hypertension and heart failure e.g. ramipril, lisinopril, enalapril
- inhibt ACE so reduces the levels of angiotenis II within the body=- decreases activity of the renin-angiotesin-aldosterone system(RAAS) = decreased arteriolar resistance, Decreased arteriolar vasoconstriction, Decreased cardiac output and Reduced potassium excretion in the kidneys
- reduce blood pressure and urinary protein excretion
What are some side effects of ACE inhibitors?
include dry cough, hyperkalaemia, headache, dizziness, fatigue, renal impairment and rarely, angioedema.
What are the 2 most important porgnostic factors in chronic kidney disease?
hypertension and proteinuria
How do ACE inhibitors redue proteinuria?
likely related to the inhibition of the preferential vasoconstriction that occurs in the efferent arteriole in the glomerulus, thus reducing GFR and reducing urinary protein excretion.
Why should you be catious when giving ACE inhibitors?
be used in caution in patients with bilateral renal artery stenosis and withheld in acute kidney injury, as the reduction in GFR can be harmful.
What 2 thing indicate that the kidney is leaky and cant filter as well as it should?
High serum creatinine-normally filtered by the glomerulus and not reabsorbed so is generally excreted as waste
Protein in urine-indicates leaky
Describe filtration, reabsorption, secretion and excretion in the kidneys?
Filtration- Glomerulus filters blood from afferetn arteriole based on size and charge of the molecule. Allows things like Na+ and glucise to be filtered through
Reabsorption- In PCT large amounts of electrolytes, water and glucose are reabsorbed via active transport and passive diffusion by the renal epithelial cells
Secretion-Substance are also secreted from tubules in to the urine, drugs and hydrogen are secreted and waste.
Excretion-Anything secreted or not reabsorbed is excreted as aste in urine
How do renal epithelial cell reabsorb proteins from tubules?
-endocytosis
proteins are hydrolysed into their amino acid constituents so they can pass into the blood stream. Almost all filtered proteins are reabsorbed
What is the most abundent protein found in normal urine?
uromodulin also called Tamm-horsfall protein
What are the different types of proteinuria?
Give an examplemof ecah type?
Overflow proteinuria:
happens when theres lots of excess protein in tubules. As much as possible will be reabsorbed into blood but reabsorption is a saturable process so there is only so much that can happen at once. So any not reabsorbed is excreted in urine.
Example-Rhabdomyolysis-rapid breakdown of damage skeletal muscle triggered by trauma, intense exercise, and certain toxins, results in muscel constituents being released into the blood stream including myoglobin=overfow proteinuria. Can also have overflow of Hb when excess free Hb is circulating due to rapid intravascular haemolysis.
Glomerular proteinuria:
glomerular filtration barrier is damaged = more/larger proteins can pass through.This excess saturates the reabsorption capacity of the tubules resulting in urinary protein loss.
Example- Diabetic nephropathy is a type of secondary glomerulapathy (meaning glomerular damge occurs secondary to something else e.g. diabetes, drugs, infection, cancer). The protein lost when glomerulus is leaky is mainly albumin, it overwhelms reabsorption capactiy of tubules and so is lost in urine
Tubular proteinuria:
-occurs when tubule are diseases or damaged=not able to reabsorb filtered proteins as well as they normally would
Example- Acute tubulointerstitial nephritis-where kidney diseases in structures outside of the glomerulus, leading to tubular dysfunction with or without renal failure. This disease can be acute or chronic and the mechanism to it is a reaction to drugs, drugs that damage the kidney are known as nephrotoxic drugs.
what are drugs that damage the kidney called?
give examples?
nephrotoxic drugs
Main 4-NSAIDS, ACE inhibitors, Aminoglycosides(e.g. gentamyosin), and contrast agents
Penicillin based ABs and chemotherapy agents e.g. cysplatin are also potentially risky
In which tyep of proteinuria is the most protein lost?
Glomerular proteinuria
What is the difference between haemturia and haemoglobinuria?
haemoglobinuria-refers to an excess of free Hb in the urine from overflow
Haematuria- refers to excess bleeding from the urinary tract itself in which case haemoglobin may be present in the urine but alongside intact RBCs
How can Hyperglycaemia (part of diabetic nephropathy) effect the kidney?
- non-enzymatic glycation of endothelial cells in efferent arteriole results in stiffening and narrowing of the vessel.
- Hyperglycaemia can also directly activate the RAA system within the kidney. Angiotensin II causes vasocontriction in the efferent arteriole = narrows = increased pressure
How does the hypertension aspect of diabetes effect the kidney?
- increased flow through the afferent arteriole=increase glomerular pressure= increased filtration=increased protein loss
- normally the glomerulus would be protected from increased systemic pressure (hypertension) by auto-regulation and afferent arteriole constriction but in diabetes the PCT reabsorbs more glucose =increased Na+ reabsorption as sodium is co-transproted with glucose= less sodium delieved to mascula densa in the DCT = less afferent arteriole vasoconstriction(therefore glomerulus not protected from increased pressure)
This= hyperfiltration= afferent arteriole vesslel thickening and reduced lumen diameter= blood supply to the kidney is compromised = relative ischaemia=recruits macrophages which secrete tgf-beta = mesangial cells secrete more extracellular matrix. This process can also be triggered by hyperglycaemia and pressure damage. The excessive extracellular matrix leads to hardening and scarring within the glomerulus known as glomerulosclerosis= reduces filtration capacity
How does hypertension and hyperglycaemia effect the cells of the glomulus?
- can damage the glomerular capillary endothelial cells. Can also result in intrinsic changes to the glomerular basement membrane. This becomes thickened in diabetic nephropathy and leaky
- podocyte foot processes are interconnected by the slit diaphragm(nephrin protein is a key component ) Damage to this may contribute to protein leak and the mesangial expansion mentioned above (which pushes apart the normal structures) may be responsible for this. Reduced nephrin expression has been observed in diabetic nephropathy. Also podocyte damage can be directly from advanced glycation products, a result of hyperglycaemia.
This all leads to protein loss of glomerulus. The presence of albuminuria represents a defect in at least one of these layers of the glomerulus
What are the 3 most common causes of CKD in the western world?
- Diabetes
- Hypertension
- Glomeruloneophritis
(these all have some common elements)
Why after a certain level of damage do all causes of CKD start to progree in a similar way?
When damage occurs to aroiund half the nephrons, the nephrons that are still working undergo adaptive hyperfiltration where blood flow is shunted to then in favour over the damaged nephrons.
This adaptive hyperfiltration in these working nephrons puts excessive pressure on their glomerular capillaries leading to glomerulosclerosis, ischaemic nephron injury, loss of filtration and eventually nephron loss. Adaptive hyperfiltration can be considered maladaptive as it leads to accelerated damage to the remaining working nephrons. This explains why after a certain degree of damge CKD progresses in a similar manner.
What ways can you screen for proteinuria in diabetes?
What are the pros and cons?
Urine dipstick test:
- primarily detects albumin so may not be the best if your looking for different types of protein being lost or other proteins in addition to albumin
- poor sensitivity to other proteins e.g.myoglobin. Might think it’s a good test for albuminuria, but because its not very sensitive if the amount of albumin lost is just a bit higher than the normal then it may not show up on the stick, eventhough this is still important
24hr urine collection test:
- measures total amount of protein in urine so could be reliable test if the patient collected every bit of their urine.
- However usually inaccurate as it relies on the patient to accurately collect exactly 24 hours worth of urine without missing a drop and collect and drop off the vessel.
Random Albumin concentration test:
-quite unreliable as it highly depends on the concentration of that urine which will depend on how well hydrated the patient is.
ACR or PCR:
- Albumin/protein, creatinine ratio of urine sample
- A reasonable estimate for the protein loss can be obtained by adjusting the measured albumin or protein concentration in the urine for the creatinine conc in the urine to account for differences in the concentration. This assumes that the creatinine excretion rate is of a certain amount per day (not always true as it varies from person to person) but using creatinine to correct the conc provides a reasonable estimate of albumin or protein loss, given the practicality of a single random urine sample.
What is the best way to screen for proetinuria in diabetes?
ACR as it has a greater sensitivity than PCR
PCR is only recommeded as an altrnative to ACR to monitior protein loss in those without diabetes and with high levels of proteinuria
If someone has diabetes what are they checked for and why ?
Albuminuria because if there is proteinuria you can assume that there’s probably vascular disease in the rest of the body too.
-Picking up on this = you can halt the damage as this is often seen before any other sogns of damage and can predict those that are more likely to progress to CKD
What is microalbuminuria?
what is macroalbuminuria?
What are they now called?
Microalbuminuria- was a termused to describe albumin loss of between 30-300mg per day. This might not result in problematic protein depletion but it is a good predictive and prognostic marker for CKD, especially in diabetes. Now called Moderate albuminuria.
Macroalbuminuria-as used to describe albumin loss of over 300mg a day. Now called severe albuminuria
Names have changed to reflect how albuminuria occurs along a spectrum not 2 distinct categories. If people attended regular screenings the smal degree of albumin loss change might be picked up ad highlight who is at risk.
What should the total portein loss and albumin loss from urine per day?
Protein loss- less than 150mg per day
albumin loss-less than 30mg per day and is usually aroung 5-10mg
What doies moderate albuminuria tell us?
-can predict the progression of CKD and give us an idea of persons vascular health
If they are losing protein in their kidneys because of the changes to the renal vasculature and to the glomerulus chances are that similar processes are going on throughout the body, Albuminuria is therefore thought to be reflective of the integrity and health of systemic vascular endothelium.
It is found to correlate with cardiovascular risk outcomes and is a predictor of cardiovascular mortality in type 1 and 2 diabetes.
What is GFR proportional too?
the clearance rate of any substance that is freely filtered and neither reabsorbed or secreted by the kidneys.
How do you calculate clearence rate?
Clearance = urinary[substance]x urine production rate/plasma[substance]
What is used to calculate GFR?
What is the slight problem and why is this allowed?
creatinine - as it is freely filtered and not reabsorbed by the kidneys
Ideally it would not be secreted either but a little is as in healthy kidneys 5-10% of the amount of creatinine that is excreted comes from secretion rather than filtration however we allow it as it allows for easy and convenient testing and there isn’t a better alternative that doesn’t require injecting something into the patient.
How can you measure creatinine clearence?
Which way is best, which way is the most common?
- use formula that needs the serum and urine concentrations of creatinine and rate of urine production
- most common in clinical practice is to use evidence based formulas that use serum creatinine without without need for urinary creatinine, and this can therefore estimate GFR. This is more practical then collecting and analysing urine from every patient. The most commonly used formula is the MDRD formula which came from the modification of diet in renal disease study.
- Isotopic methos is the best- a radioactive tracer is injected into the patient intravenously and serum concentrations of this tracer are then measured sequentially to calculate the clearance. These are done sometimes when we don’t think creatinine based estimations are reliable.
What things does the MDRD formula take inot considerationwhen when measuring serum creatinine and why?
- age, ethnicity and gender
- you cant asumme that creatinine will be the same for everyone because creatinine is generated from the conversion of creatinine and creatinine phosphate, 95% of which is found in the muscle.
Therefore serum levels of creatine are not just dependent on the filtration levels in the kidneys but also the amount produced, which is higher in someone with more muscle mass including males, younger age and those of afro Caribbean decent.
. Important that the formula takes this into account so you don’t think a healthy person is unhealthy or vice versa.
Why should we be careful with who we use the MDRD fromula on?
Creatinine levels may also depend on dietary protein consumption as some amino acids are creatinine precursors. Therefore we should be careful of using these formulas on people with certain weights and nutrition such as amputees, bodybuilders, those taking creatinine supplements or those with malnutrition or muscle wasting disease. You can always perform an isotope GFR test if worried o the reliability when using the creatinine based estimates.
What do we use the creatinine estimate for?
Find the Creatinine estimate to calculate GFR and therefor predict the stage of CKD.
What are some markers for CKD?
Albuminuria, electrolyte abnormalities, abnormalities on histology, structural abnormalities, kidney transplantation history.
with albuminurai it should persit for at least 3 months (further tests needed) before finalising diagnosis
When is using cratinine based formulae to estimate the GFR inappropriate?
When creatinine is produced in certain people in extremes (lots and not a lot) e.g. bodybuilders and amputees
Also should consider the stability of of the patients serum creatinine concentrations as Using creatinine based formulae to estimate GFR is less reliable when the serum creatinine concentration is unstable
Why is it unreliable to use a creatinine based formula to calculate the GFR for an elderly pateint for acute kidney injury?
AKI = reduction in filtration= increased plasma creatinine. However the rate of increase in serum creatinine does not parallel the fall in GFR, it can take some time at a given GFR for serum creatinine to build up and be representative of this.
Those with AKI are unwell for other reasons and these might also effect seum creatinine e.g. trauma which could increase muscle breakdown and increase serum creatine. Certain drugs such as trimethoprim which can inhibit secretion of creatinine in the tubules and therefore increase serum creatinine. Malnutrition or muscle wasting which will reduce the serum creatinine or sepsis which can also reduce serum creatinine production.
Why is it unreliable to use a creatinine based formula to calculate the GFR for a pregnant lady?
filtration rate in pregnancy increases rapidly and the drop in serum creatinine may not be seen until a couple of days, GFR estimates based on creatinine may be unreliable.
Why is it unreliable to use a creatinine based formula to calculate the GFR for a pateint with end stage renal failure about to start dialysis?
Normally some creatinine is secreted which means creatinine clearance calculations slightly overestimate clearance because they take into account the removal of secretion as well as that form filtration. As GFR falls and the amount of creatinine filtered falls, the proportion of excreted creatinine that comes from secretion increases and the creatinine excretion become less and less from what is filtered and more and more due to whats secreted.
When would using a creatinine formual to estimate GFR be appropriate?
considered a pretty reliable test in a patient with stable, early stage CKD or generally in pateints whose creatinine levels are pretty stable from day-to-day.
What are the 3 modifiable risk factors of CKD and what medication can be use to treat them?
HYPERTENSION:
Ramipril- ACE inhibitor. reduces hypertension and has a specific positive effect within the kidney. CKD can = increase in Glomerular filtration pressure which can lead to glomerular injury and proteinuria. Acts to reduce arterial perfusion pressure effecting blood coming into the glomerulus and also relaxes the efferent arterial in the glomerulus effecting blood leaving the glomerulus = reduce overall glomerular pressure, reduce glomerular injury and reduce proteinuria. therefore In CKD with proteinuria ACE inhibitors are usually favoured over other antihypertensive
HYPERGLYCAEMIA:
Insulin-Hyperglycaemia can be associated with damage to the microvasculature, this is relevent in the kidney where damage to glomerular vasculature will contribute to worsening kidney disease.
DYSLIPIDAEMIA:
Atorvastatin-High blood cholesterol is associated with atherosclerosis and sclerotic glomeruli are observed in CKD therefore treatment with statins could help alleviate this problem, as well as reducing the risk of CVD that is increased in people with CKD.
Both ACE inhibitors and statins have been shown to have anti-inflammatory effects. Which might also contribute to their Reno protective effects in CKD
Smoking cessation which is linked to both dyslipidaemia and hypertension is also really important
What are the 3 broad categories of consequneces of CKD?
Decreased excretion of molecules
decreased biosynthesis of molecules (tht a helathy kidney should make)
aktered metabolism of molecule
Describe the possibe consequences and severe consequences of decreased excretion of molecules in CKD?
Water and salt- usually maintained until GFR falls below 1-15ml per min (Stage 5 CKD) however a patient with mild to moderate CKD, despite being in relatively normal volume balance is less able to respond to rapid intake of sodium or water and therefore is prone to fluid overload,, peripheral odema and hypertenison. Severe consequneces-volume overload with pulmonary odema and heart failure
Potassium-Hyperkalaemia develops in patients with advanced CKD who don’t make much urine or if theres an additional problem like a high potassium diet. ACE inhibitors can cause or worsen hyperkalaemia so should be used with caution( this is used to treat the hypertension aspect of CKD. possible consequneces =weakness and fatigue. severe consequences = ECG changes predisposing to arrhythmias and cardiac arrest
H+ ions-increased tendency to retain hydrogen ions or protons with progressive CKD which can lead to metabolic acidosis. These patients may be treated with HCO3- supplements.
Urea- is a nitrogen waste product which can rise too much in progressive CKD or if theres also acute kidney injury present. Possible consequences- Nausea and vomiting, weakness and fatique and itch. Severe consequences-pericarditis, encephalopathy, bleeding, seizures and coma., indications for dialysis.
Uric acid-can build up in joints and cause gout.
Phosphate-can drive increased production of the parathyroid hormone and is implicated in renal bone disease
Describe the possible consequences and severe consequences with the decreased biosynthesis of certain molecules in CKD?
How can they be treated?
Erythropoietin-stimulates RBC productionless erythropoeitn made= normocytic(RBC are normal size), normochromic(means the Hb conc within those RBCs is in the normal range) anaemia – so the patients can produce normal RBCs but not enough because there is not enough erythropoietin.The treatment for renal anaemia is making sure that vital vitamins and mineral such as B12, folate andiron are replete so there arn’t any additional treatable reasons for anaemia and in later stages administering erythropoietin as a medication
Vitamin D-less hydroxylation of vitaminD to activate it = less active vit D. possible consequences=hyperparathyroidism. Severe consequneces=osteomalacia and renal bone disease.
Describe the consequences with altered metabolism in CKD?
abnormal lipid metabolism- which is why all patients should be considered for a statin. Consequences = accelerated atherogenesis and CVD.
altered metabolism of sex hormones- consequences = Significant abnormalities in sexual and reproductive function e.g. erectile dysfunction and early menopause
Both of these examples are complex and multifactorial.
Describe what affect CKD has on vitamin D, calcium?
Describe the what effefct CKD has on phosphate and the 2 main effects this has?
In CKD kidneys cant synthesise enough Vit D = less Calcium absorbed. Serum phosphate levels increase in CKD because it isn’t getting filtered due to reduction in filtration capability of kidney in CKD.
Elevated phosphate does 2 things here. 1-binds to calcium and this reduces the level of free calcium in circulation, this adds to any lowering effect on serum calcium levels that come from reduced absorption(2nd reason why calcium levels can fall in CKD). 2-thing elevated phosphate does is stimulate the release of the PTH from the parathyroid gland -this is called Secondary hyperparathyroidism, this sounds good as it will cause the release of calcium from the bone to compensate for the reduction of serum calcium in CKD but this reduces the stash of calcium in the bone too much = osteitis fibrosa where excessive amounts of calcium from bone are reabsorbed back into circulation and in the bone this loss is replaced by fibrous tissue.
How is Vit D, calcium, Parathyroid gland and parathyroid hormone all connected? in the kidney function?
Normally the kidneys help in the synthesis of Vit D= helps in the absorption of Calcium from food sources in the digestive system.
Vit D is needed in things ranging from nerve impulse conduction to muscle contraction etc.
More than 99% of calcium is stored in bone so whenever calcium is low in circulation in the body(not enough coming form food or something else is lowering it) the body has a parathyroid gland to detect this reduction and this releases PTH which unlocks the bone to release calcium and restore levels of calcium in circulation to normal. Because low levels of the Vitamin D will lead to low levels of calcium, the Parathyroid gland also releases PTH when it detects low levels of Vitamin D
What are the functions of PTH?
when there is low vit D or low calcium it is released and causes the release of calcium from the bone store(stores 99% of bodies calcium) to restore serum calcium to normal
Opens the back door of the kidney =greater excretion of phosphate = helps normalise phosphate levels and this will help normalise the PTH levels realeased =can help normalise calcium levels
What does FDF23 do?
Bone derived hormone
- levels of FGF23 are elvated in CKD for unknown reason.
- FGF23 acts on the kidneys to decrease the reabsorption and increase the secretion of phosphate resulting in lower levels of phosphate in circulation.
- cna also cause reduction in vit D and reduced renal mass
What is tertiary hyperthyroidism?
In CKD there is lots of stimulation onthe parathyroid glands so they can start to act autonomously, producing PTH spontaneously without the need for stimulation.
Why is there increased serum phosphate levels in CKD?
Why is less calcium absorbed in CKD?
Why is more PTH released in CKD?
increased phosphate= becuase kidney loses ability to filter as well= more phosphate stays in circulation
less cacium absorption-because kidnays cant synthesis vitamin D as well and this is needed for calcium absorption, also phosphate binds to serum calcium = reduces levels of free calcium
More PTH released- because Parathyroid glands detect decrease in vit D or Calcium and this causes release of PTH as this can unlock bone to release its stored calcium to restore serum calcium levels
How does the progression of CKD differ inpatients with normoalbuminuria, moderate albuminuria and severe albuminuria?
similar levels of decline in those with normo ans moderate but much fater decline in those with severe e.g. if you start with grade 2 and have normo/moderate in 10 years you will have grade 3b, but if severe will have grade 4/5
you may see a slight imporvement in kidney function in the frist 2 years fro all of them mostly due to initiation of drug treatment, However drugs just slow down the progression not treat it
What is the earlies identifying risk factor of CKD in people with diabetes?
moderate albuminuria
What is the best way to treat CKD?
Multifactorial intervention to reduce hypertension, hyperglycaemia and dyslipidaemia will slow the rate of GFR decline and this improve morbidity and Mortality associated with CKD
How would you generally manage patients with CKD?
- Treatment of reversible causes of renal failure
- Preventing or slowing the progression of renal disease
- Treatment of the complications of renal failure
- Adjusting drug doses when appropriate for the level of estimated glomerular filtration rate
- Identification and adequate preparation of the patient in whom renal replacement therapy (dialysis or kidney transplantation) will be required and early planning for this eventuality
What are the ‘big 6’ lifestyle changes thsat can prevent mild CKD getting worse?
1-Healthy eating
2-regular exercise
3-giving up smoking
4reduce alcohol
5-keep blood pressure down
6-keep diabetes under control
What are some common reversible problems involved in CKD that if corrected may result in some recovery of kidney function?
How can you treat them?
Decreased renal perfusion- contributes to CKD and includes hypovolemia (such as vomiting, diarrhoea, diuretic use, bleeding), hypotension (due to myocardial dysfunction or pericardial disease), infection (such as sepsis), and the administration of drugs which lower the eGFR (e.g. nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs)) can all reduce renal perfusion and are common causes of potentially reversible declines in renal function.
Administration of nephrotoxic drugs-Among patients with CKD, common offenders include aminoglycoside antibiotics (particularly with unadjusted doses), NSAIDs, and radiographic contrast material. The administration of such drugs should therefore be avoided or used with caution in patients with underlying CKD.
Urinary tract obstruction-should always be considered in a patient with unexplained worsening renal function. Urinary tract obstruction is a blockage that inhibits the flow of urine through its normal path. Examples include prostate enlargement, kidney stones, ureteric scars or strictures.
What is a useful investigation that can detect urinary tract obstruction?
Renal ultrasound is a useful investigation here and often shows hydronephrosis where urinary tract obstruction is present (where the kidney is swollen due to inability to drain properly)
What drugs interferes with creatinine secretion?
antibiotic trimethoprim- often used for urinary tract infections. It does not change the filtration rate (i.e. the true GFR) but may result in increased measured serum creatinine whilst the patient is taking the drug, because it interferes with and reduces creatinine secretion. It would therefore impact the estimated GFR.
What may cause the progression of CKD
progression may be due to secondary factors unrealted to the initial disease including intraglomerular hypertension and glomerular hypertrophy, which occur with the adaptive hyperfiltration that occurs in response to kidney damage and lead to glomerular scarring (glomerulosclerosis).
Additional causes may include systemic hypertension, hyperlipidemia, metabolic acidosis, and tubulointerstitial disease
How can you slow the progression of CKD?
Target renal protection- blood pressure control and reducing proteinuria (in proteinuric patients). ACE-Is and ARBs are associated with reduction in proteinuria (and blood pressure) and therefore have reno-protective effects in proteinuric CKD. In non-proteinuric CKD, they do not appear to be more beneficial than other antihypertensive agents.
Monitor drugs given- e.g.When used in CKD, common side effects of angiotensin inhibition can include a mild to moderate reduction in GFR and hyperkalaemia. These can occur after the initiation of therapy, after a dose increase, or with progressive CKD. Therefore, patients should be closely monitored.
Other therapeutic modalities also may offer some renal protection:
- Protein restriction may slow the progression of CKD, although the optimal level and type of protein intake have not been determined.
- Stopping smoking is associated with a slower rate of progression of CKD. Smoking also appears to correlate with an enhanced risk of developing kidney disease as well as increasing the rate of progression among those with existing CKD.
- Treatment of chronic metabolic acidosis with supplemental bicarbonate may slow the progression to end-stage renal disease (ESRD).
- Control of blood glucose can slow the development of albuminuria, the progression of microalbuminuria to overt proteinuria, and GFR loss in diabetic patients
What some of the main complications of renal failure and how do we treat them?
volume overload-people with CKD less able to rapidly respond tointake of sodium and water = fluid overload. Generally patients respond to a combo of dietary sodium restriction and diuretic therapy (usually a loop diuretic e.g. Furosemide). Some investigators have claimed that limiting sodium intake may also help decrease progression of CKD by lowering intraglomerular pressure.
Hyperkalaemia-normal potassium as long as aldosterone and tubula flow are maitained. Usulally develops in patients who are oliguric(where significantly less urine will reach the distal tubule) or have an additional problem such as a high-potassium diet, increased tissue breakdown, or hypoaldosteronism. Hypoaldosteronism can occur if the renin-angiotensin system is blocked, e.g. with an ACE-I or ARB.prevention measures can include a low-potassium diet and avoiding, if possible, the use of drugs that can raise the serum potassium concentration, such as NSAIDs.
Metabolic acidosis — There is an increasing tendency to retain hydrogen ions with progressive CKD. This can lead to a progressive metabolic acidosis. Metabolic acidosis may be treated with bicarbonate supplementation. This requires careful monitoring of volume status because bicarbonate is administered with sodium (as sodium bicarbonate), which can promote water retention.
Mineral and bone disorders — A tendency toward phosphate retention begins early in renal disease due to a reduction in filtered phosphate. phosphate retention is related to the development of secondary hyperparathyroidism.
Hypertension-80-5% of CKD patients has this. In the case of proteinuric CKD, treatment usually begins with an ACE-I or ARB (which are known to slow disease progression). The patient may need combined therapy in which case a diuretic is usually added next. Loop diuretic is recommended if oedema is present in patients with CKD and hypertension. The thiazide diuretics in conventional dosing become less effective as monotherapy when the eGFR falls below 20 mL/min/1.73 m2, as in these conditions significantly reduced volumes of urine will reach the distal tubule, where thiazide diuretics act. They do, however, produce an additive effect when administered together with a loop diuretic for refractory oedema
Anaemia-normocytic and normochromicdue to reduced production of erythropoietin by the kidney and to shortened red cell survival. Anaemia is a common feature in many patients with CKD and becomes increasingly common as eGFR falls below 60 mL/min/1.73 m2, particularly among diabetics. Hb concentration should therefore be checked every 3-12 months, (depending on stage of CKD). Investigation of anaemia in those with CKD should begin when the Hb level is <120mg/dL in females and <130mg/dL in males.
WHat are some bone diseases found in people with CKD?
osteitis fibrosa, osteomalacia, and adynamic bone disease
What is one of the erliest markers of abnormal mineral and bone metabolism in patients with CKD?
PTH levels
What is osteitis fibrosis and the treatment?
Osteitis fibrosa - results from secondary hyperparathyroidism and features weakened bone, where the calcified, mineral elements have been excessively resorbed (due to the action of PTH) and replaced by fibrous tissue.
Prevention and/or treatment in patients with pre-dialysis CKD - dietary phosphate restriction, the administration of oral phosphate binders (which reduce absorption of dietary phosphate), and the administration of calcitriol (or vitamin D analogs) to directly suppress the secretion of PTH.
How can you exclude non renal causes of anaemia when checking for Anaemia of CKD
‘Anaemia of CKD’ is largely diagnosed by excluding non-renal causes of anaemia. Work-up should therefore include red blood cell indices, reticulocyte count, serum iron, total iron-binding capacity, transferrin saturation, serum ferritin, B12 and folate concentrations, and testing for blood in stool
