Principles of prescribing in renal disease

What is the role of the kidney? (3)

1) Filter blood to remove waste products of metabolism

2) Keep electrolytes (Na+ and K+) and water content of the body constant (regulates blood volume and plasma osmolarity)

3) Secrete several essential hormones

What is the difference between efferent and afferent?

Afferent: enters

Efferent : leaves

Draw the kidney and the nephron

What is chronic kidney disease?

Reduction in kidney function or structural damage present for greater than 3 months.

This will lead to a build-up of waste and fluid in the body.

Classically a permanent and progressive disease.

Usually ASYMPTOMATIC and diagnosed via routine check-ups

Symptoms are often associated with complications

What are the causes of chronic kidney disease? (8)

Diabetes-->Nephropathy (high impact of sugar)

HTN

Glomerulonephritis

AKI

Medications- usually due to sustained damage

Obesity- increases the workload of the kidney

Obstructive uropathy

CVD

How can an AKI lead to CKD?

Lead to ischaemic changes that the kidney can sometimes not rebound from. A significant AKI

What is Glomerulonephritis and how can it cause CKD?

Glomerulonephritis is a condition where the glomeruli, the tiny filters in the kidneys that remove waste and excess fluid from the blood, become inflamed and damaged.

This inflammation can be caused by various factors, including infections, autoimmune disorders, or other underlying conditions.

Progressive Damage:

If glomerulonephritis is not treated or progresses, the damage to the glomeruli can become severe and lead to chronic kidney disease (CKD).

What is obstructive uropathy and how does it lead to CKD?

Obstructive uropathy, a blockage in the urinary tract

When urine cannot drain properly, it backs up into the kidneys, causing them to swell (a condition called hydronephrosis).

Prolonged hydronephrosis can lead to kidney damage.

Chronic obstruction can cause renal fibrosis which further impairs their function.

How does CVD lead to CKD?

CVD and CKD share common risk factors, including high blood pressure, diabetes, and a family history of kidney or heart disease.

High Blood Pressure:

High blood pressure can damage the small blood vessels in the kidneys, impairing their ability to filter blood effectively, leading to CKD.

Diabetes:

Diabetes can damage the blood vessels and nephrons in the kidneys, reducing their ability to filter waste and excess fluid, which can lead to CKD.

Heart Failure:

When the heart isn't pumping efficiently, blood can back up in the veins leading to the kidneys, causing fluid buildup and reducing blood flow to the kidneys, which can damage them and lead to CKD.

Kidney Damage and Blood Pressure:

Damaged kidneys may not be able to effectively filter excess water and salt from the body, leading to high blood pressure, which in turn can worsen kidney disease.

What is the presentation of CKD? (8)

Pruritus (itching)

Due to urea

Loss of appetite

Nausea

Oedema

Muscle cramps

Peripheral neuropathy

Pallor

Hypertension

What are the complications associated with CKD (5)?

Anaemia

Renal bone disease (RBD)

Cardiovascular disease

Stroke, MI, Backload of fluid, heart works harder

Peripheral neuropathy

Imbalance of electrolytes, leading to Pins and needles

Dialysis related problems

What are the main problems associated with dialysis? (5)

Anaemia

Mineral and bone disorders

Fluid overload

Acidosis

Hyperkalaemia

How does CKD lead to anaemia?

Reduced Erythropoietin (EPO) Production:

Healthy kidneys produce EPO, which stimulates the bone marrow to produce red blood cells.

In CKD, the kidneys are damaged and cannot produce enough EPO, leading to a shortage of red blood cells.

This results in fewer red blood cells to carry oxygen throughout the body, causing anemia.

Iron deficiency

Kidneys play a role in regulating iron levels in the body.

In CKD, the kidneys may not function properly, leading to iron deficiency.

How does CKD lead to renal bone disease?

Impaired Mineral and Hormone Regulation:

When kidneys are damaged, they can't effectively filter blood and regulate the levels of key minerals and hormones, leading to imbalances.

Impacts Vit D and Ca2+ and parathyroid levels disrupted so bone turnover is altered

How is CKD managed?

Monitor renal function

Suspend nephrotoxic medication if at risk of AKI (acutely)

FBC - rule out anaemia

Bone profile - rule out RBD

What are the key methods renal function is monitored?

No compelling evidence to support one calculation over another. eGFR and CrCl often are similar

eGFR (ml/min/1.73m2)

Estimated glomerular filtration rate

True GFR can be accessed via IV radioisotope

Can use EPI/MDRD EPI=newer and more accurate

CrCL

Creatinine Clearance Creatinine is a waste product from the normal wear and tear of muscles

ACR

Albumin:Creatinine ratio

Test to measure amount of albumin (protein) in the urine

What are the drawbacks for using eGFR?

Reports using standardised body surface area (BSA) of 1.73m2

Overestimates renal function in smaller patients

Underestimates renal function in larger patients

DO NOT USE IN - drug dose titrations, elderly patients or extremes of muscle mass

Compare CrCL and eGFR and ACR

eGFR

Estimates glomerular filtration, how much blood is filtered through both glomerular in the body per minute

Need to identify a kidney issue quickly and solve it. Why we use estimates

CrCL

Good for calculating how well we think the kidneys are working

Specific for individual body weight and easy to work out

Good for med dose changes

ACR

Good for assessing CKD

What is important to remember about serum creatnine and CrCL

Estimate of a patients kidney function • Not based off BSA, less likely to over/under estimate function • Provides a 'snapshot' • NB - if a patient is on renal replacement therapy creatine provides no useful information

What is the formula for CrCl

What are the limitations for CrCl ?

Caution in elderly, body builders, amputees, muscle wasting disorders and vegans

Patients with BMI <18 kg/m2 or >40 kg/m2 use ideal body weight (IBW) • Unless actual body weight is less than ideal Not accurate in periods of rapidly changing renal function (e.g. AKI)

What are the stages of kidney disease|?

Stage 1

Kidney damage with normal kidney function

90 or higher eGFR

90-100% pf kidney function

Stage 2

Kidney damage with mild loss of kidney function

89 to 60 eGFR

59-50%

Stage 3a

Mild to moderate loss of kidney function

59 to 45 eGFR

59-45%

Stage 3b

Moderate to severe loss of kidney function

44 to 30

44-10%

Stage 4

Severe loss of kidney Function

29 to 15

29-15%

Stage 5

* Your GFR number tells you how much kidney function you have. As kidney disease gets

worse, the GFR number goes down.

Kidney failure

Less than 15

Less than

15

Can also categorise using ACR

What are the principles of management for CKD?

Identify underlying cause and manage to slow progression of disease

Control DM

Control HTN

Treat glomerulonephritis

Treat complications

Metabolic acidosis – give Sodium bicarbonate which acts as a buffer

Anaemia – Erythropoietin (α, β, θ) + Iron replacement • RBD – Vitamin D • Dialysis? Renal transplant?

Why do we give Erythropoietin (α, β, θ)?

Give synthetic hormone (glycoprotein that mimics the job and causes bone marrow to produce RBC's)

What is the pharmacological management of CKD, and why is each one used (4)?

ACEi

In the long term they are renal protective

By inhibiting RAAS, you can prevent damage from this

Is nephrotoxic

Anti platelet

Prevent cardiovascular events. CKD can lead to changes in blood clotting factors and platelet function, increasing the risk of blood clots (thrombosis).

Statin- manage CVD risk

SGLT-2

Dapagliflozin/empagliflozin

Used in HF, DM and CKD

Mild diuretic effects, reduces pressure of kidneys

Reduces free circulating glucose

What is an AKI?

Acute Kidney injury

Kidney can recover, the damage isn't permanent, should rebound back to what it was

Underlying causes are not always clear

Especially prevalent in hospital

CKD and AKI are not mutually exclusive

What are the NICE guideline criteria for an AKI?

SrCr ↑ of ≥ 26 micromol/L in 48 hours

SrCr ↑ of ≥ 50% in 7 days

Urine output <0.5ml/kg/hour for >6 hours (only applicable where output can be measured, e.g. catheter)

What medications need to be on HOLD stopped with an AKI?

Stop any medications that will make AKI worse

DAMN

Diuretics

ACEi/ARB

Metformin

NSAIDs

What type of CT scan should be avoided in patients with an AKI?

CT scan with contrast media/ contrast CT

Contrast media makes blood shine a bright white

It is very nephrotoxic

What are the risk factors for an AKI?

Aged 65 and over

History of AKI

CKD (eGFR <60 mL/min/1.73 m2

Urological obstruction

Chronic conditions like HF, DM, proteinuria, liver disease

neurological/cognitive impairment where need to rely on others for fluid intake leading to it being reduced

Sepsis

Hypovolemia, hypotension, dehydration, reduced fluid intake

Oliguria

Who have used specific medication within the last week (especially if hypovolaemic), NSAIDS, ACEi, ARB's, diuretics, MRA's, antibiotics (aminoglycosides)

Exposure to Iodine based contrast agents

Cancer and cancer treatment

Immunocomprimised

What are the causes of an AKI?

Pre-renal (most common) — due to reduced perfusion of the kidneys and/or hypotension leading to a decreased glomerular filtration rate (GFR). It is usually reversible with appropriate early treatment

Intra-renal — a consequence of structural damage to the kidney, for example, tubules, glomeruli, interstitium, and intrarenal blood vessels. It may result from persistent pre-renal or post-renal causes damaging renal cells

Post-renal (least common, accounting for around 10% of AKI) — due to acute obstruction of urine flow within the renal tract resulting in increased intratubular pressure and decreased GFR

What is an mnemonic/acronym to remember the causes of an AKI?

SHTOP

Sepsis

Hypovolaemia

Toxicity

Obstruction

Parenchymal disease

What are the stages of an AKI?

Worked out automatically from blood test, will not have to interprets this yourself

What are the investigations for an AKI?

Assess:

Fluid balance, BP, urine output, examine chest and bladder

Routine blood test, ABG, VBG

Urine dip

Arrange US is suspected obstruction or not responding to fluids

What is the management for an AKI?

Correct underlying cause

Pre-renal cause

Provide IVT resuscitation

Post-renal cause

Relieve obstruction - insert catheter?

Hold nephrotoxic

What are the two types of IV fluid, and which one is used in an AKI?

Crystalloids

Water with electrolytes

This one is used in AKI

Colloids

Large proteins suspended in fluid

Designed to draw water out of the organs

Not used in AKI

With the complication hyperkalaemia what needs to be remembered?

Normal range --> 3.6 - 5.2 mmol/L

Results in potentially fatal cardiac arrhythmias (ventricular fibrillation)

Perform ECG

Remember medications can cause HYPERkalaemia along side AKI

What is the treatment for hyperkalaemia, and why do we give each one? (6)

Nebulised salbutamol

Shifts K+ into the cell

IV fluids

PO calcium resonium

Kat ion exchange resin

Swaps potassium for calcium

IV calcium gluconate

protect the heart, stabilise the membrane to prevent arrythmia

IV insulin

Shift the K+ out of the heart

IV glucose

Give glucose to prevent hypoglycemia

What are the complications of an AKI? (5)

Hyperkalaemia

Metabolic acidosis

Fluid overload

Uraemia

CKD

What can effect the pharmacokinetics of ADME?

ABSORPTION

Impaired gut wall function

Malabsorption

DISTRIBUTION

Reduced fat tissue and lean body mass

Hypoalbuminemia and

increased concentration of alpha-1-acid glycoprotein

METABOLISM

Changed expression of

metabolizing enzymes and drug transporters

EXCRETION

Impaired renal function

How does renal impairment change pharmacokinetics

Absorption

May be reduced due to uraemia causing nausea, vomiting, diarrhoea

Patient may be taking phosphate binders

May be affected by the increase in gastric pH

Distribution

Drug-Plasma protein binding reduced -

increased free (active) drug

Uraemia increases permeability of

BBB

Volume of distribution may be altered by changes in hydration state of patient

(e.g. increased Vd in oedema so need higher doses)

Metabolism

slower in CKD leading to increased ADRs

Vitamin D - need to use calcitriol or

alfacalcidol

Elimination

Glomerular filtration, renal tubular

secretion and resorption all reduced

Accumulation of drug/active

metabolites highly likely

Why is there special care needed with morphine in renal impairment, what would we give instead?

Used in pain (not chronic)

Metabolised in 2 different metebolism

both are renally excreted and are active

If have kidney issue, active metabolites need to be excreted by the kidney so don't leave carry on binding, risk toxicity

Oxycodone metabolised once is active, then again to be inactive, so when it accumulates, no effect

So this is the opioid given in patients with kidney damage

In cases of renal impairment what do we need to check? (2)

Both the medication and metabolites

Ensure neither toxically accumulate

What do we need to know before drug administration in renal impairment ?

• Many drugs are renally excreted

• Risk of accumulation

• Increased drug T1⁄2

• Drugs may have reduced efficacy

In renal impairment, if a patient is vit D deficient what do we need to give?

Vitamin D requires hydroxylation by the kidney to its active form; alfacalcidol and calcitriol are active metabolites of vitamin D which do not require hydroxylation by the kidney. Considerations related to the individuals renal impairment will need to be made when choosing a vitamin D product.

What are the prescribing approaches for renal impairment?

• Increase dosing interval • Decrease dose •Combination of dose reduction and increased interval

• Review drug choice

What are the rules around using DOAC's in renal disease?

CrCl should be used as an estimate of renal function for direct-acting oral anticoagulants (DOACs), and drugs with a narrow therapeutic index that are mainly renally excreted.

Has many indications - ensure you know the indication you are treating

Look at the individual rules for each medicine

E.g. Apixaban prophylaxis of stroke in AF

5mg BD

UNLESS 2 of the following 3 criteria are met:

>80 years old

<60kg or SrCr

<133micromol/L

This rule does NOT apply in treatment on DVT/PE

Should NSAIDS be used in renal impairment? Explain your answer?

Avoid if possible

inhibition of prostaglandin-induced vasodilation and can result in reduced renal blood flow and perfusion, especially those with renal disease

Why should ACEi/ ARBs be used on renal disease?

Block the effects of the renin-angiotensin-aldosterone system (RAAS), a system that regulates blood pressure and fluid balance.

They work by reducing glomerular pressure, which helps to protect the kidneys' filtering units (glomeruli).

CE inhibitors and ARBs can sometimes cause a temporary decline in kidney function, especially when first started or in patients with advanced kidney disease.

Hyperkalemia: They can also increase potassium levels in the blood (hyperkalemia), which can be dangerous.

May need to reduce dose in late stage CKD

Mr AK, 67 y/o, ♂

P/C - Fever, Cough, Mild chest pain

PMH - HTN

DHx - • Ramipril 5mg OM • Ibuprofen 400mg TDS PRN (for knee pain)

SHx - 86Kg

Investigations - Na 159mmol/L, Urea 8.9mmol/L, SrCr 397µmol/L, eGFR 20mL/min/1.73m2, WCC 8.0/mm3 , CRP 56mg/L

Ward Round • Diagnosed as LRTI - requires antibiotics • Start IV Co-amoxiclav 1.2g TDS • Start IVT • Monitor temp, FBC (infection markers)

NB - eGFR 20mL/min/1.73m2

Creatinine results - 2021 98µmol/L, 2022 91µmol/L, Today 397µmol/L

What would be the interventions?

What would you recommend on discharge?

Interventions -

Suspend nephrotoxics (ACEi and NSAID)

Amend co-amoxiclav dose interval

Monitor renal function and K+

Discharge - • Recommend swap ACEi to CCB

Recommend use of paracetamo'

Mrs CK, 85 y/o, ♀

P/C - SOB, palpitations

PMH - Hyperthyroidism

DHx - • Levothyroxine 125mcg OM • Amlodipine 10mg OM • Bendroflumethiazide 2.5mg OM

SHx - 65kg • Investigations - SrCr 149µmol/L

Ward Round •

ECG performed - AF

CHA2DS2VASC: 4

ORBIT: 2 low

Start anticoagulation

Patients preference to have ONCE DAILY preparation - Rivaroxaban 20mg OM prescribed

• CrCl = 25ml/min

What are the pharmacist intervention?

Dose reduce anticoagulant

Recommend starting β-blocker

Monitor U&Es, HR, BP

What is the difference between efferent and afferent?

Afferent: enters

Efferent : leaves