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October 2018
Renal problems
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Renal problems
Unit 554 October 2018
About this activity 4. Thomas MC, Weekes AJ, Broadley OJ, as an interest in academic surgery.
Cooper ME, Mathew TH. The burden of
He enjoys teaching medical students
It is estimated that over 1.7 million chronic kidney disease in Australian
patients with type 2 diabetes (the and junior doctors, and has published
Australians have biomedical
NEFRON study). Med J Aust on both benign and malignant
indicators of kidney disease such as
2006;185(3):140–44. urological conditions. He is happy to
albuminuria or reduced kidney
5. Yaxley J, Litfin T. Non-steroidal anti- be contacted with questions about
function.1 In 2013–14, 0.4 out of 100
inflammatories and the development of the management of urolithiasis.
general practice presentations analgesic nephropathy: a systematic
related to chronic kidney disease review. Ren Fail 2016;38(9):1328–34. Merlin Thomas (Case 4) MBChB,
(CKD).2 Many cases go undiagnosed, 6. Australian Institute of Health and PhD, FRACP is a professor in the
and prevalence increases with age.3 Welfare. Acute kidney injury in Department of Diabetes, Monash
Australia: a first national snapshot. Cat.
University, Melbourne and NHMRC
The most frequent cause of CKD is no. PHE 190. Canberra: AIHW, 2015.
Senior Research Fellow. His research
diabetes mellitus, followed by 7. Sewell J, Katz DJ, Shoshany O, Love C.
is focused on exploring and
glomerulonephritis and Urolithiasis: Ten things every general
practitioner should know. Aust Fam understanding the key pathways
hypertension.3 As diabetes frequently
Physician 2017;46(9):648–52. Available involved in the development and
results in albuminuria and a
at https://www.racgp.org.au/ progression of diabetic
reduction in estimated glomerular afp/2017/september/urolithiasis/
complications, and the development
filtration rate, approximately 50% of [Accessed 3 September 2018].
patients with type 2 diabetes mellitus of novel therapies for their prevention
and management. Professor Thomas
have CKD.4 Learning outcomes
has published over 300 research
One form of kidney injury that can At the end of this activity, participants articles. He is also the best-selling
lead to CKD is analgesic will be able to: author of ‘The Longevity List’ and
nephropathy. Several decades ago, ‘Fast Living Slow Ageing’.
• outline the investigative process
analgesic nephropathy accounted
used to diagnose urolithiasis Katie Trinh (Case 5) BSc (Adv)
for 15–20% of cases of end-stage
renal failure. Although this has • summarise the management of MBBS is a nephrology advanced
fallen to 1%, the effect of analgesics chronic kidney disease trainee at Westmead Hospital.
remains an important consideration Julian Yaxley (Case 3) MBBS is a
• discuss the aetiology of analgesic
in kidney failure.5 nephrology registrar working at Gold
nephropathy
The incidence of acute kidney injury Coast University Hospital.
• describe the approach to managing
(AKI) is on the rise and prevalence
diabetic kidney disease Peer reviewers
increases with age, with AKI leading
to 18,010 hospitalisations in 2012–13.6 • identify the signs and symptoms of Karen Dwyer MBBS, PhD, FRACP is
AKI results in approximately 4,670 acute kidney injury. professor of Medicine and Deputy
deaths per year, and mortality is 40% Head, School of Medicine at Deakin
greater in males than females.6 Authors University. She has trained as a
Urolithiasis affects up to 8% of Karin Jandeleit-Dahm (Case 4) MD, nephrologist and transplant
females and 15% of males, and many PhD, FRACP is an NHMRC senior physician. Professor Dwyer currently
patients initially present to a general research fellow and Deputy Head of works clinically at University Hospital
practitioners.7 Of patients who have the Diabetes Department at Central Geelong and Epworth Geelong.
had one kidney stone, 50% will have Clinical School, Monash University. Jan Radford MBBS, MPsychMed,
another at some point.7 MEd, FRACGP, FARGP,
Carol Lawson (Case 2) MBBS,
FRACGP is a general practitioner in AFANZAHPE is an associate
References professor of general practice at the
Brunswick, Victoria. Dr Lawson
1. Australian Bureau of Statistics. previously worked in the Department University of Tasmania, based in
Australian health survey: Biomedical of General Practice at Monash Launceston. Professor Radford has
results for chronic diseases, 2011–12. worked as a general practitioner in
University and has an interest in
Canberra:
medical education. the same practice since 1986. She
ABS, 2013.
has a specific clinical interest in
2. Britt H, Miller GC, Henderson J, Tahira Scott (Case 3) MBBS is a
et al. General practice activity in mental health care, which was the
nephrology registrar working at the
Australia 2013–14. General practice basis for her FARGP. Her research in
series no. 36. Sydney: Sydney
Townsville Hospital.
chronic kidney disease stems from an
University Press, 2014. [Accessed 03 interest in the secondary use of
James Sewell (Case 1) is a Victorian
September 2018].
urology registrar currently practising routinely collected electronic health
3. The Australian Kidney Foundation.
in Frankston. Dr Sewell has a special record data. Professor Radford is also
Chronic kidney disease management in
general practice. Melbourne: Kidney interest in the medical and surgical undertaking a PhD in medical
Health Australia; 2015. management of urolithiasis, as well education.
2
Renal problems check About this activity
Abbreviations
ABPM ambulatory blood
pressure monitoring
ACEI angiotensin converting
enzyme inhibitor
ACR albumin-to-creatinine ratio
AKI acute kidney injury
ARB angiotensin receptor blocker
BMI body mass index
CKD chronic kidney disease
CT computed tomography
CTKUB computed tomography of the
kidneys, ureter and bladder
DPP-4 dipeptidyl peptidase-4
DVT deep vein thrombosis
ECG electrocardiogram
eGFR estimated glomerular
filtration rate
FBE full blood evaluation
HBPM home blood pressure
monitoring
KDIGO Kidney Disease Improving
Global Outcomes
NSAIDs non-steroidal
anti‑inflammatory drugs
PPI proton pump inhibitor
PTH parathyroid hormone
SGLT2 sodium−glucose
cotransporter 2
T2DM type 2 diabetes mellitus
UTI urinary tract infection
3
Case 1 check Renal problems
CASE Question 3
1
What further investigations would you organise?
Trisha’s rocky road
Question 1
Further information
What history would you elicit? What investigation would you
Trisha’s creatinine is now 120 µmol/L (from a baseline of
do in your clinic room to help you differentiate the cause of
80 µmol/L), and her urine microscopy shows 80 erythrocytes,
Trisha’s symptoms?
20 polymorphs and no organisms. Computed tomography of
her kidneys, ureter and bladder (CTKUB) shows a 5‑mm
calculus at the right vesicoureteric junction with moderate-to-
severe proximal hydronephroureter. There are no other calculi
and no other abnormalities on her scan.
Question 4
What are the red flags for immediate referral to hospital for
treatment of renal colic?
Further information
Trisha has not had any symptoms of infection and has not
noticed any haematuria. She is a current smoker with a
40 pack-year history and is on irbesartan for hypertension.
She has not had urinary tract surgery or any other medical
history of note. She has tenderness in her right renal angle,
and her urine dipstick shows microhaematuria and leukocyte
esterase, but no nitrites.
Question 5
Question 2
Which criteria would you use to determine whether it is safe
What are your differential diagnoses for Trisha’s symptoms? to offer conservative management to Trisha?
4
Renal problems check Case 1
Answer 2
Further information
From what you have gathered, it is likely that Trisha has
Trisha follows your advice regarding conservative right ureteric colic. Classically, stranguria (painful small
management but returns to you after three weeks with voids) suggests that the stone is at the vesicoureteric
ongoing pain. You refer her to a urologist, who inserts a junction. However, cystitis and pyelonephritis remain
ureteric stent. She presents to you again with ongoing flank differentials.
pain, urinary frequency and haematuria.
Answer 3
Question 7 In patients in whom the suspected diagnosis is renal colic, you
should organise CTKUB (non-contrast CT abdomen
How will you manage Trisha?
performed prone). Ultrasonography of the renal tract should
be reserved for patients in whom ionising radiation must be
avoided. This includes pregnant women and young children.
Ultrasonography does not effectively visualise the ureters and
offers a poor estimate of stone size. Given that stone size and
location are two vital factors for determining management,
CTKUB should be performed.1
Answer 4
Anatomical:
Further information
• Single functional kidney (congenitally or surgically absent
Trisha undergoes a ureteroscopy and laser lithotripsy
kidney, non-functional kidney)
(fragmentation of the calculus). Her postoperative ureteric
stent is subsequently removed. At her next visit to see you, • Bilateral ureteric obstruction
she asks you what she can do to prevent further episodes.
Systemic:
Answer 5
Assuming the patient has none of the red flags listed in Answer 4,
there are some criteria that warrant referral for outpatient review
by a specialist rather than conservative management.
5
Case 1 check Renal problems
Generally, it is appropriate to offer conservative management Patients should remain hydrated sufficiently that the urine
to patients with stones that are 7 mm or smaller in size, as remains clear. The actual amount of fluid will depend on the
approximately 60% of these stones should eventually pass.2 time of year and the patient’s occupation, but looking at urine
provides easy feedback as to whether fluid intake is sufficient.
Answer 6
A low-salt diet will reduce urinary calcium (alteration of
Provide a script for tamsulosin 400 µg daily for utereric dietary calcium is not helpful), and a low oxalate diet can also
relaxation, paracetamol 1 g four times daily, indomethacin be useful. Acidic urine promotes stone formation. In most
50 mg orally, three times a day as needed, with or without people, urine acidity is driven by protein intake, so a lower
oxycodone 5 mg orally, four times a day as needed.3 protein diet helps to prevent stones.5
Answer 7
Urinary frequency, dysuria, haematuria from bladder irritation
and intermittent flank pain from refluxing urine are the classic
constellation of symptoms from stent pain but may often be
confused with the symptoms of a UTI.
6
Renal problems check Case 2
CASE Question 3
Question 4
Question 1
Does Nick need any more tests?
Does Nick have hypertension?
7
Case 2 check Renal problems
What medications would you recommend for Nick? ABPM night time (asleep) ≥120 ≥70
ABPM, ambulatory blood pressure monitoring; HBPM, home blood pressure monitoring
Answer 2
Nick now fits the diagnosis of hypertension. The diagnostic
process aims to:1
8
Renal problems check Case 2
Investigation for secondary causes of hypertension should be injury.4 To confirm the diagnosis of CKD, eGFR and ACR
considered in selected patients on the basis of clinical should be repeated in three months.4
suspicion or on specific findings in the history and/or
When CKD is first diagnosed, the underlying cause should be
examination.1 Investigations could include:
investigated sufficiently to exclude treatable causes such as
• renal artery imaging in young females (to exclude fibromuscular obstruction, vasculitis, nephrotic syndrome and rapidly
dysplasia), in older patients with known atherosclerotic disease progressive glomerulonephritis.5 In Australia, the most common
or in patients with a renal and/or femoral bruit1 causes of CKD are diabetic nephropathy, glomerulonephritis,
hypertension and polycystic kidney disease.4
• plasma renin-to-aldosterone ratio in patients with
moderate-to-severe hypertension, with hypertension that is Diagnostic evaluation tests recommended for all people with
difficult to control or with hypokalaemia1 CKD are:5
9
Case 2 check Renal problems
Nephrotoxic medication should be avoided in people with CKD.5 3. Blake M. Pheochromocytoma. Medscape, 2018. Available at
https://emedicine.medscape.com/article/124059-overview
In particular, Nick needs to be aware that the combination of
[Accessed 15 July 2018].
ACEI or ARB with a diuretic and non-steroidal anti-
4. The Australian Kidney Foundation. Chronic kidney disease
inflammatory drug (non-selective or selective cyclooxygenase-2 management in general practice. 3rd edn. Melbourne: Kidney
inhibitor) can result in acute kidney injury.4 Health Australia, 2015. Available at https://kidney.org.au/cms_
uploads/docs/ckd-management-in-gp-handbook-3rd-edition.pdf
Noting that Nick has CKD as a current medical problem in Nick’s [Accessed 19 July 2018].
health record, including his electronic health record (e-HR) if he
5. Johnson D, Atai E, Chan M, et al. KHA–CARI Guideline: Early
has one, will assist in adjusting drug doses, as appropriate, and chronic kidney disease: Detection, prevention and management.
avoiding the prescribing of nephrotoxic medications for Nick in Nephrology 2013;18(5):340–50. doi: 10.1111/nep.12052.
the future. The e-HR would need to provide the prescriber with 6. Department of Health. Australia’s physical activity and sedentary
renal impairment alerts related to prescribing. behaviour guidelines. Canberra: Commonwealth of Australia, 2018.
Available at www.health.gov.au/internet/main/publishing.nsf/
Placing a diagnosis in the e-HR will also assist in content/health-pubhlth-strateg-phys-act-guidelines#apaadult
systematising the monitoring of patients with CKD as this [Accessed 19 July 2018].
population of patients can then easily be identified. 7. National Health and Medical Research Council. Australian
guidelines to reduce health risks from drinking alcohol. Canberra:
People with CKD and macroalbuminuria should be reviewed Commonwealth of Australia, 2009. Available at www.nhmrc.gov.
at least every three months.4 The clinical assessment should au/health-topics/alcohol-guidelines [Accessed 19 July 2018].
include weight and blood pressure measurement, and 8. Department of Health. Pharmaceutical Benefits Scheme: General
assessing for the presence of any oedema. The following statement for lipid-lowering drugs prescribed as pharmaceutical
indices should be monitored regularly:4 benefits. Canberra: Commonwealth of Australia, 2018. Available at
www.pbs.gov.au/info/healthpro/explanatory-notes/gs-lipid-
• urea, electrolytes, creatinine and eGFR lowering-drugs [Accessed 19 July 2018].
10
Renal problems check Case 3
CASE Question 3
Question 4
How do patients with analgesic nephropathy present?
Question 1
What are the possible diagnoses?
Question 5
Question 2 How would you investigate Robyn’s renal impairment?
11
Case 3 check Renal problems
Answer 2
Many analgesic medicines are nephrotoxic and can produce
renal papillary necrosis and chronic inflammation of the renal
Question 7 interstitium. It has therefore been observed that consistent
long-term consumption of analgesic agents may lead to CKD,
What is Robyn’s prognosis?
termed analgesic nephropathy.
Answer 3
The precise analgesic agents and quantities necessary to produce
CKD are unproven. It is thought that the minimum cumulative
dosage required to generate analgesic nephropathy is daily
consumption of analgesic medicines for two consecutive years.3
12
Renal problems check Case 3
13
Case 4 check Renal problems
CASE Question 3
4
What additional tests will you order to help you confirm a
Hoon gets complicated diagnosis of diabetic kidney disease?
Question 1
What specific questions would you ask Hoon about his
kidneys and his risks for kidney problems?
Further information
14
Renal problems check Case 4
Answer 3
Initially, kidney function should be assessed by testing for
elevated albuminuria and a reduced eGFR in all people with
T2DM, from the time of their diagnosis.1
15
Case 4 check Renal problems
electrophoresis and urine protein electrophoresis are also Dipeptidyl peptidase-4 (DPP-4) inhibitors are preferred in
appropriate in older adults with proteinuria, to exclude patients with CKD because of comparable efficacy in patients
myeloma. Renal ultrasonography may also be an with renal impairment to that observed in patients with
appropriate assessment in patients with renal impairment normal renal function and a low incidence of adverse drug
of uncertain duration to exclude obstruction or cystic reactions including hypoglycaemia. However, because of their
disease and assess chronicity. differing pharmacology, differing dosing strategies may be
required. Sitagliptin, alogliptin, and the major metabolites of
Answer 4 saxagliptin and vildagliptin are predominantly eliminated into
the urine, meaning some dose reduction is required (Figure 1).
The presence and severity of CKD is a strong risk factor for
Linagliptin requires no dose adjustment in renal impairment
adverse renal outcomes, including kidney failure, the
because of its biliary metabolism.11 However, DPP-4 inhibitors
requirement for dialysis and premature mortality.6 Even in
must also be used with metformin (or a sulphonylurea) to be
individuals with established CKD, this risk can be
eligible for a Pharmaceutical Benefits Scheme subsidy, even
substantially reduced by improved and sustained diabetes
in patients with renal impairment. Using appropriately low
control, including better glucose, lipid and blood pressure
doses with sick-day rules usually makes this possible.
control, blockade of the renin-angiotensin-aldosterone system
and smoking cessation.1 The glucose-lowering effects of SGLT2 inhibitors are small
or insignificant in patients with renal impairment because of
In individuals with reduced kidney function, it is also important reduced glycosuria. Consequently, dapagliflozin may be used
to avoid, where possible, additional nephrotoxic insults (eg high if the eGFR is >60 mL/min/1.73 m2, and empagliflozin may
doses or prolonged use of over-the-counter painkillers, herbal be used if the eGFR is >45 mL/min/1.73 m2.1 Notably, the
remedies, certain antibiotics, radiographic contrast material, cardiac and renal effects of SGLT2 inhibition appear to be
hypovolaemia, hypotension, dehydration). The implementation independent of glucose-lowering and baseline renal function.7,8
of electronic health records with integrated clinical decision Glucagon-like peptide 1 receptor agonists, such as exenatide,
support has the potential to automatically reduce these risks in are cleared by the kidneys, so renal impairment increases
patients with established CKD, especially where multiple dose-dependent nausea and other side effects.
practitioners are involved in their care.
Many practitioners reluctantly fall back on insulin therapy in
Treatment with sodium-glucose co-transporter 2 (SGLT2) individuals with reduced kidney function, despite the ever-present
inhibitors may reduce the risk of kidney disease progression in risks from hypoglycaemia due to altered insulin pharmacology,
patients with T2DM, beyond their glucose-lowering actions.7,8 inadequate compensatory gluconeogenesis and flattening of
the relationship between mean glucose control and HbA1c so
Answer 5 that the impact of intensification may be underestimated.
Poor glucose control remains a significant risk factor for
adverse outcomes even in individuals with reduced kidney Answer 6
function (eGFR <60 mL/min/1.73 m2).9 If glucose-lowering Early referral and care by nephrologists may be appropriate
can be achieved safely (eg without hypoglycaemia, heart for some individuals with diabetes and an eGFR
failure or other adverse drug reactions), it is still worth <30 mL/min/1.73 m2 in order to discuss and potentially plan
pursuing in individuals with CKD. However, all classes of for renal replacement therapy.1
glucose-lowering agents require some changes in their use
for individuals with reduced kidney function. At higher levels of renal function, referral may also be
appropriate for those with CKD experiencing:
Metformin accumulates in renal impairment. However, in
most patients with CKD, metformin can still be safely used, • a sustained decrease in eGFR of ≥25%
providing its dose is reduced appropriately. Metformin doses • a sustained decrease in eGFR of 15 mL/min/1.73 m2
for Hoon should be reduced to no more than 1 g/day to ensure within 12 months
safe drug exposure and reduced risk of side effects. It is
recommended that metformin should eventually be
discontinued when eGFR is <30 mL/min/1.73 m2.1 Planning Dosing of DPP-4 inhibitors in chronic kidney disease
to temporarily discontinue metformin therapy in the event of Sitagliptin 100 mg qd 50 mg qd 25 mg qd
significant illness is also important as part of sick-day rules.1 Alogliptin 25 mg qd 12.5 mg qd 6.75 mg qd
16
Renal problems check Case 4
• anaemia
• volume overload that is difficult to control.
Conclusion
CKD is a common companion to T2DM. Approximately one in
every three patients with T2DM seen in Australian general
practice has increased albuminuria. Approximately one in every
four patients with T2DM has a persistent reduction in eGFR
below 60 mL/min/1.73 m2. Taken together, at least every
second patient with T2DM has CKD.2
References
1. The Royal Australian College of General Practitioners. General
practice management of type 2 diabetes 2016–2018. Melbourne:
RACGP, 2016. Available at www.racgp.org.au/your-practice/
guidelines/diabetes/ [Accessed 17 August 2018].
2. Thomas MC, Weekes AJ, Broadley OJ, Cooper ME, Mathew TH.
The burden of chronic kidney disease in Australian patients with
type 2 diabetes (the NEFRON study). Med J Aust 2006;185(3):
140–44.
3. Teng J, Dwyer KM, Hill P, et al. Spectrum of renal disease in
diabetes. Nephrology 2014;19(9):528–36.
4. Kidney Disease Outcomes Quality Initiative. Definition and
classification of CKD. Kidney Int Suppl 2013;3(1):19–62.
5. The Australian Kidney Foundation. Chronic kidney disease
management in general practice. 3rd edn. Melbourne: Kidney
Health Australia, 2015. Available at https://kidney.org.au/cms_
uploads/docs/ckd-management-in-gp-handbook-3rd-edition.pdf
[Accessed 19 July 2018].
6. Afkarian M, Sachs MC, Kestenbaum B, et al. Kidney disease and
increased mortality risk in type 2 diabetes. J Am Soc Nephrol
2013;24(2):302–08.
7. Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and
progression of kidney disease in type 2 diabetes. N Engl J Med
2016;375(4):323–34. doi: 10.1056/NEJMoa1515920.
8. Thomas MC, Cherney DZI. The actions of SGLT2 inhibitors on
metabolism, renal function and blood pressure. Diabetologia
2018;61(10):2098–07.
9. Shurraw S, Hemmelgarn B, Lin M, et al. Association between
glycemic control and adverse outcomes in people with diabetes
mellitus and chronic kidney disease: A population-based cohort
study. Arch Intern Med 2011;171(21):1920–27.
10. National Kidney Foundation. KDOQI clinical practice guidelines for
diabetes and CKD: 2012 Update. Am J Kidney Dis 2012;60(5):850–86.
11. Agarwal V, Giri C, Solomon RJ. The effects of glucose-lowering
therapies on diabetic kidney disease. Curr Diab Rev 2015;11(3):191–200.
17
Case 5 check Renal problems
CASE Question 3
5
What investigations would you arrange for Craig to have?
Craig is nauseated
Question 1
What is your interpretation of Craig’s blood test results?
Further information
Further information Craig tells you that his only symptoms are malaise and nausea.
He has not had any recent infections or commenced any other
You recall Craig for urgent review.
medications. He has been drinking but not eating much
because of his nausea, and passed urine normally this morning.
His blood pressure is lower than usual at 110/75 mmHg, with
Question 2
no postural drop, and his temperature and heart rate are
What further questions should you ask in your history and normal. He appears only mildly dehydrated but examination is
look for in your examination? otherwise unremarkable.
18
Renal problems check Case 5
What would you do next? Craig wants to know how to protect his kidney from further insults.
Question 8
What should you advise him?
Further information
Given that Craig’s last blood test was six months ago, this
result may be reflective of CKD. Repeat evaluation can
confirm the diagnosis of AKI or CKD, the timing of which
requires clinical judgement and suspicion for AKI.2 In the
context of his acute illness, it may be inferred that Craig has
AKI and he should be re-evaluated early.
Answer 2
Further information
The KDIGO guidelines recommend that patients be evaluated
Craig is worried that this event has caused permanent promptly to determine the cause of AKI.1 History and
damage to his kidneys. examination are important in determining the aetiology of
AKI. Pre-renal AKI is caused by renal hypoperfusion, such as
in hypovolaemia, sepsis and reduced effective arterial blood
Question 7
volume (eg heart failure, decompensated liver failure). Intrinsic
What do you tell Craig? How should you monitor his causes of AKI include acute glomerulonephritis, acute
progress? interstitial nephritis, acute tubular necrosis (due to prolonged
renal hypoperfusion), vasculitis and nephrotoxins. Post-renal
AKI due to obstruction of the urinary tract may be caused by
kidney stones, prostatic hypertrophy or malignancy.
19
Case 5 check Renal problems
You should ask Craig about his oral intake, fluid losses (such
Table 1. Commonly used oral drugs in adults requiring
as vomiting or diarrhoea) and urine output.
dose reduction or caution in renal impairment7
To determine the aetiology of his AKI, you could ask Craig
Drug Dosing recommendations and comments
questions about:
Anticoagulants used to prevent emboli in atrial fibrillation
• symptoms of acute illness (eg vomiting, diarrhoea, infection)
• systemic symptoms, such as rash or arthralgia, which may Apixaban No renally adjusted dosing
be suggestive of systemic vasculitis or a rheumatological Contraindicated when CrCl <25 mL/min
condition Rivaroxaban Standard dose: 20 mg once daily
• recent changes in medications (including supplements and CrCl 30–49 mL/min: 15 mg once daily
over-the-counter medications), and in particular non- CrCl <30 mL/min: contraindicated
steroidal anti-inflammatory drugs (NSAIDs), proton pump
Dabigatran Standard dose: 150 mg twice daily
inhibitors (PPIs) and antibiotics
(or 110 mg twice daily if >75 years)
–– you should also enquire if Craig has had recent studies CrCl 30–50 mL/min: 110 mg twice daily
with intravenous contrast CrCl <30 mL/min: contraindicated
• flank pain, which may be due to kidney stones Hypoglycaemic drugs
• obstructive lower urinary tract symptoms, such as in
Metformin Should be withheld in acute illness and if at risk of
prostatic hypertrophy.
further deterioration of renal function.
You could also examine Craig for clues to the underlying Maximum doses based on stable renal function
aetiology of his AKI, such as rash, joint swelling or a palpable CrCl 60–90 mL/min, 2 g daily
bladder. Signs of heart failure or decompensated liver failure CrCl 30–60 mL/min, 1 g daily
may also be suggestive but are unlikely in Craig’s case. CrCl 15–30 mL/min, 500 mg daily*
*In practice, metformin is generally not used if
Answer 3 CrCl <30 mL/min)4
Urine should be collected for urinalysis, microscopy/culture/ Gliclazide Dose reduction is required in severe renal impairment
Glipizide because the risk of hypoglycaemia is increased
sensitivity, red cell morphology, casts and quantification of
creatinine, albumin and protein. Urinary sodium, if low Sitagliptin Standard dose: 100 mg daily
(<20 mmol/L), may suggest pre-renal azotemia rather than CrCl 30–50 mL/min: 50 mg daily
acute tubular necrosis. However, interpretation of this would be CrCl <30 mL/min: 25 mg daily
difficult in Craig’s situation because he is on a diuretic, which
Empaglifozin Standard dose: 10 mg once daily, up to 25 mg daily
increases urinary sodium excretion. Renal ultrasonography
CrCl <45 mL/min: contraindicated
should be performed to look for urinary obstruction.3,4 Blood
tests to look for other underlying pathology should also be Analgesia
considered if there are suggestive features in the history,
Oxycodone Reduce initial dose if CrCl <30 mL/min
examination and initial urine investigations (eg dysmorphic red
Example: oxycodone/naloxone
blood cells, active urinary sediment, including red and white
Standard dose: 5/2.5 to 10/5 mg every 12 hours
blood cell casts). These blood tests may include C3, C4,
CrCl <30 mL/min: start with 2.5/1.25 mg every
antinuclear antibodies, extractable nuclear antigen, anti-double
12 hours
stranded DNA, anti-neutrophil cytoplasmic antibodies, serum
electrophoresis and serum free light chains. Pregabalin Standard dose: initially 75 mg twice daily,
up to maximum 300 mg twice daily
Answer 4 CrCl 30–60 mL/min, initially 75 mg daily,
maximum 300 mg daily
It is very important that Craig’s medications are reviewed to CrCl 15–30 mL/min, initially 25–50 mg daily,
prevent further exacerbation of his AKI, prevent toxicity of maximum 150 mg daily
renally excreted drugs that may accumulate in renal failure, and CrCl <15 mL/min, initially 25 mg daily,
cease any drugs that may be the primary cause of his AKI. maximum 75 mg daily
You should tell Craig to stop taking his combined Drugs for gout prophylaxis
antihypertensive tablets until further notice. AKI can be Allopurinol Use lower starting doses in renal impairment
exacerbated by medications such as antihypertensives, eGFR >60 mL/min/1.73 m2: 100 mg daily
(especially angiotensin converting enzyme inhibitors [ACEIs] eGFR 30–60 mL/min/1.73 m2: 50 mg once daily
or angiotensin II receptor blockers [ARBs]), diuretics and eGFR 15–30 mL/min/1.73 m2: 50 mg alternate days
NSAIDs. These medications can further exacerbate eGFR <15 mL/min/1.73 m2: 50 mg twice a week
hypovolaemic states and renal hypoperfusion.
Colchicine Standard dose: 500 µg once or twice daily
Given his acute illness, Craig should be advised to withhold CrCl <30 mL/min: initially 250 µg daily
metformin. In general, patients with eGFR <30 mL/min/1.73 m2
CrCl, creatine clearance; eGFR, estimated glomerular filtration rate
should also be advised to withhold metformin to reduce the risk
20
Renal problems check Case 5
Answer 6 References
1. Kidney Disease: Improving Global Outcomes Acute Kidney Injury
Medication review is very important in the context of renal
Work Group. KDIGO clinical practice guideline for acute kidney
impairment. Craig should discontinue esomeprazole and avoid injury. Kidney Inter Suppl 2012;2:1–138.
PPIs. His blood pressure should be assessed prior to 2. Kidney Disease: Improving Global Outcomes Acute Kidney Injury
recommencing antihypertensive medications. Given his renal Work Group. KDIGO 2012 clinical practice guideline for the
function has improved and eGFR is 80 mL/min/1.73 m2, evaluation and management of chronic kidney disease. Kidney
candesartan and hydrochlorothiazide could be re-introduced Inter Suppl 2012;3:1–150.
(with ongoing monitoring of renal function). If there is evidence of 3. The National Institute for Health and Care Excellence. Acute
kidney injury: Prevention, detection and management. London:
persistent renal dysfunction, ACEIs, ARBs and diuretics should
NICE, 2013. Available at www.nice.org.uk/guidance/cg169
be avoided until renal recovery. In such a situation, alternative [Accessed 17 August 2018].
agents such as non-dihydropyridine calcium channel blockers, 4. The Australian Kidney Foundation. Chronic kidney disease
including amlodipine, may be used to manage his blood pressure. management in general practice. 3rd edn. Melbourne: Kidney
It should be safe for Craig to continue using his metformin with Health Australia, 2015. Available at https://kidney.org.au/cms_
his current eGFR of 80 mL/min/1.73 m2. Dose reduction and uploads/docs/ckd-management-in-gp-handbook-3rd-edition.pdf
[Accessed 20 August 2018].
further additions to his T2DM management should be considered
in the context of his renal impairment. 5. The Royal Australian College of General Practitioners. General
practice management of type 2 diabetes 2016–18. Melbourne:
RACGP, 2016. Available at www.racgp.org.au/download/
Table 2. Staging of acute kidney injury in adults1 Documents/Guidelines/Diabetes/2015diabetesmanagement.pdf
[Accessed 17 August 2018]
Stage Serum creatinine Urine output
6. Geevasinga N, Coleman PL, Webster AC, Roger SD. Proton pump
1 1.5–1.9 times baseline, or <0.5 mL/kg/h for 6–12 hours inhibitors and acute interstitial nephritis. Clin Gastroenterol
≥26.5 µmol/L increase Hepatol 2006;4(5):597–604.
2 2.0–2.9 times baseline <0.5 mL/kg/h for ≥12 hours 7. Australian Medicines Handbook 2018. Adelaide: Australian
Medicines Handbook Pty Ltd, 2018. Available at https://
3 3.0 times baseline, or <0.3 mL/kg/h for ≥24 hours, amhonline.amh.net.au/ [Accessed 20 August 2018].
increase in serum creatinine or 8. Chawla LS, Eggers PW, Star RA, Kimmel PL. Acute kidney injury
to ≥353.6 µmol/L, or Anuria for ≥12 hours and chronic kidney disease as interconnected syndromes. N Engl J
initiation of renal Med 2014;371(1):58–66. doi: 10.1056/NEJMra1214243.
replacement therapy
21
Multiple choice question check Renal problems
A. Urinary frequency
This unit of check is approved for six Category 2
points in the RACGP QI&CPD program. The expected B. Painful small voids
time to complete this activity is three hours and
C. Intolerable flank pain and nausea
consists of:
D. All of the above
• reading and completing the questions for each
case study
Case 2 – Maria
–– you can do this on hard copy or by logging on to
Maria, 50 years of age, is one of your regular patients and was
the gplearning website, http://gplearning.racgp.
diagnosed with type 2 diabetes mellitus (T2DM) two weeks
org.au
ago. At the time of T2DM diagnosis, you advised Maria to have
• answering the following multiple choice questions an eye examination and you requested blood and urine tests to
(MCQs) by logging on to the gplearning website, check her kidney function. The results show that her estimated
http://gplearning.racgp.org.au glomerular filtration rate (eGFR) is 64 mL/min/1.73 m2 and her
urinary albumin-to-creatinine (ACR) is 40 mg/mmol.
–– you must score ≥80% before you can mark the
activity as ‘Complete’
Question 3
• completing the online evaluation form.
Maria’s test results indicate that she:
You can only qualify for QI&CPD points by
A. has moderately increased albuminuria
completing the MCQs online; we cannot process
hard copy answers. B. has severely increased albuminuria
If you have any technical issues accessing this activity C. will need repeat testing within the next three months
online, please contact the gplearning helpdesk on
D. will need repeat testing within seven days.
1800 284 789.
If you are not an RACGP member and would like to Further information
access the check program, please contact the
Maria had initially opted for lifestyle modification to control her
gplearning helpdesk on 1800 284 789 to purchase
blood glucose levels, but this proved inadequate, so you prescribed
access to the program.
metformin 1 g. Repeat urine tests three months after the initial
tests showed no change in eGFR and urinary ACR, confirming
severely increased albuminuria. Testing a year later shows eGFR
has decreased to 55 mL/min/1.73 m2 and remains decreased on
Case 1 – Vincent repeat testing. HbA1c has increased to 69 mmol/mol (8.5%).
22
Renal problems check Multiple choice question
Lifestyle changes that you could recommend to help with D. 255–360 µmol/L
reducing Conrad’s blood pressure include:
Further information
A. a low-phosphate diet
You arrange for an urgent referral to a nephrologist, who
B. a low-protein diet
admits Tracy to hospital for treatment. She recovers fully and,
C. reduction of salt intake to <6 g/day after being discharged, returns to see you for a follow-up
D. all of the above. appointment. You advise Tracy that she will need ongoing
monitoring of her kidney function. You also discuss her
medications and risk factors for AKI.
Further information
Repeat testing three and six months later shows eGFR results Question 8
of 55 and 50 mL/min/1.73 m2 respectively. Urinary ACR has
In Tracy’s case, the most likely cause of her AKI is:
remained at about 45 mg/mmol. Conrad’s blood pressure
remains increased at 148/98 mmHg despite his being on the A. esomeprazole
maximum dose of perindopril. You prescribe a second
B. naproxen
antihypertensive agent and refer Conrad to a nephrologist.
C. rivaroxaban
Question 6
D. ibuprofen.
Which of the following antihypertensive agents would be an
appropriate addition to Conrad’s antihypertensive regimen? Case 5 – Trini
A. Candesartan Trini, 56 years of age, has had chronic back pain for the past
B. Irbesartan five years, after falling from a ladder. She has been taking a
combination of paracetamol and codeine, and sometimes a
C. Atenolol non-steroidal anti-inflammatory drug (NSAID) for pain relief.
D. Hydrochorothiazide She comes to see you as she now needs a prescription for
the paracetamol/codeine combination. You request blood
Case 4 – Tracy tests, which show that eGFR is 45 mL/min/1.73 m2. Trini’s
notes show that her last eGFR reading, 18 months ago, was
Tracy, 50 years of age, presents with a two-day history of 80 mL/min/1.73 m2. From her clinical history, you consider a
exhaustion, nausea and loss of appetite. Three months ago, possible diagnosis of analgesic nephropathy.
she had presented with swelling and pain in her right calf and
ankle, which she had attributed to running on concrete for Question 9
about an hour four or five times a week. Initially, she was
prescribed naproxen 750 mg to relieve the pain and Which of the following is not a feature of analgesic
inflammation, and esomeprazole 20 mg to prevent any nephropathy?
gastrointestinal side effects of the naproxen. However, further A. Proteinuria
testing confirmed a diagnosis of deep vein thrombosis (DVT)
and she is currently on treatment with rivaroxaban 20 mg. B. Anaemia
She had been on naproxen and esomeprazole for three days C. Urinary red blood cell casts
before her DVT diagnosis. She no longer takes naproxen, but
finds esomeprazole helpful for bouts of gastric reflux, which D. Interstitial nephritis
she has been having more frequently in the past two months.
Occasionally, she uses ibuprofen for pain relief. Further information
You request blood tests, which show that serum creatinine is Further investigations confirm a diagnosis of analgesic
elevated. You note that her serum creatinine level, measured nephropathy and, on your advice, Trini ceases regular use of
three months ago, was 85 µmol/L. Urinalysis shows proteinuria paracetamol/codeine.
and microhaematuria. Urine output is also reduced. You
suspect that Tracy has Stage 3 acute kidney disease (AKI). Question 10
What follow-up would you organise for Trini?
Question 7
A. Annual monitoring of kidney function
Stage 3 AKI means that Tracy’s current serum creatinine level
would be in the range of: B. Absolute cardiovascular risk assessment
23
Independent learning program for GPs