eGFR < 60 for greater than 3 months with or without evidence of Kidney Damage OR

Evidence of kidney damage for greater than 3 months (+/- decreased eGFR)

1. Albuminuria
   • Elevated ACR, Albumin Excretion, PCR, Protein Excreation/day, Dipstick +1
2. persistent hematuria (exclude urological causes)
3. pathological abnormalities (abnormal biopsy)
4. structural/radiological abnormalities (scarring, polycycstic kidneys)

	ACR (mg/mmol)	Albumin excretion (mg/day)	PCR (mg/mmol)	Protein excretion mg/day	Protein reagent strip
Microalbuminuria	Male 2.5–25	30–300	Male 4–40	50–500	Trace to +1
	Female 3.5–35		Female 6-60
Macroalbuminuria	Male >25	>300	Male >40	>500	≥ +1
	Female >35		Female >60

*To assess albuminuria status, urinary albumin/creatinine ratio in first-void urine specimens is recommended, IF first-void spot is not possible, spot urine is acceptable.
* If spot urine is in the macroalbuminuria range, a 24-hour protein level is recommended

*Urine PCR can be used for quantification and monitoring of proteinuria where albuminuria measures are not available

Causes

1. Diabetic nephropathy – 36% 
2. Glomerulonephritis – 19%
3. HTN – 12%
4. Polycystic kidneys 5%
5. Reflux nephropathy
6. Tubulointerstitial disease (drug induced, heavy metals)
7. Plasma cell dyscrasias (myeloma, light chain deposition, amyloidosis)
8. Uncertain (5%)

-Age: decreased eGFR by approx. 8 every decade after 30

however if <60 still increased risk CVD and CKD progression (from AFP, How to treat states <45)

Risk Factors

• Diabetes
• Hypertension, CVD
• Family history
• Obese
• Smoker
• Age > 60
• ATSI
• History AKI

Clinical presentation of CKD

• is generally asymptomatic.
• Up to 90% of kidney function may belost before symptoms are present,
• People with CKD may not notice any symptoms until they reach Stage 5 CKD 

Look for:

• hypertension
• pruritus
• nocturia
• restless legs
• haematuria
• dyspnoea
• lethargy
• nausea/vomiting
• malaise
• anorexia

Screening

• BP
• UEC
  • If eGFR < 60mL/ min/1.73m2 repeat within 7 days
• ACR
  • first morning void
  • If ACR positive, require 2 further samples over 2 months
• Yearly: DM, HTN
• 2 yearly: Obesity, FHx, Smokers, ATSI 
• Whilst being aged 60 years of age or over is considered to be a risk factor for CKD, in the absence of other risk factors it is not necessary to routinely assess these individuals for kidney disease.
• ATSI
  • People 18-29 years without any CKD
    • Screen for CKD of risk factors as part of the annual health assessment (MBS 715)
  • People 18-29 years with one of the CKD risk factors (FMx Hx, Overweight, Smoking, DM, high BP)
    • Every 2 years: Urine ACR, eGFR, blood pressure
    • If urine ACR positive repeat twice over 3 months (preferably first morning void)
    • If eGFR < 60mL/ min/1.73m2 repeat within 7 days.

Nephrotoxins in CKD

• NSAIDs, COX-2 inhibitors
• triple whammy (NSAID, ACE, diuretic)
• Lithium
• aminogylcasides
• Radiographic contrast
• Note: trimethoprim and cimetidine cause raised creatinine, does not reflect true fall in eGFR

Investigations

• Urine
  • MSU for mcs
    • microscopy for dysmorphic red cells, red cell casts or crystals
    • check for sign of infection
    • Macroscopic haematuria requires urgent urological follow-up to exclude malignancy, regardless of whether a urine MCS has bacterial growth, as malignancy predisposes to UTI.
  • Alb Cr ratio
    • first morning void to minimise postural effect on albumin excretion, although a random urine is acceptable
  • Urine Immunoelectroporesis – Bence Jones Proteins
• Bloods
  • FBC
  • CRP
  • ESR
  • eLFT (Ur,Cr)
  • Fasting Lipids/BGL
  • CMP, HCO3
  • B12/Folate/Fe Studies/PTH
  • Signs of systemic disease (e.g., rash, arthritis, features of connective tissue disease, pulmonary symptoms or deteriorating kidney function)
    • Anti-glomerular basement membrane antibody 
    • Anti-neutrophil cytoplasmic antibody 
    • Anti-nuclear antibodies 
    • Extractable nuclear antigens 
    • Complement studies
  • Age > 40 years and possible myeloma is suspected
    • Serum and urine protein electrophoresis
  • Risk factors for HBV, HCV or HIV
    • Heb B,C, syphilis and HIV serology if not preformed in the last 12 months
• Renal USS

Management : All patients

1. Review
   1. including assessments; eGFR, urine ACR, blood pressure, absolute CV risk, HbA1c (if has T2DM) 
2. Frequency
   1. based on colour coded clinical action plan
      1. yellow every 12 months
      2. orange every 3–6 months
      3. red every 1–3 months
3. Sick day plan
   1. withhold until acute episode resolved:
      1. sulfonylureas
      2. ACE inhibitors
      3. Diuretics
      4. Metformin
      5. ARBs
      6. NSAIDs
      7. SGLT2 inhibitors

1. SNAP!
2. 5 A’s – ask, assess, advise/agree, assist, arrange
3. Limit salt < 6g/day, avoid soft drinks
4. BMI < 25, waist circumference <94cm men, < 80cm women
5. Exercise 150min/week, muscle strengthening activities
6. Stop smoking
7. Alcohol guidelines
8. Hypertension control 130/80
9. Glycaemic control Hba1c < 7%
10. 50% reduction in albuminuria
11. Lipids – use statin in anyone over 50 with CKD, or if high risk CVD
    1. Note moderate to severe CKD = high risk cardiovascular
12. Anaemia – Hb 110-115
    1. Prior to EPO stimulation, trial ferritin supplement
13. Potassium < 6 – consider dietitian, dose reduction, diuretic
14. Vaccinate influenza, pneumococcal
15. Increased fluid intake not necessary – drink to thirst

Algorithm for medicines that slow CKD progression and reduce CV risk for people with CKD

BP Management

• Most important part of CKD management
• Aim <140/90 or if DM <130/80
• starting with an ACE inhibitor or ARB up-titrated to maximum tolerated dose
• adding a calcium channel blocker and/or thiazide diuretic
• adding a beta blocker, mineralocorticoid receptor antagonist (MRA) or other blood pressure-lowering medicines as appropriate for compelling indications.
• Thiazide diuretic should be temporarily stopped during periods of illness or when dehydrated. It can be recommenced when the acute episode has resolved.

• Diuretics
  • Both
    • non-loop diuretics (e.g., thiazides) 
    • loop diuretics (e.g., frusemide)

 are effective in all stages of CKD as adjunct antihypertensive therapy

• Frusemide
  • can be used safely for management of fluid overload in all stages of CKD, including
    • when GFR is severely reduced to < 30 mL/ min/1.73m2 – 
  • Typical doses :
    • 20-120 mg/day
    • higher doses (up to 500 mg/ day) may be required at lower levels of eGFR
    • efficacy is improved by dividing the daily dose.
    • Potassium <6 and less than 25% decrease in renal function from baseline is acceptable if stabilizes in 2 months

• Beta-blockers 
  • may be useful in people with coronary heart disease, tachyarrhythmias and heart failure, but are contraindicated in asthma and heart block.
• Calcium channel blockers
  • may be used for people with angina, the elderly and those with systolic hypertension.

ACE-i/ARB

• All people with CKD should first be prescribed an ACE inhibitor or ARB, up-titrated to the maximum dose.
• Target
  • The recommended therapeutic target for albuminuria is ≥ 50% reduction
• ACEi
  • decrease albuminuria and slow progression
  • exert a renoprotective effect beyond their antihypertensive properties in some circumstances
  • For all patients with proteinuria (ACR > 30 mg/mmol, or >3 mg/mmol and DM, IHD or HTN):
    • Prescribe an ACE-I OR ARB for all patients without contraindications
  • Can drop eGFR
    • cause a reduction in glomerular blood flow, and GFR can decline when treatment is initiated
    • Providing the reduction is less than 25% within two months of starting therapy, the ACE inhibitor or ARB should be continued
    • If the reduction in GFR is more than 25% below the baseline value, the ACE inhibitor or ARB should be ceased and consideration given to referral to a Nephrologist
      • IF CR RISE BY 20%, consider bilateral renal artery stenosis
  • ACE-I Absolute Contraindications
    • Angioneurotic edema: even if not due to ACE Inhibitor
    • Pregnancy (serious Teratogenicity – black box warning)
    • Renal Artery Stenosis ( azotemia/renal failure resulting from preferential efferent arteriolar vasodilation in the renal glomerulus due to inhibition of angiotensin II)
    • ACE Inhibitor related Allergic Reaction
  • Relative Contraindications
    • Aortic Stenosis
    • Hypertrophic Cardiomyopathy (hypotension)
    • Dry Cough (10% of people)
    • hyperkalemia (occurs because aldosterone formation is reduced) 
• Angiotensin II receptor blockers
  • theoretical alternative to ACE inhibitors 
  • Combined therapy with ACE inhibitor and ARB should be avoided except with specialist advice

What is the next step? What guidance should GPs follow to decide the order of medicines?

Stabilised	ACE inhibitor or ARB  at maximum tolerated dose for 4 wks+ eGFR 25–75 +urine ACR 22.6–565 mg/mmol	Add-on therapy to slow CKD progression and reduce CV risk  : SGLT2 inhibitor dapagliflozin – 10 mg taken once daily, with or without food.No dose adjustments are required for reduced kidneyfunction, mild–moderate hepatic impairment or based on age (as per 2020 DAPA-CKD trial of people with CKD, with or without type 2 diabetes (n = 4304).
Blood Pressure	consistently > 130/80 mmHg	Blood pressure-lowering therapyAdd antihypertensives (eg, CCB, thiazide diuretic)  if target not met≥ 3 antihypertensives often required to meet target
high CV risk score	ATSI /Moari CV risk score ≥ 5% All other adults CV risk score ≥ 10%+ eGFR ≥ 15	Statin  +/- Ezetimibe Serum cholesterol target not specifically recommended for CKD
Sugar Control	HbA1C > 7% or > 53 mmol/mol	Glucose-lowering therapyMetformin + SGLT2 inhibitor are first line Add another medicine such as GLP-1 receptor agonist, if target not met

Nutrition

• Protein
  • 0.75-1.0 g/kg/day (no restriction necessary) 
• Salt
  • No greater than 100 mmol/day (or 2.3 g sodium or 6 g salt per day) 
  • Avoid adding salt during cooking or at the table 
  • Avoid salt substitutes that contain high amounts of potassium salts 
• Phosphate
  • No restriction necessary 
• Potassium
  • If persistent hyperkalaemia is present, consult A
  • ccredited Practising Dietitian regarding restricting intake and avoiding foodstuffs high in potassium 
• Fluid
  • Drink water to satisfy thirst 
  • Increased fluid intake is not necessary 
• Carbonated beverages
  • Avoidance is preferable 
  • Minimise intake to less than 250 mL per day

Diabetes and Cholesterol

• HbA1C <7% and pre prandial BSL 4-6mmol/L
• Cholesterol <4.0, LDL <2.0
• Once established Renal failure need careful not to cause hypoglycaemia
• with treatment.
  • may not require intensive control, with declining renal function
  • CKD increases the risk of hypoglycaemia for the following reasons:
    • decreased renal glucose production
    • reduced gluconeogenesis from alanine, pyruvate, glycerol, and decreased mitochondrial adenosine triphosphate/diphosphate (ATP/ADP) ratio in the liver
    • decreased glycogen reserve
    • reduced systemic response to adrenaline and glucagon
    • decreased insulin degradation (normal kidney extracts 40% insulin), which intensifies and prolongs insulin actions
    • reduced renal clearance of oral hypoglycaemic agents and their active metabolites

Acidosis

• People with eGFR < 30 mL/min/1.73m2 are at increased risk of metabolic acidosis.
• The main factor is decreased renal acid excretion compounded by a reduction in bicarbonate production. 
• Acidosis contributes to demineralization of bone and increased protein degradation, which may be associated with increased morbidity.
• Management
  • Supplementation with sodiumbicarbonate (SodiBic 840 mg capsule) may be considered in people with acidosis
  • Typical starting dose would be 1 capsule od or bd, increasing up to 2 tablets bd if needed, and titrating to keep the HCO3 level above 22mmol/L
  • Higher doses can be prescribed, but carry a higher risk of fluid overload
• Increased sodium load may worsen blood pressure control

Albuminuria

• Target: 50% reduction in urine ACR
• Albuminuria is an important prognostic feature in CKD. 
• The degree of albuminuria relates to the severity of the kidney disease and with a greater likelihood of progression to end stages of CKD.
• The amount of albuminuria can be reduced significantly by the use of an ACE inhibitor or ARB agent. 
• Management
  • Reduction in the amount of albuminuria is associated with improved outcomes
  • Reduction in salt output through reducing oral salt intake 
  • Spironolactone (use with caution on specialist advice and ensure regular monitoring of serum potassium)

Anaemia

• Anaemia of CKD is related to:
  • reduced erythropoietin production by the kidney 
  • resistance to the action of ESA
  • reduced absorption of iron
• Anaemia related to CKD usually starts to develop when the GFR is less than 60 mL/min/1.73m2 . 
• The prevalence of anaemia increases markedly with decreasing GFR.
• Target:
  • Hb 100 – 115 g/L 
  • Prior to commencement of ESA a trial of iron supplementation maintaining: Ferritin >100 µg/L; TSAT >20% 
  • Once ESA commenced, maintain: Ferritin 200-500 µg/L; TSAT 20-30%
• Management
  • trial of IV iron should be considered to maintain ferritin >100 µg/L; TSAT >20%
  • EPO therapy considered if Hb <100

Hyperparathyroidism and Increased Fracture Risk

• Target:
  • Keep PO4 in normal range (0.8-1.5 mmol/L) 
  • Keep Ca in normal range (2.2-2.6 mmol/L) 
  • Vitamin D (25-hydroxyvitamin D) levels are adequate if > 50 nmol/L 
  • Refer to Nephrologist if PTH is persistently elevated above the upper limit of normal and rising

As kidney function decreases

• Phosphate: Increase
  • the renal clearance of phosphate is diminished
  • leading to higher serum phosphate levels. 
• Calcitriol (the most active form of vitamin D) : decrease
  • because kidney function is required for its synthesis. 
• Calcium : decrease
  • levels may fall as a result of less vitamin D dependent calcium uptake from the gastrointestinal tract
• The combined effects of
  • higher phosphate
  • lower calcium
  • lower vitamin D levels 

all serve to stimulate parathyroid hormone production

and in turn elevated levels of PTH increase the resorption and release of mineral from bone. 

• These changes are associated with an increased risk of fracture and also increased cardiovascular mortality, perhaps mediated by accelerated vascular calcification.

Therefore:

• Vit D replacement required
  • suppresses hyperparathyroidism developing
  • Cholecalciferol (the form of vitamin D that comes from sun exposure)
    • can be given as a dietary supplement and will be converted to 25-hydroxyvitamin D by the liver
    • requires renal function to work
    • If kidney function is still intact, it will then be converted to calcitriol, the most active form and will help to suppress the development of secondary hyperparathyroidism.
  • Calcitriol (the most active form of vitamin D)
    •  In later stages of renal disease
    • is used in CKD for suppression of secondary hyperparathyroidism and is the preferred vitamin D in later stages of CKD when kidney function is very poor. 
    • Cholecalciferol should still be used for 25-hydroxyvitamin D deficiency in advanced CKD, including in combination with calcitriol.
• Manage Phosphate
  • Dietary restriction of phosphate
  • Use of phosphate binders, which bind dietary phosphate to prevent absorption. Commonly used binders are typically calciumbased.
  •   Sevelamer and lanthanum are available for individuals on dialysis
• Calcium
  • If phosphate is controlled, calcium will typically remain in normal range. 
  • If the level is low with normal phosphate level consider Vitamin D supplementation
  • Excess calcium administration should be avoided as this may be associated with increased risk of vascular calcification in CKD.

Hyperkalemia

• In CKD, excretion of potassium (K+) in the urine is impaired. 
• Levels may also rise with ACE inhibitors and ARBs used to treat hypertension or with use of spironolactone.
• Management
• Low K+ diet (discuss with an Accredited Practising Dietitian)
• Correct metabolic acidosis (target serum HCO3 >22 mmol/L)
• Potassium wasting diuretics (e.g., thiazides)
• Avoid salt substitutes which may be high in K+
• Resonium A powder
• Cease ACE inhibitor/ARB/spironolactone if K+ persistently > 6.0mmol/L and not responsive to above therapies
• Refer to nearest Emergency Department if K+ > 6.5 mmol/L

Uraemia 

• Uraemia is a syndrome seen in Stage 4 or 5 CKD, and is caused by the accumulation of the breakdown products of protein metabolism. 
• The symptoms include
  • Anorexia
  • nausea
  • vomiting
  • lethargy
  • confusion
  • muscle twitching
  • convulsions and coma. 
• Although urea and creatinine are the substances we measure, the symptoms are most likely due to the accumulation of other toxic end products. 
• These symptoms can lead to poor food intake and malnutrition.
• By the time uraemia becomes symptomatic, dialysis is typically indicated. 
• Management
  • Dialysis should be commenced as soon as uraemic symptoms develop
  • If non-dialysis pathway is planned:
    • a low protein diet will help control gastrointestinal symptoms
    • fluid control should be strict to avoid pulmonary oedema
    • avoid unnecessary medications
    • anti-emetics are of limited value

Depression

• Screen recurrently and maintain a high level of clinical awareness for depression
• Treatment of persistent depressive symptoms involves a combination of
  • Non-medication therapies
    • education
    • cognitive behavioural therapy
    • exercise programs
  • antidepressant medication
  • SSRIs have established safety in people with CKD

Prevent Acute Kidney Injury (AKI):

• In acutely unwell patients with CKD:
  • Check weight, BP, peripheral oedema, monitor UEC regularly;
• Consider temporarily ceasing ACE-I / ARB / diuretics in especially with hypotension / hypovolaemia (if unsure contact physician / nephrologist for advice);
• Recheck UEC once acute illness has resolved to determine new baseline and ensure ceased medications are restarted.

Other things to Manage

• Muscle cramps 
• Pruritus
• Restless Legs Syndrome
• Sleep apnoea

Medications requiring dose reduction

• Pharmacological management for CKD also includes adjusting doses of medicines cleared by the kidneys to reduce adverse effects
• Dose reduction or cessation of medicines cleared by the kidneys is generally required once eGFR is < 60 mL
• GFR can be assessed using serum creatinine-based formulae.
  • Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
  • But for  extremes of body weight unless it is first corrected to the actual GFR for that patient

CKD-EPI eGFR. × Individual’s body surface area (BSA) = eGFR result in mL/min                                   173 BSA = 0.007184 × Weight in kg0.425 × Height in cm0.725 (Du Bois formula)

• Medications include
  • Antivirals
  • Benzodiazepines
  • Opioids
  • hypoglycemic agents
    • Metformin
      • no dose adjustment required for eGFR > 45
      • maximum 1g a day if eGFR 30 – 45.
  • Insulin
  • digoxin, sotalol, atenolol
  • Thiazides, K+ sparing diuretics
  • low molecular weight heparins
  • Psychotropic, anticonvulsants
  • allopurinol, colchicine

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Shared decision making

• Enables the clinician and patient to participate jointly in making an informed health decision.
• Involves discussing the options and their benefits and harms, and considering the patient’s values, preferences and circumstances.
• Is not a one-off discussion, but an ongoing process that can be used to guide decisions about screening, investigations and treatments.
• Benefits include:

• acknowledges patient values and preferences
• enhances patient engagement
• improves patient knowledge
• supports evidence based care
• Although shared decision making can occur without tools, various decision support

• tools now exist. 
• Five questions that clinicians can use to guide shared decision making:
  • What will happen if we watch and wait?
  • What are your test or treatment options?
  • What are the benefits and harms of these options?
  • How do the benefits and harms weigh up for you?
  • Do you have enough information to make a choice?
• Advance care plans

• This can be a mix of any actions that leads to planning towards the end of life.
• Advance care planning is distinct from dialysis treatment decision making, and can occur whilst treatment is still ‘active’.
• Advance care planning should be initiated in:
• all competent patients aged 65 years and above

and

• all competent patients, irrespective of age, who fulfil one or more of the following criteria:

• the treating clinician considers that existing medical conditions will reduce life
• expectancy
• poor functional status
• chronic malnutrition
• poor quality of life

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MDT care

• Objectives
  • To provide specific therapy based on diagnosis
  • To slow down the progression of CKD
  • To evaluate and manage co-morbid conditions (e.g. diabetes, hypertension, dyslipidaemia) 
  • To prevent and manage cardiovascular disease
  • To identify, prevent and manage CKD specific complications (e.g. management of nutrition, anaemia, renal bone disease as well as fluid, electrolyte and acid-base problems)
  • To plan and prepare for renal replacement therapy (e.g. choice of dialysis modality, access-placement and care, pre-emptive transplantation)
  • To support and provide conservative care and palliative care options
• When to refer to nephrologist
  • Persistent haematuria plus proteinuria;
  • Proteinuria > 1g/day (ACR > 70, PCR > 100);
  • Patients with proteinuria not tolerating ACE/ARB;
  • Patients with very high risk CKD;
  • CKD and difficult to manage HTN on three agents;
  • Persisting anaemia despite iron therapy;
• Team players
  • GP
    • sustaining an ongoing relationship with the patient and their family
    • coordinating the care provided by others
    • ensuring that this care remains focused on the patient’s own goals and priorities.
  • Nephrologist
  • Endocrinologist/diabetologist
  • Vascular and transplant surgeon
  • Practice nurse/nurse practitioner
    • responsible for the clinical assessment and management of renal patients, from established CKD through to ESKD. 
    • as case manager will provide the continuity and follow up of care with the multidisciplinary team
  • Renal nurse
  • Dietician
    • do nutritional assessments, provide specific dietary advice and play an important role in determining dialysis start time
  • Pharmacist
    • Medication review, Specially in elderly
      • Reduced eGFR should lead to reduced doses of many drugs in the elderly
      • Polypharmacy is common in the elderly and increases the risk of falls, 
      • 0confusion and functional decline.
      •  Home Medicines Reviews and Residential Medication Management
  • physiotherapist
    • maintain their strength and mobility as their kidneys fail and to provide specific advice on exercise for patients based on individual needs.
  • Mental health professionals
  • Community health professionals
  • patient educator
    • setting up and running individual and group teaching for patients and their families. 
    • cover a broad range of topics (e.g. diet, modality selection, access, anaemia etc). 
    • encourage patient empowerment by providing support and education to develop patients self-management skills, including anaemia management
  • Family members or other lay carers
  • Social worker
    • facilitate with resolving financial and insurance matters as well as assisting with travel to clinic as well as to dialysis
  • Aboriginal Health Workers
    • will work in collaboration with the social worker to provide emotional, social and cultural support to indigenous patients and their families.