Chronic Kidney Disease

1
Chronic Kidney Disease

• Dr. Asha Gopinath
• GP Registrar

2

• A 63 year female with a 12 year history of
  hypertension and diabetes has been treated with
  metformin 1g bd, Gliclazide 80 mg bd,
  Rosuvastatin 10mg daily, Ramipril 10 mg daily,
  aspirin 75 mg daily and amlodipine 10 mg daily
  for the last two years. At annual review her
  blood pressure is 138/82 mmHg, fundi reveal
  background diabetic retinopathy, foot pulses are
  normal but she has evidence of a peripheral
  sensory loss to the ankles in both feet. Her
  results show
• HbA1c7.2(3.8-6.4)Creatinine176
  µmol/L(60-110)Which of the following drugs should
  be withdrawn?
• Aspirin Gliclazide Metformin Ramipril
  Rosuvastatin

3

• A 43-year-old male is diagnosed with diabetic
  nephropathy. If this patient had type 1 diabetes
  his chances of progressing to End Stage Renal
  Disease (ESRD) would be approximately 50. What
  percentage of type II diabetics with diabetic
  nephropathy would be expected to progress to
  ESRD?
• 15 30 45 50 55

4

• A 32-year-old male with type 1 diabetes undergoes
  a 24 hour urine collection. Which of the
  following urine albumin concentrations signify
  microalbuminuria?
• 10 mg/day 50 mg/ day 500 mg/ day
  1 g/day 3.5 g/day

5

• A 72-year-old male is being treated for
  hypertension, gout, gastro-oesophageal reflux and
  has a three year history of type 2 diabetes. He
  takes a variety of medications. You are concerned
  after requesting serum biochemistry on this
  patient.These investigations have revealed
• Serum sodium138 mmol/L (137-144)Serum
  potassium4.4 mmol/L (3.5-4.9)Serum urea12.8
  mmol/L (2.5-7.5)Serum creatinine162 µmol/L
  (60-110)In which of the following drugs would the
  dose NOT need to be reduced in light of these
  findings?
• Allopurinol Gliclazide Lansoprazole
  Lisinopril Metformin

6

• 5 A 25-year-old female presents for annual
  review. She developed diabetes mellitus at the
  age of 15 and currently is treated with human
  mixed insulin twice daily. Over the last one year
  she has been aware of episodes of dysuria and has
  received treatment with trimethoprim on 4
  separate occasions for cysytits.
• Examination reveals no specific abnormality
  except for two dot haemorrhages bilaterally on
  fundal examination. Her blood pressure is 116/76
  mmHg.
• Investigations show
• HbA1c9(3.8-6.4)Fasting plasma glucose12.1
  mmol/L(3.0-6.0)Serum sodium138 mmol/L(137-144)Seru
  m potassium3.6 mmol/L(3.5-4.9)Serum urea4.5
  mmol/L(2.5-7.5)Serum creatinine90
  µmol/L(60-110)UrinalysisGlucose 24 hour urine
  protein220 mg/24hrs(lt200)What would be the best
  therapeutic option to prevent progression of
  renal disease?
• a. Improve glycaemic control with insulin
• b. Prescribe low protein diet
• c Treat with ACEI
• d Treat with prolonged antibiotics
• e Treat with steroids

7

• 44 yr old man has a serum creat of 476 micromols/
  l itre and urea 38. Which of the following would
  be most useful in diff CRF from ARF
• Hb 9.8
• BP 165/100
• USS kidneys 7.8 cm bipolar length
• 1.2 g prot/ 24 hrs
• PTH 92 ( 10-55 )

8
CKD

• Chronic kidney disease is due to the
  progressive loss of nephrons resulting in
  permanent compromise of renal function
• Possible causes of chronic kidney diseae include
• glomerulonephritis - accounts for 25 of cases
• multisystem disease eg Diabetes
• acute pyelonephritis / tubulointerstitial
  disease
• hypertension and vascular causes
• polycystic kidney disease - the most common
  cause of familial chronic renal failure
• idiopathic in 15 of cases
• Rarely drugs - toxic nephropathy e.g. analgesic
  nephropathy
• connective tissue disease e.g. polyarteritis
  nodosa

9
Clinical features

• Symptoms
• Fatigue Dyspnoea
• Pleuritic pain Ankle Swelling
• Restless legs Nausea
• Anorexia Vomiting
• Diarrhoea Pruritus
• Reduced concentration Bone pain
• Impotence/ infertility Menorrhagia
• Signs
• Pallor BP
• Cardiomegaly Pleural effussion
• Pericarditis Pulm / peripheral oedema
• Retinopathy Prox myopathy
• Periph neuropathy
• Late Aryythmias, encephalopathy, seizures, coma

10
Classification of CKD

• Stage Description
  
  Minimum test frequency
• 1 Normal GFR
• GFR gt90 mL/min/1.73 m2 with other evidence of
  CKD
  12 monthly
• 2 Mild impairment
• GFR 60-89 ml with other
  evidence of CKD
  12 monthly
• 3 Moderate impairment GFR 30-59 ml
  
  6 monthly
• 
  
  
  (12 if stable)
• 4 Severe impairment GFR 15-29 ml
  
  3 monthly
• 
  
  (6
  if stable)
• 5 Established renal failure GFR lt 15 ml or on
  dialysis
  3 monthly
• The other evidence of CKD may be one of the
  following
• Persistent microalbuminuria

11
Estimation of the Glomerular Filtration Rate

• The GFR may be estimated using the 4-variable
  Modification of Diet in Renal Disease (MDRD)
  equation
• GFR (ml/min/1.73 m2)186 x Serum Creatinine
  µmol/l/88.4 1.154
• x age
  (years) -0.203
• x 0.742
  if female and
• x 1.21
  if African American.

12
Criteria for referral to specialist services

• Estimated GFR
• lt15 ml/min/1.73 m2 Immediate referral
• 15 29 Urgent referral
  (routine referral if known to be stable)
• 30 59 Routine referral
  if
• 
  Progressive fall in GFR/increase in serum
  creatinine
• 
  Microscopic haematuria present
• 
  Urinary PCR gt 45 mg/mmol
• 
  Unexplained anaemia (Hb lt11g), abnormal
  potassium, calcium or
  phosphate
• 
  Suspected systemic illness, eg SLE
• 
  Uncontrolled BP (gt150/90 on 3 agents)
• 60 89 Referral not
  required unless other problems present

13
Information needed for referral

• 1. General medical history
• 2. Urinary symptoms
• 3. Medication
• 4. Examination, eg. BP, oedema, palpable bladder
  or other positive findings
• 5. Urine dipstick for blood and protein
• 6. Urine protein/creatinine ratio, if proteinuria
  present -early morning urine (EMU) preferable
• (in diabetes, result of urine albumin/creat
  ratio if dipstick proteinuria negative)
• 7. Blood count
• 8. Serum creatinine, sodium, potassium, albumin,
  calcium, phosphate, cholesterol,
• 9. HbA1C (in diabetes)
• 10. All previous serum creatinine results with
  dates
• 11. Result of renal ultrasound scan if available

14
Serum creatinine concentration should be measured
at initial assessment and then at least annually
in

• Previously diagnosed CKD including
• o Identified renal pathology (e.g. polycystic
  kidney, Biopsy proven GN, reflux nephropathy)
• o Persistent proteinuria
• o Urologically unexplained haematuria
• Conditions associated with a high risk of
  silent development of obstructive kidney disease
  
• o Bladder voiding dysfunction (outflow
  obstruction, neurogenic bladder)
• o Urinary diversion surgery
• o Urinary stone disease (gtone episode/year)
• Conditions associated with a high risk of
  silent development of parenchymal kidney disease
  
• o Hypertension, diabetes mellitus, heart failure,
  
• o Atherosclerotic vascular disease
• Conditions requiring long-term treatment with
  potentially nephrotoxic drugs
• o e.g ACEIs, ARBs, NSAIDs, Lithium, Mesalazine,
  Cyclosporin, Tacrolimus

15
Testing for urinary protein

• Dipstick urinalysis for protein should be
  undertaken
• As part of the initial assessment of patients
  with
• o Newly discovered hypertension, haematuria or
  reduced GFR
• o Unexplained oedema or suspected heart failure
• o Suspected multi-system disease, e.g. SLE,
  vasculitis, myeloma
• o Diabetes mellitus
• As part of the annual monitoring of patients
  with
• o Biopsy-proven glomerulonephritis
• o Reflux nephropathy
• o Urologically unexplained haematuria or
  persistent proteinuria
• o Diabetes mellitus
• (patients with diabetes mellitus should also have
  annual testing for albumincreatinine ratio to
  exclude
• microalbuminuria if the dipstick urinalysis for
  protein is negative)
• As part of routine monitoring for patients
  receiving nephrotoxic agents eg gold,
  penicillamine

16
Confirmation of proteinuria

• If protein dipstick test is positive (1) the
  following should be undertaken
• MSU for culture to exclude UTI
• Laboratory confirmation of proteinuria,
• preferably on early morning urine (EMU) sample,
  to exclude postural proteinuria
• Positive tests for proteinuria are
• - Urine proteincreatinine ratio gt45 mg/mmol or
• Albumincreatinine ratio of gt30 mg/mmol
• Persistent proteinuria - two or more positive
  tests for proteinuria, preferably spaced by 1 to
  2 weeks
• In annual diabetes monitoring if dipstick test
  negative request albumin/creatinine ratio.
• Microalbuminuria is defined as ACR gt 2.5 mg/mmol
  (men)
• or gt3.5 mg/mmol (women)
  on 2 or 3 occasions

17
Proteinuria If found, management should include

• Quantification of proteinuria, test for
  haematuria, estimate GFR.
• -Urine PCR gt 100 mg/mmol refer to Nephrologist
  irrespective of GFR.
• - Urine PCR gt45 mg/mmol with microscopic
  haematuria refer irrespective of GFR.

18
DM with microalbuminuria or proteinuria

• Achieve good glycaemic control (HbA1c
  6.5-7.5).
• Prescription of an ACEI (or ARB in the presence
  of a firm contraindication to ACEI), titrated to
  full dose, irrespective of initial blood pressure
  
• Control of hypertension if necessary Addition
  of other antihypertensive drugs in combination to
  
• reach the blood pressure goal.
• Measurement at least once a year of
• urine albumincreatinine ratio (or
  PCR)
• serum creatinine concentration (for
  estimated GFR).
• Referral to diabetes team for review.
• Referral to a nephrologist
• as for patients without diabetes.

19
Referral for further investigation for
atherosclerotic renal artery stenosis (ARAS)

• Refractory hypertension
• (ie BP gt 150/90 mm Hg despite 3
  anti-hypertensive agents).
• Recurrent episodes of pulmonary oedema despite
  normal LV fn on Echo ( flash pulmonary oedema).
  
• Rising serum creatinine concentration (rise of
  gt20 or fall of GFR of gt15)
• -over 12 months with a high clinical
  suspicion of widespread atherosclerosis.
• -or during the first 2 months after
  initiation of ACEI or ARB treatment (Level 3DA)
• Unexplained hypokalemia with hypertension.

20
Recognition of acute renal failure (ARF)

• ARF is characterised by rapid deterioration of
  renal function over a period of hours or days
• ARF should be suspected in the context of an
  acute illness in the presence of
• A 50 rise in serum creatinine concentration
• A fall in estimated GFR of gt25 (if baseline
  unknown assume 75 ml/min/1.73m2)
• Oliguria (urinary output lt0.5 ml/kg/hr)
• Because it requires emergency treatment,
  all patients with newly detected abnormal renal
  function should be assumed to have ARF until
  proven otherwise, although the majority will turn
  out to have CKD

21
In newly diagnosed GFR lt60 ml/min/1.73 m2
Management should include

• Review of all previous measurements of serum
  creatinine
• o to estimate GFR and assess rate of
  deterioration.
• Review of medication, particularly
• o recent additions (e.g. diuretics, non-steroidal
  anti-inflammatory drugs (NSAIDs), or any
• drug capable of causing interstitial nephritis eg
  penicillins, cephalosporins, mesalazine,
• diuretics)
• Urinalysis
• o haematuria and proteinuria suggest
  glomerulonephritis, which may progress rapidly
• Clinical assessment,
• o eg. looking for sepsis, heart failure,
  hypovolaemia, palpable bladder.
• Repeat serum creatinine measurement within 5
  days
• o to exclude rapid progression.
• Check criteria for referral
• o if not indicated ensure entry into a chronic
  disease management programme.

22
Management of haematuria should include

• Check serum creatinine concentration in all
  patients
• refer to nephrologist if GFR lt 60 mL/min/1.73
  m2 .
• Check for proteinuria in all patients.
• If GFR normal
• Macroscopic haematuria, /- proteinuria
• fast track urology referral refer to
  nephrology if initial investigations negative.
• Microscopic haematuria without dipstick
  proteinuria
• Age gt50 yrs refer to urology
• Age lt50 yrs, or gt50 yrs after exclusion of
  urological cancer treat as CKD
• Microscopic haematuria with urine PCR gt 45
  mg/mmol
• - refer to nephrology.

23
Management of CKD

• Regular measurements of kidney function and
  other laboratory tests depending on the severity
  of kidney impairment
• General health advice as appropriate on
• smoking
  cessation. , weight loss ,aerobic exercise ,
  limiting alcohol intake limiting sodium intake
• Cardiovascular Prophylaxis
• For patients with 10 year risk of
  cardiovascular disease of gt 20
  Aspirin treatment if BP lt 150/90 mm Hg
• Lipidlowering drug
  therapy
• Blood pressure monitoring
• at least
  annually
• Control of hypertension
• If urine PCR lt100
  mg/mmol , Threshold 140/90 mmHg Target 130/80
• If urine PCR gt100
  mg/mmol , Threshold 130/80 mmHg Target 125/75
• o ACEIs or ARBs to be included
• if urine PCR gt100 mg/mmol
  
• in diabetic patients with
  micro-albuminuria
• If Hyperkalaemia present (serum K gt6 mmol/l)

24
CKD stage 3

• Annual measurement of Hb,
  potassium, calcium and phosphate
• If Hb lt11 and other causes excluded
• treat with erythropoiesis
  stimulating agents to maintain Hb 11-12 g/dl
• Request renal ultrasonography in
• patients with lower urinary
  tract symptoms,
• refractory hypertension
• unexpected progressive fall in
  GFR.
• Immunise against influenza and
  pneumococcus.
• Review all prescribed medication
• avoid nephrotoxic drugs including
  NSAIDs wherever possible .
• Check PTH concentration when Stage 3 first
  diagnosed.
• If raised check serum
  25-hydroxyvitamin D
• if this is low treat with
  ergocalciferol or cholecalciferol with calcium
  supplement (not
• calcium phosphate)

25
CKD Stages 4-5 additional management

• Management should be shared and should include
• 3-monthly tests serum creatinine (for GFR),
  Hb, calcium, phosphate, bicarbonate, PTH
• dietary assessment
• immunisation against hepatitis B
• investigation and treatment of phosphate
  retention and hyper-parathyroidism
• correction of acidosis
• information about options for treatment
• timely provision of dialysis access depending
  on treatment choice

26
QOF

• CKD1 - to keep a register 6 points
• CKD2 - BP in last 15 months 6 ( 90)
• CKD3 BP lt 140/85 11 ( 70)
• CKD4 CKD and BP taking
• ACEI or ARB 4 ( 80)
• Read codes- IZ12, IZ13, IZ14 for CKD 3, 4 and 5
  respectively