1. Today at VTS Hot topic CKD Group work Coffee
Microscopic/Invisible Haematuria

2. What is Chronic Kidney Diseae?
the presence of kidney damage or
decreased kidney function for three months or more, irrespective of the cause.

3. https://b.socrative.com/login/student/ Room: 339W6AWHW
What thoughts would go through your head if a doctor told you your kidneys were not working properly?
Room: 339W6AWHW

4. In a practice of 10,000 patients, approximately how many would expect to find with the following conditions?
Current CKD stage 3-5
End stage renal failure
Renal transplant
450 3

5. CKD: A Typical GP Practice of 100005 6 15 4 60
Stage of Kidney Disease 30
(GFR)
380 3 60 2
460 90 1

6. Annual cost?
£25-30,000 per year per person
1.3% NHS budget
>50% spent on the 2% who need renal replacement therapy
NICE say that 19% patients present late to renal team

7. 22,331
27,621
Total 55,000 in UK

8. Causes of CKD Diabetes Hypertension Glomerulonephritis
Structural kidney disease eg Polycystic kidneys, congenital abnormalities leading to chronic/recurrent infection
Obstructive uropathy
2/3 of causes

9. Offer testing for CKD using eGFRcreatinine and ACR to people with any of the following risk factors:
diabetes
hypertension
acute kidney injury (see recommendation 1.3.9)
cardiovascular disease (ischaemic heart disease, chronic heart failure, peripheral vascular disease or cerebral vascular disease)
structural renal tract disease, recurrent renal calculi or prostatic hypertrophy
multisystem diseases with potential kidney involvement – for example, systemic lupus erythematosus
family history of end-stage kidney disease (GFR category G5) or hereditary kidney disease
opportunistic detection of haematuria. [new 2014]
NICE 2014

10. Key messages on eGFR testing
Avoid eating meat for 12hours before eGFR test
Remember the effect of muscle mass:
African Caribbean (higher muscle mass) multiply eGFR by (NICE 2014)
Body-builders, amputees, muscle wasting disease
First eGFR<60 should be repeated within 2weeks to rule out AKI
Check urine for blood and ACR at first low eGFR

11. eGFR-cystatin C (eGFRcysC)
A more specific test for adverse outcomes
NICE recommend using this for CKD3a
May allow reclassifying as not having CKD
Not currently available in most labs
Costs more (estimate 10x)

12. Offer a renal ultrasound scan to all people with CKD who:
have accelerated progression of CKD
have visible or persistent invisible haematuria
have symptoms of urinary tract obstruction
have a family history of polycystic kidney disease and are aged over 20 years
have a GFR of less than 30 ml/min/1.73m2 (GFR category G4 or G5)
are considered by a nephrologist to require a renal biopsy. [2008, amended 2014]

13. Check ACR

14. Define accelerated progression of CKD as:
a sustained decrease in GFR of 25% or more and a change in GFR category within 12months or
a sustained decrease in GFR of 15 ml/min/1.73m2 per year. [new 2014]
NICE 2014

15. Risk factors for progression (NICE 2014)
cardiovascular disease
proteinuria
acute kidney injury
hypertension
diabetes
smoking
African, African-Caribbean or Asian family origin
chronic use of NSAIDs
untreated urinary outflow tract obstruction. [new 2014]

16. CKD 3 – what is the risk of progression?
What percentage of people progress to ESRD at 10years?
What percentage of people had progression in their CKD after 5 years? 4%
<20%
BJGP 2010;60:442

17. Is CKD 3a a disease?
Norwegian study 2006, people median age of 49
<1% of people with stage 3A disease went on to develop end stage renal disease after eight years of follow-up. BMJ 2006;333:1047
1 in 8 adults in the US may now be labelled as having chronic kidney disease, only around 1 in are being newly treated for end stage renal disease each year. Lancet 2012;379:165-80
In people aged 18-44, risk of developing ESRD only greater than risk of dying from other causes if your eGFR is <45 JAMA
NB: no proteinuria

18. The aging effect
What’s the risk of developing ESRD if you are >65 and have CVD 3a and no proteinuria?
< 1:1000
We examined the age-specific incidence of death, treated
end-stage renal disease (ESRD), and change in estimated glomerular filtration rate (eGFR) among
209,622 US veterans with CKD stages 3 to 5 followed for a mean of 3.2 years.
Possible confounders:
Note rate of death rises 5fold from G1/2 to G5
Elderly may be by definition slow progressors
Drs may be more reluctant to start RRT in the elderly
Age Affects Outcomes in CKD
O’Hare AM et al. JASN 18: ,2007

19. Fig 1 Fall in estimated glomerular filtration rate with age in men and women from the Nijmegen community cohort (5th, 50th, and 95th centiles) and among healthy kidney donors (mean and 90% prediction interval based on regression analysis of measured GFR).
Fig 1 Fall in estimated glomerular filtration rate with age in men and women from the Nijmegen community cohort (5th, 50th, and 95th centiles) and among healthy kidney donors (mean and 90% prediction interval based on regression analysis of measured GFR). Reproduced from Poggio et al9 with permission
Timothy Ellam et al. BMJ 2016;352:bmj.h6559
©2016 by British Medical Journal Publishing Group

20. Priorities in patient care
Blood pressure (140/90 or 130/80 if ACR>70/DM)
Statin therapy
Avoiding nephrotoxic medications
Monitoring for progression

21. Blood pressure reduction
Tight control more important with proteinuria (MDRD study)
Modest reduction in progression
In a meta-analysis of 84 randomized and non-randomized trials in CKD patients, for each 10mmHg drop in mean arterial pressure (MAP) there was an improvement in rate of loss of GFR of 0.18 ml/min/1.73m2/month
ACEI/AT2 generally better
Diabetics and those with proteinuria evidence is better

22. Association between rate of GFR decline after 4 months of follow-up and follow-up blood pressure.
Association between rate of GFR decline after 4 months of follow-up and follow-up blood pressure. Shown are separate linear spline regression lines for blacks and whites relating the rate of GFR decline to mean follow-up MAP after the 11 relevant baseline covariates (sex, age, diagnosis of polycystic kidney disease, protein intake, serum total and HDL cholesterol, urine protein excretion, MAP, serum transferrin, body mass index, and hemoglobin A1c) were controlled for. The number of blacks in the follow-up MAP ranges of ≤92, 93 to 98, and >98 are 9, 18, and 25, respectively. The numbers of whites in the same MAP ranges as above are 193, 149, and 144. (This analysis is restricted to patients with at least one MAP measurement after the second month of follow-up.)‏
Lee A. Hebert et al. Hypertension. 1997;30:
Copyright © American Heart Association, Inc. All rights reserved.

23. NICE recommend statin therapy for all patients with CKD
Cardiovascular risk
CKD stage
Relative risk of cardiovascular disease 3a
1.39 (1.22 to 1.58) 3b
1.9 (1.22 to 2.96) 4
4.29 (1.78 to 10.32
WHAT THIS STUDY ADDS
-Even the earliest stages of chronic kidney disease are associated with higher risk of subsequent coronary heart disease
-Assessment of chronic kidney disease in addition to conventional risk factors modestly improves prediction of risk for coronary heart disease
-It provides about half as much predictive gain as does history of diabetes or about a sixth as much as does history of smoking
Design Prospective population based cohort study.
Setting Reykjavik, Iceland.
Participants 16 958 people aged years without manifest vascular disease and with available information on stage of chronic kidney disease (defined by both estimated glomerular filtration rate and urinary protein) at study entry.
Main outcome measures Hazard ratios for time to major coronary heart disease outcomes and mortality.
Results 1210 (7%) of participants had chronic kidney disease at entry. During a median follow-up of 24 years, 
NICE recommend statin therapy for all patients with CKD
BMJ 2010;341:c4986

24. Metformin and the kidney
Lactic acidosis
Rare (5/100,000)
Serious (mortality up to 50%)
GI symptoms, thirst and altered conscious level
Dehydration may trigger
Dose adjustments
Consider stopping during intercurrent illness
Review dose with eGFR<45
Stop with eGFR<30

25. NSAIDs and CKD 1 2 3 4 5 Safe to use Never use
Safe to use
Never use
In people with CKD the chronic use of NSAIDs may be associated with
progression and acute use is associated with a reversible decrease in GFR.
Exercise caution when treating people with CKD with NSAIDs over prolonged
periods of time. Monitor the effects on GFR, particularly in people with a low baseline GFR and/or in the presence of other risks for progression. NICE

26. ACEIs/AT2 blockers
If there is a decrease in eGFR or increase in serum creatinine after starting or increasing the dose of renin–angiotensin system antagonists, but it is less than 25% (eGFR) or 30% (serum creatinine) of baseline, repeat the test in 1–2 weeks.
Do not modify the renin–angiotensin system antagonist dose if the change in eGFR is less than 25% or the change in serum creatinine is less than 30%. [2008]

27. NICE 2014

28. As CKD progresses… Anaemia Fluid retention Bone disease Lethargy
Acidosis
Depression

29. Bone metabolism and the kidney
Reduced Calcitriol production
Bone and muscle disease
Reduced Phosphate excretion
Reduced Serum Calcium
Increased Parathyroid Hormone
Increased Serum Phosphate
Calcium acetate can lead to raised calcium levels and has chalky taste
Alucaps are very effective but can lead to aluminium accumulation – cerebral effects
Alphacalcidol
Calicimimetics – not approved by NICE – for severe hyperparathyroidism
Diet restriction for phosphate: dairy, oily fish, chocolate, marmite, nuts, offal
Alphacalcidol
Calcification inc vascular disease
Diet restriction Phosphate binders:
Calcichew
Calcium acetate
Eg Phosex
Sevelamer
Alucaps
Calicimimetics
Eg Cinacalcet

30. Referral criteria (NICE 2014)
GFR less than 30 ml/min/1.73m2 (GFR category G4 or G5), with or without diabetes
ACR 70 mg/mmol or more, unless known to be caused by diabetes and already appropriately treated
ACR 30 mg/mmol or more (ACR category A3), together with haematuria
sustained decrease in GFR of 25% or more, and a change in GFR category or sustained decrease in GFR of 15 ml/min/1.73m2 or more within 12 months
hypertension that remains poorly controlled despite the use of at least 4 antihypertensive drugs at therapeutic doses
known or suspected rare or genetic causes of CKD
suspected renal artery stenosis. [2008, amended 2014]

32. Further reading NICE guidance 2014 Chronic Kidney Disease
Does stage-3 CKD matter? P Sharma et al. BJGP 2010;60:442
What are the best treatments for early chronic kidney disease? W. Saweirs and J Goddard Nephrol Dial Transplant 2007
Chronic kidney disease controversy: how expanding definitions are unnecessarily labelling many people as diseased R Moyniham BMJ 2013;347:f4298
Chronic kidney disease in elderly people: disease or disease label? T Ellam BMJ 2016;352:h6559