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Chronic kidney disease and old age
- 1. CKD in the elderly James Ritchie Salford Royal NHS Foundation Trust
- 2. “Old age is the most unexpected of all things that happens to a man.” - Leon Trotsky
- 4. Public perception A Snapshot of Ageism in the UK and across Europe. Age UK, 2011
- 5. Gender Female Male Musaiger et al. Arch Gerontol Geriatr.. 2009;48(1):50-7
- 6. Healthcare discrimination Should older people have equal access to healthcare? Davey B et al; 2003. Exploring staff views of old age and health care Help the Aged, 2007, Large survey Help the Aged, 2009, Survey Bowling et al. Fam Practice. 2006;23(4):427 - 436
- 7. USRDS.. 2001-2008 Stevens et al. Adv Chronic Kidney Dis. 2010;17(4):293-301 Healthcare discrimination
- 8. Healthcare discrimination UK Renal Registry - 2013
- 9. “The good physician treats the disease; the great physician treats the patient who has the disease.” - William Osler
- 10. Disease A state of complete physical, mental and social well-being, not merely the absence of disease or infirmity. WHO (1946) Preamble to the Constitution of the World Health Organization. WHO, New York, USA WHO Tech Rep Ser. 1994;843:1 - 129 Bayer et al. J Hist Behav Sci. 1982; 18(1):32 - 52
- 11. Perceptions Campbell et al. BMJ 1979;2(6193):757 - 762 Smith BMJ 2002; 324(7342):883 - 885 1 - Ageing 11 - Childbirth 2 - Work 12 - 2000’s 3 - Boredom 13 - Jet lag 4 - Bags under eyes 14 - Sadness 5 - Ignorance 15 - Cellulite 6 - Baldness 16 - Hangover 7 - Freckles 17 - Penis envy 8 - Big ears 18 - Pregnancy 9 - Grey hair 19 - Road rage 10 - Ugliness 20 - Loneliness
- 12. The burden of CKD USRDS.. 2001-2008 Stevens et al. Adv Chronic Kidney Dis. 2010;17(4):293-301
- 13. “We demand rigidly defined areas of doubt and uncertainty!” - Douglas Adams
- 14. Organ ageing Speizer et al. Epidemiol Rev. 1979;1:124-142 Strait et al. Heart Fail Clin. 2012;8(1):143 - 164 Age does not cause disease but lowers the threshold for symptoms to manifest.
- 15. Renal ageing Davies et al. J Clin Invest 1950;29(5):496 - 507 Hoang et al. Kidney Int 2003;64:1417 - 1424 Renal plasma flow Glomerular numbers Cortical mass
- 16. Glomerular ageing • 17% vs. 2% global sclerosis • Whole kidney Kf 3.7 vs. 6.6 • Filtration surface are 4.1 vs. 3.1 u2 x 105 • Single nephron Kf 11.2 vs. 9 • NFG 3.5 vs. 8.5 x 105 Tan et al. JASN 2009;20(1):181 - 188
- 17. “I was seldom able to see an opportunity until it had ceased to be one.” - Mark Twain
- 18. Untreated risk Age Gene / Environment Susceptibility Study (AGES) Inker et al. Am J Kidney Dis 2015;66(2):240 - 248 • 2002 - 2006 (AGES) • 2007 - 2011 (AGES- II) - 805 AGES-Kidney
- 19. Causes of CKD Unpublished data - courtesy of Dr M Raman, SRFT
- 20. “When a lot of remedies are suggested for a disease, that means it cannot be cured.” - Anton Chekhov
- 21. Blood pressure targets Denker et al. Clin Interv Aging. 2013;8:1505-1517 EWPHE SHEP STOP Syst-Eur Syst-Chin Age >60 >60 70 - 84 >60 >60 Enrollment >160 >160 >180 >160 >160 Acheived 145/85 143/68 166/85 151/79 151/81 Outcome Reduced CVM Reduced CVE Reduced CVA + death Reduced stoke and CV mortality
- 22. VALISH • Age 70 - 84; n = 3260 • Valsartan as primary therapy • <140 mmHg vs. 140 - 150 mmHg with 2.85 years follow-up Ogihara et al. Hypertension. 2010;56:196-202
- 23. HYVET Beckett et al. NEJM. 2008;358(18):1887-98 Hypertension in the Very Elderly Trial - age 80 + - Target blood pressure <150 / 80 mmHg - Indapamide +/- perindopril
- 24. Medication choice Old age Alpha - blockers Calcium channel blockers Beta - blockers Diuretics Angiotensin blockade Valbusa et al. J Hypertens. 2012(30)1:53 - 60 Kamaruzzaman et al. Age Ageing 2010.39(1):51 - 56
- 25. “All you really need to know is that the universe is a lot more complicated than you think, even if you start from a position of thinking it’s pretty damn complicated” - Douglas Adams
- 26. Polymorbidity Schneider et al. BMC 2009;82(7)
- 27. Polymorbidity Orueta et al. BMC Public Health 2013;19(318) Jones et al. British J Healthcare Manage 2013(19): 553 - 558
- 28. Cardio-renal ADHERE registry 60% CKD CHARM trial CKD associated with worse outcomes than LVF NHC sCr >222umol/L 0.53 relative risk for A2B Ahmed et al. Heart Fail Clin 2007;3(4):389 - 402 Hillege et al. Circ 2006;113(5):671 - 678 Masoudi et al. Circ 2004;110:724 - 731
- 29. “Time is a drug. Too much of if kills you.” - Terry Pratchett
- 30. Quality or quantity? Mujais et al. Clin J Am Soc Nephrol 2009;4(8):1293 - 1301
- 31. Interventions Drueke et al. NEJM 2006;355(20):2071 - 2084 Singh et al. NEJM;355(20:2085 - 2098 Pfeffer et al. NEJM 2009;361(21):2019 - 2032
- 32. “Doubt is the privilege of those who have lived a long time.” - Jose Saramago
- 33. Historical perspective “ Can we get this patient back to work? ” - John Goldsmith “ We would never take anyone over the age of 50 ” - Frank Marsh
- 34. Living status Jassal et al. NEJM 2009;361:1612 - 1613
- 35. Nursing home Kurella Tamura et al. NEJM 2009;361:1539 - 1547
- 36. Prediction of mortality Couchoud et al. Nephron Dial Transplant 2009;24(5) 1553 - 1561 REIN registry - 6 month survival data
- 37. Supportive care at 75? Murtagh et al. Nephron Dial Transplant 2007;22(7) 1955 - 1962
- 38. Supportive care at 75? Murtagh et al. Nephron Dial Transplant 2007;22(7) 1955 - 1962
- 39. Supportive care at 80? No apparent survival benefit from dialysis in the over 80’s irrespective of eGFR start point Hussain et al. Palliative Med 2013;27(9) 829 - 839
- 40. • 31 patient interviews with hospital HD patients • Mean age 76 ± 9 years • No patient perceived they had made a choice • Majority believed HD initiation was the clinician’s choice • Patients believed HD start was to prevent imminent death Patient choice Ladin et al. Nephron Dial Transplant 2016;Aug - ePub ahead of print
- 41. Thank you
Editor's Notes
- Introduction Describe YAC / transition work
- The first thing to consider is what is age / what is old age. This may be different between specialities?
- OED definition - “The latter part of life; the period of life after youth and middle age…., usually with reference to deterioration” Isadore of seville - theologian in the 14 century described six stages of life Introduced the idea of old age being defined by number and/or function This has entered popular culture e.g. As You Like It - “All the world’s a stage…And all the men and women merely players; They have their exits and their entrances, And one man in his time plays many parts, His acts being seven ages. At first, the infant, Mewling and puking in the nurse's arms” Isodore - Not all negative - for “although teetering on the edge of systemic bodily failure”, old age imposes “measure on enjoyment, breaks the force of desire, strengthens wisdom and confers more mature understanding. Senate comes from the age of the members preferred for the position. Measure of wisdom
- Europe - average perception of the start of old age is 62 years UK - 57! Is there a risk that by defining both CKD and elderly, two arbritary assignments, that we are not only creating disease, but also decrepitude?
- Question asked is “What age do you think men / women become old?” Women and men both perceive that women “become old” earlier than men This is demonstrable in popular culture… Harrison Ford - 77 Jennifer Aniston 47. Schofield 54; Holly Willoighby 34 Would be hard to explain to my wife why I’m inviting younger women to a geriatric CKD clinic…..
- 1 - Staff survey (n=1400). Wirral Hospital trust. Doctors are the outliers at 84% saying YES. What is the impact for renal medicine - concerns about not being offered RRT? 2 - >50% of patients over 60 feel symptoms are put down to advancing age without being properly considered and investigated 3 - A 2008 survey of 201 British Geriatrics Society members, carried out on behalf of Help the Aged, found that over one half (55%) would be worried about how the NHS would treat them in old age and nearly one half (47%) think that the NHS is institutionally ageist. Two thirds (66%) think older people are less likely to have their symptoms fully investigated and 72% said older people were less likely to be considered and referred on for essential treatments. Is this important when thinking about organ support? 4 - However, in simulated cases, for e.g. cardiac Ix / revasc, geriatricians are less likely to recommend referral for intervention than cardiologists. “Do as I say, not as I do?”. Perhaps shows potential value in not failing to refer due to age
- a - incident b - prevalent Haemodialysis patients in USA Biggest rise is 80+ - does this imply no discrimination - improved access to transplantation in the young - better disease management in the young Ultimately clear that organ support is not withheld
- Same trend in UK
- Should we consider CKD / renal impairment as a disease Have we invented a condition based around biochemical parameters?
- 1- Previously defined as the opposite of health. Which was defined by WHO in 1946 as (see quote): Other than a cow on a sunny day, who of us fits this??? 2 - There are social issues / societal expectations regarding diagnosis / economic considerations which can affect the perception of what is a disease. Some parts of ageing previously seen as normal have been reclassified as a disease process (osteoporosis). Other behaviours have gone the other way; homosexuality removed from DSM in 1974 3 - This questions has an important relationship to healthcare economics; where do / should we focus resources? Renal medicine takes a disproportionate part of the NHS budget e.g. HD £20k / year…
- 1 - previous 1979 survey. Participants asked if these processes represented a disease. Malaria / TB / cancer - YES. Htn ~60%. Senility 20% (same as colour blindness!) 2 - BMJ updated survey in 2002: what are the top “Non-diseases” that people complain about Other thank jokes about baldness / freckles (both of which I am availed of), the point is that the public and medical profession do not see age as pathology. We therefore need to consider how we separate true renal disease from senescance
- NHANES data (1999-2004) Huge jump in “CKD” at 70+ - is this too prevalent to be a disease - how can services cope?
- 1 - Curve A depicts reduced growth but normal decline. Curve B depicts premature decline in FEV1. Curve C depicts normal growth, no premature decline but accelerated decline. Curve D represents the optimal and ideal lung function, with normal growth and normal decline with age in a healthy individual. Individuals may show combinations of A–C, following a different curve at distinct life stages. 2 - Ejection fraction is preserved as we age; so is stroke volume. VO2max (Cardiac output x (arterial O2-venous O2)) declines with age. As SV stable, reduced CO likely related to impaired heart rate acceleration Heart and lung doctors accept a decline in function as part of the ageing process; why do we not? Perhaps an important confounder here is that CKD does not manifest symptoms; as such biological markers are a crutch we lean on too much?
- 1 - Davies and Shock demonstrated an inverse relationship between the glomerular filtration rate (GFR) and age. These investigators used the urinary clearance of inulin, a technique that remains the "gold standard," to determine GFR in 70 males aged 24 to 89 years. They observed that values during the fourth and fifth decades of life exceeded corresponding values during the seventh and eighth decades by 20% to 25% 2 - GFR fall has temporal relation to reduced renal plasma flow (occurs in 5th - 9th decade) Older patients not known to have renal disease have a 30% reduction in autopsy weight of kidneys (outer cortex) Increased prevalence glomerulosclerosis / glomerular loss as a function of age 3 - GFR also influenced by ultrafiltration coefficient ( which is considered to reflect the product of glomerular hydraulic permeability and the total filtration surface area of all glomeurlar capillaries in the two human kidneys)
- Sclerosis and loss of functioning glomeruli Wedge biopsy from ~35 DCD kidneys (age 55 above / below) 69 vs. 58 ml/min GFR Sclerosis difference not sufficient to account for GFR difference Reduced whole kidney ultrafiltration coefficient in older kidneys accounted for reduced GFR values Increased single nephron surface area and filtration coefficient - adaptive hypertrophy [Number of functioning gloms estimated from ratio of kidney filtration coefficient / single nephron coefficient (this assumes all gloms in the tissue contribute)] i.e. Reduced number of functioning gloms (but those that remain increase workload)
- Is this change in renal tissue a normal function of ageing?
- Reykjavik Study In 2002 to 2006, a total of 5,764 men and women participated in detailed evaluations of cardiovascular, neurocognitive, musculoskeletal, and metabolic phenotypes.19 The second visit (AGES-II-Reykjavik) was a repeat examination of 3,411 participants (71% of the AGES-Reykjavik survivors) in 2007 to 2011. Of these, 3,341 completed both visit days of the AGES-II-Reykjavik visit and were eligible for inclusion. Of AGES-II-Reykjavik participants, 805 were enrolled in the sub- study to measure GFR (AGES-Kidney) Iohexol GFR 1 - Wide spread of GFR - age cannot be sole influence 2 - Relation with mid-life bloods pressures and reduction in later life mGFR Is later-life CKD just an accumulation of poorly treated risk earlier - links to respiratory model Baltimore study of Aging showed only 1/3 patients had a progressive decline in creatinine clearance over time
- Marginally lower eGFR in oldest group: 36 / 35 / 33 / 30 uPCR lower in elderly group High hypertension / ARVD assigned in elderly Also high unknown - ?theraputic nihilism or uncertainty as whether this is disease….. In eldest group (n=710), over mean fu of 3.5 years, 6.6% started RRT. 53% died.
- NICE target - 135/85mmHg <80; 145 / 85 >80 (ambulatory) ACA similar (>80 140 - 145) US JNC guidelines (2014) divide at age 60 These studies show that relatively modest improvements in the elderly can result in benefit. So where should the target be / how should we achieve this?
- Valish trial Data on renal function not presented The primary end point of this study was a composite of cardiovascular events: sudden death, fatal or nonfatal stroke, fatal or nonfatal myocardial infarction, death because of heart failure, other cardiovascular death, unplanned hospitalization for cardiovascular disease, and renal dysfunction (doubling of serum creatinine to a level >2.0 mg per 100 mL or introduction of dialysis No outcome difference
- n=1933 2 year follow up Mean sCr ~90: eGFR 75 male, 55 female (sCr >150 excluded) Low baseline prevalence of prior macrovascular disease Of interests - best outcomes were in HF analysis (basically what they were being treated for!) In Renaal trial, in ~500 patients aged over 65, outcome benefits were the same in losartan treated group (reduced RRT / 2x sCr risk)
- 1 - Reduced liver mass / hepatic blood flow with increasing age. Less phase 1 hepatic metabolism. Main problem with highly protein bound drugs e.g. propranolol, verapamil. Also can get higher cons of hepatically cleared drugs - dox / beta-blockers / CCB 2 - CCB; heart failure problems; marked dependent oedema. Diastolic hypotension, wide pulse pressure this is a risk factor for mortality. 3 - reduced renal clearance. diuretics / ACEi 4 - Beta-blockers affected by both 5 - OH is most commonly associated with beta-blockers. Population data (age / co-morbidity / other drug adjusted) comes from women’s heart and health study. 3800 UK women aged 60 - 80. Only beta-blockers were an independently associated with OH Beta-blockers; harder to study due to intra-class variation 6 - Increased age is an independent risk factor for hyperkalaemia associated with ACEi (AASK trial - African American only). ACEi (though risk of first dose hypotension) have the smallest association with OH)
- 1 / 2 / 3 major coded comorbidities in Medicare data (i.e. age >65) CKD is the outlier with the proportion of patients rising with the number of comorbidities
- Basque Spain: Age >65 with CKD - n = 20797 - Prevalence 5% - 1% of these had no other comorbidity - 99%, 93%, 80%, 64% had 1 - 4 other identified comorbidities Near identical data in UK Most common comorbidity is heart failure (this calls back to the HYVET trial)
- 80% of patients with CHF are >65 years old. >75% have at least one other comorbidity 1 - ADHERE (Acute decompensated heart failure national registry); mean age 72, majority CKD. Mortality as IP rises from 2 - 8% by stage of CKD 2 - CHARM trial (candesartan in heart failure). CKD group had worse prognosis (progressive disease worse for outcome than lower LVF). No effect on treatment outcome. 3 - national heart centre. medicare / medicaid data. Mean age 78, n=17,000. CKD associated with 22% reduced probability of receiving A2 blockade despite significant (greater!) prognostic benefits Caveat - increased diastolic HF in CKD; less clear Rx
- 1 - CKD patients have reduced QoL measures compared to an age matched general population (this is not causal proof!) 2 - Functional / QoL measures worsen with stage of CKD. 3 - Effects are progressive. Longitudinal data: Mean age - 68, eGFR 25 (CKD 3-5 included). Disease diabetic / hypertensive in the main. 1186 CKD patients - Kidney Disease Quality of Life (KDQOL) questionnaire. - Between 1 and 4 years follow up significant decline in all markers of HRQOL. - Largest in physical functioning and emotion roles.
- Anaemia trials - strongest positive finding is QoL data 1 - Anaemia management improves symptoms in all HRQOL domains (CREATE) 2 - CHOIR has shown that this is not dependent on high targets (see CHOIR) These findings are not fully supported by TREAT which predominantly looked at symptoms of fatigue. Here a statistically and clinically significant improvement was seen in the EPO arm (+4.2 vs. +2.8) but no differences in Short Form 36 survey
- Should we dialyse - tricky decision Card on the table; I will work up 70+ on HD for transplant
- 1965 - Royal free. 13 mHDx patients; all young! 1970’s still very limited; Royal Free had a catchment area of 250 miles i.e. further than SRFT (home HD) Some HD patients had diabetes but this was a tiny minority - <5% cf 40% now White, “intelligent”, educated Patients had to make their case - “Force their way on”
- 80 years or older (Canada) 97 patients Started on RRT (2000-2005) 44% started PD 70% started art as IP - less independent living - high mortality Comparative is 20% of non-RRT elderly in Canada at this time required care 18 months after a discharge. Much greater proportion here. Causality not proven, however!
- USRDS data linked with MDS data (minimum data set, a registry of nursing homes) 1998-2000 3702 NH residents incident to RRT - 73 years old - almost all HD (95%) - Co-morbid burden of DM / CHF - 70% started HD as IP Does decline reflect impact of hospitalisation or HD (would think clearance of uraemia would improve things - consider the fact that 30% of OP starters to HD also declined suggests RRT contributes to worsening WHY? Physical risks / psychosocial burden travel / isolation / change in routine Or is ESRD an end-point of multi-organ dysfunction and a mode of death
- Data from US (n=512) shows good separation of survival curves based on - Age - Dementia - PVD - Hypoalbuminaemia - Surprise question REIN registry encompasses all french patients on RRT Sub-analysis of aged 75 or older (2500 training set 1600 validation) Body mass index <18.5 kg/m2 (1 point) • Congestive heart failure stages III-IV (2 points) • Peripheral vascular disease stages III-IV (2 points) • Dysrhythmia (1 point) • Active malignancy (1 point) • Severe behavioural disorder (2 points) • Total dependency for transfers (3 points) • Unplanned dialysis (2 points) Withdrawal of HD approached 20% - why did we start these patients in the first place!!
- Patients aged >75 years - had already chosen RRT or supportive care. First look suggests clear survival benefit associated with HD However, this is still not a huge difference at 2 years and RRT group have given up 50% of their time ± surgery / hospitalisation etc Median time from when eGFR was first 15 ml/min to death or study end was 588 days (range 67–2528 days) for those patients on dialysis and 540 days (range 4–2193 days) for those managed conservatively
- Patients with 2+ significant co-morbidities did not benefit from organ support Several other studies validating this finding Malignancy. Active, non‐cutaneous disease, e.g. myeloma, breast cancer. Ischaemic heart disease. As evidenced by previous myocardial infarction, angina pectoris, positive coronary angiography or other diagnostic procedure (e.g. exercise test, thallium or dobutamine stress test) or the presence of ischaemic changes on the resting ECG (as distinct from left ventricular hypertrophy). Peripheral vascular disease. To include distal aortic, renovascular, lower limb and cerebrovascular disease. Includes either symptomatic disease in these vascular territories (e.g. CVA, claudication, amputation) or significant stenoses (>50%) on vascular imaging or Doppler ultrasound. Left ventricular dysfunction. Defined as clinical evidence of pulmonary oedema, not attributable to errors in fluid balance, and/or moderate to severe left ventricular dysfunction on echocardiography. Diabetes mellitus. The presence of either type 1 or type 2 as comorbidity. Systemic collagen vascular disease. For example, systemic vasculitis, rheumatoid arthritis and systemic sclerosis, either active or requiring treatment. Other significant pathology. A condition severe enough to have an impact on survival in the general population. Examples include: severe chronic obstructive airways disease, cirrhosis, psychotic illness.
- eGFR clock is considered here; 172 CM; 269 RRT RRT group 1.6x as likely to have a hospital admission 48% CM vs. 69% RRT died in hospital 76% of CM accessed community palliative series vs. 0% of RRT!!!
- Overall, we need to be honest and communicate. Unclear if this happens… Small single centre study Looked at prevalent HD patients - does not describe how long they have been on RRT Overall picture for shared decision making appears poor