class: RWH_bg_title # .black[Kidney Disease in the Elderly] <!-- ### MOE teaching --> .RWH_footnote_title[ .RWH_footer_bold[ Rob Hunter | @renalrob ] ] .RWH_footnote_right_title[ .RWH_footer_bold[ MOE teaching | 11th July 2024 ] ] ??? Slides created with [xaringan](https://github.com/yihui/xaringan). --- # Sucking eggs - normal ageing *vs.* CKD - limited physiological reserve - realistic medicine *vs.* therapeutic nihilism - evidence gap - safety & side-effects - multi-morbidity (pros and cons) - polypharmacy - age-specific pathologies ??? Why am I talking about CKD in the elderly? - vasculitis paper - nephrotic syndrome paper --- # Overview - one case of `CKD`: - goals of therapy & risk prediction tools - SGLT2i (and other newer therapies) <br> - one case of `AKI`: - novel K binders - renal referral - FAQs: epo, dialysis, oedema, vasculitis .RWH_footnote_right[.RWH_footer_style[slides at: www.kidneyfish.net/talks/]] --- class: center, middle, inverse # .white[Case 1] ### 80F with T2DM and CKD --- # Case 1 This `80 year-old` with `T2DM` was on metformin (1g bd) and was recently started on `empagliflozin` (10 mg od) by the diabetic team at her annual review. HbA1c was 58. Her renal function has now dipped to `eGFR 40` (SCr 100 to 113 mcM). I have asked her to stop her losartan and empagliflozin. I have asked for urinalysis. I wanted to check if you would also like us to stop her metformin? -- `uACR 40 mg/mmol` | ABP 154/88 ??? ### Qs are: - what else would you like to know? - does she have CKD? - what would you do? - what are the anticipated benefits of RASi and SGLT2i? - can SGLT2i be used safely in older adults (and frailty)? <br> ### Hypothetical case. SGLT2i now everyone's business (not just diabetes, renal...) Importance of albuminuria. <br> ### Does she have CKD? Should read [Canadian study](https://pubmed.ncbi.nlm.nih.gov/34459844/) on fixed *vs* age-adapted CKD definition and accompanying editorial by [O'Hare](https://pubmed.ncbi.nlm.nih.gov/34459870/). In Alberta cohort of 80,000 adults, compared fixed eGFR threshold of 60 to define CKD with age-adapted thresholds (75 for under 40; 60 for under 65; 45 for over 65). Using a fixed threshold, 75% of CKD patients are over 65 and would be re-classified (as eGFR > 45 and uACR < 3). In this group, risks of ESKD and death were similar to non-CKD age-matched controls - suggesting fixed eGFR threshold leads to over-diagnosis of CKD in over 65s. ---  .RWH_footnote_right[.RWH_footer_style[[Ravani *et al.* (2020)](https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2770736)]] ??? Cohort study in 4 million people in Canada (2002 - 2017). Elderly patients with CKD die or get heart failure rather than ESKD. ---  .RWH_footnote_right[.RWH_footer_style[[O'Hare *et al.* (2007)](https://jasn.asnjournals.org/content/18/10/2758)]] ??? 200,000 US veterans. --- # Risk assessment [4vKFRE](https://www.kidneyfailurerisk.co.uk/) | [KDPredict](https://kdpredict.com/) --  ---  In [Lothian](https://edren.org/ren/handbook/unithdbk/ckd/ckd-summary-overview/#3_Delay_CKD_progression): - all T2DM and CKD - non-diabetic CKD and uACR > 25 (uPCR > 50) on RASi .RWH_footnote_right[.RWH_footer_style[[UKKA Clinical Practice Guidleine (2023)](https://pubmed.ncbi.nlm.nih.gov/37880609/)]] ??? Becoming increasingly complicated to navigate. How on earth to implement in elderly frail patient? --- # Sucking eggs again  Caution in extrapolating from RCTs that largely excluded frail, multi-morbid patients. But recognise significant benefit in heart failure. .RWH_footnote_right[.RWH_footer_style[[UKKA Clinical Practice Guidleine (2023)](https://pubmed.ncbi.nlm.nih.gov/37880609/)]] --- # SGLT2i RRRs Broadly consistent across diabetic and non-diabetic populations: - CVS death = 10 % - CVS death or HF hospitalisation = 20 % - AKI = 20 % - progressive CKD = 40 % .RWH_footnote_right[.RWH_footer_style[[Cardio-renal consortium meta-analysis (2022)](https://pubmed.ncbi.nlm.nih.gov/36351458/)]] ??? Advantages of RRR approach: - easier to remember - can apply to individual patient (so CKD not treated as binary variable for example) ---  [Mayne at al., CJASN 2024](https://pubmed.ncbi.nlm.nih.gov/38949880/): 2ry analysis of EMPA-KIDNEY. Relative effects preserved and absolute benefits magnified in patients at predicted risk of hospitalisation (surrogate for frailty). .RWH_footnote_right[.RWH_footer_style[[Kishi *et al.* (2024)](https://pubmed.ncbi.nlm.nih.gov/38977884/)]] ??? Theoretical risks of SGLT2i in frail elderly: falls, sarcopaenia (through reduced insulin secretion) - but so far available evidence from RCTs looks okay. Probably largely untested in very frail elderly. ### General approach to CKD in older adults 4 pillars in diabetic CKD (RASi, SGLT2i, nsMRA, GLP1ra): largely untested in older, frail patients. See [Kishi *et al.* (2024)](https://pubmed.ncbi.nlm.nih.gov/38977884/). Good evidence for RASi in elderly in context of HTN (e.g. HYVET) or heart failure. --- class: center, middle, inverse # .white[Case 2] ### 79F with AKI --- # Case 2 `79F` admitted with `pneumonia`. Smoker, EtOH XS, hip replacement, HTN on amlodipine and atenolol. Getting worse after 7 days in hospital. Not for ITU. - SCr 60 > 80 > 200 > 550 mcM - K 5.9 o/e: - ABP 110/60 (after period of systolic in 90s) - increasing O2 requirement (4L/min nasal) - JVP elevated - anuric - IVI at 250 ml/hr (already 3L +ve in 24 hrs) ??? ### Qs - What would you do? - How would you manage the hyperkalaemia? - Would you refer to renal?... ...and why? ### Hypothetical case Kussmaul breathing. pH 7.2 H 59 HCO3 12 PaCO2 3.7 BE -16 AG 33; ketones 1.4; lactate 0.9 Biopsy showed ATN. Three weeks later: - still HD-dep on HDU - line infection - HIT (peri-arrest) - ...but ultimately excellent recovery --- # Lokelma See Edren pages on [prescribing](https://edren.org/ren/handbook/prescribing-handbook/) and [hyperkalaemia](https://edren.org/ren/handbook/unithdbk/fluids-and-electrolytes/). Sodium zirconium cyclosillicate (Lokelma) now on East Region Formulary for use under specialist supervision. Highly selective K binder; works throughout GI tract; onset within 1 hr; sodium load. `Acute use`: - K > 6 mM - not getting dialysis - renal recovery expected within 72 hrs `Chronic use`: only under specialist (renal or cardiology) supervision. ??? K threshold in dialysis patients is 5.5 mM. Lokelma approved by SMC for acute and chronic use (with restrictions). On formulary for acute and chronic use in renal patients (but not yet for chronic use in heart failure). Retrospective PACS2 no longer required and discussion with renal not mandated but probably still advisable until we are all familiar and renal protocols all up online (should be imminent). For chronic use: - attending renal clinic (or cardiology) - CKD3B-5 - uPCR > 50 - unable to acheive optimal RASi - unprovoked hyperK despite optimisation of TCO2, diuretics, diet... <br> Patiromer (Valtessa) now approved by SMC for acute and chronic use - but not on Formulary. Less selective, works in distal colon, delayed onset (6 hrs), hypoMg, constipation. Will probably add to Formulary as back-up in case of supply issues. --- # Lokelma - practice points - avoid in bowel obstruction - prolonged / outpatient use should be under renal supervision - prescribe on HEPMA (10g every 8 hrs for 3 days) - anticipate 1 mM reduction by 24 hrs - switch to maintenance (5 -- 10 g od -- bd) when K < 5.5 mM - daily U&Es - usually no more than 7 days; definitely stop before discharge - if not meeting pre-approved criteria: emergency PACS2 route --- # Hyperkalaemia in elderly Remember: - diet may not be effective - diuretics - bicarbonate - trimethoprim, heparin... - treat constipation? ??? Theory that constipation may predispose to hyperK. I think unproven. 90% K absorption in the small intestine. K secreted into the colon through pathways upregalated in CKD. Thery is that slower transit times may increase K absorption. See https://pubmed.ncbi.nlm.nih.gov/32043026/ and https://pubmed.ncbi.nlm.nih.gov/37127307/. --- # Renal referral in elderly - diagnosis (vasculitis, nephrotic syndrome, myeloma...) - prognostication / advance care planning - dialysis - diuretics - iron and epo - [Edren](https://edren.org/ren/) | RIE.RenalAdvice@luht.scot.nhs.uk --- # Take-home messages - consider age-adapted eGFR thresholds (eGFR 45 if over 65) - in older adults with CKD, risks are death and heart failure - therefore focus on CVS risk reduction - uncertainty around SGLT2i (and GLP1ra) in frail / multimorbid... - ...but probably under-used; helpful to think about goal of Rx - Lokelma useful in selected cases - d/w renal - do please talk to us! .RWH_footnote_right[.RWH_footer_style[slides at: www.kidneyfish.net/talks/]] --- class: center, middle, inverse # .white[Supplemental slides] ---  .RWH_footnote_right[.RWH_footer_style[[Kishi *et al.* (2024)](https://pubmed.ncbi.nlm.nih.gov/38977884/)]] ---  ??? See also [McRae et al. (2021)](https://pubmed.ncbi.nlm.nih.gov/33558333/) - comorbidity very common in CKD (in Scotland). ---  ---  ??? QRISK3 incorporates CKD (binary variable) and can cope with extremes of age. Presumed systolc 150 for purposes of this; other data all real. ASSIGN score = 48, which approximates to 48% risk over 10 yrs but probably a bit lower. QRISK3 = 33% risk over 10 yrs. ---  --- # Safety data in older adults? Ages in DAPA-CKD and EMPA KIDNEY approx 62 +/- 12 yrs. [Zhuo et al., AJKD 2021](https://pubmed.ncbi.nlm.nih.gov/34762974/): cohort study in adults over 66 yrs with T2DM (n = 140,000). New users of SLGT2i matched to new users of DPP4i and GLP1RAs. Reduced AKI with SGLT2i (RRR 0.2 - 0.3). [Pratley et al., Lancet Healthy Longev 2023](https://pubmed.ncbi.nlm.nih.gov/37003273/): secondary analysis of VERTIS CV (RCT of ertugliflozin in T2DM with high CVS risk). Compared under 65, 65 - 75 (n = 8000), over 75 (n = 900). Broadly similar results across age-groups. [Mayne at al., CJASN 2024](https://pubmed.ncbi.nlm.nih.gov/38949880/): secondary analysis of EMPA-KIDNEY. Relative effects preserved and absolute benefits magnified in patients at predicted risk of hospitalisation (surrogate for frailty). ??? Relatively little data in frailty / significant multimorbidity.