class: RWH_bg_title # .black[Renal GP Update] ### What's new in Renal Medicine? .RWH_footnote_title[ .RWH_footer_bold[ Rob Hunter | @renalrob ] ] .RWH_footnote_right_title[ .RWH_footer_bold[ 7th Sep 2022 ] ] ??? GP update 7th Sep 2022 Slides created with [xaringan](https://github.com/yihui/xaringan). --- # Overview - **three cases** - refreshed **referral criteria** - **new drugs:** SGLT2i, novel K binders - **old chestnuts:** ACEi/ARB, T2DM, CKD in elderly / co-morbid... ??? Not time for: - **all old chestnuts:** ACEi/ARB, young patients, old patients, cardiorenal, lithium, post-AKI... - **hot topics:** ethnicity and eGFR, sick day rules --- # Take-home messages - options for **assessing risk** of ESKD - **SGLT2i** now on formulary for CKD (and T2DM and HFrEF) - **dapagliflozin 10 mg od** as add-on to RASi if uACR < 25 (uPCR > 50) - reduce **cardiovascular death**, heart failure and ESKD (by up to 30 %) - novel **K binders** to support RASi in proteinuric CKD and HFrEF <br> <br> <br> <br> **Edren pages**: [CKD](https://edren.org/ren/handbook/unithdbk/ckd/ckd-summary-overview/) | [SGLT2i](https://edren.org/ren/handbook/prescribing-handbook/general-prescribing-notes/sglt2i-how-to-start/) | [referral](https://edren.org/ren/gp-info/draft-referral-guidelines-2022/) | [hyperK](https://edren.org/ren/handbook/unithdbk/fluids-and-electrolytes/hyperkalaemia-outpatient/) --- class: RWH_black  ??? The iceberg: most CKD managed in primary care. In Scotland, around 3 - 4 % of population have CKD (https://www.scotpho.org.uk/health-wellbeing-and-disease/kidney-disease/data/scottish-data). Only 0.1% have ESKD. CKD4 will be around 0.2% of population (https://www.acpjournals.org/doi/epdf/10.7326/0003-4819-139-2-200307150-00013). --- class: center, middle, inverse # .white[Case 1] ### 85M with diabetes and CKD --- # Case 1 85M with T2DM, HTN, CKD. uACR has gone up from 35 (12 months ago) to 90. eGFR has dropped from 30 to 25 - we plan to repeat again next week. **Meds** = metformin, ramipril (10), amlodipine, atorvastatin, bendroflumethiazide, doxazosin, finasteride > .red[What extra information would be helpful?] -- <br> ABP = 140/70 | no ankle oedema | T2DM for 10 years, HbA1c in 60s > .red[What would you do?] ??? What would you do with existing medications? Add in any? Refer in? --- # Case 1 **Guidelines in diabetic kidney disease (T2DM + CKD with uACR > 3):** - **NICE** = RASi + SGLT2i (if meets marketing authorisations) - **KDIGO** = RASi + SGLT2i (if eGFR > 30) + metformin -- <br> <br> [CREDENCE trial](https://www.nejm.org/doi/full/10.1056/nejmoa1811744): - canagliflozin vs. placebo in DKD with uACR > 30 - reduced ESKD, heart failure, CVS death (RRR 30 %) ??? Marketing authorisations == GFR thresholds, which are (BNF): - empagliflozin = 45 or 30 if CVS disease or 20 if heart failure - canagliflozin = 30 - dapagliflozin = 15 --- # Case 1  ??? 30% rise in Cr a reasonable threshold - but ensure applied sensibly - e.g. not responding to chronic drift. --- # Referral [Edren referral guidelines](https://edren.org/ren/gp-info/draft-referral-guidelines-2022/) ??? NICE guidelines revised in 2021. In NICE 2014, referral if eGFR < 30. SIGN guidlines (2008) now defunct. --- # Referral < supplemental slide in case links not working > <br> <br> [Edren referral guidelines](https://edren.org/ren/gp-info/draft-referral-guidelines-2022/) - routes of referral - changes to routine referral: [4vKFRE](https://kidneyfailurerisk.co.uk/) replaces eGFR threshold ??? Implications of 4vKFRE = needs a uACR. Only in adults. Black patients under-represented in development cohorts. 4vKFRE does NOT account for the competing risk of death. 5 yr results are significant over-estimates when the competing risk of death is high (e.g. elderly) - see [Al-Wahsh *et. al.* (2021)](https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779439). --- # KDIGO traffic lights  --- # Case 1 85M with T2DM, HTN, CKD. uACR has gone up from 35 (12 months ago) to 90. eGFR has dropped from 30 to 25 - we plan to repeat again next week. **Meds** = metformin, ramipril (10), amlodipine, atorvastatin, bendroflumethiazide, doxazosin, finasteride ABP = 140/70 | no ankle oedema | T2DM for 10 years, HbA1c in 60s 4vKFRE = 21% risk of ESKD at 5 years. <br> <br> > .red[What is the most likely outcome for this patient?] --- # CKD in older patients  .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). --- class: center, middle, inverse # .white[Case 2] ### 75F with CKD --- # Case 2 75F with HTN, CKD, COPD. Was on lisinopril for HTN but stopped in hospital 2 yrs ago. BP started rising recently so lisinopril resumed at 2.5 mg od. SCr 135 > 150 (eGFR just dipped below 30 ml/min). K = 4.9 mM. Blood pressure = 175/90. uPCR = 70. **Other meds** = aspirin, inhalers, simvastatin. **Intolerances** = amlodipine. <br> > .red[What would you do?] > .red[What are the main treatment goals?] ??? - ACEi or not? - SGLT2i on not? - target ABP? - refer in? <br> <br> Target ABP: NICE says 140/90 for most; 130/80 if uACR > 70; 150/90 for frail elderly. --- # Case 2  --- # CVS risk in CKD  .RWH_footnote_right[.RWH_footer_style[[Fox *et al.* (2012)](https://www.sciencedirect.com/science/article/pii/S0140673612613506?via%3Dihub)]] ??? Meta-analysis of over 1 million individuals in combined general and high-risk populations; shape of curve almost identical for CVS mortality. --- # CVS risk in CKD  .RWH_footnote_right[.RWH_footer_style[[Fox *et al.* (2012)](https://www.sciencedirect.com/science/article/pii/S0140673612613506?via%3Dihub)]] ??? Meta-analysis of over 1 million individuals in combined general and high-risk populations; shape of curve almost identical for CVS mortality. NB US units (so divide uACR by ~10). --- # Treating BP in CKD  .RWH_footnote_right[.RWH_footer_style[[Ettehad *et. al.* (2016)](https://www.sciencedirect.com/science/article/pii/S0140673615012258?via%3Dihub)]] ??? Meta-analysis of 123 trials with 600,000 participants. --- # DAPA-CKD  .RWH_footnote_right[.RWH_footer_style[[DAPA-CKD trial (2020)](https://www.nejm.org/doi/full/10.1056/NEJMoa2024816)]] ??? n = 4000; eGFR > 25; uACR > 20; with or without DM. (T2DM in 66%). Composite endpoint = 50% reduction in eGFR, ESKD, renal death, CVS death. --- # DAPA-CKD  <br> .RWH_footnote_right[.RWH_footer_style[[DAPA-CKD trial (2020)](https://www.nejm.org/doi/full/10.1056/NEJMoa2024816)]] --- # SGLT2i **Benefits:** - reduction in all-cause and CV death, heart failure, CVS events, ESKD - in diabetes, CKD with albuminuria, HFrEF, HFpEF - typical RRR 10 - 30% - protective against AKI (!) - HR 0.75 -- **Harms:** - DKA (OR 2 - 3) - in T2DM! - fungal genital infections (OR 3 - 5) - in T2DM! - and possibly also fractures, amputations, UTIs (very low risk) -- **Guidance:** - **NICE** = add-on to RASi if uACR > 22.6 and eGFR 25 - 75 - **Lothian** = add-on to RASi if uACR > 25 or uPCR > 50 and eGFR > 15 .RWH_footnote_right[.RWH_footer_style[[Johansen & Argyropoulos (2020)](https://onlinelibrary.wiley.com/doi/10.1002/clc.23508)]] ??? EMPA-KIDNEY enrolled some patients without albuminuria - stopped early for efficacy. DELIVER trial (NEJM 2022) - efficacy in HFpEF. --- # SGLT2i prescribing in practice - [Edren SGLT2i pages](https://edren.org/ren/handbook/prescribing-handbook/general-prescribing-notes/sglt2i-how-to-start/) - dapagliflozin 10 mg od - efficacy at lowering glucose diminishes as GFR falls... - ...but still safe and likely effective at CVS protection - risks probably low in non-diabetics (no XS AEs in DAPA-CKD) - anticipate eGFR drop - no need to monitor - sick day rules (?) --- class: RWH_black  ??? Do we really have to stick all our healthy 80 year-olds on SGLT2is now? ---  ??? See also McRae et al. (2021) - comorbidity very common in CKD (in Scotland). --- class: center, middle, inverse # .white[Case 3] ### 60F with high potassium --- # Case 3 60F with T2DM and CKD. eGFR 30 (declining over years); uACR 80. ABP 170/90. Irbesartan stopped last month when K 6.0 mM. K now 4.9 mM. (TCO2 20 last year.) **Other Meds** = bisoprolol, indapamide. **Intolerances** = amlodipine, BFZ, doxazosin, spiro. <br> <br> > .red[Do we re-start the ARB?] <br> > .red[What measures can we use to keep K down?] ??? 4vKFRE = 16% at 5 yrs. --- # Hyperkalaemia - [Edren hyperK page](https://edren.org/ren/handbook/unithdbk/fluids-and-electrolytes/hyperkalaemia-outpatient/) - first decide how important ACEi/ARB will be - dietary advice (controversial) - loop or thiazide diuretics - [SGLT2i?!](https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.057736) - correct acidosis - optimise glycaemic control - sodium zirconium cyclosilicate if all of: - eGFR < 45 - uPCR > 50 - attend renal clinic - cannot tolerate RASi because of hyperK --- # Take-home messages - options for **assessing risk** of ESKD - **SGLT2i** now on formulary for CKD (and T2DM and HFrEF) - **dapagliflozin 10 mg od** as add-on to RASi if uACR < 25 (uPCR > 50) - reduce **cardiovascular death**, heart failure and ESKD (by up to 40 %) - novel **K binders** to support RASi in proteinuric CKD and HFrEF <br> <br> <br> <br> **Edren pages**: [CKD](https://edren.org/ren/handbook/unithdbk/ckd/ckd-summary-overview/) | [SGLT2i](https://edren.org/ren/handbook/prescribing-handbook/general-prescribing-notes/sglt2i-how-to-start/) | [referral](https://edren.org/ren/gp-info/draft-referral-guidelines-2022/) | [hyperK](https://edren.org/ren/handbook/unithdbk/fluids-and-electrolytes/hyperkalaemia-outpatient/) --- class: center, middle, inverse # Thank you ### .white[@renalrob] --- class: center, middle, inverse # Supplemental slides ### .white[@renalrob] --- # KDIGO traffic lights  --- # 4vKFRE  .RWH_footnote_right[.RWH_footer_style[[Potok *et al.* (2019)](https://cjasn.asnjournals.org/content/14/2/206/tab-article-info)]] ??? 250 patients with CKD 3 -- 5: both doctors and patients over-estimated risk. --- # CKD in older patients  .RWH_footnote_right[.RWH_footer_style[[O'Hare *et al.* (2007)](https://jasn.asnjournals.org/content/18/10/2758)]] ??? 200,000 US veterans. --- # Hyperkalaemia: thresholds [Edren hyperK page](https://edren.org/ren/handbook/unithdbk/fluids-and-electrolytes/hyperkalaemia-outpatient/) | [UKKA (2020)](https://ukkidney.org/sites/renal.org/files/APPENDIX%205%20-%20HYPERKALAEMIA%20ALGORITHM%20IN%20COMMUNITY.pdf) | [Heart failure (2019)](https://heart.bmj.com/content/heartjnl/105/12/904.full.pdf) - under 5.5 mM = ignore - 5.5 - 5.9 mM = review medications (reduce dose RASi?) - over 6.5 mM = stop RASi and refer urgently -- <br> - 6.0 - 6.4 mM (chronic, stable) = stop RASi if no strong indication; suspend if strong indication and restart (with binder) when K < 5.5 mM - 6.0 - 6.4 mM (AKI) = stop RASi and refer urgently - 6.0 - 6.4 mM (decompensated HF) = continue RASi but reduce dose ??? Strong indication = HFrEF or DKD with albuminuria