Nephrology Insights for Primary Care focus on AKI

Nephrology Insights for Primary Care - focus on AKI/ CKD/ Dialysis Kaarlo Hinkkala MD, FRCPC Locum Nephrologist – TBRHSC Assistant Professor - NOSM

Conflict of Interest Declaration: Nothing to Disclose Presenter: Dr. Kaarlo Hinkkala Title of Presentation: Nephrology Insights for Primary Care I have no financial or personal relationship related to this presentation to disclose.

Objectives • Brief survey across the discipline – Focus on CKD, AKI, ESRD, dialysis • Cover mainly bottom line issues • Things I wish people knew / what grinds my gears • Things you may not have realized we can do • What we actually do with a variety of problems • Avoid sedating you with clin epi, basic science, guidelines/ minutia – Going for a common sense approach here (based on evidence) • Threw in a few things purely for interest

A Cynical Approach to Nephrology… • • Stop all culprit meds Flip a coin and give either fluids or diuretics If that fails do the opposite If that fails, dialysis will temporarily fix everything – Fluids, electrolytes, uremia of course – Hyperglycemia, hypo/hyperthermia, HTN, lipids (via plex) • Goal of every nephrologist sometimes seems to be to have your patient die with perfect numbers – We often get pressured into temporizing hopeless situations until people man up and put an end to things that need to end – We’re also often asked to manage the decline • End stage cardiorenal, hepatorenal, oncology patients

AKI • Treat acute illness • Hold ace/arb/ NSAIDS/ diuretics (if not overloaded) • U/S and U/A • Consider GN and AIN in DDx – AIN – PPI, cephalosporin's, septra, NSAIDS, 5 -ASA • Hydrate as much as you think they can reasonably handle – If bicarb is low use instead of NS • • 3 amps/ 1 L d 5 w = “normal bicarb” at same rate you would use NS NS will drive down your bicarb – p. H is 5. 5 Bicarb will drive down K and will make more CO 2 (usually not an issue) Write order to change to NS once bicarb >18

• Then see where they level out and wait • HD – lytes / volume reasons or sustained anuria – Don’t dialyze acutely for uremia • Unless LOC poor or progressed now to ESRD • Cardiorenal – sometimes can’t get the fluid off without inc the Cr – Just push on and accept the Cr will go up with diuresis – Either way will get HD if we cant get the fluid off so nothing to lose • Dialysis does not heal your kidneys, it just does what they are not – No role to doing it early unless fluid is getting bad

K+ 7. 7

Toxicology / dialysis • ASA, antifreeze /methanol, Lithium • Call poison control and then us as needed • Other drugs generally have antidote / too protein bound, not dialyzed well, not toxic enough, etc • Decision to HD based on drug level, severity of symptoms, time of ingestion

IV Contrast • If important, just do the test and live with the consequences irregardless of GFR • Stop / hold any meds that will aggravate AKI • Hydrate as much as you feel comfortable – Outpt protocols - bicarb vs NS - use whatever you prefer – 150 ml/hr 1 hr prior, then 50 ml/hr x 6 hrs is a common outpt protocol • Assuming 50 kg (3 ml/kg/hr x 1 hr, then 1 ml/kg/hr x 6 hr) – If already overloaded, perhaps just hold the lasix/ace

• Risk from CT is less than cath • NAC – homeopathic, but ok to use anyway • AKI - see within 48 hrs, peaks 5 -7 d • Risk of AKI in 5 -10% range – Usually mild inc in Cr – HD - <1% • Usually has adv CKD / acute illness / temporary • Dialysis not protective against contrast • If ESRD (esp if not on PD), there is nothing to lose by giving dye – kidneys are done

LMWH – renal failure • With our current formulary would recommend: – Lovenox for everyone with normal GFR • Use 30 OD for GFR 15 -30 prophylaxis • <15 - ? heparin 5000 BID – Dalt or tinza would be fine in esrd but not allowed by pharm – Tinzaparin for therapeutic Tx if GFR <30 – Dalteparin only in oncology patients for Tx dose

• Lovenox does bioaccumulate – Dalteparin does not in esrd at least over 2 weeks – Tinza is likely even better – I have routinely used regular dose dalteparin for bridging ESRD • Practice styles vary widely for lovenox – Some programs use 30 OD even for ESRD • Likely fine at least down to gfr 15 -20 – Below that I suspect we are stuck with 5000 BID?

Mild CKD If etiology assumed to be DM, HTN, vascular disease: • Quantify proteinuria (ACR or 24 hr) and u/a • Also appreciate with most referrals – Ca/PO 4/PTH/Alb, Ferritin/ Fe sat, +/- SPEP – An u/s is not a bad idea Serologies - only if suspect GN (clinical or active urine) – ANCA, ANA, anti-GBM, C 3, C 4, CRP, RF, Hep B/C, Ig. A/Ig. M/Ig. G • HIV if clinical suspicion – INR/PTT useful in case need biopsy • Don’t call a Cr of 150 renal failure as it scares patients – Chronic kidney disease – mild/mod/severe

• If labs other than Cr ok, all I will do is Tx HTN and advise DM/ lifestyle to be optimized, quit smoking, diuretics if edema, avoid nephrotoxic drugs, things you are all competent in already • If Cr bumps up a bit but everything else fine, consider holding meds of concern and just rechecking as it can often fluctuate • I don’t know what use a BNP in adv CKD is – they will always be high – Useful normally if really high or low – check only once • Refer: – Persistent progression • If its just stuck a bit low, but everything else is optimized I don’t have much else to add • Don’t get hung up on a specific GFR – 85 M c chronic GFR 50, the kidneys will outlast him – GFR <30 – especially if progressing – Trouble managing effects of CKD – Worried about etiology

Adv CKD – PRI clinic • • • Plan for dialysis / decide modality CKD care as before Anemia / iron management Ca/PO 4/ PTH Dialysis access Multidisciplinary team – Pharm, dieticians, social work, educators, RN, dialysis access coordinators

Anemia / Arenesp • Given SC/IV q 1 -4 weeks – Started usually q 2 weeks ~1/2 wt in Kg – Side effects - idiosyncratic – Max 100 mcg q 1 week • Wont do much good beyond that • Causes for resistance – chronic inflammation, blood / marrow disorders / cancer, Fe deficiency, ongoing losses, Aluminum, PTH out of control • Tend to target Hg. B 100 -110 – Increase strokes/ thrombotic events if higher • Epo shorter half life so less convenient • Renal program covers it if has CKD

Calcium, Phosphate, PTH • In CKD – can’t activate Vit D and tend to retain PO 4 – leads to: • Calcium • PO 4 • PTH • PO 4, PTH are not an acute problem – Lead to inc vascular calcification – Bone fragility – Some people are hopeless as control of this is lifestyle dependant on diet and pill compliance

Step 1) fix Hypocalcemia • Rocaltrol – Ca, PO 4, PTH – Start 0. 25 mcg either 3 x/wk to OD – All drugs in the family are equivalent – If Ca normal, don’t use it if PO 4 more than 2 • On HD can increase the Calcium in the bath • Chronic pts tolerate lower Ca better than you think – >2 - don’t care – >1. 7 – just tweak the meds, ER only if symptomatic (numbness, weakness) • 1. 7 -1. 5 – MD risk tolerance dependant – <1. 5 – ER for sure • IV Ca gluconate and inc the rocaltrol

Step 2) fix PO 4 with binders and lifestyle • Target <1. 7 – anything under 2 -2. 5 is pretty good • Apocal 500 TID c meals, can go to 1000 -1500 mg – Ca with foods binds PO 4 – Ca on its own increases serum Ca • Sevelemer 800 -1600 TID c meals – Calcium sparing – not as potent of a binder – I use as 2 nd line add on or if hypercalcemia • Aluminum works great, but concerns of toxicity limit its use

Step 3) PTH • Can deal with PTH only after PO 4 is “reasonable”, ideally <2 • Main Tx is rocaltrol to suppress it (will inc PO 4 and Ca) • PTH Target – Higher than normal as relatively resistant to it • ESRD - 30 -60 • Stage 4 - 15 -30 • Stage 3 - 7 -15 – PTH that’s too low in adults not really a big deal, just back off rocaltrol • Parathyroidectomy when refractory – I. e. >100 -200 chronically – ++ hungry bone – Can need mega doses Ca and vit D post • Sinacalet is like a partial medical parathyroidectomy

Nephrocalcinosis • ~30 F, HD x 5+ years • Only shows up 1 hour/run, PO 4 ~4, PTH >100 • Will eventually turn into wounds

A few tips about HTN drug choice • Consider which side effect might be an issue in this patient – – CCB - edema, bradycardia HCTZ - low Na ACE/ ARB - high K, more prone to AKI (chronic diarrhea patients) B blocker - Bradycardia • Can I get 2 for 1 with a particular drug? – – – Diuretics - edema B blockers - HF / AF / tremor Help with high or low K Alpha blocker - BPH ACE, ARB – Proteinuria Hydralazine/ NTG - angina

• HCTZ ineffective with GFR <25 – Use lasix if want diuretic • I often hold ACE/ARB once GFR getting ~15 -20 – Prone to high K – ? Buy a little time before HD as they physiologically lower GFR • Alpha blockers (doxazocin) and spironolactone are often a good drug when asking “what else can I add” • No role for dual ACE/ARB • Aliskerin no clear role/ utility

ESRD Paradoxes • Patients with excellent BP/ PO 4/ lipids, less interdialytic weight gain, not obese, etc actually have increased mortality – Confounded by malnourishment, frailty, poor PO intake, weak heart, chronic disease, etc • Never shown benefit to treating lipids in ESRD – I don’t bother after GFR <30 with statins • On enough pills anyway and not doing any good – Multiple other mechanisms of CVD – esp vasc calc

ESRD – indications to start • K, bicarb, volume status that is refractory • Uremia most common reason – Had patients feel uremic with Cr 350, others feel fine at 800 • Start only once feel lousy – A bad Cr is not of itself a reason to start • It’s the company that it keeps that matters • Generally if >1000, I am skeptical if they deny uremia symptoms • Uremia is insidious – Frog in boiling water analogy • So slow you get used to it /only when taken away realize how sick you were – Chronically weaker, sleeping more, nausea, food not taste the same, dec appetite, itchy • just overall not the person they were 3 -6 mo ago as physically declining for no other reason

Modality Choice • If decision deferred, wont have fistula or PD cath in place at time of start – Default is then HD with line in town • Once decide PD – 0. 5 -2 mo to get catheter, needs 3 -4 weeks to heal, then RN time available to train – We do in IR unless has hernia, large BMI, ++prior surgery – 2 -4 mo from “lets do it” to “ready to go” • Fistula – need to see surgeon and often 3 mo to mature – Mortality benefit, can bath/swim, better clearance, doesn’t get infected, works for years once get it going, no SVC occlusion. Finicky at first and not all will mature

• PD vs HD - Mortality about the same – Individualized choice – Proximity to HD center major factor • 20% die in first year, 35% alive in 5 years – Tend to live ⅓- ¼ of projected remaining life years compared to general population – Enhanced cardiovascular illness is main factor • Death of a thousand cuts • PICC lines will destroy the vein – Unlikely to ever have a fistula there afterward – If you need it, so be it, but avoid for softer indications

PD • CAPD – continuous ambulatory PD – Usually 2 L x 4 exchanges/ day inc qhs long fill • CCPD – continuous cycler PD – Hook up at night to cycler machine 2 L x 4 -5 exchanges at night +/- a day fill • Cycler much more convenient – More alarms – More drain pain – Clearance can be an issue if a slow transporter (slower equilibration) • Fast transporter much more common • Mostly comes down to pt preference

• 3 strengths of glucose bags – Determines how much UF (ultrafiltration) • If you can drive a car, no reason you couldn’t do PD – It’s not hard – sterile connection, hang some fluid, push a couple buttons, record BP and weights • Most patients will live with Na 125 -135 and Cr 500 -800 – that’s ok – Measure adequacy by clearance in the fluid not serum creatinine • Increase from baseline may reflect loss RRF, non-compliance

PD - advantages • Home always better • Slow / steady-state/ more gentle - HD is more of a short sprint – Less acute shifting - not as fatiguing, less hypotension • • Retain residual renal Fx longer Costs system half as much as HD Ease into ESRD Travel Ascites management Save veins for later I encourage PD first (or HHD)

PD - disadvantages • 500 -800 calories / day extra glucose • Hard to get enough clearance for bigger people and more likely to be underdialyzed • Hernias / Bloating from fluid – Need surgical correction if have before starting • Catheter dependant – Can get malpositioned / tethered in omentum – Not as easy to change as HD lines • May need to hold PD/ go on HD while catheter heals as will leak • Drain pain

• More protein wasting than HD • Leak – pericatheter, hydrothorax, hydrocele • Peritonitis/ tunnel infections – Treated with IP ABX • ceftaz/ancef, and/ or vanc/tobra • FYI - 1 dose IP vanco therapeutic for 4 -5 days • Don’t give IV vanc if already on IP • Patient / family need to have some degree of competence / involvement - Burnout • Encapsulating peritoneal sclerosis - rare

HD • Generally 3 x 4 hours/ week – 4 x/week if struggle with fluid gains / removal – If really good residual function - 2 x/wk • Most have 2 -4 L removed per run – 5 L for some heavy gainers • Can set different K baths – Can adjust Na, bicarb, Ca, temp also • Partially heparinized per run

HD – Advantages • Much easier to get enough clearance • Not require as competent patient / social situation – Less likely to fall through the cracks • Can get more fluid off in a shorter time • Avoids PD issues relating to fluid in abdomen – Leaks, hernia, infections, calories • Not need to do the dialysis thing everyday

HD - Disadvantages Not home based Can leave people feeling wiped out after Cramps, hypotension common Line infections are usually more severe than peritonitis • Occasionally reactions to dialyzer • Veins can start to become a scarce commodity • Need for heparin – inc bleeding risk • • – Default is 1000 bolus, 1000/hr x 3. 5 hrs

Silver linings of HD • Never get poked for outpt labs again – Easy to monitor CBC, INR / warfarin, lytes, etc • We can do a bit of minor wound care • Captive audience for a consultant to see – Can pre-schedule a visit • HD/ PD records all in meditech now

• Already coming to an IV infusion center 3 x/week anyway – no need for CCAC/ PICC – We can dose many IV ABX q HD as GFR low enough • Ancef, vanco, tobra, ceftaz, PO cipro, etc covers a lot – PRBC support easy to do on HD • Blood given on HD is volume neutral • Arenesp also given in HD IV • IV iron routinely used – PO poorly absorbed and causes gut grief – On going losses in circuit – On enough pills anyway – I use IV Fe a lot for GIB in non renal patients too • Venofer 500 mg x 2 doses and you’re all topped up

Home HD • QOL better – At home and more likely to be able to work • Amount varies, but clearance about double – Nocturnal – 8 hrs x 3 -5 days / week • Fluid and dietary restrictions markedly relaxed – Some patients need PO 4 added to their dialysate! • HTN better controlled

• People feel better on it and almost as good as transplant patients feel – Less shifting / day-to-day fluctuations • 6 week training program – Only do if patient motivated or will burn out – Not prohibitive to learn but is more involved than PD • If I had ESRD, I’d start with PD and transition to HHD in a couple years as my residual Fx burnt out

Withdrawal off Dialysis • Good way to die (if not in CHF) – Painlessly drift into uremic coma – Sudden cardiac arrest • Takes 1/2 -2 weeks if anuric – Much longer if still peeing plenty • Feel free to use their HD line PRN once they are palliative – Also may use line in resuscitation • Need to aspirate out heparin prior to use • Saline flush then 2 cc of citrate or heparin (1000 U/m. L) afterward – Or just leave it TKVO until HD RN can lock it off for you – Reluctant allow use line in general • If not locked properly – will need to be changed – Needs to aspirate 300 -400 m. L/min or it’s useless for HD

Transplant Patient Advice • Usually on tacrolimus (or cyclosporine) and MMF – Most on low dose prednisone (occ steroid free protocol) • Never acutely stop prednisone – Best way to precipitate acute rejection • Never stop the Tacrolimus / cyclosporine even if septic • Tac has an NSAID-like vasoconstrictive effect on kidney so minimize other nephrotoxins • Prone to high K; PO 4/ mg wasting

• Inc risk of lymphoma, cervical and skin cancer • Living donor – last 15 years, deceased - 10 yr • CVS disease still very high (better than HD/PD) • Non-ATN increase in Cr needs a Bx – DDx – Ab rejection, cellular rejection, reoccurrence of prior disease, BK nephropathy, drug level too high • Tx varies from plex/IVIG, thymo/steroids, dec overall immunosuppression, adjusting drug dose

Transplant Drugs • Tacrolimus – Dm, HTN, drug-drug interactions, tremors, gout, chronic fibrosis of graft, lipids, alopecia • MMF – Diarrhea, teratogenic, cytopenia, transaminitis – MMF is not a big deal to be off for a week PRN

CRRT – Continuous Renal Replacement • Used in ICU – Regular HD 0. 5 -1 L per hour x 4 hours, 3 x/week • UF not tolerated well on pressors • Easy to get behind with fluid - easily become +10 -20 L in a week – Instead, how about we take off net 50 -200 cc/hr but do it around the clock • 50 cc/hr x 7 d is 8. 4 L, 200 cc/hr x 7 d is 34 L in a week – Intentionally made not as efficient as would otherwise deplete lytes too much as continuous • Not as good for toxicology, acute emergencies • Rapid shifting of urea/ lytes decreases osmotic pressure – Would make more prone to hypotension otherwise – Continuous exposure to heparin • Can use citrate to anticoagulate the circuit, not the patient

Aphaeresis • CRRT machines have a different filter that leaks protein / albumin so can do plasmaphersis • Allows temporization of acute crisis by removing immune antibodies, it does not stop production – Vasculitis, anti-GBM, GBS, MG, antibody mediated transplant rejection, APLA, waldenstroms / hyperviscosity, lipid disorders – TTP – supplies the deficient protein and removes Ab • Need special machine to do other cell lines – Stem cell harvest, sickle cell, blast crisis, Plt • No clear role in toxicology for pharmacokinetic reasons

Meditech • FYI – all dialysis records are in meditech • You can print out HD/PD/ Transplant patient med lists as a ready to sign order

To End with A few Random Images Purely for Interest -Audience participation requested -Some renal, others not What is happening on this EKG?

• 45 M Fulminent Pancreatitis, 3 pressers maxed and dying • Familial hyper triglyceridemia – on 3 drugs prior • Triglycerides at 35 • Lab techs could recognize his blood by the tube • Asked if could remove it • Advised not sure if clinically relevant to decrease it but nothing to lose so tried • FFP cooled him so came down on pressers briefly • Died with triglyceride of 5 and effluent cleared • Probably not of utility in acute illness according to metabolic specialist later spoke with in spite of UTD suggestion – case report / publication bias

Questions?