Treating hypertension in kidney transplant recipients

Treating hypertension in kidney transplant recipients Mark Mitsnefes, MD, MS Professor of Pediatrics Director, Clinical Translational Research Center Cincinnati Children s Hospital Medical Center University of Cincinnati Valencia, February 10, 2018

What do we KNOW WELL about hypertension in pediatric kidney transplant recipients?

Hypertension is common NAPRTCS 2003 NAPRTCS 2014 Use of antihypertensive medications

BP control following kidney transplant is not optimal All current UK kidney transplant recipients (n=428) Data collected at 6 months, 1, 2 and 5 years post transplant 25-27% had BP >95 th percentile 48-60% were using antihypertensives 30-35% had BP >95 th percentile Sinha et al, NDT 2012

Hypertension and uht were more prevalent in young adult KTRs (86.4 and 75.8%) than in paediatric KTRs (62.7 and 38.3%) according to the KDIGO definition. Dobrowolski et al, NDT 2016 HTN I: BP <90 th % or >130/80 (>18y) - KDIGO HTN II: BP >95 th % or >140/90 (>18y) - 4 th report and WHO

Ambulatory HTN is common % 90 Prevalence of ambulatory HTN 80 70 60 50 40 30 22-83% 20 10 0 Lingens 1997 Mateucci 1999 Morgan 2001 Seeman 2004 Ferraris 2007 Basiratnia 2010 Paripovic 2011 Cameron 2014 Hamdani 2017

What else do we know? Hypertension is associated with LVH >10 studies over last decade Controlled BP improves LVH* Hypertension is associated with cimt >10 studies over last decade Controlled BP improves cimt* Hypertension is associated with: Allograft dysfunction Allograft failure # *Krmar s group (Ped. Transplant 2008, 2011; AJH 2014) *Litwin et al (NDT 2008) # Mitsnefes et al (J. Peds 2003); Hamdani et al (Ped. Transplant 2017)

Mean BP <95 th percentile or Mean BP >95 th percentile No difference in allograft function

There are many causes of HTN after kidney transplant Acute rejection Chronic rejection/glomerulopathy Graft artery stenosis Native kidneys Obesity Sodium/water retention, Pick your poison Graft dysfunction (CKD) Immunosuppressive drugs corticosteroids, cyclosporine, tacrolimus

HTN post transplant: Conclusion #1 Very prevalent despite overall better transplant outcome Multifactorial causes Typically mild to moderate Frequently undertreated despite frequent follow up Monotherapy frequently ineffective; usually requires multiple drugs to control Associated with intermediate CV outcomes

Why is it so difficult to control BP post transplant? Provider? Disease? OR We care for complicated patients within a complex system that wasn t designed to address the difficult problems we encounter Courtesy of David Hooper

The knowledge of what to do in order to effectively assess and treat uncontrolled BP The knowledge of how to implement this care reliably, in the context of the complex system of clinical care Pediatr Nephrol 2016

Evidence for CCM in Managing Hypertension 2013: Jaffe et. al. Improved blood pressure control associated with a large-scale hypertension program. JAMA 310:699 705 (n=60,000) Achieved BP control in 80% of patients (baseline 43%) in 9 years 2013: Margolis et al. JAMA 310:46 56 (n=450) Achieved BP control in 71% of subjects (57% control group)

How to apply CCM to manage kidney transplant recipient?

System to Improve BP Control Aim BP Control for Kidney Transplant Recipients KEY DRIVERS Measurement and Classification Appropriate Therapy Assessment of Response Hypertension Causing Meds Effective Self- Management CARE MODEL SYSTEM SUPPORTS Registry to track care and outcomes Decision Support Planned care (previsit planning) Population Management Self-Management Support Hooper, Mitsnefes, Ped. Nephrol, 2015

Proper BP Measurement and Documentation Height Proper cuff size Manual BP (not oscillometric) Seated position Resting for 5 minutes Upper extremity Mean of two readings Recording Technique Auto calculated mean

Can systematic measurement of arm circumference lead to improvement in Process choosing correct BP cuff? Arm circumference Outcome Correct BP cuff

Missing Components Run Chart: LIB Missing BP components in Most Recent Quarter: Sep-Dec 2017 0 0 0 0 0 0 0 Mean of Two Readings Rested 5 min Arm Circumference Cuff Size Height BP Method 90% Cutoff

Physician BP classification Auto-calculated mean BP Auto-calculated percentiles RN entered 90 th percentile cut-off Auto-calculated 95 th percentile cut-off RN entered 99 th percentile + 5 cut-off Physician classifies BP using KDIGO targets * < 18 y.o.: <90 th %tile and 130/80 * 18 y.o.: <130/80

Ambulatory BP Monitoring Process Pt. performs test and returns monitor Staff extracts discrete data from monitor and enters into discrete fields in EHR (DocFlowsheets) Output: Letter automated from discrete fields. Data readily available for analysis. MD interprets discrete data, enters diagnosis/interpretation into discrete fields in EHR (DocFlowsheets)

Outputs ABPM DocFlowsheet ABPM letter in EPIC

Patient has at least one ABPM in last 13 months regardless of its results

System to Improve BP Control ABPM? Aim BP Control for Kidney Transplant Recipients KEY DRIVERS Measurement and Classification Appropriate Therapy Assessment of Response Hypertension Causing Meds Effective Self- Management CARE MODEL SYSTEM SUPPORTS Registry to track care and outcomes Decision Support Planned care (previsit planning) Population Management Self-Management Support Hooper, Mitsnefes, Peds Neph, 2015

221 children with kidney transplant from 6 centers BP was classified according to 2014 AHA Normal office and mean ABP, But BP load > 25% Transplantation, 2017

Simplified groups (4 categories) Classification based on 24-hour BP load 25% 23% 63% European guidelines Classification based on 24-hour mean BP > 95 th % 32% 51% AMBULATORY HYPERTENSION 11% CKiD suggestion MASKED HYPERTENSION 13% WCH 3% 13% 73% NORMAL BP 73% No consensus

System to Improve BP Control Aim BP Control for Kidney Transplant Recipients KEY DRIVERS Measurement and Classification Appropriate Therapy Assessment of Response Hypertension Causing Meds Effective Self- Management CARE MODEL SYSTEM SUPPORTS Registry to track care and outcomes Decision Support Planned care (previsit planning) Population Management Self-Management Support Hooper, Mitsnefes, Peds Neph, 2015

Appropriate therapy 2009 <90 th percentile or 130/80 Any class ACEI/ARB if proteinuric

Appropriate therapy 2012

CCB, ACEI, others? FAVORIT: Retrospective CCB vs. not N=4110 (1436) on CCB Chlorthalidone vs amlodipine A single-center, prospective, randomized, crossover, open-label, non-inferiority study; n=41 each group ABPM: baseline and at 8 weeks No difference in BP control No difference in survival Chlorthalidone Reduced proteinuria and edema Temporarily allograft function and serum Uric acid and Hg A1C Weinrauch et al, Int J Nep and Renovasc Dis 2018 Moes et al, AJKD 2017

8 trials 2001-2015 (n=1,502) Conclusion No advantage No disadvantage Death Graft failure Doubling creatinine Use on a case-by-case basis Hiremath et al, AJKD 2016

System to Improve BP Control Aim BP Control for Kidney Transplant Recipients KEY DRIVERS Measurement and Classification Appropriate Therapy Assessment of Response Hypertension Causing Meds Effective Self- Management CARE MODEL SYSTEM SUPPORTS Registry to track care and outcomes Decision Support Planned care (previsit planning) Population Management Self-Management Support Hooper, Mitsnefes, Peds Neph, 2015

Therapy Escalation and Follow-up Escalate therapy according to protocol Follow up BP in 2-4 weeks (at home or in clinic)

System to Improve BP Control Aim BP Control for Kidney Transplant Recipients KEY DRIVERS Measurement and Classification Appropriate Therapy Assessment of Response Hypertension Causing Meds Effective Self- Management CARE MODEL SYSTEM SUPPORTS Registry to track care and outcomes Steroid Adherence avoidance Steroid Diet minimization CNI Decision trough monitoring Support Physical activity Smoking Planned care (previsit Alcohol planning) Sex Population Management Self-Management Support Hooper and Mitsnefes, Peds Neph, 2015

Hooper, Mitsnefes, Peds Neph, 2015

How well are we doing by implementing systematic approach?

BP Control Run Chart Percent of patients with *Well-controlled Systolic and Diastolic BP Jan-2014 to Nov-2017 KDIGO targets * < 18 y.o.: <90 th %tile and 130/80 * 18 y.o.: <130/80 Completed on 12/14/2017 by F. Mostajabi. James M. Anderson Center for Health System

ABPM Control Run Chart >90% with NORMAL 24-hour MAP

> 80% with NORMAL nocturnal BP

Team work!