1. Renal disease progression in patients with TTR amyloidosis
Nikolay Bogush, MD, Rajiv Mundayat, MS, Moh-Lim Ong, MD, Shawn Robinson, MD, Stephen S. Gottlieb MD
University of Maryland, Baltimore, MD USA

2. Background
Kidney amyloid deposits are well documented in TTR amyloidosis
Most of what is known about TTR renal disease is from small observational studies (less then 75 patients)
These studies looked at patients with neurological or gastrointestinal symptoms
No studies looked at patients with predominantly cardiac disease
Hemodynamic effects of cardiac amyloidosis could impact renal function

3. Background (cont.)
The incidence of renal disease has been reported as 13–50% in these patients
The first manifestation of renal dysfunction is microalbuminuria
Among patients with proteinuria, 18.8% progressed to ESRD within 5 years
In a Portuguese cohort of 403 patients, approximately 1/3 had proteinuria, with 10% progressing to ESRD

4. Importance of understanding the renal impact of TTR
Poor renal function is associated with high morbidity and mortality in patients with heart disease
Better understanding of the incidence and progression of patients with amyloid kidney disease may improve treatment

5. Aims Identify the incidence of renal disease in TTR amyloid patients
Determine if patients with cardiac phenotype are more prone to renal impairment compared to patients with neurologic phenotype
Evaluate the rate of progression of renal disease in TTR amyloidosis
Identify the incidence of proteinuria in these patients

6. Methods Data obtained from THAOS database
Patients selected if the following were recorded:
Age
BMI
Serum Cr at baseline and 1-year follow up
728 patients fulfilled the criteria and were included in the study
What variables are reported on a sleep study report, and what do they mean?
The key metric used to stratify OSA severity is the apnea–hypopnea index (AHI), defined as the number of episodes of apnea (cessation of airflow for at least 10 seconds) and hypopnea (airflow reduction for at least 10 seconds accompanied by either a 3% or 4% oxyhemoglobin desaturation or arousal from sleep) per hour of sleep. Of note, varying definitions of hypopnea (e.g., 3% vs. 4% desaturation) can lead to markedly different AHI calculations and can limit comparisons of polysomnography reports from different sleep laboratories. The AHI based on a 4% desaturation criteria for hypopnea has been more closely associated with cardiovascular risk (28) and is the metric preferred by the Centers for Medicare & Medicaid Services. However, this definition is more restrictive and may preclude the diagnosis among some patients with classic symptoms, but without significant oxyhemoglobin desaturations, who would benefit from therapy. Regardless of the hypopnea definition, OSA is defined as an AHI ≥ 5 events/h. Mild OSA is defined as an AHI ≥ 5 and < 15, moderate OSA as an AHI ≥ 15 and < 30, and severe OSA as an AHI ≥ 30. Sleep studies also collect other data that can provide important information about a patient’s sleep. Variables typically reported include but are not limited to total sleep time (or total recording time for home sleep tests), measures of sleep quality (sleep efficiency, wake time after sleep onset, quantity of sleep stages, and degree of overall sleep fragmentation), other measures of sleep-disordered breathing (number of central vs. obstructive respiratory events, frequency of oxyhemoglobin desaturation events, time spent with an oxyhemoglobin saturation < 90%, nadir oxyhemoglobin saturation), assessment of any EEG epileptiform activity, nocturnal arrhythmia, limb movements, and video/audio recording of sleep-related behaviors.

7. Methods (cont.) Patients divided into cardiac or neurologic phenotype
Cardiac: Rhythm disturbance or heart failure without neurological or GI symptoms
Neurologic: Walking disability of any severity, GI symptoms or other neurologic symptoms
Mixed: A combination of symptoms
Kidney disease: Consistent elevation of creatinine above the upper limit of normal at the institution
Proteinuria: Protein/creatinine value > 45 mg/mmol or albumin/creatinine value > 30 mg/mmol

8. Patients included 94 Cardiac THAOS database 728 patients identified
495 Neurogenic
139 Mixed

9. Patient characteristics
All
Cardiac
Neuro
Mixed
Age, years N
728 94
495
139
Mean ± SD
48 ± 17
67 ± 14
42 ± 13
57 ± 16
Median 43 71 37 59
Sex, n (%)
Male
397 (55)
82 (87)
234 (47)
81 (58)
Female
331 (45)
12 (13)
261 (53)
58 (42)

10. Presence of hypertension
Cardiac phenotype
Neurologic phenotype

11. Presence of diabetes mellitus
Cardiac phenotype
Neurologic phenotype

12. Echo characteristics Characteristic All Cardiac Neuro
LV septum thickness N
127 54 73
Mean ± SD (median)
13.9 ± 4.6 (13)
17.9 ± 3.4 (18)
10.9 ± 2.7 (10)
RV free wall thickness 44 8 36
6.9 ± 4.8 (6.2)
8.2 ± 1.6 (8.5)
6.6 ± 5.2 (6)
LV systolic diameter
121 53 68
29.2 ± 5.7 (29)
31.8 ± 5.9 (32)
27.1 ± 4.7 (27)
LV diastolic diameter
128 57 71
43.9 ± 5.6 (440
43.7 ± 5.7 (44)
44.0 ± 5.6 (44)

13. Presence of proteinuria
Cardiac phenotype
Neurologic phenotype

14. Laboratory values Characteristic All Cardiac Neuro Mixed Estimated GFR
Mean ± SD
100 ± 40
68 ± 32
111± 36
78 ± 36
Median
100 62
108 73
Creatinine
0.94 ± 0.66
1.30 ± 0.48
0.80 ± 0.50
1.17 ± 1.0
0.81
1.2
0.76
0.92

15. Median age, GFR and presence of diabetes mellitus

16. Summary of ANCOVA: Baseline eGFR
Cardiac (n = 94)
Neurologic (n = 495)
Cardiac vs. Neurologic P
LS Means (SE)
98.79 (4.94)
(3.07)
–6.64 (5.82)
0.15
95% CI*
89.07,
99.39,
–15.75, 2.47
Based on ANCOVA with age, gender, diabetes mellitus and hypertension at enrollment as covariates

17. Change in renal function
Cardiac
Neurologic
Mixed
Pre
Post
GFR 68 65
111
110 78 75
ΔGFR
–3.1
–2.1
–3.2
Creatinine
1.30
1.33
0.80
0.83
1.17
1.16
ΔCreatinine
+0.03
–0.01

18. Summary of ANCOVA: Change from baseline to Year 1 in eGFR
Cardiac (n = 94)
Neurologic (n = 495)
Cardiac vs. Neurologic P
LS Mean (SE)
–7.49 (2.93)
–5.22 (1.82)
–2.27 (3.45)
0.41
95% CI*
–13.24, –1.74
–8.78, –1.65
–7.67, 3.12
Based on ANCOVA with age, gender, diabetes mellitus and hypertension at enrollment as covariates

19. Summary
Patients with cardiac phenotype are older than patients with neurologic phenotype and have a higher prevalence of diabetes
Cardiac phenotype patients had a higher baseline creatinine and a lower GFR
The incidence of proteinuria was higher in neurogenic phenotype

20. Summary (cont.)
When adjusted for age, gender, diabetes and hypertension, no significant difference in GFR between the cardiac and neurogenic phenotype was found
No significant difference was seen in the change in GFR or creatinine between the groups at 1-year follow up

21. Conclusions
TTR cardiac amyloidosis does not appear to increase renal disease or changes in creatinine or GFR at 1-year follow up
Lower GFR in cardiac TTR amyloidosis is probably due to comorbidities (HTN, DM and older age)
Renal function might be differentially impacted in cardiac and neurologic amyloidosis