Short didactic presentation given for project ECHO, University of New Mexico

1. Dialysis In Diabetes
Christos Argyropoulos MD, PhD, FASN
Nephrology Division, University of New Mexico
1

2. Financial Disclosures
Research funding from Dialysis Clinic Inc, a non-profit
dialysis services provider
Medical Directorship fees for Dialysis Clinic, Inc
2

3. Learning Objectives
1. alterations in glucose homeostasis conferred by the
uremic milieu
2. limitations of diagnostic tools used to evaluate glycemic
control in dialysis patients
3. glycemic targets and outcomes in the dialysis population
4. safety and effectiveness of various diabetic
pharmacotherapy regimens in diabetic dialysis patients.
3

4. Fast Facts
Diabetes is the leading cause of End Stage Renal Disease,
accounting 44% of new cases per year
Patients with diabetes on hemodialysis have the worst
survival (34% at five years)
4
US1
population
No Diabetes Diabetes
No CKD 7.7% 11.5%
CKD 17.2 31.1%
0 10 20 30 40 50 60
405060708090100
Dialysis Mortality
Time (months)
%Surviving
GN
DM

5.  Renal threshold for glucose is
180–200 mg/dL.
 Patients with renal disease and
without diabetes may develop
impaired glucose tolerance
due to higher resistance and
decreased insulin secretion
 Conversely, 1/3 of patients
with diabetes on dialysis will
have A1c < 6.0% (“burnt-out
diabetes” phenomenon)
Effects of Kidney Dysfunction and Dialysis on
Sugar Metabolism I
Semin Dial. 2014 Mar; 27(2): 135–145.
doi: 10.1111/sdi.12198

6.  Risk for hypoglycemia is higher with CKD & ESRD:
 insulin is cleared from the kidneys
 Hepatic clearance of insulin is decreased in renal disease
 20% of gluconeogenesis occurs in the kidney
 Protein-energy malnutrition
 Accumulation of guanidine compounds as natural products of
protein metabolism that act similar to biguanides
 Risk for hypoglycemia higher in the first 24 hours after
dialysis
 Improved insulin sensitivity
 Patient’s skipping meals due to dialysis (dialysis units do not
let patients eat during treatment)
 Pharmacokinetic interactions between sulfunylureas and
antibiotics
Effects of Kidney Dysfunction and Dialysis on
Sugar Metabolism II

7. Metrics of glycemic control in ESRD
Guidelines KDIGO:
A1c+home-self
monitoring

8.  There are NO randomized controlled
trials in this population
 First observational study about this
question conducted by UNM
investigators 25 years ago
− Outcomes worse when A1c>10%
 The largest study to date have found
no association between A1c and
outcomes
 Many studies find U shaped curves,
with mortality worse when A1c<6% or
>8%
 Existing guidelines:
− Let A1c rise to >7%
− Many nephrologists will tolerate 7-9%
What is the target for glycemic control in
ESRD?
Ricks et al., Diabetes 61(30):
708–715, 2012).

9.  Glyburide
 Metformin (US label
SCr>1.4-1.5 ex-US
eGFR>30)
 Alpha-glucosidase inhibitors
 Exenatide
 Glimepiride
 Sitagliptin
 Repaglinide
 Insulin (dose decrease)
 Glipizide
 Pioglitazone
− Fluid retention
 Nateglinide
 Pramlintide
 Canaglifozin/empaglifozin
(eGFR>45)
 Dapaglifozin (eGFR>60)
Diabetes medications may be
discontinued or adjusted in CKD
Reference: Reilly & Berns Seminars in Dialysis 2010; 23(2):163–168.
Farxiga/Invokana/Jardiance PIL

10.  Dose: To prevent hypoglycemia, insulin may have to be
reduced by 50% when the eGFR<10 (many patients are
firmly on their way to dialysis by then)
 Timing: a single study suggests lowering basal insulin by
25% on the day after dialysis to provent hypoglycemia
 Titration: In insulin-naïve dialysis patients start at 10-
12 units
 Many nephrologists consider insulin based regimens the
treatment of choice for patients with DM and ESRD
Treatment of Diabetes in Dialysis: Insulin
Nephrol Dial Transplant (2016) 31 (1): 8-15. DOI: https://doi.org/10.1093/ndt/gfv258

11.  Sulfonylureas: glipizide is the agent of choice
 Meglitinides:
− repaglinide is >90% metabolized by the liver
− Start at 0.5 mg po tid with meals
− May be used as monotherapy in ESRD
 Biguanides (metformin): no-no
 Thiazolidinedione (pioglitazone):
− Overall low risk of hypoglycemia
− As monotherapy may reduce A1c by 0.5-1% in ESRD
− Pioglitazone may be associated with impr survival
Treatment of Diabetes in Dialysis: Non-
insulin agents I

12.  DPP4:
− Lina(gliptin) is the only one that is cleared by the liver (no dose
adjustment): 5 mg po daily
− Sita: 25mg/day (irrespective of timing of dialysis)
 Similar efficacy to glipizide with less severe hypoglycemia in a double
blind, RCT
− Saxa 2.5 mg/day (give after dialysis – removes 25%)
− Alo: 6.25 mg/day
 GLP-1 (exenatide, liraglutide): not recommended in patients on
dialysis
 Alpha-glucosidase inhibitors: not recommended in patients
on dialysis
 Amylin analog (pramalintide): renal clearance – not
recommended
 SGLT2 inhibitors: cannot be used
Treatment of Diabetes in Dialysis: Non-
insulin agents II
Am J Kidney Dis. 2013 Apr;61(4):579-87. doi: 10.1053/j.ajkd.2012.11.043

13.  PD is a home base therapy that uses glucose containing
solutions instilled in the abdominal cavity to remove fluid
 These patients will receive an additional 600 calories per day
from the glucose in their PD fluid
 Non-glucose solutions may be used (icodextrin):
− Metabolized to maltose and maltriose which gives false high
readings on glucometers that use the pyrroloquinoline-quinone
reaction (e.g. Accu-Chek Go/Go or Accu-Chek Integra)
− If patients are on icodextrin, have to use a glucometer based on
the glucose oxidase reaction. List of compatible glucometers:
− http://www.glucosesafety.com/us/pdf/Glucose%20monitor%20list
%20US.pdf
Unique issues in patients receiving
Peritoneal Dialysis

14.  Patients with ESRD have high cardiovascular risk
 Studies on statins have been largely un-impressive
 Existing guidelines derived on the atorvastatin RCTs 4D,
AURORA (trials in the dialysis populations) and the
subgroup of SHARP (simvastatin+ezetimibe):
− Recommend avoiding initiation of these agents but
− There is no recommendation to stop them if the patients
are already receiving them
Statinization for cardiovascular risk
modification

15. Treatment of hypoglycemia: Any “juice” can
treat hypoglycemia, even those low in
potassium
mg