1. Glucose Intolerance in Potential Kidney Donors
Fasika M. Tedla, MD, MSc
Associate Professor of Clinical Medicine
Medical Director of Kidney Transplanation
SUNY Downstate Medical Center
11th Annual International Conference on
Nephrology and Hypertension
January 19, 2018

2. Case Presentation
29-year-old potential donor to his 63-year-old diabetic mother
Both parents have DM
BMI=26
OGTT: fasting=91, 2hr=135
HgbA1c=5.6
eGFR=144ml/min
24hr protein excretion = 51mg

3. Clinical Question
Is the risk-benefit ratio of him donating a kidney to his mother favorable?
Does he have normal glucose metabolism?
What is his risk of developing diabetes?
What is his risk of developing renal failure without donation?
Will donation accelerate his progression to renal failure?
What is the impact of transplantation on his mother’s survival?

4. Diabetes - Magnitude 422 million worldwide in 2014 Prevalence in US
~ ¼ (24%) undiagnosed
34% (84.1 million) adults - prediabetes
High prevalence in Black and Mexican Americans
~ 114 million American adults– diabetes or prediabetes

5. Diabetes and ESRD
USRDS ADR

6. ADA Criteria Fasting Glucose (mg/dL) 2-hour OGTT (mg/dL)
Random blood glucose
Normal
<100
<140
Impaired
100 –125 DM
≥126
≥200
≥200 + symptoms
HgbA1c
(%)
<5.7
≥6.5
ADA. Diabetes Care. 2011;34 Suppl 1:S11-61

7. ADA criteria - basis
Diabetes Care 25(Suppl 1): S5–S20, 2002

8. ADA criteria - basis
McCance et al. BMJ 1994;308:1323-8

9. Glucose Homeostasis Glu Production intake Glu Disposal
Hepatic resistance
Peripheral resistance
Curry et al. Endocrinology :572.

10. Diabetes: Insulin Secretion vs. Sensitvity
Rare Syndromes
Type I Diabetes
Type II Diabetes
Insulin sensitivity
Insulin Secretion

11. Oral Glucose Tolerance Test
Nathan et al. Diabetes Care (3):753-9.

12. The Road To Type II Diabetes
2593 aged 45-64
10yr follow up
DM from National health service registry
2h OGTT HR
<92 1
92-110
2.2
4.4
17.3
Qiao et al. Diabetic Medicine.2003:20 (12); 

13. The Road To Type II Diabetes
Knowler et al. N Engl J Med (6):

14. The Road To Type II Diabetes
Lancet Diabetes Endocrinol Nov;3(11):866-75

15. The Road To Type II Diabetes
50-81
82-86
87-90
90-94
95-99
Incidence for Q1 = ~ 1/700 person-years; mean follow up 5.7 years
Tirosh et al. N Engl J Med (14):

16. The Road To Type II Diabetes
Tirosh et al. N Engl J Med (14):

17. The Road To Type II Diabetes
Tirosh et al. N Engl J Med (14):

18. The Road To Type II Diabetes
Nichols et al. Am J Med Jun;121(6):

19. The Road To Type II Diabetes
Martin et al. Lancet. 1992; 340:

20. Clinical Question
Is the risk-benefit ratio of kidney donation to his mother favorable?
Does he have normal glucose tolerance?
What is his risk of developing diabetes?
What is his risk of developing renal failure without donation?
Will donation accelerate his progression to renal failure?
What is the impact of transplantation on his mother’s survival?

21. Risk of Nephropathy in DM
Ritz E, Orth SR. N Engl J Med. 1999; 341:

22. Risk of Nephropathy in DM
Ritz E, Orth SR. New Engl J Med. 1999; 341:

23. Impact of Family History
No diabetic nephropathy
11 probands, mean duration = 26yrs
12 siblings,mean duration = 18yrs
Diabetic nephropathy
26 probands, mean duration = 23 yrs
29 siblings, mean duration=22 yrs
Rate of nephropathy in sibs
17% with DN- Vs. 83% with DN+ probands
No Δ in duration of DM, BP, HgbA1C
Seaquist et al. N Engl J Med. 1989; 320: 1161–1165

24. Clinical Question
Is the risk-benefit ratio of kidney donation to his mother favorable?
Does he have normal glucose tolerance?
What is his risk of developing diabetes?
What is his risk of developing renal failure without donation?
Will donation accelerate his progression to renal failure?
What is the impact of transplantation on his mother’s survival?

25. Risk of Kidney Disease in Donors
Norwegian donors vs controls:1 HR for ESRD 11.4
Longer duration of follow up for donors (44 vs 26 yrs)
All donors with ESRD related to recipients and most had immunologic kidney disease
Low event rates: 9 donor ESRD, 31 total
OPTN Vs. NHANES2
96,217 donors ( ) vs 9364 NHANES III ( )
Matched with replacement
Adjusted cumulative incidence of ESRD at 15 yrs: 30.8 vs 3.9 per 10000
Underestimate of risk in non-donors
Non-donors: longer follow up and low event rates, repeatedly sampled
Competing risk : non-donors more likely to die than develop ESRD
Ascertainment bias: non-donors with advanced CKD may not be on wait list
Mjoen et al. Kidney Int. 2014;86(1):162-7.
Muzaale et al. JAMA. 2014; 311(6):

26. Identifying High-Risk Potential Donors
Estimates 15-year and lifetime risk of ESRD
Based on 7 cohorts (US [5], Candada [1], Israel [1]), median follow up 4-16 years but most 6-8 range)
Commonly recognized predictors – (Age, gender, race, systolic BP, BMI, smoking, eGFR, ACR, DM, BP medication)
98% US donors had predicted 15-year incidence of < 2%
Utility? e.g. family history of kidney disease, relevance to lifetime risk
Grams et al. N Engl J Med. 2016;374(5):

27. Non-linear Risk After Donation
Incidence of ESRD after donation increases with time1
10/10,000 at 10 years
85/10,000 at 25 years
GN-related ESRD appears earlier; diabetic and HTN ESRD later
Aggregation of risk factors may accelerate loss of renal function in donors2
HTN, DM, proteinuria
Family history increases risk of HTN and DM after donation3
Young age at donation a risk for black but not white donors4
Anjum et al. Am J Transplant Dec;16(12):
Ibrahim et al. J Transplant Dec;17(12):
Lentine et al. Transplantation Jun 15;91(11):
Wainright et al. Am J Transplant May;18(5):

28. Diabetic Nephropathy After Donation
No human study comparing impact of diabetes on donors and two-kidney controls
Donor with vs without post donation DM
Difference in rate of decline of GFR with aggregation of risk factors1
HTN, DM, proteinuria
Likely confounded by
Difference in underlying renal disease
Hyperfiltration in early DN
Ibrahim et al. J Transplant Dec;17(12):

29. Diabetic Nephropathy After Donation
Zheng et al. Nephron Exp Nephrol. 2011;119(1):e21-32.

30. Diabetic Nephropathy After Donation
Zheng et al. Nephron Exp Nephrol. 2011;119(1):e21-32.

31. Clinical Question
Is the risk-benefit ratio of kidney donation to his mother favorable?
Does he have normal glucose tolerance?
What is his risk of developing diabetes?
What is his risk of developing renal failure without donation?
Will donation accelerate his progression to renal failure?
What is the impact of transplantation on his mother’s survival?

32. Gain in Survival After Transplantation
Wolfe et al. New Engl J Med. 1999; 341(23):

33. Gain in Survival After Transplantation
Age
Gain in years
All 10
0 –19 13
20 – 39 17
40 – 59 11
60 – 64
4.3
65 – 69
2.8
70 – 74 1
Wolfe et al. N Engl J Med. 1999;341(23):

34. Clinical Question
Is the risk-benefit ratio of kidney donation to his mother favorable?
Does he have normal glucose metabolism?
What is his risk of developing diabetes?
What is his risk of developing renal failure without donation?
Will donation accelerate his progression to renal failure?
What is the impact of transplantation on his mother’s survival?

35. Conclusion OGTT results - interpret within context
History of diabetes in first-degree relatives
History of diabetic ESRD in first-degree relatives
Abnormalities of glucose metabolism - continuum
Kidney donation – risk low in short to intermediate time range. Current data likely underestimate longterm risk
Donor evaluation – focus on informing individualized risk and uncertainties rather than declaring safety of donation
Risk of kidney donation in those at risk for diabetes – likely higher
Caution in the young
Recipient prognosis?