Live Kidney Donation: What’s the risk?

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As ESRD prevalence continues to increase, the kidney transplant
list continues to grow meaning longer waiting times for deceased donor
transplantation. Living donation (LD) provides the best outcomes for patients
with ESRD and is considered safe for the donor when they are screened effectively.
However, although we have data demonstrating low morbidity and mortality
associated with living donor nephrectomy,
our longer term data has traditionally been flawed. This is primarily because previous
studies examining the long-term risk associated with LD has used the general unscreened
population as comparators. Individuals who are accepted as living donors have
passed rigorous screening and are therefore a well group, likely more so than matched general population controls. A study from Norway included controls matched
for age, race and year of birth and showed overall and cardiovascular mortality
was lower for kidney donors. A US study employed NHANES controls who were matched for age, sex, BMI and race
and reported equivalent risk of ESRD and patient survival.
Therefore, our counselling of potential donors was limited to comparisons to
the general population where we could point to no increased renal or patient survival
risk but we had little data on actual risk of similarly matched controls who
did not donate. In recent months we have 2 new studies which give us more accurate
data.
The first study was published in KI and included over
1900 kidney donors from Norway between 1963 and 2007. Crucially, the control group comprised individuals deemed eligible
for donation (n>32,000). Eligibility was determined from a population cohort
with BP<140/90 mm Hg (on no anti-hypertensives), BMI<30 kg/m2 who rated their health as ‘good’ or ‘excellent’.
Individuals were excluded if they had diabetes or cardiovascular disease. Note
that the authors had no data on renal function or albuminuria for the
controls. The results demonstrated that donors had a significantly increased
long-term risk for ESRD (hazard ratio 11.38!), cardiovascular mortality (HR 1.40)
and all-cause mortality (HR 1.30). Of note, 1519 of the donors were
first-degree relatives, all cases of ESRD occurred in living related donors and
the etiology was immunological in nature, reflecting a likely genetic component
to the renal disease in the donors.
Another study recently reported in JAMA from the
US included a cohort of >96,000 kidney donors between 1994 & 2011, >20,000 matched
controls from NHANES III and examined ESRD risk alone. Controls were gathered by excluding those with identified
contraindications to kidney donation (9364 qualified as eligible). They
were matched by age, sex, race, educational background, BMI, BP and smoking
history. Over a median follow up of 7.6 years, the donors had an increased risk
of ESRD. Specifically, the risk of ESRD was 30.8/10,000 in donors
V 3.9/10,000 in the matched non-donor controls (P <0.001). The risk
was particularly high in black individuals (risk of 74.7/10,000 in donors V
23.9/10,000 in non-donors). Interestingly, white donors (22.7/10,000) had a
similar risk of ESRD to the black non-donors with white non-donors having extremely
low risk of ESRD in this cohort (0.0/10,000; p<0.001 V white donors). The
lifetime risk of ESRD in donors was still significantly lower than unscreened non-donors
(i.e. general population) at 90/10,000 V 326/10,000 (see figure).
These studies reaffirm our belief that lifetime risk
of ESRD in LD is no higher than in the general demographically-matched
population. However the new data suggest that ESRD risk is unsurprisingly
higher than healthy screened controls, deemed eligible for donation but who
have not donated. The ESRD risk for donation appears to be particularly increased
for African Americans, likely due to genetic factors such as presence of APOL1 risk variants. However, the overall magnitude of the risk is small and I think
the findings are reassuring. The mortality data from the Norwegian study is not
particularly surprising given the robust association between reduced kidney
function and mortality in the general population. These studies still have
limitations including data ascertainment differences between donors and
controls. Also, the control groups may not be perfect but do represent an improvement
over previous studies using the unscreened general population. We are now is a
position to counsel our living donors with more accuracy regarding the risks of
living donation. In my experience, most living donors are happy to accept a
small future risk of adverse outcome to donate to a loved one.

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