Biological ageing and kidney transplantation

The aim of this thesis was to investigate the impact of biological ageing in patients with chronic kidney disease, the effect of kidney transplantation on biological ageing and longterm outcome in patients with kidney failure. We used the national Swedish renal registry (SNR), ScandiaTransplant´s database YASWA, patient records and different methods to analyze biological ageing and circulatory microbiota to address this aim.

In study I we included a national cohort of elderly kidney transplant recipients to investigate which preoperative risk factors are associated with 1, 5 and 10-year patient and graft survival. Kidney transplantation in the elderly is becoming more common worldwide, but a global standardized preoperative evaluation does not yet exist. All patients >60 years of age (n=747) which were transplanted in Sweden between 1st of Jan 2000 and 31st of Dec 2012 were included, retrospectively. We found that 5-year patient survival was not inferior in patients ≥70 years compared to patients 65-69 years and furthermore that Charlson comorbidity index (CCI) ≥ 7 was associated with a 4.6 times higher risk of death after 10 years compared to CCI<4 (chronological age excluded). The mortality risk was lower in patients with living donors and in female recipients.

In study II we studied vascular ageing, measured as coronary artery calcification and medial calcification in arteria epigastrica as predictor of all-cause mortality and cardiovascular events (CVE) in 342 patients with kidney failure. Median follow up time was 6.4 years. Medial calcification was as good predictor as coronary artery calcification, for CVE and mortality. By dividing patients in groups of low or high grade of medial calcification we found significant differences in risk of CVE (5 % vs 28%) and death (1.6% vs 14.9%), 6.4 years after KT.

In study III biological age was measured with skin autofluorescence, epigenetic clocks and Phenoage in three groups: patients with kidney failure receiving a LDKT, patients remaining in dialysis, and a population-based control group. We found signs of accelerated biological ageing in patients with kidney failure compared to the control group. This acceleration continued in patients remaining on dialysis but was mitigated in the patients receiving a KT corroborating the hypothesis of accelerated ageing in patients with kidney failure.

In study IV we investigated the circulatory microbiome in patients with CKD stage 3-4, incident dialysis patients and in LDKT recipients. Gut dysbiosis seems to be more pronounced in incident dialysis patients than in patients with CKD stage 3-4 and LDKT recipients. Kidney transplantation did not restore circulatory microbiome, and the core microbiome remained essentially the same, one year after KT.

List of scientific papers

I. Erlandsson H, Qureshi AR, Scholz T, Lundgren T, Bruchfeld A, Stenvinkel P, Wennberg L, Lindnér P. Observational study of risk factors associated with clinical outcome among elderly kidney transplant recipients in Sweden - a decade of follow-up. Transpl Int. 2021 Nov;34(11):2363-2370.
https://doi.org/10.1111/tri.14004

II. Erlandsson H, Qureshi AR, Ripsweden J, Haugen Löfman I, Söderberg M, Wennberg L, Lundgren T, Bruchfeld A, Brismar TB, Stenvinkel P. Scoring of medial arterial calcification predicts cardiovascular events and mortality after kidney transplantation. J Intern Med. 2022 Feb 2.
https://doi.org/10.1111/joim.13459

III. Ognian Neytchev# and Helen Erlandsson#, Anna Witasp, Louise Nordfors, Abdul Rashid Qureshi, Ken Iseri, Hokuto Morohoshi, Colin Selman, Thomas Ebert, Karolina Kublickiene, Peter Stenvinkel, Paul G. Shiels. Accelerated uremic ageing is mitigated after kidney transplantation, but not dialysis. #Shared first authorship. [Submitted]

IV. Hannah Craven# and Helen Erlandsson#, Dagmara McGuinness, David McGuinness, Abdul Rashid Qureshi, Denise Mafra, Umer Z. Iljaz, Peter Bergman, Peter Barany, Paul G Shiels, Peter Stenvinkel. A circulatory footprint of the core microbiome does not normalize after kidney transplantation. #Shared first authorship. [Manuscript]