Publications
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Lindahl, Jørn Petter Hanto; Åsberg, Anders; Heldal, Kristian; Jenssen, Trond; Dörje, Christina & Skauby, Morten Heier
[Show all 7 contributors for this article]
(2024).
Long-term Outcomes After Kidney Transplantation From DBD Donors Aged 70 y and Older.
Transplantation direct.
10(7).
doi:
10.1097/TXD.0000000000001660.
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Background. Transplantation of kidneys from elderly donations after brain death (DBD) donors has increased owing to organ shortages. We aimed to assess the impact on long-term kidney transplant outcomes from DBD donors aged 70 y and older compared with kidneys from younger donors. Methods. From 2007 to 2022, 2274 first single kidney transplantations from DBD donors were performed at our center. Data from 1417 kidney transplant recipients receiving a DBD organ were included and categorized into 3 groups according to donor age: 70 y and older (n = 444, median age 74 y), 60–69 y (n = 527, median age 64 y), and a reference group consisting of donors aged 45–54 y (n = 446, median age 50 y). Kaplan-Meier plots and multivariate Cox regression with correction for recipient, donor, and transplant characteristics were used to investigate patient and kidney graft survival outcomes. Results. The median patient follow-up time was 9.3 y (interquartile range, 5.3–13.1). The adjusted hazard ratios for patient death in recipients of kidneys from DBD donors aged 70 y and older compared with 60–69 y and 45–54 y were 1.12 (95% confidence interval [CI], 0.92-1.36; P = 0.26) and 1.62 (95% CI, 1.26-2.07; P < 0.001), respectively. Compared with recipients of donors aged 60–69 y and 45–54 y, the adjusted hazard ratios for kidney graft loss in recipients of donors aged 70 y and older were 1.23 (95% CI, 1.02-1.48; P = 0.029) and 1.94 (95% CI, 1.54-2.45; P < 0.001), respectively. Conclusions. Transplantation of kidneys from DBD donors aged 70 y and older resulted in acceptable long-term outcomes and is encouraging.
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Kared, Hassen; Alirezaylavasani, Amin; Lund, Kathrine Persgård; Chopra, Adity; Tietze, Lisa & Kasahara, Taissa de Matos
[Show all 17 contributors for this article]
(2023).
Hybrid and SARS-CoV-2-vaccine immunity in kidney transplant recipients.
EBioMedicine.
97.
doi:
10.1016/j.ebiom.2023.104833.
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Background Kidney transplant recipients (KTR) are at high risk for severe COVID-19 and have demonstrated poor response to vaccination, making it unclear whether successive vaccinations offer immunity and protection. Methods We conducted a serologically guided interventional study where KTR patients that failed to seroconvert were revaccinated and also monitored seroconversion of KTR following the Norwegian vaccination program. We analysed IgG anti-RBD Spike responses from dose 2 (n = 432) up to after the 6th (n = 37) mRNA vaccine dose. The frequency and phenotype of Spike-specific T and B cell responses were assessed in the interventional cohort after 3–4 vaccine doses (n = 30). Additionally, we evaluated the Specific T and B cell response to breakthrough infection (n = 32), measured inflammatory cytokines and broadly cross-neutralizing antibodies, and defined the incidence of COVID-19-related hospitalizations and deaths. The Norwegian KTR cohort has a male dominance (2323 males, 1297 females), PBMC were collected from 114 male and 78 female donors. Findings After vaccine dose 3, most KTR developed Spike-specific T cell responses but had significantly reduced Spike-binding B cells and few memory cells. The B cell response included a cross-reactive subset that could bind Omicron VOC, which expanded after breakthrough infection (BTI) and gave rise to a memory IgG+ B cell response. After BTI, KTR had increased Spike-specific T cells, emergent non-Spike T and B cell responses, and a systemic inflammatory signature. Late seroconversion occurred after doses 5–6, but 38% (14/37) of KTR had no detectable immunity even after multiple vaccine doses. Interpretation Boosting vaccination can induce Spike-specific immunity that may expand in breakthrough infections highlighting the benefit of vaccination to protect this vulnerable population.
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Thorsen, Inga Strand; Bleskestad, Inger Hjørdis; Åsberg, Anders; Jonsson, Grete; Skadberg, Øyvind & Heldal, Kristian
[Show all 7 contributors for this article]
(2023).
Klotho and Fibroblast Growth Factor 23 Are Independent of Vitamin D, and Unlike Vitamin D, Are Not Associated With Graft- and Patient Survival After Kidney Transplantation.
Transplantation direct.
9(9).
doi:
10.1097/TXD.0000000000001522.
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Background: Short-term survival after kidney transplantation is excellent but long-term survival remains suboptimal. The aim of the study was to explore the relationship between soluble α-Klotho (sKlotho) and intact fibroblast growth factor 23 (iFGF23) measured 8 wk and 1 y posttransplant with long-term graft- and patient survival in a cohort of kidney transplant recipients with deficient and nondeficient vitamin D (25[OH]D) levels. Methods: Vitamin D, sKlotho, and iFGF23 were measured 8 wk and 1 y posttransplant in 132 recipients transplanted between November 2012 and October 2013. Results: Of the 132 kidney transplant recipients, 49 had deficient vitamin D levels (<30 nmol/L) and 83 had nondeficient vitamin D levels (≥30 nmol/L) at 8 wk posttransplant. The mean age was 51 y and the median follow-up was 7.4 y. At 1 y posttransplant, vitamin D increased significantly. There were no significant differences in sKlotho or iFGF23 levels between the 2 vitamin D groups neither at 8 wk nor 1 y. sKlotho increased significantly and iFGF23 decreased significantly in the whole cohort. During the follow-up, there were 36 graft losses (27%) and 27 deaths (20%). Ninety-four percent of the transplant recipients with nondeficient vitamin D levels were alive with a well-functioning graft after 5 y using Kaplan-Meier survival estimates, compared with 84% of the patients with deficient vitamin D levels (P = 0.014). Klotho and FGF23 levels did not influence graft- and patient survival. Conclusions: In this nationwide cohort of kidney transplant recipients, long-term graft- and patient survival were significantly better in patients with vitamin D ≥30 nmol/L 8 wk posttransplant compared with those with vitamin D <30 nmol/L. sKlotho levels increased and iFGF23 levels decreased from 8 wk to 1 y posttransplant. Klotho and FGF23 levels were not associated with graft- and patient survival.
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Heldal, Torbjørn Fossum; Åsberg, Anders; Ueland, Thor; Reisæter, Anna Varberg; Pischke, Soeren & Mollnes, Tom Eirik
[Show all 11 contributors for this article]
(2023).
Systemic inflammation early after kidney transplantation is associated with long-term graft loss: a cohort study.
Frontiers in Immunology.
14.
doi:
10.3389/fimmu.2023.1253991.
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Background: Early graft loss following kidney transplantation is mainly a result of acute rejection or surgical complications, while long-term kidney allograft loss is more complex. We examined the association between systemic inflammation early after kidney transplantation and long-term graft loss, as well as correlations between systemic inflammation scores and inflammatory findings in biopsies 6 weeks and 1 year after kidney transplantation.<p> <p>Methods: We measured 21 inflammatory biomarkers 10 weeks after transplantation in 699 patients who were transplanted between 2009 and 2012 at Oslo University Hospital, Rikshospitalet, Norway. Low-grade inflammation was assessed with predefined inflammation scores based on specific biomarkers: one overall inflammation score and five pathway-specific scores. Surveillance or indication biopsies were performed in all patients 6 weeks after transplantation. The scores were tested in Cox regression models.<p> <p>Results: Median follow-up time was 9.1 years (interquartile range 7.6-10.7 years). During the study period, there were 84 (12.2%) death-censored graft losses. The overall inflammation score was associated with long-term kidney graft loss both when assessed as a continuous variable (hazard ratio 1.03, 95% CI 1.01-1.06, P = 0.005) and as a categorical variable (4th quartile: hazard ratio 3.19, 95% CI 1.43-7.10, P = 0.005). In the pathway-specific analyses, fibrogenesis activity and vascular inflammation stood out. The vascular inflammation score was associated with inflammation in biopsies 6 weeks and 1 year after transplantation, while the fibrinogenesis score was associated with interstitial fibrosis and tubular atrophy.<p> <p>Conclusion: In conclusion, a systemic inflammatory environment early after kidney transplantation was associated with biopsy-confirmed kidney graft pathology and long-term kidney graft loss. The systemic vascular inflammation score correlated with inflammatory findings in biopsies 6 weeks and 1 year after transplantation.
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Bjune, Thea; Bøe, Thea Bjerkestrand; Kjellevold, Stig Arne; Heldal, Kristian & Abedini, Sadollah
(2023).
Hyperkalemia and the use of new potassium binders a singel center experience from Vestfold Norway (The PotBind Study).
International Journal of Nephrology and Renovascular Disease.
16,
p. 73–82.
doi:
10.2147/IJNRD.S401623.
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Purpose: Hyperkalemia is a common metabolic complication of chronic kidney disease (CKD) and is associated with several serious adverse events. We aimed to treat/prevent hyperkalemia using the new of potassium-binders, allowing maintained renin-angiotensin-aldosterone system inhibitors (RAASi) treatment in proteinuric CKD and/or congestive heart failure (CHF) patients.
Patients and Methods: We conducted a retrospective cohort study in long-term users of potassium binders for chronic hyperkalemia. Patients aged 18 years and older, treated with potassium-binders and who met the reimbursement criteria and indication for RAASi treatment were included.
Results: Fifty-seven percent of the patients were males and mean age was 65 years. During the study period, no patients were admitted to hospital due to hyperkalemia after initiation of potassium binders. Potassium maximum values were significantly lower after treatment. Few patients reported major side effects, and discontinuation was mostly due to normokalemia. We found no significant changes in bicarbonate, serum creatinine or GFR stage after starting potassium binder treatment. All patients on RAASi treatment before initiating potassium-binders were retained on RAASi treatment.
Conclusion: New potassium binders in clinical practice are an easy and safe treatment with few side effects and good tolerance, that significantly lowers the risk of hyperkalemia. Furthermore, and most importantly, patients can be maintained on RAASi treatment.
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Hovd, Markus Herberg; Åsberg, Anders; Munthe, Ludvig Andre; Heldal, Kristian; Reisæter, Anna Varberg & Vaage, John T.
[Show all 8 contributors for this article]
(2023).
Humoral vaccine response and breakthrough infections in kidney transplant recipients during the COVID-19 pandemic: a nationwide cohort study.
EClinicalMedicine.
60.
doi:
10.1016/j.eclinm.2023.102035.
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Background Kidney transplant recipients (KTRs) experienced reduced SARS-CoV-2 vaccine response and were at increased risk of severe COVID-19. It is unknown if level of vaccine induced anti-receptor binding domain IgG (anti-RBD IgG) correlates with protection from and survival following COVID-19. We aimed to evaluate the effect of vaccine response on risk of breakthrough infections (BTI) and COVID-19 death in KTRs. Methods We performed a nationwide study, examining the competing risk of SARS-CoV-2 infection, COVID-19 related/unrelated death, and vaccine efficacy as assessed by level of anti-RBD IgG response 4–10 weeks after each vaccination. The study included all KTR in Norway alive and with a functioning graft on February 20th, 2020, and events after November 11th, 2022 were right-censored. A pre-pandemic reference-cohort from January 1st 2019 to January 1st 2020 was included to evaluate excess mortality. The study was conducted at Oslo University Hospital, Rikshospitalet, Norway. Findings The study included 3607 KTRs (59 [48–70] years) with a functioning graft at February 20th, 2020, who received (median [IQR]) 4 [3–4] vaccines (range 2–6, 99% mRNA). Anti-RBD IgG was measured in 12 701 serum samples provided by 3213 KTRs. Vaccine response was assessed 41 [31–57] days after vaccination. A total of 1090 KTRs were infected with SARS-CoV-2, 1005 (92%) were BTI, and vaccine response did not protect against BTI. The hazard ratio for COVID-19 related death 40 days post-infection was 1.71 (95% CI: 1.14, 2.56) comparing vaccine response levels (≥5 vs. ≥5000 BAU/mL). No excess non-COVID-19 mortality was registered in KTRs surviving SARS-CoV-2 infection compared to a 2019 pre-pandemic reference. Interpretation Our findings suggested that SARS-CoV-2 mRNA vaccine response did not predict protection against infection, but prevention of fatal disease progression in KTRs and greater vaccine response further reduced the risk of COVID-19 death. No excess non-COVID-19 mortality was seen during the pandemic.
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Tsarpali, Vasiliki; Midtvedt, Karsten; Lønning, Kjersti; Bernklev, Tomm; Åsberg, Anders & Fawad, Haris
[Show all 10 contributors for this article]
(2022).
A Comorbidity Index and Pretransplant Physical Status Predict Survival in Older Kidney Transplant Recipients: A National Prospective Study.
Transplantation direct.
8(4),
p. e1307–e1307.
doi:
10.1097/TXD.0000000000001307.
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Kidney transplantation (KT) is considered the best treatment for end-stage kidney disease (ESKD). In the increasing elderly ESKD population, KT should be reserved for carefully selected candidates who are expected to experience favorable outcomes. We aimed to prospectively evaluate pretransplant recipient factors that may predict patient survival and can eventually guide therapeutic decisions in elderly with ESKD.
Methods: Recipient factors were evaluated in KT candidates aged ≥65 y. Comorbidity was assessed at waitlisting according to the Liu comorbidity index (LCI). Health-related quality of life outcomes were measured using the Kidney Disease Quality of Life Short Form, version 1.3. The Cox proportional hazard regression was used to evaluate predictors of patient survival.
Results: We included 192 recipients, with a mean age of 72.1 (4.1) y, who were transplanted with kidneys from deceased brain-dead donors. During a median observation period of 4.6 (3.2-6.3) y, 66 recipients died. Elevated LCI consistently predicted poor patient survival. In recipients with LCI ≥4, dialysis >2 y comprised a 2.5-fold increase in mortality risk compared with recipients on dialysis ≤2 y. Self-reported pretransplant physical function was also proven to be a significant positive predictor of survival.
Conclusion: The implementation of LCI and a physical function score during the evaluation of older kidney transplant candidates may improve the selection and thereby optimize posttransplant outcomes.
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Heldal, Torbjørn Fossum; Åsberg, Anders; Ueland, Thor; Reisæter, Anna Varberg; Pischke, Søren Erik & Mollnes, Tom Eirik
[Show all 10 contributors for this article]
(2022).
Inflammation in the early phase after kidney transplantation is associated with increased long-term all-cause mortality.
American Journal of Transplantation.
ISSN 1600-6135.
22,
p. 2016–2027.
doi:
10.1111/ajt.17047.
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In the general population low-grade inflammation has been established as a risk factor for all-cause mortality. We hypothesized that an inflammatory milieu beyond the time of recovery from the surgical trauma could be associated with increased long-term mortality in kidney transplant recipients (KTRs). This cohort study included 1044 KTRs. Median follow-up time post-engraftment was 10.3 years. Inflammation was assessed 10 weeks after transplantation by different composite inflammation scores based on 21 biomarkers. We constructed an overall inflammation score and five pathway-specific inflammation scores (fibrogenesis, vascular inflammation, metabolic inflammation, growth/angiogenesis, leukocyte activation). Mortality was assessed with Cox regression models adjusted for traditional risk factors. A total of 312 (29.9%) patients died during the follow-up period. Hazard ratio (HR) for death was 4.71 (95% CI:2.85-7.81, p
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Tsarpali, Vasiliki; Midtvedt, Karsten; Lønning, Kjersti; Bernklev, Tomm; Åsberg, Anders & Lippe, Nanna von der
[Show all 8 contributors for this article]
(2022).
Poor physical function trajectory predicts impaired patient survival in older recipients of deceased donor kidneys: A prospective cohort study.
Transplantation direct.
8(11),
p. e1374–e1374.
doi:
10.1097/TXD.0000000000001374.
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Optimized health-related quality of life (HRQOL) at the time of kidney transplantation (KT) is associated with improved survival. In older KT recipients, we aimed to prospectively evaluate if HRQOL evolution during the first posttransplant year was associated with long-term patient survival.
Methods: Recipients older than 65 y at KT who received an organ from a deceased brain-dead donor and survived >12 mo posttransplant were eligible. HRQOL was assessed pre-KT, at 10 wk, 6 mo, and 12 mo post-KT, using the Kidney Disease Quality of Life Short Form version 1.3 survey. A mixed-effect model was used to explore HRQOL evolution during the first posttransplant year in long-term survivors compared with nonsurvivors. Distinct HRQOL clusters were identified using a group-based trajectory modeling and their association with patient survival was investigated with Cox proportional hazard regression models.
Results: We included 192 elderly recipients of deceased brain-dead donor kidneys who were transplanted from 2013 to 2020. Eleven died during the first year leaving 181 for evaluation (male, 125; mean age at KT, 72 y [65-84 y]). During a median observation time post-KT of 4.9 y (11.1-8.5 y), 57 recipients died. In survivors, all the generic and kidney-specific HRQOL domains substantially improved during the first year, whereas in nonsurvivors HRQOL deteriorated. Three longitudinal HRQOL trajectories indicating poor, fair, and good HRQOL evolution were identified. Poor physical function trajectory was significantly associated with higher mortality risk independent of covariates, as compared with good physical trajectory (hazard ratio, 2.38; 95% confidence interval, 1.15-5.01).
Conclusions: In elderly KT recipients, detection of declining posttransplant physical function may imply impaired survival. Systematic HRQOL monitoring following KT provides added value when evaluating mortality and may guide therapeutic decisions.
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Heldal, Kristian; Åsberg, Anders; Abedini, Sadollah; Jenssen, Trond Geir; Reisæter, Anna Varberg & Bergan, Stein
[Show all 7 contributors for this article]
(2021).
Estimert glomerulær filtrasjonshastighet som mål på nyrefunksjon.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
142(1),
p. 48–51.
doi:
10.4045/tidsskr.21.0501.
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Estimert glomerulær filtrasjonshastighet er etablert som
klinisk rutinemål for nyrefunksjon, men estimatet har
begrensninger og kan ikke brukes i alle kliniske situasjoner.
Estimert glomerulær filtrasjonshastighet har en høy
variasjonskoeffisient, og ved avvik i pasientens høyde, vekt
eller muskelmasse kan estimatet bli unøyaktig. Hvis det er
avgjørende å ha et nøyaktig mål på nyrefunksjonen, kan man
måle glomerulær filtrasjonshastighet ved hjelp av en
eksogen substans.
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Witczak, Bartlomiej J; Pischke, Søren E.; Reisæter, Anna V.; Midtvedt, Karsten; Ludviksen, Judith K & Heldal, Kristian
[Show all 10 contributors for this article]
(2021).
Elevated Terminal C5b-9 Complement Complex 10 Weeks Post Kidney Transplantation Was Associated With Reduced Long-Term Patient and Kidney Graft Survival.
Frontiers in Immunology.
12.
doi:
10.3389/fimmu.2021.738927.
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Background: The major reason for graft loss is chronic tissue damage, as interstitial fibrosis and tubular atrophy (IF/TA), where complement activation may serve as a mediator. The association of complement activation in a stable phase early after kidney transplantation with long-term outcomes is unexplored. Methods: We examined plasma terminal C5b-9 complement complex (TCC) 10 weeks posttransplant in 900 patients receiving a kidney between 2007 and 2012. Clinical outcomes were assessed after a median observation time of 9.3 years [interquartile range (IQR) 7.5–10.6]. Results: Elevated TCC plasma values (≥0.7 CAU/ml) were present in 138 patients (15.3%) and associated with a lower 10-year patient survival rate (65.7% vs. 75.5%, P < 0.003). Similarly, 10-year graft survival was lower with elevated TCC; 56.9% vs. 67.3% (P < 0.002). Graft survival was also lower when censored for death; 81.5% vs. 87.3% (P = 0.04). In multivariable Cox analyses, impaired patient survival was significantly associated with elevated TCC [hazard ratio (HR) 1.40 (1.02–1.91), P = 0.04] along with male sex, recipient and donor age, smoking, diabetes, and overall survival more than 1 year in renal replacement therapy prior to engraftment. Likewise, elevated TCC was independently associated with graft loss [HR 1.40 (1.06–1.85), P = 0.02] along with the same covariates. Finally, elevated TCC was in addition independently associated with death-censored graft loss [HR 1.69 (1.06–2.71), P = 0.03] as were also HLA-DR mismatches and higher immunological risk. Conclusions: Early complement activation, assessed by plasma TCC, was associated with impaired long-term patient and graft survival.
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Tsarpali, Vasiliki; Midtvedt, Karsten; Lønning, Kjersti; Bernklev, Tomm; Lippe, Nanna von der & Reisæter, Anna Varberg
[Show all 8 contributors for this article]
(2021).
Health-Related Quality of Life in Older Kidney Transplant Recipients: A National Cohort Study of Short- and Longer-Term Outcomes.
Kidney Medicine.
3(6),
p. 974–983.
doi:
10.1016/j.xkme.2021.05.007.
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Rationale & Objective
Assessing the optimal therapy for older patients (aged ≥65 years) with end-stage kidney disease requires knowledge of longevity and health-related quality of life (HRQoL) outcomes. Kidney transplantation prolongs survival but its long-term impact on HRQoL in older recipients is not well defined. We aimed to prospectively evaluate HRQoL changes from enlisting until 3 years posttransplantation and examine pretransplantation predictors of posttransplantation outcomes.
Study Design
Prospective cohort study.
Setting & Participants
Patients 65 years and older enlisted at the Norwegian National Transplant Center between January 2013 and November 2016.
Predictors
Kidney transplantation, dialysis vintage, and pretransplantation comorbidity assessed using the Liu Comorbidity Index.
Outcomes
HRQoL, assessed using the Kidney Disease Quality of Life Short Form, version 1.3.
Analytical Approach
HRQoL scores obtained at 3 years posttransplantation were compared with those obtained pretransplantation and after 1 year using a paired-sample t test. Multivariable linear mixed-effect models were used to identify possible predictors of HRQoL changes over time.
Results
Among 289 patients included, 220 (mean age, 71.5 years) had undergone transplantation and 136 had completed the 3-year HRQoL follow-up by October 2020. Posttransplant HRQoL, both generic and kidney specific, substantially improved and the benefit persisted for 3 years. For wait-listed candidates remaining on dialysis, HRQoL gradually deteriorated, and recipients who died within 3 years posttransplantation experienced no improvement during the first year. Moderately elevated pretransplantation comorbidity scores and prolonged dialysis vintage independently predicted poor HRQoL outcomes posttransplantation. Recipients receiving dialysis for 1 year or longer with pretransplantation comorbidity scores ≥ 7 experienced a marked and sustained physical deterioration after transplantation.
Limitations
Homogenous and highly selected population.
Conclusions
Transplantation is associated with a sustained HRQoL improvement and should be the preferred treatment for selected older patients. The value of a pretransplant comorbidity score to predict posttransplantation outcomes warrants further evaluation and may improve the selection process.
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Flemmen, Heidi Øyen; Simonsen, Cecilia Smith; Berg-Hansen, Pål; Moen, Stine Marit; Kersten, Hege & Heldal, Kristian
[Show all 7 contributors for this article]
(2020).
Prevalence of multiple sclerosis in rural and urban districts in Telemark county, Norway.
Multiple Sclerosis and Related Disorders.
ISSN 2211-0348.
45.
doi:
10.1016/j.msard.2020.102352.
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Objective: To explore the trends in prevalence and incidence of multiple sclerosis (MS) in Telemark, Norway (latitude 58.7-60.3˚N), over the past two decades, with focus on differences between rural and urban areas.
Methods: Data from all patients with a confirmed diagnosis of MS in Telemark since 1993 were prospectively recorded and collected in a retrospective chart review. Prevalence estimates on January 1st 1999, 2009 and 2019, and incidence rates at five-year intervals between 1999 and 2018 were calculated and all results were adjusted to the European Standard Population. The study population was divided into urban and rural residency using a Norwegian governmental index.
Results: We registered 579 patients with MS in Telemark between 1999 and 2019. The adjusted prevalence estimates for January 1st 1999, 2009 and 2019 were 105.8/105, 177.1/105 and 260.6/105, respectively. In 2019, the prevalence estimates were 250.4/105 in urban and 316.2 /105 in rural areas. Between 1999 and 2018, the yearly incidence increased from 8.4/105 to 14.4/105.
Conclusions: The prevalence of MS in Telemark is among the highest ever reported in Norway, consistent with an increasing incidence in the county over the past twenty years. The even higher prevalence in the rural areas is unlikely to be explained by possible risk factors like latitude, exposure to sunlight and diet. Further studies on differences between urban and rural areas are required to reveal possible new risk factors.
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Petraglia, Lucas & Heldal, Kristian
(2019).
Kidney Transplant in Elderly.
In Musso, Carlos G. (Eds.),
Clinical Nephrogeriatrics.
Springer.
ISSN 9783030187101.
p. 189–199.
doi:
10.1007/978-3-030-18711-8_13.
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Kidney transplant in the elderly has its own characteristics, such as the increasing proportion of elderly recipients, extended criteria for donor allocation, better survival rates compared to their dialysis counterparts, higher prevalence of frailty, lower prescription adherence, particular immunosuppressant protocols, as well as high incidence of death with a functioning organ due to cardiovascular disease, infection, or malignancy. In summary, kidney transplantation is an attractive treatment option for end-stage renal disease patients that after a standard medical evaluation are found eligible.
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Heldal, Kristian; Midtvedt, Karsten; Lønning, Kjersti; Iversen, Tor; Hernæs, Kjersti Helene & Tsarpali, Vasiliki
[Show all 8 contributors for this article]
(2019).
Kidney transplantation: an attractive and cost-effective alternative for older patients?—a cost–utility study.
Clinical Kidney Journal (CKJ).
ISSN 2048-8505.
12(6),
p. 888–894.
doi:
10.1093/ckj/sfz018.
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In the elderly, kidney transplantation is associated with increased survival and improved health-related quality of life compared with dialysis treatment. We aimed to study the short-term health economic effects of transplantation in a population of elderly kidney transplant candidates. Self-perceived health, quality-adjusted life years (QALYs) and costs were evaluated and compared 1 year before and 1 year after kidney transplantation in patients included in a single-centre prospective study of 289 transplant candidates ≥65 years of age. Self-perceived health and QALYs both significantly improved after transplantation. At 1 year, the costs per QALY were substantially higher for transplantation (€88 100 versus €76 495), but preliminary analyses suggest a favourable long-term health economic effect. Kidney transplantation in older kidney transplant recipients is associated with improved health but also with increased costs the first year after engraftment when compared with remaining on the waiting list. Any long-term cost-effectiveness needs to be confirmed in studies with longer observation times.
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Avilia-Poletti, Debora; Azevedo, Leticia de; Lommi, Candela; Heldal, Kristian & Musso, Carlos G.
(2019).
Hyperchloremic metabolic acidosis in the kidney transplant patient.
Postgraduate medicine.
ISSN 0032-5481.
131(3),
p. 171–175.
doi:
10.1080/00325481.2019.1592360.
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Hyperchloremic metabolic acidosis of renal origin results from a defect in renal tubular acidification mechanism, and this tubular dysfunction can consist of an altered tubular proton secretion or bicarbonate reabsorption capability. Studies have documented that all forms of renal tubular acidosis (RTA), type I to IV, are documented in kidney transplant patients. Among RTA pathophysiologic mechanisms have been described the renal mass reduction, hyperkalemia, hyperparathyroidism, graft rejection, immunologic diseases, and some drugs such as renin-angiotensin-aldosterone blockers, and calcineurin inhibitors. RTA can lead to serious complications as is the case of muscle protein catabolism, muscle protein synthesis inhibition, renal osteodystrophy, renal damage progression, and anemia promotion. RTA should be treated by suppressing its etiologic factor (if it is possible), avoiding hyperkalemia, and/or supplying bicarbonate or a precursor (citrate). In conclusion: Hyperchloremic metabolic acidosis of renal origin is a relatively frequent complication in kidney transplantation patients, which can be harmful, and should be adequately treated in order to avoid its renal and systemic adverse effects.
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Gibbs, Charlotte Christine; Thalamus, Jacob; Kristoffersen, Doris Tove; Svendsen, Martin Veel; Holla, Øystein Lunde & Heldal, Kristian
[Show all 8 contributors for this article]
(2019).
QT prolongation predicts short-term mortality independent of comorbidity.
Europace.
ISSN 1099-5129.
21(8),
p. 1254–1260.
doi:
10.1093/europace/euz058.
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A prolonged corrected QT interval (QTc) ≥500 ms is associated with high all-cause mortality in hospitalized patients. We aimed to explore any difference in short- and long-term mortality in patients with QTc ≥500 ms compared with patients with QTc <500 ms after adjustment for comorbidity and main diagnosis. Methods and results Patients with QTc ≥500 ms who were hospitalized at Telemark Hospital Trust, Norway between January 2007 and April 2014 were identified. Thirty-day and 3-year all-cause mortality in 980 patients with QTc ≥500 ms were compared with 980 patients with QTc <500 ms, matched for age and sex and adjusting for Charlson comorbidity index (CCI), previous admissions, and main diagnoses. QTc ≥500 ms was associated with increased 30-day all-cause mortality [hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.38–2.62; P < 0.001]. There was no significant difference in mortality between patients with QTc ≥500 ms and patients with QTc <500 ms who died between 30 days and 3 years; 32% vs. 29%, P = 0.20. Graded CCI was associated with increased 3-year all-cause mortality (CCI 1–2: HR 1.62, 95% CI 1.34–1.96; P < 0.001; CCI 3–4: HR 2.50, 95% CI 1.95–3.21; P < 0.001; CCI ≥5: HR 3.76, 95% CI 2.85–4.96; P < 0.001) but was not associated with 30-day all-cause mortality. QTc ≥500 ms is a powerful predictor of short-term mortality overruling comorbidities. QTc ≥500 ms also predicted long-term mortality, but this effect was mainly caused by the increased short-term mortality. For long-term mortality, comorbidity was more important.
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Heldal, Kristian; Midtvedt, Karsten; Hartmann, Anders; Reisæter, Anna Varberg; Heldal, Torbjørn Fossum & Bergan, Stein
[Show all 8 contributors for this article]
(2018).
Estimated glomerular filtration rate in stable older kidney transplant recipients-are present algorithms valid? A national cross-sectional cohort study.
Transplant International.
ISSN 0934-0874.
31(6),
p. 629–638.
doi:
10.1111/tri.13137.
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Several equations have been developed for estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD), but none were developed based on data from elderly kidney transplant recipients (KTR). The primary aim of this study was to evaluate different creatinine-based equations in stable elderly KTR. A national cross-sectional study was per- formed using data from 263 consecutive kidney transplant recipients 60 years or older who performed a routine GFR measurement one year after engraftment. GFR was measured by iohexol clearance calculation based on two samples. eGFR was calculated from a range of different crea- tinine-based equations using information obtained at the time of GFR measurement. Bias, precision, and accuracy were evaluated for each equa- tion. All equations apart from Nankivell had accuracy (P30) > 80%. The BIS1, FAS, LMR CR , and Cockcroft & Gault equations in recipients older than 70 years and the FAS, LMR CR , and MDRD in recipients 60 – 69 years old had nonsignificant bias. The CKD-EPI had significant bias in both groups. If one should choose a single equation for follow-up of individual CKD progression in all recipients ≥ 60 years, the FAS or LMR CR equations are probably the best alternatives.
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Lønning, Kjersti; Heldal, Kristian; Bernklev, Tomm; Brunborg, Cathrine; Andersen, Marit Helen & Lippe, Nanna von der
[Show all 10 contributors for this article]
(2018).
Improved Health-Related Quality of Life in Older Kidney Recipients 1 Year After Transplantation.
Transplantation direct.
doi:
10.1097/TXD.0000000000000770.
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Background: We aimed to evaluate changes in health-related quality of life (HRQoL) in patients 65 years or older from time of kidney transplantation (KTx) until 1 year postengraftment. Methods: A single-center prospective study was conducted. HRQoL was measured pre-KTx and at 2, 6, and 12 months postengraftment using self-reported Kidney Disease and Quality of Life shortform version 1.3. Intraindividual scores before and after KTx were evaluated. Liu Comorbidity Index was registered at enlisting. short-form-36 scores were additionally compared with scores from an age-matched population. Results: From January 1, 2013, until November 30, 2016, a total of 289 waitlisted patients were included. By September 1, 2017, 134 had reached 1 year postengraftment, and valid questionnaires were available in 120 (90%) patients. Mean age at KTx was 71.6 years (±4.3 years), 71% were male. Living donor was used in 21%, and preemptive KTx was performed in 30% of the recipients. Median waiting time for KTx from deceased donor was 16 months (range, 0.6-50.5 months). A total of 79 (66%) recipients had a Liu Comorbidity Index score of 3 or less. All HRQoL scores except the domain social function improved at 2 months postengraftment and remained stable or continued to improve at 1 year. HRQoL scores 12 months postengraftment were similar to those described in an age-matched general population except for the domain social function which remained at a significantly lower level. Time in dialysis was the most important variable associated with impaired HRQoL postengraftment. Conclusions: HRQoL scores showed clinically significant improvement in older KTx recipients 1 year posttransplant.
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Lønning, Kjersti; Midtvedt, Karsten; Heldal, Kristian & Andersen, Marit Helen
(2018).
Older kidney transplantation candidates' expectations of improvement in life and health following kidney transplantation: semistructured interviews with enlisted dialysis patients aged 65 years and older.
BMJ Open.
8(6).
doi:
10.1136/bmjopen-2017-021275.
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Objective: The aim was to study the expectations of improvement in life and health following kidney transplantation (KTx) in a population of wait-listed patients ≥65 years with end-stage kidney disease. Design: Qualitative research with individual in-depth interviews. Setting: Patients on dialysis enlisted for a KTx from a deceased donor were included from an ongoing study of older patients’ perspectives on KTx. Qualitative face-to-face interviews were conducted in a safe and familiar setting, and were analysed thematically using the theoretical framework of lifespan. Informants: Fifteen patients (median age 70 years, range 65–82) from all parts of Norway were interviewed. Informants were included consecutively until no new information was gained. Results: Two main themes were evident: receiving a kidney is getting life back and grasp the chance. In addition, the themes ‘hard to loose capacity and strength’, ‘reduced freedom’ and ‘life on hold’ described the actual situation and thereby illuminated the informants’ expectations. The informants tried to balance positive expectations and realism towards KTx, and they were hoping to become free from dialysis and to live a normal life. Conclusion: This study shows that older KTx candidates comprise a heterogeneous group of patients who take individual approaches that allow them to maintain autonomy and control while waiting for a transplant. This study provides new knowledge about the older KTx candidates relevant for clinicians, patients and researchers.
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Gibbs, Charlotte; Thalamus, Jacob; Heldal, Kristian; Holla, Øystein Lunde; Haugaa, Kristina & Hysing, Jan
(2017).
Predictors of mortality in high-risk patients with QT prolongation in a community hospital.
Europace.
ISSN 1099-5129.
20(1),
p. f99–f107.
doi:
10.1093/europace/eux286.
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Heldal, Kristian; Hartmann, Anders; Lønning, Kjersti; Leivestad, Torbjørn; Reisæter, Anna Varberg & Line, Pål Dag
[Show all 8 contributors for this article]
(2017).
Should patients older than 65 years be offered a second kidney transplant?
BMC Nephrology.
18(13).
doi:
10.1186/s12882-016-0426-0.
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Background: Age and number of recipients in need of kidney re-transplantation are increasing. Re-transplantation practices and outcomes in elderly recipients are not previously explored. We aimed to retrospectively evaluate the outcomes of recipients 65 years and older receiving their second deceased donor allograft. Methods: The study was designed as a retrospective registry based study. All recipients 65 years or older who received a deceased donor kidney transplant at Oslo University Hospital between 2000 and 2014 were included in the study. Survival outcomes were compared between recipients of first (TX1) and second (TX2) allograft. Survival analyses were performed using the Kaplan–Meier method and Cox proportional hazard models with patient survival, uncensored graft survival and death-censored graft survival as outcomes in the analyses. Results: Seven hundred and thirty-tree recipients > 65 years received a first (n = 687) or second (n = 46) deceased donor kidney transplant. Five years uncensored graft survival rates were 64% in TX 2 and 67% in TX 1 (P= 0.789). Estimated five years graft survival rates censored for death with functioning graft were 88% in TX2 and 90% in TX1 (P=0.475). Adjusted hazard ratio for uncensored graft loss (TX2 vs. TX1) was 1.24 (95% CI 0.77 – 2.00). Adjusted hazard ratio for graft loss censored for death with functioning graft (TX2 vs. TX1) was 1.70 (0.72-4.02). Conclusions: Older recipients of second transplants have outcomes that are comparable to the outcomes of age-matched first transplant recipients, and far better than previously documented for older transplant candidates remaining on dialysis treatment. Advanced age by itself should not be a contraindication for re-transplantation. Best results are achieved with short time on dialysis before re-transplantation.
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Lønning, Kjersti; Midtvedt, Karsten; Leivestad, Torbjørn; Reisæter, Anna Varberg; Line, Pål Dag & Hartmann, Anders
[Show all 7 contributors for this article]
(2016).
Are Octogenarians with End-Stage Renal Disease Candidates for Renal Transplantation?
Transplantation.
ISSN 0041-1337.
100(12),
p. 2705–2709.
doi:
10.1097/TP.0000000000001363.
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BACKGROUND:
Elderly patients are the fastest growing group in need of renal transplantation. This study puts focus on renal transplant recipients in their eightieth year or older at time of engraftment. Is there evidence to support an absolute upper age limit for renal transplantation?
METHODS:
Recipients in their eightieth year or older, transplanted between 1983 and 2015, were included. Data were retrieved from the Norwegian Renal Registry in the end of October 2015. Graft and patient survival were compared to recipients aged 70-79 years at transplantation.
RESULTS:
47 patients older than 79 years were transplanted in the defined period. Median age 80.1 years, 81 % were male. Median time on dialysis prior to transplantation was 18.5 months. All patients received an allograft from a deceased donor (median donor age 61.8 years). In the death censored graft survival model, there was no statistical difference between the groups. We found improved patient and graft survival after introduction of mycophenolate mofetil and induction with basiliximab. Patients transplanted before 2000 had increased risk of death compared to those transplanted after 2000; HR 3.2 (95% CI 1.2-8.7). Median uncensored graft survival for patients transplanted after the year 2000 was 5.0 year (95% CI 2.4-7.6). Median patient survival was 5.0 years (3.1-6.9) and five year patient survival was 55 %.
CONCLUSION:
Age by itself should not be an absolute contraindication against renal transplantation. An estimated five years survival rate of 55 % post-engraftment for an 80 years old patient is in our opinion more than acceptable.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
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Midtvedt, Karsten; Lønning, Kjersti & Heldal, Kristian
(2014).
Managing End-Stage Renal Disease in Older Patients: A Single Centre Experience with Renal Transplantation in the Elderly.
Advances in Nephrology.
ISSN 2356-6779.
2014:516381.
doi:
10.1155/2014/516381.
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Heldal, Kristian; Hartmann, Anders; Leivestad, Torbjørn; Foss, Aksel & Midtvedt, Karsten
(2011).
Risk variables associated with the outcome of kidney recipients > 70 years of age in the new millennium.
Nephrology, Dialysis and Transplantation.
ISSN 0931-0509.
26(8),
p. 2706–2711.
doi:
10.1093/ndt/gfq786.
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Heldal, Kristian; Hartmann, Anders; Leivestad, Torbjørn; Lien, Bjørn; Foss, Aksel & Midtvedt, Karsten
(2011).
Nyretransplantasjon er et alternativ også for pasienter over 70 år.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
20(131),
p. 2004–2007.
doi:
10.4045/tidsskr.10.1391.
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Heldal, Kristian; Leivestad, Torbjørn; Hartmann, Anders; Svendsen, Martin Veel; Lien, Bjørn H. & Midtvedt, Karsten
(2008).
Kidney transplantation in the elderly - the Norwegian experience.
Nephrology, Dialysis and Transplantation.
ISSN 0931-0509.
23(3),
p. 1026–1031.
doi:
10.1093/ndt/gfm719.
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Kongerud, Ingrid Charlotte; Midtvedt, Karsten; Solbu, Marit Dahl; Øvrehus, Marius Altern; Eikrem, Øystein Solberg & Eide, Ivar Anders
[Show all 10 contributors for this article]
(2026).
Can sodium-glucose cotransporter 2 (SGLT2) inhibition preserve renal structure and function in de novo kidney transplant recipients? Protocol for a randomised, double-blind, placebo-controlled trial assessing the efficacy of dapagliflozin on kidney structure, function and safety in kidney transplant recipients in Norway—the DEAK study.
doi:
10.1136/bmjopen-2026-117263.
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Introduction Recent studies have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease in people at high cardiovascular risk, with or without type 2 diabetes. To date, all published studies have excluded kidney transplant recipients (KTRs). The Dapagliflozin Early After Kidney Transplantation (DEAK) study aims to prospectively evaluate the effects of the SGLT2 inhibitor dapagliflozin on kidney function, histopathology and metabolic outcomes among de novo KTRs.
Methods and analyses This nationwide, investigator-initiated, single-transplant-centre, randomised, placebo-controlled, prospective clinical trial with two parallel groups aims to enrol 330 de novo adult KTRs (aged 18–75 years) with an estimated glomerular filtration rate (eGFR) of at least 25 mL/min/1.73 m². Participants are enrolled 6–8 weeks after transplantation and randomised 1:1 to receive dapagliflozin 10 mg/day or placebo for 3 years. Recipients with conditions that may intermittently affect kidney function, such as recent acute rejection or ongoing infection, are ineligible for inclusion.
The primary endpoint of the study is the difference in the chronic eGFR slope between treatment groups over 3 years, estimated using the European Kidney Function Consortium equation. Secondary and safety endpoints include changes in measured GFR (iohexol clearance), urinary albumin/creatinine ratio, blood pressure, infections and safety clinical chemistry. Exploratory endpoints evaluated after 1.5 years include changes in body composition and glucose tolerance; between-group differences in urinary metabolomics; transplant kidney biopsy inflammation and fibrosis scores (n=140) and kidney biopsy messenger RNA and protein expression (n=50). The protocol also includes a 10-year poststudy registry follow-up of eGFR slope, cardiovascular events and graft and patient survival.
Ethics and dissemination The study protocol (EudraCT number: 2022-002428-10) has been approved by the Norwegian Medical Products Agency, the Regional Committee for Medical Research Ethics in Southeast Norway (REK Southeast number 426076) and by the data protection offices at the participating hospitals. The main results will be published in international, peer-reviewed scientific journals.
Trial registration number NCT05788276.
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Midtvedt, Karsten; Vaage, John T.; Heldal, Kristian; Munthe, Ludvig Andre; Lund-Johansen, Fridtjof & Åsberg, Anders
(2022).
Fourth dose of the SARS-CoV-2 vaccine in kidney transplant recipients with previously impaired humoral antibody response.
American Journal of Transplantation.
ISSN 1600-6135.
doi:
10.1111/ajt.17091.
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Heldal, Kristian; Lønning, Kjersti & Midtvedt, Karsten
(2013).
QUESTION65-A LONGITUDINAL STUDY DESCRIBING HRQOL IN ESRD PATIENTS OVER 65 YEARS LISTED FOR KIDNEY TRANSPLANTATION.
Transplant International.
ISSN 0934-0874.
26,
p. 268–268.
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Heldal, Kristian; Hartmann, Anders; Leivestad, Torbjørn; Svendsen, Mette; Lien, Bjørn & Midtvedt, Karsten
(2008).
Premature patient death in kidney transplant recipients over 70 years of age is not predicted by scoring of co-morbidity AT transplantation.
American Journal of Transplantation.
ISSN 1600-6135.
8,
p. 364–364.
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Heldal, Kristian; Leivestad, Torbjørn; Hartmann, Anders; Svendsen, Martin Veel & Midtvedt, Karsten
(2007).
Dialysis for more than 12 months prior to renal transplantation is an independent risk factor for real old kidney recipients - Data from 271 recipients > 70 years old.
Nephrology, Dialysis and Transplantation.
ISSN 0931-0509.
22,
p. 379–379.
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Heldal, Kristian; Leivestad, Torbjørn; Hartmann, Anders; Svendsen, Martin Veel & Midtvedt, Karsten
(2007).
Kidney transplantation beyond 70 years - Is it worthwhile? A single centre experience with 301 patients over a time period of 16 years.
Nephrology, Dialysis and Transplantation.
ISSN 0931-0509.
22,
p. 376–376.
Full text in Research Archive
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Heldal, Kristian; Leivestad, Torbjørn; Hartmann, Anders; Lien, Bjørn H.; Svendsen, Martin Veel & Midtvedt, Karsten
(2007).
Renal transplantation in geriatric patients - Is it madness or worthwhile? A single centre experience with 102 patients beyond 75 years of age.
Transplant International.
ISSN 0934-0874.
20,
p. 188–188.
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June 8, 2022 8:19 AM
- Last modified
Nov. 5, 2025 4:26 PM
