Hyperparathyroidism and parathyroidectomy in patients on renal replacement therapy

Abstract

Background. Secondary hyperparathyroidism (sHPT) is characterized by over function of the parathyroid glands and disturbances in mineral metabolism as a result of renal failure. It is common among patients with end-stage renal disease (ESRD) and it often persists after successful renal transplantation. sHPT is associated with osteoporosis and cardiovascular morbidity and mortality. There are two main ways to treat this condition, either by medical therapy or surgical removal of the parathyroid glands, parathyroidectomy (PTX). Another complication in patients with ESRD is New-Onset Diabetes After Transplantation (NODAT). Immunosuppressive medications and personal risk factors for diabetes mellitus have been associated with the condition. We aimed to study the effect of PTX on the risk of death, cardio-/cerebrovascular events (CVE), and hip fractures. We also studied the incidence of NODAT at our department and whether there is an association between NODAT and sHPT.
Methods. A nested index-referent study was performed within the Swedish Renal Registry (SRR). Patients on maintenance dialysis or with renal transplant at the time of PTX were included. The PTX patients were randomly matched for age, sex and underlying renal disease with up to five referent patients who had not undergone PTX. To calculate survival time and hazard ratios (HR), indexes and referents were assigned the calendar date (d) of the PTX of the index patient. The risk of death, CVE, and fractures after PTX were calculated using crude and adjusted Cox proportional hazards regressions. Data were extracted from patient charts to calculate the incidence of NODAT, and logistic regressions were performed to analyze potential risk factors for NODAT including sHPT.
Results. There were 20 056 patients in the SRR between 1991 and 2009. Of these, 579 (423 on dialysis and 156 with a renal transplant at d) incident patients with PTX were matched with 1234/736 non-PTX patients. The adjusted relative risk of death was a HR of 0.80 [95% confidence interval (CI) 0.65–0.99] for dialysis patients who had undergone PTX compared with matched patients who had not. Corresponding result for the patients with a renal allograft at d was a HR of 1.10 (95% CI 0.71–1.70). The results for CVE:s were a HR of 1.24 (95% CI 1.03–1.49) for dialysis patients with PTX compared to non-PTX dialysis patients and a HR of 0.53 (95% CI 0.34–0.84) for transplanted patients. The HR for hip fractures in PTX patients was 0.40 (95% CI 0.18–0.88) compared to non-PTX patients. We found a first-year post-transplant incidence of NODAT of 15%, and an odds ratio (OR) of 4.25 (95% CI 1.13-15.92) for the association between PTH levels above twice the normal range and NODAT.
Conclusions. PTX was associated with improved survival in patients on maintenance dialysis. However, there was no survival advantage after PTX in patients with a functioning renal allograft. PTX was associated with a higher risk of CVE after PTX for patients on maintenance dialysis. This was in contrast to some previous studies. However, the risk was lower for patients with a functioning renal allograft at the time of PTX. Parathyroidectomy was associated with a reduced risk of hip fractures in women with sHPT. The first-year cumulative incidence of NODAT was 15% at our department between the years 2000 and 2011. We showed an association between elevated levels of PTH and NODAT in transplanted patients

Abstract (Swedish)

Background. Secondary hyperparathyroidism (sHPT) is characterized by over function of the parathyroid glands and disturbances in mineral metabolism as a result of renal failure. It is common among patients with end-stage renal disease (ESRD) and it often persists after successful renal transplantation. sHPT is associated with osteoporosis and cardiovascular morbidity and mortality. There are two main ways to treat this condition, either by medical therapy or surgical removal of the parathyroid glands, parathyroidectomy (PTX). Another complication in patients with ESRD is New-Onset Diabetes After Transplantation (NODAT). Immunosuppressive medications and personal risk factors for diabetes mellitus have been associated with the condition. We aimed to study the effect of PTX on the risk of death, cardio-/cerebrovascular events (CVE), and hip fractures. We also studied the incidence of NODAT at our department and whether there is an association between NODAT and sHPT.
Methods. A nested index-referent study was performed within the Swedish Renal Registry (SRR). Patients on maintenance dialysis or with renal transplant at the time of PTX were included. The PTX patients were randomly matched for age, sex and underlying renal disease with up to five referent patients who had not undergone PTX. To calculate survival time and hazard ratios (HR), indexes and referents were assigned the calendar date (d) of the PTX of the index patient. The risk of death, CVE, and fractures after PTX were calculated using crude and adjusted Cox proportional hazards regressions. Data were extracted from patient charts to calculate the incidence of NODAT, and logistic regressions were performed to analyze potential risk factors for NODAT including sHPT.
Results. There were 20 056 patients in the SRR between 1991 and 2009. Of these, 579 (423 on dialysis and 156 with a renal transplant at d) incident patients with PTX were matched with 1234/736 non-PTX patients. The adjusted relative risk of death was a HR of 0.80 [95% confidence interval (CI) 0.65–0.99] for dialysis patients who had undergone PTX compared with matched patients who had not. Corresponding result for the patients with a renal allograft at d was a HR of 1.10 (95% CI 0.71–1.70). The results for CVE:s were a HR of 1.24 (95% CI 1.03–1.49) for dialysis patients with PTX compared to non-PTX dialysis patients and a HR of 0.53 (95% CI 0.34–0.84) for transplanted patients. The HR for hip fractures in PTX patients was 0.40 (95% CI 0.18–0.88) compared to non-PTX patients. We found a first-year post-transplant incidence of NODAT of 15%, and an odds ratio (OR) of 4.25 (95% CI 1.13-15.92) for the association between PTH levels above twice the normal range and NODAT.
Conclusions. PTX was associated with improved survival in patients on maintenance dialysis. However, there was no survival advantage after PTX in patients with a functioning renal allograft. PTX was associated with a higher risk of CVE after PTX for patients on maintenance dialysis. This was in contrast to some previous studies. However, the risk was lower for patients with a functioning renal allograft at the time of PTX. Parathyroidectomy was associated with a reduced risk of hip fractures in women with sHPT. The first-year cumulative incidence of NODAT was 15% at our department between the years 2000 and 2011. We showed an association between elevated levels of PTH and NODAT in transplanted patients

• author: Ivarsson, Kerstin
• supervisor: Martin Almquist; Naomi Clyne; Shahriar Akaberi
• opponent: associate professor Nilsson, Inga-Lena, Karolinska Institute, Stockholm
• organization: Nephrology; Clinical studies in CKD (research group)
• alternative title: Hyperparathyroidism and parathyroidectomy in patients on renal replacement therapy
• publishing date: 2020
• type: Thesis
• publication status: published
• subject: Urology and Nephrology
• keywords: Secondary hyperparathyroidism, End-stage renal disease, Parathyroidectomy, New-onset diabetes after transplantation, Maintenance dialysis, Renal transplantation, Survival, Cardiovascular event, Hip fracture
• in: Lund University, Faculty of Medicine Doctoral Dissertation Series
• issue: 2020:25
• pages: 81 pages
• defense location: Åke Nordén, BMC hus H, Sölvegatan 19 i Lund
• defense date: 2020-04-03 09:00:00
• ISSN: 1652-8220
• ISBN: 978-91-7619-885-8
• language: English
• LU publication?: yes
• id: 852457d3-efcd-4417-a1ce-87de539950f9
• date added to LUP: 2020-03-07 15:51:38
• date last changed: 2020-03-31 15:17:28