Persistent hyperparathyroidism as a risk factor for long-term graft failure: the need to discuss indication for parathyroidectomy

Araujo, Maria Júlia Correia Lima Nepomuceno; Ramalho, Janaina; Elias, Rosilene Motta; Jorgetti, Vanda; Nahas, William Carlos; Custódio, Melani Ribeiro; Moysés, Rosa M.A.; David‐Neto, Elias

doi:10.1016/j.surg.2017.12.010

Cited by 49 publications

(59 citation statements)

References 30 publications

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“…As the ideal PTH post‐transplant is not known, our results were based on a PTH cutoff of 150 pg/mL three months post‐transplant. While different cutoffs were suggested in previous studies, 10,11 a cutoff of 150 pg/mL at 6 months was found the best to predict pHPT 1 year post‐transplant 10 and was therefore chosen in this study. The levels of potentially important covariates such as vitamin D and FGF‐23 were not available for inclusion in the multivariate analyze as well as the data for medication non‐compliance, a possible confounder affecting PTH levels.…”

Section: Discussionmentioning

confidence: 99%

“…While the association between pretransplant CKD‐mineral bone density (MBD) markers and graft failure has been studied, 9 data regarding the association of post‐transplant pHPT with renal allograft outcome are limited. pHPT 1 year post‐transplant was associated with an increased risk of long‐term death‐censored graft failure 10 . PTH above the upper limit of normal few years post‐transplant (mean of 5.1 years) was associated with a 46% higher risk of death and an 85% higher risk of graft loss compared with low/normal values 11 .…”

Section: Introductionmentioning

confidence: 98%

“…pHPT 1 year post-transplant was associated with an increased risk of longterm death-censored graft failure. 10 PTH above the upper limit of normal few years post-transplant (mean of 5.1 years) was associated with a 46% higher risk of death and an 85% higher risk of graft loss compared with low/normal values. 11 PTH measured as early as 10 weeks post-transplant was associated with a composite end point of cardiovascular (CVS) events, graft loss, and all-cause mortality.…”

mentioning

confidence: 94%

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Early persistent hyperparathyroidism post‐renal transplantation as a predictor of worse graft function and mortality after transplantation

Isakov

Ghinea

Beckerman

et al. 2020

Clinical Transplantation

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pHPT has been reported in up to 80% of renal transplant recipients (RTR) during the first year after kidney transplantation. 1 There is marked variation in the reported prevalence related mainly to differences in diagnostic criteria and absence of a clear definition to post-renal transplantation pHPT. Inappropriately high PTH levels post-transplant contribute to post-transplant complications such as hypercalcemia, hypophosphatemia, elevated fibroblast growth factor 23 (FGF-23), and nephrocalcinosis. 2,3 Studies showed an association between PTH and risk of hypertension (HTN), left ventricular hypertrophy, heart failure, coronary artery disease, and mortality. 4-8 While the association between pretransplant CKD-mineral bone density (MBD) markers and

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

mentioning

confidence: 94%

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Early persistent hyperparathyroidism post‐renal transplantation as a predictor of worse graft function and mortality after transplantation

Isakov

Ghinea

Beckerman

et al. 2020

Clinical Transplantation

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“…PTX should be performed properly since persistent hyperparathyroidism deteriorates kidney function [44]. In transplanted kidney, however, there is a long-standing controversy regarding whether PTX affects graft kidney function [45].…”

Section: Discussionmentioning

confidence: 99%

Disrupted tubular parathyroid hormone/parathyroid hormone receptor signaling and damaged tubular cell viability possibly trigger postsurgical kidney injury in patients with advanced hyperparathyroidism

Sato

Kikkawa

Yamamoto

et al. 2019

Clinical Kidney Journal

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Background Parathyroidectomy (PTX) that alleviates clinical manifestations of advanced hyperparathyroidism, including hypercalcemia and hypophosphatemia, is considered the best protection from calcium overload in the kidney. However, little is known about the relationship between postsurgical robust parathyroid hormone (PTH) reduction and perisurgical renal tubular cell viability. Post-PTX kidney function is still a crucial issue for primary hyperparathyroidism (PHPT) and tertiary hyperparathyroidism after kidney transplantation (THPT). Methods As a clinical study, we examined data from 52 consecutive patients (45 with PHPT, 7 with THPT) who underwent PTX in our center between 2015 and 2017 to identify post-PTX kidney injury. Their clinical data, including urinary liver-type fatty acid-binding protein (L-FABP), a tubular biomarker for acute kidney injury (AKI), were obtained from patient charts. An absolute change in serum creatinine level of 0.3 mg/dL (26.5 µmol/L) on Day 2 after PTX defines AKI. Post-PTX calcium supplement dose adjustment was performed to strictly maintain serum calcium at the lower half of the normal range. To mimic post-PTX-related kidney status, a unique parathyroidectomized rat model was produced as follows: 13-week-old rats underwent thyroparathyroidectomy (TPTX) and/or 5/6 subtotal nephrectomy (NX). Indicated TPTX rats were given continuous infusion of a physiological level of 1-34 PTH using a subcutaneously implanted osmotic minipump. Immunofluorescence analyses were performed by polyclonal antibodies against PTH receptor (PTHR) and a possible key modulator of kidney injury, Klotho. Results Patients’ estimated glomerular filtration rate (eGFR) did not have any clinically relevant change (62.5 ± 22.0 versus 59.4 ± 21.9 mL/min/1.73 m2, NS), whereas serum calcium (2.7 ± 0.18 versus 2.2 ± 0.16 mmol/L, P < 0.0001) and phosphorus levels (0.87 ± 0.19 versus 1.1 ± 0.23 mmol/L, P < 0.0001) were normalized and PTH decreased robustly (181 ± 99.1 versus 23.7 ± 16.8 pg/mL, P < 0.0001) after successful PTX. However, six patients who met postsurgical AKI criteria had lower eGFR and greater L-FABP than those without AKI. Receiver operating characteristics (ROC) analysis revealed eGFR <35 mL/min/1.73 m2 had 83% accuracy. Strikingly, L-FABP >9.8 µg/g creatinine had 100% accuracy in predicting post-PTX-related AKI. Rat kidney PTHR expression was lower in TPTX. PTH infusion (+PTH) restored tubular PTHR expression in rats that underwent TPTX. Rats with TPTX, +PTH and 5/6 NX had decreased PTHR expression compared with those without 5/6 NX. 5/6 NX partially cancelled tubular PTHR upregulation driven by +PTH. Tubular Klotho was modestly expressed in normal rat kidneys, whereas enhanced patchy tubular expression was identified in 5/6 NX rat kidneys. This Klotho and expression and localization pattern was absolutely canceled in TPTX, suggesting that PTH indirectly modulated the Klotho expression pattern. TPTX +PTH recovered tubular Klotho expression and even triggered diffusely abundant Klotho expression. 5/6 NX decreased viable tubular cells and eventually downregulated tubular Klotho expression and localization. Conclusions Preexisting tubular damage is a potential risk factor for AKI after PTX although, overall patients with hyperparathyroidism are expected to keep favorable kidney function after PTX. Patients with elevated tubular cell biomarker levels may suffer post-PTX kidney impairment even though calcium supplement is meticulously adjusted after PTX. Our unique experimental rat model suggests that blunted tubular PTH/PTHR signaling may damage tubular cell viability and deteriorate kidney function through a Klotho-linked pathway.

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“…In terms of renal HPT, it is relevant to discuss the problem of persistent HPT in patients with a successful kidney transplant. There is evidence that this problem is not infrequent, affecting up to 62% of transplant patients after one year ( 31 ). For them, parathyroidectomy is necessary to protect the kidney graft from hypercalcemia.…”

Section: Parathyroidectomy and Survival: The Case Against Postponing mentioning

confidence: 99%

Parathyroid surgery during the COVID-19 pandemic: Time to think about the “New Normal”

Montenegro¹,

Brescia²,

Arap³

et al. 2020

Clinics

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Persistent hyperparathyroidism as a risk factor for long-term graft failure: the need to discuss indication for parathyroidectomy

Cited by 49 publications

References 30 publications

Early persistent hyperparathyroidism post‐renal transplantation as a predictor of worse graft function and mortality after transplantation

Early persistent hyperparathyroidism post‐renal transplantation as a predictor of worse graft function and mortality after transplantation

Disrupted tubular parathyroid hormone/parathyroid hormone receptor signaling and damaged tubular cell viability possibly trigger postsurgical kidney injury in patients with advanced hyperparathyroidism

Parathyroid surgery during the COVID-19 pandemic: Time to think about the “New Normal”

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