Does the Parathyroidectomy Endanger the Transplanted Kidney?

Chudziński, Witold; Wyrzykowska, M.; Nazarewski, Sławomir; Durlik, M.; Gałązka, Zbigniew

doi:10.1016/j.transproceed.2016.01.054

Cited by 14 publications

(6 citation statements)

References 18 publications

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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]. Calcimimetics may be an alternative treatment option.…”

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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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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“…Chudzinski et al [17] tried to answer the question: does PTX endanger the transplanted kidney? They found that PTX did not significantly impair the transplanted kidney function; however, transient reductions in graft function occurred in the early postoperative period.…”

Section: Discussionmentioning

confidence: 99%

Value of Intraoperative Parathyroid Hormone Assay during Parathyroidectomy in Dialysis and Renal Transplant Patients with Secondary and Tertiary Hyperparathyroidism

El-Husseini

Wang

Edon

et al. 2017

Nephron

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Background: In dialysis and renal transplant patients with secondary and tertiary hyperparathyroidism (HPT), the value of intraoperative parathyroid hormone (ioPTH) during parathyroidectomy (PTX) and its association with long-term PTH levels are unknown. The present study aims at evaluating the relationship of ioPTH with long-term PTH levels post-PTX in dialysis and renal transplant patients in a single-center study. Methods: The ioPTH was measured in 57 dialysis patients (33 females and 24 males) and 18 renal transplant recipients (12 males and 6 females) who underwent PTX from 2005 to 2015 for refractory HPT. Near-total PTX was performed in 56 patients and total PTX with autotransplantation in 20 patients. The PTH monitoring included 3 samples: pre-intubation, 10- and 20-min (pre-ioPTH, 10-ioPTH, and 20-ioPTH) post parathyroid gland excision. Patients were followed up for up to 5 years. Results: In the dialysis group, the median (25th–75th percentile) pre-, 10-, and 20-ioPTH levels were 1,447 pg/mL (938–2,176), 143 pg/mL (78–244) and 112 pg/mL (59–153) respectively. In the renal transplant group, pre-, 10-, and 20-ioPTH levels were 273 pg/mL (180–403), 42 pg/mL (25–72), and 34 pg/mL (23–45) respectively. All patients in the transplant group had a functional kidney transplant at the time of PTX with a median serum creatinine of 1.3 mg/dL (1.2–1.7) and estimated glomerular filtration rate of 55 mL/min (40–60). The median time between renal transplant and PTX surgeries was 22 months (7–81). The last median follow-up PTH level was 66 pg/mL (15–201) in the dialysis group and 54 pg/mL (17–72) in the transplant group (p = 0.438). The mean time for last PTH post-PTX was 2.3 ± 2.0 years. In both groups, there was no significant difference between 20-ioPTH and any-time post-PTX PTH levels (p = 0.6 and p = 0.9). Nineteen patients (25%) were readmitted within 90 days because of hypocalcemia. One patient in the dialysis group was readmitted for post-PTX hematoma evacuation. No patient required repeat PTX because of recurrent HPT that was refractory to medical therapy. Only one dialysis patient required repeat PTX because the first procedure failed. Conclusions: The 20-ioPTH is a good indicator of long-term PTH levels in dialysis and renal transplant patients. Hypocalcemia is a common complication, particularly in dialysis patients, and it is the main reason for readmission after PTX. Hypoparathyroidism is a potential concern after PTX in dialysis patients.

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“…The ERBP suggest that parathyroidectomy should be considered as a last resort, particularly in the first 12-18 months post-transplant. Also, several retrospective studies indicated that post-transplant parathyroidectomy could be associated with a temporary decline in the transplant function [22,30,[59][60][61][62][63][64]. We believe that waitlisted patients requiring parathyroidectomy should be ideally operated before transplantation.…”

Section: Parathyroidectomymentioning

confidence: 96%

The management of mineral and bone disease after kidney transplantation: A narrative overview

Buttigieg¹,

Bugeja²,

Shaheen³

et al. 2019

Trends in Transplant

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Post-transplant mineral bone disease (PT-MBD) is associated with increased morbidity and mortality in kidney transplant recipients. Bone abnormalities can range from adynamic bone disease to severe persistent hyperparathyroidism with associated hypercalcemia and hypophosphataemia. In addition, these patients can develop other complications such as osteopenia and osteoporosis; further increasing the risk of fragility fractures. Appropriate management is challenging, given the lack of robust evidence. Bone turnover biomarkers and imaging studies are not entirely validated to differentiate between these pathological entities. Available interventions to control high turnover bone disease include calcimimetic drugs (Cinacalcet) and surgical parathyroidectomy. Cinacalcet has been shown to improve bone biochemistry and reduce the number of required parathyroidectomies. However, none of the meta-analyses identified a significant reduction in the overall mortality. Cinacalcet remains the treatment of choice for high turnover bone disease in the first year after transplantation, sometimes serving as a precursor to the surgery. In general, severe hyperparathyroidism does not respond adequately to cinacalcet alone, and many of these patients would eventually require parathyroidectomy. In our opinion, total parathyroidectomy should be avoided as this leads to undetectable PTH and subsequent adynamic bone disease. Anti-resorptive treatment, on the other hand, is indicated for proven osteoporosis if excretory graft function permits. In this narrative review, we provide an overview of the management of PT-MBD, based on the current best available evidence.

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Does the Parathyroidectomy Endanger the Transplanted Kidney?

Cited by 14 publications

References 18 publications

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

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

Value of Intraoperative Parathyroid Hormone Assay during Parathyroidectomy in Dialysis and Renal Transplant Patients with Secondary and Tertiary Hyperparathyroidism

The management of mineral and bone disease after kidney transplantation: A narrative overview

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