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Kato K, Nakashima A, Morishita M, Ohkido I, Yokoo T. Parathyroid gland volume and treatment resistance in patients with secondary hyperparathyroidism: a 4-year retrospective cohort study. Clin Kidney J 2025; 18:sfae391. [PMID: 39927252 PMCID: PMC11803308 DOI: 10.1093/ckj/sfae391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Indexed: 02/11/2025] Open
Abstract
Background The role of parathyroid gland (PTG) ultrasonography in the management of secondary hyperparathyroidism after the introduction of calcimimetics remains unclear. Recent investigations have prompted renewed interest in the use of PTG ultrasonography for assessing treatment resistance to calcimimetics and determining the optimal timing for surgical intervention. This study aimed to explore the hypothesis that the PTG volume correlates with the calcimimetic dose. Methods We retrospectively observed outpatients undergoing haemodialysis at baseline and a 4-year follow-up. PTG volume was measured using ultrasonography between January and December 2017 and January and December 2021. We examined the association between baseline PTG volume and calcimimetic doses after 4 years. Results Of the 121 patients {median age 64 years [interquartile range (IQR) 54-72]}, 71 had PTG nodules on ultrasonography and the median total PTG volume was 34 mm3 (IQR 0-178). In the short dialysis vintage group, baseline parathyroid hormone levels tended to correlate with baseline calcimimetic doses; however, this trend was not observed in the extended dialysis vintage group. Baseline PTG volume correlated with the cinacalcet-equivalent calcimimetic dose (correlation coefficient 0.46; P < .001) after 4 years. The calcimimetic dose in the group with an estimated PTG volume >500 mm3 was ≈80 mg/day higher than that in the non-PTG nodule group after 4 years. In multivariate linear regression analysis, PTG volume >500 mm3 was associated with a high calcimimetic dose at 4 years in all analysis models. Conclusions Assessing PTG volume using ultrasonography may help predict high calcimimetic doses.
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Affiliation(s)
- Kazuhiko Kato
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
- Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan
- Department of Nephrology, Morishita Memorial Hospital, Kanagawa, Japan
| | - Akio Nakashima
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
| | | | - Ichiro Ohkido
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
| | - Takashi Yokoo
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
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Mao J, You H, Wang M, Ba Y, Qian J, Cheng P, Lu C, Chen J. Single-cell RNA sequencing reveals transdifferentiation of parathyroid chief cells into oxyphil cells in patients with uremic secondary hyperparathyroidism. Kidney Int 2024; 105:562-581. [PMID: 38142040 DOI: 10.1016/j.kint.2023.11.027] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 10/28/2023] [Accepted: 11/17/2023] [Indexed: 12/25/2023]
Abstract
The parathyroid gland is one of the main organs that regulate calcium and phosphorus metabolism. It is mainly composed of chief cells and oxyphil cells. Oxyphil cell counts are low in the parathyroid glands of healthy adults but are dramatically increased in patients with uremia and secondary hyperparathyroidism (SHPT). Increased oxyphil cell counts are related to drug treatment resistance, but the origin of oxyphil cells and the mechanism of proliferation remain unknown. Herein, three types of parathyroid nodules (chief cell nodules, oxyphil cell nodules and mixed nodules, respectively) excised from parathyroid glands of uremic SHPT patients were used for single-cell RNA sequencing (scRNA-seq), other molecular biology studies, and transplantation into nude mice. Through scRNA-seq of parathyroid mixed nodules from three patients with uremic SHPT, we established the first transcriptomic map of the human parathyroid and found a chief-to-oxyphil cell transdifferentiation characterized by gradual mitochondrial enrichment associated with the uremic milieu. Notably, the mitochondrial enrichment and cellular proliferation of chief cell and oxyphil cell nodules decreased significantly after leaving the uremic milieu via transplantation into nude mice. Remarkably, the phenotype of oxyphil cell nodules improved significantly in the nude mice as characterized by decreased mitochondrial content and the proportion of oxyphil cells to chief cells. Thus, our study provides a comprehensive single-cell transcriptome atlas of the human parathyroid and elucidates the origin of parathyroid oxyphil cells and their underlying transdifferentiating mechanism. These findings enhance our understanding of parathyroid disease and may open new treatment perspectives for patients with chronic kidney disease.
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Affiliation(s)
- Jianping Mao
- Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Huaizhou You
- Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Mengjing Wang
- Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | | | - Jing Qian
- Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
| | - Ping Cheng
- Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
| | - Chuhan Lu
- Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
| | - Jing Chen
- Division of Nephrology, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
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Sun L, Wang Z, Zheng M, Hang Z, Liu J, Gao X, Gui Z, Feng D, Zhang D, Han Q, Fei S, Chen H, Tao J, Han Z, Ju X, Gu M, Tan R. Mineral and bone disorder after kidney transplantation: a single-center cohort study. Ren Fail 2023; 45:2210231. [PMID: 37183797 DOI: 10.1080/0886022x.2023.2210231] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2023] Open
Abstract
BACKGROUND The assessment and prevention of mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been standardized. This study aimed to evaluate MBD one year after kidney transplantation (KT) and identify the influencing factors of MBD. METHODS A total of 95 KTRs in our center were enrolled. The changes in bone mineral density (BMD) and bone metabolism biochemical markers, including serum calcium (Ca), phosphorus(P), 25-hydroxyvitamin D(25(OH)vitD), intact parathyroid hormone (iPTH), bone alkaline phosphatase, osteocalcin (OC), type I collagen N-terminal peptide and type I collagen C-terminal peptide (CTx), over one year after KT were assessed. The possible influencing factors of BMD were analyzed. The relationships between bone metabolism biochemical markers were evaluated. The indicators between groups with or without iPTH normalization were also compared. RESULTS MBD after KT was manifested as an increased prevalence of hypophosphatemia and bone loss, persistent 25(OH)vitD deficiency, and partially decreased PTH and bone turnover markers (BTMs). Femoral neck BMD was positively correlated with body mass index (BMI) and postoperative 25(OH)vitD, and negatively correlated with postoperative PTH. Lumbar spine BMD was positively correlated with BMI and preoperative TG, and negatively correlated with preoperative OC and CTx. BMD loss was positively associated with glucocorticoid accumulation. Preoperative and postoperative iPTH was negatively correlated with postoperative serum P and 25(OH)vitD, and positively correlated with postoperative Ca and BTMs. The recipients without iPTH normalization, who accounted for 41.0% of all KTRs, presented with higher Ca, lower P, higher BTMs, advanced age, and a higher prevalence of preoperative parathyroid hyperplasia. CONCLUSIONS MBD persisted after KT, showing a close relationship with hyperparathyroidism, high bone turnover, and glucocorticoid accumulation.
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Affiliation(s)
- Li Sun
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zijie Wang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ming Zheng
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhou Hang
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jiawen Liu
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiang Gao
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zeping Gui
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dengyuan Feng
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dongliang Zhang
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qianguang Han
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Shuang Fei
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hao Chen
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jun Tao
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhijian Han
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaobing Ju
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Min Gu
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ruoyun Tan
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Ильичева ЕA, Шурыгина ИА, Дремина НН, Берсенев ГА, Григорьев ЕГ. [The role of calcium sensitive and vitamin D receptors in the pathogenesis of sporadic multiple parathyroid gland disease]. PROBLEMY ENDOKRINOLOGII 2023; 69:24-34. [PMID: 37448244 PMCID: PMC10350607 DOI: 10.14341/probl13207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/21/2023] [Accepted: 02/20/2023] [Indexed: 07/15/2023]
Abstract
BACKGROUND Sporadic multiple parathyroid gland disease is ¼ cases of primary hyperparathyroidism (PHPT). However, a single tactic for diagnosing and operating volume in patients with this variant of PHPT has not yet been developed. One of the possible directions in the search for pathogenetically substantiated methods of diagnosis and treatment is the study of the molecular genetic features of the disease and associated clinical and laboratory factors. AIM To study the features of the expression of calcium sensitive (CaSR) and vitamin D (VDR) receptors on the surface of parathyroid cells in primary hyperparathyroidism with solitary and multiple lesions of the parathyroid glands, as well as its changes under the influence of a decrease in the filtration function of the kidneys. MATERIALS AND METHODS In a single center observational prospective study with retrospective data collection, there were patients who during 2019-2021. operated on for PHPT, secondary hyperparathyroidism (SHPT) and all cases of tertiary hyperparathyroidism (THPT) operated during 2014-2021. The expression of CaSR, VDR and its relationship with the main laboratory parameters, the clinical variant of hyperparathyroidism, and the morphological substrate were studied. RESULTS The study included 69 patients: 19 with multiple and 25 with solitary PTG near PHPT, 15 with SHPT, 10 with THPT. A statistically significant decrease in the frequency of detection of normal expression of CaSR and VDR receptors occurs in any morphological variant of hyperparathyroidism and is observed in 93-60% of drugs. A decrease in the normal expression of CaSR in hyperplasia is detected statistically significantly less frequently than in adenoma (p≤0.01). The median expression intensity in adenoma was 2.5 (2:3), in hyperplasia 3.5 (3-4) (p≤0.01). The difference in the molecular mechanisms of the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma (PHPT with solitary adenoma) or hyperplasia (SHPT and PHPT with multiple PTG lesions) is realized in the frequency of maintaining normal CaSR expression in the PTG tissue. These mechanisms are implemented at the local level, their variability does not change under the influence of RRT. A common molecular genetic mechanism for the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma or hyperplasia has been found to reduce the frequency of maintaining normal VDR expression in PTG (up to 7-13%), p<0.01. This mechanism is implemented at the local level, its variability changes under the influence of RRT, reaching statistically significant differences in patients with THPT. CONCLUSION The study demonstrates the features of changes in the expression of CaSR and VDR in PHPT with multiple lesions of the parathyroid glands. The relationship between the expression of these receptors and the clinical variant of hyperparathyroidism, the morphological substrate, the main laboratory parameters, and renal function was shown.
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Affiliation(s)
| | | | | | | | - Е. Г. Григорьев
- Иркутский научный центр хирургии и травматологии; Иркутский государственный медицинский университет
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Persistent hyperparathyroidism in long-term kidney transplantation: time to consider a less aggressive approach. Curr Opin Nephrol Hypertens 2023; 32:20-26. [PMID: 36250468 DOI: 10.1097/mnh.0000000000000840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Persistent hyperparathyroidism affects 50% of long-term kidney transplants with preserved allograft function. Timing, options and the optimal target for treatment remain unclear. Clinical practice guidelines recommend the same therapeutic approach as patients with chronic kidney disease. RECENT FINDINGS Mild to moderate elevation of parathyroid hormone (PTH) levels in long-term kidney transplants may not be associated with bone loss and fracture. Recent findings on bone biopsy revealed the lack of association between hypercalcaemic hyperparathyroidism with pathology of high bone turnover. Elevated PTH levels may be required to maintain normal bone volume. Nevertheless, several large observational studies have revealed the association between hypercalcemia and the elevation of PTH levels with unfavourable allograft and patient outcomes. Both calcimimetics and parathyroidectomy are effective in lowering serum calcium and PTH. A recent meta-analysis suggested parathyroidectomy may be performed safely after kidney transplantation without deterioration of allograft function. SUMMARY Treatment of persistent hyperparathyroidism is warranted in kidney transplants with hypercalcemia and markedly elevated PTH levels. A less aggressive approach should be applied to those with mild to moderate elevation. Whether treatments improve outcomes remain to be elucidated.
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Systematic Review of the Treatment of Persistent Hyperparathyroidism Following Kidney Transplantation. Biomedicines 2022; 11:biomedicines11010025. [PMID: 36672533 PMCID: PMC9855347 DOI: 10.3390/biomedicines11010025] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 12/15/2022] [Accepted: 12/19/2022] [Indexed: 12/25/2022] Open
Abstract
Chronic kidney disease-mineral and bone disorder is one of the complications associated with chronic kidney disease. About 10-50% of patients following kidney transplantation have persistent hyperparathyroidism. Hypercalcaemic hyperparathyroidism has a negative impact on the kidney transplant outcome; therefore, it requires treatment. The data regarding the treatment of persistent hyperparathyroidism provided in scientific publications are divergent and contradictory. Therefore, the aim of our systematic review was to evaluate the efficacy of persistent hyperparathyroidism treatment in patients following kidney transplantation. The Cochrane, PubMed, and Scopus databases were browsed independently by two authors. The search strategy included controlled vocabulary and keywords. The effectiveness of calcitriol, paricalcitol, cinacalcet, and parathyroidectomy was compared and analysed. The mean calcium and parathormone (PTH) concentrations per patient in the group of paricalcitol increased by 1.27% and decreased by 35.14% (n = 248); in the group of cinacalcet decreased by 12.09% and 32.16% (n = 368); and in the group of parathyroidectomy decreased by 19.06% and 86.49% (n = 15) at the end of the study compared to the baseline (n = 244, n = 342 and n = 15), respectively. Paricalcitol, cinacalcet, and parathyroidectomy decreased the intact PTH level. Cinacalcet and parathyroidectomy lowered calcium levels in renal transplant patients with hypercalcaemia. Conversely, paricalcitol increased the serum calcium concentration. Cinacalcet seems to be a good candidate in the treatment of post-transplant hyperparathyroidism.
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Xiang Z, Wang M, Miao C, Jin D, Wang H. Mechanism of calcitriol regulating parathyroid cells in secondary hyperparathyroidism. Front Pharmacol 2022; 13:1020858. [PMID: 36267284 PMCID: PMC9577402 DOI: 10.3389/fphar.2022.1020858] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 09/15/2022] [Indexed: 12/03/2022] Open
Abstract
A common consequence of chronic renal disease is secondary hyperparathyroidism (SHPT) and is closely related to the mortality and morbidity of uremia patients. Secondary hyperparathyroidism (SHPT) is caused by excessive PTH production and release, as well as parathyroid enlargement. At present, the mechanism of cell proliferation in secondary hyperparathyroidism (SHPT) is not completely clear. Decreased expression of the vitamin D receptor (VDR) and calcium-sensing receptor (CaSR), and 1,25(OH)2D3 insufficiency all lead to a decrease in cell proliferation suppression, and activation of multiple pathways is also involved in cell proliferation in renal hyperparathyroidism. The interaction between the parathormone (PTH) and parathyroid hyperplasia and 1,25(OH)2D3 has received considerable attention. 1,25(OH)2D3 is commonly applied in the therapy of renal hyperparathyroidism. It regulates the production of parathormone (PTH) and parathyroid cell proliferation through transcription and post-transcription mechanisms. This article reviews the role of 1,25(OH)2D3 in parathyroid cells in secondary hyperparathyroidism and its current understanding and potential molecular mechanism.
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Cianciolo G, Tondolo F, Barbuto S, Angelini A, Ferrara F, Iacovella F, Raimondi C, La Manna G, Serra C, De Molo C, Cavicchi O, Piccin O, D'Alessio P, De Pasquale L, Felisati G, Ciceri P, Galassi A, Cozzolino M. A roadmap to parathyroidectomy for kidney transplant candidates. Clin Kidney J 2022; 15:1459-1474. [PMID: 35892022 PMCID: PMC9308095 DOI: 10.1093/ckj/sfac050] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Indexed: 11/25/2022] Open
Abstract
Chronic kidney disease mineral and bone disorder may persist after successful kidney transplantation. Persistent hyperparathyroidism has been identified in up to 80% of patients throughout the first year after kidney transplantation. International guidelines lack strict recommendations about the management of persistent hyperparathyroidism. However, it is associated with adverse graft and patient outcomes, including higher fracture risk and an increased risk of all-cause mortality and allograft loss. Secondary hyperparathyroidism may be treated medically (vitamin D, phosphate binders and calcimimetics) or surgically (parathyroidectomy). Guideline recommendations suggest medical therapy first but do not clarify optimal parathyroid hormone targets or indications and timing of parathyroidectomy. There are no clear guidelines or long-term studies about the impact of hyperparathyroidism therapy. Parathyroidectomy is more effective than medical treatment, although it is associated with increased short-term risks. Ideally parathyroidectomy should be performed before kidney transplantation to prevent persistent hyperparathyroidism and improve graft outcomes. We now propose a roadmap for the management of secondary hyperparathyroidism in patients eligible for kidney transplantation that includes the indications and timing (pre- or post-kidney transplantation) of parathyroidectomy, the evaluation of parathyroid gland size and the integration of parathyroid gland size in the decision-making process by a multidisciplinary team of nephrologists, radiologists and surgeons.
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Affiliation(s)
- Giuseppe Cianciolo
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Francesco Tondolo
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Simona Barbuto
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Andrea Angelini
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Francesca Ferrara
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Francesca Iacovella
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Concettina Raimondi
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Gaetano La Manna
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Carla Serra
- Interventional, Diagnostic and Therapeutic Ultrasound Unit, Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Universitaria Sant’Orsola Malpighi Hospital, Bologna, Italy
| | - Chiara De Molo
- Interventional, Diagnostic and Therapeutic Ultrasound Unit, Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Universitaria Sant’Orsola Malpighi Hospital, Bologna, Italy
| | - Ottavio Cavicchi
- Department of Otolaryngology Head and Neck Surgery, IRCSS Azienda Ospedaliero Universitaria di Bologna, Policlinico Sant'Orsola, Bologna, Italy
| | - Ottavio Piccin
- Department of Otolaryngology Head and Neck Surgery, IRCSS Azienda Ospedaliero Universitaria di Bologna, Policlinico Sant'Orsola, Bologna, Italy
| | - Pasquale D'Alessio
- Department of Otolaryngology Head and Neck Surgery, IRCSS Azienda Ospedaliero Universitaria di Bologna, Policlinico Sant'Orsola, Bologna, Italy
| | - Loredana De Pasquale
- Department of Otolaryngology, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy
| | - Giovanni Felisati
- Department of Otolaryngology, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy
| | - Paola Ciceri
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy
| | - Andrea Galassi
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy
| | - Mario Cozzolino
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy
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Tsujita M, Doi Y, Obi Y, Hamano T, Tomosugi T, Futamura K, Okada M, Hiramitsu T, Goto N, Isaka Y, Takeda A, Narumi S, Watarai Y. Cholecalciferol Supplementation Attenuates Bone Loss in Incident Kidney Transplant Recipients: A Prespecified Secondary Endpoint Analysis of a Randomized Controlled Trial. J Bone Miner Res 2022; 37:303-311. [PMID: 34747516 PMCID: PMC9298992 DOI: 10.1002/jbmr.4469] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 10/12/2021] [Accepted: 11/04/2021] [Indexed: 12/23/2022]
Abstract
Vitamin D deficiency, persistent hyperparathyroidism, and bone loss are common after kidney transplantation (KTx). However, limited evidence exists regarding the effects of cholecalciferol supplementation on parathyroid hormone (PTH) and bone loss after KTx. In this prespecified secondary endpoint analysis of a randomized controlled trial, we evaluated changes in PTH, bone metabolic markers, and bone mineral density (BMD). At 1 month post-transplant, we randomized 193 patients to an 11-month intervention with cholecalciferol (4000 IU/d) or placebo. The median baseline 25-hydroxyvitamin D (25[OH]D) level was 10 ng/mL and 44% of participants had osteopenia or osteoporosis. At the end of the study, the median 25(OH)D level was increased to 40 ng/mL in the cholecalciferol group and substantially unchanged in the placebo group. Compared with placebo, cholecalciferol significantly reduced whole PTH concentrations (between-group difference of -15%; 95% confidence interval [CI] -25 to -3), with greater treatment effects in subgroups with lower 25(OH)D, lower serum calcium, or higher estimated glomerular filtration rate (pint < 0.05). The percent change in lumbar spine (LS) BMD from before KTx to 12 months post-transplant was -0.2% (95% CI -1.4 to 0.9) in the cholecalciferol group and -1.9% (95% CI -3.0 to -0.8) in the placebo group, with a significant between-group difference (1.7%; 95% CI 0.1 to 3.3). The beneficial effect of cholecalciferol on LS BMD was prominent in patients with low bone mass pint < 0.05). Changes in serum calcium, phosphate, bone metabolic markers, and BMD at the distal radius were not different between groups. In mediation analyses, change in whole PTH levels explained 39% of treatment effects on BMD change. In conclusion, 4000 IU/d cholecalciferol significantly reduced PTH levels and attenuated LS BMD loss after KTx. This regimen has the potential to eliminate vitamin D deficiency and provides beneficial effects on bone health even under glucocorticoid treatment. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Affiliation(s)
- Makoto Tsujita
- Department of Transplant Nephrology and Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan.,Department of Kidney Transplantation, Masuko Memorial Hospital, Nagoya, Japan
| | - Yohei Doi
- Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Yoshitsugu Obi
- Division of Nephrology, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Takayuki Hamano
- Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan.,Department of Nephrology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Toshihide Tomosugi
- Department of Transplant Nephrology and Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Kenta Futamura
- Department of Transplant Nephrology and Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Manabu Okada
- Department of Transplant Nephrology and Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Takahisa Hiramitsu
- Department of Transplant Nephrology and Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Norihiko Goto
- Department of Transplant Nephrology and Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Yoshitaka Isaka
- Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Asami Takeda
- Department of Nephrology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Shunji Narumi
- Department of Transplant Nephrology and Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Yoshihiko Watarai
- Department of Transplant Nephrology and Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
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Bokuda K, Morimoto S, Seki Y, Takano N, Ichihara A. Effect of Pretransplant Use of Calcimimetic on Parathyroid Function after Renal Transplantation. Int J Endocrinol 2021; 2021:1999777. [PMID: 34616449 PMCID: PMC8490070 DOI: 10.1155/2021/1999777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 09/16/2021] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE Persistence of hyperparathyroidism (HPT) after renal transplantation leads to undesirable outcomes such as increase in cardiovascular events, graft dysfunction, and increased mortality. Options for therapy include medical management with calcimimetic or operative management. The present study was undertaken to evaluate the natural history of HPT after renal transplantation and to determine risk factors for persistent HPT in the era of calcimimetic. DESIGN The study is a retrospective review of data from 74 consecutive patients who underwent renal transplantation at our institution from April 2011 to November 2019. METHODS The natural history of HPT after renal transplantation and associations between intact parathyroid hormone (PTH) level after transplantation and clinical variables such as age, sex, duration of pretransplant dialysis, and use of calcimimetic before transplantation were evaluated. RESULTS Intact PTH decreased after renal transplantation in most of the patients without receiving parathyroidectomy. Known risk factors of persistent HPT did not associate with intact PTH level after renal transplantation in patients who had been receiving calcimimetic before transplantation. CONCLUSION In conclusion, we have found that HPT after renal transplantation could be managed successfully by medical treatments. When predicting the prognosis of HPT after transplantation, pretransplant use of calcimimetic should be taken into consideration.
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Affiliation(s)
- Kanako Bokuda
- Department of Endocrinology and Hypertension, Tokyo Women's Medical University, Tokyo, Japan
| | - Satoshi Morimoto
- Department of Endocrinology and Hypertension, Tokyo Women's Medical University, Tokyo, Japan
| | - Yasufumi Seki
- Department of Endocrinology and Hypertension, Tokyo Women's Medical University, Tokyo, Japan
| | - Noriyoshi Takano
- Department of Endocrinology and Hypertension, Tokyo Women's Medical University, Tokyo, Japan
| | - Atsuhiro Ichihara
- Department of Endocrinology and Hypertension, Tokyo Women's Medical University, Tokyo, Japan
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11
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Verdelli C, Tavanti GS, Corbetta S. Intratumor heterogeneity in human parathyroid tumors. Histol Histopathol 2020; 35:1213-1228. [PMID: 32468569 DOI: 10.14670/hh-18-230] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Parathyroid tumors are the second most common endocrine neoplasia after thyroid neoplasia. They are mostly associated with impaired parathormone (PTH) synthesis and release determining the metabolic and clinical condition of primary hyperparathyroidism (PHPT). PHPT is the third most prevalent endocrine disorder, mainly affecting postmenopausal women. Parathyroid benign tumors, both adenomas of a single gland or hyperplasia involving all the glands, are the main histotypes, occurring in more than 95% of PHPT cases. The differential diagnosis between benign and malignant parathyroid lesions is a challenge for clinicians. It relies on histologic features, which display significant overlap between the histotypes with different clinical outcomes. Parathyroid adenomas and hyperplasia have been considered so far as a unique monoclonal/polyclonal entity, while accumulating evidence suggest great heterogeneity. Intratumor parathyroid heterogeneity involves tumor cell type, as well as tumor cell function, in terms of PTH synthesis and secretion, and of expression patterns of membrane and nuclear receptors (calcium sensing receptor, vitamin D receptor, α-klotho receptor and others). Intratumor heterogeneity can also interfere with cell molecular biology, in regard to clonality, oncosuppressor gene expression (such as MEN1 and HRPT2/CDC73), transcription factors (GCM2, TBX1) and microRNA expression. Such heterogeneity is likely involved in the phenotypic variability of the parathyroid tumors, and it should be considered in the clinical management, though at present target therapies are not available, with the exception of the calcium sensing receptor agonists.
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Affiliation(s)
- C Verdelli
- Laboratory of Experimental Endocrinology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | - G S Tavanti
- Laboratory of Experimental Endocrinology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | - S Corbetta
- Endocrinology and Diabetology Service, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.,Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
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12
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Relative hypophosphatemia early after transplantation is a predictor of good kidney graft function. Clin Exp Nephrol 2019; 23:1161-1168. [PMID: 31214874 DOI: 10.1007/s10157-019-01756-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Accepted: 06/02/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND Phosphate level is a potent independent risk factor for cardiovascular disease and mortality in patients with chronic kidney disease. The association between hypophosphatemia and kidney function in kidney transplant patients is uncertain. METHODS In total, 90 kidney transplant recipients were divided into two groups: one group of patients with hypophosphatemia and the other group without hypophosphatemia. The recipients with hypophosphatemia were identified as having less than or equal to the lowest quartile of serum phosphate levels at 1-, 3-, and 12-month post-transplant. The cumulative kidney survival rates were calculated for each group using the Kaplan-Meier method, and the adjusted hazard ratio (HR) was calculated using the Cox regression model. RESULTS The mean age of patients was 47 years and the median follow-up period was 58 months. During the follow-up period, the following results were demonstrated in 90 transplant patients: graft loss (n = 6), mortality (n = 3). According to the Kaplan-Meier analysis results, the patients with hypophosphatemia demonstrated a significantly lower risk of 30% decline in eGFR compared to those without hypophosphatemia at 1- and 3-month post-transplant, but not at 12-month post-transplant. After adjusting for confounding factors, hypophosphatemia at 1- and 3-month post-transplant was an independent predictor of good kidney survival (HR 0.31, 95% CI 0.10-0.82 and HR 0.31, 95% CI 0.07-0.92, respectively). CONCLUSIONS Our findings suggest that hypophosphatemia during the first 3 months after kidney transplantation was associated with better kidney survival.
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13
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Susantitaphong P, Vadcharavivad S, Susomboon T, Singhan W, Dumrongpisutikul N, Jakchairoongruang K, Eiam-Ong S, Praditpornsilpa K. The effectiveness of cinacalcet: a randomized, open label study in chronic hemodialysis patients with severe secondary hyperparathyroidism. Ren Fail 2019; 41:326-333. [PMID: 31014177 PMCID: PMC6493313 DOI: 10.1080/0886022x.2018.1562356] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Background: Secondary hyperparathyroidism (SHPT) is associated with high incidences of cardiovascular disease, bone fracture, and mortality. This study was conducted to demonstrate the effectiveness of cinacalcet treatment on chronic kidney disease-mineral bone disorder (CKD-MBD) markers in chronic hemodialysis patients with severe SHPT. Methods: In phase 1, 30 adult HD patients were randomized to cinacalcet or control groups for 12 weeks to explore the achievement of >30% reduction of iPTH. In phase 2, 45 patients were participated to further explore the effect of cinacalcet on CKD-MBD parameters for 24-week follow up and 12 additional weeks after cinacalcet discontinuation. Results: In phase 1, the baseline serum iPTH levels were not different [1374 (955, 1639) pg/mL in the control group vs. 1191 (1005, 1884) pg/mL in the cinacalcet group], the percentage of patients achieving iPTH target were significantly higher in the treatment group [80% vs. 13%, p = .001]. In phase 2, the significant reductions of iPTH, FGF-23, tartrate-resistant acid phosphatase 5b, and slightly decreased size of parathyroid gland and stabilized vascular calcification were observed at 24-week follow up and markedly rebounded after discontinuation of cinacalcet. Conclusions: The effectiveness of cinacalcet were still obviously demonstrated even in chronic HD patients with severe SHPT. In addition, the improvements of bone markers and FGF-23, and stabilization of vascular calcification were observed. Therefore, cinacalcet can provide salutary effects on CKD-MBD in severe SHPT and might be an initially effective PTH-lowering therapy prior to surgical parathyroidectomy as well as an alternative treatment in the patients unsuitable for surgery. Clinical trial registration: ClinicalTrials.gov: NCT02056730. Date of registration: February 4, 2014.
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Affiliation(s)
- Paweena Susantitaphong
- a Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital , Chulalongkorn University , Bangkok , Thailand
| | | | - Teerada Susomboon
- b Department of Pharmacy Practice , Chulalongkorn University , Bangkok , Thailand
| | - Wanchana Singhan
- b Department of Pharmacy Practice , Chulalongkorn University , Bangkok , Thailand
| | | | | | - Somchai Eiam-Ong
- a Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital , Chulalongkorn University , Bangkok , Thailand
| | - Kearkiat Praditpornsilpa
- a Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital , Chulalongkorn University , Bangkok , Thailand
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14
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Kitamura M, Mochizuki Y, Kitamura S, Mukae Y, Nakanishi H, Ota Y, Muta K, Yamashita H, Obata Y, Iwata T, Nishikido M, Kawanami S, Takashima M, Sasaki H, Sakai H, Mukae H, Nishino T. Prediction of Nonadherence and Renal Prognosis by Pre-Transplantation Serum Phosphate Levels. Ann Transplant 2019; 24:260-267. [PMID: 31073118 PMCID: PMC6530439 DOI: 10.12659/aot.914909] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Background Identifying characteristics of patients at high risk of poor adherence before transplantation would be advantageous. However, the optimal approach for characterizing such patients remains unknown. We aimed to evaluate the association between factors for hemodialysis nonadherence and post-transplant renal prognosis. We hypothesized that these factors would influence post-transplantation adherence and worsen renal prognosis. Material/Methods We reviewed patients on hemodialysis who underwent kidney transplantation at our hospital between 2000 and 2017 to identify risk factors associated with poor prognosis. The patients’ background and pre-transplantation data, known hemodialysis nonadherence factors, serum phosphate and potassium levels, and interdialytic weight gains were evaluated. The primary endpoint was renal death. We also evaluated the fluctuation of calcineurin inhibitor concentration and weight gain after transplantation. Results Seventy-seven patients were eligible, and the mean observational period was 83.2 months (standard deviation, 50.5). Thirteen patients reached the endpoint. Cox proportional hazards regression analysis showed that pre-transplantation serum phosphate level was a risk factor for renal death (p<0.05), while serum potassium levels and weight gain were not. In addition, fluctuation of calcineurin inhibitor concentration was observed in patients with higher phosphate levels before transplantation (p=0.03). Weight gain after transplantation was not associated with the hemodialysis nonadherence factors. Conclusions High pre-transplantation serum phosphate levels are considered to represent poor drug adherence and/or an unhealthy lifestyle. Patient education that conveys the importance of adhering to medications and provides nutritional guidance is crucial for improving post-transplantation renal prognosis.
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Affiliation(s)
- Mineaki Kitamura
- Division of Blood Purification, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan.,Department of Nephrology, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan
| | - Yasushi Mochizuki
- Division of Blood Purification, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan.,Department of Urology, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan
| | - Satoko Kitamura
- Division of Blood Purification, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan.,Department of Nephrology, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan
| | - Yuta Mukae
- Department of Urology, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan
| | - Hiromi Nakanishi
- Department of Urology, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan
| | - Yuki Ota
- Department of Nephrology, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan
| | - Kumiko Muta
- Department of Nephrology, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan
| | - Hiroshi Yamashita
- Department of Nephrology, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan
| | - Yoko Obata
- Department of Nephrology, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan
| | - Takahisa Iwata
- Department of Urology, Isahaya General Hospital, Isahaya, Nagasaki, Japan
| | | | - Sachiko Kawanami
- Department of Nursing, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan
| | - Miwa Takashima
- Division of Dietary Service, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan
| | - Hitoshi Sasaki
- Hospital Pharmacy, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan
| | - Hideki Sakai
- Division of Blood Purification, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan.,Department of Urology, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan
| | - Hiroshi Mukae
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki City, Nagasaki, Japan
| | - Tomoya Nishino
- Department of Nephrology, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan
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15
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Laucyte-Cibulskiene A, Boreikaite E, Aucina G, Gudynaite M, Rudminiene I, Anisko S, Vareikiene L, Gumbys L, Valanciene D, Ryliskyte L, Strupas K, Rimsevicius L, Miglinas M. Usefulness of pretransplant aortic arch calcification evaluation for kidney transplant outcome prediction in one year follow-up. Ren Fail 2018; 40:201-208. [PMID: 29619867 PMCID: PMC6014335 DOI: 10.1080/0886022x.2018.1455588] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Vascular calcification (VC) is linked to post-transplant cardiovascular events and hypercalcemia which may influence kidney graft function in the long term. We aimed to evaluate whether pretransplant aortic arch calcification (AoAC) can predict post-transplant cardiovascular or cerebrovascular events (CVEs), and to assess its association with post-transplant plasma calcium levels and renal function in one-year follow-up. Our single-center observational prospective study enrolled 37 kidney transplant recipients (KTR) without previous history of vascular events. Two radiologists evaluated pretransplant AoAC on chest X-ray as suggested by Ogawa et al. in 2009. Cohen’s kappa coefficient was 0.71. The mismatching results were repeatedly reviewed and resulted in consensus. Carotid-femoral (cfPWV) and carotid-radial pulse wave velocity (crPWV) was measured using applanation tonometry before and one year after transplantation. Patient clinical, biochemical data, and cardiovascular/CVE rate were monitored within 1 year. We found out that eGFR1year correlated with eGFRdischarge and calcium based on hospital discharge data (β = 0.563, p = .004 and β = 51.360, p = .026, respectively). Multivariate linear regression revealed that donor age, donor gender, and recipient eGFRdischarge (R-squared 0.65, p = .002) better predict eGFR1year than AoAC combined with recipient eGFRdischarge (R-squared 0.35, p = .006). During 1-year follow-up, four (10.81%) patients experienced cardiovascular events, which were predicted by PWV ratio (HR 7.549, p = .045), but not related to AoAC score (HR 1.044, p = .158). In conclusion, KTR without previous vascular events have quite low cardiovascular/CVE rate within 1-year follow-up. VC evaluated as AoAC on pretransplant chest X-ray together with recipient eGFRdischarge could be related to kidney function in one-year follow-up.
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Affiliation(s)
- Agne Laucyte-Cibulskiene
- a Clinic of Gastroneterology, Nephrourology and Abdominal Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University , Vilnius , Lithuania
| | | | - Gediminas Aucina
- b Faculty of Medicine , Vilnius University , Vilnius , Lithuania
| | - Migle Gudynaite
- c Centre of Nephrology, Vilnius University Hospital Santaros Clinics , Vilnius , Lithuania
| | - Ilona Rudminiene
- c Centre of Nephrology, Vilnius University Hospital Santaros Clinics , Vilnius , Lithuania
| | - Sigita Anisko
- c Centre of Nephrology, Vilnius University Hospital Santaros Clinics , Vilnius , Lithuania
| | - Loreta Vareikiene
- c Centre of Nephrology, Vilnius University Hospital Santaros Clinics , Vilnius , Lithuania
| | - Liutauras Gumbys
- d Centre of Radiology and Nuclear Medicine , Vilnius University Hospital Santaros Clinics , Vilnius , Lithuania
| | - Dileta Valanciene
- b Faculty of Medicine , Vilnius University , Vilnius , Lithuania.,d Centre of Radiology and Nuclear Medicine , Vilnius University Hospital Santaros Clinics , Vilnius , Lithuania
| | - Ligita Ryliskyte
- b Faculty of Medicine , Vilnius University , Vilnius , Lithuania
| | - Kestutis Strupas
- a Clinic of Gastroneterology, Nephrourology and Abdominal Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University , Vilnius , Lithuania
| | - Laurynas Rimsevicius
- a Clinic of Gastroneterology, Nephrourology and Abdominal Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University , Vilnius , Lithuania
| | - Marius Miglinas
- a Clinic of Gastroneterology, Nephrourology and Abdominal Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University , Vilnius , Lithuania
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16
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Vulpio C, Bossola M. Parathyroid Nodular Hyperplasia and Responsiveness to Drug Therapy in Renal Secondary Hyperparathyroidism: An Open Question. Ther Apher Dial 2017; 22:11-21. [PMID: 28980761 DOI: 10.1111/1744-9987.12604] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 06/01/2017] [Accepted: 07/13/2017] [Indexed: 11/29/2022]
Abstract
The goal of the pharmacological therapy in secondary hyperparathyroidism (SHPT) is to reduce serum levels of parathyroid hormone and phosphorus, to correct those of calcium and vitamin D, to arrest or reverse the parathyroid hyperplasia. However, when nodular hyperplasia or an autonomous adenoma develops, surgery may be indicated. We reviewed the literature with the aim of defining if the echographic criteria predictive of unresponsiveness of SHPT to calcitriol therapy are valid also in the cinacalcet era and if drug therapy may reverse nodular hyperplasia of parathyroid gland (PTG). The responsiveness to therapy and regression of the nodular hyperplasia of PTG remains an open question in the calcimimetic era as well as the cutoff between medical and surgical therapy. Prospective studies are needed in order to clarify if an earlier use of cinacalcet in moderate SHPT might arrest the progression of parathyroid growth and stabilize SHPT.
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Affiliation(s)
- Carlo Vulpio
- Department of Surgery, Catholic University of Sacred Heart, Rome, Italy
| | - Maurizio Bossola
- Department of Surgery, Catholic University of Sacred Heart, Rome, Italy
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17
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Nakamura M, Ishida H, Takiguchi S, Tanaka K, Marui Y. Pathologic Features of Parathyroid Glands Associated With the Pathogenesis of Long-lasting Persistent Hyperparathyroidism After Kidney Transplantation in Long-term Dialysis Patients. Transplant Proc 2016; 48:874-7. [PMID: 27234756 DOI: 10.1016/j.transproceed.2015.12.108] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 12/30/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Persistent hyperparathyroidism in kidney transplant recipients may be prolonged for a few years, and in these cases, parathyroidectomy is indicated even if graft function is satisfactory. The aim of this study was to characterize the parathyroid glands in long-term dialysis recipients and determine the pathogenesis of persistent hyperparathyroidism. METHODS We analyzed 44 parathyroid glands resected from 11 patients who underwent parathyroidectomy after kidney transplantation. The histopathologic types and weights of all the parathyroid glands were evaluated. RESULTS The mean dialysis period was 15.8 years, and the time from kidney transplantation to parathyroidectomy ranged from 3.5 to 89 months. Nodular hyperplasia was present in parathyroid glands in all cases. The mean glandular weight was 396.0 ± 299.0 mg, and the maximum glandular weight was 3200 mg. Seven patients who underwent parathyroidectomy >1 year after kidney transplantation (late PT) were compared with 4 patients who underwent parathyroidectomy within 10 months after transplantation (early PT). The maximum (442.9 vs 1503 mg; P = .018) and mean (312.5 ± 177.4 mg vs 1135.6 ± 977.7 mg; P = .001) glandular weights were significantly lower in patients who underwent late PT compared with those who received early PT. Based on the histopathologic type and glandular weight of each parathyroid gland, nodular hyperplasia in glands ≤150 mg was common in patients who underwent late PT. CONCLUSIONS The presence of nodular hyperplasia in parathyroid glands with a low weight may be involved in long-lasting persistent hyperparathyroidism in patients undergoing long-term dialysis.
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Affiliation(s)
- M Nakamura
- Department of Transplant Surgery, Tokai University School of Medicine, Isehara-city, Kanagawa, Japan.
| | - H Ishida
- Department of Transplant Surgery, Tokai University School of Medicine, Isehara-city, Kanagawa, Japan
| | - S Takiguchi
- Department of Transplant Surgery, Tokai University School of Medicine, Isehara-city, Kanagawa, Japan
| | - K Tanaka
- Kidney Center, Toranomon Hospital, Minato-ku, Tokyo, Japan
| | - Y Marui
- Toranomon Branch Hospital, Kawasaki-city, Kanagawa, Japan
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18
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Abstract
BACKGROUND Persistent hyperparathyroidism (HPT) after renal transplantation (RTx), termed tertiary HPT (THPT), is not uncommon. However, risk factors and appropriate operative procedures for THPT are poorly understood. METHODS A retrospective study of patients who underwent RTx without pre-transplant parathyroidectomy (PTx) was performed at our hospital between January 2001 and March 2011. Risk factors for the development of THPT were investigated by comparing THPT and non-THPT groups. We retrospectively analyzed patients with THPT who underwent total PTx with forearm autograft. Pre- and postoperative (1 year after PTx) laboratory results were analyzed for PTx efficacy. RESULTS Data for 520 patients were analyzed. On multivariate analysis, long dialysis duration (p = 0.009, hazard ratio (HR) 1.01), large maximum parathyroid gland size before RTx (p = 0.003, HR 1.23), pre-RTx high intact parathyroid hormone (iPTH) (p = 0.041, HR 1.01), post-RTx (<2 weeks) high calcium (Ca) (p < 0.001, HR 25.04), and post-RTx high alkaline phosphatase (ALP) (p = 0.027, HR 0.99) were identified as risk factors for THPT. Patients who underwent PTx showed significant improvement compared with baseline for serum Ca, phosphorus, iPTH, and ALP. Serum creatinine showed no significant difference. CONCLUSIONS Several risk factors for THPT development were identified. PTx for patients with THPT significantly improved serum Ca, iPTH, ALP, and phosphorous levels. There was no significant difference in renal function after PTx. Therefore, total PTx with forearm autograft may be an appropriate surgical approach for patients with THPT.
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19
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Nel JD, Epstein S. Metabolic Bone Disease in the Post-transplant Population: Preventative and Therapeutic Measures. Med Clin North Am 2016; 100:569-86. [PMID: 27095646 DOI: 10.1016/j.mcna.2016.01.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Post-transplant bone disease contributes significantly to patients' morbidity and mortality after transplantation and has an impact on their quality of life. This article discusses the major contributors to mechanisms causing bone loss, highlighting the role of preexisting disease in both kidney and liver failure and contributions from glucocorticoids and calcineurin inhibitors. Suggested monitoring and investigations are reviewed as well as treatment as far as the current literature supports, emphasizing the difference between kidney and liver recipients.
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Affiliation(s)
- Johan Daniël Nel
- Division of Nephrology, Department of Medicine, Tygerberg Hospital and University of Stellenbosch, PO Box 241, Cape Town, Western Cape 8000, South Africa.
| | - Sol Epstein
- Mt Sinai School of Medicine, New York, NY, USA; University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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20
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Fukagawa M, Drüeke TB. Parathyroidectomy or Calcimimetic to Treat Hypercalcemia after Kidney Transplantation? J Am Soc Nephrol 2016; 27:2221-4. [PMID: 26772195 DOI: 10.1681/asn.2015121349] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Affiliation(s)
- Masafumi Fukagawa
- Division of Nephrology, Endocrinology, and Metabolism, Tokai University School of Medicine, Isehara, Japan; and
| | - Tilman B Drüeke
- Institut National de la Santé et de la Recherche Médicale Unit 1018, Team 5, Centre de Recherche en Epidémiologie et Santé des Populations, Hôpital Paul Brousse, Paris-Sud University and Versailles Saint-Quentin-en-Yvelines University (Paris-Ile-de-France-Ouest University), Villejuif, France
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21
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D’Marco L, Bellasi A, Mazzaferro S, Raggi P. Vascular calcification, bone and mineral metabolism after kidney transplantation. World J Transplant 2015; 5:222-230. [PMID: 26722649 PMCID: PMC4689932 DOI: 10.5500/wjt.v5.i4.222] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2015] [Revised: 09/01/2015] [Accepted: 11/17/2015] [Indexed: 02/05/2023] Open
Abstract
The development of end stage renal failure can be seen as a catastrophic health event and patients with this condition are considered at the highest risk of cardiovascular disease among any other patient groups and risk categories. Although kidney transplantation was hailed as an optimal solution to such devastating disease, many issues related to immune-suppressive drugs soon emerged and it became evident that cardiovascular disease would remain a vexing problem. Progression of chronic kidney disease is accompanied by profound alterations of mineral and bone metabolism that are believed to have an impact on the cardiovascular health of patients with advanced degrees of renal failure. Cardiovascular risk factors remain highly prevalent after kidney transplantation, some immune-suppression drugs worsen the risk profile of graft recipients and the alterations of mineral and bone metabolism seen in end stage renal failure are not completely resolved. Whether this complex situation promotes progression of vascular calcification, a hall-mark of advanced chronic kidney disease, and whether vascular calcifications contribute to the poor cardiovascular outcome of post-transplant patients is reviewed in this article.
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22
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Taweesedt PT, Disthabanchong S. Mineral and bone disorder after kidney transplantation. World J Transplant 2015; 5:231-242. [PMID: 26722650 PMCID: PMC4689933 DOI: 10.5500/wjt.v5.i4.231] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Revised: 09/11/2015] [Accepted: 10/27/2015] [Indexed: 02/05/2023] Open
Abstract
After successful kidney transplantation, accumulated waste products and electrolytes are excreted and regulatory hormones return to normal levels. Despite the improvement in mineral metabolites and mineral regulating hormones after kidney transplantation, abnormal bone and mineral metabolism continues to present in most patients. During the first 3 mo, fibroblast growth factor-23 (FGF-23) and parathyroid hormone levels decrease rapidly in association with an increase in 1,25-dihydroxyvitamin D production. Renal phosphate excretion resumes and serum calcium, if elevated before, returns toward normal levels. FGF-23 excess during the first 3-12 mo results in exaggerated renal phosphate loss and hypophosphatemia occurs in some patients. After 1 year, FGF-23 and serum phosphate return to normal levels but persistent hyperparathyroidism remains in some patients. The progression of vascular calcification also attenuates. High dose corticosteroid and persistent hyperparathyroidism are the most important factors influencing abnormal bone and mineral metabolism in long-term kidney transplant (KT) recipients. Bone loss occurs at a highest rate during the first 6-12 mo after transplantation. Measurement of bone mineral density is recommended in patients with estimated glomerular filtration rate > 30 mL/min. The use of active vitamin D with or without bisphosphonate is effective in preventing early post-transplant bone loss. Steroid withdrawal regimen is also beneficial in preservation of bone mass in long-term. Calcimimetic is an alternative therapy to parathyroidectomy in KT recipients with persistent hyperparathyroidism. If parathyroidectomy is required, subtotal to near total parathyroidectomy is recommended. Performing parathyroidectomy during the waiting period prior to transplantation is also preferred in patients with severe hyperparathyroidism associated with hypercalcemia.
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Borrego Utiel FJ, Bravo Soto JA, Merino Pérez MJ, González Carmelo I, López Jiménez V, García Álvarez T, Acosta Martínez Y, Mazuecos Blanca MA. Effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism. Nefrologia 2015; 35:363-73. [PMID: 26306956 DOI: 10.1016/j.nefro.2015.06.018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Accepted: 01/16/2015] [Indexed: 10/23/2022] Open
Abstract
INTRODUCTION Secondary hyperparathyroidism is highly prevalent in kidney transplant recipients, and commonly results in hypercalcaemia; an association to osteopenia and bone fractures has also been observed. Paricalcitol has proved effective to control secondary hyperparathyroidism in chronic kidney disease in both dialysed and non-dialysed patients, with a low hypercalcaemia incidence. Currently available experience on paricalcitol use in kidney transplant recipients is scarce. Our main aim was to show the effect of paricalcitol on mineral bone metabolism in kidney transplant recipients with secondary hyperparathyroidism. MATERIAL AND METHODS A retrospective multicentre study in kidney transplant recipients aged>18 years with a 12-month or longer post-transplantation course, stable renal function, having received paricalcitol for more than 12 months, with available clinical follow-up for a 24-month period. RESULTS A total of 69 patients with a 120 ± 92-month post-transplantation course were included. Baseline creatinine was 2.2 ± 0.9 mg/dl y GFR-MDRD was 36 ± 20 ml/min/1.73 m(2). Paricalcitol doses were gradually increased during the study: baseline 3.8 ± 1.9 μg/week, 12 months 5.2 ± 2.4 μg/week; 24 months 6.0 ± 2.9 μg/week (P<.001). Serum PTH levels showed a significant fast decline: baseline 288 ± 152 pg/ml; 6 months 226 ± 184 pg/ml; 12 months 207 ± 120; 24 months 193 ± 119 pg/ml (P<.001). Reduction from baseline PTH was ≥30% in 42.4% of patients at 12 months y in 65.2% of patients at 24 months. Alkaline phosphatase showed a significant decrease in first 6 months followed by a plateau: baseline 92 ± 50 IU/l; 6 months 85 ± 36 IU/l, 12 months 81 ± 39 IU/l (P<.001). Overall, no changes were observed in serum calcium and phosphorus, and in urine calcium excretion. PTH decline was larger in patients with higher baseline levels. Patients with lower baseline calcium levels showed significantly increased levels (mean increase was 0.5-0.6 mg/dl) but still within normal range, whereas patients with baseline calcium>10mg/dl showed gradually decreasing levels. Fifteen (21.7%) patients had received prior calcitriol therapy. When shifted to paricalcitol, such patients required paricalcitol doses significantly larger than those not having received calcitriol. Paricalcitol was used concomitantly to cinacalcet in 11 patients with significant PTH reductions being achieved; clinical course was similar to other patients and paricalcitol doses were also similar. CONCLUSIONS Paricalcitol is an effective therapy for secondary hyperparathyroidism in kidney transplant recipients. Overall, no significant changes were observed in calcium and phosphorus levels or urinary excretion. Patients having previously received calcitriol required higher paricalcitol doses. When used in patients receiving cinacalcet, paricalcitol results in a significant PTH fall, with paricalcitol doses being similar to those used in patients not receiving cinacalcet.
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Affiliation(s)
- Hirotaka Komaba
- Division of Nephrology, Endocrinology and Metabolism; Tokai University School of Medicine; Isehara Japan
| | - Masafumi Fukagawa
- Division of Nephrology, Endocrinology and Metabolism; Tokai University School of Medicine; Isehara Japan
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25
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Goto S, Komaba H, Fukagawa M. Pathophysiology of parathyroid hyperplasia in chronic kidney disease: preclinical and clinical basis for parathyroid intervention. NDT Plus 2015; 1:iii2-iii8. [PMID: 25983967 PMCID: PMC4421132 DOI: 10.1093/ndtplus/sfn079] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2008] [Accepted: 03/14/2008] [Indexed: 01/15/2023] Open
Abstract
Secondary hyperparathyroidism is characterised by excessive secretion of parathyroid hormone and parathyroid hyperplasia, resulting in both skeletal and extraskeletal consequences. Recent basic and clinical studies have brought considerable advances in our understanding of the pathophysiology of parathyroid hyperplasia and have also provided practical therapeutic approaches, especially with regard to indications for parathyroid intervention. In this context, it is quite important to recognize the development of nodular hyperplasia, because the cells in nodular hyperplasia are usually resistant to calcitriol treatment. Patients with nodular hyperplasia should undergo parathyroid intervention including percutaneous ethanol injection therapy (PEIT). Selective PEIT of the parathyroid gland is an effective approach in which the enlarged parathyroid gland with nodular hyperplasia is 'selectively' destroyed by ethanol injection, and other glands with diffuse hyperplasia are then managed by medical therapy. With a more focused attention to applying parathyroid intervention, we can expect significant improvement in the management of secondary hyperparathyroidism in dialysis patients.
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Affiliation(s)
- Shunsuke Goto
- Division of Nephrology and Kidney Center , Kobe University School of Medicine , Kobe 650-0017 , Japan
| | - Hirotaka Komaba
- Division of Nephrology and Kidney Center , Kobe University School of Medicine , Kobe 650-0017 , Japan
| | - Masafumi Fukagawa
- Division of Nephrology and Kidney Center , Kobe University School of Medicine , Kobe 650-0017 , Japan
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26
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Hirukawa T, Kakuta T, Nakamura M, Fukagawa M. Mineral and bone disorders in kidney transplant recipients: reversible, irreversible, and de novo abnormalities. Clin Exp Nephrol 2015; 19:543-55. [DOI: 10.1007/s10157-015-1117-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Accepted: 04/12/2015] [Indexed: 12/18/2022]
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Yamada S, Tokumoto M, Taniguchi M, Toyonaga J, Suehiro T, Eriguchi R, Fujimi S, Ooboshi H, Kitazono T, Tsuruya K. Two Years of Cinacalcet Hydrochloride Treatment Decreased Parathyroid Gland Volume and Serum Parathyroid Hormone Level in Hemodialysis Patients With Advanced Secondary Hyperparathyroidism. Ther Apher Dial 2015; 19:367-77. [PMID: 25851690 DOI: 10.1111/1744-9987.12292] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
The long-term effect of cinacalcet hydrochloride treatment on parathyroid gland (PTG) volume has been scarcely investigated in patients with moderate to advanced secondary hyperparathyroidism (SHPT). The present study was a prospective observational study to determine the effect of cinacalcet treatment on PTG volume and serum biochemical parameters in 60 patients with renal SHPT, already treated with intravenous vitamin D receptor activator (VDRA). Measurement of biochemical parameters and PTG volumes were performed periodically, which were analyzed by stratification into tertiles across the baseline parathyroid hormone (PTH) level or PTG volume. We also determined the factors that can estimate the changes in PTG volume and the achievement of the target PTH range by multivariable analyses. Two years of cinacalcet treatment significantly decreased the serum levels of PTH, calcium, and phosphate, followed by the improvement of achieving the target ranges for these parameters recommended by the Japanese Society for Dialysis Therapy. Cinacalcet decreased the maximal and total PTG volume by about 30%, and also decreased the serum PTH level independent of the baseline serum PTH level and PTG volume. Ten out of 60 patients showed 30% increase in maximal PTG after 2 years. Multivariable analysis showed that patients with nodular PTG at baseline and patients with higher serum calcium and PTH levels at 1 year were likely to exceed the target range of PTH at two years. In conclusion, cinacalcet treatment with intravenous VDRA therapy decreased both PTG volume and serum intact PTH level, irrespective of the pretreatment PTG status and past treatment history.
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Affiliation(s)
- Shunsuke Yamada
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan.,Department of Internal Medicine, Fukuoka Dental College, Fukuoka, Japan
| | - Masanori Tokumoto
- Department of Internal Medicine, Fukuoka Dental College, Fukuoka, Japan
| | - Masatomo Taniguchi
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan
| | - Jiro Toyonaga
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan.,Fukuoka Renal Clinic, Fukuoka, Japan
| | - Takaichi Suehiro
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan.,Fukuoka Renal Clinic, Fukuoka, Japan
| | - Rieko Eriguchi
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan.,Fukuoka Renal Clinic, Fukuoka, Japan
| | | | - Hiroaki Ooboshi
- Department of Internal Medicine, Fukuoka Dental College, Fukuoka, Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan
| | - Kazuhiko Tsuruya
- Department of Medicine and Clinical Science, Kyushu University, Fukuoka, Japan.,Department of Integrated Therapy for Chronic Kidney Disease, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Nakai K, Fujii H, Yoshikawa M, Kono K, Yonekura Y, Goto S, Ishimura T, Takeda M, Fujisawa M, Nishi S. Effect of cinacalcet cessation on hyperparathyroidism in kidney transcaplant patients after long-term dialysis therapy. Clin Exp Nephrol 2015; 19:1184-8. [PMID: 25782729 DOI: 10.1007/s10157-015-1107-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2014] [Accepted: 03/03/2015] [Indexed: 10/23/2022]
Abstract
BACKGROUND Cinacalcet is a promising therapy widely used in dialysis patients with hyperparathyroidism resistant to conventional therapy. However, reports regarding the influence of cinacalcet cessation after long-term use on kidney transplantation patients are few. METHODS This retrospective observational study included 40 dialysis patients who underwent kidney transplantation. Creatinine, corrected calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone levels were assessed before and after kidney transplantation according to pretransplant treatment of chronic kidney disease-mineral and bone disorder. RESULTS Ultrasonography revealed enlargement of the parathyroid in all patients treated with cinacalcet. Although the data at the time of kidney transplantation were comparable, the serum levels of calcium, alkaline phosphatase, and intact parathyroid hormone after kidney transplantation were higher in patients treated with cinacalcet than in those treated without. However, serum phosphate levels in the cinacalcet group were slightly higher at the time of kidney transplantation and significantly lower 3 months later. CONCLUSIONS Mineral abnormalities persisted in kidney transplant patients with enlarged parathyroid glands after discontinuation of cinacalcet treatment. Parathyroidectomy should be considered in kidney transplant candidates with the risk of developing refractory hyperparathyroidism after transplantation.
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Affiliation(s)
- Kentaro Nakai
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Hideki Fujii
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
| | - Mikiko Yoshikawa
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Keiji Kono
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Yuriko Yonekura
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Shunsuke Goto
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Takeshi Ishimura
- Division of Urology, Department of Organs Therapeutics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masashi Takeda
- Division of Urology, Department of Organs Therapeutics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masato Fujisawa
- Division of Urology, Department of Organs Therapeutics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shinichi Nishi
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
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Jäger MD, Emmanouilidis N, Jackobs S, Kespohl H, Hett J, Musatkin D, Tränkenschuh W, Schrem H, Klempnauer J, Scheumann GFW. Presence of small parathyroid glands in renal transplant patients supports less-than-total parathyroidectomy to treat hypercalcemic hyperparathyroidism. Surgery 2013; 155:22-32. [PMID: 24621404 DOI: 10.1016/j.surg.2013.06.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2012] [Accepted: 06/20/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Parathyroid glands (PG) are rarely analyzed in renal transplant (RTX) patients. This study analyzes comparatively PG of RTX and end-stage renal disease (ESRD) patients. The clinical part of the study evaluates if total parathyroidectomy with autotransplantation (TPT+AT) treats appropriately hypercalcemic hyperparathyroidism in RTX patients. METHODS TPT+AT was performed in 15 of 23 RTX and 21 of 27 ESRD patients. Remaining patients underwent less-than-total PT. Volume and stage of hyperplasia were determined from 86 PG of RTX and 109 PG of ESRD patients. Patients were categorized according to the presence of small PG (volume < 100 mm(3)). Calcium homeostasis and hyperparathyroidism were evaluated 2 years after PT in RTX patients. RESULTS PG of RTX patients were significantly smaller, but similar hyperplastic in comparison to PG of ESRD patients. Small PG were more frequent in RTX than in ESRD patients (19% vs 6%) and mainly graded normal or diffuse hyperplastic (94%). Forty-seven percent of RTX, but only 14% of ESRD, patients receiving a total PT possessed ≥1 small PG (P < .05). Overall, PT treated successfully hypercalcemic hyperparathyroidism. However, TPT+AT caused permanent hypocalcemia in 50% of RTX patients without small PG and even in 83% of RTX patients with small PG. All RTX patients receiving less-than-total PT were normocalcemic at 2-year follow-up. Logistic regression revealed a 10.7 times greater risk of permanent hypocalcemia in RTX patients with small PG receiving TPT+AT compared with RTX patients without small PG receiving TPT+AT or RTX patients undergoing less-than-total PT. CONCLUSION Surgeons performing PT should be aware of the high frequency of small and less diseased PG in RTX patients. In this context, TPT+AT might overtreat hypercalcemic hyperparathyroidism in RTX patients, especially when small PG are present.
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Affiliation(s)
- Mark D Jäger
- Klinik für Allgemein-, Viszeral- and Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany.
| | - Nikos Emmanouilidis
- Klinik für Allgemein-, Viszeral- and Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany
| | - Steffan Jackobs
- Klinik für Allgemein-, Viszeral- and Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany
| | - Holger Kespohl
- Klinik für Allgemein-, Viszeral- and Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany
| | - Julian Hett
- Klinik für Allgemein-, Viszeral- and Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany
| | - Denis Musatkin
- Klinik für Allgemein-, Viszeral- and Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany
| | | | - Harald Schrem
- Klinik für Allgemein-, Viszeral- and Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany
| | - Jürgen Klempnauer
- Klinik für Allgemein-, Viszeral- and Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany
| | - Georg F W Scheumann
- Klinik für Allgemein-, Viszeral- and Transplantationschirurgie, Medizinische Hochschule Hannover, Hannover, Germany
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Fukagawa M, Yokoyama K, Koiwa F, Taniguchi M, Shoji T, Kazama JJ, Komaba H, Ando R, Kakuta T, Fujii H, Nakayama M, Shibagaki Y, Fukumoto S, Fujii N, Hattori M, Ashida A, Iseki K, Shigematsu T, Tsukamoto Y, Tsubakihara Y, Tomo T, Hirakata H, Akizawa T. Clinical Practice Guideline for the Management of Chronic Kidney Disease-Mineral and Bone Disorder. Ther Apher Dial 2013; 17:247-88. [DOI: 10.1111/1744-9987.12058] [Citation(s) in RCA: 251] [Impact Index Per Article: 20.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Vulpio C, Bossola M, Di Stasio E, Tazza L, Silvestri P, Fadda G. Histology and immunohistochemistry of the parathyroid glands in renal secondary hyperparathyroidism refractory to vitamin D or cinacalcet therapy. Eur J Endocrinol 2013; 168:811-9. [PMID: 23520248 DOI: 10.1530/eje-12-0947] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Cinacalcet is a new effective treatment of secondary hyperparathyroidism (SHPT) in hemodialysis patients (HP), but the alterations of parathyroid gland (PTG) hyperplasia determined by cinacalcet and vitamin D have not been extensively investigated in humans. METHODS We performed histological analyses of 94 PTGs removed from 25 HP who underwent parathyroidectomy (PTx) because of SHPT refractory to therapy with vitamin D alone (group A=13 HP and 46 PTGs) or associated with cinacalcet (group B=12 HP and 48 PTGs). The number, weight, the macroscopic cystic/hemorrhagic changes, and type of hyperplasia of PTG (nodular=NH, diffuse=DH) were assessed. In randomly selected HP of group A (4 HP and 14 PTGs) and group B (4 HP and 15 PTGs), the labeling index of cells positive to Ki-67 and TUNEL and the semiquantitative score of immunohistochemistry staining of vitamin D receptor, calcium-sensing receptor, and vascular endothelial growth factor-α (VEGF-α) were measured in the entire PTGs and in the areas with DH or NH. RESULTS The number and weight of single and total PTG of each HP were similar in the two groups as well as the number of PTG with macroscopic cystic/hemorrhagic areas. TUNEL, Ki-67, and VEGF-α scores were higher in NH than in DH areas. CONCLUSION This observational study of a highly selected population of HP, submitted to PTx because SHPT refractory to therapy, shows that the macroscopic, microscopic, and immunochemistry characteristics of PTG in HP who received or did not receive cinacalcet before PTx did not differ significantly.
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Affiliation(s)
- Carlo Vulpio
- Istituto di Clinica Chirurgica, Università Cattolica del Sacro Cuore, Largo A. Gemelli, 8, Rome 00168, Italy.
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Nakamura M, Tanaka K, Marui Y, Tomikawa S. Clinicopathological analysis of persistent hypercalcemia and hyperparathyroidism after kidney transplantation in long-term dialysis patients. Ther Apher Dial 2013; 17:551-6. [PMID: 24107283 DOI: 10.1111/1744-9987.12018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Deceased donor kidney transplantation in long-term dialysis patients in Japan has been increasing because of a severe lack of donors. Parathyroid glands of long-term dialysis patients often show qualitative morphological changes from diffuse to nodular hyperplasia. Only a few studies have reported the clinicopathological analysis of persistent hyperparathyroidism after kidney transplantation in long-term (>10 years) dialysis patients. This study on consecutive deceased donor kidney transplantation performed from 2002 to 2010 measured biochemical parameters related to bone and mineral disorders and examined parathyroid tissues in parathyroidectomy cases. Thirty-four subjects (22 males; mean age, 53.8 ± 7.9 years; mean dialysis period, 14.4 ± 4.3 years) were enrolled. Multivariate analysis of potential predictors for the hypercalcemia group at 12 months after transplantation showed that pre-transplantation and early post-transplantation calcium and parathyroid hormone levels were significant determinants. Pathological examination showed that a number of glands showed nodular hyperplasia, even in small glands weighing < 100 mg. In long-term dialysis patients, hyperparathyroidism and hypercalcemia developed at an early stage after transplantation and persisted for a long period (>4 years), with nodular hyperplasia being found even in low-weight parathyroid glands. Pre-transplant high calcium and parathyroid hormone levels were the predictors for the prolonged hypercalcemia. Persistent hyperparathyroidism was considered to be caused by remaining nodular hyperplasia, even if the glands were small. Although the best treatment option is to perform a parathyroidectomy in the waiting period before transplantation, we suggest that it be performed in cases with prolonged hypercalcemia of >6 months after transplantation.
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Affiliation(s)
- Michio Nakamura
- Department of Transplant Surgery, Tokai University School of Medicine, Isehara, Kanagawa, Japan
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Tomida K, Hamano T, Ichimaru N, Fujii N, Matsui I, Nonomura N, Tsubakihara Y, Rakugi H, Takahara S, Isaka Y. Dialysis vintage and parathyroid hormone level, not fibroblast growth factor-23, determines chronic-phase phosphate wasting after renal transplantation. Bone 2012; 51:729-36. [PMID: 22796419 DOI: 10.1016/j.bone.2012.06.027] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Revised: 06/07/2012] [Accepted: 06/27/2012] [Indexed: 12/11/2022]
Abstract
PURPOSE Fibroblast growth factor 23 (FGF23), rather than parathyroid hormone (PTH), has been shown to be the major factor behind hypophosphatemia in the early period after renal transplantation. However, it is not clear whether phosphate wasting persists in the chronic phase. Purpose of our study is to elucidate whether FGF23 can also explain phosphate wasting, if any, in the chronic phase. METHODS In this cross-sectional observational study, we enrolled 247 recipients who had received a graft more than 1 year prior to this study. We compared the phosphate metabolism of recipients and predialysis chronic kidney disease (CKD) patients who are matched on age and estimated glomerular filtration rate (eGFR). We also investigated the determinants of tubular reabsorption of phosphate normalized for glomerular filtration rate (TmP/GFR), as an index of renal threshold for phosphate. RESULTS Recipients had a median dialysis vintage of 27.0 months and eGFR 41.2 mL/min/1.73 m(2). Whereas hypophosphatemia (<2.4 mg/dL) was observed in 6.1% of the recipients, 55.2% had TmP/GFR lower than 2.4 mg/dL. Recipients showed significantly lower TmP/GFR in all CKD stages than their predialysis counterparts, indicating that phosphate wasting persists in the chronic phase. Compared to predialysis patients, the recipients in stages 2T and 3T showed lower phosphate and higher intact PTH levels, despite a higher percentage being active vitamin D users. However, in stage 4T, phosphate retention masked relative hypophosphatemia. FGF23 was higher in the recipients across all CKD stages, but adjustment for vitamin D prescription revealed that transplantation had no effect on FGF23. Multiple regression analysis in the recipients showed significant negative associations of intact PTH and dialysis vintage with TmP/GFR. CONCLUSIONS Renal phosphate wasting persists in the chronic-phase renal transplantation recipients even with normophosphatemia. Persistent hyperparathyroidism and longer dialysis vintage, not FGF23, was associated with renal phosphate wasting in the chronic phase. Such an impact on phosphate metabolism of the factors determined in dialysis period could be called as "uremic memory". This novel finding in the chronic phase is in sharp contrast to the previous finding in the early phase that FGF23 levels are determinants of phosphate wasting.
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Affiliation(s)
- Kodo Tomida
- Department of Kidney Disease and Hypertension, Osaka General Medical Center, 3-1-56 Bandai-higashi, Osaka, 558-8558, Japan
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The Japanese Society for Dialysis Therapy. Clinical Practice Guideline for CKD-MBD. ACTA ACUST UNITED AC 2012. [DOI: 10.4009/jsdt.45.301] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Komaba H, Kakuta T, Fukagawa M. Diseases of the parathyroid gland in chronic kidney disease. Clin Exp Nephrol 2011; 15:797-809. [DOI: 10.1007/s10157-011-0502-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2011] [Accepted: 07/08/2011] [Indexed: 12/31/2022]
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Messa P, Cafforio C, Alfieri C. Clinical impact of hypercalcemia in kidney transplant. Int J Nephrol 2011; 2011:906832. [PMID: 21760999 PMCID: PMC3132802 DOI: 10.4061/2011/906832] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2011] [Revised: 03/31/2011] [Accepted: 04/20/2011] [Indexed: 12/20/2022] Open
Abstract
Hypercalcemia (HC) has been variably reported in kidney transplanted (KTx) recipients (5–15%). Calcium levels peak around the 3rd month after KTx and thereafter slightly reduce and stabilize. Though many factors have been claimed to induce HC after KTx, the persistence of posttransplant hyperparathyroidism (PT-HPT) of moderate-severe degree is universally considered the first causal factor. Though not proven, there are experimental and clinical suggestions that HC can adversely affect either the graft (nephrocalcinosis) and other organs or systems (vascular calcifications, erythrocytosis, pancreatitis, etc.). However, there is no conclusive evidence that correction of serum calcium levels might avoid the occurrence of these claimed clinical effects of HC. The best way to reduce the occurrence of HC after KTx is to treat as best we can the secondary hyperparathyroidism (SHP) during the uraemic stages. The indication to Parathyroidectomy (PTX), either before or after KTx, in order to prevent or to treat, respectively, HC after KTx, is still a matter of debate which has been revived by the availability of the calcimimetic cinacalcet for the treatment of PT-HPT. However, we still need to better clarify many points as regards the potential adverse effects related to either PTX or cinacalcet use in this clinical set, and we are waiting for the results of future randomized controlled trials to achieve some more definite conclusions on this topic.
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Affiliation(s)
- Piergiorgio Messa
- Nefrologia, Dialisi e Trapianto Renale, Ospedale Maggiore-Policlinico-Mangiagalli-Regina Elena, IRCCS, 20122 Milano, Italy
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Copley JB, Wüthrich RP. Therapeutic management of post-kidney transplant hyperparathyroidism. Clin Transplant 2011; 25:24-39. [PMID: 20572835 DOI: 10.1111/j.1399-0012.2010.01287.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Left uncontrolled, persistent post-kidney transplant hyperparathyroidism (HPT) may lead to or exacerbate pre-existing bone and cardiovascular disease. Parathyroidectomy has long been the primary treatment option for long-term uncontrolled HPT in post-kidney transplant patients. However, patients with contraindications for surgery and parathyroidectomy-associated complications, including graft loss, highlight the need for other approaches. Conventional medical therapies have limited impact on serum calcium (Ca) and parathyroid hormone (PTH) levels. Bisphosphonates and calcitonin, used to spare bone loss, and phosphorus supplementation, to correct hypophosphatemia, do not directly regulate PTH or Ca. Although vitamin D supplementation can reduce PTH, it is often contraindicated because of hypercalcemia. Studies of the calcimimetic cinacalcet in patients with post-kidney transplant HPT suggest that it can rapidly reduce serum PTH and Ca concentrations while increasing serum phosphorus concentrations toward the normal range. Although the clearest application for cinacalcet is the non-surgical treatment of hypercalcemic patients with persistent HPT, current indications for other transplant patients are as yet uncertain. Further studies are needed to determine the utility of cinacalcet in patients with spontaneous resolution of HPT or low bone turnover. This review discusses the pathophysiology of post-kidney transplant HPT, associated complications, and current options for clinical management.
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Komaba H, Koizumi M, Fukagawa M. Parathyroid resistance to FGF23 in kidney transplant recipients: back to the past or ahead to the future? Kidney Int 2011; 78:953-5. [PMID: 21030971 DOI: 10.1038/ki.2010.283] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Fibroblast growth factor 23 (FGF23) modulates the metabolism of minerals and vitamin D. In chronic kidney disease (CKD), this process is disturbed owing to decreased parathyroid expression of FGF23's receptor complex Klotho-FGF receptor 1. In this issue, Krajisnik and colleagues demonstrate that similar alterations occur in parathyroid glands from kidney transplant recipients in association with a decline in allograft function. Is it possible that these data can be extrapolated to general early-stage CKD patients?
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Affiliation(s)
- Hirotaka Komaba
- Division of Nephrology, Endocrinology, and Metabolism, Tokai University School of Medicine, Isehara, Japan
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Wada Y, Kunimura T, Sato S, Hisayuki T, Sato M, Imataka H, Yamashita N, Akizawa T, Moroboshi T. Proliferating potential and apoptosis in the development of secondary hyperparathyroidism: a study based on Ki-67 immunohistochemical staining and the terminal dUTP nick-end labeling assay. Ther Apher Dial 2008; 12:319-28. [PMID: 18789120 DOI: 10.1111/j.1744-9987.2008.00594.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Secondary hyperparathyroidism (SHPT) is a common complication in hemodialysis (HD) patients. SHPT progresses from initial diffuse hyperplasia (diffuse) to early nodularity (early), then to multinodular hyperplasia (nodular), and finally to a single nodule (single) consisting of uniform parenchymal cells. We analyzed the roles of proliferation and apoptosis in SHPT progression. Seventy-four parathyroid glands from 36 HD patients with SHPT, and 10 parathyroid glands from 10 non-HD patients without SHPT were used for analysis. The former were classified as diffuse (N = 17), early (N = 22), nodular (N = 20), and single (N = 15); the latter were classified as normal (N = 10). To analyze proliferating cells we used Ki-67, and to detect apoptotic cells, we used the terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick-end labeling (TUNEL) assay. Concerning the Ki-67 labeling index (LI), the incremental order was single, nodular, early, diffuse, and normal. Oxyphilic cells and around the central portion of each lesion were distinctly stained by Ki-67. Concerning the TUNEL LI, the incremental order was early, diffuse, nodular, single, and normal. Chief cells and around the peripheral portion of each lesion were distinctly stained by TUNEL. In the progression from early to nodular, for oxyphilic cells, the Ki-67 LI increased and the TUNEL LI decreased; for chief cells, the Ki-67 LI decreased and the TUNEL LI showed no significant change. We considered that proliferative activity increases and that the apoptosis rate decreases as SHPT progresses from diffuse to single. Moreover, the specific differences in the rate of proliferation and apoptosis between oxyphilic and chief cells might be associated with SHPT progression.
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Affiliation(s)
- Yukihiro Wada
- First Department of Pathology, Showa University School of Medicine, Tokyo, Japan.
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Komaba H, Fukagawa M. Regression of parathyroid hyperplasia by calcimimetics--fact or illusion? Nephrol Dial Transplant 2008; 24:707-9. [DOI: 10.1093/ndt/gfn717] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Taniguchi M, Tokumoto M, Tsuruya K, Hirakata H, Iida M. Intravenous calcitriol therapy in an early stage prevents parathyroid gland growth. Nephrol Dial Transplant 2008; 23:3662-9. [PMID: 18515308 PMCID: PMC2568009 DOI: 10.1093/ndt/gfn264] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Both the phenotypic alterations of parathyroid (PT) cells, e.g. down-regulation of the calcium-sensing receptor, and the increase of the PT cell number in nodular hyperplasia are the main causes of refractory secondary hyperparathyroidism. It is of great importance to prevent PT growth in an early stage. METHODS To examine a more effective method of calcitriol therapy for the prevention of PT hyperplasia, we randomized haemodialysis patients with mild hyperparathyroidism to receive either daily orally administered calcitriol (n = 33) or intravenous calcitriol (n = 27) over a 12-month study period. Calcitriol was modulated so as to keep the serum intact PTH level between 100 and 150 pg/ml. RESULTS Both groups showed similar reductions of the serum PTH level and similar increases in serum calcium. In both groups, there were no significant changes in the serum phosphate level. Long-term daily oral calcitriol therapy failed to prevent the increase of both maximum PT volume and total volume, as assessed by ultrasonography; however, intravenous calcitriol therapy successfully suppressed this progression. In the daily, oral group, both the bone-specific alkaline phosphatase (BAP) and the N-telopeptide cross-linked of type I collagen (NTX) significantly decreased, which was probably due to the PTH suppression. However, these bone metabolism markers remained stable in the intravenous group. The total dosage of calcitriol during the study was comparable in both groups. CONCLUSIONS These data indicate that intravenous calcitriol therapy in an early stage of secondary hyperparathyroidism is necessary to prevent PT growth and to keep a good condition of bone metabolism.
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Affiliation(s)
- Masatomo Taniguchi
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Higashi-Ku, Fukuoka 812-8582, Japan.
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Schlosser K, Rothmund M, Maschuw K, Barth PJ, Vahl TP, Suchan KL, Fernández ED. Graft-dependent Renal Hyperparathyroidism Despite Successful Kidney Transplantation. World J Surg 2008; 32:557-65. [DOI: 10.1007/s00268-007-9337-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Bibliography. Current world literature. Parathyroids, bone and mineral metabolism. Curr Opin Endocrinol Diabetes Obes 2007; 14:494-501. [PMID: 17982358 DOI: 10.1097/med.0b013e3282f315ef] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Current World Literature. Curr Opin Nephrol Hypertens 2007; 16:388-93. [PMID: 17565283 DOI: 10.1097/mnh.0b013e3282472fd5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Fukagawa M, Nakanishi S, Fujii H, Hamada Y, Abe T. Regulation of parathyroid function in chronic kidney disease (CKD). Clin Exp Nephrol 2006; 10:175-9. [PMID: 17009074 DOI: 10.1007/s10157-006-0432-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2006] [Accepted: 06/30/2006] [Indexed: 12/31/2022]
Abstract
In chronic kidney disease (CKD), several abnormalities in bone and mineral metabolism develop in the majority of patients. The parathyroid plays a very important role in regulating bone and mineral metabolism; thus, control of parathyroid function is one of the main targets of the management of CKD-mineral and bone disorder (CKD-MBD). In the development of secondary hyperparathyroidism, it has recently been suggested that fibroblast growth factor 23 (FGF23) plays a crucial role, both as a phosphaturic factor and as a suppressor of active vitamin D (1,25D) production in the kidney. FGF23 is originally secreted to prevent hyperphosphatemia in CKD, but this occurs at the expense of low 1,25D and hyperparathyroidism ("trade-off" hypothesis revisited). Furthermore, recent data suggest that FGF23 could be another useful marker for the prognosis of hyperparathyroidism, because a high serum level may reflect the cumulative dose of vitamin D analogues previously administered. We have also demonstrated that severe hyperparathyroidism was associated with the production and secretion of a new form of parathyroid hormone (PTH) molecule, which can be detected by third-generation assays for PTH, but not by the second-generation assays. For the regression of already established nodular hyperplasia, the more advanced type of parathyroid hyperplasia, it is certainly necessary, in the near future, to develop new agents that specifically induce apoptosis in parathyroid cells. Until such agents are developed, prevention and early recognition of nodular hyperplasia is mandatory for the effective and safe management of hyperparathyroidism in CKD.
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Affiliation(s)
- Masafumi Fukagawa
- Division of Nephrology and Dialysis Center, Kobe University School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
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