Calcimimetics: a new tool for management of hyperparathyroidism and renal osteodystrophy in patients with chronic kidney disease

Calcimimetics: a new tool for management of hyperparathyroidism and renal osteodystrophy in patients with chronic kidney disease. Epidemiologic, clinical, and basic scientific studies led to an explosion in our understanding of disorders of mineral metabolism in the chronic kidney disease (CKD) patient. These advances are not always translated into improved care of renal osteodystrophy in CKD-5 patients. The introduction of a new class of drugs, calcimimetics, allows improved control of abnormal calcium/phosphorus metabolism. The calcimimetics compliment, rather than replace, current treatment options for secondary hyperparathyroidism in the chronic disease patient.     

Giant intrathyroidal parathyroid cyst with hyperparathyroidism: a case report

Parathyroid cysts are rare lesions. A correct pre-operative diagnosis is rarely formulated. The Authors report a case of young woman with hyperparathyroidism do to a giant intrathyroidal parathyroid cyst. Aetiology, diagnosis and management are discussed.     

慢性肾脏病患者甲状旁腺激素水平对肾性贫血的影响

目的 探讨慢性肾脏病（CKD）患者甲状旁腺激素（PTH）升高致红细胞寿命缩短的机制。 方法 以住院初治的CKD患者75例（按eGFR分为1～2期、3～4期和5期）和健康对照组30例为对象。免疫发光法测全段甲状旁腺激素（iPTH）;流式细胞术测红细胞表面磷脂酰丝氨酸（PS）外翻水平及红细胞内钙离子浓度（[Ca2+]i）。 结果 （1）随着肾功能的减退,CKD3～4期及5期患者 iPTH、[Ca2+]i及红细胞表面PS外翻水平逐渐升高、贫血逐渐加重,明显高于CKD1～2期和对照组（均P < 0.05）。（2）CKD3～4期或5期患者Hb与iPTH和红细胞表面PS外翻水平呈负相关（r = -0.830和-0.791,均P < 0.01）;iPTH与 [Ca2+]i和红细胞表面PS外翻水平呈正相关（r = 0.882和0.924,均P < 0.01）,与血钙浓度呈负相关（r = -0.544, P < 0.01）;红细胞表面PS外翻水平与 [Ca2+]i呈正相关（r = 0.923,P < 0.01）,与血钙浓度无相关（r = -0.138,P = 0.365）。（3）[Ca2+]i（Y）对iPTH（X）的直线回归方程：Y=3.327+0.213X（F=21.529,P < 0.05）;红细胞表面PS外翻水平（Y）对iPTH（X1）及[Ca2+]i（X2）的多元线性回归方程：Y=-0.303+0.283X2+0.139X1（F = 6.59,P < 0.01）。 结论 iPTH增加红细胞内钙离子浓度,引起红细胞表面PS外翻增多,致红细胞寿命缩短而加重肾性贫血。     

Tuberculosis complicating tertiary hyperparathyroidism in a patient with end-stage renal disease: a case report

A 36-year-old Nigerian woman on thrice-weekly dialysis presented with symptoms and signs of hypercalcaemia. Laboratory findings were consistent with tertiary hyperparathyroidism. Parathyroid hormone levels remained elevated and she underwent elective parathyroidectomy. Intra-operatively all 4 parathyroid glands and local lymph nodes showed necrotising granulomas with occasional acid-fast bacilli, pathognomonic of tuberculosis (TB). Post-operatively she completed a full course of anti-TB therapy and at 9 months she experienced complete resolution in her plasma biochemistry and was essentially symptom-free. This is a rare yet fascinating cause of hypercalcaemia in a dialysis patient and is the first recorded case of tubercular involvement of parathyroid tissue in a case of tertiary hyperparathyroidism. This report demonstrates the coexistence of 2 diseases that simultaneously worsened hypercalcaemia and thus emphasises the importance of the differential diagnosis and of careful histological examination post-operation.     

血清高水平甲状旁腺激素-非透析慢性肾脏疾病患者的隐形杀手

维持性血液透析患者血清甲状旁腺激素(Parathyroid hormone,PTH)水平显著增高,PTH与患者心功能下降、营养状态恶化以及死亡率的增加密切相关.然而,临床实践发现,部分慢性肾脏疾病(Chronic kidney disease,CKD)3-4期、甚至CKD1期的患者血清PTH水平也增高,PTH对此类患者的影响如何,目前报道较为少见.本文结合文献就FTH对非透析CKD患者的心血管系统、骨代谢、营养状况及预后的影响作一综述.     

血清高水平甲状旁腺激素-非透析慢性肾脏疾病患者的隐形杀手

维持性血液透析患者血清甲状旁腺激素(Parathyroid hormone,PTH)水平显著增高,PTH与患者心功能下降、营养状态恶化以及死亡率的增加密切相关.然而,临床实践发现,部分慢性肾脏疾病(Chronic kidney disease,CKD)3-4期、甚至CKD1期的患者血清PTH水平也增高,PTH对此类患者的影响如何,目前报道较为少见.本文结合文献就FTH对非透析CKD患者的心血管系统、骨代谢、营养状况及预后的影响作一综述.     

血清高水平甲状旁腺激素-非透析慢性肾脏疾病患者的隐形杀手

维持性血液透析患者血清甲状旁腺激素(Parathyroid hormone,PTH)水平显著增高,PTH与患者心功能下降、营养状态恶化以及死亡率的增加密切相关.然而,临床实践发现,部分慢性肾脏疾病(Chronic kidney disease,CKD)3-4期、甚至CKD1期的患者血清PTH水平也增高,PTH对此类患者的影响如何,目前报道较为少见.本文结合文献就FTH对非透析CKD患者的心血管系统、骨代谢、营养状况及预后的影响作一综述.     

Vascular changes in chronic renal disease patients with secondary hyperparathyroidism

BACKGROUND: Secondary hyperparathyroidism (SHPT) and its metabolic consequences - high serum phosphate and calcium x phosphate (Ca x P) product - are associated with cardiovascular disease in chronic kidney disease (CKD). We evaluated the relationship between PTH, mineral metabolism, vascular reactivity and arterial stiffness in patients with CKD. METHODS: The study included 31 CKD patients and 12 matched controls. Brachial artery diameter was recorded at baseline and after reactive hyperemia (flow-mediated vasodilation) and 0.45 mg of trinitrate, to analyze the flow-dependent and flow-independent responses. Large vessel stiffness was evaluated on the common carotid artery. RESULTS: Compared with controls, both flow-mediated (5.8% +/- 4.3% vs. 11.6% +/- 5.4%; p<0.001) and flow-independent (11.7% +/- 7.6% versus 23% +/- 7.5%; p<0.001) vasodilation were reduced in CKD. Flow-mediated vasodilation was negatively correlated with PTH (r=-0.416, p<0.05) and age (r=-0.365, p<0.05) and positively with flow-independent vasodilation (r=0.483, p<0.01). Blood pressure, dialysis duration, hematocrit and serum levels of Ca, P, and Ca x P product, lipids, and medications did not influence flow-mediated function. Carotid distension correlated independently and negatively with age (r=-0.681, p<0.01) and Ca x P product (r=-0.496, p<0.01) but was not influenced by PTH. CONCLUSION: In CKD, PTH adversely affects vascular reactivity, possibly by interfering with endothelial function, while large vessel distension is influenced by Ca x P product but not by PTH. This result suggests a dual mechanism of vascular aggression in SHPT: an endothelial effect mediated by PTH and a media/adventitial effect linked to alterations in mineral metabolism.     

Hyperuricemia is associated with secondary hyperparathyroidism in patients with chronic kidney disease

International Urology and Nephrology - Hyperuricemia is common among patients with chronic kidney disease (CKD). In the general population, hyperuricemia is associated with secondary...     

早期慢性肾脏病患者肾组织甲状旁腺激素的表达及其作用

目的 探讨早期慢性肾脏病(CKD)患者肾组织甲状旁腺激素(PTH)表达和分布,以及其在CKD进展中的可能作用.方法 选取2009年至2012年间本科收治并经肾活检确诊的CKD 1期及2期的肾小球肾炎患者82例为研究对象.另取8例肾移植配型不符或肾肿瘤患者的正常肾组织作对照.受试者均检测Scr、BUN、血钙、磷、PTH及25(OH) VitD3等.以Cockcroft-Gault (CG)公式计算肌酐清除率(Ccr),双血浆99mTc-DTPA清除率法检测GFR.根据肾间质炎性细胞浸润程度,将患者分为轻、中、重组,用免疫组化方法观察肾组织PTH表达和分布；用Image-Pro Plus图像分析软件计算各例肾组织PTH阳性染色吸光度(A)值,并比较PTH表达强度差异.结果CKD1期及2期的肾小球肾炎患者的外周血钙、磷、25(OH) VitD3及PTH水平均处于正常范围,PTH与上述其他指标间无相关.不同病理类型肾小球肾炎患者肾组织均可见PTH表达,主要位于肾小管,而肾小球及肾间质也有少量分布,其表达强度均显著高于对照组(P＜0.01),且随肾间质炎性细胞浸润增多,PTH表达增强.各病理类型间肾组织PTH表达强度差异无统计学意义.结论 早期CKD(1期及2期)患者肾组织PTH表达增强,且早于外周血PTH的改变及矿物质和骨代谢紊乱,可能与局部炎性反应程度相关.     

A parathyroid cyst and an adenoma associated with primary hyperparathyroidism: report of a case

A case of a parathyroid cyst associated with an adenoma in a different gland is reported. A 55-year-old female was explored with preoperative diagnosis of primary hyperparathyroidism after endoscopic removal of a right ureteral stone. The operation revealed a cyst, 20 x 10 mm in size at the left lower gland, and a solid tumor, 32 x 12 x 7 mm in size and 1,300 mg in weight in the left upper gland. Histological examination disclosed a parathyroid cyst and an oxyphilic and chief cell adenoma, respectively. Postoperative course was uneventful including normalized serum Ca level. To our knowledge, 59 cases of parathyroid cysts have been reported in the Japanese literature, of which 31 were in the hyperparathyroid status. The most common causes were cystic degeneration of the adenomas. A parathyroid cyst with a concomitant adenoma in a different gland like our case is very rare. This is the first reported case in Japan and the sixth reported case in the world literature.     

Ectopic and supernumerary parathyroid glands in patients with refractory renal hyperparathyroidism

BackgroundThe aims of this study were to determine the rate of ectopic and supernumerary parathyroid glands and the outcome of surgical therapy in patients with refractory renal hyperparathyroidism.Materials and MethodsA retrospective review of all patients who underwent parathyroidectomy for refractory renal hyperparathyroidism was completed. Operative and pathology reports were reviewed, and the number and location of resected parathyroid glands, patient outcomes, and follow-up were determined.ResultsDuring the period 1993–2019, a total of 68 patients underwent subtotal or total parathyroidectomy for renal hyperparathyroidism. Of those, 59 patients (87%) were on dialysis for an average of 6.7 years. We determined that 18 patients (26%) had 24 ectopic parathyroid glands, including 9 (13%) patients with 11 supernumerary glands. A total of 2 patients had a supernumerary gland in a normal anatomic location. Of the 24 ectopic glands, 14 (58%) were in the thymus. After parathyroidectomy, 4 patients (5.9%) had persistent hyperparathyroidism, 6 patients (8.8%) developed recurrent hyperparathyroidism, and 2 patients (3%) had permanent hypoparathyroidism.ConclusionEctopic and supernumerary parathyroid glands occurred in 26% and 16% of patients with renal hyperparathyroidism, respectively, and the thymus was the most common location. Thorough neck exploration and transcervical thymectomy are important to help reduce persistent and recurrent hyperparathyroidism after parathyroidectomy for renal hyperparathyroidism.     

The risk of acute renal failure in patients with chronic kidney disease

Few studies have defined how the risk of hospital-acquired acute renal failure varies with the level of estimated glomerular filtration rate (GFR). It is also not clear whether common factors such as diabetes mellitus, hypertension and proteinuria increase the risk of nosocomial acute renal failure independent of GFR. To determine this we compared 1,746 hospitalized adult members of Kaiser Permanente Northern California who developed dialysis-requiring acute renal failure with 600,820 hospitalized members who did not. Patient GFR was estimated from the most recent outpatient serum creatinine measurement prior to admission. The adjusted odds ratios were significantly and progressively elevated from 1.95 to 40.07 for stage 3 through stage 5 patients (not yet on maintenance dialysis) compared to patients with estimated GFR in the stage 1 and 2 range. Similar associations were seen after controlling for inpatient risk factors. Pre-admission baseline diabetes mellitus, diagnosed hypertension and known proteinuria were also independent risk factors for acute kidney failure. Our study shows that the propensity to develop in-hospital acute kidney failure is another complication of chronic kidney disease whose risk markedly increases even in the upper half of stage 3 estimated GFR. Several common risk factors for chronic kidney disease also increase the peril of nosocomial acute kidney failure.     

Recurrent secondary hyperparathyroidism due to implanted parathyroid tissue: a case report

Hyperparathyroidism is a common complication of chronic renal failure. Although many patients can be managed by conservative measures, surgery is sometimes necessary. One of two operations can be performed: subtotal parathyroidectomy or total parathyroidectomy with reimplantation of parathyroid tissue into muscle. A case is presented of a patient who underwent the first and then the second of these procedures for recurrent hyperparathyroidism. A further recurrence was found to be caused by the implanted parathyroid tissue in a forearm muscle, requiring a third procedure for control of the disorder.     

Oral alendronate can suppress bone turnover but not fracture in kidney transplantation recipients with hyperparathyroidism and chronic kidney disease

Post-transplantation bone diseases negatively affect the quality of life of solid organ recipients. Secondary or tertiary hyperparathyroidism is a frequent complication in kidney transplantation (KTx) recipients. Treatment with immunosuppressive agents including glucocorticoids can lead to deterioration in bone metabolism in these patients. In the present study, we explored the effects of a three-year treatment period with oral alendronate (ALN) in long-term KTx recipients. Post-KTx recipients were recruited (n = 24, M/F = 12/12, mean age 52.0 ± 7.8 years) into this study. All patients were prescribed methylprednisolone (4.07 ± 0.86 mg/day) with various immunosuppressive agents. Before treatment with oral ALN (35 mg/week), the mean concentrations of intact parathyroid hormone (iPTH) and 25-hydroxyvitamin D were 139.2 ± 71.4 pg/mL and 20.8 ± 4.1 ng/mL, respectively. After 36 months of ALN treatment, mean iPTH levels increased slightly (+20.9 %). Treatment with ALN reduced bone-specific alkaline phosphatase (?35.4 %), serum type I collagen N-terminal telopeptide (?31.2 %) and osteocalcin (?55.6 %) levels. ALN did not increase bone mass after 24 months. Four patients with the highest baseline iPTH levels suffered a clinical osteoporotic fracture during the 36-month ALN treatment period. Higher iPTH levels with chronic kidney disease (CKD) at baseline were associated with the incidence of new clinical fractures during ALN treatment. In conclusion, anti-resorptive therapy with ALN can suppress bone turnover even when iPTH concentration is elevated in long-term KTx recipients. However, hyperparathyroidism with CKD seems to be associated with new clinical fractures during ALN treatment.     

Radio-guided surgery in recurrent renal hyperparathyroidism: report of a case

BACKGROUND: It has been demonstrated that radio-guided surgery offers several advantages in treating primary hyperparathyroidism. Even if it is considered less helpful in renal hyperparathyroidism, it could be of tremendous advantage in the treatment of persistent or recurrent secondary hyperparathyroidism. METHODS: We report a case of recurrent secondary hyperparathyroidism treated by the use of radio-guided surgery. The preoperative assessment consisting of ultrasonography, magnetic resonance imaging, and 99mTc-sestamibi scintigraphy identified a parathyroid in the upper mediastinum. The patient underwent a radio-guided neck re-exploration that allowed a rapid localization and excision of the ectopic gland, which was located in the anterosuperior mediastinum, in front of the trachea, between the innominant and the left common carotid artery. RESULTS: The operative time was 45 minutes. The patient was discharged on the first postoperative day. A decrease in serum calcium and parathyroid hormone was observed subsequently. A follow-up of 6 months did not show any recurrence. CONCLUSIONS: The case reported indicates that radio-guided surgery can help surgeons detect parathyroid tissue in selected cases of renal hyperparathyroidism.     

Treatment of secondary hyperparathyroidism in patients with chronic renal failure by total parathyroidectomy and parathyroid autograft.

Sixty-one patients with chronic renal failure and secondary hyperparathyroidism underwent total parathyroidectomy and parathyroid autograft. Symptoms relieved by parathyroidectomy included bone pain, pruritus, soft tissue calcification, muscle weakness and healing of fractures. Serum parathormone levels measured before and after operation in 48 patients returned to normal in all but two patients. Serum alkaline phosphatase levels also returned toward normal after operation, except in one patient with a retained parathyroid gland. Complete radiographic studies before and after operation were available in 30 of 61 patients. Twenty-three of 24 patients with osteitis fibrosa had evidence of healing, and in one patient no change occurred. Osteosclerosis noticed in 23 patients improved slightly in eight patients, did not change in 14 and became worse in one. Pathologic examinations revealed 45 patients to have diffuse hyperplasia and 16 nodular hyperplasia. There were two early postoperative deaths, in the first 30 days, and 16 late postoperative deaths, from four months to four years afterward. In no case did the operation contribute to death. Some patients required the administration of supplemental calcium after operation, but in no instance did profound hypocalcemia occur. No patient developed recurrent hyperparathyroidism.     

Pin1 and secondary hyperparathyroidism of chronic kidney disease: gene polymorphisms and protein levels

Background: Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is a key regulator of PTH mRNA stability. Secondary hyperparathyroidism (SHPT), which is characterized by elevated serum PTH levels, is a common complication of CKD. We investigated the possible associations between CKD with SHPT (CKD SHPT) and single-nucleotide polymorphisms of the Pin1 gene and compared the levels of the Pin1 protein in the CKD SHPT patients with those of the controls.

Methods: The study group included 251 CKD SHPT patients and 61 controls. One putative functional SNP (single nucleotide polymorphism) in the Pin1 promoter (rs2233679C?>?T: c.?667C?>?T) is the main object. Genotyping was performed on purified DNA using polymerase chain reaction-restriction (PCR) and restriction fragment length polymorphisms (RFLP). The levels of Pin1 were measured in serum using an enzyme-linked immunosorbent assay.

Results: Genotyping showed that CT?+?TT in the Pin1 promoter was significantly more common in the CKD SHPT group than in the control group (p<.05). The correlation analysis demonstrated that a significant difference in the C to T transition in the Pin1 promoter contributed to CKD SHPT (χ²=12.47, p<.05; Odds ratios (OR)?=?1.26, 95% confidence (CI) intervals =1.06–1.49). The multivariate logistic regression analysis reported that the OR and 95%CI were 12.693 and 2.029–75.819 (p<.05), respectively, in the Pin1 gene promoter ?667T variant genotypes (CT?+?TT) after adjusting for other factors, and those values in Pin1 were 0.310 and 0.122–0.792 (p<.05).

Conclusion: The ?667T genetic variants in the Pin1 promoter contribute to an increased risk of CKD SHPT and may be biomarkers of susceptibility to CKD SHPT.