Secondary Hyperparathyroidism In Chronic Kidney Disease Research Articles

Skeletal parathyroid hormone hyporesponsiveness: a neglected, but clinically relevant reality in chronic kidney disease.

Defining the optimal parathyroid hormone (PTH) target in chronic kidney disease (CKD) is challenging, especially for bone outcomes, due to the substantial variability in the skeleton's response to PTH. Although PTH hyporesponsiveness is as integral a component of CKD-mineral bone disorder as elevated PTH levels, clinical awareness of this condition is limited. In this review, we will discuss factors and mechanisms contributing to PTH hyporesponsiveness in CKD. This knowledge may provide clues towards a personalized approach to treating secondary hyperparathyroidism in CKD. Indicates a link between disturbed phosphate metabolism and impaired skeletal calcium sensing receptor signaling as an important mediator of PTH hyporesponsiveness in CKD. Further, cohort studies with diverse populations point towards differences in mineral metabolism control, rather than genetic or environmental factors, as drivers of the variability of PTH responsiveness. Skeletal PTH hyporesponsiveness in CKD has a multifactorial origin, shows important interindividual variability, and is challenging to estimate in clinical practice. The variability in skeletal responsiveness compromises PTH as a biomarker of bone turnover, especially when considering populations that are heterogeneous in ethnicity, demography, kidney function, primary kidney disease and mineral metabolism control, and in patients treated with bone targeting drugs.

Parathyroid carcinoma case-report in a patient with multinodular goiter and chronic kidney disease: difficulties in diagnosis and treatment (observation from practice)

We would like to present a clinical case of severe primary hyperparathyroidism due to a parathyroid carcinoma of atypical location in a patient with chronic kidney disease of complex etiology and multinodular goiter. Patient S., 59 years old, was followed-up for a long time in tertiary referral hospitals for “chronic tubulointerstitial nephritis with nephrosclerosis”, secondary hyperparathyroidism due to chronic kidney disease (CKD) G3–4, osteoporosis, and a multinodular euthyroid colloid goiter. In July 2021 she was referred to the Endocrinology Research Centre in order to clarify the diagnosis because of the persistence of an extremely high level of parathyroid hormone (PTH) despite cinacalcet treatment. During examination, primary hyperparathyroidism, a left parathyroid gland lesion, multinodular goiter with subclinical thyrotoxicosis, and vitamin D deficiency were diagnosed. After the removal of the left parathyroid gland lesion (histologically confirmed parathyroid carcinoma) and a left-sided hemithyroidectomy, hypocalcemia («hungry bone syndrome») developed, but the level of parathyroid hormone remained elevated. After 3–18 months after surgery, no data for relapse of primary hyperparathyroidism was obtained. The persistent moderate increase in PTH was regarded as secondary hyperparathyroidism in CKD and hypocalcemia. Complex therapy of osteoporosis with the antiresorptive drug denosumab, vitamin D and its active metabolite, calcium preparations, and parathyroidectomy led to a significant increase in bone mineral density (BMD) and no repeated fractures 18 months after surgery.Conclusion. In patients with pre-dialysis CKD and high PTH levels, it is necessary to make a differential diagnosis between primary (PHPT) and secondary hyperparathyroidism (SHPT). Severe manifestations of primary hyperparathyroidism can be suspicious for parathyroid carcinoma.

Brown Tumour in Chronic Kidney Disease: Revisiting an Old Disease with a New Perspective.

Osteitis fibrosa cystica (OFC) and Brown Tumours are two related but distinct types of bone lesions that result from the overactivity of osteoclasts and are most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors, such as hyperactivation of the renin-angiotensin-aldosterone system and chronic inflammation, may also contribute to the occurrence of these diseases through osteoclast activation. Moreover, hotspot KRAS mutations were identified in these lesions, placing them in the spectrum of RAS-MAPK-driven neoplasms, which were until recently thought to be reactive lesions. Some risk factors contributed to the occurrence of OFC and Brown Tumours, such as age, gender, comorbidities, and certain medications. The diagnosis of OFC and Brown Tumours includes clinical symptoms involving chronic bone pain and laboratory findings of hyperparathyroidism. In radiological imaging, the X-ray and Computed tomography (CT) scan could show lytic or multi-lobular cystic alterations. Histologically, both lesions are characterized by clustered osteoclasts in a fibrotic hemorrhagic background. Based on the latest understanding of the mechanism of OFC, this review elaborates on the manifestation, diagnosis, and available therapies that can be leveraged to prevent the occurrence of OFC and Brown Tumours.

Management of Secondary Hyperparathyroidism in Chronic Kidney Disease: A Focus on the Elderly.

Secondary hyperparathyroidism (SHPT) is a major complication of chronic kidney disease (CKD), responsible for skeletal and vascular damage with increased risk of bone fractures, cardiovascular events, and mortality. However, the optimal serum parathormone (PTH) levels for improving clinical outcomes remain uncertain. Treatment of SHPT is based on nutritional therapy, phosphate binders, vitamin D, and calcimimetics, but none of these interventions has ever been tested against placebo in randomized controlled trials. Treatment of SHPT in the elderly should consider the many peculiarities of aging in terms of physiopathology, quality of life, symptoms, subjective perception of disease, drug load, and the modifying effect of treatment on disease-related outcomes. Unfortunately, peculiarities of SHPT among elderly CKD patients are mainly unexplored. The present review aims to provide a reasonable merging of evidence regarding the management of SHPT in CKD, with more actual concepts on how to care for older patients.

Paricalcitol For CKD-MBD Associated With Secondary Hyperparathyroidism: A Case Series Focus On TRAP5b, b-ALP, and DKK-1

Chronic kidney disease (CKD) lead to secondary hyperparathyroidism (sHPT) that caused by phosphate retention and hypocalcemia. This condition known as mineral and bone disorder (CKD-MBD). The increase in parathyroid hormone would increase bone turnover that result in an increased risk of bone fractures, and vascular calcification. These will increase the levels of tartrate-resistant acid phosphatase 5b (TRAP5b), and bone-specific alkaline phosphatase (b-ALP), which is a marker of bone turnover, and also dickkopf-related protein 1 (DKK-1), which is an inhibitor of the Wnt pathway. Secondary hyperparathyroidism in CKD also caused by calcitriol deficiency. Paricalcitol is a synthetic calcitrol analogue used to reduce parathyroid hormone (iPTH) with minimal calcemic and phosphatemic activity. Vitamin D receptor activation by paricalcitol will decrease TRAP5b, b-ALP, and DKK-1. In this study we reported 9 cases of CKD-MBD with Hemodialysis (HD) and associated with sHPT. Four of nine cases received 5μg paricalcitol every HD (twice a week) while the others five is not. Level of iPTH, phosphate, calcium, TRAP5b, b-ALP, and DKK-1 were measured before initiation of study and after three months treatment. According to this study, t he paricalcol administration suppresses the increase in iPTH level , bone turnover and vascular calcification showed by decreasing or supresses the increase b- ALP , TRAP5b , DKK-1 leves without increasing calcium and phosphate levels.

Secondary and Tertiary Hyperparathyroidism in Chronic Kidney Disease: An Endocrine and Renal Perspective.

Secondary Hyperparathyroidism (SHP) seen as a frequent complication in Chronic Kidney Disease (CKD) has many pathogenetic peculiarities that are still incompletely defined and understood. During the long course of chronic renal failure, SHP can also transform sometimes into the hypercalcemic state characterized by quasi-autonomous production of Parathyroid Hormone from the parathyroid glands: a disorder that is termed Tertiary Hyperparathyroidism. The clinical consequences of SHP in CKD are protean, encompassing bone and mineral abnormalities but as recently identified, also several metabolic and cardiovascular problems, the most important of which is vascular calcification. There have been several advances in the therapeutic armamentarium available for the treatment of SHP, though clear demonstration of a benefit regarding major clinical outcomes with any of the new agents is still lacking. This narrative review summarizes the current understanding about this disorder and highlights some of the recent research on the subject.

The effectiveness of nutritional vitamin D supplementation and selective vitamin D receptor agonists treatment on secondary hyperparathyroidism in chronic kidney diseases patients

Background: secondary hyperparathyroidism (SHPT) is an early complication of chronic kidney disease (CKD). Maintaining the level of 25(OH)D and parathyroid hormone concentrations in the target range reduce its associated complications (fractures and cardiovascular calcification).
 Aims: to examine the effectiveness of vitamin D supplementation and selective vitamin D receptor agonists treatment on SHPT in CKD.
 Material and methods: prospective observational study to evaluate the efficacy and safety of vitamin D therapy SHPT in 54 in patients with CKD. The first phase (24 weeks) – treatment of suboptimal 25-hydroxycalciferol (25(OH)D) levels. The second (16 weeks) – treatment colecalciferol-resistant SHPT by combination of cholecalciferol with paricalcitol. Blood samples were taken to assess parathyroid hormone (PTH), 25(OH)D, creatinine, calcium, phosphorus levels and calcium excretion.
 Results: After 8 weeks of cholecalciferol treatment all patients achieved 25(OH)D levels above 20 ng/ml, however 78% of patients still had SHPT. After 16 weeks, the decrease of PTH was achieved in all patients, but significantly only in patients with CKD 2 (19.2%, p< 0.01) and 3 (31%, p <0.05), compared with CKD 4 (17%, p >0.05). After 24 weeks of therapy, PTH normalized in all patients with CKD 2, in 15 (79%) with CKD 3 and in 9 (50%) patients with CKD 4. Cholecalciferol treatment resulted in a substantial increase in 25(OH)D levels with minimal or no impact on calcium, phosphorus levels and kidney function.
 After 24 weeks we initiated combination therapy (cholecalciferol and paricalcitol) for patients with colecalciferol-resistant SHPT (n=13). PTH levels decreased from 149.1±13.4 to 118.2±14.1 pg/ml at 8 weeks, and to 93.1±9.7 pg/ml (p <0.05) at 16 weeks of treatment. No significant differences in serum calcium, phosphorus or urinary calcium levels. Normalization of PTH was achieved in all patients with CKD 3 and in 8 patients with stage 4. One patient with CKD 4 needed an increase in paricalcitol dose.
 Conclusion: Cholecalciferol can be used in correcting vitamin D deficiency in patients with all stages of CKD, however, its effectiveness in reducing PTH in stage 4 is limited. Selective analogs, such as paricalcitol, were well-tolerated and effectively decreased PTH levels.

The Emerging Role of Nutritional Vitamin D in Secondary Hyperparathyroidism in CKD.

In chronic kidney disease (CKD), hyperphosphatemia induces fibroblast growth factor-23 (FGF-23) expression that disturbs renal 1,25-dihydroxy vitamin D (1,25D) synthesis; thereby increasing parathyroid hormone (PTH) production. FGF-23 acts on the parathyroid gland (PTG) to increase 1α-hydroxylase activity and results in increase intra-gland 1,25D production that attenuates PTH secretion efficiently if sufficient 25D are available. Interesting, calcimimetics can further increase PTG 1α-hydroxylase activity that emphasizes the demand for nutritional vitamin D (NVD) under high PTH status. In addition, the changes in hydroxylase enzyme activity highlight the greater parathyroid 25-hydroxyvitmain D (25D) requirement in secondary hyperparathyroidism (SHPT); the higher proportion of oxyphil cells as hyperplastic parathyroid progression; lower cytosolic vitamin D binding protein (DBP) content in the oxyphil cell; and calcitriol promote vitamin D degradation are all possible reasons supports nutritional vitamin D (NVD; e.g., Cholecalciferol) supplement is crucial in SHPT. Clinically, NVD can effectively restore serum 25D concentration and prevent the further increase in PTH level. Therefore, NVD might have the benefit of alleviating the development of SHPT in early CKD and further lowering PTH in moderate to severe SHPT in dialysis patients.

Secondary hyperparathyroidism among Nigerians with chronic kidney disease.

Secondary hyperparathyroidism (SHPT) is a manifestation of chronic kidney disease mineral bone disorder (CKD-MBD). SHPT is common in patients with chronic kidney disease (CKD) and is associated with significant morbidity and mortality. A cross- sectional descriptive study involving 230 patients with CKD. The mean age of the study population was 44.17±15.24 years. The median intact parathyroid hormone and alkaline phosphatase levels were 96pg/ml (range 4-953pg/ml) and 88 iu/l (range 10-800 iu/l) respectively. The mean (with standard deviation) calcium, serum phosphate, calcium phosphate product and haemoglobin levels were 2.22±0.29mmol/l, 1.8±0.62mmol/l, 3.94±1.42mmol2/l2 and 9.90±1.87g/dl respectively. Majority of patients had advanced CKD with 70.3% of patients in stage G5. The prevalence rates of SHPT, hypocalcaemia, hyperphosphataemia, elevated alkaline phosphatase and elevated calcium phosphate product were 55.2%, 34.8%, 66.1%, 42.2% and 25.2% respectively.Univariate analysis revealed that SHPT was associated with hypocalcaemia, hyperphosphataemia, elevated alkaline phosphatase, proteinuria, anaemia, hypertension, left ventricular hypertrophy and stage of kidney disease; being worse with advancing kidney disease. Independently associated with SHPT were hypocalcaemia (OR=4.84), hyperphosphataemia (OR=3.06), and elevated alkaline phosphatase (OR=2.04). The prevalence of SHPT in CKD is high, occurs early and is independently associated with hypocalcaemia, hyperphosphataemia and elevated alkaline phosphatase. The prevalence of SHPT also increases with worsening renal function.

Persistent fibroblast growth factor 23 signalling in the parathyroid glands for secondary hyperparathyroidism in mice with chronic kidney disease

Secondary hyperparathyroidism, in which parathyroid hormone (PTH) is excessively secreted in response to factors such as hyperphosphataemia, hypocalcaemia, and low 1,25-dihydroxyvitamin D (1,25(OH)2D) levels, is commonly observed in patients with chronic kidney disease (CKD), and is accompanied by high levels of fibroblast growth factor 23 (FGF23). However, the effect of FGF23 on the parathyroid glands (PG) remains controversial. To bind to FGF receptors, FGF23 requires αKlotho, which is highly expressed in the PG. Here, we examined the effects of Fgfr1–3, αKlotho, or Fgfr1–4 ablation specifically in the PG (conditional knockout, cKO). When mice with early to mid-stage CKD with and without cKO were compared, plasma concentrations of calcium, phosphate, FGF23, and 1,25(OH)2D did not change significantly. In contrast, plasma PTH levels, which were elevated in CKD mice, were significantly decreased in cKO mice. PG from CKD mice showed augmentation of cell proliferation, which was significantly suppressed by cKO. Parathyroid tissue cultured for 4 days showed upregulation of PTH secretion and cell proliferation in response to FGF23. Both these effects were inhibited by cKO. These findings suggest that FGF23 is a long-term inducer of parathyroid cell proliferation and PTH secretion, and is one cause of secondary hyperparathyroidism in CKD.

Pharmacological Management of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease.

Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD) and is part of the CKD-mineral bone disorder (CKD-MBD). SHPT is associated with increased risk of fracture and mortality; thus, SHPT control is recommended as kidney function declines. Effective SHPT management becomes more difficult once skeletal and cardiovascular adverse effects associated with severe SHPT have become established. However, interventional studies to lower parathyroid hormone (PTH) have so far shown inconsistent results in improving patient-centred outcomes such as mortality, cardiovascular events and fracture. Pharmacological treatment effect on PTH level is also inconsistent between pre-dialysis CKD and dialysis patients, which adds to the complexity of SHPT management. This review aims to give an overview on the pathophysiology, pharmacological and non-pharmacological treatment for SHPT in CKD including some of the limitations of current therapeutic options.

Current recommended 25-hydroxyvitamin D targets for chronic kidney disease management may be too low.

It is uncertain whether increasing 25-hydroxyvitamin D (25-D) levels in chronic kidney disease (CKD) patients above those recommended by current guidelines result in progressive amelioration of secondary hyperparathyroidism. Our objective was to identify a potential therapeutic 25-D target which optimally lowers plasma parathyroid hormone (PTH) without producing excessive hypercalcemia or hyperphosphatemia in CKD. We performed a cross-sectional analysis of 14,289 unselected stage 1-5 CKD patients from US primary care and nephrology practices utilizing a laboratory-based CKD clinical decision support service between September 2008 and May 2012. Estimated glomerular filtration rate (eGFR), plasma PTH, and serum 25-D, calcium, and phosphorus results were analyzed. In CKD stages 3-5, progressively higher 25-D pentiles contained progressively lower mean PTH levels. Regression analysis of log PTH on 25-D was significant in all CKD stages with no evidence of a decreasing effect of 25-D to lower PTH until 25-D levels of 42-48ng/ml. Progressively higher 25-D concentrations were not associated with increased rates of hypercalcemia or hyperphosphatemia. We found evidence for an optimal level of 25-D above which suppression of PTH progressively diminishes. This level is more than twice that currently recommended for the general population. We found no association between these higher 25-D levels and hyperphosphatemia or hypercalcemia. Additional prospective trials seem appropriate to test the idea that 25-D levels around 40-50ng/ml could be a safe and effective treatment target for secondary hyperparathyroidism in CKD.

Tolerance and efficacy of a low dose of the calcimimetic agent cinacalcet in controlling moderate to severe secondary hyperparathyroidism in hemodialysis patients.

Secondary hyperparathyroidism is almost a constant feature in chronic kidney disease (CKD) patients maintained on hemodialysis (HD). Calcimimetic agents appear to offer an alternative to surgery in controlling secondary hyperparathyroidism in these patients. Recent studies provide conflicting data on the benefits, efficacy and tolerance of cinacalcet as first-line therapy for the treatment of secondary hyperparathyroidism in CKD. This study was designed to investigate the efficacy and tolerance of a low dose of the calcimimetic agent cinacalcet in patients on long-term HD having moderate to severe secondary hyperparathyroidism. Twenty five adult male patients on HD for more than three years were included in the study. All had moderate to severe secondary hyperparathyroidism with serum intact parathyroid hormone (iPTH) >50 pmol/L, resistant to conventional treatment. We used the targets of Chronic Kidney Disease: Outcomes Quality Initiative (K/DOQI) clinical guidelines as optimal target of serum iPTH, calcium and phosphate. Patients were administered cinacalcet as a single oral daily dose of 30 mg and were followed-up for six months. Cinacalcet treatment for six months resulted in a significant reduction in the serum phosphate and iPTH levels while the serum calcium levels remained unchanged. Thirty-six percent of the patients attained the recommended serum iPTH levels, 40% achieved significant reduction of the serum iPTH levels and 24% showed no favorable response. Only one patient dropped out because of severe gastrointestinal symptoms. Our results suggest that treatment of CKD patients, having moderate to severe secondary hyperparathyroidism, with low-dose cinacalcet is effective and well tolerated.

Which outcome in chronic kidney disease-mineral and bone disorder patients?

Dear Editor, Secondary hyperparathyroidism (SHPT) is one the major complications in dialysis patients. Hyperphosphatemia, hypocalcemia, low serum vitamin D levels are greatly involved into the physiopathology of SHPT in chronic kidney disease (CKD), in which the down-regulation of parathyroid Vitamin D Receptor (VDR) and Calcium Sensing Receptor (CaSR) represent a critical step. Moreover, new data demonstrate that the Fibroblast Growth Factor 23 (FGF-23) plays an important role in the regulation of calcium-phosphate-vitamin D axis in CKD. Thus, new insights into the pathogenesis of SHPT give the possibility to have different treatments of this condition in CKD. SHPT causes both bone (osteitis fibrosa) and extra-skeletal disease (cardiovascular and soft-tissue calcifications, altered erythropoiesis, endocrine dysfunctions) (1). Clinical targets for serum phosphate (P), calcium (Ca), and parathyroid hormone (PTH) levels have been elucidated by the Kidney Dialysis Outcomes Quality Initiative (K/DOQI) Working Group (2). Since alterations in mineral and bone metabolism have classically been named renal osteodystrophy and classified based on bone biopsy, recently, KDIGO (Kidney Disease: Improving Global Outcomes) proposed a new definition for this disease: the CKD-Mineral and Bone Disorder (CKD-MBD) (3). In addition to hypocalcemia and hyperphosphatemia, CKD-MBD is characterized by abnormalities of bone volume, turnover, mineralization, and growth as well as vascular calcification (VC). In fact, VC seems to link abnormalities in serum Ca and P levels and the enhanced mortality risk associated with CKD-MBD. Impressively, VC starts early in CKD and patients with CKD-3, -4 and -5 not undergoing hemodialysis present a significant amount of calcium deposition in the coronary arteries (40-80%). During the last decade, many efforts have been made to try to decrease VC progression. The control of serum PTH levels and calcium- and phosphate-load, using aluminum- and calcium phosphate binders, more selective vitamin D receptors activators, and cinacalcet clearly represent our current pharmacological tools to improve quality of life and reduce mortality in CKD (4). In their manuscript, Rostami et al. (5) showed quality of life in dialysis patients affected by CKD-MBD in Iran. Interestingly, quality of like associated with serum Ca levels, serum calcium-phosphate product levels, and serum PTH levels. Furthermore, hospitalizations were associated with serum P levels. Thus, management of CKD-MBD included phosphate binders (both calcium-based and calcium-free), vitamin D, and cinacalcet, even if treatment of this dramatic complication of CKD remains suboptimal for most patients.

FIBROBLAST GROWTH FACTOR 23 AND KLOTHO PROTEIN IN THE PATHOGENESIS OF SECONDARY HYPERPARATHYROIDISM

One of the main problems in patients with chronic kidney disease (CKD) is a disturbance of calcium-phosphorus metabolism, especially in chronic hemodialysis. Besides classical endocrine axis parathyroid-kidney, in recent years was established the existence of a new endocrine axis the bone-kidney, which gives a better explanation of the calcium and phosphorus metabolism abnormalities, pathophysiology of secondary hyperparathyroidism in CKD. FGF23 is a circulating factor synthesized in osteocytes. It inhibits renal phosphate reabsorption and activity of 1-alphahydroxylase. Anti-aging Klotho protein is a potent co-factor of FGF23. This review presents the mechanisms of the interaction of these elements of the newly discovered axis in normal settings and secondary hyperparathyroidism.

Фактор роста фибробластов 23 и белок Klotho в патогенезе вторичного гиперпаратиреоза

One of the main problems in patients with chronic kidney disease (CKD) is a disturbance of calcium-phosphorus metabolism, especially in chronic hemodialysis. Besides classical endocrine axis parathyroid-kidney, in recent years was established the existence of a new endocrine axis the bone-kidney, which gives a better explanation of the calcium and phosphorus metabolism abnormalities, pathophysiology of secondary hyperparathyroidism in CKD. FGF23 is a circulating factor synthesized in osteocytes. It inhibits renal phosphate reabsorption and activity of 1-alphahydroxylase. Anti-aging Klotho protein is a potent co-factor of FGF23. This review presents the mechanisms of the interaction of these elements of the newly discovered axis in normal settings and secondary hyperparathyroidism.

PUK5 - Cost-Effectiveness of Paricalcitol in End Stage Chronic Kidney Disease Secondary Hyperparathyroidism Patients on Dialysis, in Brazil

PUK5 - Cost-Effectiveness of Paricalcitol in End Stage Chronic Kidney Disease Secondary Hyperparathyroidism Patients on Dialysis, in Brazil

Switching between parathormone (PTH) assays: the impact on the diagnosis of renal osteodystrophy

Clinical guidelines for decision-making in chronic kidney disease (CKD) consider parathormone (PTH) levels. The measured PTH values differ if novel full length PTH(1-84) assays are used instead of earlier intact iPTH assays. In this study we analyzed how the classification of CKD patients alters when iPTH assays are switched to PTH(1-84) assays. Plasma samples were collected prior to dialysis sessions from 110 consecutive CKD patients on maintenance hemodialysis. PTH levels were determined with iPTH assays (Elecsys, Architect and DiaSorin Liaison N-tact) and PTH(1-84) assays (Elecsys and Liaison). Using KDIGO guidelines patients were classified as being below, above and in the recommended target range (RTR) of PTH. The results of classification with different assays were evaluated and, a novel calculation method of RTR was implemented. The prevalence of patients with PTH in RTR is comparable with each assay, but the individual patients differed. PTH(1-84) Elecsys and Liaison assays classified more patients as being below RTR than iPTH Elecsys and Architect but not Liaison N-tact assay (27.3%, 22.7% vs. 41%, 31.8%, and 36.4%, respectively). In turn, PTH(1-84) Elecsys and Liaison assays identified less CKD patients with PTH above the RTR than iPTH except N-tact assays (6.4%, 10% vs. 16.3%, 19%, and 6.3%, respectively). Using our calculation method, our discrimination values for PTH(1-84) assays to achieve classification identical to that with iPTH Elecsys were lower than those recommended by the manufacturer. Current guidelines for the treatment of secondary hyperparathyroidism in CKD should consider the type of assays used for PTH measurement. Each laboratory should assess its own RTR for PTH tests to achieve comparable classification. The presented calculation is simple, it mimics an everyday situation, switching from one assay to another one, and provides useful RTR values for PTH tests.

Role of Vitamin D Receptor Activators in Cardio-Renal Syndromes

The involvement of vitamin D deficiency in cardiovascular morbidity and mortality is attracting great interest. In patients with chronic kidney disease this association is stronger because vitamin D levels decrease as a result of renal progressive impairment. In chronic kidney disease secondary hyperparathyroidism commonly occurs in response to persistent hypocalcemia and hyperphosphatemia; moreover, parathyroid gland volume increases, vascular calcification is accelerated, and structural and functional modifications of the left ventricle are observed. These alterations entail both cardiac and renal involvement, resulting in cardio-renal syndrome. Recent studies concluded that vitamin D administration seems to have cardioprotective and renoprotective effects and improve peripheral vascular disease, vascular calcification, cardiac outcome, and blood pressure control. In clinical practice, therefore, the use of this hormone may play an important role in cardio-renal syndrome prevention.

Diuretics, calciuria and secondary hyperparathyroidism in the Chronic Renal Insufficiency Cohort

Secondary hyperparathyroidism is a common complication of chronic kidney disease (CKD) that is associated with bone disease, cardiovascular disease and death. Pathophysiological factors that maintain secondary hyperparathyroidism in advanced CKD are well-known, but early mechanisms of the disease that can be targeted for its primary prevention are poorly understood. Diuretics are widely used to control volume status and blood pressure in CKD patients but are also known to have important effects on renal calcium handling, which we hypothesized could alter the risk of secondary hyperparathyroidism. We examined the relationship of diuretic treatment with urinary calcium excretion, parathyroid hormone (PTH) levels and prevalence of secondary hyperparathyroidism (PTH ≥ 65 pg/mL) in a cross-sectional study of 3616 CKD patients in the Chronic Renal Insufficiency Cohort. Compared with no diuretics, treatment with loop diuretics was independently associated with higher adjusted urinary calcium (55.0 versus 39.6 mg/day; P < 0.001), higher adjusted PTH [67.9, 95% confidence interval (CI) 65.2-70.7 pg/mL, versus 52.8, 95% CI 51.1-54.6 pg/mL, P < 0.001] and greater odds of secondary hyperparathyroidism (odds ratio 2.1; 95% CI 1.7-2.6). Thiazide monotherapy was associated with lower calciuria (25.5 versus 39.6 mg/day; P < 0.001) but only modestly lower PTH levels (50.0, 95% CI 47.8-52.3, versus 520.8, 95% CI 51.1-54.6 pg/mL, P = 0.04) compared with no diuretics. However, coadministration of thiazide and loop diuretics was associated with blunted urinary calcium (30.3 versus 55.0 mg/day; P <0.001) and odds of hyperparathyroidism (odds ratio 1.3 versus 2.1; P for interaction = 0.05) compared with loop diuretics alone. Loop diuretic use was associated with greater calciuria, PTH levels and odds of secondary hyperparathyroidism compared to no treatment. These associations were attenuated in patients who were coadministered thiazides. Diuretic choice is a potentially modifiable determinant of secondary hyperparathyroidism in CKD.