|Year : 2015 | Volume
| Issue : 6 | Page : 708-712
Correlation of serum parathyroid hormone with mineral bone disease in chronic kidney disease patients
Rajeshwari S Vhora1, Avinash Munde2, Charan Bale3, Arjun Lal Kakrani4
1 Department of Emergency Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, India
2 Assistant Professor, Medicine, Vikhe Patil Medical College, Ahemadnagar, India
3 Department of Nephrology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, India
4 Professor & HOD, Medicine, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, India
|Date of Web Publication||19-Nov-2015|
Rajeshwari S Vhora
D3 Clover Garden, 4 Naylor Road, Off Mangaldas Road, Pune - 411 001, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Mineral bone disease (MBD) is a systemic disorder of mineral and bone metabolism due to chronic kidney disease (CKD). Bone disease in CKD is due to secondary hyperparathyroidism. Serum intact parathyroid hormone (iPTH) level estimation is a potential noninvasive method for the diagnosis of MBD at early stage. Aim: Treating renal bone disease should be one of the primary aims of therapy for CKD. Evaluation of the biochemical parameters of CKD-MBD (primarily phosphorus, calcium, parathyroid hormone, and Vitamin D levels) as early as CKD stage 3, and an assessment of bone status (by the best means available), should be used to guide treatment decisions. The adverse effects of high phosphorus intake relative to renal clearance (including stimulation of hyperparathyroidism) precede hyperphosphatemia, which presents late in CKD. Early reduction of phosphorus load may ameliorate these adverse effects. Evidence that calcium load may influence progression of vascular calcification with effects on mortality, should also be considered when choosing the type and dose of phosphate binder to be used. MBD in CKD has high morbidity and mortality and hence it is important to detect it at an early stage. iPTH levels can be highly sensitive and it is one of the useful noninvasive biochemical parameters to detect MBD in CKD. Materials and Methods: This was an observational study carried out in a tertiary care teaching hospital. The study involved 60 patients of CKD. Detailed history, physical examination, and biochemical parameters were assessed in all of them. Results: There was a significant association between hypertension, diabetes with nephropathy, and highly significant association between serum iPTH and raised blood urea levels in MBD group, however there was no significant association between duration of CKD, hemoglobin, creatinine, uric acid, phosphorous, calcium, and alkaline phosphatase with MBD. Conclusions: MBD in CKD can be detected at early stage by the use of noninvasive methods of estimation of serum iPTH levels.
Keywords: Chronic kidney disease, intact parathyroid hormone, kidney disease improving global outcomes, kidney disease outcomes quality initiative, mineral bone disease, secondary hyperparathyroidism, upper limit of normal
|How to cite this article:|
Vhora RS, Munde A, Bale C, Kakrani AL. Correlation of serum parathyroid hormone with mineral bone disease in chronic kidney disease patients. Med J DY Patil Univ 2015;8:708-12
|How to cite this URL:|
Vhora RS, Munde A, Bale C, Kakrani AL. Correlation of serum parathyroid hormone with mineral bone disease in chronic kidney disease patients. Med J DY Patil Univ [serial online] 2015 [cited 2020 Nov 25];8:708-12. Available from: https://www.mjdrdypu.org/text.asp?2015/8/6/708/169947
| Introduction|| |
"Chronic kidney disease (CKD)-mineral and bone disorder (MBD)" is a broad clinical syndrome that develops as a systemic disorder of mineral and bone metabolisms as a result of CKD that can be manifested by any one or a combination of the following:
Abnormalities of calcium, phosphorus, parathyroid hormone (PTH), and Vitamin D metabolism;
Abnormalities of bone turnover, mineralization, volume, linear growth, and strength; and
Vascular or soft tissue calcification. 
Bone disease in patient with CKD is usually asymptomatic. Symptoms appear late in the course of MBD. Increase in PTH is secondary hyperparathyroidism (SHPT) which occurs in most patients with CKD.  SHPT is often unrecognized and inadequately treated in patients with early stages of CKD when therapy would have greater benefits.  Once SHPT progresses to an uncontrolled stage it is associated with elevated calcium, phosphorus, and calcium Χ phosphorus product.
High-turnover metabolic bone disease in chronic kidney disease
High-turnover bone disease is the result of the development of SHPT. It has been known for many years that hyperplasia of the parathyroid glands and high levels of PTH in blood occurs early in the course of CKD.
Low-turnover metabolic bone disease in chronic kidney disease (adynamic bone disease)
Low-turnover bone disease commonly observed in patients with kidney disease, especially in patients who are on dialysis, and is characterized by an extremely slow rate of bone formation.
The retention of phosphorus, decreases in the levels of calcitriol, intrinsic alterations within the parathyroid gland that give rise to increased PTH secretion as well as increased parathyroid growth, skeletal resistance to the actions of PTH, and hypocalcemia. ],[
The present study was carried out to detect MBD at early stage by noninvasive serum intact parathyroid hormone (iPTH) estimation in CKD patients.
In patients with an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m 2 , the kidney disease improving global outcomes (KDIGO) guidelines recommend monitoring of serum phosphorus, calcium, PTH, and alkaline phosphatase (AP) based on the presence and magnitude of abnormalities, and rate of CKD progression.
| Materials and Methods|| |
This was an observational study, approved by the Ethical Review Board of a tertiary care teaching hospital. The present study was conducted in Dialysis Unit, Nephrology OPD and medicine wards of the hospital from August 2010 to August 2012. The study involved 60 adult patients (>18 years) of CKD who were on hemodialysis or not on dialysis.
According to kidney disease improving global outcomes guidelines of chronic kidney disease:
eGFR ≤50 mL/min/1.73 m 2 .
Ultra sound examination showing contracted kidney, that is, <8 cm and/or loss of corticomedullary differentiation and increased echogenicity.
Markedly enlarged kidneys in patients with autosomal dominant polycystic kidney disease, diabetic nephropathy, and amyloidosis.
Acute kidney injury, acute on CKD, genito-urinary malignancy.
The patients were evaluated by taking a detailed clinical history, physical examination, and blood investigations like blood urea level (BUL), serum creatinine level, serum electrolytes, calcium, phosphorus, alkaline phosphatase (ALP), and iPTH. Ultasonography abdomen and pelvis was done for all patients.
PTH levels were performed by conventional radio-immuno assay which detects the middle and COOH terminal fragment which are biologically active fragments. In CKD both the inactive fragments cannot be cleared off due to failing kidneys. The intact PTH has a high specificity and sensitivity is a gold standard for diagnosis of SHPT. ],[
MBD in our patients was diagnosed on the basis of clinical, biochemical, and radiological features.
Associations were explored with Chi-square test and tests of validity such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with their 95% confidence intervals (CIs).
| Results|| |
Out of 60 patients, 19 patients were between the age group of 50-59 years [Table 1], 20 (33.33%) patients had CKD of <1-year duration, 32 (53.33%) patients had one to 3 years duration, and 8 (13.33%) patients had 3 years or more than 3 years duration. This suggests that there was no correlation between duration of CKD and MBD [Table 2].
Out of 60 CKD patients, 48 (80%) patients were diagnosed to have MBD and 12 (20%) patients did not have MBD. Forty patients (66.67%) were on maintenance hemodialysis and 20 (33.33%) patients were not on hemodialysis or never underwent hemodialysis. Out of 40 CKD patients who underwent hemodialysis, 34 patients had MBD and six patients did not have MBD. Out of 20 CKD patients who never underwent hemodialysis 14 patients had MBD where as six patients did not have MBD.
Etiology-wise out of 60 CKD patients, maximum number of patients 33 (55%) had hypertensive and diabetic nephropathy in combination. Out of 60 CKD patients 57 (95%) patients had raised serum iPTH levels. Out of 57 patients with raised iPTH, 47 (82.4%) patients had MBD. Out of 3 (5%) patients with normal iPTH levels 1 (33.33%) patient had MBD, χ2 = 4.29, (P = 0.03) sensitivity -97.92% (95% CI: 87.5, 99.9), specificity -16.67% (95% CI: 2.9, 49.1), PPV -82.46% (95% CI: 69.6, 90.8), NPV -66.67% (95% CI: 12.5, 98.2) [Table 3].
Mean and standard deviation (SD) of iPTH with MBD was 164 (37.3) (Z = 7.63, P < 0.0001), mean and SD of iPTH with no MBD was 97.1 (23.1). There was highly significant association between iPTH levels and raised BUL according MBD in study group.
There was no significant association between hemoglobin, creatinine, uric acid, phosphorous, calcium, and ALP levels according to MBD in study group [Table 4].
|Table 4: Comparison of biochemical parameters according to MBD in study group|
Click here to view
| Discussion|| |
Mineral bone disorder secondary to CKD is one of the major concern and important cause of morbidity and mortality in dialysis patients. The overall prevalence of hyperparathyroidism, based on the kidney disease outcome quality initiative (KDOQI) guidelines, is 34.3%, with US, UK, and Japan having incidence of 47.6%, 33.1%, and 19.9% respectively. 
The maximum number of patients that is 19 patients (31.67%) out of 60 was within the age group of 50-69, which suggests that incidence of CKD increases with advanced age, however it was statistically not significant when compared with the mean occurrence of MBD in other study groups.
Nakai  and Kumchev et al.  in their respective studies also showed that there is no correlation between age and MBD of patient.
In this study 32 (53.33%) patients were found with duration of CKD between 1 and 3 years and association between the duration of CKD and MBD was not statistically significant. Pecovnic Balon et al.  Gabay et al.  and Torres et al.  in their respective studies also concluded the same results.
In our study out of 40 CKD patients who underwent hemodialysis, 34 patients had MBD and 6 patients did not have MBD. Out of 20 CKD patients who never underwent hemodialysis, 14 patients had MBD and 6 patients did not have MBD.Values of χ2 = 1.87 and P = 0.05 in those patients who never underwent hemodialysis, compared to patients who underwent hemodialysis indicate that there was no statistically significant correlation between MBD and hemodialysis. Ritz et al.  reported in their studies that there were no qualitative differences between the findings in bones of patients undergoing dialysis and for those with stable advanced uremia.
In our study 95% CKD patients had hyperparathyroidism, out of which 82.4% had MBD. One (33.33%) patient had MBD even though the serum iPTH was normal. In our study the sensitivity of serum iPTH test for detection of MBD at early stage was 97.92%, which was highly significant but specificity was low 16.67%.
Clinically, serum iPTH is used as a surrogate biomarker to predict bone turnover. However, studies evaluating the ability of the serum concentration of intact PTH to predict both low- and high-turnover bone diseases have been disappointing. In general, the risk of high-turnover bone disease increases with the concentration of intact PTH. ],[ However, the ability to reliably predict the presence of high-turnover bone disease is poor until intact PTH levels of 450-500 pg/mL are reached. Levels of intact PTH <100 pg/mL are fairly reliable for the prediction of low-turnover bone disease,  but again, not perfect. As it was observed in our studies raised iPTH was associated with MBD. Based primarily on these studies, the K/DOQI guidelines recommend a target intact PTH level 150-300 pg/mL. 
Chonchol et al.  found a progressive increase in serum PTH levels with declining kidney functions. This increase in PTH is generally associated with serum calcium and serum phosphorus levels within the normal ranges. In patients with early kidney disease raised the levels of PTH were present.
Arici et al.  found secondary HPT occurs in most patients with CKD and develops early in the course of the disease.
In present study group there was no significant association between hemoglobin, serum creatinine, serum uric acid, serum phosphorus, serum calcium, serum ALP, and MBD, P value was 0.05.
Mondry et al.  and Barnas et al.  also concluded in their study that there was no statistically significant correlation between serum creatinine and MBD.
Lastly, we mentioned some limitations of the study. Sample size was small so specificity of iPTH was estimated with poor precision indicated by wide 95% CI. Due to invasiveness of bone biopsy test and lack of consent for bone biopsy we could not diagnose renal osteodystrophy by histophotometry.
| Conclusion|| |
It can be concluded that raised serum parathyroid levels were highly sensitive, but poorly specific for detection of MBD in CKD.
The evidence-based KDIGO guidelines highlight the gaps in evidence that must be filled to achieve the better diagnosis and management of CKD-MBD. This is an extremely complex disorder with interplay between several biochemical parameters, patient demographics, and additional comorbidities. As a result, there are no universal treatment algorithms that should be applied to all patients with CKD-MBD. Rather, physicians needs to treat the patients as an individuals and react to changes in the full spectrum of CKD-MBD parameters. 
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Moe S, Drüeke T, Cunningham J, Goodman W, Martin K, Olgaard K, et al.
Definition, evaluation, and classification of renal osteodystrophy: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006;69:1945-53.
Pena YT, Soyibo AK, McGrowder D, Clarke TR, Barton EN. The importance of bone biomarkers in the diagnosis of renal osteodystrophy. West Indian Med J 2010;59:332-7.
Chonchol M, Locatelli F, Abboud HE, Charytan C, de Francisco AL, Jolly S, et al. A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet HCl in participants with CKD not receiving dialysis. Am J Kidney Dis 2009;53:197-207.
Reiss E, Canterbury JM, Kanter A. Circulating parathyroid hormone concentration in chronic renal insufficiency. Arch Intern Med 1969;124:417-22.
Arnaud CD. Hyperparathyroidism and renal failure. Kidney Int 1973;4:89-95.
Heidbreder E, Götz R, Schafferhans K, Heidland A. Diminished parathyroid gland responsiveness to hypocalcemia in diabetic patients with uremia. Nephron 1986;42:285-9.
Slatopolsky E, Brown A, Dusso A. Role of phosphorus in the pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis 2001;37:S54-7. [PubMed].
Statistics shown in the DOPPS Annual Report can be cited as 2012 Annual Report of the Dialysis Outcomes and Practice Patterns Study: 2007.
Kumchev EP, Tzvetkova SB, Enchev ED, Yaneva MP, Dimitrova RH, Botushanova AD, et al.
Influence of age, sex and body weight on renal osteodystrophy in predialysis patients with chronic renal failure. Folia Med (Plovdiv) 2000;42:28-33.
Nakai T. BMD decrease is associated with Alkaline Phosphatase and C-PTH in HD patients. Dial Transplant 2002;31:788-91.
Pecovnik Balon B, Hojs R, Zavratnik A, Kos M. Bone mineral density in patients beginning hemodialysis treatment. Am J Nephrol 2002;22:14-7.
Gabay C, Ruedin P, Slosman D, Bonjour JP, Leski M, Rizzoli R. Bone mineral density in patients with end-stage renal failure. Am J Nephrol 1993;13:115-23.
Torres A, Lorenzo V, Hernández D, Rodríguez JC, Concepción MT, Rodríguez AP, et al. Bone disease in predialysis, hemodialysis, and CAPD patients: Evidence of a better bone response to PTH. Kidney Int 1995;47:1434-42.
Ritz E, Malluche HH, Krempien B. Mehls O. Bone histology in renal insufficiency, In: John Wiley & Sons, New York, 1977;145:6.
Wang M, Hercz G, Sherrard DJ, Maloney NA, Segre GV, Pei Y. Relationship between intact 1-84 parathyroid hormone and bone histomorphometric parameters in dialysis patients without aluminum toxicity. Am J Kidney Dis 1995;26:836-44.
Qi Q, Monier-Faugere MC, Geng Z, Malluche HH. Predictive value of serum parathyroid hormone levels for bone turnover in patients on chronic maintenance dialysis. Am J Kidney Dis 1995;26:622-31.
Arici M, Erturk H, Altun B, Usalan C, Ulusoy S , Erdem Y, et al. Bone mineral density in haemodialysis patients: A comparative study of dual-energy X-ray absorptiometry and quantitative ultrasound . Nephrol Dial Transplant 2000;15:1847-51.
Mondry A, Hetzel GR, Willers R, Feldkamp J, Grabensee B. Quantitative heel ultrasound in assessment of bone structure in renal transplant recipients. Am J Kidney Dis 2001;37:932-7.
Barnas U, Schmidt A, Seidl G, Kaider A, Pietschmann P, Mayer G. A comparison of quantitative computed tomography and dual X-ray absorptiometry for evaluation of bone mineral density in patients on chronic hemodialysis. Am J Kidney Dis 2001;37:1247-52.
London G, Coyne D, Hruska K, Malluche HH, Martin KJ. The new kidney disease: Improving global outcomes (KDIGO) guidelines - Expert clinical focus on bone and vascular calcification. Clin Nephrol 2010;74:423-32.
[Table 1], [Table 2], [Table 3], [Table 4]