Abstract
Background
Severe secondary hyperparathyroidism (SHPT) is a frequent consequence of long-term hemodialysis and remains a major management challenge in resource-limited settings. The comparative benefit of surgical parathyroidectomy (PTx) and medical therapy with the calcimimetic cinacalcet is still debated, particularly where access and adherence barriers exist.
Methods
A retrospective cohort analysis was conducted at Baraha Medical City, Sudan, including adults on maintenance hemodialysis with severe SHPT (intact parathyroid hormone (iPTH) ≥ 800 pg/mL) treated between 2018 and 2022. Participants received either PTx (n = 41) or cinacalcet (n = 68). The principal endpoint was biochemical improvement within 3–6 months, defined as iPTH < 600 pg/mL or ≥ 30% reduction from baseline. Secondary outcomes included symptomatic relief, correction of serum calcium and phosphate, treatment adherence, complications, and one-year mortality.
Results
A biochemical response was achieved in over 90% of surgical patients compared with 47.1% of those treated with cinacalcet (p < 0.001). At 3–6 months, symptom improvement was noted in 75% of the PTx group versus 54% of the cinacalcet group (p = 0.04). Surgery also resulted in higher normalization rates for calcium and phosphate. At one-year, sustained symptom control persisted in 90.2% of surgical patients versus 29.4% with cinacalcet (p < 0.001). Hospitalizations and mortality were numerically lower after PTx, though not statistically significant. High adherence to cinacalcet was observed in only 27.9%, with discontinuation mainly due to financial or supply limitations.
Conclusions
PTx produced superior biochemical and clinical outcomes compared with cinacalcet, although the impact of calcimimetic therapy was hindered by restricted availability and suboptimal adherence. Extended follow-up is needed to evaluate long-term skeletal and cardiovascular effects and explore delivery models that improve treatment continuity.
Clinical trial registration
This was a retrospective observational cohort study and not a prospective interventional clinical trial; therefore, trial registration was not applicable.
Keywords: Secondary hyperparathyroidism, Parathyroidectomy, Cinacalcet, CKD–MBD, Hemodialysis
Background
Secondary hyperparathyroidism (SHPT) is a frequent and progressive complication of end-stage kidney disease in patients receiving maintenance hemodialysis [1, 2]. Persistent disruptions in calcium, phosphate, and vitamin D balance stimulate progressive parathyroid hyperplasia and excessive secretion of parathyroid hormone [3]. When inadequately controlled, SHPT can lead to bone remodeling disorders, soft-tissue and vascular calcification, and heightened risks of cardiovascular disease and death [4, 5]. Even with advances in dialysis efficiency and phosphate management, severe SHPT continues to pose significant treatment challenges, particularly in resource-limited settings [6].
Current international guidelines recommend medical management using combinations of calcimimetics, vitamin D receptor activators (VDRAs), and phosphate binders, with parathyroidectomy (PTx) reserved for refractory or symptomatic cases [7, 8]. Cinacalcet, an oral calcimimetic, effectively suppresses PTH and improves mineral balance in patients on dialysis [9–11]. However, its use is limited in resource-constrained settings because of cost, gastrointestinal intolerance, and the need for uninterrupted long-term therapy [3, 4, 12, 13]. In Sudan, the availability of cinacalcet remains unreliable. Only a small fraction of patients are eligible for complete coverage through national health insurance, whereas the majority must purchase the medication out of pocket and frequently encounter interruptions in supply [14].
Surgical PTx remains a valuable option when medical therapy fails or symptoms persist [15, 16]. Although surgery produces rapid and durable biochemical control, it requires experienced teams, peri-operative calcium support, and continued monitoring to avoid recurrence or adynamic bone disease [17]. Comparative data evaluating the effectiveness of PTx versus cinacalcet in low-resource environments are scarce [18].
The present study compares biochemical and clinical outcomes of PTx and cinacalcet therapy in Sudanese hemodialysis patients with severe SHPT, aiming to provide locally relevant evidence on treatment effectiveness, adherence, and health-system limitations [19].
Methods
Study design and setting
This was a retrospective observational cohort study conducted at Baraha Medical City (BMC), a tertiary nephrology referral center in Khartoum State, Sudan, which provides chronic hemodialysis and surgical services for patients with advanced SHPT. Medical records of adult patients with end-stage renal disease (ESRD) on maintenance hemodialysis who attended regular follow-up visits at BMC between January 2018 and December 2022 were reviewed.
Participants
Adult patients (≥ 18 years) receiving maintenance hemodialysis for at least 6 months were eligible if they had severe SHPT, defined as intact parathyroid hormone (iPTH) ≥ 800 pg/mL with persistent hyperphosphatemia and/or SHPT-related symptoms despite medical therapy, with or without hypercalcemia [3]. Patients were excluded if they had previous parathyroid surgery, active malignancy, severe infection, primary hyperparathyroidism, incomplete medical records or a follow-up duration shorter than six months. Those who had received cinacalcet prior to PTx were also excluded to prevent potential carry-over effects [3]. All eligible patients with adequate records during the study period were consecutively included. Given the retrospective nature of the study, a predetermined sample size was not calculated. All eligible cases with complete data were therefore included in the analysis.
Treatment allocation
Assignment to PTx or cinacalcet therapy was non-randomized and determined by the treating nephrologist in consultation with each patient. Treatment selection was influenced by the patient’s clinical presentation, degree of biochemical imbalance, insurance status, access to medication, and the anticipated surgical waiting time. All consecutive patients who met the eligibility criteria during the study period were included to minimize selection bias. Patients referred for PTx at other centers but followed post-operatively at BMC were also enrolled.
Treatment protocols
PTx procedures included subtotal resection, involving removal of three and one-half glands with a small remnant left in situ; total PTx with autotransplantation, entailing excision of all glands followed by forearm autograft; and limited resection, defined as removal of one to three visibly enlarged glands when full exploration was not feasible or only partial hypertrophy was evident [6]. Preoperative imaging was performed mainly with neck ultrasonography, and nuclear scintigraphy was used infrequently when available [7]. Postoperative management included intravenous calcium supplementation and oral VDRAs at the discretion of attending clinicians [8].
Cinacalcet therapy was initiated at 30 mg/day and titrated up to 90 mg/day according to clinical tolerance and serial biochemical results [9]. Medication adherence was defined as a medication-possession ratio ≥ 80%, based on pharmacy refill records and pill counts [10]. Patients meeting this adherence threshold were analyzed as a high-adherence subgroup to estimate pharmacologic effectiveness among compliant users.
Data collection
Demographic, clinical, and biochemical data were collected retrospectively using a standardized data abstraction form. Variables included age, sex, dialysis duration, primary kidney disease, and comorbidities such as diabetes and cardiovascular disease. Baseline SHPT-related symptoms were recorded as documented by the treating nephrologist.
Biochemical parameters obtained at baseline and during follow-up included iPTH, serum calcium, phosphate, alkaline phosphatase (ALP), and 25-hydroxy vitamin D. Laboratory data were obtained from BMC hospital records. All assays were performed at the central BMC laboratory using standardized methods, thereby maintaining consistency across measurements.
For the cinacalcet group, data on prescribed dose, adherence, side effects, and reasons for discontinuation were extracted. For the PTx group, surgical details included type of procedure, perioperative complications, length of hospital stay, and recurrence of SHPT. Because transient post-treatment hypocalcemia events were not consistently documented in clinical records, only persistent cases were analyzed.
Outcomes
The primary outcome was biochemical response at 3–6 months, defined as a reduction in iPTH to < 600 pg/mL or a ≥ 30% decrease from baseline [11]. Secondary outcomes included normalization of calcium (8.4–10.2 mg/dL) and phosphate (2.5–4.5 mg/dL), improvement in SHPT-related symptoms, treatment-related complications, hospitalization within six months, 12-month all-cause mortality, recurrence of severe SHPT (iPTH ≥ 800 pg/mL), and, where applicable, re-initiation of cinacalcet after PTx [12].
Symptom relief was identified from clinical records as documentation of reduced bone pain, pruritus, or fatigue reported by the patient and confirmed by the nephrologist at follow-up visits. Improvement was analyzed as a binary variable (improved vs. not improved). Sustained symptom control was defined as continued improvement over at least two consecutive visits within 12 months [13].
Mortality data were obtained from hospital records and, when necessary, confirmed through telephone contact with patient families. Economic and access-related variables included drug availability, insurance coverage, surgical waiting time, and cost-related treatment interruption or discontinuation.
Statistical analysis
Data were analyzed using IBM SPSS Statistics, version 25.0 (IBM Corp., Armonk, NY, USA). Continuous variables are presented as mean ± standard deviation (SD) or median [interquartile range, IQR], as appropriate, and categorical variables as frequencies and percentages. Between group comparisons employed the Student’s t test or Mann–Whitney U test for continuous data and Fisher’s exact test for categorical variables [16].
Risk ratios (RRs) with 95% confidence intervals (CIs) served as the primary measures of association, and absolute risk differences (ARDs) were calculated to enhance clinical interpretability. Mean or median differences were reported for continuous outcomes. Odds ratios (ORs) were used only when event counts were low (< 5 per cell) or within sensitivity regression analyses.
Baseline data were complete. At 12 months, outcome data were missing for less than 15% of patients due to loss to follow-up or incomplete documentation; these cases were excluded from 12-month analyses, and no data imputation was performed.
To adjust for potential confounders, multivariable Poisson regression with robust variance was applied, incorporating age, diabetes, dialysis duration, comorbidity burden, and baseline ALP as covariates. Firth’s penalized logistic regression was additionally used as a sensitivity model to reduce small-sample bias. All tests were two-tailed, and a p value < 0.05 was considered statistically significant.
Results
Patient characteristics
A total of 134 hemodialysis patients with severe SHPT were screened, of whom 109 met the inclusion criteria and were analyzed (Fig. 1). Among them, 41 (37.6%) underwent PTx, and 68 (62.4%) received cinacalcet therapy. All participants had complete baseline data. Follow-up information for the primary and secondary outcomes was available for all patients at 3–6 months and for 94 (86.2%) at 12 months; the remaining cases were lost to follow-up or had died.
Fig. 1.
Flow chart shows the selection of the study population
At baseline, both treatment groups were broadly comparable in demographic and clinical characteristics, including mean age (53.6 ± 11.2 vs. 55.1 ± 10.4 years), sex distribution (63.4% vs. 61.8% male), median duration on dialysis (5.4 vs. 5.1 years), and primary kidney disease, which was predominantly diabetic or hypertensive nephropathy. Diabetes mellitus and hypertension were the most common comorbid conditions across the cohort.
Baseline biochemical and clinical characteristics are summarized in Table 1. Patients selected for PTx were more frequently symptomatic at baseline (75.0% vs. 54.4%; RR = 1.38, 95% CI 1.02–1.87; ARD = 20.6%) and more likely to have refractory biochemical abnormalities (87.8% vs. 58.8%; RR = 1.49, 95% CI 1.16–1.91; ARD = 29.0%). Serum calcium, phosphate, and ALP were significantly higher among PTx patients, suggesting more advanced biochemical derangement; whereas median iPTH levels were markedly elevated in both cohorts, slightly higher in the PTx cohort (1550 pg/mL [IQR 1360–1830]) compared with cinacalcet-treated patients (1420 pg/mL [1210–1680]).
Table 1.
Baseline characteristics, treatment access, and indications in parathyroidectomy and Cinacalcet groups
| Parameter | Parathyroidectomy (n = 41) |
Cinacalcet (n = 68) |
RR/MD (95% CI) | ARD % (95% CI) | P-value |
|---|---|---|---|---|---|
| Demographics and Clinical Profile | |||||
| Mean age (years), mean ± SD | 53.6 ± 11.2 | 55.1 ± 10.4 | MD − 1.5 (–5.7 to 2.7) | – | 0.486 |
| Male gender n (%) | 26 (63.4%) | 42 (61.8%) | 1.03 (0.73 to 1.46) | + 1.6 (–17.2 – 20.4) | 0.867 |
| Dialysis duration (years), median [IQR] | 5.4 (3.5–8.3) | 5.1 (3.2–7.8) | MD 0.3 (–1.0 to 1.5) | – | 0.672 |
| Baseline Biochemical Profile | |||||
| iPTH (pg/mL), median [IQR] | 1550 (1360–1830) | 1420 (1210–1680) | MD 62 (–51 to 175) | – | 0.287 |
| Serum calcium (mg/dL), median [IQR] | 10.4 (9.8–10.9) | 9.5 (9.0–9.9) | MD + 0.9 (0.4 to 1.4) | – | 0.002 |
| Serum phosphate (mg/dL), median [IQR] | 6.2 (5.5–6.9) | 5.4 (4.8–6.0) | MD + 0.8 (0.3 to 1.3) | – | 0.006 |
| ALP (IU/L), median [IQR] | 368 (295–452) | 322 (261–411) | MD 46 (–12 to 104) | – | 0.118 |
| Primary Kidney Disease | |||||
| Diabetic kidney disease n (%) | 20 (48.8%) | 31 (45.6%) | 1.07 (0.69 to 1.65) | + 3.2 (–16.9 to 23.3) | 0.783 |
| Hypertensive nephrosclerosis n (%) | 11 (26.8%) | 17 (25.0%) | 1.07 (0.56 to 2.01) | + 1.8 (–13.9 to 17.5) | 0.830 |
| Glomerulonephritis n (%) | 6 (14.6%) | 9 (13.2%) | 1.11 (0.43 to 2.88) | + 1.4 (–10.6 to 13.4) | 0.800 |
| Other etiologies n (%) | 4 (9.8%) | 11 (16.2%) | 0.60 (0.21 to 1.72) | –6.4 (–18.5 to 5.7) | 0.381 |
| Indications for Treatment of severe SHPT | |||||
| iPTH ≥ 800 pg/mL n (%) | 41 (100%) | 68 (100%) | – | – | – |
| Symptomatic SHPT n (%) | 30 (75.0%) | 37 (54.4%) | 1.38 (1.02 to 1.87) | + 20.6 (1.3 to 39.9) | 0.039 |
| Refractory biochemical abnormalities n (%) | 36 (87.8%) | 40 (58.8%) | 1.49 (1.16 to 1.91) | + 29.0 (10.2 to 47.8) | 0.004 |
| Calciphylaxis/severe bone disease n (%) | 7 (17.1%) | 8 (11.8%) | 1.45 (0.56 to 3.74) | + 5.3 (–7.9 to 18.5) | 0.381 |
| Access and Affordability | |||||
| Full insurance coverage n (%) | 6 (14.6%) | 0 (0%) | – | + 14.6 (5.0 to 24.2) | 0.007 |
| Wait time (days), median [IQR] | 78 (54–152) | 9 (5–17) | MD 69 (48 to 90) | – | < 0.001 |
| Discontinuation due to cost n (%) | 0 (0%) | 26 (38.2%) | – | –38.2 (–51.2 to − 25.2) | < 0.001 |
Data are presented as mean ± SD, median [IQR], or number (%) as appropriate. iPTH = intact Parathyroid Hormone; ALP = Alkaline Phosphatase; SHPT = Secondary Hyperparathyroidism; RR = Risk Ratio; ARD = Absolute Risk Difference; MD = Mean or Median Difference; CI = Confidence Interval
Phosphate binder and oral VDRA were used by 70% and 64% of patients, respectively, with no significant intergroup difference (p > 0.05). These therapies were continued after intervention as clinically indicated.
Treatment access and affordability
Marked inequalities in access to therapy were evident (Table 1). Although PTx is formally covered under the national health-insurance scheme, only 6 patients (14.6%) in the surgical group obtained full reimbursement, while the remainder paid partially or entirely out-of-pocket. In contrast, cinacalcet was not included in the public insurance formulary and was unavailable in government hospitals. Patients had to purchase it privately at substantial out-of-pocket costs, leading to frequent discontinuation. Overall, 38.2% of cinacalcet users discontinued therapy primarily because of financial constraints. The median waiting time from treatment decision to initiation was considerably longer for PTx (78 days) than for cinacalcet (9 days), underscoring persistent system-level limitations in procedural availability.
Primary and secondary outcomes
Parathyroidectomy group: surgical details and outcomes
Among the 41 PTx patients, 28 (68.3%) underwent total PTx with forearm autotransplantation, while 9 (21.9%) had subtotal PTx and 4 (9.8%) underwent limited resection. The median hospital stay was 5 days [IQR 4–7]. Postoperative complications were infrequent and manageable. Clinically significant hypocalcemia requiring calcium supplementation occurred in 7 (17.1%) patients, and hematoma in 4 (9.8%); no wound infection or vocal-cord injury was observed. Reoperation was required in 2 (4.9%) patients for recurrent SHPT, and cinacalcet re-initiation was necessary in 3 (7.3%) patients due to biochemical relapse (Table 2).
Table 2.
Surgical characteristics, complications and postoperative course in the parathyroidectomy group (n = 41)
| Parameter / Event | Frequency n (%) |
|---|---|
| Type of Surgery Performed | |
| Total parathyroidectomy with forearm autograft | 28 (68.3%) |
| Subtotal parathyroidectomy | 9 (21.9%) |
| Limited parathyroidectomy | 4 (9.8%) |
| Postoperative Complications | |
| Clinically significant hypocalcemia | 7 (17.1%) |
| Postoperative hematoma | 4 (9.8%) |
| Reintervention and relapse | |
| Repeat surgery for persistent/recurrent SHPT | 2 (4.9%) |
| Implant removal (autograft excision) | 1 (2.4%) |
| Re-initiation of cinacalcet post- parathyroidectomy | 3 (7.3%) |
Data are presented as number (%).SHPT = Secondary Hyperparathyroidism
Cinacalcet group: dosing, adherence, and outcomes
All 68 cinacalcet-treated patients began at 30 mg daily, with dose escalation to 60 mg achieved in roughly half of them within the first 6–8 weeks. Treatment adherence was suboptimal, as only 19 patients (27.9%) maintained adequate adherence (≥ 80% coverage), while nearly three-quarters discontinued therapy by week 12. The leading causes of discontinuation were financial hardship and limited drug availability, as cinacalcet was neither covered by insurance nor supplied in public hospitals. Patients obtained the medication privately at an average cost of 150–250 USD per month, and 26 patients (38.2%) discontinued therapy for cost-related reasons.
Adverse effects were mostly gastrointestinal, including nausea, anorexia, and vomiting, with persistent hypocalcemia observed in a minority of patients. Symptom recurrence was common after treatment interruption, often within three months, and approximately one in eight patients ultimately required referral for PTx due to medical treatment failure. Key parameters of dosing, adherence, adverse effects, and treatment continuation are summarized in Table 3.
Table 3.
Cinacalcet dosing, adherence, adverse effects, and treatment continuation (n = 68)
| Parameter / Event | Value or Frequency n (%) |
|---|---|
| Dosing and Adherence | |
| Initial prescribed dose | 30 mg/day |
| Dose escalation achieved | 60 mg/day in 35 (51.5%) |
| Time to dose escalation (weeks), median [IQR] | 6 [6–8] |
| High adherence (≥ 80% coverage) | 19 (27.9%) |
| Overall discontinuation by week 12 | 50 (73.5%) |
| Discontinuation due to cost/unavailability | 26 (38.2%) |
| Continued therapy > 6 months | 14 (20.6%) |
| Adverse Effects | |
| Nausea | 19 (27.9%) |
| Anorexia | 12 (17.6%) |
| Vomiting | 7 (10.3%) |
| Persistent hypocalcemia | 11 (16.2%) |
| Muscle cramps | 4 (5.9%) |
| Recurrence/Treatment Failure n (%) | |
| Early symptom recurrence (< 3 months after discontinuation) | 29 (42.6%) |
| Any recurrence during follow-up (among continuers) | 22 (32.4%) |
| Restarted cinacalcet due to rebound | 7 (10.3%) |
| Referred for parathyroidectomy after failure/discontinuation | 9 (13.2%) |
| Access and Affordability | |
| Average monthly out-of-pocket cost (USD) | 150–250 |
| Access via national insurance | Not available |
| Availability in public hospitals | Not available; private purchase |
| Discontinuation due to cost or unavailability | 26 (38.2%) |
Data are presented as median [IQR] or number (%). IQR = Interquartile Range; SHPT = Secondary Hyperparathyroidism; USD = United States Dollars
Primary outcome – biochemical response
At 3–6 months, biochemical response was achieved in 90.2% of patients who underwent PTx compared with 47.1% of those treated with cinacalcet (p < 0.001; Table 4). The median reduction in iPTH was greater after surgery (–980 pg/mL [IQR − 1280 to − 760]) than with cinacalcet (–420 pg/mL [IQR − 620 to − 270]; p < 0.001).
Table 4.
Symptoms, biochemical, and clinical outcomes in parathyroidectomy and Cinacalcet groups
| Outcome | Parathyroidectomy (n = 41) |
Cinacalcet (n = 68) |
RR (95% CI) | ARD % (95% CI) | P-value |
|---|---|---|---|---|---|
| Symptom improvement (3–6 months) | |||||
| Any symptom improvement | 30 (75.0%) | 37 (54.4%) | 1.38 (1.01 to 1.88) | + 20.6 (0.7 to 40.5) | 0.043 |
| Bone pain relief | 29 (70.7%) | 29 (42.6%) | 1.66 (1.16 to 2.37) | + 28.1 (8.4 to 47.8) | 0.005 |
| Pruritus relief | 31 (77.5%) | 34 (50.0%) | 1.55 (1.13 to 2.13) | + 27.5 (7.9 to 47.1) | 0.010 |
| Fatigue relief | 32 (80.0%) | 40 (58.8%) | 1.36 (1.02 to 1.82) | + 21.2 (0.3 to 42.1) | 0.049 |
| Biochemical response (3–6 months) | |||||
| iPTH < 600 pg/mL or ≥ 30% reduction | 37 (90.2%) | 32 (47.1%) | 1.91 (1.48 to 2.47) | + 43.1 (25.7 to 60.5) | < 0.001 |
| Calcium normalization | 36 (87.8%) | 40 (58.8%) | 1.49 (1.17 to 1.89) | + 29.0 (11.0 to 47.0) | 0.004 |
| Phosphate normalization | 32 (78.1%) | 35 (51.5%) | 1.52 (1.14 to 2.04) | + 26.6 (7.3 to 45.9) | 0.008 |
| ALP reduction ≥ 30% | 31 (75.6%) | 26 (38.2%) | 1.98 (1.37 to 2.86) | + 37.4 (17.2 to 57.6) | < 0.001 |
| Clinical outcomes (12 months) | |||||
| Sustained symptom control | 37 (90.2%) | 20 (29.4%) | 3.06 (2.03 to 4.62) | + 60.8 (43.5 to 78.1) | < 0.001 |
| SHPT recurrence | 4 (9.8%) | 9 (13.2%) | 0.74 (0.24 to 2.28) | –3.4 (–16.7 to 9.9) | 0.623 |
| Hospitalization within 6 months | 7 (17.0%) | 23 (33.8%) | 0.50 (0.23 to 1.07) | –16.8 (–32.6 to − 1.0) | 0.064 |
| All-cause mortality (12 months) | 4 (9.8%) | 12 (17.6%) | 0.56 (0.19 to 1.61) | –7.8 (–20.3 to 4.7) | 0.268 |
Data are presented as number (%). ALP = Alkaline Phosphatase; iPTH = intact Parathyroid Hormone; SHPT = Secondary Hyperparathyroidism; RR = Risk Ratio; ARD = Absolute Risk Difference; CI = Confidence Interval
In unadjusted analyses, biochemical response at 3–6 months was more frequent after parathyroidectomy than with cinacalcet (RR 1.91; 95% CI 1.48–2.47; p < 0.001; Table 4). In multivariable Poisson regression with robust variance adjusting for age, diabetes status, dialysis duration, comorbidity burden, and baseline ALP, treatment modality remained the strongest independent predictor of biochemical response, with the adjusted effect estimate remaining close to the unadjusted association. Sensitivity analysis using Firth’s penalized logistic regression yielded concordant findings. All analyses were conducted using complete cases without data imputation.
Comparative outcomes between parathyroidectomy and cinacalcet
At 3–6 months, PTx was associated with greater symptom improvement and biochemical normalization than cinacalcet. Surgical patients achieved higher rates of calcium and phosphate normalization and larger ≥ 30% reductions in ALP. By 12 months, sustained symptom control persisted in 90.2% of PTx patients compared with 29.4% of those receiving cinacalcet.
Recurrence of severe SHPT was infrequent in both groups. Although hospitalization (17.0% vs. 33.8%) and all-cause mortality (9.8% vs. 17.6%) were numerically lower after PTx, these differences did not reach statistical significance (Table 4).
Subgroup analyses
Within the cinacalcet group, treatment adherence markedly influenced biochemical outcomes. Patients with high adherence achieved biochemical control more frequently than those with lower adherence (62.5% vs. 41.3%; RR = 1.51 [95% CI 1.01 to 2.26]; ARD + 21.2%; p = 0.04).
Among surgical patients, biochemical and clinical outcomes were comparable across operative techniques. Total, subtotal, and limited PTx achieved similar efficacy, although transient hypocalcemia was slightly more frequent after subtotal procedures. Long-term biochemical control remained equivalent among the surgical subgroups.
Baseline ALP strata (≤ 300 IU/L vs. > 300 IU/L) did not significantly modify the treatment effect, indicating consistent benefits of PTx over cinacalcet across baseline biochemical profiles.
Discussion
This study compared the effectiveness of PTx and cinacalcet therapy among Sudanese hemodialysis patients with severe SHPT. Surgical management achieved substantially greater biochemical control and symptom improvement than calcimimetic therapy, consistent with findings from large international registries and meta-analyses [1–3, 10, 18–20].
Interpretation of these findings must, however, consider treatment adherence, health-system limitations, and the economic constraints typical of resource-limited environments.
Treatment effectiveness and adherence
PTx achieved rapid and sustained biochemical improvements of PTH and mineral metabolism parameters, whereas the effectiveness of cinacalcet was constrained mainly by poor adherence and early discontinuation. Less than one-third of patients on cinacalcet achieved high adherence, but among those who did, biochemical control was significantly better. This highlights adherence as the principal determinant of therapeutic success, echoing earlier studies demonstrating that consistent cinacalcet use can prevent progression to severe SHPT and delay the need for surgery [4–6, 21]. Importantly, inadequate biochemical control in advanced CKD has been consistently associated with excess cardiovascular risk and increased mortality, underscoring the clinical consequences of treatment interruption and poor adherence [22, 23].
Systemic factors strongly influenced adherence. High out-of-pocket costs, limited insurance coverage, and recurrent supply interruptions led to treatment discontinuation in nearly 40% of cinacalcet users. Similar challenges have been described in other African and Asian dialysis programs [5, 11, 24–27]. Strengthening drug procurement systems and incorporating calcimimetics into national essential medicines lists could improve access, adherence, and long-term outcomes.
In this study, interruptions to cinacalcet therapy were influenced not only by economic and access-related constraints but also by clinically relevant safety considerations. Persistent hypocalcemia was identified in 16.2% of patients treated with cinacalcet, a finding that warrants attention given the substantially elevated baseline iPTH levels characterizing this cohort. In the context of severe secondary hyperparathyroidism, pharmacological suppression of parathyroid hormone may increase vulnerability to sustained hypocalcemia, which can be symptomatic and physiologically consequential rather than a transient laboratory abnormality. From a clinical perspective, the occurrence of hypocalcemia therefore represents a valid and independent justification for discontinuing cinacalcet, alongside challenges related to cost, availability, and adherence [4]. Acknowledging both pharmacological risk and health-system limitations enables a more balanced interpretation of the real-world effectiveness of calcimimetic therapy in resource-limited dialysis settings.
Surgical safety and long-term considerations
PTx was performed safely, with mostly transient hypocalcemia and minor haematomas as notable complications. No wound infections or vocal-cord injuries occurred, aligning with international surgical series that report low complication rates and durable remission following PTx [2, 13, 18]. Nevertheless, continued follow-up is required to monitor for delayed complications such as adynamic bone disease or recurrent SHPT. None were observed within the 12-month observation period, but long-term surveillance using bone turnover markers and imaging is warranted to assess skeletal recovery and mineral metabolism stability.
Alternative pharmacologic options
Novel calcimimetic formulations may help overcome adherence barriers. Intravenous etelcalcetide, administered at the end of dialysis sessions, has demonstrated superior PTH suppression and adherence compared with oral cinacalcet in randomized trials [9, 10]. Although not yet available in Sudan, its introduction could reduce pill burden and minimize cost-related discontinuation. Evaluating its cost-effectiveness and feasibility within national insurance frameworks should be prioritized once supply chains stabilize.
Economic and health-system considerations
Economic inequity was a major determinant of treatment choice. Although PTx is nominally covered by national insurance, most patients still paid out of pocket, while cinacalcet remained entirely excluded from public reimbursement and unavailable in government hospitals. These structural barriers explain the low adherence and high discontinuation rates observed.
Although a formal cost-effectiveness analysis was not performed, the data suggest that PTx may be a more economically sustainable intervention in low-resource contexts. Its one-time cost contrasts sharply with the recurrent expenses of long-term cinacalcet therapy, which averaged 150–250 USD per month. Modeling studies in comparable settings indicate that PTx becomes cost-saving over time when medication adherence is poor or supply chains are unreliable [12]. Expanding public funding for surgery and ensuring uninterrupted calcimimetic access are both critical to equitable SHPT care.
Methodological considerations and limitations
This study’s retrospective design and clinician-guided treatment allocation may have introduced selection bias, with sicker or more symptomatic patients more likely referred for surgery. Symptom improvement was identified from physician documentation rather than standardized patient-reported tools, introducing potential information bias. Despite multivariable adjustment, unmeasured confounding from variables such as nutritional status, dialysis adequacy, or socioeconomic factors cannot be excluded. The single-center nature and modest sample size also limit generalizability, and the 12-month follow-up period was insufficient to assess long-term cardiovascular or skeletal outcomes. Future research using prospective designs, validated symptom measures, and causal-inference approaches would strengthen the evidence base [11].
Clinical and policy implications
Both PTx and cinacalcet remain integral components of SHPT management. PTx offers definitive and durable biochemical control, whereas calcimimetic therapy provides a noninvasive alternative for patients who are unsuitable for surgery or awaiting operative access. Improving outcomes for these patients demands an integrated, system-level strategy that expands surgical services through workforce training and shorter waiting periods, secures reliable and affordable access to calcimimetics within public insurance programs, and enhances patient awareness and treatment adherence through coordinated multidisciplinary care [11, 16, 29]. A unified framework that engages nephrologists, surgeons, pharmacists, and policymakers is crucial to narrow treatment disparities and align national practices with international guidelines.
Conclusion
In this cohort of Sudanese hemodialysis patients with severe SHPT, PTx achieved superior biochemical and clinical outcomes compared with cinacalcet. However, both strategies were constrained by limited accessibility and financial barriers.
Strengthening surgical infrastructure, ensuring affordable and reliable access to calcimimetic, and extending long-term follow-up are essential to improve SHPT care in resource-limited settings.
Adopting WHO and KDIGO recommendations, especially inclusion of calcimimetics in national essential medicines lists, could enhance adherence, reduce complications, and align local nephrology practice with global standards [10, 28, 29].
Acknowledgements
Not applicable.
Author contributions
All authors have contributed to the manuscript. MS conceived and designed the study. MS and NA collected the data. MS and NA performed the data analysis and interpretation. MS and NA drafted the manuscript. MS critically revised the manuscript. Both authors read and approved the final manuscript.
Funding
The authors received no funding for this study.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethical approval
The study protocol was approved by the Baraha Medical City Ethics and Research Committee (BMC-0938-14-04-2018). All data were anonymized and stored in password-protected files accessible only to the research team. Informed consent was waived due to the retrospective nature of the study. The study was conducted in accordance with the Declaration of Helsinki and relevant institutional and national guidelines.
Consent of publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.