Abstract
Chronic kidney disease–mineral and bone disorder (MBD) is a common complication in dialysis patients, contributing to soft tissue and vascular calcifications. Metastatic pulmonary calcification, though frequently found at autopsy, is rarely recognized clinically, particularly among patients on peritoneal dialysis (PD). We report the case of a 40-year-old Tunisian woman with end-stage renal disease of unknown etiology, treated with PD since 2015 using dextrose-based dialysis solutions with a calcium concentration of 2.5 mEq/L. Icodextrin was considered but not prescribed due to financial constraints and lack of insurance coverage. The patient had secondary hyperparathyroidism, persistent hyperphosphatemia, and hypocalcemia. Management relied on oral calcium carbonate, as noncalcium phosphate binders were unavailable. Following subtotal parathyroidectomy, histology confirmed nodular hyperplasia. A drop in parathyroid hormone levels to 9 ng/L was observed and hyperphosphatemia and hypocalcemia persisted despite ongoing calcium supplementation. In 2022, the patient presented with nonspecific respiratory symptoms. Chest computed tomography revealed diffuse pulmonary calcifications and flower-like bronchovascular deposits. Lung biopsy confirmed metastatic pulmonary calcinosis. Calcium supplementation was discontinued, and the patient was transitioned to hemodialysis. She was lost to follow-up 1 month later. This case underscores the importance of individualized management of MBD in patients undergoing PD, particularly in low-resource settings where access to essential treatments remains limited. It emphasizes the importance of context-specific monitoring and preventive strategies to avoid severe complications.
Introduction
Chronic kidney disease–mineral and bone disorder (CKD-MBD) is a common complication in patients undergoing dialysis. 1 It contributes significantly to vascular and soft tissue calcifications, increasing the risk of cardiovascular morbidity and mortality. 2 Metastatic pulmonary calcification (MPC) is a lesser-known but important manifestation of CKD-MBD, particularly in patients with end-stage renal disease (ESRD). 3 It results from the deposition of calcium salts within the pulmonary interstitium. 3 While MPC is typically asymptomatic, severe forms can lead to respiratory failure. Autopsy data suggest that up to 60% to 75% of dialysis patients may have undetected MPC. 3 However, despite this high prevalence, clinically apparent cases remain rare, especially among those receiving peritoneal dialysis (PD).4-6
We report a rare case of MPC in a patient undergoing PD. Through this presentation, we discuss the challenges of managing CKD-MBD in PD patients, particularly in low-resource settings where access to some treatments may be limited.
Case Presentation
A 40-year-old Tunisian woman with ESRD of unknown etiology was initiated on continuous ambulatory PD in 2015 using 1.36% dextrose-based solutions. The initial peritoneal equilibration test (PET) revealed a slow peritoneal solute transfer rate. At baseline, laboratory tests showed persistent hyperparathyroidism, accompanied by hypocalcemia and hyperphosphatemia (Table 1).
Laboratory Findings at the Initiation of Peritoneal Dialysis (2015) and at the Diagnosis of Metastatic Pulmonary Calcinosis (2022).
Treatment included oral calcium carbonate (2 g/day) during meals to bind dietary phosphate and 1 g/day between meals to correct hypocalcemia, along with dietary phosphate restriction. Vitamin D analogs were withheld due to persistently elevated phosphate levels. Calcium-free phosphate binders were not available in our country. Clinical follow-up was irregular, but the patient remained stable for the first 5 years. In January 2020, a repeat PET showed a fast peritoneal solute transfer rate, prompting a switch to automated PD. The PD prescription consisted of 1.36% and 2.27% dextrose-based solutions exchanged overnight, both with a calcium concentration of 2.5 mEq/L. The peritoneal cavity remained dry during the daytime. Use of icodextrin was considered but not prescribed due to financial constraints and lack of insurance coverage. After 3 months, the weekly Kt/V urea was 1.7. Parathyroid hormone (PTH) levels remained above 9 times the upper normal limit, with persistent hyperphosphatemia (2 mmol/L) and hypocalcemia (1.9 mmol/L). Parathyroid scintigraphy revealed 4 hyperfunctioning foci. Histological examination following subtotal (7/8) parathyroidectomy confirmed parathyroid hyperplasia. Oral calcium carbonate was continued postoperatively, as the patient had persistent hypocalcemia and hyperphosphatemia (ranging from 1.9 to 2 mmol/L). Vitamin D analogs were not prescribed due to uncontrolled phosphate levels. In November 2022, the patient presented with asthenia, and chest pain. Physical examination revealed tachypnea, oxygen saturation of 94% on room air, and blood pressure of 130/80 mmHg. She was anuric, but showed no clinical signs of fluid overload. Dermatological and osteoarticular examinations were normal. Laboratory findings are summarized in Table 1. Serum vitamin D was not assessed, as 25-hydroxyvitamin D is not routinely measured in our center. A computed tomography (CT) pulmonary angiogram ruled out embolism but revealed calcified consolidations in the left middle and lower lobes and the lingula. Calcified nodules were seen in the right upper lobe, left middle lobe, and right lower lobe, with calcified atelectasis. “Flower-like” bronchovascular calcifications were also noted, suggestive of MPC (Figure 1). No radiological signs of pulmonary congestion were present. Acid-fast bacilli testing on sputum was negative. A CT-guided transthoracic lung biopsy showed subepithelial calcifications (Figure 2), with no evidence of granulomas or malignancy. Oral calcium supplementation was discontinued, and the patient was switched to chronic hemodialysis. She was lost to follow-up 1 month later.
Axial chest computed tomography scan showing bilateral parenchymal calcifications (arrows) consistent with metastatic pulmonary calcinosis.
Hematoxylin and eosin stain, 10×. Pulmonary parenchyma showing architectural distortion with multiple calcifications of varying size.
Discussion
MPC is a recognized but underreported complication of advanced CKD, particularly rare in PD patients.4-6 It arises from secondary hyperparathyroidism, hyperphosphatemia, metabolic acidosis, and dysregulated mineral metabolism. 7 Clinically, MPC is often silent but may cause dyspnea, chest pain, restrictive lung disease, hypoxemia, or respiratory failure.8,9 Sawka et al. 6 described a PD patient with chronic cough caused by tracheobronchial calcinosis, highlighting the potential clinical burden and progression of this complication. The management of MPC includes the use of noncalcium-based phosphate binders to reduce phosphate level, and cinacalcet to suppress PTH in cases of secondary hyperparathyroidism. Sodium thiosulfate has shown benefit in selected cases of calciphylaxis or progressive calcification; however, it was not prescribed in our patient due to its unavailability in our country. Parathyroidectomy remains an option in refractory cases of secondary hyperparathyroidism, as was performed in our patient. Dietary phosphate restriction is also an essential component of management.1,3,4,8-10 An important consideration is that patients on PD may present with hypoalbuminemia. 11 Failure to correct serum calcium for albumin in this context may lead to overtreatment with calcium supplementation. In addition, a profound decline in PTH levels after parathyroidectomy can predispose to adynamic bone disease, limiting skeletal incorporation of calcium and phosphate. 1 In this setting, continued calcium supplementation may increase the calcium–phosphate product and promote ectopic calcification. 2
The severe and delayed manifestation of extraosseous calcification in our patient highlights the limitations of current monitoring strategies for CKD-MBD in dialysis patients. While routine follow-up relies primarily on biochemical parameters such as PTH, calcium, and phosphate levels, these markers alone may be insufficient to detect early or asymptomatic soft tissue calcifications. Radiological screening could be beneficial in selected high-risk patients with a long-standing mineral imbalance.1,12 This case underscores the need to define clear indications for combining hemodialysis with PD when available therapies fail to control mineral imbalance. Although this approach was not used in our patient, it might have improved phosphate control and potentially altered the disease course.13,14 Another concern is the relevance of the calcium-phosphate product in the development of severe extraosseous calcifications such as MPC. Since the 2017 KDIGO guidelines, the management of CKD-MBD has shifted toward targeting serum calcium and phosphate levels independently, rather than relying on their product. 1 However, in our patient, persistent hypocalcemia did not prevent the occurrence of MPC, even after parathyroidectomy, suggesting that factors beyond serum calcium levels may contribute to ongoing ectopic calcification. Although the overall management of our patient was suboptimal—largely due to the unavailability of certain therapies, this scenario reflects a frequent challenge in real-world clinical practice, particularly in under-resourced regions. Based on our literature review and the differences between PD and hemodialysis, we believe that an individualized and context-adapted approach to CKD-MBD management may be warranted in PD patients. Unfortunately, the lack of PD-specific studies remains a major limitation in establishing tailored recommendations for this population.11,14
Conclusion
This case underscores the importance of early recognition and individualized management of CKD-MBD, particularly in settings with limited access to key therapies. It also highlights the need for further research focused on PD patients to better define monitoring strategies and therapeutic thresholds that may help prevent life-threatening extraosseous calcifications.
Footnotes
Acknowledgements
We would like to acknowledge the healthcare team involved in the management of the patient described in this report.
Ethical Considerations
Ethical approval to report this case series was obtained from the local Research Ethics Committee at the Rabta University Hospital (CO14-24).
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.